Systems and methods for sample use maximization

• US 9,677,993 B2
• Filed: 07/01/2015
• Issued: 06/13/2017
• Est. Priority Date: 01/21/2011
• Status: Active Grant

• Current Assignee: Labrador Diagnostics LLC (FIG LLC (d/b/a Fortress Investment Group LLC))
• Original Assignee: Theranos Incorporated
• Inventors: Young, Daniel, Holmes, Elizabeth A., Nugent, Anthony, Siegel, Michael, Wistort, Ryan
• Primary Examiner(s): Geisel, Kara E
• Assistant Examiner(s): Smith, Maurice
• Application Number:
  US14/789,967
• Publication Number:
  US 20160047834A1
• Time in Patent Office: 713 Days
• Field of Search: 356244-246, 356440, 356433, 435 792, 435 2
• 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 21/07 Centrifugal type cuvettes G01N21/09 takes 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
• 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 for handling a bodily fluid sample, the method comprising:

receiving in an instrument a cartridge, wherein the cartridge contains the bodily fluid sample, wherein;

the bodily fluid sample has a volume of 250 microliters or less;

the instrument comprises;

i) a centrifuge comprising at least a first bucket, and ii) a pipette comprising a nozzle, and

the cartridge further contains;

i) a first tip, ii) a second tip, and iii) a tip seal,

wherein the first tip and second tip each have a first open end and a second open end, wherein the first open end of each tip is configured to engage with the nozzle of the pipette and the second open end of each tip is configured to permit the movement of fluid into or out of the tip;

engaging the first open end of the first tip with the nozzle of the pipette;

aspirating at least a portion of the bodily fluid sample into the engaged first tip through the second open end of the first tip;

pressing with the pipette the second open end of the engaged first tip containing the at least a portion of the bodily fluid sample into the tip seal such that the second open end of the first tip is capped with and sealed by the tip seal;

inserting with the pipette the sealed first tip into the bucket of the centrifuge and disconnecting the sealed first tip from the pipette nozzle; and

centrifuging the sealed first tip in the bucket of the centrifuge.

2. The method of claim 1, wherein the bodily fluid sample is a blood sample obtained from a fingerstick.

3. The method of claim 1, wherein upon centrifuging the sealed first tip, the sample in the sealed first tip is separated into a supernatant and a pellet.

4. The method of claim 3, wherein the method further comprises:

engaging the first open end of the second tip with the nozzle of the pipette; and

aspirating at least a portion of the supernatant from the sealed first tip into the second tip.

5. The method of claim 4, wherein the supernatant comprises blood plasma or blood serum.

6. The method of claim 5, further comprising using at least a portion of the supernatant to perform at least one assay for an analyte.

7. The method of claim 3, wherein the pellet contains red blood cells and white blood cells.

8. The method of claim 7, further comprising:

imaging at least a portion of the sealed first tip, wherein the imaged portion of the sealed first tip contains the pellet; and

determining the hematocrit of the sample.

9. The method of claim 7, further comprising:

removing the supernatant from the sample in the sealed first tip; and

resuspending the pellet in a reagent which acts as a lysing agent for the red blood cells.

10. The method of claim 9, further comprising:

centrifuging the sealed first tip comprising the resuspended pellet, such that upon centrifuging the sealed first tip, the resuspended pellet is separated into a supernatant comprising lysed red blood cells and a pellet comprising white blood cells.

11. A method for handling a bodily fluid sample, the method comprising:

receiving in an instrument a cartridge, wherein the cartridge contains the bodily fluid sample, wherein;

the bodily fluid sample has a volume of 250 microliters or less;

the instrument comprises;

i) a centrifuge comprising at least a first bucket, and ii) a pipette comprising a nozzle, and

the cartridge further contains;

i) a first tip, ii) a second tip, and iii) a tube having an open end and an opposing closed end, wherein the first tip and second tip each have a first open end and a second open end, wherein the first open end of each tip is configured to engage with the nozzle of the pipette and the second open end of each tip is configured to permit the movement of fluid into or out of the tip, and wherein the open end of the tube is configured to engage with the nozzle of the pipette;

engaging the first open end of the first tip with the nozzle of the pipette;

aspirating at least a portion of the bodily fluid sample into the engaged first tip through the second open end of the first tip;

dispensing the at least a portion of the fluid sample from the engaged first tip into the tube;

disengaging the engaged first tip from the pipette nozzle;

engaging the open end of the tube comprising the at least a portion of the fluid sample with the pipette nozzle;

inserting with the pipette the tube comprising the at least a portion of the fluid sample into the first bucket of the centrifuge and disconnecting the tube from the pipette nozzle; and

centrifuging the tube in the bucket of the centrifuge.

12. The method of claim 11, wherein the bodily fluid sample is a blood sample obtained from a fingerstick.

13. The method of claim 11, wherein upon centrifuging the tube, the sample in the tube is separated into a supernatant and a pellet.

14. The method of claim 13, wherein the method further comprises:

engaging the first open end of the second tip with the nozzle of the pipette; and

aspirating at least a portion of the supernatant from the tube into the second tip.

15. The method of claim 14, wherein the supernatant comprises blood plasma or blood serum.

16. The method of claim 15, further comprising using at least a portion of the supernatant to perform at least one assay for an analyte.

17. The method of claim 13, wherein the pellet contains red blood cells and white blood cells.

18. The method of claim 17, further comprising:

imaging at least a portion of the tube, wherein the imaged portion of the tube contains the pellet; and

determining the hematocrit of the sample.

19. The method of claim 17, further comprising:

removing the supernatant from the sample in the tube; and

resuspending the pellet in a reagent which acts as a lysing agent for the red blood cells.

20. The method of claim 19, further comprising:

centrifuging the tube comprising the resuspended pellet, such that upon centrifuging the tube, the resuspended pellet is separated into a supernatant comprising lysed red blood cells and a pellet comprising white blood cells.

21. An instrument comprising:

i) a centrifuge comprising at least a first bucket, ii) a pipette comprising a nozzle, and iii) a housing, wherein;

the centrifuge and pipette are within the housing,

the housing comprises a door through which a cartridge containing a tip or tube may be inserted, the pipette is configured to, upon the insertion of a cartridge containing a tip or tube into the housing of the instrument;

i) engage with its nozzle a tip or tube in the cartridge, ii) move the engaged tip or tube from the cartridge to the centrifuge, iii) insert the engaged tip or tube into the bucket of the centrifuge, and iv) disconnect the engaged tip or tube from the nozzle into the bucket of the centrifuge, such that the tip or tube is parked in the bucket of the centrifuge.

22. The instrument of claim 21, the instrument further comprising:

iv) the cartridge, wherein the cartridge contains;

A) a first tip, B) a second tip, and C) a tip seal,

wherein the first tip and second tip each have a first open end and a second open end, wherein the first open end of each tip is configured to engage with the nozzle of the pipette and the second open end of each tip is configured to permit the movement of fluid into or out of the tip.

23. The instrument of claim 21, the instrument further comprising:

iv) the cartridge, wherein the cartridge contains;

A) a first tip, B) a second tip, and C) a tube having an open end and an opposing closed end, wherein the first tip and second tip each have a first open end and a second open end, wherein the first open end of each tip is configured to engage with the nozzle of the pipette and the second open end of each tip is configured to permit the movement of fluid into or out of the tip, and wherein the open end of the tube is configured to engage with the nozzle of the pipette.