US Pat. No. 9,457,306

REGULATED VACUUM OFF-GASSING OF GAS FILTER FOR FLUID PROCESSING SYSTEM AND RELATED METHODS

Life Technologies Corpora...

1. A method for filtering a gas, the method comprising:
sparging a gas through a liquid within a compartment of a container, the container comprising a flexible bag;
passing the sparged gas from the container through a gas filter of a filter assembly; and
applying a partial vacuum to the gas filter so that the partial vacuum assists in drawing the sparged gas through the gas
filter.

US Pat. No. 9,272,896

LABELS, CONTAINERS, SYSTEM AND METHODS FOR PROVIDING REAGENTS

LIFE TECHNOLOGIES CORPORA...

1. A method of adding a supplement of an additive into a container comprising:
(a) providing said container comprising:
i. a bottom panel;
ii. a front panel, a back panel, each having a height to width ratio of between 1.0 to 1.0 and 3.5 to 1.0;
iii. a first side panel, and a second side panel;
iv. a first top panel and an access port top panel; and
v. an access port comprised within the access port top panel, and,
(b) accessing said container through the access port with a device for adding the supplement or the additive;
(c) adding the supplement or the additive to the container;
wherein the height to width ratio of said container is selected in such a way that the device passing through the access port
can touch any point on the bottom panel when the container is resting on the bottom panel, and the device passing through
the access port can touch any point on the back panel when the container is resting on the back panel, and wherein the device
can point directly at the corner formed by the interception of the back panel and the bottom panel.

US Pat. No. 9,115,397

FLUORESCENT CHEMICAL COMPOUNDS HAVING HIGH SELECTIVITY FOR DOUBLE STRANDED DNA, AND METHODS FOR THEIR USE

LIFE TECHNOLOGIES CORPORA...

1. A method of detecting the presence or absence of double stranded DNA in a sample, the method comprising:
providing a sample suspected of containing double stranded DNA;
contacting the sample with a chemical compound to prepare a test sample;
illuminating the test sample with energy; and
detecting emission of energy from the test sample;
wherein the chemical compound has the structure:
wherein:
n is 0;
X is oxygen;
R?, R2, R3, R4, R5, R6, R7, R8, R10and R11independently comprise hydrogen, a hydroxyl group, an alkoxy group, a thiol, a thioalkyl, a thioaryl, a halogen, an alkyl
group, an alkenyl group, an alkynyl group, an aromatic group, a primary amine group, a secondary amine group, a tertiary amine
group, a reactive group, or combinations thereof, wherein at least one of R1, R2, R3and R4comprises an aromatic group or an alkynyl group;

R9comprises an aromatic group or alkyl-aromatic group; and

R12is an alkyl group.

US Pat. No. 9,527,084

VERTICAL CLAMP DEVICE

Life Technologies Corpora...

1. A method of engaging a flow cell component, the method comprising:
inserting the flow cell component into a vertical receptacle of a carriage of a clamp device when the carriage is in the insert
position, the clamp device comprising:

the carriage including a vertical receptacle to receive the flow cell component, the carriage translatable between the insert
position and a closed position;

a fluidics interface block including a fluidics interface to engage flow ports of the flow cell component;
an electronic interface setting to engage electronic pads of the flow cell; and
a drive component to translate the carriage between the insert position and the closed position, the fluidics interface block
to motivate the fluidics interface into contact with the flow ports of the flow cell component and the electronic interface
to engage the electronic pads of the flow cell component when the carriage is in the closed position; and

moving the carriage to the closed position, the flow cell component engaged between the fluidics interface and the electronic
interface in the closed position, wherein the drive component is prevented from moving the carriage to the closed position
when the flow cell component is absent from the vertical receptacle.

US Pat. No. 9,309,566

METHODS, COMPOSITIONS, SYSTEMS, APPARATUSES AND KITS FOR NUCLEIC ACID AMPLIFICATION

LIFE TECHNOLOGIES CORPORA...

1. A method for paired end sequencing comprising:
(a) conducting a forward sequencing reaction on a template polynucleotide attached to a surface and having at least one cleavable
scissile moiety by (i) hybridizing a first primer to the template polynucleotide, (ii) extending the first primer by conducting
primer extension reactions by polymerase-catalyzed successive nucleotide incorporations and forming a first extension strand
hybridized to the template polynucleotide, and (iii) identifying the incorporated nucleotides in the first extension strand;

(b) inducing cross-linking between a nucleoside of the template polynucleotide and a nucleoside of the first extension strand;
(c) cleaving the template polynucleotide by reacting the scissile moiety with heat, irradiation, at least one chemical, or
at least one enzyme, to form a truncated template polynucleotide and forming a terminal 3? phosphate group, converting the
terminal 3? phosphate group to an —OH group, and removing a portion of the cleaved template polynucleotide; and

(d) conducting a reverse sequencing reaction on the first extension strand by extending the terminal 3? OH group on the truncated
template polynucleotide with primer extension reactions by polymerase-catalyzed successive nucleotide incorporations and forming
a second extension strand, and (iii) identifying the incorporated nucleotides in the second extension strand.

US Pat. No. 9,114,104

PROTEINASE K INHIBITORS, METHODS AND COMPOSITIONS THEREFOR

Life Technologies Corpora...

1. A composition comprising at least one alkoxysuccinyl-peptidyl-haloalkyl ketone,
wherein the peptidyl portion of the ketone consists of SEQ ID NO:7 or SEQ ID NO:9; and
wherein the halo of haloalkyl is mono- or di-chloro, bromo, or iodo and the alkyl of haloalkyl or alkoxy is C1-C3 alkyl.

US Pat. No. 9,062,080

HYDROPHOBIC DIACRYLAMIDE COMPOUND

Life Technologies Corpora...

1. A compound of the formula:

or monosilylated derivative thereof, wherein R1 or R2 are independently selected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a
combination thereof or represent a direct bond between a nitrogen and a hydroxylated carbon, and R3, R4, R5, R6, R7, R8, R9, or R10 are independently selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, oxycarbonyl, aryl, ether derivatives
thereof, silyl, or a combination thereof.

US Pat. No. 9,390,227

VISUALIZATION TOOL FOR QPCR GENOTYPING DATA

Life Technologies Corpora...

1. A non-transitory computer-readable storage medium encoded with instructions, executable by a processor, for a visualization
tool for genotyping data, the instructions comprising:
providing instructions for a thermal cycling instrument to perform a full thermal cycle run;
receiving by the processor a first data set at a first time for a sample during the run, wherein the first data set comprises
a first intensity signal for a first probe and a first intensity signal for a second probe;

receiving by the processor a second data set at a second time for the sample during the run, wherein the second data set comprises
a second intensity signal for the first probe and a second intensity signal for the second probe;

presenting an end user with a visualization tool, wherein the visualization tool provides a display of the data selected from:
generating by the processor a first plot from the first data set and displaying the first plot, wherein the display provides
a first confidence value for the first data set; and;

generating by the processor a second plot from the second data set and displaying the second plot, wherein the display provides
a second confidence value for the second data set; and

stopping the thermal cycle run and calling the genotype before run completion when confidence values exceed a defined threshold.

US Pat. No. 9,376,655

FILTER SYSTEMS FOR SEPARATING MICROCARRIERS FROM CELL CULTURE SOLUTIONS

Life Technologies Corpora...

1. A filter system for separating microcarriers from a fluid medium, the filter system comprising:
a substantially rigid support housing having a floor with a side wall upstanding therefrom, the floor and the side wall bounding
a chamber; and

a filter assembly being removably disposable within the chamber of the support housing, the filter assembly comprising:
a container bounding a sterile compartment adapted to hold a fluid;
an inlet port through which fluid flows into the compartment, the inlet port being removably attachable to the support housing;
an outlet port through which fluid flows out of the compartment; and
a filter disposed within the compartment, the filter dividing the compartment into an inlet chamber that is fluidly coupled
with the inlet port and an outlet chamber that is fluidly coupled with the outlet port, the filter allowing a medium to pass
therethrough but preventing microcarriers disposed in the medium from passing therethrough, the filter comprising a porous
bag or sock that bounds the inlet chamber, the porous bag or sock being coupled with the inlet port either directly or through
a tube.

US Pat. No. 9,228,976

METHOD AND APPARATUS FOR DETECTING NUCLEOTIDES

Life Technologies Corpora...

1. A system comprising:
a substrate defining a pore extending through the substrate and including at least three voltage carrying regions disposed
along the pore;

a plurality of interconnects, each interconnect of the plurality of interconnects uniquely connected to a voltage carrying
region of the at least three voltage carrying regions;

one or more power supplies in electrical communication with the plurality of interconnects and defining potential differences
between at least two pairs of voltage carrying regions selected from the at least three voltage carrying regions; and

one or more meters to measure a difference in electrical characteristics of each of the at least two pairs of voltage carrying
regions, the electrical characteristic indicative of a base sequence of a nucleic acid.

US Pat. No. 9,243,085

HYDROPHILIC POLYMERIC PARTICLES AND METHODS FOR MAKING AND USING SAME

Life Technologies Corpora...

1. A method of forming a particle, the method comprising:
promoting a seed particle in an aqueous suspension to form a disperse phase within the aqueous suspension, wherein promoting
the seed particle includes mixing a solvent and a promoting agent with the seed particle;

adding a hydrophilic monomer having a hydrophobic protection group to the disperse phase;
in the disperse phase, polymerizing a plurality of mer units of the hydrophilic monomer, thereby forming a polymeric particle
including a plurality of the hydrophobic protection groups; and

converting the polymeric particle to a hydrogel particle.
US Pat. No. 9,139,665

HYDROPHILIC POLYMERIC PARTICLES AND METHODS FOR MAKING AND USING SAME

Life Technologies Corpora...

1. A method of forming a particle, the method comprising:
in a disperse phase within an aqueous suspension, polymerizing a plurality of mer units of an acrylamide monomer having a
first hydrophobic protection group and a diacrylamide crosslinker having a second hydrophobic protection group, thereby forming
a polymeric particle including a plurality of the first and second hydrophobic protection groups; and

converting the polymeric particle to a hydrophilic particle.

US Pat. No. 9,057,694

COMPOSITIONS AND METHODS FOR IMPROVING RESOLUTION OF BIOMOLECULES SEPARATED ON POLYACRYLAMIDE GELS

LIFE TECHNOLOGIES CORPORA...

1. A polyacrylamide gel for the separation of biomolecules, comprising a stacking gel and a separating gel, wherein the stacking
gel comprises linear, non-crosslinked polyacrylamide at a concentration of from 0.005% to 1%, and wherein the separating gel
does not comprise linear, non-crosslinked polyacrylamide.
US Pat. No. 9,045,795

METHODS TO CONTROL DISSOLVED GAS

Life Technologies Corpora...

1. A method to reduce error in detecting nucleotide reactions, the method comprising:
flowing at least one nucleotide solution from one of at least two containers of a sensor system into an electronic sensor
system including a sensor sensitive to detect a byproduct of nucleotide incorporation including pH changes, each container
including a different nucleotide solution, the sensor system entering an idle mode after flowing;

cycling the at least two containers through at least two cycles, each cycle including depressurizing the at least two containers
for a first period and pressurizing the at least two containers for a second period; and

pressurizing the at least two containers when the sensor system enters an active mode.

US Pat. No. 9,476,855

PARTICLE ANALYZING SYSTEMS AND METHODS USING ACOUSTIC RADIATION PRESSURE

Life Technologies Corpora...

1. A method of analyzing particles with a particle analyzer comprising:
acoustically and hydrodynamically focusing particles to the approximate center of a channel having an electrolytic fluid therein;
flowing the particles through a pore of the channel separating two electrodes between through which an electric current flows;
and

detecting the signal wherein the particles displace their own volume of electrolyte momentarily increasing the impedance of
the pore to produce the signal.

US Pat. No. 9,476,093

POLYMERIZATION OF NUCLEIC ACIDS USING ACTIVATION BY POLYPHOSPHOROLYSIS (APP) REACTIONS

Life Technologies Corpora...

1. A method for amplifying a target nucleic acid by an activation by polyphosphorolysis (APP) reaction comprising the steps
of:
(a) annealing to a template strand of the target nucleic acid a complementary activatable oligonucleotide P* having a non-extendable
nucleotide at its 3? terminus and having no mismatched nucleotides at or near its 3? terminus, so that the terminal nucleotide
is hybridized to the template strand when the oligonucleotide P* is annealed,

(b) polyphosphorolyzing the resulting duplex with:
1) one or more polyphosphorolyzing agents selected from the group consisting of a compound of the general formula I:

wherein n is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;
a compound of general formula II:

wherein n and/or m are selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, with the proviso that n
and m cannot both be 0, and

X is selected from the group consisting of:

 and
2) an enzyme having polyphosphorolysis activity that activates the oligonucleotide P* by removal of the hybridized terminal
nucleotide, and

(c) polymerizing a nucleic acid by extending the activated oligonucleotide P* on the template strand in presence of four nucleoside
triphosphates and a nucleic acid polymerase to synthesize the desired nucleic acid strand; and

(d) repeating the steps (a)-(c) as necessary to amplify the target nucleic acid.

US Pat. No. 9,266,108

NANOLITER ARRAY LOADING

Life Technologies Corpora...

1. A system for holding a plurality of biomolecular samples, comprising:
a receptacle comprising a plurality of wells disposed within a substrate;
a plurality of sample chips disposed inside respective wells of the receptacle, each chip comprising an array of sample wells
and

a loader interface structure comprising an upper portion and a lower portion, the lower portion configured to hold the sample
chips, wherein the upper portion is disposed above the plurality of wells of the receptacle while the lower portion is disposed
inside at least some of the plurality of wells of the receptacle.

US Pat. No. 9,127,306

METHODS AND APPARATUSES FOR NUCLEIC ACID SHEARING BY SONICATION

Life Technologies Corpora...

1. A method for preparing nucleic acid fragments from a sample of purified nucleic acid, the method comprising:
providing a sample of purified nucleic acid;
adding particles to the sample;
sonicating a suspension of the sample and the particles to produce nucleic acids fragments; and
collecting at least a portion of the nucleic acid fragments.

US Pat. No. 9,358,300

TRANSFECTION REAGENTS

LIFE TECHNOLOGIES CORPORA...

1. A transfection complex formed in an aqueous medium, said transfection complex comprising:
an expressible nucleic acid;
a compound having the structure:

  or a polycation thereof;
wherein R4 is a straight-chain, branched or cyclic, alkyl or alkenyl group having 8 to 24carbon atoms, R5 is an alkyl group substituted with one or more amines and one or more alcohols, and R7 is H or a carbohydrate; and

at least one protein or peptide transfection enhancer.
US Pat. No. 9,347,087

METHODS AND COMPOSITIONS FOR EXOSOME ISOLATION

Life Technologies Corpora...

1. A method for the isolation of exosomes from a biological fluid sample comprising:
a) adding polyethylene glycol having a molecular weight of from 3000 to 8000 daltons to the biological fluid sample,
b) incubating the biological fluid sample with the polyethylene glycol,
c) isolating the precipitated exosomes from the biological fluid sample; and
d) isolating nucleic acid from the exosomes.
US Pat. No. 9,434,805

POLYMER PARTICLES, NUCLEIC ACID POLYMER PARTICLES AND METHODS OF MAKING AND USING THE SAME

Life Technologies Corpora...

1. A method of making polymer particles, said method comprising:
making an aqueous gel reaction mixture including an acrylamide monomer or a derivative thereof, a bis-acrylamide, and a nucleic
acid fragment;

forming an emulsion comprising dispersed aqueous phase of gel reaction mixture in a continuous phase;
adding an initiator oil comprising at least one polymerization initiator to the continuous phase; and
performing a polymerization reaction to form polymer particles conjugated to the nucleic acid fragment;
wherein the initiator oil is present in a volume % relative to a volume % of the gel reaction mixture of between about 1 vol
% to about 20 vol %.

US Pat. No. 9,255,299

COMPOSITIONS AND METHODS FOR DETECTION OF MYCOBACTERIUM AVIUM PARATUBERCULOSIS

LIFE TECHNOLOGIES CORPORA...

1. A method for differentially detecting Mycobacterium avium paratuberculosis (MAP) comprising:
obtaining nucleic acids from a sample;
contacting the nucleic acids from the sample with at least one primer set, having one forward primer and one reverse primer,
wherein the at least one primer set is selected from: SEQ ID NO: 6 and SEQ ID NO: 7; or SEQ ID NO: 9 and SEQ ID NO: 10; or
SEQ ID NO: 12 and SEQ ID NO: 13; or SEQ ID NO: 15 and SEQ ID NO: 16; or SEQ ID NO: 18 and SEQ ID NO: 19; or SEQ ID NO: 21
and SEQ ID NO: 22; or SEQ ID NO: 24 and SEQ ID NO: 25; or SEQ ID NO: 27 and SEQ ID NO: 28; or SEQ ID NO: 30 and SEQ ID NO:
31; or SEQ ID NO: 33 and SEQ ID NO: 34; or SEQ ID NO: 36 and SEQ ID NO: 37; or SEQ ID NO: 39 and SEQ ID NO: 40; or SEQ ID
NO: 42 and SEQ ID NO: 43; or SEQ ID NO: 45 and SEQ ID NO: 46; or SEQ ID NO: 48 and SEQ ID NO:49; and full complements thereof;

amplifying at least one MAP-specific target nucleic acid from the sample to form an amplified nucleic acid,
wherein the at least one MAP-specific target nucleic acid is selected from the group consisting of SEQ ID NO:1, SEQ ID. NO:
2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO:5, and full complements thereof, wherein the foregoing target nucleic acids are present
in MAP organisms and absent in non-MAP Mycobacterium Avium Complex (MAC) organisms, wherein the non-MAP MAC organism is selected from the group consisting of Mycobacterium avium subsp. Avium (MAA), Mycobacterium avium subsp silvaticum (MAS), and Mycobacterium subsp hominissuis (MAH),

wherein detecting the amplified nucleic acid confirms the presence of a MAP organism in the sample.

US Pat. No. 9,143,581

SYSTEMS AND METHODS FOR LABORATORY ASSAY VALIDATION OR VERIFICATION

LIFE TECHNOLOGIES CORPORA...

1. A computer program product comprising a tangible and a non-transitory computer readable storage medium whose contents include
a program with instructions to perform a method for generating a protocol for an assay and one or more software modules for
performing the method, wherein the software modules include at least one of a guideline module, a protocol module, and a report
module, wherein the method comprises:
storing in a database device at least one performance characteristic parameter of an assay and storing in the database device
at least one standardized analytical validation protocol for each assay of a plurality of assays and assay types;

receiving a performance characteristic parameter selection and an assay selection from a client device of a laboratory through
a communications device using the analytical validation protocol module and wherein the performance characteristic parameter
selection comprises a laboratory location and the one or more performance characteristic parameters;

retrieving one or more performance characteristic parameters and a standardized analytical validation protocol from the database
device based on the performance characteristic parameter selection and the assay selection; sending the client device the
one or more performance characteristic parameters and one or more study variable values of the standardized analytical validation
protocol through the communications device and wherein the one or more study variable values comprises an acceptance criterion;

receiving from the client device one or more amendments to the one or more performance characteristic parameters and one or
more study variable values of the standardized analytical validation protocol through the communications device; and

generating the analytical validation protocol for the assay based on the one or more amendments.

US Pat. No. 9,310,315

METHODS FOR DETECTING DEFECTS IN INORGANIC-COATED POLYMER SURFACES

Life Technologies Corpora...

1. A material comprising a surface defect, comprising:
a) a substrate comprising a hydrophobic surface;
b) a hydrophilic layer covering at least a portion of the hydrophobic surface, wherein the hydrophilic layer comprises a defect
that leaves a portion of the hydrophobic surface exposed; and

c) a lipophilic, fluorescent substance comprising a fluorescent moiety and a lipophilic moiety, wherein the lipophilic, fluorescent
substance is in contact with the exposed hydrophobic surface of the substrate.

US Pat. No. 9,273,353

INSTRUMENT FOR MONITORING POLYMERASE CHAIN REACTION OF DNA

Life Technologies Corpora...

1. An instrument comprising:
an apparatus configured to hold a plurality of spaced-apart reaction regions;
a light source configured to direct an excitation beam toward the apparatus;
a detector configured to receive emission beams from the apparatus;
an excitation beam path disposed from the light source to the apparatus;
an emission beam path disposed from the apparatus to the detector; and
a lens disposed along the excitation beam path and along the emission beam path, the lens configured to direct the excitation
beam to more than one of the reaction regions simultaneously.

