Systems and methods for multi-analysis

• US 9,810,704 B2
• Filed: 02/18/2014
• Issued: 11/07/2017
• Est. Priority Date: 02/18/2013
• Status: Active Grant

• Current Assignee: Labrador Diagnostics LLC (SoftBank Group Corp.)
• Original Assignee: Theranos Incorporated
• Inventors: Holmes, Elizabeth A., Balwani, Sunny, Chen, Michael, Frankovich, John K., Frenzel, Gary, Anekal, Samartha, Lath, Adrit, Loo, Alexander, Pangarkar, Chinmay, Roy, Joy, Smith, Timothy, Young, Daniel
• Primary Examiner(s): Ghafoorian, Reza
• Application Number:
  US14/183,500
• Publication Number:
  US 20140296089A1
• Time in Patent Office: 1,358 Days
• 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 point-of-service, benchtop biological sample processing device comprising:

a housing containing therein;

an automated sample handling system comprising a fluid handling apparatus comprising a pipette having a nozzle configured to;

a) engage and hold a pipette tip and b) to engage and hold a microscopy cuvette, wherein said microscopy cuvette is configured to engage said pipette nozzle;

a first detection station comprising an electronic optical sensor;

a second detection station comprising a light source and an electronic optical sensor or sensing device;

a cytometry station comprising an imaging device and a stage for receiving said microscopy cuvette;

a centrifuge;

a convective flow unit to provide thermally conditioned airflow to maintain a desired air temperature range in the housing;

one or more temperature sensors to provide feedback to a controller to adjust air temperature;

a fan for exhausting air flow through a filtered outlet on the housing;

a cartridge receiving location;

wherein the automated sample handling system is configured to have fluid handling apparatus movable to individually access each of the following;

first detection station, second detection station, cytometry station, centrifuge, and cartridge receiving location.

2. The biological sample processing device of claim 1, wherein the biological sample has a volume of no greater than 500 microliters.

3. The biological sample processing device of claim 1, wherein the second detection station comprises a nucleic acid assay station, wherein the light source and electronic optical sensor or sensing device of the second detection station are contained within the nucleic acid assay station.

4. The biological sample processing device of claim 3, wherein the nucleic acid assay station comprises a thermal block.

5. The biological sample processing device of claim 3, wherein the nucleic acid assay station comprises at least a first well and a second well, and the first well is configured for the measurement of the fluorescence of samples and the second well is configured for the measurement of the turbidity of samples.

6. The biological sample processing device of claim 1, wherein the biological sample processing device further comprises a third detection station, wherein the cartridge further contains a fourth assay unit, wherein the fourth assay unit comprises gear teeth, and wherein the biological sample processing device is configured to transport the fourth assay unit to the third detection station by using a gear mechanism to engage the gear teeth in the assay unit.

7. The biological sample processing device of claim 1, wherein the biological sample processing device further contains therein a barometer.

8. The biological sample processing device of claim 1, wherein the electronic optical sensor is selected from the group of electronic optical sensors consisting of photodiodes, photomultiplier tubes (PMTs), Charge-Coupled Devices (CCDs), super-cooled CCD arrays, CMOS sensors, photodetectors, photon counting detectors, avalanche photodiodes, avalanche photodiode arrays, pin diodes, spectrophotometers, and electronic cameras.

9. A method for performing multiple assays with a biological sample, the method comprising:

providing a point-of-service, benchtop biological sample processing device

comprising a housing containing therein;

an automated sample handling system comprising a fluid handling apparatus comprising a pipette having a nozzle configured to;

a) engage and hold a pipette tip and b) to engage and hold a microscopy cuvette, wherein said microscopy cuvette is configured to engage said pipette nozzle;

a first detection station comprising an electronic optical sensor;

a second detection station comprising a light source and an electronic optical sensor;

a cytometry station comprising an imaging device and a stage for receiving said microscopy cuvette; and

a cartridge, wherein the cartridge is insertable into and removable from the biological sample processing device, and wherein the cartridge contains i) a biological sample, ii) at least a first, a second, and a third fluidically isolated assay unit, and iii) all reagents that are required to perform a first, second, and third assay comprising A) at least one luminescence assay;

B) at least one absorbance, turbidimetric, fluorescence, or colorimetric assay; and

C) at least one cytometry assay, and wherein the first assay unit is configured to perform a luminescence assay, the second assay unit is configured to perform an absorbance, turbidimetric, fluorescence, or colorimetric assay, the third assay unit is configured to perform a cytometry assay, and

transferring, by the fluid handling apparatus of the automated sample handling system, said microscopy cuvette to said stage of said cytometry station;

transferring by the automated sample handling system at least a portion of the biological sample to each of the first, second, and third assay units;

transferring by the automated sample handling system the first assay unit containing biological sample to the first detection station;

transferring by the automated sample handling system the second assay unit containing biological sample to the second detection station;

transferring by the automated sample handling system the third assay unit containing biological sample to the cytometry station, wherein said third assay unit comprises said microscopy cuvette configured to perform a cytometry assay, said microscopy cuvette having at least one cavity configured to accept a sample, and having at least one pick-up interface configured to engage with said fluid handling apparatus, said transferring comprising said pipette nozzle engaging and holding said pick-up interface of said microscopy cuvette and moving said microscopy cuvette by said pipette while said microscopy cuvette is held by said pipette nozzle; and

transferring from the cartridge to the first, second, and third assay units, respectively, all reagents required for the performance of the first, second, and third assays to the respective assay units;

wherein the sample processing device also contains a centrifuge;

a convective flow unit to provide thermally conditioned airflow to maintain a desired air temperature range in the housing;

one or more temperature sensors to provide feedback to a controller to adjust air temperature;

a fan for exhausting air flow through a filtered outlet on the housing.

10. The method of claim 9, wherein the biological sample has a volume of no greater than 500 microliters.

11. The method of claim 9, wherein a turbidimetric assay is performed in the second assay unit, and wherein the turbidity of the turbidimetric assay is measured over a period of time.

12. The method of claim 9, wherein the electronic optical sensor is selected from the group of electronic optical sensors consisting of photodiodes, photomultiplier tubes (PMTs), Charge-Coupled Devices (CCDs), super-cooled CCD arrays, CMOS sensors, photodetectors, photon counting detectors, avalanche photodiodes, avalanche photodiode arrays, pin diodes, spectrophotometers, and electronic cameras.

13. The method of claim 9, wherein the cytometry assay comprises determining the number of at least one type of cell per selected volume of biological sample, the at least one type of cell being selected from the group consisting of:

monocytes, lymphocytes, neutrophils, basophils, and eosinophils.

14. The method of claim 9, wherein the biological sample is from a subject, and wherein prior to insertion of the cartridge into the biological sample processing device, the subject'"'"'s insurance coverage is checked.

15. The method of claim 9, wherein the biological sample processing device further comprises a third detection station, wherein the cartridge further contains a fourth assay unit, wherein the fourth assay unit comprises gear teeth, and wherein the method further comprises transporting the fourth assay unit to the third detection station by rotation of a gear mechanism, wherein rotation of the gear mechanism engages the gear teeth in the fourth assay unit and moves the fourth assay unit into the third detection station.

16. The method of claim 9, wherein the cartridge comprises a lid and a locking feature, wherein the lid comprises an engagement feature which is configured to optionally engage the locking feature in the cartridge, and wherein the engagement feature does not engage the locking feature in the cartridge upon insertion of the cartridge into the sample processing device.

17. The method of claim 9, wherein the second detection station comprises a nucleic acid assay station, wherein the light source and electronic optical sensor or sensing device of the second detection station are contained within the nucleic acid assay station.