US Pat. No. 9,347,888

DETECTION OF BACTERIA EXHIBITING A RESISTANCE TO CARBAPENEMS

1. A process for detecting whether at least one carbapenem-resistant bacterial strain is present in a biological sample, comprising:
contacting the biological sample with a culture medium to obtain an inoculated culture medium, the culture medium comprising
(i) at least one chromogenic substrate, and (ii);

incubating the inoculated culture medium to culture the carbapenem-resistant bacterial strain if present in the biological
sample; and

detecting whether the carbapenem-resistant bacterial strain is present on or in the culture medium.

US Pat. No. 9,353,398

METHOD FOR ISOLATING A SAMPLE WELL OF A TEST CARD FOR ANALYSIS, AND RESULTING TEST CARD

1. A method for isolating at least one fluid sample well laid out in a test card for analysis, said test card including a
plate having at least one first main face from which is laid out at least one channel communicating with at least said well,
this first face being coated with a membrane provided with an adhesive and which will cover said channel with a covering area,
the method for isolation including:
a phase for introducing a fluid sample into at least said well,
a phase for isolating said well, along an isolation area (Zi), consisting of exerting a force on at least one portion of the
covering area of the adhesive membrane for displacing it until causing it to fit the shape of the wall of a first channel
so as to allow adhesion of said covering area of the adhesive membrane onto the wall of the first channel along the isolation
area (Zi),

comprising exerting a force on the covering area of the adhesive membrane located overhanging the first channel in order to
ensure displacement of the adhesive from the isolation area (Zi) in an obturation area (Zo) for the sample well, contiguous
to the isolation area (Zi), wherein the isolation area comprises a portion of the first channel and the obturation area comprises
a portion of a second channel which opens into the first channel at an intersection between the first channel and the second
channel, wherein axes of the first and second channels are not aligned.

US Pat. No. 9,382,571

METHOD FOR DETECTING DELTA HAEMOLYSIN OF STAPHYLOCOCCUS AUREUS BY MASS SPECTROMETRY DIRECTLY USING A BACTERIAL POPULATION

HOSPICES CIVILS DE LYON, ...

1. A method for studying a sample containing a bacterial population of Staphylococcus aureus by a mass spectrometry technique comprising the following steps:
a) placing the sample in contact with the medium allowing ionization by action of a laser beam of the molecules present in
the sample,

b) ionizing the molecules present in the sample by means of a laser beam,
c) accelerating the ionized molecules obtained by a potential difference,
d) letting the ionized and accelerated molecules freely move in at least one tube under reduced pressure,
e) detecting at least one portion of the ionized and accelerated molecules which have freely moved, so as to measure the time
they took for covering at least one tube under reduced pressure and for obtaining a signal corresponding to the number of
detected ionized molecules at a given instant,

f) calculating the mass over charge ratio [m/z] of the detected molecules, so as to obtain a signal corresponding to the number
of ionized molecules of a same mass over charge ratio [m/z], depending on the m/z ratio of the detected molecules,

g) determining either directly or indirectly whether the ionized molecules obtained in step b), there were or not ionized
molecules of a mass/charge ratio [m/z] equal to 3005±5 Th or equal to 3035±5 Th,

h) issuing a decision conditioned by the results obtained in step g).

US Pat. No. 9,470,510

SYSTEMS AND METHODS FOR DETECTING FALLEN CONTAINERS SUITABLE FOR APPARATUS FOR AUTOMATED EVALUATION OF MICROORGANISM GROWTH IN TEST SAMPLES

bioMerieux, Inc., Durham...

1. An automated misfeed and/or fallen container detection system comprising:
a conveyor providing a travel path for groups of elongated containers;
a rotating wheel in cooperating alignment with the conveyor, the wheel having a plurality of circumferentially spaced apart
pockets, each pocket configured to accept a single upright elongated container;

a plurality of spaced apart sensors including (i) at least one lower sensor configured to transmit a respective optical signal
across the container travel path proximate the wheel at a height that is less than a width dimension of the containers, the
at least one lower sensor including a first lower sensor that transmits a respective first optical signal across a front edge
portion of a pocket of the wheel facing the conveyor at a loading position and (ii) at least one upper sensor that is positioned
proximate the wheel configured to transmit an optical signal at a height corresponding to a top portion of an upright container
to thereby allow detection of different orientations and positions of fallen containers and/or container jam or blockage conditions;

a pair of laterally spaced apart sidewalls facing each other across the conveyor, wherein the sidewalls have a parallel segment
that merges into a curved segment where the sidewalls travel toward each other proximate the rotating wheel to have a width
that is more narrow proximate the wheel than along the parallel segment, wherein the first lower sensor is held outside the
curved segment of one of the sidewalls; and

a bridge member that extends across and above the curved segment of the sidewalls held by the housing, wherein the at least
one upper sensor is held by the bridge member.

US Pat. No. 9,322,048

KIT FOR IDENTIFYING BACTERIA FROM THE BACILLUS CEREUS GROUP

1. A diagnostic kit for identifying bacteria of the Bacillus cereus group comprising a container of a selective or nonselective reaction medium with a pH between 6.8 and 8.0, said medium comprising
at least one inhibitor of Gram-negative bacteria and a first substrate, which first substrate is a fluorescent phosphatidylcholine
phospholipase C (PC-PLC) substrate, wherein the reaction medium does not contain an inhibitor of Gram-positive bacteria.
US Pat. No. 9,377,474

PRODEFENSIN-A6 ASSAY METHOD FOR THE IN VITRO DIAGNOSIS OF COLORECTAL CANCER

1. A monoclonal anti-Prodefensin-A6 antibody that (i) is specific for the propeptide of the Prodefensin-A6 protein, or (ii)
recognizes an epitope including an amino acid sequence selected from the group consisting of the amino acid sequences of:
(a) X1X2X3X4X5X6X7X8R (SEQ ID NO: 7), in which X1 is V or L, X2 is T or L, X3 is P, S or C, X4 is P or S, X5 is W or T, X6 is A, Q, M, C or E, X7 is I, E or D and X8 is F, Y, S or L;

(b) X1X2X3X4X5X6HX7 (SEQ ID NO: 13), in which X1 is S or T, X2 is C or absent, X3 is T, L or E, X4 is H or R, X5 is I, F or E, X6 is G or V and X7 is C or N;

(c) X1HPX2X3X4X5X6X7 (SEQ ID NO: 17), in which X1 is P or W, X2 is W or E, X3 is S, A, Q or W, X4 is M, L, R or P, X5 is H, F, W or G, X6 is V or A and X7 is I or V; and

(d) X1HX2X3X4X5 (SEQ ID NO: 22), in which X1 is Y or N, X2 is E, D or Q, X3 is T, N, R, M or K, X4 is W, H or F and X5 is P or G.

US Pat. No. 9,394,573

DETECTION OF MECA VARIANT STRAINS OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

1. A method of amplifying in a sample a methicillin-resistant Staphylococcus aureus (MRSA) which comprises an insertion of a SCCmec cassette within Staphylococcus aureus chromosomal DNA, wherein the SCCmec cassette comprises a mecA variant element, the method comprising:
performing on the sample an amplification reaction utilizing an oligonucleotide set consisting of:
a. a first oligonucleotide having a nucleic acid sequence that specifically hybridizes to chromosomal Staphylococcus aureus DNA in an extremity junction region, and

b. a second oligonucleotide having a nucleic acid sequence that specifically hybridizes to a mecA variant,
wherein each of the first oligonucleotide and the second oligonucleotide is oriented such that, under amplification conditions,
if the sample contains the MRSA, the region of the MRSA between the hybridizing site of the first oligonucleotide and the
hybridizing site of the second oligonucleotide is amplified as a single amplicon.

US Pat. No. 9,285,384

DEVICE FOR PREPARING AND/OR TREATING A BIOLOGICAL SAMPLE

BIOMERIEUX, (FR)

1. A device for preparing, treating, and/or analyzing a biological sample, comprising:
an assembly of storage chambers and/or reaction chambers intended for receiving a fluid, said chambers having shared walls
so as to form an assembly of adjacent chambers aligned along a chamber alignment axis, said walls including a membrane or
septum, said septum being able to be pierced by a needle, then recovering its seal once the needle is removed, the septum
or septa constituting the wall(s) being located in a plane traversed by the chamber alignment axis,

means for moving said fluid from and/or towards at least one of said chambers of the assembly, said movement means comprising:
a needle connected to a transfer compartment,
suction/delivery means for said liquid connected to the needle upstream therefrom and separately from the volume of the chambers
of the assembly, and

driving means arranged to translate the needle and the assembly of chambers relative to each other along the chamber alignment
axis, such that the needle pierces the septum, and

a chamber configured for storing, a reaction waste the chamber being disposed upstream from the transfer compartment and being
in fluid connection with the transfer compartment.

US Pat. No. 9,074,262

NUCLEIC ACID SEQUENCES THAT CAN BE USED AS PRIMERS AND PROBES IN THE AMPLIFICATION AND DETECTION OF ALL SUBTYPES OF HIV-1

bioMerieux, B. V., Boxte...


US Pat. No. 9,435,789

ARTICLE FOR BIOLOGICAL ANALYSIS

1. An article for biological analysis, comprising:
a first sheet;
a second sheet, superimposed on said first sheet, said first and second sheets being joined on all of their sides in order
to form a sealed package;

at least one analysis device, placed inside said package; and
rigid desiccation means, also constituting a means of perforating the first or second sheet of said package, in order to access
the analysis device, wherein

one of said first and second sheets contains a notch which constitutes a preferential folding area; and
said notch is in direct contact with said rigid desiccation means at least during folding of the package at the preferential
folding area.

US Pat. No. 9,273,360

DETECTION OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

1. A method of detecting in a sample a methicillin-resistant Staphylococcus aureus (MRSA) having an insertion of an SCCmec cassette within Staphylococcus aureus chromosomal DNA, the method comprising
(a) performing on the sample an amplification and detection reaction that detects the presence of a junction of an inserted
SCCmec cassette and Staphylococcus aureus chromosomal DNA, and

(b) performing on the sample an amplification and detection reaction that detects the presence of mecA gene,
wherein if the sample contains MRSA, the presence of both the junction and mecA in the sample is detected.

US Pat. No. 9,480,428

ASSEMBLY FOR DETERMINING THE PRESENCE OR ABSENCE OF AN ANALYTE IN A BLOOD SAMPLE AND ANALYSIS UNIT COMPRISING SUCH AN ASSEMBLY

24. An assembly for assaying the presence or absence of at least one analyte in a sample of human or animal blood obtained
by piercing skin or a blood vessel of the human or animal, the assembly comprising at least:
a hand transportable support;
a strip which is attached to the support and which includes an application area for applying the blood sample and at least
one reagent required for a blood analysis;

a container configured to collect, store and provide the blood sample to the strip, said container being removably connected
to the support in such a manner that the container may be alternatively arranged either in a storage configuration or in a
use configuration in which the container may be placed close to the application area; and

a piercing member configured to pierce the skin or the blood vessel, the piercing member being non-removably attached to the
support while in use.

US Pat. No. 9,394,534

METHOD AND MEANS FOR ENRICHMENT, REMOVAL AND DETECTION OF GRAM-POSITIVE BACTERIA

1. A method for the enrichment, for the removal, for the capture and/or for the detection of bacteria from a sample, comprising
the steps:
a) contacting and/or incubating a sample with a biotinylated polypeptide comprising
(i) an enzymatically non-active cell wall binding domain of a phage tail protein selected from the group consisting of SEQ
ID NO: 19-33, and

(ii) a domain comprising a sequence selected from the group consisting of SEQ ID NO: 1-18,
b) contacting and/or incubating polypeptide-bacteria-complexes obtained in step a) with a carrier supplied with a biotin-binding
substance, and

c) separating a carrier-polypeptide-bacteria-complex, obtained in step b), from the sample.

US Pat. No. 9,358,738

ASEPTIC BLOW, FILL AND SEAL METHODS OF FABRICATING TEST SAMPLE CONTAINERS AND ASSOCIATED SYSTEMS AND CONTAINERS

bioMerieux, Inc., Durham...

1. An aseptic method of fabricating a culture container, comprising:
providing at least one supply of sterile organism growth media with at least one flow path that extends to respective mold
stations;

providing at least one supply of sterile elastomeric stoppers with an electromechanical delivery system that feeds a respective
stopper to a respective upper portion of a container body held at a respective mold station;

forming parisons at the mold stations;
introducing flowable sterile sensor material into the parisons at the mold stations;
blow molding the parisons into a respective container body before, during or after the introducing step;
curing the sensor material so that it attaches to an inner surface of the container body;
sealing the container body to form a sterile container that does not require autoclaving; and
flowing sterilized organism growth media from the provided at least one supply of sterile organism growth media after introducing
the sensor material.

US Pat. No. 10,046,320

KIT FOR PREPARING A SAMPLE

1. A kit for preparing a sample of material, the kit comprisinga container having an open end;
a pipette for transferring the material to and from the container, the pipette having an open tip for drawing and dispensing the material;
an airtight cap configured to seal the open end of the container in an airtight manner and to allow the pipette tip to enter the container through the cap;
the cap and the pipette comprising cooperating stop portions for preventing the pipette from advancing into the container upon engagement of the stop portions;whereinthe pipette, the cap and the container are mutually configured such that upon engagement of the cooperating stop portions, the tip of the pipette stops above a first predetermined level but below a second predetermined level in the container;the first predetermined level being a level for a first substance;
the second predetermined level being a level for a second substance, and
the first level being lower than the second level;
the pipette, the cap and the container are mutually configured such that upon engagement of the cooperating stop portions the pipette tip is positioned approximately midway between the first and the second levels.
US Pat. No. 9,410,188

METHOD AND KIT FOR DISCRIMINATING BETWEEN BREAST CANCER AND BENIGN BREAST DISEASE

1. A method comprising the following steps:
a) obtaining a biological sample comprising mRNA from a patient and optionally reverse transcribing the mRNA to produce cDNA,
b) contacting the mRNA or the cDNA from the biological sample with at least four reagents, each reagent comprising at least
one oligonucleotide respectively specific for each of at least four different target genes, wherein the at least four reagents
comprise reagents specific for no more than 28 target genes, the no more than 28 target genes selected from the group consisting
of genes respectively comprising the full length nucleic acid sequences set forth in SEQ ID NO: 1 to 44, and the at least
four reagents being specific for at least four different target genes that comprise the full length nucleic acid sequences
set forth in:

1) SEQ ID NO: 1 and
2) SEQ ID NO: 2 or 3; and
3) SEQ ID NO: 4; and
4) SEQ ID NO: 5 or 6; and
c) measuring an expression level for each of the at least four target genes to obtain an expression profile for the patient.