US Pat. No. 9,249,461

SCAFFOLDED NUCLEIC ACID POLYMER PARTICLES AND METHODS OF MAKING AND USING

Life Technologies Corpora...

1. A method of sequencing a template nucleic acid comprising:
(a) disposing a particle in a reaction chamber comprising or capacitively coupled to a field effect transistor, wherein the
particle includes a non-nucleosidic polymer network and a plurality of template nucleic acids attached to the non-nucleosidic
polymer network through its volume at an average density of at least 6.9×104 per ?m3, the particle having a coefficient of variance of volume of not greater than 15%, the non-nucleosidic polymer network includes
a polyacrylamide gel having a total monomer percentage in a range of 3% to 20% and being permeable to proteins having a size
in the range of 50 kilodaltons to 200 kilodaltons;

(b) performing a polymerase extension reaction on a primer annealed to one or more of the plurality of template nucleic acids
to incorporate a nucleotide into the primer; and

(c) detecting a signal output in the field effect transistor indicative of the incorporation of the nucleotide into the primer.
US Pat. No. 9,243,241

SEPARATION AND PURIFICATION OF NUCLEIC ACID FROM PARAFFIN-CONTAINING SAMPLES

Life Technologies Corpora...

1. A method for separating micro ribonucleic acid from a paraffin-containing sample comprising:
(a) heating the sample at a temperature of from 50° C. to 85° C. for from 1 to 60 minutes in the presence of an ionic detergent
and a protease,

(b) remove the aqueous phase from the sample,
(c) add ethanol to the aqueous phase to a final concentration of 35% and apply to a first silica column,
(d) collect the eluate from the silica column of step (c),
(e) adjust the ethanol concentration of the eluate of step (d) to 75% and apply to a second silica column and;
(f) elute the micro ribonucleic acid from the second silica column using water.

US Pat. No. 9,140,706

LABELING REAGENTS AND METHODS OF THEIR USE

Life Technologies Corpora...

1. A compound of Formula IA or a tautomer or salt thereof:

wherein,
L is a linker;
R1 is a halogen;

R2 is a halogen;

R3 is —COO?, —SO3?, substituted azenyl, PEG, phosphate, or bisphosphonate; and

Ra is a reporter molecule.

US Pat. No. 9,128,044

CHEMICAL SENSORS WITH CONSISTENT SENSOR SURFACE AREAS

Life Technologies Corpora...

1. A chemical sensor comprising:
a chemically-sensitive field effect transistor including a floating gate conductor having an upper surface;
a material defining an opening extending to the upper surface of the floating gate conductor, the material comprising a first
dielectric underlying a second dielectric; and

a conductive element contacting the upper surface of the floating gate conductor and extending a distance along a sidewall
of the opening, the distance defined by a thickness of the first dielectric.

US Pat. No. 9,044,694

DEVICE FOR CAPTURE AND LYSIS OF MICROORGANISMS FROM LIQUIDS

Life Technologies Corpora...

1. A device for capture and lysis of microorganisms from a liquid comprising:
a) a filter housing consisting of a hollow body defining a fluid path, having an upper input end adapted for receiving a liquid,
a lower outflow end, and a filter cavity therebetween;

b) a filter, having an input face and an output face, secured within the filter cavity in an orientation perpendicular to
the fluid path wherein the filter is configured such that fluid can enter the input end of the housing and then pass through
the filter before exiting the output end, wherein the filter divides the filter cavity into an upper input cavity between
the input end of the housing and the input face of the filter, and a lower output cavity between the output face of the filter
and the output end of the housing;

c) at least one bead disposed within the input cavity, wherein the bead can move freely within the input cavity when the device
is agitated and the bead is about 10 ?m to about 100 ?m in diameter;

d) a first sealing means for removably sealing the input end, wherein the first sealing means is selected from a cap and a
plug; and

e) a second sealing means for removably sealing the output end, wherein the second sealing means is selected from a cap and
a plug.

US Pat. No. 9,476,854

ELECTRIC FIELD DIRECTED LOADING OF MICROWELL ARRAY

Life Technologies Corpora...

1. An apparatus comprising:
a device substrate including an array of sensors, each sensor of the array of sensors including an electrode structure disposed
at a surface of the device substrate; and

a well structure overlying the surface of the device substrate and defining an array of wells at least partially corresponding
with the array of sensors, the well structure including an electrode layer and an insulative layer.

US Pat. No. 9,447,409

LYSIS BUFFERS FOR EXTRACTING NUCLEIC ACIDS

LIFE TECHNOLOGIES CORPORA...

1. A composition comprising 250 to 500 mM ethylene glycol tetraacetic acid and each of the following: a detergent, a reducing
agent, and an enzyme, wherein the detergent is selected from one or more of N-lauroyl sarcosine, sodium deoxycholate, cetyltrimethylammonium
bromide, dodecyl ?-D-maltoside, nonanoyl-N-methylglucamide, polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether,
sodium dodecyl sulfate, and combinations thereof, wherein the reducing agent comprises one or more of tris(2-carboxyethyl)phosphine,
dithioerythritol, and dithiothreitol, and wherein the enzyme is selected from caspase, chymotrypsin, pepsin, proteinase K,
thrombin, Staphylococcus V8 protease, pronase, papain, Bacillus sp. E1A protease, and trypsin and combinations thereof.

US Pat. No. 9,321,053

VERTICAL CLAMP DEVICE

Life Technologies Corpora...

1. A clamp device comprising:
a carriage including a vertical receptacle to receive a flow cell component and having an arm, the carriage translatable between
an insert position and a closed position;

a translatable receptacle guide to engage the carriage when the carriage is in the insert position;
a fluidics interface block including a fluidics interface to engage flow ports of the flow cell component;
an electronic interface setting to engage electronic pads of the flow cell; and
a drive component translatable between the insert position and the closed position, the fluidics interface block to motivate
the fluidics interface into contact with the flow ports of the flow cell component and the electronic interface to engage
the electronic pads of the flow cell component when the drive component is in the closed position.

US Pat. No. 9,267,914

ELECTRIC FIELD DIRECTED LOADING OF MICROWELL ARRAY

Life Technologies Corpora...

1. A method of forming a sensor apparatus, the method comprising:
applying a first insulative layer over a device substrate, the device substrate including an array of sensors, each sensor
of the array of sensors including an electrode structure at the surface of the device substrate;

applying an electrode layer over the first insulative layer;
applying a second insulative layer over the electrode layer; and
forming an array of wells in the first insulative layer, the electrode layer and the second insulative layer, the array of
wells substantially corresponding with the electrodes of the sensors of the array of sensors.

US Pat. No. 9,067,954

HYDROPHOBIC DIACRYLAMIDE COMPOUND

Life Technologies Corpora...

1. A compound of the formula:

or monosilylated derivative thereof, wherein R4, R5, or R6 are independently selected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a
combination thereof, and R1, R2, R3, R7, R8, or R9 are independently selected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a
combination thereof.

US Pat. No. 9,481,477

FLUID MANIFOLD SYSTEM WITH ROTATABLE PORT ASSEMBLY

Life Technologies Corpora...

1. A manifold port assembly comprising:
a housing bounding a compartment and having an inlet port and six outlet ports formed thereon and communicating with the compartment;
and

a carousel bounding three spaced apart fluid paths that extend therethrough from a corresponding first end to an opposing
corresponding second end, at least a portion of each fluid path being spaced apart from the housing and being radially enclosed
by the carousel, the carousel being rotatably disposed within the compartment of the housing so that when the first end or
the second end of each fluid path is aligned with the inlet port on the housing, the other of the first end or second end
of each fluid path is aligned with a corresponding different one of each of the six outlet ports, wherein each fluid path
has a central longitudinal axis extending along the length thereof that is arched, each arch having a different curvature.

US Pat. No. 9,389,183

FLUOROGENIC HYDRAZINE-SUBSTITUTED COMPOUNDS

Life Technologies Corpora...

1. A hydrazinyl-substituted compound of Formula I:

or a stereoisomer, tautomer, hydrate, solvate, or salt thereof;
wherein,
X is H or an analyte selected from the group consisting of an amino acid, a peptide, a protein, a carbohydrate, a polysaccharide,
a nucleoside, a nucleotide, an oligonucleotide, a nucleic acid polymer, a drug, a lipid, a synthetic polymer, malondialdehyde,
and 4-hydroxynonenal;

R1 is selected from the group consisting of H, alkyl and substituted alkyl;

R1a is H;

R2, R4, R5, R6, R7, R8, R9 and R10 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl,
acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino,
aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino,
(carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO3?, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl,
heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; and

R3 is selected from the group consisting of alkoxy, substituted alkoxy, amino, substituted amino, hydrazinyl, substituted hydrazinyl,
analyte substituted hydrazinyl, alkyl, substituted alkyl, acyl, acylamino, acyloxy, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino,
aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl
ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO3?, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl,
heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; or

R2 and R3, R3 and R4, or R2, R3 and R4 are taken together to form a fused heterocyclyl group, a fused substituted heterocyclyl group, a fused aryl group, a fused
substituted aryl group, a fused heteroaryl group or a fused substituted heteroaryl group.

US Pat. No. 9,268,903

SYSTEMS AND METHODS FOR SEQUENCE DATA ALIGNMENT QUALITY ASSESSMENT

Life Technologies Corpora...

1. A method for classifying alignments of paired nucleic acid sequence reads, comprising:
disposing a nucleic acid sample within a sample chamber of a sequencing instrument, the nucleic acid sample comprising a plurality
of target nucleic acids, the target nucleic acids including first and second tags, the first tag being derived from a first
region of a polynucleotide and the second tag being derived from a second region of the polynucleotide, the first and second
tags being separated by an insert region;

detecting, by a detection device, a plurality of signals representative of the sequence of at least one of the target nucleic
acids of the nucleic acid sample;

generating, by a computing device comprising a processor and memory, a paired nucleic acid sequence read from the plurality
of signals, the paired nucleic acid sequence read including a first read of the first tag and second read of the second tag;

determining, by the computing device, potential alignments for the first and second reads of the paired nucleic acid sequence
read to a reference sequence, wherein each potential alignment satisfies a minimum threshold mismatch constraint;

identifying, by the computing device, potential paired alignments of the paired nucleic acid sequence read, wherein a distance
between the first and second reads of each potential paired alignment is within an estimated insert size range; and

calculating, by the computing device, an alignment score for each potential paired alignment based on:
a distance between the first and second reads, and
a total number of mismatches for the first and second reads.
US Pat. No. 9,342,651

COMPUTATIONAL METHODS FOR TRANSLATING A SEQUENCE OF MULTI-BASE COLOR CALLS TO A SEQUENCE OF BASES

Life Technologies Corpora...

1. A system for resequencing a DNA fragment using color calls, comprising:
a DNA sequencer in communication with a processor;
the DNA sequencer configured to:
perform a sequence-by-ligation process using a DNA sample and probes labeled with color dyes, wherein the probes interrogate
two or more nucleotides at a time with the color dyes according to a multi-base code, the sequence-by-ligation process comprising:

performing multiple ligation reaction cycles, wherein a ligated probe is generated with each ligation reaction cycle,
detecting the ligated probe after the ligation reaction cycle to obtain a color call for the ligated probe, and
producing a string of read color calls for a DNA fragment from the DNA sample, the string of read color calls encoded with
the multi-base code; and

the processor configured to:
obtain the string of read color calls from the DNA sequencer,
obtain a reference sequence,
map the string of read color calls to the reference sequence,
extract a base sequence from the reference sequence,
encode the base sequence as a string of reference color codes according to the multi-base code,
align the string of read color calls with the string of reference color codes and detect mismatches in the alignment,
annotate one or more mismatches of the string of read color calls as inconsistent,
correct the one or more mismatches of the string of read color calls, wherein the processor corrects at least one mismatch
of the string of read color calls by replacing the mismatch with its corresponding color call from the string of reference
color codes, and

decode the string of read color calls to bases producing a read sequence for the DNA fragment.

US Pat. No. 9,291,566

STABLE INDIUM-CONTAINING SEMICONDUCTOR NANOCRYSTALS

Life Technologies Corpora...

1. A method of detecting a target in a sample, the method comprising:
contacting a biological sample with a population of water-dispersible semiconductor nanocrystals in an aqueous medium, wherein
each nanocrystal comprises a core consisting essentially of indium and phosphorus, and a shell consisting essentially of zinc
and sulfur, wherein the shell is directly on the surface of the core, wherein the quantum yield of the semiconductor nanocrystals
when dispersed in the aqueous medium is at least 35%, and wherein the population of nanocrystals is non-toxic to cells or
tissues; and

detecting the fluorescence emission of the population of semiconductor nanocrystals.

US Pat. No. 9,150,922

CYANINE COMPOUNDS AND THEIR APPLICATION AS QUENCHING COMPOUNDS

Life Technologies Corpora...

1. A compound having the formula:

wherein R2 is alkyl, substituted, alkyl, alkoxy, substituted alkoxy, sulfoalkyl, substituted sulfoalkyl, aminoalkyl, substituted aminoalkyl,
reactive group, carrier molecule, or solid support;

R3 is alkyl, substituted alkyl, sulfoalkyl, reactive group, carrier molecule, or solid support;

R4 is alkyl, substituted alkyl, sulfoalkyl, reactive group, carrier molecule, or solid support; or

R3 and R4 taken together form a 5- or 6-membered saturated ring or a substituted 5- or 6-membered saturated ring;

each R5 is independently hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, fused benzene, substituted fused benzene,
trifluoromethyl, sulfoalkyl, substituted sulfoalkyl, aminoalkyl, substituted aminoalkyl, halogen, reactive group, carrier
molecule, or solid support;

R22, R23, R24, R25 and R26 are independently hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, aminoalkyl, substituted
aminoalkyl, hydroxyl, halogen, thioether, carbonyl, substituted carbonyl, sulfo, substituted sulfo, sulfoalkyl, reactive group,
carrier molecule, or solid support; or

a member independently selected from
R22 in combination with R23;

R23 in combination with R24;

R24 in combination with R25; and

R25 in combination with R26;

together with the atoms to which they are joined, form a ring which is a 5-, 6- or 7-membered cycloalkyl, a substituted 5-,
6- or 7-membered cycloalkyl, a 5-, 6- or 7-membered heterocycloalkyl, a substituted 5-, 6- or 7-membered heterocycloalkyl,
a 5-, 6- or 7-membered aryl, a substituted 5-, 6- or 7-membered aryl, a 5-, 6- or 7-membered heteroaryl, or a substituted
5-, 6- or 7-membered heteroaryl; and

A is

R12 is alkyl, substituted, alkyl, alkoxy, substituted alkoxy, sulfoalkyl, substituted sulfoalkyl, aminoalkyl, substituted aminoalkyl,
a substituted or unsubstituted aromatic, heteroaromatic, cyclic or heterocyclic moiety, reactive group, carrier molecule,
or solid support;

R10, R11, R13, R14, R15, R16, R17 and R18 are independently hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, sulfo, substituted sulfo, sulfoalkyl, substituted
sulfoalkyl, amino, substituted amino, aminoalkyl, substituted aminoalkyl, trifluoromethyl, halogen, reactive group, carrier
molecule, or solid support; or

a member independently selected from
R10 in combination with R11;

R11 in combination with R13;

R13 in combination with R14;

R14 in combination with R15;

R15 in combination with R16;

R11 in combination with R17; and

R17 in combination with R18;

together with the atoms to which they are joined, form a ring which is a 5-, 6- or 7-membered cycloalkyl, a substituted 5-,
6- or 7-membered cycloalkyl, a 5-, 6- or 7-membered heterocycloalkyl, a substituted 5-, 6- or 7-membered heterocycloalkyl,
a 5-, 6- or 7-membered aryl, a substituted 5-, 6- or 7-membered aryl, a 5-, 6- or 7-membered heteroaryl, or a substituted
5-, 6- or 7-membered heteroaryl; or

a member independently selected from
R12 in combination with R16;

R12 in combination with R18,

R12 in combination with R11;

R10 in combination with R?;

R11 in combination with R?; or

R? in combination with R?;
together with the atoms to which they are joined, form a ring which is a 5-, 6- or 7-membered heterocycloalkyl, a substituted
5-, 6- or 7-membered heterocycloalkyl, a 5-, 6- or 7-membered heteroaryl, or a substituted 5-, 6- or 7-membered heteroaryl;
and

R? and R? are hydrogen, alkyl or aminoalkyl.

US Pat. No. 9,116,117

CHEMICAL SENSOR WITH SIDEWALL SENSOR SURFACE

Life Technologies Corpora...

1. A chemical sensor comprising:
a chemically-sensitive field effect transistor including a floating gate conductor; and
a material defining an opening overlying the floating gate conductor, the material comprising a conductive element having
an inner surface defining a lower portion of a sidewall of the opening, and a dielectric on the conductive element and having
an inner surface defining an upper portion of the sidewall, wherein the inner surface of the conductive element is substantially
aligned with the inner surface of the dielectric.

US Pat. No. 9,403,985

METHINE-SUBSTITUTED CYANINE DYE COMPOUNDS

Life Technologies Corpora...

1. A complex comprising a nucleic acid reporter compound non-covalently associated with a nucleic acid molecule, wherein the
nucleic acid reporter compound has the formula:

wherein:
each R1 is independently hydrogen, carboxy, sulfo, phosphate, phosphonate, amino, hydroxyl, trifluoromethyl, halogen, alkyl, substituted
alkyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, aminoalkyl,
substituted aminoalkyl, fused benzene, substituted fused benzene, reactive group, solid support or carrier molecule,

wherein the reactive group is an acrylamide, a carboxylic acid, an activated ester of a carboxylic acid, a succinimidyl ester
of a carboxylic acid, a carboxylic ester, an acyl azide, an acyl nitrile, an aldehyde, an alkyl halide, an anhydride, an aniline,
an amine, an aryl halide, an azide, an aziridine, a boronate, a diazoalkane, a haloacetamide, a haloalkyl, a halotriazine,
a hydrazine, a hydrazide, an imido ester, an isocyanate, an isothiocyanate, a maleimide, a phosphoramidite, a reactive platinum
complex, a silyl halide, a sulfonyl halide, a thiol or a photoactivatable group;

wherein the carrier molecule is an amino acid, an antibody or fragment thereof, an avidin, a streptavidin, a biotin, a blood
component protein, an enzyme, an enzyme inhibitor, a peptide, a protein, a polysaccharide, a dextran, a nucleoside, a nucleotide,
an oligonucleotide, a nucleic acid polymer, a hapten, a psoralen, a drug, a small-molecule drug, a tyramide, a hormone, an
IgG binding protein, a fluorescent protein, a growth factor, a lectin, a lipopolysaccharide, a lipid, a lipid assembly, a
synthetic polymer, a polymeric microparticle, a metal binding protein, a metal chelating moiety, a non-biological microparticle,
a peptide toxin, a phosphotidylserine-binding protein, a structural protein, a microorganism, a biological cell or a virus;
and

wherein the solid support is a microfluidic chip, a silicon chip, a microscope slide, a microplate well, silica gels, polymeric
membranes, particles, derivatized plastic films, glass beads, cotton, plastic beads, alumina gels, polysaccharides, polyvinylchloride,
polypropylene, polyethylene, Sepharose, poly(acrylate), polystyrene, poly(acrylamide) polyol, agarose, agar, cellulose, dextran,
starch, FICOLL, heparin, glycogen, amylopectin, mannan, inulin, nitrocellulose, diazocellulose, nylon, latex bead, magnetic
bead, paramagnetic bead, or superparamagnetic bead;

t is an integer from 1 to 4;
R2 is an alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, alkoxy, substituted
alkoxy, carboxy, carboxyalkyl, hydroxy, hydroxyalkyl, sulfo, sulfoalkyl, amino, aminoalkyl, alkylamino, dialkylamino, or trialkylammonium;

at least one of R3, R4, and R5 is an alkyl, substituted alkyl, a 5-, 6- or 7-membered heterocycloalkyl, a substituted 5-, 6- or 7-membered heterocycloalkyl,
a 5-, 6- or 7-membered cycloalkyl, a substituted 5-, 6- or 7-membered cycloalkyl, a 5-, 6- or 7-membered heteroaryl, a substituted
5-, 6- or 7-membered heteroaryl, a 5-, 6- or 7-membered aryl or a substituted 5-, 6- or 7-membered aryl; and the remaining
R3, R4 or R5 are hydrogen;

X is S, O or Se; and
D is a substituted pyridinium, unsubstituted pyridinium, substituted benzoxazolium, unsubstituted benzoxazolium, substituted
benzathiazolium or unsubstituted benzathiazolium moiety, or a tautomer thereof.

