Systems and methods for multi-analysis

• US 10,627,418 B2
• Filed: 05/23/2016
• Issued: 04/21/2020
• Est. Priority Date: 09/25/2011
• Status: Active Grant

• Current Assignee: Labrador Diagnostics LLC (SoftBank Group Corp.)
• Original Assignee: Theranos IP Company, LLC
• Inventors: Wasson, James, Ko, Pey-Jiun, Roy, Joy, Holmes, Elizabeth A.
• Primary Examiner(s): Whatley, Benjamin R
• Application Number:
  US15/161,533
• Publication Number:
  US 20160370396A1
• Time in Patent Office: 1,429 Days
• Field of Search: None
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1855 using phase changes in a medium
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/5082 Test tubes per se
• CPC Class Codes: B01L 3/50855 using modular assemblies of strips or of individual wells
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 9/06 Test-tube stands; Test-tube holders
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/543 for disposable pipette tips, e.g. racks or cassettes
• CPC Class Codes: C12Q 1/42 involving phosphatase
• CPC Class Codes: C12Q 1/52 involving transaminase
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/70 involving virus or bacteriophage immunoassay for viruses G01N33/56983
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 2015/012 Red blood cells
• CPC Class Codes: G01N 2015/016 White blood cells
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 2035/00138 Slides
• CPC Class Codes: G01N 2035/00148 : Test cards, e.g. Biomerieux or McDonnel multiwell test cards
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/00306 : Housings, cabinets, control panels (details)
• CPC Class Codes: G01N 2035/00326 : Analysers with modular structure
• CPC Class Codes: G01N 2035/00356 : Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/00366 : Several different temperatures used
• CPC Class Codes: G01N 2035/00425 : Heating or cooling means associated with pipettes or the like, e.g. for supplying sample/reagent at given temperature
• CPC Class Codes: G01N 2035/00435 : Refrigerated reagent storage
• CPC Class Codes: G01N 2035/00495 : Centrifuges
• CPC Class Codes: G01N 2035/00633 : logging process history of individual samples
• CPC Class Codes: G01N 2035/0449 : using centrifugal transport of liquid
• CPC Class Codes: G01N 2035/0474 : Details of actuating means for conveyors or pipettes
• CPC Class Codes: G01N 2035/0486 : Gearing, cams
• CPC Class Codes: G01N 2035/0491 : Position sensing, encoding; closed-loop control
• CPC Class Codes: G01N 2035/0493 : Locating samples; identifying different tube sizes
• CPC Class Codes: G01N 2035/0494 : Detecting or compensating piositioning errors
• CPC Class Codes: G01N 21/25 : Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
• CPC Class Codes: G01N 21/27 : using photo-electric detection G01N21/31 takes precedence; circuits for computing concentration logarithmic circuits G06G7/24; photometric circuits in general G01J
• CPC Class Codes: G01N 2201/024 : Modular construction
• CPC Class Codes: G01N 2201/04 : Batch operation; multisample devices
• CPC Class Codes: G01N 2201/12 : Circuits of general importance; Signal processing
• CPC Class Codes: G01N 33/5005 : involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/54306 : Solid-phase reaction mechanisms
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/56972 : White blood cells
• CPC Class Codes: G01N 33/56983 : Viruses
• CPC Class Codes: G01N 33/62 : involving urea
• CPC Class Codes: G01N 33/6827 : Total protein determination, e.g. albumin in urine
• 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 33/92 : involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: G01N 35/00 : Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: G01N 35/00029 : provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
• CPC Class Codes: G01N 35/00623 : of instruments
• CPC Class Codes: G01N 35/00871 : Communications between instruments or with remote terminals
• CPC Class Codes: G01N 35/0092 : Scheduling
• CPC Class Codes: G01N 35/026 : having blocks or racks of reaction cells or cuvettes
• CPC Class Codes: G01N 35/04 : Details of the conveyor system G01N35/021 - G01N35/028 take precedence
• 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: G01N 35/1009 : Characterised by arrangements for controlling the aspiration or dispense of liquids
• CPC Class Codes: G01N 35/1011 : Control of the position or alignment of the transfer device
• CPC Class Codes: G01N 35/1065 : Multiple transfer devices
• CPC Class Codes: G01N 35/1072 : with provision for selective pipetting of individual channels
• CPC Class Codes: Y10T 436/111666 : Utilizing a centrifuge or compartmented rotor
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack

Abstract

Systems and methods are provided for sample processing. A device may be provided, capable of receiving the sample, and performing one or more of a sample preparation, sample assay, and detection step. The device may be capable of performing multiple assays. The device may comprise one or more modules that may be capable of performing one or more of a sample preparation, sample assay, and detection step. The device may be capable of performing the steps using a small volume of sample.

Claims

1. A method of performing three or more assays for detecting a plurality of analytes in a biological sample from a subject, comprising:

providing a cartridge in a refrigerated condition at a temperature less than room temperature,

receiving the biological sample and the cartridge in a biological sample processing system, wherein;

a) the cartridge comprises;

a plurality of components including sample vessels, reagent units, and at least three assay units for performing the three or more assays to detect a plurality of analytes in the biological sample; and

b) the biological sample processing system comprises;

a sample handling system including a pipette; and

at least two detection units;

heating at least one portion of the cartridge using a movable heater on the biological sample processing system, wherein said heating comprises moving said movable heater from a first position to a second position wherein in the second position, at least a portion of the cartridge is inside the heater to pre-heat reagent units or assay units that are in the cartridge when the cartridge is in the biological sample processing system;

using said sample handling system for aliquoting at least a diluted portion of the sample into one of the plurality of said components while the cartridge remains inside the biological sample processing system;

decoupling one or more of said plurality of components from the cartridge while the cartridge remains inside the biological sample processing system to form one or more decoupled components;

performing in the biological sample processing system the three or more assays, wherein the three or more assays are performed at least partially in parallel and comprises leaving one or more of the one or more decoupled components of the cartridge at a location in the device separate from the cartridge;

detecting the plurality of analytes with at least one of the at least two detection unit in the biological sample processing system; and

after detecting the plurality of analytes, returning any decoupled components back to the cartridge while the cartridge remains inside the biological sample processing system;

wherein each of the reagent units is a container, a tube, a pipette tip, or a vessel;

wherein each of the assay units is a cuvette, a container, a tube, a pipette tip, or a vessel.

2. The method of claim 1, wherein the biological sample is a blood sample.

3. The method of claim 2, wherein the blood sample obtained from the subject is about 500 μ

l or less.

4. The method of claim 2, wherein the three or more assays are performed from a single blood sample obtained from the subject.

5. The method of claim 2, wherein the blood sample is a plasma sample.

6. The method of claim 1, wherein the biological sample processing system comprises at least four assay units and performs four or more assays at least partially in parallel, wherein the four or more assays comprise a nucleic acid amplification, and immunoassay, and wherein the plurality of analytes comprise an antibody, antigen, nucleic acid, and cell.

7. The method of claim 6, further comprising performing a cytometric assay and wherein the biological sample processing system further comprises a cytometer.

8. The method of claim 1, wherein the biological sample processing system further comprises a centrifuge.

9. The method of claim 1, wherein the biological sample processing system further comprises a housing.

10. The method of claim 9, wherein the cartridge comprises the at least three assay units and all reagents for performing the three or more assays, and the housing comprises the sample handling system, the heater and the at least one of said at least two detection units.

11. The method of claim 10, wherein the cartridge further comprises at least one tip and the sample handling system comprises at least one pipette nozzle, wherein the pipette nozzle is configured to engage with the at least one tip.

12. The method of claim 1, where the cartridge in the refrigerated condition has temperature in the range of about 0°

C. to about 8°

C.

13. The method of claim 1, where the cartridge in the refrigerated condition has temperature in the range of about −

20°

C. to about 8°

C.