US Pat. No. 9,266,902

LABELLING REAGENTS HAVING A PYRIDINE NUCLEUS BEARING A DIAZOMETHYL FUNCTION, PROCESS FOR SYNTHESIS OF SUCH REAGENTS AND PROCESSES FOR DETECTION OF BIOLOGICAL MOLECULES

UNIVERSITE DE STRASBOURG,...

1. A labelling reagent of formula (D):
in which:
R1 represents a detectable label or at least two detectable labels linked together by at least one multimeric structure, the
detectable label or the at least two detectable labels being independently selected from the group consisting of biotin, fluorophors,
fluorescent groups, and luminescent groups, wherein the excitation wavelength of the fluorophors and the fluorescent groups
is greater than 450 nm,

R2 represents: H, NO2, Cl, Br, F, I, OR, SR, NR2, R, NHCOR, CONHR, or COOR, where R=an alkyl or an aryl group,

R4 represents: H, an alkyl group, or an aryl group, and

L is a linking arm comprising a linear chain of at least two covalent bonds.
US Pat. No. 9,249,208

CITRULLINE PEPTIDES DERIVED FROM FIBRIN AND RECOGNIZED BY RHEUMATOID ARTHRITIS SPECIFIC AUTOANTIBODIES, AND THE USE THEREOF

1. A method for detecting the presence of ACPAs in a biological sample comprising:
bringing said biological sample into contact with at least one peptide chosen from the group consisting of:
a peptide consisting of the sequence X1PAPPPISGGGYX2AX3 (SEQ ID NO: 1) in which X1, X2 and X3 each represent a citrullyl residue or an arginyl residue, and at least one of the residues X2 and X3 is a citrullyl residue; and

a peptide of 5 to 25 amino acids comprising a fragment of at least 5 consecutive amino acids of the peptide consisting of
SEQ ID NO: 1, including at least X2 or X3 as a citrullyl residue, or

an antigenic composition comprising said at least one peptide under conditions that allow the formation of an antigen/antibody
complex with the ACPAs possibly present in said sample;

detecting the antigen/antibody complex possibly formed.
US Pat. No. 9,062,099

PRODEFENSIN-A6 ASSAY METHOD FOR THE IN VITRO DIAGNOSIS OF COLORECTAL CANCER

1. An in vitro method for diagnosing colorectal cancer using a biological sample obtained from a patient suspected of having
colorectal cancer, comprising:
assaying for the level of the Prodefensin-A6 protein present in the biological sample using at least one antibody or antibody
fraction specific for the Prodefensin-A6 protein; and

determining whether the level of the Prodefensin-A6 protein is indicative of the patient having colorectal cancer,
wherein the level of the Prodefensin-A6 protein is assayed by detecting any of the signal peptide or the propeptide of the
Prodefensin-A6 protein, whether as part of the intact Prodefensin-A6 protein or a fragment thereof, to the exclusion of the
mature Defensin-A6 protein or fragments of the mature Defensin-A6 protein.

US Pat. No. 9,447,371

HOLDER FOR CULTURE PLATES WITH DE-NESTING FEATURE

BIOMERIEUX, INC., Durham...

1. An apparatus for holding a plurality of culture plates in a stacked arrangement in which the culture plates are placed
vertically above each other in a stack, the stacked arrangement of culture plates including a bottom plate in the stacked
arrangement, wherein the culture plates contain nesting features wherein an upper portion of one culture plate is in a nested
relationship with an adjacent culture plate by virtue of the upper portion being received within a bottom portion of the adjacent
culture plate in the stacked arrangement, the apparatus comprising:
a holder holding the stacked arrangement of culture plates;
the holder having a base, the base defining an opening wherein the bottom culture plate may be withdrawn from the base;
wherein the base further comprises a structure passively and completely de-nesting the bottom culture plate from the adjacent
culture plate by moving the bottom culture plate laterally such that the upper region of the bottom culture plate is no longer
received with the bottom portion of the adjacent culture plate while retaining the bottom culture plate within the holder
thereby facilitating withdrawal of the bottom culture plate from the base via the opening.

US Pat. No. 9,371,924

ONE-PIECE FLAP DEVICE, INJECTION-MOULDED FROM ELASTIC MATERIAL

1. A one-piece flap device made of elastic material, which separates two distinct volume spaces, said flap device comprising:
a) a substantially cylindrical body comprising a through conduit,
b) a flap that seals an aperture of the through conduit of said body when the flap is in a closed position and is within said
body, and

c) an arm connecting the body of said flap device to said flap, said arm being in an elastic stress position regardless of
the position of said flap when inside said body, wherein:

the body comprises at least one peripheral lip;
a part of an outer face of the flap is pressed against an inner face of the peripheral lip by an elastic force of the arm
in the closed position;

the flap is configured to be moved from the closed position to an open position in a direction that opposes the elastic force
of the arm; and

a first end of the arm is attached to an exterior surface of the body and a second end of the arm is attached to the flap.

US Pat. No. 9,162,326

INCUBATION SYSTEM WITH LOW TEMPERATURE ENCLOSURE

bioMerieux, Inc., Durham...

3. A method of modifying a stand-alone, self-contained incubator, the method comprising the steps of:
a) obtaining a kit at a site where the incubator is located, the kit comprising (1) a base containing a machine generating
cold air, (2) an enclosure having a first compartment surrounding the incubator and a second compartment surrounding an electronics
module in a top portion of the incubator, the first compartment and the second compartment being separated from each other
using a baffle in contact with the incubator, and (3) a temperature sensor, the base having a first opening for egress of
cold air and a second opening for return of air to the base;

b) placing the incubator on the base, wherein the stand-alone, self-contained incubator has an exterior and an interior and
one or more access features on the exterior providing access to the interior of the incubator, the incubator having a heating
element for maintaining the temperature of the interior of the incubator at a nominal incubation temperature;

c) placing the enclosure on the base in a manner such that the enclosure surrounds the incubator and defines a space between
the exterior of the incubator and the enclosure, the enclosure placed on the base such that the first and second openings
in the base are peripheral to the incubator and are in communication with the space such that cold air may emanate from the
base, circulate on the exterior of the incubator, and return to the base in a closed loop; and

d) placing the temperature sensor in the space between the enclosure and the incubator and communicatively coupling the temperature
sensor and the machine generating the cold air so as to permit temperature feedback regulation of the operation of the machine
generating the cold air.

US Pat. No. 9,150,900

AUTOMATED TRANSFER MECHANISM FOR MICROBIAL DETECTION APPARATUS

bioMerieux, Inc., Durham...

1. A detection apparatus for rapid non-invasive detection of microorganism growth in a specimen sample, comprising:
(a) a sealable specimen container having an internal chamber with a culture medium disposed therein for culturing any microorganisms
that may be present in said specimen sample;

(b) a housing enclosing an interior chamber therein, said housing further comprising an entrance location therein configured
to receive said specimen container in a vertical orientation;

(c) a holding structure contained within said housing and comprising a plurality of horizontally oriented wells for holding
one or more of said specimen containers;

(d) a detection unit located within said interior chamber for the detection of microorganism growth in said specimen container;
and

(e) a multi-axis robotic transfer arm within said housing configured to automatically transfer said specimen container from
said entrance location to said holding structure, wherein said multi-axis robotic transfer arm comprises:

at least one horizontal support rail in a first horizontal axis and a moveable vertical support rail, wherein said vertical
support rail is supported by said at least one horizontal support rail and moveable along said horizontal support rail,

a horizontal slide rail in a second horizontal axis, said horizontal slide rail supporting a movable robotic head and gripper
mechanism, wherein said robotic head and gripper mechanism are moveable along said horizontal slide rail in said second horizontal
axis away from and toward said holding structure, and

wherein said horizontal slide rail further comprises a pivot plate and a pivot slot, wherein said robotic head and gripper
mechanism is coupled to said pivot plate and said pivot plate further comprises a moveable pivot slot cam follower, wherein
said cam follower is moveable between a first position in said pivot slot and a second position in said pivot slot, and wherein
said robotic head and gripping mechanism rotate from a vertical orientation to a horizontal orientation by said movement of
said cam follower from said first position in said pivot slot to said second position in said pivot slot.

US Pat. No. 9,128,058

METHOD FOR SEPARATION AND CHARACTERIZATION OF MICROORGANISMS USING IDENTIFIER AGENTS

bioMerieux, Inc., Durham...

1. A method of characterizing and/or identifying a microorganism, comprising:
(a) obtaining a test sample known to contain or that may contain microorganisms;
(b) selectively lysing non-microorganism cells in said test sample to produce a lysed test sample;
(c) layering said lysed test sample over a density cushion in a container;
(d) adding an identifier agent to said lysed test sample and/or said density cushion;
(e) centrifuging said container to separate microorganisms from other components of said test sample, said microorganisms
passing through said density cushion and forming a pellet of microorganisms at the bottom of said container;

(f) interrogating said pellet using optical spectroscopy to produce measurements which identify the microorganisms, wherein
said optical spectroscopy comprises intrinsic fluorescence; and

(g) characterizing and/or identifying the microorganisms in the pellet based on the produced measurements.
US Pat. No. 9,110,079

METHOD AND KIT FOR ESTABLISHING AN IN VITRO PROGNOSIS ON A PATIENT EXHIBITING SIRS

HOSPICES CIVILS DE LYON (...

1. An in vitro method of providing a survival prognosis for a patient having SIRS, the method comprising:
measuring expression levels of a combination of target genes from biological material of a sample obtained from the patient
using reagents specific for the respective target gene products that are selected from the group consisting of probes, primers,
antibodies, and antibody fragments;

comparing the expression levels to one or more predetermined thresholds indicative of a survival prognosis for the patient;
and

providing a survival prognosis for the patient so that care for the patient is able to be determined in accordance with the
survival prognosis,

wherein the combination of target genes includes at least one CX3CR1 gene and at least one other target gene selected from
the group consisting of S100A8, S100A9, IL-10, TNFA, HLA-DR, CIITA, and IRAK3.

US Pat. No. 9,945,857

METHOD AND KIT FOR DETERMINING THE PROBABILITY THAT A PATIENT WILL DEVELOP A SEVERE CASE OF DENGUE

1. A method of determining whether a patient infected with dengue virus will develop severe dengue, comprising:obtaining a blood sample collected from the patient infected with dengue virus;
measuring the expression level of platelet factor 4 from the blood sample; and
comparing the expression level of platelet factor 4 to a reference value obtained from individuals having dengue virus infections without developing severe dengue,
wherein, if the expression level of platelet factor 4 is less than the reference value, it is determined that the patient will develop severe dengue.

US Pat. No. 9,523,110

CULTURE CONTAINERS WITH INTERNAL TOP COATING OVER GAS BARRIER COATING AND ASSOCIATED METHODS

bioMerieux, Inc., Durham...

1. A container for culturing a test sample, comprising:
a molded monolithic single layer polymeric container body having an upwardly extending, visually transmissive wall with an
inner surface and a wall thickness that is between about 0.2 mm and 10 mm;

a thin gas barrier coating having a thickness between about 1 nm and 1000 microns comprising silica on the inner surface of
the container body, wherein the gas barrier coating is visually transmissive;

an internal top coating directly on the gas barrier coating, wherein the internal top coating is visually transmissive and
the internal top coating is selected from the group consisting of a polyester, polyvinylidene chloride (PVDC), polyvinyl alcohol
(PVOH), poly(acrylonitrile) (PAN), polyamide (PA), a polyurethane, an acrylic polymer, a polyetheramine, a metal oxide, a
polypropylene film with reprocessed/recycled polyhydroxyamino ether (PHAE), a poly-para-xylylene polymer, acetylene, and any
combination thereof; and

a cap sealably attached to the container body to define a sealed container,
wherein the sealed container has an oxygen transmission rate (OTR) after exposure to 121 degrees C. for 15 minutes and throughout
a one year shelf life that is between about 0.0001-0.04 (cc/package/day/atm, measured at 20 degrees C., 40% RH), and

wherein the container body has only two inner coating layers, the gas barrier coating as a first inner coating layer and the
internal top coating as a second inner coating layer.

US Pat. No. 9,422,598

METHOD AND KIT FOR THE PROGNOSIS OF COLORECTAL CANCER

1. A method comprising:
extracting total RNA from a peripheral blood sample obtained from a patient suspected of having or having colorectal cancer;
contacting the total RNA, or cDNA or cRNA obtained from the total RNA, with one or more reagents specific for at least one
target gene and no more than 100 target genes; and

measuring the expression level of the at least one target gene and no more than 100 target genes,
wherein the at least one target gene and no more than 100 target genes includes the NEAT1 gene.
US Pat. No. 9,290,548

PROTEINS USED FOR THE DIAGNOSIS OF LYME BORRELIOSIS

1. A nucleic acid encoding a chimeric protein, the chimeric protein comprising:
(i) at least one amino acid sequence having at least 50% sequence identity with any of the amino acid sequences selected from
the group consisting of SEQ ID NOS: 1-5; and

(ii) at least one amino acid sequence having at least 80% sequence identity with any of the amino acid sequences selected
from the group consisting of SEQ ID NOS: 6-8,

wherein the chimeric protein comprises at least one amino acid sequence of (i) and at least one amino acid sequence of (ii)
that are from different Borrelia strains or species.

US Pat. No. 9,061,045

METHOD FOR PRONGF ASSAY FOR IN VITRO DIAGNOSIS OF CANCER IN PARTICULAR BREAST, THYROID OR LUNG CANCER AND THERAPEUTIC USE OF PRONGF

1. A method for treating breast, thyroid, lung, or prostate cancer, comprising administering a pharmaceutical composition
comprising a therapeutically effective amount of a nerve growth factor precursor (ProNGF) inhibitor to a patient having breast,
thyroid, lung, or prostate cancer, wherein the ProNGF inhibitor is an siRNA that decreases expression of ProNGF or a ProNGF
receptor.

US Pat. No. 9,841,377

SAMPLE TEST CARDS

bioMerieux, Inc., Durham...

1. A sample test card, comprising:
(a) a card body defining:
a first surface and a second surface opposite said first surface, such that the first surface faces an opposite direction
from the second surface,

a fluid intake port, and
a plurality of sample wells disposed between said first and second surfaces, said first and second surfaces sealed with a
sealant tape covering said plurality of sample wells; and

(b) a fluid channel network disposed in both said first surface and said second surface and connecting said fluid intake port
to said sample wells, said fluid channel network comprising:

at least one distribution channel,
a plurality of fill channels connected to said at least one distribution channel, said fill channels comprising a first fill
channel disposed in said first surface and a second fill channel disposed in said second surface,

a plurality of through-channels connected to one or more of said second fill channels and forming a conduit to the first fill
channel on the first surface, and

a plurality of horizontally oriented fill ports connecting said second fill channels to said sample wells, wherein each of
the fill ports extends in a widthwise direction of the card body, wherein each of the fill ports extends perpendicular to
a portion of the second fill channels, wherein said fill channels have a reduced cross-section compared to said fill ports.