US Pat. No. 9,400,273

7-HYDROXYCOUMARIN-BASED CELL-TRACKING REAGENTS

Life Technologies Corpora...

1. A method for tracking cell proliferation, differentiation, and/or function, the method comprising the steps of:
a) incubating a mixture of cells and a compound selected from

or a pharmaceutically acceptable salt thereof;

b) providing a stimulus to the mixture to elicit a fluorescent signal; and
c) analyzing the stimulated mixture.

US Pat. No. 9,388,375

METHODS AND APPARATUS FOR GAS STREAM MASS TRANSFER WITH A LIQUID

Life Technologies Corpora...

1. A method for oxygenating a culture of cells or microorganisms, the method comprising:
a) delivering into a compartment of a container a culture comprised of (i) cells or microorganisms and (ii) medium, the culture
having an exposed top surface disposed within the compartment;

b) mixing the culture within the container; and
c) blowing a stream of a gas containing oxygen over at least a portion of the top surface of the culture while the culture
is being mixed so that the blowing stream of gas produces turbulence on the top surface that is sufficient to produce a mass
transfer of oxygen between the gas and the culture, the mass transfer being sufficient to oxygenate the culture for growing
the cells or microorganisms.

US Pat. No. 9,334,542

COMPOSITIONS AND METHODS FOR DETECTION OF MICROORGANISMS OF THE MYCOBACTERIUM AVIUM COMPLEX EXCLUDING MYCOBACTERIUM AVIUM PARATUBERCULOSIS

LIFE TECHNOLOGIES CORPORA...

1. A method for differentially detecting a non-Mycobacterium avium subsp. paratuberculosis (non-MAP) Mycobacterium Avium Complex (MAC) organism selected from the group consisting of Mycobacterium avium subsp. Avium (MAA), Mycobacterium avium subsp silvaticum (MAS), and Mycobacterium subsp hominissuis (MAH), from a Mycobacterium avium subsp. paratuberculosis (MAP) organism comprising:
amplifying from a sample at least one non-MAP-specific target nucleic acid selected from the group consisting of SEQ ID NO:1,
SEQ ID. NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and full complements thereof,
comprising contacting nucleic acids from the sample with at least one primer set that can hybridize to and amplify the at
least one non-MAP-specific target nucleic acid, under conditions suitable for amplification; and

detecting an amplified nucleic acid, wherein detecting the amplified nucleic acid is indicative of the presence of a non-MAP
MAC organism in the sample.

US Pat. No. 9,321,996

SERUM-FREE MAMMALIAN CELL CULTURE MEDIUM, AND USES THEREOF

Life Technologies Corpora...

1. A method of producing a recombinant polypeptide or a viral protein in vitro, comprising: culturing a recombinant CHO cell
in suspension in a serum-free and protein-free cell culture medium, under conditions suitable for the expression of said polypeptide,
or viral protein, wherein the medium comprises a transferrin substitute and an insulin substitute and supports increased CHO
cell growth in suspension as compared to culture in FMX-8 medium, wherein said transferrin substitute comprises iron or an
iron containing compound and said insulin substitute comprises zinc or a zinc containing compound, wherein said cell suspension
culture is without supplementation of serum and without supplementation of protein, and wherein the cultivation of the CHO
cell does not require that the CHO cell express an exogenous recombinant protein.
US Pat. No. 9,315,861

ENHANCED LIGATION REACTIONS

Life Technologies Corpora...

1. A method for ligating nucleic acids comprising:
(a) forming a first single-stranded nick on a nucleic acid duplex by hybridizing a polynucleotide to a first and second oligonucleotide,
wherein the first and second oligonucleotides abut each other, and wherein one end of the polynucleotide, the first oligonucleotide
or the second oligonucleotide is attached to a surface;

(b) closing the first single-stranded nick by conducting a nucleic acid ligation reaction in the presence of a ligase and
an agent that catalyzes removal of an adenylate group from a terminal 5? phosphate of a nucleic acid.

US Pat. No. 9,138,711

STABLE NANOPARTICLES AND METHODS OF MAKING AND USING SUCH PARTICLES

Life Technologies Corpora...

1. A population of nanoparticles, comprising:
a plurality of core/shell nanocrystals, each including,
a semiconductor core;
an intermediate semiconductor shell layer comprising more than one monolayer disposed over the semiconductor core;
an external semiconductor shell layer disposed over the intermediate semiconductor shell layer; and
a hydrophilic organic layer in direct contact with the external semiconductor shell layer, wherein the hydrophilic organic
layer comprises a plurality of hydrophilic ligands, each comprising a hydrophilic functional group that imparts aqueous dispersibility
to the nanocrystal, wherein the hydrophilic ligands are selected from dipeptides, tridentate thiol ligands, and functionalized
phosphonate or phosphinate ligands, wherein the tridentate thiol ligands are selected from the group consisting of compounds
of Formula I, II, III, IV, V, and VI:


wherein R1, R2, and R3, when taken alone, are independently H, halo, hydroxyl, (—(C?O)—C1-C22 or —(C?O)CF3) alkanoyl, C1-C22 alkyl, C1-C22 heteroalkyl, ((CO)OC1-C22) alkylcarbonato, or (—(CO)NH(C1-C20) or —(CO)N(C1-C20)2) alkylcarbamoyl;

R4, and R5, when taken alone, are independently H, C1-C20 alkyl, or C6-C18 aryl; and
R6 is H or a polyethylene glycol moiety.

US Pat. No. 9,366,676

FLUORESCENT CHEMICAL COMPOUNDS HAVING HIGH SELECTIVITY FOR DOUBLE STRANDED DNA, AND METHODS FOR THEIR USE

Life Technologies Corpora...

1. A chemical compound having the structure:

wherein:
n is a non-negative integer;
X is oxygen or sulfur;
R13, R14, R15, R16, R17, R18, R20, and R21 independently comprise hydrogen, a hydroxyl group, an alkoxy group, a thiol, a thioalkyl, a thioaryl, a halogen, an alkyl
group, an alkenyl group, an alkynyl group, an aromatic group, a primary amine group, a secondary amine group, a tertiary amine
group, a reactive group, or combinations thereof wherein one of R13, R14, R15, R16, R17 comprises an aromatic group and R19 is an aromatic or alkylaromatic group

R22 is an alkyl group.

US Pat. No. 9,309,557

NUCLEIC ACID AMPLIFICATION

Life Technologies Corpora...

1. A method for nucleic acid amplification, comprising:
A. forming a reaction mixture within a continuous liquid phase under nucleic acid synthesis conditions by distributing at
least two different polynucleotide templates comprising both a first primer binding sequence and a second primer binding sequence,
into an array of reaction chambers, wherein the array or reaction chambers is on a support and contains a first universal
primer that does not include any target-specific sequence, by introducing a polymerase, a second universal primer in solution,
and said at least two different polynucleotide templates into different reaction chambers of the array, wherein the first
primer binding sequence is complementary or identical to at least a portion of the first universal primer and the second primer
binding sequence is complementary or identical to at least a portion of the second universal primer;

B. forming at least two substantially monoclonal nucleic acid populations by using the polymerase to amplify under isothermal
conditions a single one of each of said at least two different polynucleotide templates within said different reaction chambers,
by partially denaturing and without first compartmentalizing, within the same reaction mixture of step (a) in the continuous
liquid phase, wherein the different reaction chambers are in fluid communication with each other during the amplifying;

C. after the amplifying, distributing a plurality of additional polynucleotide templates into the array of reaction chambers;
and

D. amplifying under the isothermal conditions, at least one polynucleotide template of the plurality of additional polynucleotide
templates, thereby forming an additional substantially monoclonal nucleic acid population within each of at least one additional
reaction chamber of the array of reaction chambers that does not include any other substantially monoclonal nucleic acid population.

US Pat. No. 9,279,749

LASER MICRODISSECTION METHOD AND APPARATUS

Life Technologies Corpora...

1. A method for laser microdissection comprising the steps of:
providing a first substrate having an upper surface;
providing a membrane having an upper surface and a lower surface;
applying a layer of a biological material to upper surface of the membrane;
placing the membrane in contact with the first substrate such that the lower surface of the membrane contacts the upper surface
of the first substrate;

providing a second substrate having a surface with a transfer film disposed thereon, wherein the transfer film has adhesive
characteristics upon activation by electromagnetic energy;

identifying at least one targeted portion of the biological material to be microdissected;
bringing the transfer film into juxtaposition with the first substrate on the side of the biological material in the location
of the at least one targeted portion of the biological material;

activating a first laser source so as to describe at least one closed or substantially closed path around the at least one
targeted portion of the biological material to be microdissected, the first laser source eroding the biological material along
the described path and defining an interior portion of the biological material and an exterior portion of the biological material;

activating a second laser source and directing the second laser source at the interior portion of the biological material
so as to activate at least one region of the transfer film so that the at least one activated region of the transfer film
adheres to the interior portion of the biological material; and

separating the transfer film and the at least one adhered targeted portion of the biological material from the first substrate.
US Pat. No. 9,090,946

SE33 MUTATIONS IMPACTING GENOTYPE CONCORDANCE

LIFE TECHNOLOGIES CORPORA...

1. A method comprising:
a. providing a forward primer capable of annealing to SE33 locus 5? of a short tandem repeat region,
b. providing a reverse primer, the reverse primer comprising 10 or more contiguous nucleotides of the inverse complement of
positions 316, 317, and 324 of SEQ ID NO: 3, wherein SEQ ID NO 3 comprises a T at position 316, A at position 317, or A at
position 324,

c. amplifying a nucleic acid with the forward and reverse primers,
d. separating the amplification products by capillary electrophoresis,
e. comparing the amplification product to an allelic ladder, and
f. identifying the presence of the amplification products.
US Pat. No. 9,309,558

NUCLEIC ACID AMPLIFICATION

Life Technologies Corpora...

1. A method for nucleic acid amplification, comprising:
(a) forming a reaction mixture by contacting, within a continuous liquid phase under nucleic acid synthesis conditions:
a plurality of different target polynucleotide templates in solution, each containing a first primer binding sequence and
a second primer binding sequence, wherein the support contains only one type of primer;

a support containing multiple copies of a first universal primer that does not include any target-specific sequence and includes
a sequence that is complementary or identical to the first primer-binding sequence, and the support does not include a primer
containing a sequence that is complementary or identical to the first primer binding sequence, wherein the support contains
only one type of primer;

multiple copies of a second universal primer in solution, wherein the second universal primer includes a sequence that complementary
or identical to the second primer-binding sequence and is optionally pre-hybridized to one or more of the target polynucleotide
templates; and

a polymerase; and
(b) forming two or more substantially monoclonal populations that are linked to the support, by clonally amplifying, by partially
denaturing and without first compartmentalizing, within the same reaction mixture of step (a) in the continuous liquid phase,
at least two of the target polynucleotide templates on the support using the first and second universal primers under isothermal
amplification conditions.

US Pat. No. 9,164,070

COLUMN ADC

Life Technologies Corpora...

1. A chemical detection circuit, comprising:
a column of chemically-sensitive pixels, each pixel comprising:
a chemically-sensitive transistor; and
a row selection device;
a column interface circuit coupled to the column of chemically-sensitive pixels;
an analog-to-digital converter (ADC) coupled to the column interface circuit, the ADC including an offset cancellation circuit;
an output terminal comprising two pins for low-voltage differential signaling; and
a serializer circuit including
a plurality of shift registers to shift data to bit alignment logic for data alignment,
a pair of ping-pong registers to receive the aligned data and latch each parallel word with timing overlap, and
a first multiplexer to select at least one of the ping-pong registers to output data to an encoder;
a serializer coupled to the output terminal and configured to receive encoded data from the encoder; and
a driver to output data from the serializer to the output terminal, wherein the serializer is configured to transmit data
signals by low-voltage differential signaling.

US Pat. No. 9,314,751

METHODS AND APPARATUS FOR MIXING AND SHIPPING FLUIDS

Life Technologies Corpora...

1. A method for shipping a fluid, the method comprising:
removably securing a retention ring to a shipping vessel that bounds a chamber, the retention ring having a plurality of catches
disposed thereon;

inserting a collapsible bag within the chamber of the shipping vessel so that a plurality of alignment tabs secured to the
collapsible bag are removably secured to corresponding catches of the retention ring;

dispensing a fluid into a compartment of the collapsible bag, the shipping vessel being removably positioned on a movable
first cart such that a lower end of the shipping vessel is supported on the first cart;

coupling the first cart directly to a first docking station, the first docking station comprising a stand and a first drive
motor assembly mounted thereon;

mixing the fluid within the compartment of the collapsible bag by using the first drive motor assembly to rotate a drive shaft
extending between the first drive motor assembly and the collapsible bag, the drive shaft passing into the chamber of the
shipping vessel through an opening formed at an upper end of the shipping vessel, the upper end of the shipping vessel being
disposed above the lower end of the shipping vessel;

separating the first cart from the first docking station;
removing the shipping vessel containing the collapsible bag and fluid from the first cart;
shipping the shipping vessel removed from the first cart and containing the collapsible bag and fluid to a second location;
positioning the shipping vessel on a movable second cart;
coupling the second cart to a second docking station, the second docking station comprising a stand and a second drive motor
assembly mounted thereon; and

mixing the fluid within the compartment of the collapsible bag by using the second drive motor assembly to rotate a drive
shaft extending between the second drive motor assembly and the collapsible bag.

US Pat. No. 9,309,520

METHODS AND COMPOSITIONS FOR SYNTHESIS OF NUCLEIC ACID MOLECULES USING MULTIPLE RECOGNITION SITES

LIFE TECHNOLOGIES CORPORA...

1. An isolated nucleic acid molecule comprising:
(a) a first topoisomerase recognition site;
(b) a first site specific recombination site;
(c) a nucleic acid segment;
(d) a second site specific recombination site; and
(e) a second topoisomerase recognition site;
wherein the first site specific recombination site and the second site specific site do not recombine with each other.
US Pat. No. 9,212,388

DIRECT QUANTITATIVE PCR ABSENT MINOR GROOVE BINDERS

LIFE TECHNOLOGIES CORPORA...

1. A method comprising combining a fluorescently labeled probe and a filter paper contacted to a specimen in a reaction vessel,
performing a quantitative real-time polymerase chain reaction (qrtPCR) and detecting a level of fluorescence emanating from
the reaction vessel with a charge coupled device during a thermal cycle while the paper is in the reaction vessel, wherein
the probe is not conjugated with a minor groove binder and the probe is a reverse complement to a multicopy locus.
US Pat. No. 9,175,354

DETECTION OF SALMONELLA ENTERICA SUBSPECIES ENTERICA SEROVAR ENTERITIDIS IN FOOD AND ENVIRONMENTAL SAMPLES, METHODS AND COMPOSITIONS THEREFOR

Life Technologies Corpora...

1. A method for determining the presence of S. Enteritidis in a sample comprising:
combining the sample with a culture medium for enriching Salmonella species for a time sufficient to generate a sample enriched for said species;

extracting nucleic acid from at least some of the enriched sample to obtain extracted nucleic acid;
contacting the extracted nucleic acid with at least one primer pair selected from a first primer pair of SEQ ID NO:1 and SEQ
ID NO:3, a second primer pair of SEQ ID NO:10 and SEQ ID NO: 12, and a third primer pair of SEQ ID NO: 13 and SEQ ID NO: 15,
under real-time polymerase chain reaction (PCR) amplification conditions to generate amplified nucleic acid; and

detecting at least some of the amplified nucleic acid, thereby determining the presence of S. Enteritidis in the sample, wherein the method does not cross-react with S. Paratyphi C.

US Pat. No. 9,145,361

SDP-CONTAINING HETEROBIFUNCTIONAL AGENTS

LIFE TECHNOLOGIES CORPORA...

18. A method of click-labeling a carrier molecule or solid support, said method comprising:
contacting said carrier molecule or solid support comprising a nucleophilic group X and having the formula Rb—X with a compound of Formula IA or a salt thereof:


wherein
L is a linker,
R1 is a halogen,

R2 is a halogen,

R3 comprises a water solubilizing group, and

Ra is a click-reactive group selected from the group consisting of an alkyne reactive moiety, an azide reactive moiety, a diene,
a dienophile, an epoxide or an aziridine compound;

and
forming a compound of Formula I or a salt thereof:

wherein
L is the linker,
Ra is the click-reactive group, and

Rb is the carrier molecule or solid support comprising the nucleophilic group X.

US Pat. No. 9,097,663

GEL ELECTROPHORESIS, IMAGING, AND ANALYSIS METHODS, DEVICES, SYSTEMS, AND MATERIALS

LIFE TECHNOLOGIES CORPORA...

1. A gel electrophoresis device comprising:
a housing;
a gel processing system said gel processing system comprising at least one, optionally more than one, gel holder configured
to hold a gel cassette in a vertical orientation, and at least one, optionally more than one, buffer reservoir;

a gel illumination system;
an image capture system, said image capture system being configured to provide real time imaging of at least one electrophoresis
gel during an electrophoresis run, wherein said real-time imaging comprises simultaneously imaging a gel, visible or fluorescent
bands, and migration of the visible or fluorescent bands; and

an image analysis system;
wherein the gel processing system, the gel illumination system, the image capture system, and the image analysis system are
all housed within the housing, and wherein the systems are operably associated and automated.

US Pat. No. 9,080,968

METHODS AND SYSTEMS FOR POINT OF USE REMOVAL OF SACRIFICIAL MATERIAL

Life Technologies Corpora...

1. A sensor, comprising:
an array of chemically-sensitive field effect transistors (chemFETs), each chemFET in the array having a floating gate structure
including an upper surface;

a dielectric layer over the upper surfaces of the floating gate structures of the chemFETs in the array, the dielectric layer
including cavities extending to the upper surfaces of the floating gate structures and corresponding to sensing surfaces of
the chemFETs;

a conformal protective layer over the sensing surfaces, sidewalls of the cavities, and top surface of the array.

US Pat. No. 9,067,910

CHEMILUMINESCENT COMPOSITIONS, METHODS, ASSAYS AND KITS FOR OXIDATIVE ENZYMES

Life Technologies Corpora...

1. A dioxetane of the form (I):
where T is

wherein R can independently be any branched alkyl or cycloalkyl group which provides stabilization for the dioxetane or where
both R groups together form a cycloalkyl or polycycloalkyl moiety spiro bound to the dioxetane ring, wherein each R group
or the spiro bound moiety can be unsubstituted or substituted with one or more electron withdrawing groups or electron-donating
groups, or groups providing oxidative isozyme substrate recognition, and

wherein R1 comprises an aryl group, or an alkyl group of 1-20 carbon atoms, which can be optionally substituted with 1 or more halogen
atoms; and

wherein R2, R3, R4, and R6 can be independently H, or are selected from the group consisting of halo (F, Cl, Br, I), trialkylammonium (—NR3+), alkylamido (—NHCOR, (—NRCOR), arylamido (—NHCOAr, NRCOAr, NArCOAr), arylcarbamoyl (—NHCOOAr, —NRCOOAr), alkylcarbamoyl
(—NHCOOR, NRCOOR), cyano (—CN), nitro (—NO2), ester (—COOR, COOAr), alkyl- or arylsulfonamido (—NHSO2R, —NHSO2Ar), trifluoromethyl (—CF3), alkyl (—R), aryl (—Ar), alkyl- or arylamidosulfonyl (—SO2NHCOR, —SO2NHCOAr), alkyl- or arylsulfonyl (—SO2R, —SO2Ar), alkyl- or arylthioethers (—SR, —SAr), alkoxy (—OR), or aryloxy (—OAr) substituents, and

wherein R5 is a group that can be removed upon activation by an oxidative enzyme; and

wherein X is selected from the group consisting of S, N and O.

US Pat. No. 9,404,887

CHEMICAL COATING OF MICROWELL FOR ELECTROCHEMICAL DETECTION DEVICE

Life Technologies Corpora...

