Systems and methods for sample use maximization

• US 9,464,981 B2
• Filed: 12/05/2014
• Issued: 10/11/2016
• Est. Priority Date: 01/21/2011
• Status: Active Grant

• Current Assignee: Labrador Diagnostics LLC (SoftBank Group Corp.)
• Original Assignee: Theranos Incorporated
• Inventors: Gibbons, Ian, Nugent, Anthony J., Delacruz, Anthony, Young, Daniel L., Holmes, Elizabeth A., Drake, Andrew, Kemp, Timothy Michael, Balwani, Sunny, Pangarkar, Chinmay
• Primary Examiner(s): Geisel, Kara E
• Assistant Examiner(s): Alli, Iyabo S
• Application Number:
  US14/562,066
• Publication Number:
  US 20150185234A1
• Time in Patent Office: 676 Days
• Field of Search: 356/246, 356432-433, 356/244, 356/319, 435/238.1, 435/238.2, 435/288, 4352871-2873
• US Class Current: 1/1
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B04B 5/0421 pivotably mounted
• CPC Class Codes: C12Q 1/42 involving phosphatase
• CPC Class Codes: C12Q 1/48 involving transferase
• CPC Class Codes: C12Q 1/52 involving transaminase
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6809 Methods for determination or identification of nucleic acids involving differential detection
• CPC Class Codes: C12Q 1/689 for bacteria
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 1/4077 by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 2001/4083 sedimentation
• CPC Class Codes: G01N 2035/00495 Centrifuges
• CPC Class Codes: G01N 2035/1018 Detecting inhomogeneities, e.g. foam, bubbles, clots
• CPC Class Codes: 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
• CPC Class Codes: 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
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence
• CPC Class Codes: G01N 21/59 Transmissivity G01N21/25 takes precedence
• CPC Class Codes: G01N 2333/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin G01N2333/665, corticotropin G01N2333/695
• CPC Class Codes: G01N 2333/62 Insulins
• CPC Class Codes: G01N 2333/91188 : transferring nitrogenous groups (2.6)
• CPC Class Codes: G01N 2333/96463 : Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
• CPC Class Codes: G01N 33/5308 : for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: G01N 33/54326 : Magnetic particles
• CPC Class Codes: 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
• CPC Class Codes: G01N 33/56972 : White blood cells
• CPC Class Codes: G01N 33/56983 : Viruses
• CPC Class Codes: G01N 33/573 : for enzymes or isoenzymes
• CPC Class Codes: G01N 33/74 : involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
• CPC Class Codes: G01N 33/743 : Steroid hormones
• CPC Class Codes: G01N 33/80 : involving blood groups or blood types or red blood cells white blood cells G01N33/56972
• CPC Class Codes: G01N 33/82 : involving vitamins or their receptors
• CPC Class Codes: G01N 33/92 : involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: 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
• CPC Class Codes: G06T 2207/30004 : Biomedical image processing
• CPC Class Codes: G06T 2207/30168 : Image quality inspection
• CPC Class Codes: G06T 3/4084 : in the transform domain, e.g. fast Fourier transform [FFT] domain scaling
• CPC Class Codes: G06T 7/0002 : Inspection of images, e.g. flaw detection
• CPC Class Codes: G06T 7/0012 : Biomedical image inspection
• CPC Class Codes: G16C 20/20 : Identification of molecular entities, parts thereof or of chemical compositions
• CPC Class Codes: 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

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

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.

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

3. 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.

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

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

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

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

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

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

10. 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.

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

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

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.

13. 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.

14. 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.

15. 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.

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

17. 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.

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