US Pat. No. 9,447,372

DETECTOR ARRANGEMENT FOR BLOOD CULTURE BOTTLES WITH COLORIMETRIC SENSORS

bioMerieux, Inc., Durham...

1. A detection system for blood culture bottle incorporating a colorimetric sensor subject to change of color due to change
in pH or CO2 of a sample medium within the blood culture bottle, comprising:
a sensor LED illuminating the colorimetric sensor;
a reference LED illuminating the colorimetric sensor;
a control circuit for selectively and alternately activating the sensor LED and the reference LED; and
a photodetector, the photodetector measuring reflectance from the colorimetric sensor during the selective and alternating
illumination of the colorimetric sensor with the sensor LED and the reference LED and generating intensity signals;

a computer comprising machine executable instructions, wherein the machine executable instructions are configured to:
receive the intensity signals from the photodetector; and
determine a distance of the bottle from a home position based on the intensity signals,
the computer including a non-transitory memory storing a calibration relationship between intensity signals for the reference
LED as a function of distance of the bottle from the home position in relation to the detection system,

wherein the non-transitory memory further stores a calibration relationship between intensity signals for the sensor LED as
a function of distance of the bottle from the home position and wherein the machine executable instructions are configured
to compensate for a drop in intensity signals from the sensor LED due to the bottle being positioned a distance away from
the home position in accordance with calibration relationships for the sensor LED and the reference LED,

wherein the reference LED is selected to have a peak wavelength of illumination such that the intensity signals of the photodetector
from illumination by the reference LED are not substantially affected by changes in the color of the colorimetric sensor,
and

wherein the peak wavelength of illumination of the reference LED is below about 490 nm.
US Pat. No. 9,365,894

METHODS AND KITS FOR AVOIDING AMPLIFICATION OF CONTAMINATING NUCLEIC ACIDS

1. A method of specifically amplifying a nucleic acid of interest, comprising:
treating a biological sample chemically or enzymatically to permit conversion of one type of nucleic acid base to another
type of base, the biological sample being selected from the group consisting of tissue, blood, serum, saliva, circulating
cells of a patient, a food product, an agricultural product, and an environmental product;

adding amplification primers and amplification reagents to the biological sample, each primer being constituted of three different
types of bases and being specific to a converted nucleic acid of interest or to a nucleic acid that is complementary to the
converted nucleic acid of interest, the primers comprising at least one modified nucleotide selected from the group consisting
of alpha-oligonucleotides, PNAs, LNAs, and 2?-O-alkyl ribonucleotides; and

amplifying the converted nucleic acid of interest provided that the nucleic acid of interest was present in the biological
sample,

wherein amplification of contaminating nucleic acids is circumvented by converting the one type of nucleic acid base to another
type of base prior to adding the amplification reagents, which are a source of contaminating nucleic acids, to the biological
sample.

US Pat. No. 9,359,631

METHOD FOR OBSERVING A SAMPLE

1. A method for observing a sample, comprising the steps of:
a) providing a volume of a substantially transparent medium having a first refractive index (nint) and having a first convex, rounded or facetted surface, wherein the angular deviation of the surface with respect to a sphere
with center C is less than 12.5° or wherein the facetted surface comprises at least 10 facets, and a second substantially
planar surface, said first surface separating said volume from an ambient medium having a second refractive index (next) that is lower than said first index, the sample to be observed being contained in said volume or disposed within said volume
or deposited on said first surface;

b) observing said sample through said second substantially planar surface; and
c) determining the presence of a substance or an object in the sample by detection during said step b) of a luminous ring
matched to said volume.

US Pat. No. 9,347,083

CULTURE MEDIUM CONTAINING A SPORE GERMINATION INHIBITING OR DELAYING COMPOUND

1. A liquid medium for the culture and detection of coagulase-positive staphylococci, comprising:
peptones;
at least one metabolic substrate capable of being degraded by a metabolic activity of the coagulase-positive staphylococci
to cause the pH of the medium to vary;

a pH indicator capable of detecting pH variation of the medium due to degradation of the metabolic substrate, the pH indicator
being a chromophore or fluorophore; and

D-alanine in an amount from 0.05 mol/L to 1 mol/L in the liquid culture medium.
US Pat. No. 9,347,943

PROTEINS USED FOR THE DIAGNOSIS OF LYME BORRELIOSIS

1. A polypeptide comprising an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID
NOs: 8-14.
US Pat. No. 9,170,263

METHOD FOR QUANTIFYING PROTEINS BY MASS SPECTROMETRY

UNIVERSITE CLAUDE BERNARD...

1. A method for the quantitative detection of a target protein in a sample, comprising the following steps:
a) treatment of the sample in order to generate peptides,
b) quantitative assaying of at least one proteotypic peptide generated from the target protein, via a mass spectrometry technique
implementing the following steps i) to vii):

i) ionizing of the proteotypic peptide to give precursor ions which are filtered according to their mass m/z, and selecting
a given precursor ion having a mass (m/z)1 according to the target protein sought,

ii) fragmenting of the selected precursor ion into first-generation fragment ions,
iii) filtering the first-generation fragment ions generated according to their mass m/z, and selecting a given first-generation
fragment ion having a mass (m/z)2 according to the target protein sought,

iv) fragmenting the selected first-generation fragment ion into second-generation fragment ions,
v) detecting of at least a part of the second-generation fragment ions so as to give a series of quantitative measurements,
vi) selecting of at least one quantitative measurement associated with a second-generation ion, and
vii) correlating the at least one selected quantitative measurement associated with the second-generation ion to the amount
of proteotypic peptide generated and to the amount of target protein present in the sample, with the implementation of a calibration
step, wherein said calibration step is performed using a calibration curve or internal calibration with a heavy peptide, wherein
said selected quantitative measurement is performed by multiple reaction monitoring3 (MRM3), and wherein said selected first-generation fragment ion having a (m/z)2 is a doubly-charged peptide which has a proline or a histidine in position 1.

US Pat. No. 9,085,792

METHODS FOR INOCULATING CULTURE MEDIA ON PETRI DISHES BY MEANS OF VIBRATION FREQUENCIES

1. A method for inoculating at least one agar culture medium, contained in a Petri dish, with at least one sample which may
contain microorganisms, said method comprising the steps of:
a) providing at least one agar culture medium contained in a Petri dish;
b) providing the sample which may contain microorganisms in liquid form;
c) depositing the sample in liquid form onto the lid of the Petri dish such that said sample can be transferred from the lid
to the agar culture medium; and

d) dispersing the sample, initially deposited onto the lid, onto the agar culture medium, by vibrating the Petri dish.
US Pat. No. 9,063,141

LISTERIA BACTERIOPHAGE TAILSPIKE PROTEIN AND USES THEREOF

1. An isolated chimeric polypeptide comprising a P825Orf2 amino acid sequence at least 75% identical to the amino acid sequence
of SEQ ID NO: 2, wherein the polypeptide has binding specificity for Listeria cells fused to a heterologous polypeptide.
US Pat. No. 9,551,020

METHOD OF DETECTING AT LEAST ONE MECHANISM OF RESISTANCE TO CARBAPENEMS BY MASS SPECTROMETRY

BIOMERIEUX, INC., Durham...

1. A method of detecting a KPC protein in a sample from a microorganism, the method comprising:
subjecting the sample to MS/MS spectrometry in MRM mode and detecting whether one or more KPC fragments selected from the
group consisting of SEQ ID NOS: 20-33, 1094, 1096, and 1097 is present, wherein detection of any of the KPC fragments by the
MRM mass spectrometry indicates the presence of KPC protein in the sample.

US Pat. No. 9,506,932

METHOD OF DETECTING AT LEAST ONE MECHANISM OF RESISTANCE TO CEPHALOSPORINS BY MASS SPECTROMETRY

BIOMERIEUX, INC., Durham...

1. A method of detecting a CTX-M protein in a sample from a microorganism, the method comprising:
subjecting the sample to MRM mass spectrometry and detecting whether one or more CTX-M fragments selected from the group consisting
of in SEQ ID NOS: 446-478, 480-495, 2009-2013, 2015, 2017, 2019, 2021-2027, 2029, 2030, 2032, 2034-2039, 2042-2051, 2054,
2055, 2057-2063, 2065-2067, 2069-2074, 2076-2078, and 2081-2092 is present, wherein detection of any of the CTX-M fragments
by the MRM mass spectrometry indicates the presence of CTX-M protein in the sample.

US Pat. No. 9,309,552

METHOD FOR DETECTING STREPTOCOCCUS AGALACTIAE USING ESTERASE ACTIVITY

1. A method for specifically detecting and identifying Streptococcus agalactiae from among other bacteria species having esterase activity in a sample suspected of containing Streptococcus agalactiae, the method comprising:
inoculating the sample on a reaction medium comprising:
at least one synthetic esterase enzymatic substrate selected from the group consisting of halogenated indoxyloctanoate derivatives,
halogenated indoxylnonanoate derivatives, and halogenated indoxyldecanoate derivatives that Streptococcus agalactiae are incapable of using at less than 18 hours after inoculation, the esterase enzymatic substrate being configured so that
bacteria that use the substrate exhibit a detectable modified appearance that is distinguishable from bacteria that have not
used the substrate;

a synthetic non-esterase enzymatic substrate capable of being used by Streptococcus agalactiae, the non-esterase enzymatic substrate being configured so that it confers on a colony that uses the non-esterase enzymatic
substrate a detectable modified appearance that is distinguishable from the detectable modified appearance when the esterase
substrate is used by a colony and from a colony that has not used the non-esterase enzymatic substrate;
wherein:
Streptococcus agalactiae incubated on the reaction medium exhibit a detectable modified appearance that is distinguishable from other bacteria that:

use the esterase substrate and not the non-esterase substrate; or
do not use the esterase substrate and do not use the non-esterase substrates; or
use both the esterase substrate and the non-esterase substrate;
the esterase and non-esterase enzymatic substrates are present in the reaction medium at a concentration of 10 to 2000 mg/L;
a bacteria exhibiting a detectable modified appearance attributable to the esterase enzymatic substrate at 18 hours after
inoculation indicates that the colony is not of the species Streptococcus agalactiae;
a presence of a colony that does not exhibit a detectable modified appearance attributable to the esterase enzymatic substrate
at 18 hours of incubation and exhibits a detectable modified appearance attributable to the non-esterase enzymatic substrate
indicates that the sample contains Streptococcus agalactiae;
and the detectable modified appearance is a change of color of the colony that is visualized by the naked eye, or fluorescence
of the colony.

US Pat. No. 9,464,308

METHOD FOR TRANSCRIPTIONAL AMPLIFICATION OF NUCLEIC ACIDS COMBINING STEPS OF DIFFERENT TEMPERATURES

1. A method of transcriptional amplification, comprising:
a) obtaining a mixture by combining (i) a biological sample comprising nucleic acids, (ii) amplification primers, (iii) amplification
reagents including enzymes required for amplification, and (iv) at least one polyol capable of stabilizing the enzymes required
for amplification;

b) denaturing the nucleic acids by heating the mixture at a temperature of 46° C. or more; and
c) transcriptionally amplifying at least one target nucleic acid at a temperature of 46° C. or more when present in the mixture;
wherein the at least one polyol is selected from the group consisting of lactose, sorbitol, sucrose, trehalose, and mannitol.

US Pat. No. 9,528,990

FLUOROGENIC/FLUORESCENT PROBES DERIVATIVE FROM SULFOXANTHENE, AND USE THEREOF

CENTRE NATIONAL DE LA REC...

1. A fluorogenic substrate of formula I or II:

wherein qu. is a fluorescence quencher group selected from the group consisting of:
—NO2;

—N?N—R1; R1 being any organic group that does not obscure the corresponding azo bond;

—NHCO-Pept.; Pept. being a peptide residue or any organic group that does not obscure the corresponding amide bond;
—O-Glyc.; Glyc. being an oligoglycoside residue that does not obscure the corresponding glycosidic bond;
—O—C(O)—R2; —O—P(O)(OR2)(OR2?) and —O—S(O)2—R2; R2 and R2? being independently a hydrogen atom or any organic group that does not obscure the corresponding ester bond; and


 Ra, Rb, Rc, Rd and Re being independently a hydrogen atom or any organic group that does not obscure the corresponding arylether bond.

US Pat. No. 10,005,996

DEVICE FOR THE CULTURING OF MICROORGANISMS AND ASSOCIATED PROCESS

ARJO WIGGINS FINE PAPERS ...

1. A device for the culturing and/or isolation and/or detection and/or identification and/or counting of at least one target microorganism in a sample liable to contain it, wherein it comprises a support and a nutrient medium;said support comprising:
a hydrophilic fibrous substrate,
at least one porous layer in contact with one of the faces of the fibrous substrate, comprising a pigment or a mixture of pigments and at least one binder, said pigment having a size of less than 5 ?m and the amount of said pigment or said mixture of pigments being between 50 and 97% by dry weight, with respect to the dry weight of the porous layer;
said nutrient medium being included in the fibrous substrate.

US Pat. No. 9,576,181

BIO-IMAGING METHOD

1. A method for defining an isolation area around an object of interest in a cell culture vessel, the method comprising:
obtaining one or more images of the cell culture vessel using one or more of a plurality of illumination sources, each illumination
source being capable of illuminating the vessel from a different direction;

selecting an image or combination of images for further processing;
applying a circular object detection transformation to identify one or more objects of interest being substantially circular
objects in the cell culture vessel, the one or more objects of interest being representative of isolated colonies in the cell
culture vessel and determining a center of an object of interest;

applying a binarizing step to obtain a binarized image of the object of interest and other objects, wherein a center of the
binarized image corresponds to the center of the object of interest;

iteratively forming concentric circles with increasing radius, wherein the concentric circles are centered on the center of
the binarized image;

identifying coronas, wherein a corona is delimited by two circles having successive radius values; and
for each corona:
determining a presence and a location of other objects located in the corona to determine the presence and the location of
the other objects, and

determining a clearance angle defining an angular sector free of the other objects around the object of interest to define
an isolation area around the object of interest and to define the availability of the object of interest to be picked.

US Pat. No. 9,856,503

COMBINED DETECTION INSTRUMENT FOR CULTURE SPECIMEN CONTAINERS AND INSTRUMENT FOR IDENTIFICATION AND/OR CHARACTERIZATION OF A MICROBIAL AGENT IN A SAMPLE

bioMerieux, Inc., Durham...