1. A device comprising:
an array of chemical sensitive field effect transistor sensors, a sensor of the array of chemical sensitive field effect transistor
sensors including a sensor pad;

a well structure defining an array of wells disposed over the array of chemical sensitive field effect transistor sensors,
a well of the array of wells corresponding with the sensor pad of the sensor of the array of chemical sensitive field effect
transistor sensors, the well structure defining a sidewall of the well, a bottom of the well disposed over the sensor pad;
and

a silane chemical disposed on the sidewall and not the bottom of the well of the array of wells, the silane chemical having
the formula R—[Yn]-Si—[X1X2X3], wherein R is an organofunctional group, Y is (CH2) or (C2H4O), n is an integer, and [X1X2X3]
comprises one or more hydrolysable groups.

US Pat. No. 9,334,523

SUBSTRATES AND METHODS FOR STAINING LIVE STEM CELLS

LIFE TECHNOLOGIES CORPORA...

1. A composition comprising a substrate contacted with a live stem cell, wherein the substrate is cell permeable and is capable
of being modified by an enzyme specific to the live stem cell into a modified substrate, wherein the modified substrate is
both permeable and detectable such that the live stem cell can be identified by detecting the presence of the modified substrate,
wherein the substrate and the modified substrate are non-toxic, and wherein the substrate is a xanthene derivative, the xanthene
derivative is a fluorescein derivative, the fluorescein derivative is a fluorescein diphosphate and the fluorescein diphosphate
has the structure of formula II:

where:
R1, R2, R3, and R4 are individually chosen from alkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl;
R6 and R7 are individually chosen from H, alkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl;
X and Y are individually chosen from H, halogen, amino alkoxy, SH, SR, alkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl;
Z and R5 are individually chosen from H, COOH, COOR, OH, amino, alkoxy, halogen, alkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl;
and
m and n individually range from 1 to 3.

US Pat. No. 9,315,859

DDAO COMPOUNDS AS FLUORESCENT REFERENCE STANDARDS

Life Technologies Corpora...

1. A method comprising:
(a) contacting a sample which may comprise at least one target polynucleotide with at least one probe and a reference dye
to form a mixture, wherein each of the at least one probes comprises a target-specific moiety, a reporter dye and a quencher
dye, wherein each target-specific moiety is an oligonucleotide and is specific for a different target and each reporter dye
is different from the other reporter dyes and is different from the reference dye, and wherein the reference dye has formula
(I):


wherein:
each of R1 to R3 and R6 to R8 is independently —H, halogen, —CO2H, —CO2R, —SO3H, —SO3R, —CH2CO2H, —CH2CO2R, —CH2SO3H, —CH2SO3R, —CH2NH2, —CH2NHR, —NO2, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkoxy, and substituted C1-C6 alkoxy, wherein R is C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkoxy, and substituted C1-C6 alkoxy;

R4 and R5 taken separately are selected from C1-C6 alkyl, and C1-C6 substituted alkyl, or R4 and R5 taken together are selected from C3-C7 cycloalkyl, C4-C7 unsaturated cycloalkyl, C3-C7 substituted cycloalkyl, or C4-C7 substituted unsaturated cycloalkyl;

(b) amplifying a target polynucleotide in the mixture to form an amplified mixture;
(c) measuring fluorescence emitted by the reference dye; and
(d) measuring fluorescence emitted by at least one reporter dye.

US Pat. No. 9,094,211

SYSTEMS AND METHODS FOR IDENTIFYING AN INDIVIDUAL

LIFE TECHNOLOGIES CORPORA...

1. A method of identifying an individual comprising the steps of:
a) retrieving individualized identification information comprising a plurality of partial individualized identification hashes
of the individual each partial identification hash comprising individualized biometric data of a first class and a partial
individualized biometric data of a second class;

b) retrieving the plurality of partial individualized identification hashes;
c) accessing at least one interrogation database comprising a plurality of interrogation biometric data of the second class;
d) hashing each of the plurality of interrogation biometric data of the second class together with the individualized biometric
data of the first class to form a plurality of interrogation database identification hashes;

e) comparing each of the plurality, of interrogation database identification hashes with the plurality of partial individualized
identification hashes; and

f) reporting whether a match is identified.

US Pat. No. 9,297,762

SPATIAL POSITIONING OF SPECTRALLY LABELED BEADS

Life Technologies Corpora...

1. A multiplex assay detection apparatus, comprising:
a plurality of spectrally labeled bodies bound to a surface of a solid support,
wherein the spectrally labeled bodies are spatially resolved and each comprise a plurality of different fluorescent labels
used to encode discrete and different emission spectra wherein each emission spectrum has a plurality of signals at differing
wavelengths;

an excitation energy source configured to excite the plurality of spectrally labeled bodies;
a sensor configured to detect the emission spectrum of each spectrally labeled body; and
a processor configured to utilize machine-readable code including a library of identifiable substances and their associated
emission spectra to identify the identifiable substance associated with each spectrally labeled body.

US Pat. No. 9,255,258

NUCLEOTIDE TRANSIENT BINDING FOR SEQUENCING METHODS

Life Technologies Corpora...

1. A system comprising: a polymerase which is bound with a template nucleic acid molecule that is bound to a polymerization
initiation site, and a nucleotide which is transiently bound to the active site of the polymerase in a template-dependent
manner, and a cation that inhibits nucleotide incorporation by the polymerase, where the cation is present at a concentration
that inhibits nucleotide incorporation by the polymerase, and where the polymerase is a mutant RB69 polymerase comprising
the amino acid sequence of SEQ ID NO:5.

US Pat. No. 9,228,948

SPATIAL POSITIONING OF SPECTRALLY LABELED BEADS

Life Technologies Corpora...

1. A method comprising:
restraining a plurality of spectrally labeled bodies with affinity binding so as to define a multiplexed array, wherein the
spectrally labeled bodies are spatially resolved and comprise a plurality of fluorescent labels used to encode discrete and
different emission spectra wherein each emission spectrum has a plurality of signals at differing wavelengths;

directing an image of the multiplexed array of bodies onto a sensor to sense spectra generated by the bodies; and
identifying the bodies from the spectra sensed by the sensor.

US Pat. No. 9,134,271

PARTICLE QUANTIFYING SYSTEMS AND METHODS USING ACOUSTIC RADIATION PRESSURE

Life Technologies Corpora...

1. A method for quantifying the amount of analyte bound to a particle in a flow cytometer comprising:
binding a particle having a known amount of a calibration dye and the particle having a specificity for an analyte to the
analyte having a lifetime related signal to form an analyte-particle complex;

acoustically and hydrodynamically focusing the analyte-particle complex;
passing the analyte-particle complex through an interrogation zone through which a light from a light source is passed wherein
the interrogation zone is located within a flow cytometer;

measuring the signal related to the binding event in the interrogation zone;
measuring an overlapping signal from the calibration dye; and
calculating the amount of analyte present by comparing the analyte related signal to the calibration dye signal.

US Pat. No. 9,096,898

METHOD OF DETERMINING THE NUCLEOTIDE SEQUENCE OF OLIGONUCLEOTIDES AND DNA MOLECULES

LIFE TECHNOLOGIES CORPORA...

1. A method of analyzing a nucleic acid molecule, the method comprising:
(a) providing a template/primer duplex;
(b) contacting the duplex with a single type of unlabeled and unblocked deoxyribonucleotide in the presence of a polymerase
under conditions that allow extension of the primer by incorporation of at least one deoxyribonucleotide to the 3? end of
the primer, wherein the contacting occurs in a reaction cell; and

(c) non-optically detecting in the reaction cell whether extension of the primer has occurred.

US Pat. No. 9,355,213

VISUALIZATION TOOL FOR QPCR GENOTYPING DATA

Life Technologies Corpora...

1. A non-transitory computer-readable storage medium encoded with instructions, executable by a processor, for a visualization
tool for genotyping data, the instructions comprising:
providing instructions for a thermal cycling instrument to perform a full thermal cycle run;
receiving by the processor a first data set at a first time for a sample during the run, wherein the first data set comprises
a first intensity signal for a first probe and a first intensity signal for a second probe;

receiving by the processor a second data set at a second time for the sample during the run, wherein the second data set comprises
a second intensity signal for the first probe and a second intensity signal for the second probe;

presenting an end user with a visualization tool, wherein the visualization tool provides a display of the data selected from:
generating by the processor a first plot from the first data set and displaying the first plot, wherein the display provides
a first confidence value for the first data set; and;

generating by the processor a second plot from the second data set and displaying the second plot, wherein the display provides
a second confidence value for the second data set; and

stopping the thermal cycle run and calling the genotype before run completion when confidence values exceed a defined threshold.

US Pat. No. 9,212,385

FLUORINATED RESORUFIN COMPOUNDS AND THEIR APPLICATION

Life Technologies Corpora...

1. A compound having the formula:

wherein
A is OR8 or NR9R10;

E is OR8 or NR9R10;

wherein
R8 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted heteroalkyl, unsubstituted heteroalkyl, substituted heterocycloalkyl,
unsubstituted heterocycloalkyl, substituted carboxyalkyl, unsubstituted carboxyalkyl, substituted sulfoalkyl, unsubstituted
sulfoalkyl, substituted acyl, unsubstituted acyl, substituted haloalkyl, unsubstituted haloalkyl, substituted alkoxy, unsubstituted
alkoxy, carrier molecule, or solid support;

R9 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted heteroalkyl, unsubstituted heteroalkyl, substituted heterocycloalkyl,
unsubstituted heterocycloalkyl, substituted carboxyalkyl, unsubstituted carboxyalkyl, substituted sulfoalkyl, unsubstituted
sulfoalkyl, substituted acyl, unsubstituted acyl, substituted haloalkyl, unsubstituted haloalkyl, substituted alkoxy, unsubstituted
alkoxy, carrier molecule, or solid support;

R10 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted heteroalkyl, unsubstituted heteroalkyl, substituted heterocycloalkyl,
unsubstituted heterocycloalkyl, substituted carboxyalkyl, unsubstituted carboxyalkyl, substituted sulfoalkyl, unsubstituted
sulfoalkyl, substituted acyl, unsubstituted acyl, substituted haloalkyl, unsubstituted haloalkyl, substituted alkoxy, unsubstituted
alkoxy, carrier molecule, or solid support; or

a member independently selected from
R9 in combination with R10;

R9 in combination with R3;

R9 in combination with R6;

R10 in combination with R4; and

R10 in combination with R5
together with the atoms to which they are joined, form a ring which is a 5-, 6- or 7-membered heterocycloalkyl, a substituted
5-, 6- or 7-membered heterocycloalkyl, a 5-, 6- or 7-membered heteroaryl, or a substituted 5-, 6- or 7-membered heteroaryl;

R1 is substituted alkyl, unsubstituted alkyl, substituted heteroalkyl, unsubstituted heteroalkyl, substituted aryl, unsubstituted
aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heterocycloalkyl, unsubstituted heterocycloalkyl, OR8 or NR9R10
X1 is oxygen or sulfur;

X is oxygen;
R2 is hydrogen, halogen, substituted alkyl, unsubstituted alkyl, substituted alkoxy, unsubstituted alkoxy, substituted alkylthio,
unsubstituted alkylthio, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, sulfo, nitro,
carboxyl, hydroxyl, a carrier molecule, or a solid support;

R3 is hydrogen, halogen, substituted alkyl, unsubstituted alkyl, substituted alkoxy, unsubstituted alkoxy, substituted alkylthio,
unsubstituted alkylthio, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, sulfo, nitro,
carboxyl, hydroxyl, a carrier molecule, or a solid support;

R4 is hydrogen, halogen, substituted alkyl, unsubstituted alkyl, substituted alkoxy, unsubstituted alkoxy, substituted alkylthio,
unsubstituted alkylthio, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, sulfo, nitro,
carboxyl, hydroxyl, a carrier molecule, or solid support;

R5 is hydrogen, halogen, substituted alkyl, unsubstituted alkyl, substituted alkoxy, unsubstituted alkoxy, substituted alkylthio,
unsubstituted alkylthio, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, sulfo, nitro,
carboxyl, hydroxyl, a carrier molecule, or a solid support;

R6 is hydrogen, halogen, substituted alkyl, unsubstituted alkyl, substituted alkoxy, unsubstituted alkoxy, substituted alkylthio,
unsubstituted alkylthio, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, sulfo, nitro,
carboxyl, hydroxyl, a carrier molecule, or a solid support;

R7 is hydrogen, halogen, substituted alkyl, unsubstituted alkyl, substituted alkoxy, unsubstituted alkoxy, substituted alkylthio,
unsubstituted alkylthio, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, sulfo, nitro,
carboxyl, hydroxyl, a carrier molecule, or a solid support; or

a member independently selected from
R2 in combination with R3; and

R6 in combination with R7
together with the atoms to which they are joined, form a ring which is a 5-, 6- or 7-membered cycloalkyl, a substituted 5-,
6- or 7-membered cycloalkyl, a 5-, 6- or 7-membered heterocycloalkyl, a substituted 5-, 6- or 7-membered heterocycloalkyl,
a 5-, 6- or 7-membered aryl, a substituted 5-, 6- or 7-membered aryl, a 5-, 6- or 7-membered heteroaryl, or a substituted
5-, 6- or 7-membered heteroaryl;

with the proviso that at least one member selected from R2, R3, R4, R5, R6 and R7 is fluorine.

US Pat. No. 9,181,472

MAGNESIUM-BASED COATINGS FOR NANOCRYSTALS

Life Technologies Corpora...

1. A bright nanocrystal comprising a core and a shell, wherein the bright nanocrystal: a) has a characteristic fluorescence
emission wavelength in the visible range, b) is photostable, and c) provides fluorescence intensity that is at least about
twice the fluorescence intensity of a conventional nanocrystal having a CdSe core that is sized to have the same emission
wavelength as the bright nanocrystal, wherein the core comprises ZnSe or ZnCdSe and the shell consists essentially of ZnS
and MgS, wherein the amount of MgS in the shell is sufficient to increase the photostability of the nanocrystal relative to
an otherwise identical nanocrystal that does not contain magnesium in its shell.

US Pat. No. 9,309,565

KARYOTYPING ASSAY

Life Technologies Corpora...

1. A method for determining the copy number of at least one test locus on at least one chromosome in a test sample, the method
comprising:
interrogating at least one test locus on at least one chromosome in the test sample with at least one primer and at least
one probe, wherein the interrogating includes quantifying the copy number of at least one test locus, and wherein the at least
one test locus is located on a region of the chromosome that is not within a copy number variable region (CNVR) on the chromosome;
and

determining the copy number of at least one chromosome in the test sample on which at least one of the interrogated test loci
is located.

US Pat. No. 9,422,384

HYDROPHOBIC DIACRYLAMIDE COMPOUND

Life Technologies Corpora...

1. A method of forming a polymer, the method comprising:
forming an emulsion having a hydrophobic phase including a monomer and a compound of the formula:

or monosilylated derivative thereof, wherein R4, R5, or R6 are independently selected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a
combination thereof, and R1, R2, R3, R7, R8, or R9 are independently selected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a
combination thereof; and

polymerizing the monomer and the compound to form the polymer.

US Pat. No. 9,512,465

METHODS AND COMPOSITIONS FOR LABELING NUCLEIC ACIDS

Life Technologies Corpora...

1. A method of differentially labeling DNA, comprising steps of:
contacting a first cell with an effective amount of a first nucleoside analogue that comprises a first azide group such that
the nucleoside analogue is incorporated into DNA of the first cell;

contacting a second cell with an effective amount of a second nucleoside analogue that comprises a second azide group such
that the nucleoside analogue is incorporated into DNA of the second cell;

contacting the first cell with a first reagent comprising a first label attached to a first substituted triarylphoshine, such
that a Staudinger ligation occurs between the first azide and first substituted triarylphosphine; and

contacting the second cell with a second reagent comprising a second label attached to a second substituted triarylphosphine,
such that a Staudinger ligation occurs between the second azide and second substituted triarylphosphine.

US Pat. No. 9,423,323

MODIFIED CARBOCYANINE DYES AND THEIR CONJUGATES

Life Technologies Corpora...

1. A compound having a structure of the formula:
wherein R3 is -L-Rx, L is C6 alkyl, Rx is a phosphoramidite, R2, R4 and R12 is methyl, and Z is O.
US Pat. No. 9,144,575

ANTI-VIRAL AZIDE CONTAINING COMPOUNDS

LIFE TECHNOLOGIES CORPORA...

1. A method of treating a subject infected with a plant, an insect or an animal virus and in need of treatment for the infection,
the method comprising:
administering to the subject a therapeutically effective amount of an azide-modified fatty acid or pharmaceutically acceptable
salt thereof,

wherein the fatty acid is one that is attached directly or indirectly to a protein through a palmitoylation pathway reaction
in a cell, wherein, the infectivity of the virus is inhibited, thereby treating the subject.

US Pat. No. 9,868,826

POLYMER SUBSTRATES FORMED FROM CARBOXY FUNCTIONAL ACRYLAMIDE

Life Technologies Corpora...

1. A method of forming a particle, the method comprising:
in a disperse phase within an aqueous suspension, polymerizing a plurality of mer units having the formula:

wherein R1 is an alkyl group having between 3 and 10 carbons or is a polyether group having between 1 and 10 ether units, wherein R2 is a linear or branched alkyl group having between 3 and 8 carbons or a silyl group, and wherein R3 is hydrogen or an alkyl group having between 1 and 6 carbons;

thereby forming a polymeric particle including a plurality of hydrophobic protection groups; and
converting the polymeric particle to a hydrophilic particle.

US Pat. No. 9,194,000

METHODS AND APPARATUS FOR MEASURING ANALYTES USING LARGE SCALE FET ARRAYS

Life Technologies Corpora...

1. A method of making a bead array, the method comprising:
contacting a substrate having a surface comprising discrete reaction sites disposed within a flow cell with a solution introduced
into the flow cell and including a population of different beads, the surface includes 103 of the discrete reaction sites; and

applying centrifugal force to the substrate or the solution, or both, such that at least a subpopulation of the population
of different beads associates with the discrete reaction sites.

US Pat. No. 9,487,603

HYDROPHILIC POLYMERIC PARTICLES AND METHODS FOR MAKING AND USING SAME

LIfe Technologies Corpora...

1. A system comprising:
an array of wells, at least one well of the array of wells being operatively connected with an ISFET sensor; and
a plurality of hydrogel particles having a coefficient of variance of not greater than 5%, at least one of the hydrogel particles
of the plurality of hydrogel particles being disposed in a well of the array of wells.

US Pat. No. 9,453,264

DIRECT QUANTITATIVE PCR ABSENT MINOR GROOVE BINDERS

LIFE TECHNOLOGIES CORPORA...

5. A method comprising combining a fluorescently labeled probe and a filter paper contacted to a specimen in a reaction vessel,
performing a quantitative real-time polymerase chain reaction (qrtPCR) and detecting a level of fluorescence emanating from
the reaction vessel with a charge coupled device during a thermal cycle while the paper is in the reaction vessel, wherein
the probe is not conjugated with a minor groove binder and the probe is a reverse complement to a target nucleic acid from
a virus and the specimen is not from a child less than a month old.

US Pat. No. 9,270,264

SYSTEM FOR REDUCING NOISE IN A CHEMICAL SENSOR ARRAY

Life Technologies Corpora...

1. A system comprising:
a power supply;
a clock circuitry to generate a plurality of clock signals, each clock signal of the plurality of clock signals being synchronous
with a primary clock signal, and the first, second, and third clock signals of the plurality of clock signals being asynchronous
to each other; and

a plurality of switchers, each switcher of the plurality of switchers communicatively coupled to the power supply and the
clock circuitry, wherein

a first switcher of the plurality of switchers receives the first clock signal, a second switcher of the plurality of switchers
receives the second clock signal, and a third switcher of the plurality of switchers receives the third clock signal,

the first, second and third switchers are disposed on the same substrate,
the first, second, and third clock signals have different frequencies,
the first clock signal has a frequency greater than a frequency of the second clock signal and the second clock signal has
a frequency greater than the frequency of the third clock signal, wherein the frequency of the first clock signal is a multiple
of the frequency of the second clock signal and is a multiple of the frequency of the third clock signal, and

a rising edge of the first clock signal is offset in a range of ½ to (n?1)/2 cycles of the primary clock signal, where “n”
is the number of cycles of the primary clock signal in a cycle of the second clock signal.

US Pat. No. 9,475,012

GAS SPARGERS AND RELATED CONTAINER SYSTEMS

LIFE TECHNOLOGIES CORPORA...

