# US 9,464,981 B2 · Systems and methods for sample use maximization

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- Number: US 9,464,981 B2
- Document ID: US9464981B2
- Status: Granted
- Kind: B2
- Application number: 14/562,066
- Filed: 2014-12-05
- Published: 2015-07-02
- Granted: 2016-10-11
- Earliest claimed: 2011-01-21
- Assignees: Theranos, Inc.
- Applicants: Theranos, Inc.
- Inventors: Ian Gibbons; Anthony J. Nugent; Anthony Delacruz; Daniel L. Young; Elizabeth A. Holmes; Andrew Drake; Timothy Michael Kemp; Sunny Balwani; Chinmay Pangarkar
- Web page: https://patentgrep.com/patent/US9464981B2

## CPC

- G01N 21/07: Centrifugal type cuvettes (G01N21/09 takes precedence)
- B01L 3/0275: {Interchangeable or disposable dispensing tips}
- B04B 5/0421: {pivotably mounted}
- C12Q 1/42: involving phosphatase
- C12Q 1/48: involving transferase
- C12Q 1/52: involving transaminase
- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- C12Q 1/6809: Methods for determination or identification of nucleic acids involving differential detection
- C12Q 1/689: for bacteria
- G01N 1/4077: {by other techniques involving separation of suspended solids}
- G01N 21/00: Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light (G01N3/00 - G01N19/00 take precedence)
- G01N 21/0303: {Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment (G01N21/031 - G01N21/15 take precedence)}
- G01N 21/51: inside a container, e.g. in an ampoule (G01N21/53 takes precedence)
- G01N 21/59: Transmissivity (G01N21/25 takes precedence)
- G01N 33/5308: {for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites}
- G01N 33/54326: {Magnetic particles}
- G01N 33/54393: {Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding}
- G01N 33/56972: {White blood cells}
- G01N 33/56983: {Viruses}
- G01N 33/573: for enzymes or isoenzymes
- G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors}
- G01N 33/743: {Steroid hormones}
- G01N 33/80: involving blood groups or blood types {or red blood cells (white blood cells G01N33/56972)}
- G01N 33/82: involving vitamins {or their receptors}
- G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)}
- G01N 35/10: Devices for transferring samples {or any liquids} to, in, or from, the analysis apparatus, e.g. suction devices, injection devices {(G01N35/0099 takes precedence)}
- G06T 3/4084: in the transform domain, e.g. fast Fourier transform [FFT] domain scaling
- G06T 7/0002: {Inspection of images, e.g. flaw detection}
- G06T 7/0012: {Biomedical image inspection}
- H04N 23/64: {Computer-aided capture of images, e.g. transfer from script file into camera, check of taken image quality, advice or proposal for image composition or decision on when to take image}
- B01L 2300/168: Specific optical properties, e.g. reflective coatings
- C12Q 2600/158: Expression markers
- G01N 2001/4083: {sedimentation}
- G01N 2035/00495: {Centrifuges}
- G01N 2035/1018: {Detecting inhomogeneities, e.g. foam, bubbles, clots}
- G01N 2333/575: Hormones
- G01N 2333/62: Insulins
- G01N 2333/91188: transferring nitrogenous groups (2.6)
- G01N 2333/96463: Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
- G06T 2207/30004: Biomedical image processing
- G06T 2207/30168: Image quality inspection
- G16C 20/20: Identification of molecular entities, parts thereof or of chemical compositions
- 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
- B04B: CENTRIFUGES (high-speed drum mills B02C19/11; domestic spin driers D06F; analysing, measuring or monitoring physical or chemical properties of samples during centrifuging, see the relevant subclasses for these procedures, e.g. G01N)
- 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
- G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- H04N: PICTORIAL COMMUNICATION, e.g. TELEVISION
- G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE

## Abstract

The present invention provides systems, devices, and methods for point-of-care and/or distributed testing services. The methods and devices of the invention are directed toward automatic detection of analytes in a bodily fluid. The components of the device can be modified to allow for more flexible and robust use with the disclosed methods for a variety of medical, laboratory, and other applications. The systems, devices, and methods of the present invention can allow for effective use of samples by improved sample preparation and analysis.

