# US 2014/0193806 A1 · Real-time detection of influenza virus

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- Number: US 2014/0193806 A1
- Document ID: US20140193806A1
- Status: Published application
- Kind: A1
- Application number: 14/155,150
- Filed: 2014-01-14
- Published: 2014-07-10
- Earliest claimed: 2006-05-10
- Assignees: Theranos, Inc.
- Applicants: Theranos, Inc.
- Inventors: Elizabeth A. Holmes; Ian Gibbons
- Web page: https://patentgrep.com/patent/US20140193806A1

## CPC

- G01N 33/56983: {Viruses}
- B01L 3/5027: {by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip}
- C12Q 1/701: {Specific hybridization probes}
- G01N 33/54366: {Apparatus specially adapted for solid-phase testing}
- B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)}
- B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
- B01L 2200/142: Preventing evaporation
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2300/044: pierceable, e.g. films, membranes
- B01L 2300/0672: Integrated piercing tool
- B01L 2300/0874: Three dimensional network
- B01L 2400/0481: squeezing of channels or chambers
- B01L 2400/049: vacuum
- B01L 2400/0683: mechanically breaking a wall or membrane within a channel or chamber
- G01N 2333/11: Orthomyxoviridae, e.g. influenza virus
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention provides system and methods for detecting an analyte indicative of an influenza viral infection in a sample of bodily fluid. The present invention also provides for systems and method for detection a plurality of analytes, at least two of which are indicative of an influenza viral infection in a sample of bodily fluid.

## Claims

### Claim at position 1

1-70. (canceled)

### Claim 71

A method of performing a trend analysis on the concentration of an analyte indicative of an influenza viral infection in a subject, comprising:
a) providing a fluidic device comprising at least one sample collection unit and an immunoassay assembly containing immunoassay reagents;
b) actuating said fluidic device and directing said immunoassay reagents within said fluidic device;
c) allowing a sample of bodily fluid obtained from said subject to react with said immunoassay reagents contained within said assay immunoassay assembly to yield a detectable signal indicative of the presence of said analyte in said sample;
d) detecting said detectable signal generated from said analyte collected in said sample of bodily fluid; and
e) repeating steps a) through d) for one or more further bodily fluid samples obtained from said subject over a period of time to detect concentrations of said analyte over said period of time, thereby performing said trend analysis.

### Claim 72 (depends on 71)

The method of claim 71, wherein said immunoassay reagents comprise a first antibody that binds specifically to a hemagglutinin, and a second antibody that binds specifically to a neuraminidase.

### Claim 73 (depends on 72)

The method of claim 72, wherein the hemagglutinin is selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, and H16, and the neuraminidase is selected from the group consisting of N1, N2, N3, N4, and N5.

### Claim 74 (depends on 72)

The method of claim 72, wherein the hemagglutinin is H5 and the neuraminidase is N1, or wherein the hemagglutinin is H1 and the neuraminidase is N1.

### Claim 75 (depends on 72)

The method of claim 72, wherein detecting said detectable signal is indicative of an influenza viral infection selected from an influenza type A viral infection, an influenza type B viral infection, and an influenza type C viral infection.

### Claim 76 (depends on 71)

The method of claim 71, wherein said immunoassay assembly further comprises a plurality of channels in fluid communication with said sample collection unit or with said immunoassay assembly.

### Claim 77 (depends on 71)

The method of claim 71, wherein said one or more further bodily fluid samples are obtained at a frequency selected from once a week and twice a week.

### Claim 78

A method of performing a trend analysis on the concentration of influenza viral particles in each of a plurality of bodily fluid samples obtained from a subject suspected of containing influenza viral particles, comprising:
a) providing an immunoassay assembly, wherein the assembly comprises a first antibody that binds specifically to a first antigen, wherein the first antibody is bound to a surface of the assembly;
b) reacting a bodily fluid sample obtained from said subject in the immunoassay assembly in the presence of immunoassay reagents comprising a second antibody that binds specifically to a second antigen which is distinct from the first antigen, wherein the second antibody is labeled with a detectable label, wherein either the first antigen comprises a hemagglutinin and the second antigen comprises a neuraminidase, or the first antigen comprises a neuraminidase and the second antigen comprises a hemagglutinin, and wherein said reaction yields an immune complex comprising the first antibody bound to the first antigen, and the second antibody bound to the second antigen;
c) washing the assembly to remove excess immunoassay reagents;
d) detecting a signal generated by the detectable label from the immune complex, thereby indicating the presence of the particle; and
e) repeating steps a) through d) for one or more further bodily fluid samples obtained from the subject over a period of time to detect concentrations of said analyte over said period of time, thereby performing said trend analysis on the concentration of an analyte indicative of an influenza viral infection in a subject.