1. A sparger comprising:
a base comprising:
a tubular member having a first end and an opposing second end and an interior surface bounding a passage extending therebetween;
a first flange encircling and radially outwardly projecting from the tubular member; and
a second flange encircling and radially outwardly projecting from the tubular member, the second flange being spaced apart
from the first flange; and

a flexible sparging sheet secured to the first flange so that a compartment is formed between the first flange and the sparging
sheet, the passage of the tubular member communicating with the compartment, at least a portion of the sparging sheet being
gas permeable so that gas passed through the tubular member and into the compartment passes out through the sparging sheet.

US Pat. No. 9,194,840

SENSOR ARRAYS AND METHODS FOR MAKING SAME

Life Technologies Corpora...

1. A system comprising:
a sensor including a sensor pad; and
a well wall structure defining a well operatively connected to the sensor pad, the sensor pad associated with a lower surface
of the well, the well wall structure defining an upper surface and a wall surface extending between the upper surface and
the lower surface, the upper surface defined by an upper buffer material having an intrinsic buffer capacity of at least 2×1017 groups/m2 and not greater than 1×1021 groups/m2, the wall surface being defined by a wall material having an intrinsic buffer capacity of not greater than 1.7×1017 groups/m2.

US Pat. No. 9,058,646

SIMULTANEOUS ACQUISITION OF BIOMETRIC DATA AND NUCLEIC ACID

LIFE TECHNOLOGIES CORPORA...

1. A system for collection of a biological sample comprising a nucleic acid sample and at least one ridge and valley signature
of an individual comprising:
a. at least a first imaging component comprising a scanning surface configured to permit an energy way to penetrate the scanning
surface, wherein the energy wave is configured to image the at least one ridge and valley signature of an appendage of the
individual;

b. a substrate positioned upon the scanning surface, wherein the substrate is configured to permit the collection of the at
least one ridge and valley signature of the appendage through the substrate and to permit collection of the biological sample
as the appendage is withdrawn from the substrate and wherein the substrate is chemically modified with a chemical functional
group selected from the group consisting of an amino group, a chloromethyl group, a hydroxyl group, a carboxyl group and a
quaternary amino group.

US Pat. No. 9,657,281

POLYMERASE COMPOSITIONS, METHODS OF MAKING AND USING SAME

Life Technologies Corpora...

1. A composition comprising an isolated recombinant polypeptide comprising a polymerase polypeptide having an amino acid sequence
at least 90% identical to SEQ ID NO: 35 and maintaining substitutions H46R, E446Q, H572R, N487R, D423K, and H281M, wherein
the isolated recombinant polypeptide has DNA polymerase activity.
US Pat. No. 9,476,892

COMPOSITION AND METHOD FOR MEASURING THALLIUM INFLUX AND EFFLUX

Life Technologies Corpora...

1. A method for detecting the activity of potassium ion channel in a cell, the method comprising:
providing a loading buffer solution to the cell, the loading buffer solution comprising a thallium indicator and a physiological
concentration of chloride ions, wherein the thallium indicator is an acetoxymethyl ester of a xanthene-based compound comprising
a thallium ion-complexing moiety, wherein the thallium ion-complexing moiety is 2-methoxy-aniline-N,N-diacetic acid or a derivative
thereof, and wherein the chloride ions are at a concentration of about 50 mM to about 150 mM;

providing a stimulus buffer to the cell, wherein the stimulus buffer comprises thallium at a concentration of about 0.1 mM
to about 5.0 mM, thereby causing thallium influx into the cell through the potassium ion channel; and

measuring a change in at least one optical property of the thallium indicator in response to thalium influx thereby detecting
the activity of the potassium ion channel.

US Pat. No. 9,314,764

APPARATUS FOR ASSAY, SYNTHESIS AND STORAGE, AND METHODS OF MANUFACTURE, USE, AND MANIPULATION THEREOF

Life Technologies Corpora...

2. A method of loading a platen having opposing surfaces and a plurality of through-holes extending between the surfaces,
the method comprising:
(a) providing a sample mixture to be loaded into the through-holes;
(b) dipping the platen into the mixture, thereby loading at least some of the through-holes with the sample and leaving a
portion of the mixture on at least one surface of the opposing surfaces; and

(c) retaining at least some of the loaded sample in (b) within at least one of the through-holes while passing the platen
through a fluid that has an affinity for the at least one surface but that is immiscible with the mixture, thereby wiping
the portion of the mixture from the at least one surface.

US Pat. No. 9,388,420

ALKYNYL-DERIVATIZED CAP ANALOGS, PREPARATION AND USES THEREOF

Life Technologies Corpora...

1. A biological cell comprising a 1,4-disubstituted triazole-derivatized capped RNA.
US Pat. No. 9,139,667

CONJUGATED POLYMERIC PARTICLE AND METHOD OF MAKING SAME

Life Technologies Corpora...

1. A method of conjugating a biomolecule to a substrate, the method comprising:
exchanging a positive ion ionically associated with a negatively charged group of the biomolecule with a positively-charged
counter ion having two to four hydrocarbon groups to form a biomolecule complex including the positively-charged counter ion
ionically associated with the charged group of the biomolecule;

dispersing the biomolecule complex in a nonaqueous solvent; and
coupling the biomolecule complex to the substrate in the presence of the nonaqueous solvent thereby conjugating the biomolecule
to the substrate.

US Pat. No. 9,289,735

SYSTEMS FOR INACTIVATING FLUID CULTURES THROUGH HEATING

Life Technologies Corpora...

1. A fluid heating system comprising:
a tank assembly having an interior surface bounding a chamber, the tank assembly comprising:
a sidewall encircling the chamber and extending between a first end and an opposing second end, the first end bounding an
opening to the chamber; and

a lid movable between a first position wherein the opening to the chamber is exposed and a second position wherein the lid
is disposed over the opening;

a collapsible bag removably disposed within the chamber of the tank assembly, the collapsible bag bounding a compartment adapted
to hold a fluid;

means for controlling the temperature of fluid within the collapsible bag when the collapsible bag is positioned within chamber
of the tank assembly; and

a mixing element disposed within the compartment of the collapsible bag.

US Pat. No. 9,263,638

PREPARATION OF STABLE, BRIGHT LUMINESCENT NANOPARTICLES HAVING COMPOSITIONALLY ENGINEERED PROPERTIES

LIFE TECHNOLOGIES CORPORA...

1. A dispersion of nanocrystals, comprising
a population of luminescent semiconductor nanocrystals dispersed in an organic solvent system, wherein each nanocrystal in
the population comprises a crystalline CdSeTe core and a protective, passivating overlayer, wherein the core comprises CdaSebTec in which the ratio a:(b+c) is in the range of about 0.7 to about 1.5 and the ratio c:(b+c) is in the range of about 0.001
to about 0.20.

US Pat. No. 9,540,606

STIRRED TANK REACTOR SYSTEMS AND METHODS OF USE

Life Technologies Corpora...

1. A method of mixing a fluid, the method comprising:
positioning a flexible bag into a chamber of a support housing;
delivering a fluid into a compartment of the flexible bag; and
moving a mixing element within the compartment of the flexible bag so as to mix the fluid therein, the step of moving the
mixing element comprising:

removably inserting a drive shaft into a tubular connector having a first end and an opposing second end, the first end of
the tubular connector being connected to the bag, the second end of the tubular connector being secured to an impeller disposed
within the compartment of the flexible bag; and

rotating the drive shaft so that the impeller rotates relative to the bag.

US Pat. No. 9,535,080

METHOD AND APPARATUS FOR AUTOMATED SAMPLE MANIPULATION

Life Technologies Corpora...

1. An apparatus comprising:
a platform including a horizontal surface and a channel extending in the horizontal surface to receive an array of compartments;
the array of compartments disposed in the channel, the array including one row of compartments disposed in a plurality of
columns, the one row, the array including first and last compartments at opposite ends of the each row and further compartments
located between the first and last compartments of the row;

a magnet disposed in the channel of the platform;
a translation device including a mounting;
a pipette tip attached to the mounting of the translation device; and
the apparatus programmed to facilitate relative movement of the array and the magnet within the channel to apply and remove
a magnetic field from the first compartment of the row of the array and further programmed to control the translation device
to position the pipette tip in compartments of the row of the array;

wherein, when the magnetic field is applied to the first compartment, the magnet is not positioned adjacent to a compartment
of the further compartments located between the first and last compartments of the respective one or more rows.

US Pat. No. 9,376,698

MUTANT DNA POLYMERASES

LIFE TECHNOLOGIES CORPORA...

1. An isolated mutant Tfi DNA polymerase comprising an amino acid sequence having at least 95% identity to SEQ ID NO:2 with
a D?A point mutation at amino acid position 144 of SEQ ID NO:2 and an E?D point mutation at position 437 of SEQ ID NO:2.
US Pat. No. 9,228,227

SYNTHESIS OF 2?, 3?-DIDEOXYNUCLEOSIDES FOR AUTOMATED DNA SYNTHESIS AND PYROPHOSPHOROLYSIS ACTIVATED POLYMERIZATION

Life Technologies Corpora...

1. A method for preparing a 2?,3?-dideoxyguanosine support structure, the method comprising:
(a) reacting 2?,3?-dideoxyguanosine with N,N-dimethylformamide dimethylacetal, to obtain a first intermediate;
(b) reacting the first intermediate with 4,4-dimethoxytriphenylmethyl chloride to obtain a second intermediate comprising
a dimethylformamide protecting group;

(c) cleaving the dimethylformamide protecting group off the second intermediate to obtain a third intermediate;
(d) reacting the third intermediate with adipic anhydride to obtain a 2?,3? dideoxy guanosine derivative; and
(e) coupling the 2?,3? dideoxy guanosine derivative to a solid support,thereby obtaining the 2?,3?-dideoxyguanosine support structure.
US Pat. No. 9,139,666

HYDROPHILIC POLYMERIC PARTICLES AND METHODS FOR MAKING AND USING SAME

Life Technologies Corpora...

1. A method of forming a particle, the method comprising:
polymerizing a plurality of mer units of a hydrophilic monomer having a hydrophobic protection group, thereby forming a polymeric
particle including a plurality of the hydrophobic protection groups;

removing at least a portion of plurality of the hydrophobic protection groups from the polymeric particle to form a hydrophilic
particle; and

binding an oligonucleotide to the hydrophilic particle.
US Pat. No. 9,068,221

METHOD OF ANALYSIS OF GENETIC MARKERS

Life Technologies Corpora...

1. A method of detecting an allele of a human identification panel, the method comprising:
binding specifically a set of probes to a single stranded nucleic acid segment derived from a locus of the human identification
panel, the segment including a microsatellite region having between 5 and 30 k-mer repeat units, wherein k is in a range of
2 to 6, the set of probes including a first subset of k-mer binding probes complementary to the k-mer repeat units;

directing the segment through a porin protein nanopore of a nanopore device with an applied voltage, the bound set of probes
being stripped from the segment as the segment passes through the porin protein nanopore;

measuring with the nanopore device an ion current signal including current spikes corresponding to the stripping of probes
of the first subset of k-mer binding probes as the segment passes through the protein nanopore of the nanopore device, a number
of current spikes of the ion current signal indicative of the number of k-mer repeat units;

detecting the allele based on a characteristic of the current spikes of the ion current signal, wherein the characteristic
includes the number of the current spikes.

US Pat. No. 9,046,477

SPATIAL POSITIONING OF SPECTRALLY LABELED BEADS

Life Technologies Corpora...

1. A method comprising:
restraining a plurality of spectrally labeled bodies with affinity binding so as to define a multiplexed array, wherein the
spectrally labeled bodies are spatially resolved and comprise a plurality of fluorescent labels used to encode discrete and
different absorption and emission spectra wherein each emission spectrum has a plurality of signals at differing wavelengths;

directing an image of the multiplexed array of bodies onto a sensor to sense spectra generated by the bodies; and
identifying the bodies from the spectra sensed by the sensor.

US Pat. No. 9,868,945

LINKING METHODS, COMPOSITIONS, SYSTEMS, KITS AND APPARATUSES

LIFE TECHNOLOGIES CORPORA...

1. A composition comprising an active B st DNA polymerase enzyme, or a mutant or fragment thereof that can catalyze nucleotide
incorporation, covalently linked to a first polynucleotide, a second polynucleotide which is hybridized to the first polynucleotide
and a sequencing primer capable of hybridizing to the second polynucleotide, wherein the second polynucleotide is a single
stranded DNA (ssDNA) template that is covalently linked to a surface and wherein the composition is present in an aqueous
solution with an ionic strength equal to or greater than 200 mM.

US Pat. No. 9,594,870

TIME-WARPED BACKGROUND SIGNAL FOR SEQUENCING-BY-SYNTHESIS OPERATIONS

Life Technologies Corpora...

1. A method of sequencing a polynucleotide strand using a sequencing apparatus and reactor array adapted to perform sequencing-by-synthesis
operations, comprising:
flowing a series of nucleotide reagents onto a reactor array from an inlet to an outlet, wherein the reactor array has multiple
reaction confinement regions having different signal responses due to their different locations along a flow path of the nucleotide
reagents from the inlet to the outlet, wherein the polynucleotide strand is located in a loaded reaction confinement region
of the reactor array;

receiving signal data relating to chemical reactions resulting from the flowing of the series of nucleotide reagents onto
the reactor array having multiple reaction confinement regions, wherein the signal data include an output signal of an empty
reaction confinement region and an output signal of the loaded reaction confinement region;

determining an empty reaction confinement region function that models the output signal of a representative empty reaction
confinement region;

determining a time-warped empty reaction confinement region function by applying a time transformation to the empty reaction
confinement region function, wherein the time transformation changes a time scale of the empty reaction confinement region
function thereby adjusting for systematic time lag differences due to the location of the representative empty reaction confinement
region along the flow path of the nucleotide reagents from the inlet to the outlet;

applying the time-warped empty reaction confinement region function to the output signal of the loaded reaction confinement
region detected during the flowing to generate a corrected output signal; and

analyzing the corrected output signal to estimate a number of nucleotide incorporations having occurred for the polynucleotide
strand located in the loaded reaction confinement region in response to the flowed nucleotide reagents.

US Pat. No. 9,513,284

PYRENYLOXYSULFONIC ACID FLUORESCENT AGENTS

LIFE TECHNOLOGIES CORPORA...

1. A compound having structure VI:

wherein
designates a linker arm covalently attached to a reactive group, wherein the linker arm comprises a branched- or straight-chain,
saturated or unsaturated chain of atoms and wherein the linker arm is attached to the pyrene nucleus by a nitrogen;

the reactive group comprises a hydrazide; and
s and t are independently selected from the integers from 0 to 3, with the proviso that at least one of s and t is at least
1.

US Pat. No. 9,121,047

SYSTEM AND METHODS FOR MAKING AND PROCESSING EMULSIONS

Life Technologies Corpora...

1. A method of generating an amplified sample, the method comprising:
generating an emulsion from a carrier fluid and a sample fluid with an emulsion generator, the emulsion generator including
a carrier fluid port to receive the carrier fluid, a sample fluid port to receive the sample fluid, and an emulsion outlet
port, the emulsion generator including a membrane to generate an emulsion including the carrier fluid and the sample fluid,
the emulsion exiting the emulsion generator via the emulsion outlet port, the sample fluid including conjugated beads;

heating the emulsion to an amplification condition with a heater of an amplification device, the amplification device including
an inlet port in fluid communication with the emulsion outlet port and to receive the emulsion, the amplification device including
an effluent port, the amplified emulsion exiting the amplification device via the effluent port, the amplified emulsion including
amplified beads derived from the conjugated beads; and

breaking the emulsion following heating with a centrifuge device, the centrifuge device including an inlet conduit in fluid
communication with the effluent port and to receive the emulsion after heating, the centrifuge device further including a
rotor to receive a tube and a slinger to dispense the amplified emulsion received via the inlet conduit to the tube when the
rotor is spinning, the amplified beads being dispensed to the tube.

US Pat. No. 9,103,757

LASER CAPTURE MICRODISSECTION (LCM) EXTRACTION DEVICE AND DEVICE CARRIER, AND METHOD FOR POST-LCM FLUID PROCESSING

LIFE TECHNOLOGIES CORPORA...

1. A method for extracting biomolecules from a portion of cells from a cell sample on a carrier, wherein the cell sample includes
a plurality of cells, the method comprising:
contacting a stand-off portion of the carrier to a substrate, wherein the stand-off portion is configured to maintain a distance
between the substrate and a transfer film, wherein a cell sample is included on the substrate;

transferring a portion of cells selected for analysis from the cell sample included on the substrate to the transfer film,
wherein the transfer film is included on the carrier;

mating the carrier to an extraction device, wherein the extraction device is configured to remove biomolecules from the portion
of cells selected for analysis, wherein the extraction device comprises:

a carrier-receiving portion comprising a plurality of flanges, wherein the carrier-receiving portion comprises an inner surface,
wherein the carrier-receiving portion further includes a landing portion having a landing surface, the landing surface defining
an inner opening, and

a conduit interconnected to the carrier-receiving portion, the conduit extending between a first opening on the carrier-receiving
portion and a second opening at a second end, wherein the carrier-receiving portion is adapted to receive the carrier and
to form a reservoir by the carrier contacting the landing portion, wherein the carrier mating with the carrier-receiving portion
closes the inner opening to seal the inner opening to prevent fluid flow through a bottom surface;

deflecting the flanges by passing a at least a portion of the carrier between the flanges so as secure the carrier to the
extraction device in a compression-fit engagement;

forming the reservoir with the transfer film by contacting the stand-off portion to the landing surface, wherein the stand-off
portion and landing surface are configured so that the stand-off portion is not included in the reservoir;

providing fluid into the reservoir to extract biomolecules from the portion of cells from the transfer film; and
removing the fluid from the reservoir.

US Pat. No. 9,901,887

SYSTEMS AND METHODS FOR MAKING AND PROCESSING EMULSIONS

Life Technologies Corpora...

11. An integrated apparatus comprising:
an emulsion generator including a carrier fluid port to receive a carrier fluid, a sample vial to receive a sample fluid immiscible
with the carrier fluid, a displacement fluid port, and an emulsion outlet port, the emulsion generator including a membrane
to generate an emulsion including the carrier fluid and the sample fluid, the emulsion exiting the emulsion generator via
the emulsion outlet port, a tube extending from the displacement fluid port into the sample vial;

an amplification device including an inlet port in fluid communication with the emulsion outlet port and to receive the emulsion,
the amplification device including a heater to subject the emulsion to amplification conditions and including an effluent
port, the amplified emulsion exiting the amplification device via the effluent port; and

a centrifuge device including:
a rotor to receive a centrifuge tube and including a slinger to dispense the amplified emulsion to the centrifuge tube;
a lid disposed over the rotor and including an opening;
an adapter secured to the lid in the opening, the adapter including a casing having a cavity and defining a port through the
lid, the adapter including a carriage disposed in the cavity of the casing and axially moveable within the casing, the adaptor
including a motivator to apply force to the carriage in an axial direction away from the lid, the carriage defining a bore
to receive a needle or cannula to extend through the carriage, port, and opening, the needle or cannula coupled to a tube
in fluid communication with the effluent port of the amplification device.

US Pat. No. 9,809,849

METHODS AND SYSTEMS FOR PURE DYE INSTRUMENT NORMALIZATION

Life Technologies Corpora...

1. A method for normalizing laboratory instruments with pure dyes, comprising:
providing at least one reference instrument and a test instrument, each instrument comprising at least one excitation filter
and at least one emission filter arranged in pairs;

providing a plurality of pure dyes, each dye comprising a fluorescent component and contained in a pure dye plate comprising
a plurality of wells;

generating fluorescent spectra from the reference instrument and the test instrument for multiple pure dyes across multiple
filter combinations;

creating a pure dye matrix, Mref, for the reference instrument and a pure dye matrix, M, for the test instrument;
calculating correction factors for each filter pair and multiplying the correction factors by the pure dye spectra;
normalizing the corrected pure dye spectra;
generating multicomponent data.

US Pat. No. 9,495,741

METHODS AND SYSTEMS FOR STREAMLINING OPTICAL CALIBRATION

LIFE TECHNOLOGIES CORPORA...