1. An automated system for rapid detection of a microbial agent in a sample and identifying the microbial agent, comprising,
in combination:
a detection instrument receiving a specimen container containing a sample, the detection instrument including a heated enclosure
for incubating the specimen container and a detection unit interrogating the specimen container to detect whether the specimen
container is positive for the presence of a microbial agent in the sample;

a supply of disposable separation devices; and
an identification/characterization instrument receiving a specimen container detected positive by the detection instrument,
the characterization/identification instrument comprising:

a sample removal apparatus operative to remove a portion of the sample from the specimen container and add the portion to
a separation device obtained from the supply of separation devices;

a separation and concentration station operative on the separation device after receiving the portion of the sample so as
to separate the microbial agent from other products in the sample and concentrate the microbial agent within the separation
device;

a centrifuge located within the separation and concentration station, the centrifuge capable of concentrating the microbial
agent in a portion of the separation device, wherein the separation device comprises an internal capillary tube and a lower
portion that is capable of being removed from the separation device, and wherein a peripheral portion of the capillary tube
contains the concentrated microbial agent; and

a module interrogating the concentrated microbial agent using mass spectrometry, the module including a subsystem configured
to obtain a sample of the concentrated microbial agent from the separation device by removing the lower portion of the separation
device, the module further comprising a computer programmed to identify the microbial agent to the family, genus, species,
and/or strain level from data obtained from the interrogation of the concentrated microbial agent;

wherein the detection instrument and the identification/characterization instrument are integrated into a single system and
operate in a substantially fully automated manner to detect a specimen container for being positive for microbial growth,
and then identify the microbial agent.

US Pat. No. 9,606,120

INTERFERING PEPTIDES AND METHOD FOR DETECTING MICROORGANISMS

1. A method for in vitro detection of a microorganism M using a biological sample comprising:
performing an immunoassay that includes contacting the biological sample with an interfering peptide and a binding partner
for (i) an antibody AbM directed against a target protein of the microorganism M, or (ii) the target protein of the microorganism M; and

determining whether a complex has formed between the binding partner and (i) the antibody AbM, or (ii) the target protein;

wherein:
formation of the complex indicates that the microorganism M is present;
the interfering peptide has a peptide sequence S of 7 to 12 amino acids that is included in the peptide sequence of the target
protein of the microorganism M;

the sequence S is aligned with respect to a peptide sequence S? of 7 to 12 amino acids that is included in the peptide sequence
of an antigenic protein of an interfering microorganism M? different from the target microorganism M;

the sequences S and S? exhibit at least 50% identity over their length of 7 to 12 amino acids and at least 4 identical or
analogous contiguous amino acids;

the sequences S and S? have identical lengths or exhibit a difference of 1 or 2 amino acids distributed at one and/or the
other end of the sequences;

the interfering peptide blocks false positive results linked to the presence of antibodies AbM? directed against the antigenic protein of the interfering microorganism M?; and

one of the microorganism M and the microorganism M? is hepatitis C virus (HCV) and the other of the microorganism M and the
microorganism M? is selected from the group consisting of Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis, Pseudomonas entomophila, and Pseudomonas putida (GB-1 strain); or

one of the microorganism M and the microorganism M? is human immunodeficiency virus HIV-1 and the other of the microorganism
M and the microorganism M? is Mycoplasma pneumoniae.

US Pat. No. 9,562,260

NUCLEIC ACID AMPLIFICATION REACTION STATION FOR DISPOSABLE TEST DEVICES

BIOMERIEUX, INC., Durham...

14. A disposable nucleic acid amplification test device comprising:
a first chamber containing a first reaction reagent;
a second chamber containing a second reaction reagent;
an intermediate chamber between the first chamber and the second chamber;
an externally, mechanically actuated flow control element selectively providing fluid communication between the first chamber
and the intermediate chamber; and

a cover connected to the test device moveable from a first position covering the first chamber to a second position exposing
the first chamber so as to enable a user to supply the sample into the first chamber directly.

US Pat. No. 9,388,404

PROTEIN DISULFIDE ISOMERASE ASSAY METHOD FOR THE IN VITRO DIAGNOSIS OF COLORECTAL CANCER

1. An isolated peptide comprising the amino acid sequence of SEQ ID NO:3, wherein the peptide has from 1 to 6 additional amino
acid residues on at least one side of the amino acid sequence of SEQ ID NO:3 that are different from the corresponding amino
acid residues of the protein disulfide isomerase (PDI) amino acid sequence.

US Pat. No. 10,144,039

METHOD FOR CLEANING TEST SAMPLE WELLS, AND CLEANING HEAD USING SAID METHOD

1. A method for cleaning at least one test sample well, provided in a diagnostic test card, using at least one cleaning head comprising at least one cleaning tube delivering, at its free end, a cleaning fluid, and a suction tube mounted within the cleaning tube for aspirating a contaminated cleaning fluid from its free end located in proximity to the free end of the cleaning tube, the method comprising:providing a relative displacement between the test card and the cleaning head, so that the test card occupies a cleaning position wherein the cleaning tube delivers, at its free end, the cleaning fluid inside the sample well to be cleaned and the suction tube aspirates the contaminated cleaning fluid,
in the cleaning position, abutting the free end of the cleaning tube on the test card,
delivering the cleaning fluid from the free end of the cleaning tube along a delivery direction, in a direction of a transverse bottom wall of the sample well, and simultaneously aspirating the contaminated cleaning fluid with the aspiration tube,
thereby allowing an air intake between the outside and the inside of the free end of the cleaning tube, along a direction perpendicular to the delivery direction, thus creating a cleaning fluid vortex within the sample well when the contaminated cleaning fluid is aspirated.
US Pat. No. 9,823,239

PROCESS FOR DETERMINING THE SUSCEPTIBILITY TO NOSOCOMIAL INFECTIONS

HOSPICES CIVILS DE LYON, ...

1. A process for determining the susceptibility of a patient with septic shock to nosocomial infections, comprising the following
steps:
taking a first biological sample from said patient up to 48h after an onset of septic shock;
taking a second biological sample from said patient at least 24h after the first biological sample is taken, and up to 10
days after the onset of septic shock; and

measuring the expression of soluble CD127 in the first biological sample and in the second biological sample using anti-soluble
CD127 antibodies, whereby a concentration of soluble CD127 in the first biological sample and a concentration of soluble CD127
in the second biological sample is obtained;

wherein an increased susceptibility to nosocomial infections in the patient is indicated when the concentration of soluble
CD127 in the second biological sample is not significantly reduced compared to the concentration of soluble CD127 in the first
biological sample.

US Pat. No. 9,804,591

JOB SCHEDULER FOR ELECTROMECHANICAL SYSTEM FOR BIOLOGICAL ANALYSES

1. A scheduling method of a processor-controlled system including a plurality of machines and at least one processor, configured
to be stored in the system and adapted to execute, via the at least one processor, a plurality of non-preemptible electromechanically
driven jobs J1 . . . Jn, with deterministic execution times e1 . . . en, each job of the plurality of non-preemptible electromechanically driven jobs being statically assigned to one of m independent
machines M1 . . . Mm of the plurality of machines, for setting a release time r1 . . . rn for each job J1 . . . Jn so as to minimize a completion time of overall set of jobs, while respecting precedence constraints comprising:
for a predetermined set of pairs Jx and Jy of the plurality of jobs, a delay between completion of Jy and start of Jx range within a minimum delay d?xy and a maximum delay d+xy:

d?xy?rx?(ry+ey)?d+xy and respecting exclusion constraints comprising:
for a predetermined set of pairs Ji and Jk of the plurality of jobs, one of two determinations of exclusion constraint is fulfilled, the two determinations being:

ri?rk+ek OR ri+ei?rk
so that execution periods of Jk and Ji do not overlap,
the method comprising the steps, executed on the one or more processors, of:
A) building a frontier set including a plurality of Difference Bound Matrix (DBM) zones that collect release times satisfying
the precedence constraints;

B) selecting one of the plurality of DBM zones and removing it from the frontier set;
C) responsive to the selected DBM zone not satisfying at least one exclusion constraint of one pair Ji and Jk of the predetermined set of pairs, building one restricted zone of the selected DBM zone per each of the two determinations
resolving a conflict defined by (ri?rk+ek or ri+ei?rk);

D) checking if the restricted DBM zones are non-empty and adding the non-empty restricted DBM zones to the frontier set; and
E) repeating the steps B to D until a selected DBM zone satisfies all the exclusion constraints.
US Pat. No. 9,726,602

METHOD FOR OBSERVING BIOLOGICAL SPECIES

1. A process for observing biological species on a culture medium contained in a container having at least one translucent
face, the process comprising the steps:
a) directing a light beam onto one portion of said translucent face, so as to define at least one illuminated region and at
least one non-illuminated region of said face; and

b) acquiring an image of a portion of the surface of said culture medium illuminated by said light beam, the acquisition being
carried out through said or at least one said non-illuminated region of said translucent face and along an optical acquisition
axis forming an angle (?) greater than or equal to 10° with the direction of propagation of said light beam.

US Pat. No. 9,863,948

METHOD FOR THE IN VITRO PREDICTION OF THE PROBABILITY OF A PATIENT DEVELOPING SEVERE DENGUE, BASED ON A BLOOD SAMPLE

1. A method comprising:
assaying an amount of leucine-rich alpha-2 glycoprotein in a blood sample from a person having or suspected of having a dengue
virus infection.

US Pat. No. 9,802,188

METHODS, SYSTEMS, AND COMPUTER PROGRAM PRODUCTS FOR DETECTING A DROPLET

bioMerieux, Inc., Durham...

1. A method for operating a pipette comprising:
providing a pipette including a pipette pressure detector that measures pressure at an internal portion of the pipette;
positioning the pipette at a distance above a surface;
dispensing a fluid from a pipette tip attached to the pipette;
measuring pipette pressure in real-time at the internal portion of the pipette at given sampling time intervals during the
step of dispensing the fluid from the pipette tip to generate a plurality of pipette pressure values;

determining a plurality of pressure differences, wherein the step of determining the plurality of pressure differences comprises
calculating the difference between at least one previously measured pipette pressure value and a most recently measured pipette
pressure value;

estimating a plurality of rate of change in pipette pressure values during a given time interval, wherein the step of estimating
the plurality of rate of change in pipette pressure values during the given time interval comprises multiplying a most recently
determined pressure difference by a weighting factor to give a weighted pressure difference and summing the weighted pressure
difference with a weighted previously calculated pressure difference to provide a rate of change in pipette pressure, and
comparing the rate of change in pipette pressure to an upper pressure related threshold and a lower pressure related threshold;

detecting formation of the droplet at a distal end of the pipette tip when at least one of the plurality of rate of change
in pipette pressure values is greater than or equal to the upper pressure related threshold and another one of the plurality
of rate of change in pipette pressure values is less than or equal to the lower pressure related threshold; and

stopping the dispensing of the fluid from the pipette tip when the droplet is detected or moving the pipette when the droplet
is detected.

US Pat. No. 9,739,788

DETECTOR ARRANGEMENT FOR BLOOD CULTURE BOTTLES WITH COLORIMETRIC SENSORS

BioMerieux, Inc., Durham...

1. A detection system comprising:
a blood culture bottle comprising a sample medium;
a colorimetric sensor positioned in the blood culture bottle and subject to change of color due to change in pH or CO2 of the sample medium;

a sensor LED illuminating the colorimetric sensor;
a reference LED illuminating the colorimetric sensor;
a control circuit configured to selectively and alternately activating the sensor LED and the reference LED; and
a photodetector, the photodetector configured to measure reflectance from the colorimetric sensor during the selective and
alternating illumination of the colorimetric sensor with the sensor LED and the reference LED and configured to generate intensity
signals;

a computer receiving the intensity signals, the computer including a memory storing a calibration relationship between intensity
signals for the reference LED as a function of distance of the bottle from a home position in relation to the detection arrangement;

wherein the reference LED has a peak wavelength of illumination between 750 and 900 nm.

US Pat. No. 9,738,864

DETECTION DEVICE, SYSTEM AND METHOD MAKING IT POSSIBLE TO DETECT THE PRESENCE OF A MICRO-ORGANISM IN A SAMPLE OR INSIDE A CONTAINER

1. A detection device for detecting the presence of at least one microorganism in the contents of a container comprising a
wall with a translucent zone, said detection device comprising:
a) at least one light source configured to illuminate the contents of the container by emitting an excitation light beam through
the translucent zone of the container;

b) at least one detector positioned at an angle of set value in relation to the direction of the excitation light beam to
detect at least one reaction light beam emitted in response to the reaction of the excitation light beam with the contents
of the container; and

c) at least one adjustable connector configured to attach the at least one light source and the at least one detector to an
outside wall of the container at a first fixed position and in proximity to the translucent zone and permit movement of the
at least one light source and the at least one detector in relation to the translucent zone to one or more other fixed positions
on the outside wall of the container,
wherein the at least one connector is positioned entirely outside of the container.
US Pat. No. 9,689,041

METHOD AND KIT FOR DETERMINING IN VITRO THE PROBABILITY FOR AN INDIVIDUAL TO SUFFER FROM COLORECTAL CANCER

1. A method comprising:
measuring an amount of at least one expression product expressed from at least one target gene selected from the group consisting
of the FAM198B, MYBL1, PDZK11P1, and VSIG10 genes,

wherein the amount of the expression product is measured using a peripheral blood sample obtained for in vitro colorectal
cancer testing from an individual.

US Pat. No. 9,926,323

FOLATE DERIVATIVES, USEFUL IN PARTICULAR IN THE CONTEXT OF THE FOLATE ASSAY

1. A method of in vitro assaying of folate(s) in a sample, the method comprising:(a) Contacting the sample with a folate binding partner in the presence of a folate conjugate decarboxylated in the ? position and suitable for emitting a signal in a non-radioisotopic competition immunoassay, the folate conjugate corresponding to general formula (III):
wherein:X is a linear aliphatic saturated hydrocarbon chain containing from 2 to 10 carbon atoms;
Y? is one of the following general formula (IV) or (V):


wherein R1 is —NH—, —O—, or —S—; and
M is a marker molecule capable of directly or indirectly generating a detectable signal,wherein the folate conjugate does not consist of either a NSP-DMAE-HD-pteroate compound or a NSP-DMAE-HEG-pteroate compound represented the following formulae (A) and (B):
(b) measuring a signal intensity from the folate conjugate bound with the folate binding partner; and
(c) identifying a concentration of the folate(s) present in the sample by referencing a calibration curve comprising a relationship between the measured signal intensity and the concentration of the folate(s).
US Pat. No. 9,902,988

METHOD FOR ISOLATING MICROORGANISMS ON A CULTURE MEDIUM, AND RELATED DEVICE

1. A method for isolating at least one microorganism from a sample, comprising:
(a) supplying a device for isolation of at least one microorganism, the device comprising
a bottom layer impermeable to water;
a nutrient layer, arranged on the bottom layer, comprising a support impregnated with a calendered, dehydrated culture medium;
an isolating layer permeable to the elements comprised in the nutrient layer, able to retain the at least one microorganism
on its surface and covering the whole or a portion of the nutrient layer; and

a protective top layer;
(b) depositing a defined volume of the sample on the isolating layer;
(c) isolating the at least one microorganism by exhaustion or by coating the sample using isolating means;
(d) incubating the device for a predetermined time and at a predetermined temperature allowing growth of the at least one
microorganism; and

(e) rehydrating the culture medium with a predetermined volume of liquid before or simultaneously with one or more of step
(b), step (c), and step (d).

