Systems and methods for fluid and component handling

• US 10,371,710 B2
• Filed: 10/30/2015
• Issued: 08/06/2019
• 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 R., Frankovich, John Kent, Holmes, Elizabeth A., Smith, Timothy, Chen, Michael, Young, Daniel
• Primary Examiner(s): Bowers, Nathan A
• Application Number:
  US14/928,087
• Publication Number:
  US 20160124009A1
• Time in Patent Office: 1,376 Days
• CPC Class Codes: B01L 2200/023 adapted for different sizes of tubes, tips or container
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/041 Connecting closures to device or container
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/0279 co-operating with positive ejection means
• CPC Class Codes: B01L 3/5021 Test tubes specially adapted for centrifugation purposes centrifuges B04B5/04
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/50855 using modular assemblies of strips or of individual wells
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 2035/00326 Analysers with modular structure
• CPC Class Codes: G01N 2035/00495 Centrifuges
• CPC Class Codes: G01N 2035/00881 network configurations
• CPC Class Codes: G01N 2035/0094 optimisation; experiment design
• 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 35/10 : 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 35/1065 : Multiple transfer devices
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

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 at least three different assays selected from immunoassays, cytometric assays, and general chemistry assays on a biological sample, the method comprising:

a) introducing a biological sample having a volume of no greater than 500 microliters into a benchtop point-of-care sample processing device, wherein the device comprises a housing for containing all of the following;

i) a sample handling system comprising a pipette assembly;

ii) a first detection station comprising an optical sensor;

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

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

v) a fluidically isolated sample collection unit configured to retain a biological sample;

vi) an assay station comprising at least a first, a second, a third, and a fourth independently movable and fluidically isolated assay unit;

vii) a communication unit configured to electronically connect said biological sample processing device with another device or with a network; and

viii) a controller, wherein the controller comprises a local memory and is operatively coupled to the sample handling system, the detection station, and the communication unit;

b) with the aid of the pipette assembly, transferring a portion of the biological sample to each of the first, second, third, and fourth assay units, wherein a different assay is performed in each of the first, second, third, and fourth assay units;

c) with the aid of the pipette assembly, transferring the first, second, third, and fourth assay units to the detection station or cytometry station, wherein assay units comprising immunoassays or general chemistry assays are transferred to the detection station and assay units comprising cytometric assays are transferred to the cytometry station;

d) with the aid of the detection station or cytometry station, obtaining data measurements of the assay performed in each of the first, second, third, and fourth assay units.

2. The method of claim 1, wherein said performing of said at least three different assays comprises performing at least assay selected from the group of assays consisting of an immunoassay, a nucleic acid assay, a cytometry assay, and a general chemistry assay comprising a chromogen.

3. The method of claim 1, wherein said performing of said at least three different assays comprises performing at least two assays selected from the group of assays consisting of an immunoassay, a nucleic acid assay, a cytometry assay, and a general chemistry assay comprising a chromogen.

4. The method of claim 1, wherein said processing of said biological sample comprises performing an immunoassay, a nucleic acid assay, and a general chemistry assay comprising a chromogen.

5. The method of claim 1, wherein said processing of said biological sample comprises performing an immunoassay, a cytometric assay, and a general chemistry assay comprising a chromogen.

6. The method of claim 1, wherein said processing of said biological sample comprises performing a nucleic acid assay, a cytometric assay, and a general chemistry assay comprising a chromogen.

7. The method of claim 1, wherein said processing of said biological sample comprises performing an immunoassay, a nucleic acid assay, and a cytometric assay.

8. A method of processing a biological sample, comprising:

a) introducing a sample having a volume of 500 microliters or less into a benchtop, point-of-care biological sample processing device comprising a housing for containing all of the following;

i) a sample handling system comprising a pipette assembly;

ii) at least a first and a second fluidically isolated vessel;

iii) a diluent; and

iv) a centrifuge, wherein the sample comprises bodily fluid at a first concentration;

v) a first detection station comprising an optical sensor;

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

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

viii) a fluidically isolated sample collection unit configured to retain a biological sample;

ix) an assay station comprising at least a first, a second, a third, and a fourth independently movable and fluidically isolated assay unit;

x) a communication unit configured to electronically connect said biological sample processing device with another device or with a network; and

xi) a controller, wherein the controller comprises a local memory and is operatively coupled to the sample handling system, one of the first or second detection station, and the communication unit;

b) with the aid of the sample handling system, introducing at least a portion of the sample into the centrifuge;

c) centrifuging the sample, to generate a centrifuged sample;

d) with the aid of the pipette assembly, removing at least a portion of the centrifuged sample from the centrifuge; and

e) with the aid of the pipette assembly, mixing at least a portion of the centrifuged sample with the diluent to generate a diluted sample, wherein the diluted sample comprises bodily fluid at a second concentration, and the second concentration of bodily fluid is one-half or less of the first concentration of bodily fluid; and

,

f) with the aid of the pipette assembly, transferring at least a portion of the diluted sample to at least one of the first and the second fluidically isolated vessels.

9. The method of preparing a biological sample claim 8, comprising:

a) introducing a biological sample and at least one isolated vessel into a sample processing device comprising a centrifuge and a sample handling system;

b) with the aid of the sample handling system, introducing at least a portion of the biological sample into the centrifuge, wherein the centrifuge comprises one or more cavities and wherein the one or more cavities are configured to receive a total of no more than 500 microliters between all of the one or more cavities;

c) centrifuging the sample, to generate a centrifuged sample;

d) with the aid of the sample handling system, removing at least a portion of the centrifuged sample from the centrifuge; and

e) with the aid of the sample handling system, transferring centrifuged sample removed from the centrifuge from step d) into the fluidically isolated vessel.

10. The method of claim 8, comprising transferring at least a portion of the diluted sample to the first fluidically isolated vessel and transferring at least a portion of the diluted sample to the second fluidically isolated vessel.

11. The method of claim 8, further comprising resuspending a portion of the centrifuged sample.

12. The method of claim 11, further comprising transferring at least a portion of the resuspended sample to at least one of the fluidically isolated vessels.

13. The method of claim 8, wherein said processing of said biological sample comprises processing for at least one of an immunoassay, a nucleic acid assay, a cytometric assay, and a general chemistry assay comprising a chromogen.