1. A method for calibrating a biological instrument comprising:
executing a pre-scan calibration comprising:
acquiring an image of at least one biological sample array;
evaluating the image to determine fluorescence levels;
modifying the fluorescence levels by adjusting an excitation source with an exposure time and a duty cycle to provide strong
fluorescence levels without saturation;

determining a first region of interest within the image, wherein the first region of interest comprises a first plurality
of locations on the at least one biological array; and

identifying within the first region of interest, a plurality of image elements associated with each of the first plurality
of locations on the at least one biological array.

US Pat. No. 9,458,485

SYSTEM AND METHODS FOR MAKING AND PROCESSING EMULSIONS

Life Technologies Corpora...

1. An integrated apparatus comprising:
an emulsion generator including a carrier fluid port to receive a carrier fluid, a sample vial to receive a sample fluid immiscible
with the carrier fluid, a displacement fluid port, and an emulsion outlet port, the emulsion generator including a membrane
to generate an emulsion including the carrier fluid and the sample fluid, the emulsion exiting the emulsion generator via
the emulsion outlet port, a tube extending from the displacement fluid port into the sample vial;

an amplification device including an inlet port in fluid communication with the emulsion outlet port and to receive the emulsion,
the amplification device including a heater to subject the emulsion to amplification conditions and including an effluent
port, the amplified emulsion exiting the amplification device via the effluent port; and

a centrifuge device including an inlet conduit in fluid communication with the effluent port and to receive the amplified
emulsion, the centrifuge device further including a rotor to receive a centrifuge tube and including a slinger to dispense
the amplified emulsion received via the inlet conduit to the centrifuge tube when the rotor is spinning.

US Pat. No. 9,365,839

POLYMERASE COMPOSITIONS AND METHODS

Life Technologies Corpora...

1. A mutant DNA polymerase comprising the amino acid sequence of SEQ ID NO:7.

US Pat. No. 9,304,084

SPATIAL POSITIONING OF SPECTRALLY LABELED BEADS

Life Technologies Corpora...

11. A method for making a multiplex assay, comprising:
affixing a plurality of spectrally labeled bodies to an assay substrate in a spatially resolved configuration, wherein each
of the spectrally labeled bodies include a plurality of different markers used to encode discrete and different emission spectra,
wherein each emission spectrum has a plurality of signals at differing wavelengths.

US Pat. No. 9,110,015

METHOD AND SYSTEM FOR DELTA DOUBLE SAMPLING

Life Technologies Corpora...

1. A system for performing delta double sampling, comprising:
a pixel, comprising:
a chemically-sensitive sensor for providing an input signal in response to a chemical reaction;
a select transistor for providing a reference sample;
a sampling circuit configured to take the reference sample from the select transistor and an input signal sample from the
chemically-sensitive sensor through the select transistor;

a comparator circuit to output a first comparison result of the reference sample to a reference voltage and to perform analog-to-digital
conversion by outputting a second comparison result that includes a signal indicating a value of the input signal sample in
comparison to a digital threshold reference signal; and

a latch to provide a control signal to the sampling circuit in response to the first comparison result and output a digital
signal value in response to the second comparison result.

US Pat. No. 9,732,112

SYNTHESIS OF 2?,3?-DIDEOXYNUCLEOSIDES FOR AUTOMATED DNA SYNTHESIS AND PYROPHOSPHOROLYSIS ACTIVATED POLYMERIZATION

Life Technologies Corpora...

1. A method for preparing a 2?,3?-dideoxyadenosine support structure, the method comprising:
(a) reacting 2?,3?-dideoxyadenosine with 4,4-dimethoxytriphenylmethyl chloride to obtain a first intermediate;
(b) reacting pentane-1,3,5-tricarboxylic acid with oxalyl chloride to obtain a second intermediate;
(c) reacting the first intermediate with the second intermediate to obtain a 2?,3?-dideoxyadenosine derivative; and
(d) coupling the 2?,3?-dideoxyadenosine derivative to a solid support, thereby obtaining the 2?,3?-dideoxyadenosine support
structure.

US Pat. No. 9,515,676

METHODS AND COMPUTER PROGRAM PRODUCTS FOR COMPRESSION OF SEQUENCING DATA

Life Technologies Corpora...

1. A compression method, comprising:
measuring a waveform associated with a chemical event occurring on a sensor array, the measuring including digitizing voltage
signals using an analog to digital converter to produce a plurality of frames of measured values for the waveform, the voltage
signals generated by the sensor array in response to the chemical event, wherein the chemical event is indicative of a number
of nucleotide incorporations in a genetic sequencing reaction, wherein the waveform comprises at least one region associated
with expected measured values and at least one region associated with unpredictable measured values;

applying a first compression process to the waveform using a processor, the first compression process including an averaging
of one or more frames in one or more portions of the waveform to form frame-averaged data, wherein a number of frames of frame-averaged
data is less than a number of frames in the plurality of frames of measured values;

applying a keyframe delta compression to the frame-averaged data using the processor, wherein the keyframe delta compression
comprises calculating a difference between a current frame of the frame-averaged data and a previous frame of the frame-averaged
data associated with the waveform;

forming a compressed data structure including a keyframe of the frame-averaged data and a plurality of the calculated differences
subsequent to the keyframe, wherein the compressed data structure represents the keyframe and the plurality calculated differences
in a number of bytes that is less than an original number of bytes representing the frame-averaged data;

determining compression information corresponding to one or more compressed data structures;
storing the compression information and the one or more compressed data structures in a memory; and
applying a second compression process to the waveform using the processor, the second compression process including a truncating
of data corresponding to a portion of the waveform that is not related to a nucleotide incorporation component of the waveform.

US Pat. No. 9,493,414

DEVELOPMENT OF NOVEL DETERGENTS FOR USE IN PCR SYSTEMS

Life Technologies Corpora...

16. A method for synthesizing a target nucleic acid comprising the steps of:
a) combining said target nucleic acid with at least one polymerase and at least one compound selected from:
wherein each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,
26, 27, 28, 29, or 30,as part of a reaction mixture; and
b) synthesizing said target nucleic acid.
US Pat. No. 9,365,838

CONJUGATES OF BIOMOLECULES TO NANOPARTICLES

Life Technologies Corpora...

1. A composition, comprising a polymerase-nanoparticle conjugate including a polymerase linked to a nanoparticle, wherein
the conjugate has polymerase activity, and wherein the polymerase-nanoparticle conjugate includes a template nucleic acid
molecule, a polymerization initiation site, and lacks a helicase.

US Pat. No. 9,139,319

PACKAGING SYSTEMS AND METHODS FOR COLD CHAIN SHIPMENTS

Life Technologies Corpora...

1. A packaging system for cold chain shipment, the packaging system comprising:
a container having interior surface portions defining an interior volume;
a plurality of cellulose sheets comprising respective cellulose elements, at least two of the plurality of cellulose sheets
disposed along respective interior surface portions of the container, the plurality of cellulose sheets defining a space configured
to receive an item for cold chain shipment; and

a cold source disposed within the interior volume;
wherein adjacent cellulose elements of the cellulose sheets define a plurality of pockets configured to trap a gas and contact
the item for cold chain shipment.

US Pat. No. 9,073,650

FLUID MANIFOLD SYSTEMS

Life Technologies Corpora...

1. A fluid manifold system comprising:
a first manifold comprising first portions of opposing flexible sheets welded together to form a fluid flow path therebetween,
a fluid inlet communicating with the fluid flow path; and

a plurality of receiving containers in fluid communication with the fluid flow path of the first manifold, each receiving
container bounding a compartment, the plurality of receiving containers comprising second portions of the same continuous
opposing flexible sheets welded together so as to form the receiving containers, the receiving containers being integral with
the first manifold with the compartments for the receiving containers being bounded between the opposing flexible sheets;

wherein the fluid flow path of the first manifold comprises:
a primary flow path communicating with the fluid inlet of the first manifold; and
a plurality of spaced apart secondary flow paths that branch off of the primary flow path, each secondary flow path being
in fluid communication with a corresponding one of the plurality of receiving containers, each secondary flow path having
a diameter that is smaller than a diameter of the primary flow path and smaller than a diameter of the compartment of each
of the receiving containers;

wherein each receiving container further comprises a tubular connector in communication with the compartment thereof, each
tubular connector being spaced apart from the secondary flow path communicating with the corresponding receiving container.

US Pat. No. 9,062,079

HYDROPHOBIC DIACRYLAMIDE COMPOUND

Life Technologies Corpora...

1. A compound of the formula:

wherein R1 and R2 are independently selected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives
thereof, or a combination thereof, and R3, R4, R5, R6, and R7 are independently selected from hydrogen, alkyl, heteroalkyl,
cycloalkyl, hydroxyalkyl, acyl, oxycarbonyl, aryl, ether derivatives thereof, a silyl, or a combination thereof.

US Pat. No. 10,072,298

GENE FUSIONS AND GENE VARIANTS ASSOCIATED WITH CANCER

LIFE TECHNOLOGIES CORPORA...

1. A method of detecting a CEP85L-ROS1 gene fusion in a sample from a subject, the method comprising:generating a reaction mixture comprising nucleic acid from the sample and a pair of primers that specifically hybridize to a target nucleic acid comprising the sequence of SEQ ID NO:17 , wherein the sample comprises the target nucleic acid;
amplifying the target nucleic acid using the pair of primers, thereby producing amplicons;
sequencing the amplicons; and
detecting the presence of a CEP85L-ROS1 gene fusion comprising the sequence of SEQ ID NO:17 in the sequenced amplicons.

US Pat. No. 9,808,799

APPARATUS FOR AND METHOD OF PROCESSING BIOLOGICAL SAMPLES

Life Technologies Corpora...

1. A bioprocessing cartridge comprising:
a first bioprocessing chamber, wherein the first bioprocessing chamber includes first solid support, and wherein the first
solid support comprises a cell lysate clarification filter;

a second bioprocessing chamber, wherein the second bioprocessing chamber has a fluid volume between about 250 ?l and about
100 ml and includes a second solid support, wherein the second solid support comprises a plurality of magnetic beads;

a plurality of fluid channels in fluid communication with the at least one bioprocessing chamber, wherein at least two of
the plurality of fluid channels have differentially sized diameters;

at least one access valve, wherein the access valve is placed within a flow path between a fluid connector and one of the
plurality of fluid channels, each fluid connector configured to fluidly connect the cartridge to at least one fluid container;
and

at least one control fluid connector, wherein the at least one control fluid connector is configured to form a sealed connection
with a control fluid manifold and to provide a control fluid to actuate the at least one access valve.

US Pat. No. 9,518,285

CHEMILUMINESCENT COMPOSITIONS, METHODS, ASSAYS AND KITS FOR OXIDATIVE ENZYMES

LIFE TECHNOLOGIES CORPORA...

1. An assay kit for the detection of the presence of an oxidative enzyme in an aqueous sample, comprising a dioxetane of formula
(I):

where T is

where R can independently be any branched alkyl or cycloalkyl group which provides stabilization for the dioxetane or where
both R groups together form a cycloalkyl or polycycloalkyl moiety spiro bound to the dioxetane ring, wherein each R group
or the spiro bound moiety can be unsubstituted or substituted with one or more electron-withdrawing groups or electron donating
groups, or groups providing preferential oxidative isozyme substrate recognition, and

wherein R1 is an aryl group, or an alkyl group of 1-20 carbon atoms, which can be optionally substituted with 1 or more halogen atoms,
and

wherein R2, R3, R4, and R6 can be independently H, or are selected from the group consisting of halo (F, Cl, Br, I), trialkylammonium (—NR3+), alkylamido (—NHCOR, (—NRCOR), arylamido (—NHCOAr, NRCOAr, NArCOAr), arylcarbamoyl (—NHCOOAr, —NRCOOAr), alkylcarbamoyl
(—NHCOOR, NRCOOR), cyano (—CN), nitro (—NO2), ester (—COOR, COOAr), alkyl- or arylsulfonamido (—NHSO2R, —NHSO2Ar), trifluoromethyl (—CF3), alkyl (—R), aryl (—Ar), alkyl- or arylamidosulfonyl (—SO2NHCOR, —SO2NHCOAr), alkyl- or arylsulfonyl (—SO2R, —SO2Ar), alkyl- or arylthioethers (—SR, —SAr), alkoxy (—OR), or aryloxy (—OAr) substituents, and

wherein R5 is a group that can be removed upon activation by an oxidative enzyme; and

wherein X is selected from the group consisting of S, N and O.
US Pat. No. 9,481,872

NUCLEIC ACID-FREE THERMOSTABLE ENZYMES AND METHODS OF PRODUCTION THEREOF

Life Technologies Corpora...

1. An active thermostable enzyme preparation that is substantially free of nucleic acids as determined by an assay for measuring
incorporation of a nucleotide in the absence of an exogenous nucleic acid template.
US Pat. No. 9,458,500

METHOD OF DETERMINING THE NUCLEOTIDE SEQUENCE OF OLIGONUCLEOTIDES AND DNA MOLECULES

Life Technologies Corpora...

1. An apparatus for DNA sequencing comprising:
a) at least one reaction chamber including a DNA primer/template system which produces a detectable reaction event when a
DNA polymerase enzyme incorporates an unlabeled and unblocked deoxyribonucleotide monophosphate onto the 3? end of the primer
strand;

b) a component for introducing into, and evacuating from, said reaction chamber at least one reagent selected from the group
consisting of: buffers, electrolytes, DNA template, DNA primer, unlabeled and unblocked deoxyribonucleotides, and polymerase
enzymes;

c) a system for converting said detectable reaction event into an electrical signal based on an electrical potential generated
from said detectable reaction event in the at least one reaction chamber; and

d) a voltmeter configured to measure said electrical signal in the at least one reaction chamber.

US Pat. No. 9,440,925

SDP-CONTAINING HETEROBIFUNCTIONAL AGENTS

Life Technologies Corpora...

2. A kit for click-labeling a carrier molecule or solid support, wherein said kit comprises:
a) a compound of Formula IA or a salt thereof:

wherein
L is a linker,
R1 is a halogen,

R2 is a halogen,

R3 comprises a water solubilizing group, and

Ra is a click-reactive group; and

b) instructions for click-labeling the carrier molecule or solid support.
US Pat. No. 9,416,413

ALTERNATIVE NUCLEOTIDE FLOWS IN SEQUENCING-BY-SYNTHESIS METHODS

LIFE TECHNOLOGIES CORPORA...

1. A method for improving homopolymer classification accuracy, comprising:
providing a template polynucleotide strand, a primer, and a polymerase in a microwell, the template polynucleotide strand
being coupled to or associated with a bead;

successively exposing the template polynucleotide strand to a plurality of each of four kinds of dNTP reagent flows, each
dNTP reagent flow having a single kind of dNTP, wherein the plurality of reagent flows are selected according to an ordering,
the ordering being such that (a) a flow of one kind of dNTP reagent is always followed by a flow of a different kind of dNTP
reagent, (b) at least one flow of each kind of dNTP reagent is followed by a flow of the same kind of dNTP reagent after a
single intervening flow of a different kind of dNTP reagent, and (c) the number of flows of each of the four kinds of dNTP
reagent flows in the ordering is the same, wherein the successively exposing comprises consecutively repeating the plurality
of reagent flows according to the ordering one or more times; and

obtaining, using a sensor configured to provide information about reactions taking place in the microwell, an incorporation
signal comprising values generally proportional to a number of dNTP incorporation(s) that result when a base in the template
polynucleotide strand is complementary to one of the flowed dNTP reagents.

US Pat. No. 9,409,942

METHODS FOR PRODUCTION OF PROTEINS

LIFE TECHNOLOGIES CORPORA...

1. A pre-stained protein molecular weight ladder composition comprising a plurality of homogeneously stained populations of
proteins, each stained population of proteins having a known and different molecular weight, the molecules comprising each
homogeneously stained protein population having a mobility during gel electrophoresis and having the property that if they
were further incubated with dye their mobility during gel electrophoresis would remain unchanged.

US Pat. No. 9,346,063

CENTRIFUGE AND METHOD FOR LOADING A DEVICE

Life Technologies Corpora...

1. A centrifuge device comprising:
a motor operable to spin in a first direction and in a second direction opposite the first direction;
a rotor coupled to a motor, the rotor to spin within a plane in the first direction or the second direction responsive to
the motor, the rotor having a recess and an axle projecting from a side of the recess; and

a carrier slidably and pivotally coupled to the axle, the carrier including a first tab on a first side and a second tab on
a second side, the carrier to slide along the axle and to rotate about the axle out of the plane and engage the rotor with
the first tab at a first angle in response to the rotor spinning in the first direction, the carrier to slide along the axle
and to rotate about the axle out of the plane and engage the rotor with the second tab at a second angle in response to the
rotor spinning in the second direction.

US Pat. No. 9,284,524

HEAT EXCHANGER SYSTEM WITH FLEXIBLE BAG

Life Technologies Corpora...

1. A heat exchanger system comprising:
a heat exchanger comprising:
a body plate having a first side face and an opposing second side face, the body plate bounding a fluid channel disposed between
the opposing side faces and extending between an inlet port and an outlet port; and

a first side plate having an inside face; and
a flexible first bag comprised of one or more sheet of polymeric material, the first bag bounding a fluid pathway that extends
between a fluid inlet and a fluid outlet, the first bag being removably retained between the body plate and the first side
plate so that at least a portion of the first bag rests against the first side face of the body plate when the fluid pathway
of the first bag is filled with a fluid, the fluid channel of the body plate being sealed from fluid communication with the
fluid pathway of the first bag.

US Pat. No. 9,243,284

ENZYMATIC NUCLEIC ACID SYNTHESIS: COMPOSITIONS AND METHODS FOR INHIBITING PYROPHOSPHOROLYSIS

Life Technologies Corpora...

1. A composition comprising a reaction mixture containing a modified nucleotide including a gamma phosphate group attached
to a molecular and/or atomic tag, a nucleotide polymerizing agent, a primer, a template and a polyphosphate compound containing
at least four phosphate groups.

US Pat. No. 9,134,269

METHODS AND APPARATUS FOR MEASURING ANALYTES USING LARGE SCALE FET ARRAYS

Life Technologies Corpora...

1. An apparatus comprising:
a device structure including an array of sensors, a sensor of the array of sensors including an electrode pad disposed at
a surface of the device structure and forming a portion of an ion sensitive field effect transistor; and

a wall structure disposed over the surface of the device structure defining an array of wells substantially corresponding
with the array of sensors, wherein the electrode pad of the sensor of the array of sensors underlies a surface of a well proximal
to the device structure, the wall structure including at least one layer including a polymeric material.

US Pat. No. 9,063,081

ULTRA-FAST NUCLEIC ACID SEQUENCING DEVICE AND A METHOD FOR MAKING AND USING THE SAME

Life Technologies Corpora...

1. A field effect transistor type detector, comprising:
a silicon substrate including a device, the device comprising:
a source region;
a drain region; and
at least one detecting region between the source and drain regions, the at least one detecting region having a recess or an
opening; and

an insulator disposed about the recess or opening separating a polymer from the device when the polymer passes through the
recess or opening;

wherein a charge on a component of the polymer passing through the recess or opening induces an image charge sufficient to
increase the conductivity of the detecting region by an amount related to the charge of the component of the polymer, the
device to detect the component of the polymer based on the conductivity of the detecting region.

US Pat. No. 10,131,936

DDAO COMPOUNDS AS FLUORESCENT REFERENCE STANDARDS

Life Technologies Corpora...

1. A kit for amplification comprising:a buffer,
a selection of nucleotides,
a reference dye, and
instructions for carrying out an assay;
wherein the reference dye has a structure according to formula (I):

wherein:
each of R1 to R3 and R6 to R8 is independently —H, halogen, —CO2H, —CO2R, —SO3H, —SO3R, —CH2CO2H, —CH2CO2R, —CH2SO3H, —CH2SO3R, —CH2NH2, —CH2NHR, —NO2, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkoxy, and substituted C1-C6 alkoxy, wherein R is C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkoxy, and substituted C1-C6 alkoxy;
R4 and R5 taken separately are selected from C1-C6 alkyl, and C1-C6 substituted alkyl, or R4 and R5 taken together are selected from C3-C7 cycloalkyl, C4-C7 unsaturated cycloalkyl, C3-C7 substituted cycloalkyl, or C4-C7 substituted unsaturated cycloalkyl.

US Pat. No. 10,035,116

FLUID MIXING SYSTEM WITH TILTABLE SUPPORT HOUSING

Life Technologies Corpora...