## Claims

### Claim 1

A method of detecting the presence or concentration of an analyte in a sample fluid contained in a container comprising:
(a) illuminating the container along a first region having a first path length to yield a first measurement of light intensity transmitted across the first path length;
(b) determining that the first measurement falls outside a predetermined dynamic range of transmitted light intensity;
(c) moving the sample fluid to another region in the same container having another path length;
(d) illuminating the same container along the another region to yield another measurement of light intensity transmitted across the another path length; and
(e) repeating steps (c) and (d) as needed on the same container until a measurement of light intensity falls within the predetermined dynamic range, thereby detecting the presence or concentration of the analyte.

### Claim 2 (depends on 1)

The method of claim 1, wherein measurement of the light intensity is obtained by imaging.

### Claim 3 (depends on 1)

The method of claim 1, wherein the sample is moved from a first region of the container having a first path length to a second region of the container having another path length by aspirating the sample.

### Claim 4 (depends on 3)

The method of claim 3 wherein an end of the container is attached to a pipette which is configured to aspirate the sample.

### Claim 5 (depends on 3)

The method of claim 3 wherein the sample is moved up or down the length of the container.

### Claim 6 (depends on 1)

The method of claim 1, wherein the container is a pipette tip.

### Claim 7 (depends on 1)

The method of claim 1, wherein the container is conically shaped.

### Claim 8 (depends on 1)

The method of claim 1, wherein the container has two open ends.

### Claim 9 (depends on 8)

The method of claim 8, wherein a first open end has a greater diameter than a second open end.

### Claim 10 (depends on 1)

The method of claim 1, wherein the container has a plurality of distinct widths to permit transmission of light along a plurality of varying path lengths.

### Claim 11 (depends on 1)

The method of claim 1, wherein the container volume is less than 100 microliters.

### Claim 12

A method of measuring an analyte concentration in a sample fluid comprising:
(a) providing the sample contained in a container dimensioned with a plurality of distinct widths to permit transmission of light along a plurality of varying path lengths that correspond to the plurality of distinct widths;
(b) illuminating the container along at least one of the plurality of path lengths; and
(c) imaging the container to measure a first light intensity transmitted across said at least one of the plurality of path lengths, for the determination of the concentration of the analyte based on the measured first light intensity;
(d) imaging the same container to measure a second light intensity transmitted across another path length corresponding to another distinct width of the container;
(e) comparing said first light intensity and the second light intensity; and
(f) determining an analyte concentration based on said comparing step.

### Claim 13 (depends on 12)

The method of claim 12, further comprising selecting a desired detection path length by one or more of the following: (a) moving a light source relative to the sample, (b) moving a detector relative to the sample, or (c) moving the sample within the container relative to the light source.

### Claim 14 (depends on 12)

The method of claim 12, wherein the illumination is provided by a light source and the imaging is provided by a detector, wherein the light source and the detector are on opposing sides of the container.

### Claim 15 (depends on 12)

The method of claim 12, wherein the illumination is provided by a light source and the imaging is provided by a detector, wherein the light source and the detector are on the same side of the container.

### Claim 16 (depends on 12)

The method of claim 12, wherein the plurality of path lengths are orthogonal to the length of the container.

### Claim 17 (depends on 12)

The method of claim 12, wherein the container has a first open end and a second open end, wherein the first open end has a smaller width than the second open end.

### Claim 18 (depends on 17)

The method of claim 17, wherein the second open end is configured to connect to a fluid handling device.

### Claim 19 (depends on 2)

The method of claim 2, further comprising deconvoluting a line scan of the image and detecting the presence or concentration of an analyte.