US Pat. No. 9,874,568

METHOD OF DETECTING AT LEAST ONE MECHANISM OF RESISTANCE TO CARBAPENEMS BY MASS SPECTROMETRY

BIOMERIEUX, INC., Durham...

1. A method of detecting a VIM protein in a sample, comprising:
subjecting the sample to MS/MS spectrometry in MRM mode and detecting whether one or more VIM fragments selected from the
group consisting of SEQ ID NOs: 314-318 and 320-346 is present, wherein detection of any of the VIM fragments by the MRM mass
spectrometry indicates the presence of VIM protein in the sample.

US Pat. No. 9,874,570

METHOD OF DETECTING AT LEAST ONE MECHANISM OF RESISTANCE TO CEPHALOSPORINS BY MASS SPECTROMETRY

BIOMERIEUX, INC., Durham...

1. A method of detecting a TEM protein in a sample, comprising:
subjecting the sample to MS/MS spectrometry in MRM mode and detecting whether one or more TEM fragments selected from the
group consisting of SEQ ID NOS: 166-230, 232-257, 259-261, 1923, 1927, and 1928 is present, wherein detection of any of the
TEM fragments by the MRM mass spectrometry indicates the presence of TEM protein in the sample.

US Pat. No. 9,778,260

PROCESS FOR THE DETECTION AND EARLY SEROTYPING OF THE DENGUE VIRUS

1. A process for detecting an NS1 protein of a dengue virus, comprising:
contacting a blood sample from an individual with a ligand immobilized on a solid support that is specific for SEQ ID NO:
1 to capture NS1 protein if present in the blood sample; and

detecting whether the NS1 protein has been captured with mass spectrometry.
US Pat. No. 9,771,621

METHOD AND KIT FOR PERFORMING A COLORECTAL CANCER ASSAY

1. A method comprising:
extracting total RNA from a peripheral blood sample obtained from a patient suspected of having or having colorectal cancer;
contacting the total RNA, or cDNA or cRNA obtained from the total RNA, with reagents specific for at least five and no more
than 100 target genes; and

measuring the expression level of the at least five and no more than 100 target genes,
wherein the at least five and no more than 100 target genes includes the CD247, RRAS2, SH2D1B, LCK, and GZMB genes.
US Pat. No. 9,726,670

METHOD FOR THE ASSAY OF LIVER FATTY ACID BINDING PROTEIN, ACE AND CA 19-9 FOR THE IN VITRO DIAGNOSIS OF COLORECTAL CANCER

1. A method comprising:
assaying amounts of Liver Fatty Acid-Binding Protein (L-FABP), Carcinoembryonic Antigen (CEA), and Carbohydrate Antigen 19.9
(CA 19-9) in a biological fluid sample from a person suspected of having colorectal cancer.

US Pat. No. 9,632,031

SYSTEM FOR IN VITRO DETECTION AND/OR QUANTIFICATION BY FLUOROMETRY

1. A system for the in vitro detection and/or quantification by fluorometry of at least one analyte in a sample of fluid,
the system comprising:
a radiation source emitting a main beam in a given wavelength called emission wavelength;
an optical splitter arranged at the output of the radiation source for splitting the main beam into a first sample-energizing
beam and a second reference beam;

a first photodetector designed for providing a first analog detection signal in response to detecting a fluorescence ray emitted
by the sample, in a so-called fluorescence wavelength as a result of the excitation induced by the first energizing beam;

a second photodectector designed for providing at the output a second analog detection signal in response to a detection of
the second reference beam;

a generator outputting a sinusoidal carrier signal at a predefined frequency called carrier frequency, and at least one digital
demodulation signal at this same carrier frequency, wherein the sinusoidal carrier signal is in the form of a set of several
periodic sinusoidal iterations at the carrier frequency, a time difference between two consecutive iterations being higher
than a period of sinusoidal iterations, and wherein a first iteration of the sinusoidal carrier signal is used to check if
the first analog detection signal is above a predefined minimum threshold;

a digital/analog converter connected to the generator for converting the sinusoidal carrier signal into an analog modulation
signal at the carrier frequency, wherein if said first analog detection signal is below said minimum threshold, a return loop
is provided for reducing said analog modulation signal;

an amplitude modulator connected to the digital/analog converter and to the radiation source to modulate in amplitude the
main beam at the carrier frequency by applying the analog modulation signal on said radiation source;

an analog/digital converter connected to the photodetectors to convert the first analog detection signal into a first digital
fluorescence signal and the second analog detection signal into a second digital reference signal;

digital processing means connected to the generator and to the analog/digital converter, designed, on the one hand to process
the first digital fluorescence signal by demodulation at the carrier frequency in order to calculate a first so-called fluorescence
value characteristic of the amplitude of the fluorescence ray and, on the other hand, process the second digital reference
signal by demodulation at the carrier frequency in order to calculate a second so-called reference value characteristic of
the amplitude of the reference beam; and

a means for comparing the first fluorescence value and the second reference value to calculate a final result for establishing
the detection and/or quantification of the analyte.

US Pat. No. 9,982,298

PROCESS AND KIT FOR DETERMINING IN VITRO THE IMMUNE STATUS OF AN INDIVIDUAL

HOSPICES CIVILS DE LYON, ...

1. A process for determining in vitro the immune status of an individual having Systemic Inflammatory Response Syndrome comprising:a. obtaining a blood sample from the individual,
b. contacting the blood sample with at least two reagents specific to at least two products of expression of at least two target genes independently selected from the group consisting of HLA-DR, CD, S100A9, S100A8, ABIN-3, IRAK-M, LY64, CIITA, TNF, IL-10, GBP1, MMP7, CXCL1, CXCL10, COX2, FCN1, TNFAIP6, CXCL7, CXCL5, PID1 and RHOU,
c. measuring expression levels of said at least two target genes in the blood sample, and
d. comparing each of the expression levels of said at least two target genes respectively with an expression level for each of the at least two target genes in healthy individuals,
e. determining that the individual has a deregulated immune response by determining whether at least one component of an immune response of the individual is deregulated,
wherein a difference in the expression level of each of said at least two target genes relative to the expression level for each of the at least two target genes in healthy individuals indicates that at least one component of the immune response of the individual is deregulated, and
f. administering an immunostimulant or immunosuppressor to the individual with a deregulated immune response,
wherein:
the immunostimulant is selected from the group consisting of interleukins, growth factors, interferons, Toll agonists, blocking antibodies, transferrins, and apoptosis-blocking molecules, and
the immunosuppressor is selected from the group consisting of glucocorticoids, cytostatic agents, molecules that act on immunophilins, and cytokines.

US Pat. No. 9,969,758

ANTIMICROBIAL COMPOUNDS

1. An antimicrobial compound of formula (I):
or a salt thereof,
wherein R1 is:
a peptide part P1 consisting of a linear sequence of one to five amino acid residues, wherein at least one of the amino acid residues is a ?-chloroalanine residue; or
a peptide part P2 of formula (II):

wherein X is hydrogen or chlorine, and
Y is hydrogen or a linear sequence of one to four amino acid residues; and
wherein if X is hydrogen, Y is not hydrogen and an alanine residue is not in the N-terminal position of the linear amino acid sequence or bound to another amino acid residue via a peptide bond between the ? amino function of the alanine residue and the ? carboxylic acid function of another amino acid residue.
US Pat. No. 9,891,223

METHOD OF ASSAYING LEUKOCYTE ELASTASE INHIBITOR FOR THE IN VITRO DIAGNOSIS OF COLORECTAL CANCER

1. A method comprising:
assaying the expression levels of Leukocyte Elastase Inhibitor and Liver Fatty Acid-Binding Protein in a biological fluid
sample from a person suspected of having colorectal cancer, wherein:

the biological fluid sample is selected from the group consisting of samples of whole blood, serum, plasma, urine, saliva,
effusions, bone marrow, and stool extract, and

the assaying is performed by passing the biological fluid sample through a mass spectrometer.

US Pat. No. 9,878,849

DEVICE, SYSTEM AND METHOD FOR PUSHING AN OBJECT ACROSS A SURFACE BY MEANS OF A MAGNETIC CONTACT ELEMENT DRIVEN BY ANOTHER MAGNETIC ELEMENT

1. A device for conveying an object in order to move said object from an initial position to a final position, on a conveying
surface, said conveying device comprising:
at least one conveying belt rotationally mobile with the aid of corresponding driving means and which is located under the
conveying surface, said at least one conveying belt making it possible to define a first conveying path on the conveying surface;

a magnetic driving device comprising:
at least one first magnetic means integral with said at least one conveying belt and displaced with said conveying belt below
the conveying surface; and

at least one second magnetic means positioned on the conveying surface and suitable for moving on said conveying surface,
driven by said at least one first magnetic means through the conveying surface;

a contact device suitable for applying a contact force onto an external wall of the object,
wherein, when said at least one conveying belt is moving in the presence of an object on the conveying surface, the second
magnetic means is moved on the conveying surface, along the first conveying path, driven by the first magnetic means, and
wherein the second magnetic means pushes onto the external wall of the object, and

wherein the contact device simultaneously applies at least one contact force onto the external wall of the object to enable
guided movement of said object on the conveying surface.

US Pat. No. 9,833,779

METHODS, SYSTEMS, AND COMPUTER PROGRAM PRODUCTS FOR DETECTING PIPETTE TIP INTEGRITY

bioMerieux, Inc., Durham...

1. A method comprising:
collecting pressure data while aspirating a gas into a pipette tip attached to a pipette, the pressure data including a plurality
of pressure values measured at an internal portion of the pipette and taken over a given time interval, the plurality of pressure
values including a maximum pressure value and a minimum pressure value;

estimating a pressure range value between the maximum pressure value and the minimum pressure value;
responsive to the pressure range value being greater than or equal to a lower threshold and the pressure range value being
less than or equal to an upper threshold, determining that the pipette tip attached to the pipette is properly functioning,
or

responsive to the pressure range value being less than a lower threshold or the pressure range value being greater than an
upper threshold, determining that the pipette tip attached to the pipette is not properly functioning; and

responsive to the pressure range value being greater than or equal to the lower threshold and the pressure range value being
less than or equal to the upper threshold, determining that the pipette tip attached to the pipette is suitable for use, or

responsive to the pressure range value being less than the lower threshold or the pressure range value being greater than
the upper threshold, determining that the pipette tip is defective, clogged, and/or improperly attached to the pipette.

US Pat. No. 9,790,534

METHODS FOR SEPARATION, CHARACTERIZATION AND/OR IDENTIFICATION OF MICROORGANISMS USING SPECTROSCOPY

bioMerieux, Inc., Durham...

1. A method of characterizing and/or identifying an unknown microorganism from a test sample, comprising:
(a) obtaining a test sample known to contain or that may contain an unknown microorganism;
(b) selectively lysing non-microorganism cells that may be present in said test sample to produce a lysed sample;
(c) layering said lysed sample on a density cushion in a container, wherein said density cushion has a homogeneous density;
(d) centrifuging said container to separate said unknown microorganism from other components of said lysed sample, said unknown
microorganism passing through said density cushion to form a microorganism pellet at the bottom of said container;

(e) spectroscopically interrogating said pellet in situ to produce an excitation/emission matrix (EEM) of said unknown microorganism,
wherein said spectroscopic interrogation comprises intrinsic fluorescence in front face mode; and

(f) characterizing and/or identifying said unknown microorganism in said pellet by comparison of the excitation/emission matrix
with spectroscopic measurements taken, or spectroscopic properties predicted, of known microorganisms.

US Pat. No. 9,784,654

METHOD FOR TREATING AT LEAST ONE BIOLOGICAL SAMPLE CONTAINING A TARGET MICROORGANISM

1. A device for processing at least one biological sample capable of containing at least one target microorganism within at
least one container, said device comprising:
at least one displacement device for generating the displacement of the contents of the at least one container;
at least one site for receiving the at least one container, the at least one container being configured to receive the at
least one biological sample within the at least one container wherein the site is delimited by a wall fixed on a base and
the at least one displacement device, movable with respect to the base, wherein the at least one container comprises a flexible
material to allow the at least one container to be compressed against the wall,

wherein the at least one displacement device is movable with respect to the wall to exert a pressure onto the outer surface
of the at least one container comprising the flexible material to impose on the at least one container a deformation for generating
at least two displacements of the contents of the at least one container at at least two different intensities comprising:

a weakest displacement intensity allowing the homogenization of the at least one biological sample wherein the at least one
displacement device is displaced from it/their first position(s) to it/their second position(s), and vice versa, leading the
contents of the at least one container to be displaced from a level n, corresponding to a level of the contents at rest, to
a homogenization level nh, distinct from the level n, and vice versa and a strongest displacement intensity in a direction
of the wall allowing a generation of an increased displacement of the contents to a level n+1, which is different from levels
n and nh, such that the contents come into contact with at least one culture, at least one analysis device, or a combination
thereof, positioned inside the at least one container, between level n+1 inclusive and level nh exclusive,

wherein the at least one displacement device is selected from a movable arm, a movable blade, a movable wall and a moveable
applicator.

US Pat. No. 9,757,723

SAMPLE TEST CARDS

bioMerieux, Inc., Durham...

1. A sample test card, comprising:
(a) a card body defining a first surface and a second surface opposite said first surface, a fluid intake port and a plurality
of sample wells in which biological reagents have been deposited disposed between said first and second surfaces, said first
and second surfaces sealed with a sealant tape covering said plurality of sample wells;

(b) a fluid channel network connecting said fluid intake port to said sample wells, said fluid channel network comprising
at least one distribution channel, and a plurality of fill channels connecting said at least one distribution channel to said
sample wells, wherein each of said fill channels connects said distribution channel to individual sample wells; and

(c) two or more fluid over-flow reservoirs comprising a first fluid over-flow reservoir and a second fluid over-flow reservoir,
said two or more over-flow reservoirs being connected to said distribution channel downstream from said sample wells by a
fluid over-flow channel, wherein the two or more fluid over-flow reservoirs are connected to the distribution channel in series,
such that the first fluid over-flow reservoir is connected directly to the distribution channel via the fluid over-flow channel
and the first fluid over-flow reservoir connects the second fluid over-flow reservoir to the distribution channel, and wherein
the second fluid over-flow reservoir is configured to receive fluid from the first fluid over-flow reservoir.