1. A fluid mixing system comprising:a support housing bounding a chamber;
a flexible container disposed within the chamber of the support housing, the flexible container being adapted to hold a fluid;
means for mixing a fluid contained within the flexible container by repeatedly moving the support housing and the flexible container contained therein; and
means for mixing a fluid contained within the flexible container without movement of the support housing, the means comprising a mixing element movably disposed within the flexible container.
US Pat. No. 9,733,212

SHARPLY RESOLVING LABELED PROTEIN MOLECULAR WEIGHT STANDARDS

LIFE TECHNOLOGIES CORPORA...

1. A pre-labeled protein standard set comprising a plurality of labeled proteins, each protein having a known and different
molecular weight ranging from 10 Da to 260 kDa, wherein one or more of said plurality of labeled proteins is a selectively
labeled protein comprising a heterologous chromophore or a heterologous fluorophore label conjugated to a first amino acid,
wherein said selectively labeled protein has fewer than one lysine residue per ten kilodalton (kDa) molecular weight of said
selectively labeled protein, wherein at least a first selectively labeled protein comprises an amino acid sequence that has
at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 14.

US Pat. No. 9,671,363

CHEMICAL SENSOR WITH CONSISTENT SENSOR SURFACE AREAS

Life Technologies Corpora...

1. A method for manufacturing a chemical sensor, the method comprising:
forming a chemically-sensitive field effect transistor including a floating gate conductor having an upper surface;
forming a material defining an opening extending to the upper surface of the floating gate conductor, the material comprising
a first dielectric underlying a second dielectric; and

forming a conductive element contacting the upper surface of the floating gate conductor and extending a distance along a
sidewall of the opening, wherein forming the material and forming the conductive element include:

forming the first dielectric on the floating gate conductor, the first dielectric defining a cavity extending to the upper
surface of the floating gate conductor;

depositing the second dielectric thereon;
etching the second dielectric to expose the upper surface of the floating gate conductor, thereby defining the opening; and
forming the conductive element within the opening.

US Pat. No. 9,540,689

METHOD OF DETERMINING THE NUCLEOTIDE SEQUENCE OF OLIGONUCLEOTIDES AND DNA MOLECULES

Life Technologies Corpora...

1. A method for sequencing DNA, comprising:
a) providing a primer/template system comprising a template sequence hybridized to a primer oligonucleotide and a DNA polymerase
that lacks 5? to 3? exonuclease activity;

b) contacting the primer/template system with a single type of deoxyribonucleotide under conditions that produce a detectable
signal when the DNA polymerase incorporates a deoxyribonucleotide onto the 3? end of the primer oligonucleotide, wherein the
single type of deoxyribonucleotide is an unlabeled and unblocked deoxyribonucleotide, and wherein the contacting occurs in
a reaction chamber;

c) converting, with a device, the detectable signal into an electrical signal based on an electrical potential generated across
the device by the detectable signal, wherein the converting occurs in the reaction chamber, and wherein the amplitude of the
electrical signal corresponds to the number of nucleotides incorporated onto the 3? end of the primer oligonucleotide by the
DNA polymerase; and

d) detecting the electrical signal generated by the detectable signal produced in the reaction chamber.

US Pat. No. 9,506,930

MONITORING AND MANIPULATING CELLULAR TRANSMEMBRANE POTENTIALS USING NANOSTRUCTURES

LIFE TECHNOLOGIES CORPORA...

1. A method for assaying changes in transmembrane potential, the method comprising:
providing at least one target, wherein the target is a cell, cellular fraction, or artificial membrane structure;
contacting the target with at least one semiconductor nanocrystal to form a treated target, wherein each nanocrystal further
comprises a hydrophobic surface coating;

stimulating the treated target, such that the transmembrane potential of the target changes, wherein the at least one semiconductor
nanocrystal emits light in direct response to a voltage fluctuation resulting from the change in transmembrane potential of
the target, wherein the light is directly emitted from the at least one semiconductor nanocrystal without transfer of energy
to a second molecule that then emits an optical signal;

assaying emission by detecting the directly emitted light from the at least one semiconductor nanocrystal; and
correlating the emission with the change in transmembrane potential.

US Pat. No. 9,493,656

PHENYL XANTHENE DYES

Life Technologies Corpora...

1. A lipid soluble fluorescent phenyl xanthene dye having a structure of formula I:

where A is —OH or NR3?R3?;
B is ?O or =N+R6?R6?;
R1 is selected from hydrogen, Rx, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or alternatively, R1 may be taken together with R2 to form part of a benzo, naptho or polycyclic aryleno group
which is optionally substituted with one or more of the same or different Ra or suitable Rb groups;

R2 is selected from hydrogen, Rx, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or alternatively, R2 may be taken together with R1 to form part of a benzo, naptho or polycyclic aryleno group
which is optionally substituted with one or more of the same or different Ra or suitable Rb groups;

R3?, when present, is selected from hydrogen, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the
same or different Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different
Ra or suitable Rb groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or
different Ra or suitable Rb groups;

R3?, when present, is selected from (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or, alternatively, R3? may be taken together with R4 to form a 5- or 6-membered ring which is optionally substituted
with one or more of the same or different Ra or suitable Rb groups;

R4 is selected from hydrogen, Rx, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or, alternatively, when A is —NR3?R3?, R4 may be taken together with R3? to form a 5- or 6-membered ring which
is optionally substituted with one or more of the same or different Ra or suitable Rb groups;

R5 is selected from hydrogen, Rx, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or, alternatively, when B is —NR6?R6?+, R5 may be taken together with R6? to form a 5- or 6-membered ring which
is optionally substituted with one or more of the same or different Ra or suitable Rb groups;

R6?, when present, is selected from (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or, alternatively R6? may be taken together with R5 to form a 5- or 6-membered ring which is optionally substituted
with one or more of the same or different Ra or suitable Rb groups;

R6?, when present, is selected from hydrogen, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the
same or different Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different
Ra or suitable Rb groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or
different Ra or suitable Rb groups;

R7 is selected from hydrogen, Rx, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or, alternatively, R7 may be taken together with R8 to form part of a benzo, naptho or polycyclic aryleno group
which is optionally substituted with one or more of the same or different Ra or suitable Rb groups, or alternatively, when
B is —NR6?R6?+, R7 may be taken together with R6? to form a 5- or 6-membered ring optionally substituted with one or more
of the same or different Ra or suitable Rb groups;

R8 is selected from hydrogen, Rx, (C1-C20) alkyl or heteroalkyl optionally substituted with one or more of the same or different
Rb groups, (C5-C20) aryl or heteroaryl optionally substituted with one or more of the same or different Ra or suitable Rb
groups and (C6-C40) arylalkyl or heteroaryl alkyl optionally substituted with one or more of the same or different Ra or suitable
Rb groups, or, alternatively, R8 together with R7 may form part of a benzo, naptho or polycyclic aryleno group which is optionally
substituted with one or more of the same or different Ra or suitable Rb groups;

R11 and/or R15 are selected from alkyl, heteroalkyl, alkoxy, halo, haloalkyl, amino, alkylthio, cyano, isocyano, mercaptocyanato, nitro,
and sulfinyl, and R12, R13, and R14 are, independently, selected from hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, alkoxy, halo, haloalkyl, amino, alkylthio,
cyano, isocyano, cyanato, mercaptocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, carboxyl, and carboxyamide;

Rx is selected from —NRcRc, —ORd, —SRd, halo, haloalkyl, —CN, —NC, —OCN, —SCN, —NO, —NO2, —N3, —S(O)Rd, —S(O)2Rd, —S(O)2ORd, —S(O)NRcRc, —S(O)2NRcRc, —OS(O)Rd, —OS(O)2Rd, —OS(O)2NRcRc, —C(O)Rd, —C(O)ORd, —C(O)NRcRc, —C(NH)NRcRc, —OC(O)Rd, —OC(O)ORd, —OC(O)NRcRc and —OC(NH)NRcRc;

Ra is selected from hydrogen, (C1-C8) alkyl or heteroalkyl, (C5-C20) aryl or heteroaryl and (C6-C28) arylalkyl or heteroarylalkyl;

Rb is selected from —NRcRc, ?O, —ORd, ?S, —SRd, ?NRd, ?NORd, halo, haloalkyl, —CN, —NC, —OCN, —SCN, —NO, —NO2, ?N2, —N3, —S(O)Rd, —S(O)2Rd, —S(O)2ORd, —S(O)NRcRc, —S(O)2NRcRc, —OS(O)Rd, —OS(O)2Rd, —OS(O)2NRcRc, —OS(O)2ORd, —OS(O)2NRcRc, —C(O)Rd, —C(O)ORd, —C(O)NRcRc, —C(NH)NRcRc, —OC(O)Rd, —OC(O)ORd, —OC(O)NRcRc and —OC(NH)NRcRc;

each Rc is independently hydrogen or Rd, or alternatively, each Rc is taken together with the nitrogen atom to which it is bonded to form a 5- to 8-membered saturated or unsaturated ring which
may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted
with one or more of the same or different Ra or Rd groups;

each Rd is independently Ra or Ra substituted with one or more of the same or different Ra or Re groups;

each Re is selected from —NRaRa, ?O, —ORa, ?S, —SRa, ?NRa, ?NORa, halo, haloalkyl, —CN, —NC, —OCN, —SCN, —NO, —NO2, ?N2, —N3, —S(O)Ra, —S(O)2Ra, —S(O)2ORa, —S(O)NRaRa, —S(O)2NRaRa, —OS(O)Ra, —OS(O)2Ra, —OS(O)2NRaRa, —OS(O)2ORd, —OS(O)2NRaRa, —C(O)Ra, —C(O)ORa, —C(O)NRaRa, —C(NH)NRcRa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRaRa and —OC(NH)NRaRa; and

wherein at least one of A, B, R1, R2, R4, R5, R7, R8, and R11-R15 has one or more lipophilic substituted groups selected from
(C4-C20) alkyls, (C5-C40) aryls, and/or (C6-C40) arylalkyls.

US Pat. No. 9,410,153

COMPOSITIONS AND METHODS FOR INHIBITION OF NUCLEIC ACIDS FUNCTION

Life Technologies Corpora...

1. A composite nucleic acid inhibitory molecule which comprises:
a 5? stem loop structure that does not bind to a target nucleic acid molecule, wherein the loop of the stem loop structure
consists of a non-nucleotide loop, and

a target binding nucleic acid segment which is 20 to 200 nucleotides in length, wherein the target binding nucleic acid segment
is modified to increase binding affinity to its target,

wherein the target nucleic acid molecule is a long non-coding RNA, and
wherein the stem loop structure is only at the 5? end of the target binding nucleic acid segment and
wherein the non-nucleotide loop is chosen from polyethylene glycol, C2-C18 alkane diol, styrene, stilbene, triazole, tetrazole,
poly abasic nucleoside, polysaccharide, peptide, polyamide, hydrazone, oxyimine, polyester, disulfide, polyamine, polyether,
peptide nucleic acid, cycloalkane, polyalkene, aryl, a combination thereof, and a derivative thereof.

US Pat. No. 9,410,923

ULTRA-FAST NUCLEIC ACID SEQUENCING DEVICE AND A METHOD FOR MAKING AND USING THE SAME

Life Technologies Corpora...

1. A detector comprising:
a source region;
a drain region;
a detection region disposed between the source region and the drain region, the detection region defining a distance between
the source region and the drain region on the order of the size of a single nucleotide base; and

a channel formed over the source region, the drain region, and the detection region;
wherein a charge on a component of a polymer passing through the channel induces an image charge sufficient to change the
conductivity of the detection region by an amount related to the charge of the component of the polymer, the device to detect
the component of the polymer based on the conductivity of the detection region.

US Pat. No. 9,410,187

METHODS OF USING FET LABELED OLIGONUCLEOTIDES THAT INCLUDE A 3??5? EXONUCLEASE RESISTANT QUENCHER DOMAIN AND COMPOSITIONS FOR PRACTICING THE SAME

Life Technologies Corpora...

1. A method for detecting the production of a primer extension product in a primer extension reaction mixture, said method
comprising:
(a) producing a primer extension mixture comprising a template nucleic acid, a nucleic acid polymerase having 3??5? exonuclease
activity, and a FET labeled oligonucleotide comprising a target-binding sequence, a fluorophore, a nucleic acid intercalator,
and a quencher, wherein said nucleic acid intercalator and said quencher are covalently bonded to the 3? end of said FET labeled
oligonucleotide;

(b) subjecting said primer extension mixture to primer extension reaction conditions; and
(c) detecting a fluorescent signal from said FET labeled oligonucleotide in said mixture, whereby a change in said fluorescent
signal is indicative of the presence of a primer extension product in said mixture.

US Pat. No. 9,404,920

METHODS AND APPARATUS FOR DETECTING MOLECULAR INTERACTIONS USING FET ARRAYS

Life Technologies Corpora...

1. A method for detecting bimolecular interactions, the method comprising:
providing a sample analyzer comprising an array of sensors, a given sensor in the array of sensors comprising: a chemFET including
a first gate dielectric between a substrate and a floating gate, and having a characteristic threshold voltage affected by
trapped charge in the first gate dielectric, and a transistor including a second gate dielectric between a gate terminal and
the substrate, wherein the gate terminal is coupled to the floating gate of the chemFET, and the second gate dielectric has
a thickness less than that of the first gate dielectric;

removing the trapped charge via the transistor by providing an electrical path for charge from the floating gate to the substrate;
providing at least one molecular species to the array of sensors; and
detecting a molecular interaction between the at least one molecular species and a second molecular species by detecting the
changes in electrical properties of the chemFET.

US Pat. No. 9,372,181

FLUORESCENT METAL ION INDICATORS WITH LARGE STOKES SHIFTS

Life Technologies Corpora...

1. A compound for the detection of metal ions, wherein the compound comprises:
a metal chelating BAPTA moiety; and,
a fluorophore comprising a nitrogen atom covalently bonded to one or two C?O groups or to one SO2 group, wherein the nitrogen atom is optionally substituted with a H, alkyl, or substituted alkyl group, wherein the nitrogen
atom in the fluorophore is covalently bonded to the metal chelating moiety by a linker, —(CR2)n—, wherein each R group is independently hydrogen, alkyl, or substituted alkyl; and n is 1-10.

US Pat. No. 9,341,631

LONG WAVELENGTH FLUOROGENIC INTRACELLULAR ION INDICATORS THAT ARE WELL RETAINED IN THE CYTOSOL

Life Technologies Corpora...

6. A method for identifying intracellular metal ions in a sample containing cells, comprising:
contacting the sample with an intracellular ion indicator compound, wherein the compound comprises a metal chelating moiety,
a fluorophore moiety and four or more lipophilic groups (GL) covalently bonded to the fluorophore moiety, through a linker wherein the lipophilic groups, when present in a live cell,
are cleaved resulting in four or more negatively charged groups;

incubating the sample for a period of time sufficient for the compound to enter a cell;
cleaving the four or more lipophilic groups; and
illuminating the sample with an appropriate wavelength, whereby the intracellular ions are identified, wherein the fluorophore
moiety and the four or more lipophilic groups (GL) covalently bonded to the fluorophore moiety has the structure:


wherein R9 and R10 are each independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino,
acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy,
aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy,
cyano, halo, hydroxy, nitro, SO3?, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl,
heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl and -L-(GL)w;

L is a linker;
GL is a lipophilic group that comprises an ester;

w is 1 or 2; and
p and q are each independently 0, 1 or 2.
US Pat. No. 9,260,757

HUMAN SINGLE NUCLEOTIDE POLYMORPHISMS

LIFE TECHNOLOGIES CORPORA...

1. A kit for human identification comprising: at least one pair of oligonucleotide primers for amplification of at least one
locus selected from SEQ ID NO: 1 (D13S317), SEQ ID NO: 2 (TH01), SEQ ID NO: 3 (vWA), SEQ ID NO: 4(D12S391), and SEQ ID NO:
5 (D6S1043) wherein one primer of the pair hybridizes to a SNP nucleobase within a primer binding site of the at least one
locus and at least one primer of the pair comprises a fluorescent label.

US Pat. No. 9,239,313

ION-SENSING CHARGE-ACCUMULATION CIRCUITS AND METHODS

Life Technologies Corpora...

1. An ion-sensitive circuit, comprising:
a charge-accumulation device to accumulate a plurality of charge packets as a function of an ion concentration of a fluid,
including

a first charge control electrode, above a first electrode semiconductor region, to control entry of charge into a gate semiconductor
region in response to a first control signal applied to the first electrode,

an electrically floating gate structure above a gate semiconductor region and below an ion-sensitive passivation surface configured
to receive the fluid, the floating gate including a gate electrode, at least two metal layer electrodes, and corresponding
via interconnections configured to electrically connect the gate electrode and at least two metal layer electrodes,

a second charge control electrode, above a second electrode semiconductor region, to control transmission of the plurality
of charge packets out of the gate semiconductor region and into a drain diffusion region in response to a second control signal
applied to the second electrode, and

a drain diffusion region to receive the plurality of charge packets from the gate semiconductor region via the second electrode
semiconductor region; and

at least one control and readout transistor to generate an output voltage as a function of the accumulated plurality of charge
packets at the drain diffusion region of the charge accumulation device, wherein the output voltage is representative of the
ion concentration of the solution.

US Pat. No. 9,234,239

SYSTEMS AND METHODS FOR ERROR CORRECTION IN DNA SEQUENCING

Life Technologies Corpora...

1. A method for obtaining sequence information about a template polynucleotide, the method comprising:
selecting a plurality of probes, each probe including at least one detectable label, and the plurality of probes including
a quantity N of different types of detectable labels;

combining the plurality of probes with the template polynucleotide for sequencing using a polynucleotide sequencer, wherein
each probe is complementary to one or more nucleotides within a sequence length K of the template polynucleotide, and the
template polynucleotide has a quantity L of nucleotide base types within the sequence length K;

measuring the combined template polynucleotide and probes to obtain encoded data representative of nucleotides within the
sequence length K of the template polynucleotide, the encoded data including a quantity M of detectable characteristics, wherein
each of said M detectable characteristics is one of said N different types of detectable labels, wherein said K, L, M, and
N quantities are such that a quantity NM is greater than a quantity LK, and wherein the encoded data is redundant regarding a characteristic of, or a sequence relationship between or among, one
or more of the nucleotides within the sequence length K of the template polynucleotide; and

decoding the encoded data to obtain sequence information of the template polynucleotide, wherein decoding the encoded data
includes detecting and resolving at least one of an error or an ambiguity in an identity of one or more nucleotides in the
template polynucleotide.

US Pat. No. 9,169,515

METHODS AND SYSTEMS FOR NUCLEIC ACID SEQUENCING VALIDATION, CALIBRATION AND NORMALIZATION

Life Technologies Corpora...

1. A method of processing nucleic acid sequencing data during a nucleic acid sequencing experiment, comprising:
placing a set of control solid supports each having a plurality of synthetic nucleic acid sequences attached thereto in a
detection area of a nucleic acid sequencing instrument, wherein the set of control solid supports comprises plural groups
of control solid supports that each have the same synthetic nucleic acid sequences attached thereto and wherein the synthetic
nucleic acid sequences are designed such that the synthetic nucleic acid sequences produce a predefined pattern of observable
signals during the nucleic acid sequencing experiment;

placing a template solid support having a nucleic acid sample to be sequenced attached thereto in a detection area of the
nucleic acid sequencing instrument along with the set of control solid supports;

performing a first ligation cycle to attach dye-labeled probe sequences to the synthetic nucleic acid sequences attached to
the control solid supports and to the nucleic acid sample attached to the template solid support;

detecting the dye-labeled probes attached to each of the synthetic nucleic acid sequences and the nucleic acid sample after
the first ligation cycle;

performing a second ligation cycle to attach a dye-labeled probe sequences to the synthetic nucleic acid sequences attached
to the control solid supports and to the nucleic acid sample attached to the template solid support;

detecting the dye-labeled probes attached to each of the synthetic nucleic acid sequences and the nucleic acid sample after
the second ligation cycle;

comparing an intensity of the detected dye-labeled probes attached to the synthetic nucleic acid sequences after the first
ligation cycle with an intensity of the detected dye-labeled probes attached to the synthetic nucleic acid sequences after
the second ligation cycle; and

adjusting an intensity of the detected dye-labeled probes attached to the nucleic acid sample after the second ligation cycle
based on the compared intensities,

wherein the predefined pattern of observable signals comprises transitions based on 12 of the 16 color transitions available
when using 4 colors between consecutive ligation cycles while prohibiting transitions of the same color.