14. The method of claim 1, wherein the heater comprises a thermoelectric device.

15. The method of claim 14, wherein the heater further comprises a fan.

16. The method of claim 14, wherein the heater further comprises a plurality of holes sized to engage portions of vessels in the cartridge.

17. The method of claim 14, wherein the heater is located to direct heat towards an underside of the cartridge when the cartridge is in a cartridge receiving location.

18. The method of claim 14, wherein heater is located to direct heat directly towards only a portion of an underside of the cartridge when the cartridge is in a cartridge receiving location.

19. A method of performing three or more assays for detecting a plurality of analytes in a biological sample from a subject, comprising:

providing a cartridge in a refrigerated condition at a temperature less than room temperature,

receiving the biological sample and the cartridge in a biological sample processing system, wherein;

b) the cartridge comprises;

a plurality of components including sample vessels, reagent units, and at least three assay units for performing the three or more assays to detect a plurality of analytes in the biological sample; and

b) the biological sample processing system comprises;

a sample handling system including a pipette; and

at least two detection units;

heating at least one portion of the cartridge using a movable heater on the biological sample processing system, wherein said heating comprises moving said movable heater from a first position to a second position wherein in the second position, at least a portion of the cartridge is inside the heater to pre-heat reagent units or assay units that are in the cartridge when the cartridge is in the biological sample processing system;

using said sample handling system for aliquoting at least a diluted portion of the sample into one of the plurality of said components while the cartridge remains inside the biological sample processing system;

decoupling one or more of said plurality of components from the cartridge while the cartridge remains inside the biological sample processing system to form one or more decoupled components;

performing in the biological sample processing system the three or more assays, wherein the three or more assays are performed at least partially in parallel and comprises leaving one or more of the one or more decoupled components of the cartridge at a location in the device separate from the cartridge;

detecting the plurality of analytes with at least one of the at least two detection unit in the biological sample processing system; and

after detecting the plurality of analytes, returning any decoupled components back to the cartridge while the cartridge remains inside the biological sample processing system;

wherein each of the reagent units is a container, a tube, a pipette tip, or a vessel;

wherein each of the assay units is a cuvette, a container, a tube, a pipette tip, or a vessel;

where the cartridge in the refrigerated condition has temperature in the range of about 2°

C. to about 8°

C.

20. A method of performing three or more assays for detecting a plurality of analytes in a biological sample from a subject, comprising:

providing a cartridge in a refrigerated condition at a temperature less than room temperature,

receiving the biological sample and the cartridge in a biological sample processing system, wherein;

c) the cartridge comprises;

a plurality of components including sample vessels, reagent units, and at least three assay units for performing the three or more assays to detect a plurality of analytes in the biological sample; and

b) the biological sample processing system comprises;

a sample handling system including a pipette; and

at least two detection units;

heating at least one portion of the cartridge using a movable heater on the biological sample processing system, wherein said heating comprises moving said movable heater from a first position to a second position wherein in the second position, at least a portion of the cartridge is inside the heater to pre-heat reagent units or assay units that are in the cartridge when the cartridge is in the biological sample processing system;

using said sample handling system for aliquoting at least a diluted portion of the sample into one of the plurality of said components while the cartridge remains inside the biological sample processing system;

decoupling one or more of said plurality of components from the cartridge while the cartridge remains inside the biological sample processing system to form one or more decoupled components;

performing in the biological sample processing system the three or more assays, wherein the three or more assays are performed at least partially in parallel and comprises leaving one or more of the one or more decoupled components of the cartridge at a location in the device separate from the cartridge;

detecting the plurality of analytes with at least one of the at least two detection unit in the biological sample processing system; and

after detecting the plurality of analytes, returning any decoupled components back to the cartridge while the cartridge remains inside the biological sample processing system;

wherein each of the reagent units is a container, a tube, a pipette tip, or a vessel;

wherein each of the assay units is a cuvette, a container, a tube, a pipette tip, or a vessel;

wherein the heater is mounted below a cartridge receiving location in the device.