US Pat. No. 9,574,219

DEVICE FOR SAMPLING A SPECIMEN CONTAINER

BIOMERIEUX, INC., Durham...

1. An apparatus comprising:
a plurality of disposable, single use devices configured for both sampling a specimen container having a closure sealing the
interior of the specimen container from the environment and for separation of a microbial agent in a test sample withdrawn
from the specimen container, each of the plurality of disposable, single use device comprising;

a needle,
a body coupled to the needle and defining a lytic chamber in fluid communication with the needle;
a port forming an opening in the body, the port in fluid communication with the lytic chamber;
a separation chamber in communication with the lytic chamber;
a capillary tube having a closed bottom, the separation chamber sized to contain a concentrated microorganism pellet at the
closed bottom, the capillary tube located within the separation chamber; and

a valve connecting the lytic chamber with the separation chamber;
a sample removal apparatus;
an identification and/or characterization module comprising:
a computer operably connected to the identification and/or characterization module, the computer programmed to identify the
concentrated microorganism to family, genus, species, and/or strain level from data obtained from interrogation of the concentrated
microorganism pellet; and

a robotic gripping apparatus having a plurality of rotational joints and a pneumatic gripper placed on one of the rotational
joints, the robotic gripping apparatus coupled to the sample removal apparatus, the robotic gripping apparatus configured
to access and transfer the plurality of disposable, single use combined devices.

US Pat. No. 10,047,387

SYSTEM AND METHOD FOR AUTOMATICALLY VENTING AND SAMPLING A CULTURE SPECIMEN CONTAINER

BIOMERIEUX, INC., Durham...

1. An automated method for sampling a liquid specimen container in the form of a bottle having a closure sealing the interior of the specimen container from the environment comprising the steps of:(a) automatically and with the aid of a robotic transfer mechanism releasably grasping a sampling device having a needle, a chamber connected to the needle and a port connected to the chamber and connecting the port to a pneumatic system;
(b) automatically moving the robotic transfer mechanism so as to place the sampling device in a position proximate to the bottle;
(c) loading the sampling device with a selective lytic agent prior to the step of inserting the needle of the sampling device through the closure of the bottle;
(d) holding the bottle in a rack and moving the rack so as to place the bottle in upward orientation;
(e) automatically inserting the needle of the sampling device through the closure so as to place the needle into the interior of the bottle sampling device;
(f) altering the pressure within the bottle while the bottle is in an upwards orientation using the pneumatic system and the sampling device to substantially equalize the pressure in the bottle to the atmospheric pressure;
(g) moving the rack so as to place the bottle into a downward orientation; and
(h) drawing a portion of the liquid sample contained in the bottle into the chamber of the sampling device while the bottle is in the downward orientation by applying a vacuum to the port of the sampling device using the pneumatic system.

US Pat. No. 10,011,385

LABEL APPLICATOR

bioMerieux, Inc., Durham...

1. A label applicator comprising:a body having a first side and a second side, the second side comprising a curved surface, wherein at least one pathway extends from the first side of the body to the curved surface on the second side of the body;
a base positioned proximate to the first side of the body;
at least one first resilient member having a defined length between a first end and a second end, wherein the at least one first resilient member extends through the at least one pathway, the first end of the at least one first resilient member engages with the base, and the second end of the at least one first resilient member extends beyond the curved surface; and
at least one second resilient member engaging the body and the base,
wherein the second end of the at least one first resilient member is configured to removably attach to a label, wherein the at least one first resilient member moves independently of the body such that pressure initially applied to the label as the label is attached to the second end compresses the second end toward the curved surface of the body, and wherein, upon the pressure causing the second end to reach the curved surface, further pressure compresses the body toward the base.

US Pat. No. 10,006,074

AUTOMATED MICROBIAL DETECTION APPARATUS

bioMerieux, Inc., Durham...

1. An automated detection apparatus for rapid non-invasive detection of microorganism growth in a test sample, comprising:(a) a housing enclosing an interior chamber;
(b) a holding structure contained within said interior chamber and comprising a plurality of wells each for holding a sealable specimen container;
(c) a container locator device comprising a rotatable disk containing one or more locator wells each capable of holding one of said specimen containers and a rotatable turntable for rotating the sealable specimen container within an entrance location, said rotatable disk configured to rotate in a horizontal plane about a vertical axis and thereby locate said specimen containers among one or more container work-flow stations;
(d) an automated loading mechanism for automated loading of said specimen container into said interior chamber, said automated loading mechanism comprises a conveyor belt and a guide rail, said conveyor belt configured to deposit one of said specimen containers into one of said locator wells, said guide rail positioned to guide said specimen container into said locator well; and
(e) an automated transfer mechanism located within said interior chamber configured for automated transfer of said specimen container within said interior chamber, wherein said automated transfer mechanism comprises a multi-axis robotic transfer arm, the robotic transfer arm further comprising:
a horizontal slide supporting a robotic head and a gripper mechanism; and
a pivot plate comprising a pivot plate guide rail, a pivot slot, and a pivot slot cam follower operable to allow the robotic head to slide along the horizontal slide,
wherein the gripper mechanism is configured to pick up the specimen container at the container pick-up station,
wherein the robotic head rotates from a vertical orientation to a horizontal orientation as the robotic head slides along the horizontal slide, and
wherein the specimen container is transferred to one of the plurality of wells in the holding structure in the horizontal orientation; and
(f) a detection unit located within said interior chamber for the detection of microorganism growth in said specimen container.

US Pat. No. 10,007,995

METHOD, SYSTEM AND COMPUTER PROGRAM PRODUCT FOR PRODUCING A RAISED RELIEF MAP FROM IMAGES OF AN OBJECT

1. A method for obtaining a model of an object surface from a plurality of images of said object (107), wherein the object (107) is illuminated with one or more illumination sources (104, 105, 106), the method comprising:obtaining a set of images each comprising an array of pixels and representing similar views of an object, wherein the similar views are obtained under different illumination conditions;
defining a model function (f) that expresses the known pixel intensity values of the images in terms of the following unknown model components:
a first model component (A) representing the albedo of the object (107) at each pixel location, the first model component being an albedo value which is the same for the plurality of images;
a second model component (L) representing an intensity of illumination for each image, the second model component being an illumination source intensity value which is the same for all pixels of each image;
a third model component (V) representing a specific illumination direction, the third model component being an illumination vector which is different for each image and the same for all pixels of each image;
a fourth model component (N) representing surface normal directions of the object surface at each pixel position, the fourth model component being a normal vector which is the same for all images;
performing one or more sequences of minimization operations to minimize a difference function between the pixel values obtained from the set of images and pixel values calculated using said model function (f), each minimization operation being performed by allowing one of said model components (A, L, V, N) to vary while the others remain unchanged;
outputting the fourth model component (N) as said model of the object surface, wherein model function (f) comprises a modified model function (g), wherein the model function (f) related to the first, second, third and fourth model components (A, L, V, N) is equal to the modified model function (g) related to a first, second and third model sub-components (A?, L?, V?) and the fourth model component (N), wherein
the first model sub-component (A?) is adapted by a first structuring component (WA), to reproduce the surface properties of the object (107);
the second model sub-component (L?) is adapted by a second structuring component (WL), to reproduce the illumination conditions of the illumination sources (104, 105, 106); and
the third model sub-component (V?) is adapted by a third structuring component (WV), to reproduce the illumination conditions of the illumination sources (104, 105, 106).

US Pat. No. 9,957,473

DEVICE FOR PREPARING BIOLOGICAL SAMPLES

1. A device for preparing a biological sample, comprising:a fixed support comprising a base that extends in a first plane, and an upper surface opposed to and inclined relative to the first plane of the base,
a filtration block on the upper surface and configured to be removable from the fixed support,
the filtration block comprising a collecting tank, the collecting tank comprising a wall and a filtering device, the filtering device extending in a second plane and dividing the collecting tank into a collection area that retains the biological sample before passing through the filtering device, and a suction area, the suction area being configured to be connected to a suction device,
wherein the second plane of the filtering device is inclined relative to the first plane of the base of the fixed support, and
the fixed support is fixed relative to the incline of the second plane.
US Pat. No. 9,944,974

METHOD FOR THE SPECIFIC ISOLATION OF NUCLEIC ACIDS OF INTEREST

1. A method for selective isolation of microorganisms of interest in a liquid biological sample comprising or likely to comprise:microorganisms of interest whose cell membrane or capsid does not contain cholesterol, and
untargeted elements, i.e.:
untargeted cells whose cell membrane contains cholesterol, and
optionally, viruses with envelopes containing cholesterol, and
optionally mycoplasmas containing cholesterol, and
optionally, debris of microorganisms of interest and/or of untargeted cells,
said method comprising the following steps:
a) bringing the liquid biological sample into contact with a saponin formulation, in order to destabilize the cell membranes containing cholesterol or the viral envelopes containing cholesterol or the membranes of mycoplasmas containing cholesterol,
b) performing osmotic shock of the untargeted cells in order to lyse them specifically,
c) adding a solution of at least one enzyme able to lyse free nucleic acids derived from the untargeted elements lysed in solution in the sample, allowing the microorganisms of interest to be obtained selectively, and
in step a), after steps a) and b), or after step c), adding an agent for precipitating the unlysed microorganisms of interest in solution in the sample.
US Pat. No. 9,933,426

METHOD AND KIT FOR DETERMINING THE PROBABILITY THAT A PATIENT WILL DEVELOP A SEVERE CASE OF DENGUE

1. A method of determining whether a patient infected with dengue virus will develop severe dengue, comprising:obtaining a blood sample collected from the patient infected with dengue virus;
measuring the expression level of olfactomedin 4 from the blood sample; and
comparing the expression level of olfactomedin 4 to a reference value obtained from individuals having dengue virus infections without developing severe dengue,
wherein, if the expression level of olfactomedin 4 is greater that the reference value, it is determined that the patient will develop severe dengue.
US Pat. No. 9,902,987

METHOD FOR DETECTING AND DIRECTLY IDENTIFYING A MICROORGANISM IN A BIOLOGICAL SAMPLE BY AN OPTICAL ROUTE

1. A method for detecting a target microorganism present in a sample, the method comprising:
incubating, in a homogenizing bag, a sample mixture containing the sample and a culture medium for 6 to 48 hours to permit
growth of the target microorganism;

transferring at least a fraction of the incubated sample mixture from the homogenizing bag to a secondary container that contains
a reaction mixture to detect microorganisms in the combined reaction mixture and incubated sample mixture, the reaction mixture
comprising a dye, membrane stain, or a fluorescent compound, that colors or causes to fluoresce the microorganisms present
in the combined reaction mixture and incubated sample mixture;

immersing, in the combined reaction mixture and incubated sample mixture, a substrate configured to specifically capture the
target microorganism; and

monitoring for an appearance of coloration or fluorescence of the capture substrate, wherein coloration or fluorescence of
the capture substrate indicates that the target microorganism is fixed on the capture substrate.

US Pat. No. 9,890,196

EZRIN ASSAY METHOD FOR THE IN VITRO DIAGNOSIS OF COLORECTAL CANCER

CENTRE NATIONALE DE RECHE...

1. A peptide comprising an amino acid sequence having at least 85% sequence identity with the epitope of SEQ ID No.4+SEQ ID
No.5 or SEQ ID No.6+SEQ ID No.7, wherein (i) the peptide has no more than 20 amino acid residues between SEQ ID No.4 and SEQ
ID No.5 or between SEQ ID No.6 and SEQ ID No.7, and (ii) the peptide has no more than 10 additional amino acid residues on
each side of the amino acid sequence.

US Pat. No. 9,795,959

METHODS, SYSTEMS, AND COMPUTER PROGRAM PRODUCTS FOR VERIFYING DISPENSING OF A FLUID FROM A PIPETTE

bioMerieux, Inc., Durham...

1. A method comprising:
collecting pressure data while dispensing fluid from a pipette tip attached to a pipette, the pressure data including a plurality
of pressure values measured at an internal portion of the pipette and taken over a given time interval, the plurality of pressure
values including a maximum pressure value and a minimum pressure value;

estimating a pressure range value between the maximum pressure value and the minimum pressure value; and
responsive to the pressure range value being greater than or equal to a first threshold, determining that the fluid included
a liquid, or

responsive to the pressure range value being less than the first threshold, determining that the fluid did not include a liquid;
estimating a pressure area ratio that identifies at least two pressure data curves, each of the at least two pressure data
curves corresponding to at least a portion of the plurality of pressure values;

comparing the pressure area ratio to a second threshold; and
responsive to the pressure area ratio being greater than the second threshold, determining that the fluid included a sufficient
amount of the liquid, or

responsive to the pressure area ratio being less than or equal the second threshold, determining that the fluid did not include
a sufficient amount of the liquid.

US Pat. No. 10,059,975

METHODS FOR THE ISOLATION AND IDENTIFICATION OF MICROORGANISMS

bioMerieux, Inc., Durham...

1. A method of identifying microorganism from a test sample, comprising:(a) obtaining a test sample known to contain or that may contain microorganisms;
(b) selectively lysing non-microorganism cells in said test sample to produce a lysed sample;
(c) layering the lysed sample over a density cushion in a container, wherein said density cushion has a density selected from the range consisting of from about 1.025 to about 1.12 g/ml;
(d) centrifuging the container at a speed and/or duration such that the density cushion does not comprise a density gradient before or after the centrifugation to separate microorganisms from other components of said lysed sample, said microorganisms passing through said density cushion to form the pellet of microorganisms at the bottom of said container;
(e) spectroscopically interrogating said pellet to produce an excitation-emission matrix (EEM) of said unknown microorganism, wherein said spectroscopic interrogation comprises intrinsic fluorescence, and
(f) identifying the microorganisms from the pellet by comparison of the spectroscopic measurements with spectroscopic measurements taken, or spectroscopic properties predicted, of known microorganisms, to the family level, genus level, species level, and/or strain level.
US Pat. No. 10,040,829

METHODS FOR PRODUCING PEPTIDES INCLUDING HERV-W ENVELOPE MOTIFS AND FOR PRODUCING ANTIBODIES SPECIFIC FOR THE PEPTIDES

1. A method comprising:chemically synthesizing a peptide; or
performing genetic engineering to produce the peptide,
wherein the peptide is no longer than the receptor binding domain of the HERV-W envelope protein and comprises:
an N-terminus motif including an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 29;
a C-terminus motif including an amino acid sequence selected from the group consisting of SEQ ID NO: 30 to SEQ ID NO: 40; and
at least one motif between the N-terminus and the C-terminus including an amino acid sequence selected from the group consisting of SEQ ID NO: 41, SEQ ID NO: 42, and SEQ ID NO: 73.

US Pat. No. 10,006,075

AUTOMATED LOADING MECHANISM FOR MICROBIAL DETECTION APPARATUS

bioMerieux, Inc., Durham...