US Pat. No. 9,139,874

BI-DIRECTIONAL SEQUENCING COMPOSITIONS AND METHODS

Life Technologies Corpora...

1. A method for obtaining sequence information from a portion of a nucleic acid template, comprising:
hybridizing a first primer to a template strand;
sequencing a portion of the nucleic acid template, wherein the sequencing includes extending the first primer, thereby forming
an extended first primer product that is complementary to a portion of the nucleic acid template;

introducing a nick into a portion of the template strand that is hybridized to the extended first primer product; wherein
the nick includes a free 5? end and a free 3? end in the template strand;

degrading a portion of the template strand from the free 5? end of the nick using a degrading agent, thereby generating a
single-stranded portion of the extended first primer product, wherein a portion of the extended first primer product remains
hybridized to an undegraded portion of the template strand; and

sequencing at least some of the single-stranded portion of the extended first primer product.

US Pat. No. 9,120,097

VERTICAL CLAMP DEVICE

Life Technologies Corpora...

1. A clamp device comprising:
a carriage including a vertical receptacle to receive a flow cell component and having an arm, the carriage translatable between
an insert position and a closed position;

a motivator to apply force to the carriage in the direction of the closed position away from the insert position;
a fluidics interface block including a fluidics interface to engage flow ports of the flow cell component;
an electronic interface setting to engage electronic pads of the flow cell, a setting guide associated with the electronic
interface to provide force to the flow cell component in a direction away from the electronic interface; and

a drive component translatable between the insert position and the closed position, the fluidics interface block to motivate
the fluidics interface into contact with the flow ports of the flow cell component and the electronic interface to engage
the electronic pads of the flow cell component when the drive component is in the closed position.

US Pat. No. 9,061,903

SULFONATE MODIFIED NANOCRYSTALS

Life Technologies Corpora...

1. A population of nanoparticles, comprising:
a plurality of nanoparticles dispersed in an organic solvent, wherein each nanoparticle includes a nanocrystal core including
a first semiconductor material, a shell including a second semiconductor material, and an outer layer comprising ligands that
each comprise a sulfonate, nitrate, borate, or fluorous anion group, wherein the anion group is bound to one or more metal
atoms of the second semiconductor material at the surface of the shell, wherein if the ligand comprises sulfonate, then the
sulfonate is selected from the group consisting of trifluoromethanesulfonate (triflate), fluoromethanesulfonate, methanesulfonate
(mesylate), nitrophenylsulfonate (nosylate), trifluorethylsulfonate, phenylsulfonate (besylate), and toluenesulfonate (tosylate).

US Pat. No. 10,107,828

CLAMP DEVICES FOR RECEIVING A CARTRIDGE AND METHODS FOR USING SAME

LIFE TECHNOLOGIES CORPORA...

18. A method of engaging a cartridge including fluidic ports on a first side and electronic contacts on a second side opposite the first side, the method comprising:applying the cartridge into a clamp device comprising:
a frame;
a carriage slidably engaged with the frame and including a receptacle to receive a cartridge including fluidics ports and electronic contacts, the carriage slidable between an open position and a closed position;
a fluidics interface to engage the fluidics ports of the cartridge when the carriage is in a closed position;
an electronic interface to engage the electronic contacts of the cartridge when the carriage is in the closed position;
a driver to draw the fluidics interface and the electronic interface together, the cartridge secured between the electronic interface and the fluidics interface; and
a sensor system to detect the presence of the cartridge in the receptacle;
motivating the carriage toward a closed position; and
detecting the cartridge with the sensor system, the sensor system preventing the driver from drawing the fluidics interface and the electronic interface together in the absence of the device.

US Pat. No. 9,555,451

METHOD FOR TREATING A SEMICONDUCTOR DEVICE

Life Technologies Corpora...

1. A method of treating a sensor array, the sensor array including a plurality of sensors and an isolation structure, a sensor
of the plurality of sensors having a sensor pad exposed at a surface of the sensor array, the isolation structure disposed
between the sensor pad and sensor pads of other sensors of the plurality of sensors, the method comprising:
exposing at least the sensor pad and the isolation structure to a treatment solution including an organo-silicon compound,
an organic acid, and an organic solvent; and

rinsing the treatment solution from the sensor pad.

US Pat. No. 9,494,951

TEMPERATURE CONTROL OF CHEMICAL DETECTION SYSTEM

Life Technologies Corpora...

1. An apparatus, comprising:
a chemical detection device including a sensor chip mounted thereon comprising a plurality of chemical sensors formed in a
circuit-supporting substrate and a microwell array disposed on the circuit-supporting substrate;

a valve block to fluidly couple a plurality of reagent containers to the chemical detection device;
a heat exchanger; and
a controller to control a fluid connection between the valve block and the chemical detection device, wherein the controller
is configured to adjust a temperature of a selected reagent from the plurality of reagent containers, via the heat exchanger,
prior to the selected reagent entering the chemical detection device;

wherein the sensor chip has an inlet for inflow of a fluid and an outlet for outflow of the fluid; and
wherein the sensor chip has a first temperature sensor placed at the inlet, a second temperature sensor placed at the outlet,
and third and fourth temperature sensors placed at two opposite corners of the sensor chip, and wherein the first, second,
third, and fourth temperature sensors are coupled to the controller.

US Pat. No. 9,482,614

INSTRUMENT FOR MONITORING POLYMERASE CHAIN REACTION OF DNA

LIFE TECHNOLOGIES CORPORA...

1. An instrument comprising:
an apparatus configured to hold a plurality of spaced-apart reaction regions;
a light source configured to direct an excitation beam toward the plurality of reaction regions;
a detector configured to receive emission beams from the reaction regions;
a first path from the light source to the apparatus, the instrument configured to direct the excitation beam along the first
path from the light source to the plurality of spaced-apart reaction regions;

a second path from the apparatus to the detector, the instrument configured to direct emissions along the second path from
the plurality of spaced-apart reaction regions to the detector to produce a data signal; and

a lens disposed along the first path and along the second path, the lens configured to direct the excitation beam to more
than one of the reaction regions simultaneously.

US Pat. No. 9,476,885

WATER-DISPERSABLE NANOPARTICLES

Life Technologies Corpora...

1. A method for making a water-dispersable nanoparticle comprising:
a. providing a nanocrystal coated with a surface layer comprising a hydrophobic ligand, and dissolved or dispersed in a non-aqueous
solvent;

b. contacting the nanocrystal dispersion with a phase transfer agent and an aqueous solution comprising a hydrophilic ligand,
to form a biphasic mixture having an aqueous phase and a non-aqueous phase; and

c. maintaining the mixture under conditions that cause the nanocrystal to migrate from the non-aqueous solvent into the aqueous
phase.

US Pat. No. 9,457,139

KITS FOR SYSTEMS AND METHODS USING ACOUSTIC RADIATION PRESSURE

Life Technologies Corpora...

1. A kit comprising at least one reagent for use in an acoustic apparatus, wherein the acoustic apparatus is configured to
include at least a first and a second fluid stream, the kit comprising:
a first liquid medium, wherein the first liquid medium is configured to be used in the first fluid stream of the acoustic
apparatus and comprises a red blood cell lysis fluid and a heavy salt;

a second liquid medium, wherein the second liquid medium is configured to be used in the second fluid stream of the acoustic
apparatus and comprises a buffer;

a reagent for labeling white blood cells; and
wherein, when the kit is in use, a first acoustic contrast exists between the first liquid medium and white blood cells labeled
with the reagent and a second acoustic contrast exists between the second liquid medium and the white blood cells labeled
with the reagent, wherein the first acoustic contrast is different from the second acoustic contrast.

US Pat. No. 9,410,118

CELL CULTURE MEDIA AND METHODS

Life Technologies Corpora...

1. A method of making a eukaryotic cell culture medium, feed or supplement composition comprising a protected and stable labile
component, the method comprising:
(i) adding a minimal volume of an aqueous solution to a dry powder format of a medium, feed or supplement comprising a labile
component to make a paste;

(ii) mixing the paste vigorously to prepare a microsuspension;
(iii) optionally, adding an effective amount of an anti-oxidant to the microsuspension to form a mixture;
(iv) encapsulating the microsuspension of (ii), or the mixture of (iii), in a capsular material to form a bead; and
(v) drying the bead to form the composition containing said protected and stable labile component.
US Pat. No. 9,410,194

COMPOSITIONS, KITS AND METHODS FOR SYNTHESIS AND/OR DETECTION OF NUCLEIC ACIDS

LIFE TECHNOLOGIES CORPORA...

1. A polymerase chain reaction (PCR) composition, comprising:
a thermostable DNA polymerase; and
a combination of PCR inhibitor blocking agents comprising fish gelatin and bovine serum albumin (BSA), wherein the bovine
serum albumin is at a concentration of 0.05 mg/mL to 0.8 mg/mL and wherein the fish gelatin is at a concentration of 0.05%
(w/v) to 0.8% (w/v).

US Pat. No. 9,375,716

PINCH FLOW REGULATOR

Life Technologies Corpora...

1. A valve comprising:
a housing base defining a lower cavity and comprising a pinch structure within the lower cavity, a gas inlet providing external
access to the lower cavity, a base fluid inlet, and a base fluid outlet;

a housing cover defining an upper cavity and comprising a cover fluid inlet and a cover fluid outlet, the cover fluid inlet
in fluidic communication with the base fluid outlet between the upper cavity and the lower cavity, the cover fluid outlet
providing external access from the upper cavity;

a diaphragm disposed between the housing base and the housing cover and fluidically separating the lower cavity from the upper
cavity;

a pinch plate disposed in the lower cavity and comprising a pinch point disposed opposite the pinch structure; and
a pinch tube in fluidic communication between the base fluid inlet and the base fluid outlet in the lower cavity, the pinch
tube extending between the pinch structure and the pinch point.

US Pat. No. 9,371,557

NUCLEIC ACID AMPLIFICATION

Life Technologies Corpora...

1. A method for nucleic acid amplification, comprising:
(a) forming a reaction mixture including a continuous liquid phase containing (i) a plurality of separate supports containing
a first universal primer that does not include any target-specific sequence, (ii) a second universal primer in solution, (iii)
a plurality of different polynucleotide templates containing both a first primer binding sequence and a second primer binding
sequence, wherein the first primer binding sequence is complementary or identical to at least a portion of the first universal
primer and the second primer binding sequence is complementary or identical to at least a portion of the second universal
primer, and (iv) a polymerase; and

(b) forming two or more substantially monoclonal populations, each linked to a different support, by clonally amplifying,
within the same reaction mixture of step (a) in the continuous liquid phase, at least two of the polynucleotide templates
on different separate supports under isothermal amplification conditions using the first and second universal primers by partially
denaturing and without compartmentalizing the polynucleotide templates.

US Pat. No. 9,334,531

NUCLEIC ACID AMPLIFICATION

Life Technologies Corpora...

1. A method for nucleic acid amplification, comprising:
a) distributing at least two different polynucleotide templates onto an array of reaction sites on a support wherein the array
of reaction sites comprise the same first universal primer that does not include a template sequence by introducing a single
one of each of said different polynucleotide templates into at least two different reaction sites of the array, wherein the
polynucleotide templates each include the same first universal primer binding site, the same second universal primer binding
site, and are present within a reaction mixture in a single continuous liquid phase; and

b) forming at least two substantially monoclonal nucleic acid populations by amplifying, by partially denaturing and without
compartmentalizing and within the same reaction mixture of step (a) in the continuous liquid phase, each of the single polynucleotides
within said at least two reaction sites, wherein the amplifying is performed using a second universal primer in solution that
can hybridize to the second universal primer binding site within the polynucleotide templates, and wherein said at least two
reaction sites are in fluid communication with each other during the amplifying.

US Pat. No. 9,322,055

SYSTEM AND METHOD FOR DETERMINING COPIES-PER-UNIT-VOLUME USING PCR AND FLOW CONTROL OF DROPLETS

Life Technologies Corpora...

1. A method for quantification of a target nucleic acid in a sample, the method comprising:
forming a plurality of discrete sample portions, each of the plurality of discrete sample portions comprising a portion of
the sample, and a reaction mixture;

amplifying the plurality of discrete sample portions to form a plurality of discrete processed sample portions including at
least one discrete processed sample portion containing nucleic acid amplification reaction products;

detecting fluorescence signals from the at least one of the plurality of discrete processed sample portions to determine a
presence of the at least one target nucleic acid;

determining the respective volumes of the plurality of discrete processed sample portions, wherein the determining the respective
volumes comprises imaging the plurality of discrete processed sample portions; and

estimating the number of copies-per-unit-volume of the at least one target nucleic acid in the sample based on the number
of discrete processed sample portions determined to contain the at least one target nucleic acid therein.

US Pat. No. 9,267,170

SYSTEMS AND METHODS FOR BIOLOGICAL ANALYSIS

Life Technologies Corpora...

1. A case for containing a plurality of biological samples, the case comprising:
a base;
a substrate attached to the base, the substrate comprising a plurality of reaction regions configured to receive one or more
biological samples; and

a cover comprising an inner surface, the cover configured to be attached to the base; and
wherein the inner surface includes a central area and a recessed area disposed about the central area, the central area configured
to cover the reaction regions, the recessed area being offset from the central area in a direction normal to the inner surface;

wherein during use the base, the central area, and the recessed area together provide a cavity containing the substrate;
wherein the recessed area comprises a trough disposed along a perimeter of the central area, the trough comprising a bottom
surface that is offset from the central area in a direction normal to the inner surface; and

wherein the bottom surface has a depth that varies along the perimeter.
US Pat. No. 9,212,393

METHOD OF DETERMINING THE NUCLEOTIDE SEQUENCE OF OLIGONUCLEOTIDES AND DNA MOLECULES

Life Technologies Corpora...

1. An apparatus for DNA sequencing comprising:
(a) at least one reaction chamber including a DNA primer/template system which produces a detectable signal when a DNA polymerase
enzyme incorporates an unlabeled and unblocked deoxyribonucleotide monophosphate onto the 3? end of the primer strand;

(b) a system for introducing into, and evacuating from, said reaction chamber at least one reagent selected from the group
consisting of: buffers, electrolytes, DNA template, DNA primer, deoxyribonucleotides, and polymerase enzymes;

(c) a system for converting said detectable signal into an electrical signal based on an electrical potential generated from
said detectable signal in the at least one reaction chamber; and

(d) a system for measuring the electrical signal generated by the detectable signal produced in the at least one reaction
chamber.

US Pat. No. 9,149,803

FLUIDICS SYSTEM FOR SEQUENTIAL DELIVERY OF REAGENTS

Life Technologies Corpora...

1. A fluidics system for delivering selected reagents to a flow cell, the fluidics system comprising:
a fluidics circuit including a fluidics node having a fluid outlet in fluid communication with the flow cell, the fluidics
node in fluid communication with at least one waste port through a plurality of passages without intervening valves, each
passage of the plurality of passages providing a distinct fluid path between the fluidics node and the at least one waste
port, each fluid inlet of a plurality of fluid inlets in unique fluid communication with a passage of the plurality of passages,
the each fluid inlet of the plurality of fluid inlets uniquely coupled to an associated reagent reservoir of a plurality of
reagent reservoirs, the fluidics circuit free of valves;

a plurality of reagent valves, wherein each reagent valve of the plurality of reagent valves is uniquely disposed between
a fluid inlet from the plurality of fluid inlets and the associated reagent reservoir of the plurality of reagent reservoirs;

a wash inlet for introducing a wash solution from a wash valve to the fluidics circuit; and
a control unit programmed to (a) deliver a sequence of selected reagents through the plurality of fluid inlets to the flow
cell, and (b) in between delivery of each selected reagent, to wash the fluidics circuit with the wash solution and to prime
the fluidics circuit with one of the selected reagents and the wash solution, wherein a portion of fluid flowing from a first
fluid inlet of the plurality of fluid inlets flows through the fluidics node past a second fluid inlet of the plurality of
fluid inlets and to the at least one waste port without entering the fluid outlet.

US Pat. No. 9,145,556

COMPOSITIONS AND METHODS FOR INHIBITION OF NUCLEIC ACIDS FUNCTION

Life Technologies Corpora...

1. A composite nucleic acid inhibitory molecule which comprises: a 5? stem loop structure that does not bind to a target nucleic
acid molecule, wherein the loop of the stem loop structure consists of a non-nucleotide loop, and a target binding nucleic
acid segment which is greater than 6 nucleotides in length, wherein the target binding nucleic acid segment is modified to
increase binding affinity to its target, wherein the target nucleic acid molecule is a microRNA (miRNA), and wherein the stem
loop structure is only at the 5? end of the target binding nucleic acid segment and wherein the non-nucleotide loop is chosen
from polyethylene glycol, C2-C18 alkane diol, styrene, stilbene, triazole, tetrazole, poly abasic nucleoside, polysaccharide,
peptide, polyamide, hydrazone, oxyimine, polyester, disulfide, polyamine, polyether, peptide nucleic acid, cycloalkane, polyalkene,
aryl, a combination thereof, and a derivative thereof.
US Pat. No. 9,127,246

METHODS FOR CONDENSING A HUMID GAS

Life Technologies Corpora...

1. A method for processing a fluid, the method comprising:
sparging a fluid within the compartment of a container with an initial gas so that the initial gas passes through a portion
of the fluid to form a humid gas within the compartment;

passing the humid gas out of the compartment of the container and into a flexible condenser bag;
cooling the humid gas within the condenser bag so as to separate the humid gas within the condenser bag into a condensed fluid
and a dehumidified gas; and

removing the condensed fluid and the dehumidified gas from the condenser bag.

US Pat. No. 9,909,964

METHOD OF PREPARING QUALITY CONTROL MATERIAL FOR FFPE

LIFE TECHNOLOGIES CORPORA...

1. A method for preparing a sample for formalin fixation and paraffin embedding (FFPE), comprising:
(a) obtaining a defined amount of cellular material comprising a known amount of test cells and a known amount of background
cells in a mixture, where the test cells include at least one pre-determined detectable genetic mutation and the background
cells do not include the at least one pre-determined detectable genetic mutation;

(b) mixing the cellular material with a gelling polymer, creating a gel/cellular material;
(c) adding the gel/cellular material to a mold with a defined shape until the gelling polymer solidifies; and
(d) slicing the solidified material to a uniform and defined size,where the ratio of test cells to background cell is maintained in the slice.
US Pat. No. 9,855,287

ANTI-VIRAL AZIDE CONTAINING COMPOUNDS

LIFE TECHNOLOGIES CORPORA...

1. A pharmaceutical composition comprising:
an azide-modified fatty acid or pharmaceutically acceptable salt thereof;
at least one anti-viral agent; and
a pharmaceutically acceptable excipient,wherein the fatty acid is one that is attached directly or indirectly to a protein through a palmitoylation pathway in a cell.

US Pat. No. 9,534,092

PURIFICATION SYSTEMS AND METHODS

Life Technologies Corpora...

1. A method of preparing hydrogel polymeric particles, the method comprising:
filtering a plurality of hydrogel polymeric particles through a first filter having a pore size at a first permeate velocity
to provide a first subset of hydrogel polymeric particles in the permeate and having a first particle size distribution; and

filtering the first subset of hydrogel polymeric particles through a second filter having the pore size at a second permeate
velocity to provide a second subset of hydrogel polymeric particles in the retentate derived from the first subset of hydrogel
polymeric particles and having a second particle size distribution narrower than the first particle size distribution;

wherein the average particle size of the second subset of hydrogel polymeric particles is in a range of 0.3 micrometers to
1.5 micrometers;

wherein the first and second permeate velocities are different.
US Pat. No. 9,528,083

HEAT EXCHANGER SYSTEM WITH FLEXIBLE BAG

Life Technologies Corpora...

1. A heat exchanger system comprising:
a heat exchanger comprising a body having a first side face and an opposing second side face, the body bounding a fluid channel
disposed between the opposing side faces and extending between an inlet port and an outlet port; and

a flexible first bag comprised of one or more sheet of polymeric material, the first bag bounding a fluid pathway that extends
between a fluid inlet and a fluid outlet, the first bag being removably retained against the first side face of the body of
the heat exchanger, the fluid channel of the body of the heat exchanger being sealed from fluid communication with the fluid
pathway of the first bag.