### Claim 79 (depends on 78)

The method of claim 78, wherein the hemagglutinin is selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, and H16, and the neuraminidase is selected from the group consisting of N1, N2, N3, N4, and N5.

### Claim 80 (depends on 78)

The method of claim 78, wherein the hemagglutinin is H5 and the neuraminidase is N1, or wherein the hemagglutinin is H1 and the neuraminidase is N1.

### Claim 81 (depends on 78)

The method of claim 78, wherein detecting said detectable signal is indicative of an influenza viral infection selected from an influenza type A viral infection, an influenza type B viral infection, and an influenza type C viral infection.

### Claim 82 (depends on 78)

The method of claim 78, wherein said immunoassay assembly further comprises a plurality of channels in fluid communication with said sample collection unit or with said immunoassay assembly.

### Claim 83 (depends on 78)

The method of claim 78, wherein said one or more further bodily fluid samples are obtained at a frequency selected from once a week and twice a week.

### Claim 84

A method of detecting a trend in the concentration of influenza viral particles in a plurality of bodily fluid samples obtained from a subject, comprising:
a) allowing a bodily fluid sample suspected of containing an influenza viral particle to react with a first immunoassay reagent and a second immunoassay reagent, both of which immunoassay reagents are contained within an immunoassay assembly of a cartridge, wherein said first immunoassay reagent binds to a hemagglutinin molecule to form a first immune complex on said influenza viral particle, and wherein said second immunoassay reagent binds to a neuraminidase molecule to form a second immune complex on said influenza viral particle, said immune complexes yielding one or more detectable signals that indicate the simultaneous presence of hemagglutinin and neuraminidase on said influenza viral particle wherein either the first or second immunoassay reagent is immobilized on a solid support;
b) detecting said one or more detectable signals generated from said immune complexes, wherein said simultaneous presence of hemagglutinin and neuraminidase is indicative of the presence of and concentrations of said influenza viral particles in the sample; and
c) repeating steps a) and b) for one or more further bodily fluid samples obtained from the subject over a period of time to detect concentrations of said analyte over said period of time, thereby performing said trend analysis.

### Claim 85 (depends on 84)

The method of claim 84, wherein the volume of each bodily fluid sample is less than about 500 microliters.

### Claim 86 (depends on 84)

The method of claim 84, wherein detection of said hemagglutinin and neuraminidase is indicative of an influenza viral infection selected from an influenza type A viral infection, an influenza type B viral infection, and an influenza type C viral infection.

### Claim 87 (depends on 84)

The method of claim 84, wherein said hemagglutinin is selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, and H16, and said neuraminidase is selected from the group consisting of N1, N2, N3, N4, and N5.

### Claim 88 (depends on 84)

The method of claim 84, wherein said hemagglutinin is H5 and said neuraminidase is N1, or wherein said hemagglutinin is H1 and said neuraminidase is N1.

### Claim at position 20

89-91. (canceled)

### Claim 92 (depends on 84)

The method of claim 84, wherein said cartridge comprises at least one sample collection unit and an immunoassay assembly containing immunoassay reagents.

### Claim 93 (depends on 84)

The method of claim 84 further comprising actuating said cartridge and directing said immunoassay reagents within said cartridge.

### Claim 94 (depends on 84)

The method of claim 84, wherein said sample of bodily fluid suspected of containing said influenza viral particle reacts with said immunoassay reagents contained within said immunoassay assembly based on a protocol transmitted from an external device.

### Claim 95 (depends on 94)

The method of claim 94, wherein the protocol is wirelessly transmitted from said external device.

### Claim 96 (depends on 84)

The method of claim 84, further comprising the step of transmitting said detectable signal to an external device.

### Claim 97 (depends on 96)

The method of claim 96, wherein the external device is a server.

### Claim 98 (depends on 84)

The method of claim 84, wherein the cartridge comprises a plurality of channels providing fluid communication between said sample collection unit and said immunoassay assembly.

### Claim 99 (depends on 84)

The method of claim 84, wherein said cartridge comprises an identifier, a sample collection unit, and an immunoassay assembly comprising said immunoassay reagents; an identifier detector reads said identifier and communicates to a communication assembly that transmits information of said identifier to an external device; a protocol associated with said identifier, said protocol being transmitted from said external device in response to the transmission of said information of said identifier to said external device; and wherein said sample of bodily fluid collected in said sample collection unit reacts with said immunoassay reagents based on said protocol to yield said detectable signal indicative of the presence of said viral particle.

### Claim 100 (depends on 84)

The method of claim 84, wherein said one or more further bodily fluid samples are obtained at a frequency selected from once a week and twice a week.