1. An automated detection apparatus for rapid non-invasive detection of microorganism growth in a test sample, comprising: a housing enclosing an interior chamber;a holding structure having a plurality of wells for holding one or more specimen containers, wherein the holding structure further comprises a retention feature operable to hold the specimen container in one of the plurality of wells, the retention feature comprising a canted coiled spring and a v-shaped holding plate, and wherein said holding structure further comprises an agitation assembly;
a detection unit located within said interior chamber for the detection of microorganism growth in the specimen container;
an automated loading mechanism for automated loading of said specimen container into said interior chamber, wherein said automated loading mechanism comprises a first end and a second end, said automated loading mechanism further comprising a container loading station located at said first end, a conveyor belt, one or more guide rails, and a container entrance location located at said second end, and wherein said conveyor belt is configured to transport said specimen container from said loading station to said container entrance location, and subsequently through said container entrance location, wherein said one or more guide rails guide the specimen container into a single file line at the second end of the automated loading mechanism;
a container locator device located within said housing, said container locator device comprising a rotatable disk containing one or more locator wells each capable of holding a single specimen container and a pusher arm attached to a pusher motor via a pusher support structure, said rotatable disk configured to rotate in a horizontal plane about a vertical axis and thereby locate said specimen containers among a plurality of work-flow stations comprising a container imaging station, a container pick-up station, and a container transfer station , wherein the pusher arm rotates around a vertical axis through the pusher support structure to advance the single specimen container to a downstream instrument when the single specimen container reaches the container transfer station; and wherein said conveyor belt is configured to place one of said specimen containers into one of said locator wells.

US Pat. No. 10,002,276

BARCODE-READING DEVICE AND MACHINE INCLUDING SUCH A DEVICE FOR AUTOMATED ANALYSIS OF A SAMPLE

1. A bar code reader device (10) comprising a bar code reader apparatus (12) having:a) a light emitter system (14) having an incident light source (16) emitting incident light towards a useful illuminated zone;
b) a light recovery system (28) having a reflected light conditioning system (30), and which recovers light reflected from a useful viewing zone and through the reflected light conditioning system (30); and
c) a photoelectric sensor (26) for converting the reflected light recovered through the reflected light conditioning system (30) into an electrical signal representative of the recovered reflected light;
the device (10) being characterized in that it includes an auxiliary optical system (36) that is arranged permanently in the working viewing zone at a distance from the sensor (26) and in series with the reflected light conditioning system (30) in such a manner that a fraction but not all of the useful viewing zone is intercepted by the auxiliary optical system (36).
US Pat. No. 9,977,020

PROTEINS USED FOR THE DIAGNOSIS OF LYME BORRELIOSIS

1. A chimeric polypeptide comprising (i) a first amino acid sequence comprising any of the amino acid sequences of SEQ ID Nos: 1, 3, 5 and 6, and (ii) a second amino acid sequence comprising any of the amino acid sequences of SEQ ID Nos: 2, 4 and 7.

US Pat. No. 9,951,369

DEVICE DESIGNED TO RECEIVE A BIOLOGICAL SAMPLE

1. A device designed to receive at least one biological sample, the device comprising:at least one leak-proof container designed to receive at least one biological sample, the at least one leak-proof container comprising an enclosure, at least one filling means, and at least one closing means designed to hermetically close the at least one filling means;
at least one sampling means positioned inside the enclosure of the at least one leak-proof container, the at least one sampling means designed to sample biological and/or physicochemical information from the at least one biological sample, the at least one sampling means further designed to be analysed after the biological and/or physicochemical information is sampled and/or placed in a release position;
at least one receptacle comprising at least one disinfecting agent designed to be released inside the at least one leak-proof container after the at least one receptacle is opened; and
when the at least one sampling means is designed to be analysed after the biological and/or physicochemical information is sampled, at least one analysis restricting means designed to restrict the analysis of the at least one sampling means;
wherein at least one of at least a portion of the at least one sampling means and/or at least a portion of the at least one analysis restricting means is/are designed to shift from a first position to a second position, wherein the first position is designed to prevent the analysis of the at least one sampling means and/or the release of the at least one sampling means from the at least one leak-proof container, wherein the second position is designed to provide for analysis of the at least one sampling means and/or release of the sampling means from the at least one leak-proof container; and
wherein at least one of the portion of the at least one sampling means and the portion of the at least one analysis restricting means is connected to the at least one receptacle such that an opening of the at least one receptacle is mechanically induced by shifting from the first position to the second position.
US Pat. No. 9,995,751

METHOD FOR DETECTING AT LEAST ONE MECHANISM OF RESISTANCE TO GLYCOPEPTIDES BY MASS SPECTROMETRY

1. A method of detection, for at least one microorganism contained in a sample, of at least one marker of resistance to a glycopeptide that is vancomycin, comprising detection, by MS/MS mass spectrometry in MRM mode, of at least one peptide of said microorganism selected from the Van type peptides of SEQ ID No. 5 to 16, 29 to 35, 59 to 71, 80 to 83, 85 to 91, 95 to 102, 104 to 120, 122 to 139 or 141 to 154.

US Pat. No. 10,053,721

ANTIMICROBIAL RESISTANCE STATUS DETERMINATION DEVICE AND METHOD

bioMerieux, Inc., Durham...

1. A device for determining the antimicrobial resistance status of a microorganism from a sample bottle in which a microbial culture has grown, the device comprising:(a) a housing having at least one chamber for receiving a sample;
(b) an agitation device operably connected to the housing and configured to agitate the housing, wherein the agitation device is a step motor configured to rock the housing at least +/?18° from horizontal:
(c) a light source positioned to direct light through a side of the chamber; and
(d) a photodetector positioned such that light transmitted or scattered by the sample is sensed by the photodetector.
US Pat. No. 10,144,912

USE OF POLYMER FILM FOR PACKAGING A CULTURE MEDIUM

1. A polymer film for packaging at least one microorganism culture medium, said film comprising at least one layer of polystyrene and at least one heat-sealing layer, wherein at least one of the layers is microperforated so as to include perforations having sizes of between 10 ?m and 50 ?m and the film has an average water vapour permeability of between 30.0 g/m2×24 hours and 140.0 g/m2×24 hours.
US Pat. No. 10,132,800

METHOD FOR MEASURING THE PLASMA CONCENTRATION OF AN ANALYTE DIRECTLY ON A WHOLE BLOOD SAMPLE

1. A method of measuring an amount of analyte in a whole blood sample, wherein the method comprises:performing a calibration of the method,
wherein the calibration comprises:
providing a plurality of calibration whole blood samples;
measuring an haematocrit level and an analyte amount directly in each of the plurality of calibration whole blood samples;
measuring an analyte amount in a plasma sample from each of the plurality of calibration whole blood samples; and
calculating polynomial coefficients of relation DP=Pa(DST, DH) from values of haematocrit level and analyte amount measured in the plurality of calibration whole blood samples, and values of analyte amount measured in the plasma samples from the plurality of calibration whole blood samples,
where DP is the measured analyte amount in plasma, DST is the measured analyte amount in whole blood, DH is the measured haematocrit level, and Pa is a non-constant polynomial of a degree greater than or equal to 1 having as indeterminate values the measured analyte amount, DST, and the measured haematocrit level, DH, said relation having polynomial coefficients depending on the analyte;
measuring an analyte amount directly in the whole blood sample;
calculating a corrected analyte amount according to the relation:
DP=Pa(DST, DH)
where DP is the corrected analyte amount, DSTis the measured analyte amount, and DH is the measured haematocrit level Pa DST DH; and
providing the calculated value of the corrected analyte amount.

US Pat. No. 10,144,948

METHOD OF SAMPLING AND/OR DEPOSITING A SAMPLE OF BIOLOGICAL MATTER AND DEVICE IMPLEMENTING SUCH METHOD

1. A device (2) for sampling and depositing all or part of a sample (11) of biological matter (7), which is crude, enriched or cultured through contact with a semi-solid culture medium such as an agar medium (8), and intended to be deposited into a container (9) or onto an analysis plate (14), comprising:a probe (3) equipped with a pointed and closed terminal end (4),
a cooling means intended for frosting the terminal end (4),
driving means (5) intended:
for exerting a pressure from the probe (3) onto the sample (11) so as to freeze all or part of the water contained in the sample (11) in order to stick it to the terminal end (4),
for separating all or part of the sample (11) from the culture medium (8),
to bring all or part of the sample (11) to the container (9) or the analysis plate (14) and at least one contact sensor which stops the descent of the driving means (5) once contact between the terminal (4) and the biological matter (7) is made.

US Pat. No. 10,099,220

OBTURATION DEVICE FOR APPLYING A METHOD FOR ISOLATING A SAMPLE WELL OF A TEST CARD FOR ANALYSIS, AND RESULTING TEST CARD AND PROCESSING MACHINING USING THE OBTURATION DEVICE

1. An obturation device for applying a method for isolating at least one sample well (2) laid out in a test card (1) for analysis,wherein said test card includes a support (3) having at least one first main face (4, 5) from which is laid out at least one channel (9a, 9b, 9c) communicating with at least said well (2), the first face (4, 5) being coated with a membrane (17) provided with an adhesive (18) and which will cover said channel (9a, 9c), with a covering area (171),
wherein the test card includes an isolation area for the sample well comprising a portion of a first channel and an obturation area for the sample well comprising a portion of a second channel, contiguous to the isolation area (Zi), which opens into the first channel at an intersection between the first channel and the second channel, wherein axes of the first and second channels are not aligned;
and wherein the device includes a system (22) for exerting a force on at least one portion of a covering area (171) of the adhesive membrane (17) for displacing the membrane until causing the membrane to at least locally fit the shape of the wall (91) of a first channel (9a, 9c) so as to isolate said well (2) with respect to the channel by driving out the adhesive from the isolation area (Zi) of the first channel into the obturation area (Zo) of the second channel, by applying the force on the adhesive membrane.
US Pat. No. 10,072,300

KIT FOR THE PROGNOSIS OF COLORECTAL CANCER

1. A method for detecting gene expression, comprising:obtaining a blood sample collected from a human having colorectal cancer; and
detecting expression levels of the BST1, MGST1, HP, RCAN3, and SRA1 genes from the blood sample by hybridization, amplification, or sequencing wherein detecting the expression levels comprises detecting RNA transcripts transcribed from the genes, cDNAs complementary to the RNA transcripts, or cRNAs complementary to the cDNAs, wherein:
the BST1 gene has the nucleotide sequence shown in SEQ ID NO: 1;
the MGST1 gene has the nucleotide sequence shown in SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, or 10;
the HP gene has the nucleotide sequence shown in SEQ ID NO: 11 or 12;
the RCAN3 gene has the nucleotide sequence shown in SEQ ID NO: 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22; and
the SRA1 gene has the nucleotide sequence shown in SEQ ID NO: 23 or 24.
US Pat. No. 10,144,947

METHOD FOR DETECTING, IDENTIFYING AND ENUMERATING MICRO-ORGANISMS IN A POROUS SUPPORT DRY-IMPREGNATED WITH A DEHYDRATED REACTION MEDIUM

1. A device comprising a porous support comprising at least one dehydrated reaction medium in powder form distributed throughout the thickness of the porous support, wherein the reaction medium is a visualization medium and/or a culture medium and said porous support has a thickness of between 0.5 and 2 mm and is calendered.
US Pat. No. 10,119,114

DEVICE FOR THE LYSIS OF MICROORGANISMS PRESENT IN AN ENVIRONMENTAL OR CLINICAL SAMPLE AND THE EXTRACTION OF NUCLEIC ACIDS FROM SAID MICROORGANISMS FOR ANALYSIS

1. A cartridge which can be positioned inside an air collection device and receive a means for recovering nucleic acids, said cartridge being substantially cylindrical and having an upper end and lower end, said cartridge comprising a microorganism retaining zone, said retaining zone comprising microorganism lysis means for lysing the microorganisms, whereinthe upper end of the cartridge is open,
the lower end is constituted of a wall, having, in its center, an orifice, there being, along an extension of said orifice, a duct extending, inside said cartridge, and
the microorganism retaining zone comprises a material configured to retain the microorganisms, configured to keep the lysis means in place, and configured to dissolve in the presence of a liquid to release the lysis means from the material.

US Pat. No. 10,105,697

METHODS, SYSTEMS, AND COMPUTER PROGRAM PRODUCTS FOR DETECTING A SURFACE USING A PIPETTE AND/OR POSITIONING A PIPETTE

bioMerieux, Inc., Durham...

1. A method comprising:measuring a pipette pressure at an internal portion of a pipette to generate a plurality of pipette pressure values;
determining a pressure difference relative to at least one previously measured pipette pressure value;
estimating a rate of change in pipette pressure, wherein estimating the rate of change in pipette pressure comprises weighting the pressure difference to provide a weighted pressure difference;
estimating at least one statistical variable corresponding to the rate of change in pipette pressure;
comparing the at least one statistical variable to at least one pipette pressure related threshold; and
responsive to comparing the at least one statistical variable to the at least one pipette pressure related threshold, estimating a pipette position.

US Pat. No. 10,068,760

MALDI-TOF MASS SPECTROMETERS WITH DELAY TIME VARIATIONS AND RELATED METHODS

bioMerieux, Inc., Durham...

1. A delayed extraction (DE) matrix assisted laser desorption ionization (MALDI) time of-flight mass spectrometer (TOF MS), comprising:a housing enclosing an analysis flow path;
a laser in communication with the analysis flow path;
a variable voltage input;
an extraction plate connected to the variable voltage input;
a flight tube in the housing;
a detector in communication with the flight tube; and
a variable delay time module in communication with the laser and the variable voltage input configured to operate the variable voltage input with a plurality of different delay times during signal acquisition of a single sample to thereby obtain signal with a plurality of different focus masses at the detector.

US Pat. No. 10,207,263

METHODS, SYSTEMS, AND COMPUTER PROGRAM PRODUCTS FOR DETECTING PIPETTE TIP INTEGRITY

bioMerieux, Inc., Durham...

1. A computer system, comprising:a processor; and
a memory coupled to the processor, the memory comprising computer readable program code embodied therein that, when executed by the processor, causes the processor to perform operations comprising:
collecting pressure data while a gas is aspirated into a pipette tip attached to a pipette, the pressure data including a plurality of pressure values measured at an internal portion of the pipette and taken over a given time interval, the plurality of pressure values including a maximum pressure value and a minimum pressure value;
estimating a pressure range value between the maximum pressure value and the minimum pressure value while the gas is aspirated into the pipette tip attached to the pipette;
responsive to the pressure range value being greater than or equal to a lower threshold and the pressure range value being less than or equal to an upper threshold, determining that the pipette tip attached to the pipette is properly functioning, or
responsive to the pressure range value being less than a lower threshold or the pressure range value being greater than an upper threshold, determining that the pipette tip attached to the pipette is not properly functioning; and
responsive to the pressure range value being greater than or equal to the lower threshold and the pressure range value being less than or equal to the upper threshold, determining that the pipette tip attached to the pipette is suitable for use, or
responsive to the pressure range value being less than the lower threshold or the pressure range value being greater than the upper threshold, determining that the pipette tip is defective, clogged, and/or improperly attached to the pipette.
US Pat. No. 10,184,144

IDENTIFICATION AND/OR CHARACTERIZATION OF A MICROBIAL AGENT USING TAXONOMIC HIERARCHICAL CLASSIFICATION

bioMerieux, Inc., Durham...

1. A method for rapid identification and/or characterization of a microbial agent present in a sample, comprising the steps of:obtaining analytic test data of the microbial agent in the sample, the analytic test data comprising mass spectrometry data generated by a mass spectrometer;
transforming the analytic test data, wherein transforming comprises computing a natural logarithm of the analytic test data and calculating a first derivative of the natural logarithm values, thereby minimizing strain to strain variations in the analytic test data within an organism group; and
with the aid of a programmed computer, performing a multi-level classification algorithm coded as a set of processing instructions operating on the transformed analytic test data, wherein the multi-level classification algorithm is selected from the group consisting of a minimum distance calculation and a K-nearest neighbor classification algorithm, the multiple levels corresponding to different levels in a taxonomic hierarchy for microbial agents suspected of being in the sample.

US Pat. No. 10,174,068

METHODS OF FUNCTIONALIZATION AND REAGENTS USED IN SUCH METHODS USING AN AZA-ISATOIC ANHYDRIDE OR A DERIVATIVE THEREOF, BIOLOGICAL MOLECULES THUS TREATED AND KITS

1. A functionalizing reagent of formula (I):
wherein:
Y represents Z4 or the group C—X3—R3;
R1, R2 and R3 represent, independently of one another, hydrogen (H) or a group of interest, where at least one of the radicals R1, R2 and R3 represents the group of interest;
the group of interest is a marker, a labelling precursor, or a ligand;
X1, X2 and X3 represent, independently of one another, a linkage;
only one of the radicals Z1, Z2, Z3 and Z4 represents nitrogen (N) when Y represents Z4, and the other radicals each represent carbon with hydrogen (CH); and
only one of the radicals Z1, Z2 and Z3 represents nitrogen (N) when Y represents the group C—X3—R3, and the other radicals each represent carbon with hydrogen (CH).

US Pat. No. 10,301,665

DEVICE AND METHOD FOR DISPENSING A SUSPENSION OF MICROORGANISMS

1. A method for isolating microorganisms contained in a suspension of microorganisms, comprising the following steps:a) depositing a suspension of microorganisms on a culture medium that is deposited on a support,
b) placing an applicator on the suspension of microorganisms without penetrating the culture medium to dispense the suspension of microorganisms in at least two different volumes of distinct thicknesses under the applicator, and
c) incubating the culture medium for a time and at a predetermined temperature so as to allow growth of the microorganisms, wherein:
the applicator comprises at least first and second surfaces of contact that are positioned in contact with the suspension of microorganisms;
each surface defines a plane such that at least two planes are parallel to one another and a distance between the two parallel planes is a height h; and
each plane faces and is parallel to an interface between the suspension of microorganisms and the culture medium.

US Pat. No. 10,255,688

ANALYSIS METHOD INCLUDING THE DETERMINATION OF A POSITION OF A BIOLOGICAL PARTICLE

1. A method for analyzing a sample receiving biological particles, among which is a particle of interest, the sample being arranged between a first light source and an optical system, the optical system carrying out an optical conjugation between an object plane and an image plane wherein is located an image sensor, and the sample being located inside a fluidic chamber delimited on a side of the image sensor by an upper slide, the method comprising:illuminating a reference point located on a face of the upper slide by a laser beam focused by the optical system;
using the image sensor to receive an image of a spot formed by of the laser beam, wherein the laser beam, the image sensor, and the optical system are arranged such that a focusing point of the laser beam is in the object plane;
adjusting a distance, along an axis parallel to the optical axis of the optical system, between the sample located in the fluidic chamber and the optical system based upon the image and by detecting specular reflection of the laser beam on the upper slide, wherein the reference point is positioned in the object plane of the optical system when said specular reflection is detected;
offsetting the object plane of the optical system relatively to the reference point, along an axis parallel to the optical axis of the optical system, by a known distance as a useful distance, and so as to place the particle of interest outside of the object plane of the optical system;
using the first light source, illuminating of a region receiving the particle of interest, as an illuminated region;
using the image sensor, acquiring a holographic image of the illuminated region, as a reference image or defocused image;
using the reference image, digitally constructing a series of reconstructed images, each associated with a simulation of a predetermined offset of the object plane along the optical axis of the optical system; and
using the series of reconstructed images, determining a distance along an axis parallel to the optical axis of the optical system, between the particle of interest and the object plane.

US Pat. No. 10,252,262

SAMPLE TEST CARDS

BIOMERIEUX, INC., Durham...

1. A method for filling a test sample card with a test sample, the method comprising the following steps of:a) providing a test sample containing or suspected of containing a microorganism;
b) providing a sample test card, the sample test card comprising:
a card body defining a first surface and a second surface opposite the first surface, a fluid intake port and a plurality of sample wells disposed between the first and second surfaces;
a fluid channel network connecting the fluid intake port to the sample wells, the fluid channel network comprising at least one distribution channels, a plurality of fill channels operatively connecting the at least one distribution channel to the sample wells; and
wherein the test card further comprises one or more fluid over-flow reservoirs, the over-flow reservoirs being operatively connected to the distribution channel by a fluid over-flow channel;
c) filling or loading the test sample into the sample test card via the fluid intake port;
wherein the plurality of sample wells are substantially filled with the test sample; and
d) subsequently directing air or a non-aqueous liquid into the fluid channel network to reduce well-to-well contamination.

US Pat. No. 10,240,213

METHOD FOR IN VITRO DIAGNOSIS OR PROGNOSIS OF TESTICULAR CANCER

1. A method of detecting at least one HERV-W mRNA transcript, comprising:obtaining a biological sample that is collected from a person suspected of suffering from testicular cancer; and
detecting whether one or more HERV-W mRNA transcripts are expressed by assaying the biological sample,
wherein the one or more HERV-W mRNA transcripts include an HERV-W mRNA transcript expressed from a genomic sequence having at least 99% sequence identity with SEQ ID NO: 4.

US Pat. No. 10,214,764

SEPARATION DEVICE FOR USE IN THE SEPARATION, CHARACTERIZATION AND/OR IDENTIFICATION OF MICROORGANISMS

BIOMERIEUX, INC., Durham...

10. A method comprising the steps of:separating, without banding and isopycnic sedimentation, at least a portion of a liquid sample in a container, the container comprising:
a longitudinal axis;
an upper portion having an opening;
a lower portion extending from the opening, the lower portion having a generally cylindrical outer shape, the lower portion comprising
an internal chamber, the internal chamber comprising an upper reservoir, and a middle tapered section connecting the upper reservoir to a capillary tube of diameter smaller than that of the upper reservoir, the upper reservoir, the middle tapered section and the lower capillary tube arranged around the longitudinal axis of the container;
an optical window transparent to light and configured for the interrogation of a portion of the capillary tube;
a closure cap operably positioned about the opening; wherein the container comprises a density cushion; and
centrifuging the container for a sufficient time and/or force that substantially prevents a density gradient from forming within the density cushion;
pelletizing at least a portion of the liquid sample from the centrifuging step so as to form an isolated, pelletized microorganism or contaminant sample;
interrogating at least a portion of the isolated, pelletized microorganism or contaminant sample from the pelletizing step; and
characterizing and/or identifying one or more of microorganisms or contaminants present in the isolated, pelletized microorganism or contaminant sample.
US Pat. No. 10,167,494

METHOD FOR DETECTION, CHARACTERIZATION AND/OR IDENTIFICATION OF MICROORGANISMS IN A SEALED CONTAINER

bioMerieux, Inc., Durham...

1. A method for detecting and identifying an unknown microorganism that may be present in a test sample, said method comprising:(a) inoculating a specimen container comprising a culture medium with said test sample;
(b) detecting growth of said unknown microorganism in said specimen container using a first spectroscopic technique to obtain at least two time-dependent measurements of a growth composition comprising said sample and correlating said measurements to indicate growth of said unknown microorganism in said culture medium;
(c) subsequently separating said unknown microorganism from said culture medium by centrifugation of said test sample through a homogeneous density cushion to generate a microorganism pellet;
(d) interrogating the microorganism pellet in situ using front face mode intrinsic fluorescence spectroscopy to produce measurements; and
(e) identifying said unknown microorganism in the microorganism pellet to the species level based on the produced intrinsic fluorescence measurements; and
wherein steps (b), (c), and (d) are carried out in a sealed container and wherein said interrogation step (d) is non-invasive.

US Pat. No. 10,168,284

METHOD AND SYSTEM FOR DETECTING AND MEASURING FLUORESCENCE SIGNALS

1. A method of analyzing a sample to be tested to determine the presence of or to quantify an analyte in the sample by employing a reaction which produces a reaction medium derived from the sample and possessing fluorescence properties, the reaction medium being located within a well, the reaction medium and the well forming an analysis assembly which possesses fluorescent properties in response to illumination by a light source producing a light signal, the light source being movable along a first surface S1 of the well, the method comprising:illuminating, at a moment t=T0, the first surface S1 of the well by means of the light source, before introduction of the reaction medium into the well, from one or more positions of the light source;
detecting, at a moment t=T0, a fluorescence signal from only a second surface S2 of the well, for each of the one or more positions of the light source, in response to the illumination, and before introduction of the reaction medium into the well, to produce a first signal;
illuminating, at a moment t=T1, the analysis assembly by means of the light source moveable along the first surface S1, after introduction of the reaction medium into the well, from the one or more positions of the light source;
detecting, at a moment t=T1, a fluorescence signal from only the analysis assembly from the second surface S2, for each of the one or more positions of the light source, in response to the illumination, and after introduction of the reaction medium into the well, to produce a second signal;
performing a calculation operation on the first signal and the second signal to produce a resulting signal corresponding to emission of the fluorescence signal produced solely by the reaction medium.
US Pat. No. 10,309,965

METHOD AND KIT FOR DETERMINING THE PROBABILITY THAT A PATIENT WILL DEVELOP A SEVERE CASE OF DENGUE

1. A kit for determining whether a patient will develop severe dengue, comprising:a binding partner for platelet factor 4; and
a binding partner for at least one member selected from the group consisting of dengue virus NS1 protein, olfactomedin 4, and ?2-macroglobulin.

US Pat. No. 10,293,338

METHOD AND DEVICE FOR TRANSFERRING PART OF A LIQUID HOUSED IN A CONTAINER

1. A method of transferring a portion of a liquid contained in a container provided with a plug, the method comprising:using a hollow needle passing through the plug of the container to put the inside of the container into communication with a pressure chamber for pressurizing a fluid, which pressure chamber is provided with a septum that is penetrable by the hollow needle and presents a volume that is variable as a result of relative movement between the hollow needle and the septum;
causing the hollow needle and the septum to approach each other over a determined stroke so as to increase the pressure inside the pressure chamber, and, consequently, inside the container, until a transfer pressure is reached immediately prior to the hollow needle passing through the septum; continuing to cause the hollow needle and the septum to approach each other so that the hollow needle passes through the septum so as to open out into a distribution chamber at a pressure that is lower than the transfer pressure so that, under the effect of this pressure difference, a portion of the liquid is transferred through the hollow needle from the container into said distribution chamber;
flowing the liquid transferred into the distribution chamber through a filter system in order to extract a portion of the liquid; and
adapting the pressure in the pressure chamber as a function of the volume of fluid contained inside the container.

US Pat. No. 10,247,740

DETECTOR ARRANGEMENT FOR BLOOD CULTURE BOTTLES WITH COLORIMETRIC SENSORS

bioMerieux, Inc., Durham...

1. A detection arrangement for blood culture bottle incorporating a colorimetric sensor subject to change of color due to change in pH or CO2 of a sample medium within the blood culture bottle, comprising:a sensor LED illuminating the colorimetric sensor;
a reference LED illuminating the colorimetric sensor;
a control circuit for selectively and alternately activating the sensor LED and the reference LED; and
a photodetector, the photodetector measuring reflectance from the colorimetric sensor during the selective and alternating illumination of the colorimetric sensor with the sensor LED and the reference LED, the photodetector generating intensity signals in response to the alternating illumination of the colorimetric sensor with the sensor LED and the reference LED;
a computer comprising machine executable instructions, wherein the machine executable instructions are configured to:
receive the intensity signals from the photodetector; and
determine a displacement of the bottle from a home position based on the intensity signals;
wherein the reference LED is selected to have a peak wavelength of illumination such that the intensity signals of the photodetector from illumination by the reference LED are not substantially affected by changes in the color of the colorimetric sensor, and
wherein the peak wavelength of illumination of the reference LED is below about 490 nm.
US Pat. No. 10,233,477

CULTURE MEDIUM FOR MICROORGANISMS INCLUDING PARA-AMINOBENZOIC ACID AS A SELECTIVE AGENT

1. A culture medium for the detection of at least one target microorganism comprising:at least one natural or synthetic fermentation or enzymatic substrate of the at least one target microorganism; and
selective agents, wherein the selective agents consist of:
bile salts,
at least one agent selected from the group consisting of para-amino benzoic acid, a derivative of para-amino benzoic acid, a salt thereof, and combinations thereof, and
optionally at least one of Novobiocin, Vancomycin, Amphotericin, and Cefsulodin;
wherein a concentration of the para-amino benzoic acid, a derivative of para-amino benzoic acid, and/or a salt thereof ranges from 0.05 to 1 g/L;
the derivative of para-amino benzoic acid comprises a para-amino benzoic skeleton;
the at least one target microorganism is a Salmonella genus bacterium;
the at least one natural or synthetic fermentation or enzymatic substrate comprises at least one chromogenic or fluorogenic substrate; and
a hydrolysation of the at least one natural or synthetic fermentation or enzymatic substrate distinguishes the at least one target microorganism from non-target microorganisms in the culture medium by causing a change in color or fluorescence, respectively, in the target microorganism.
US Pat. No. 10,281,470

METHOD AND KIT FOR DETERMINING THE PROBABILITY THAT A PATIENT WILL DEVELOP A SEVERE CASE OF DENGUE

1. A kit for determining whether a patient will develop severe dengue, comprising:a binding partner for olfactomedin 4; and
a binding partner for at least one member selected from the group consisting of dengue virus NS1 protein, platelet factor 4, and ?2-macroglobulin.