Fluidic devices and systems for sample preparation or autonomous analysis

• US 9,822,356 B2
• Filed: 04/22/2013
• Issued: 11/21/2017
• Est. Priority Date: 04/20/2012
• Status: Active Grant

• Current Assignee: Talis Biomedical Corporation (Baker Bros. Advisors LP), California Institute of Technology
• Original Assignee: California Institute of Technology, Slipchip Corporation
• Inventors: Ismagilov, Rustem F., Shen, Feng, Li, Liang, Hsu, Yu-Hsiang, Begolo, Stefano, Karymov, Mikhail, Selck, David, McCalla, Stephanie, Homewood, Philip James
• Primary Examiner(s): White, Dennis M
• Application Number:
  US13/868,028
• Publication Number:
  US 20130309679A1
• Time in Patent Office: 1,674 Days
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0678 Facilitating or initiating evaporation
• CPC Class Codes: B01L 2300/045 whereby the whole cover is slidable
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 2400/065 sliding valves
• 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B01L 3/52 : Containers specially adapted for storing or dispensing a reagent B01L3/02 takes precedence; containers for medical or pharmaceutical purposes A61J1/00; containers in general B65D; storing or dispensing test elements G01N33/4875; automated reagent dispensing G01N35/1002
• 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: C12N 15/1003 : Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
• CPC Class Codes: G01N 33/525 : Multi-layer analytical elements

Abstract

The present invention relates to fluidic devices for preparing, processing, storing, preserving, and/or analyzing samples. In particular, the devices and related systems and methods allow for preparing and/or analyzing samples (e.g., biospecimen samples) by using one or more of capture regions and/or automated analysis.

Claims

1. A sample preparation device comprising:

(i) a first layer comprising a plurality of first chambers, said plurality of first chambers comprising a sample chamber configured for receiving a sample, a washing chamber comprising a washing buffer for washing the sample and an eluting chamber comprising an elution buffer for eluting the sample;

(ii) a second layer comprising one or more second chambers; and

(iii) an intermediate layer disposed between said first and second layers, wherein said intermediate layer comprises a membrane matrix,

wherein at least one of said plurality of first chambers, at least one of said one or more second chambers, and the membrane matrix are able to be connected by relative movement.

2. The device of claim 1, wherein said membrane matrix is configured to connect two or more of said plurality of first chambers and at least one of said one or more second chambers.

3. The device of claim 1, wherein the sample chamber, at least one of said one or more second chambers, and the membrane matrix are configured to be connected by a first relative movement;

wherein the washing chamber, at least one of said one or more second chambers, and the membrane matrix are configured to be connected by a second relative movement; and

wherein the eluting chamber, at least one of said one or more second chambers, and the membrane matrix are configured to be connected by a third relative movement.

4. The device of claim 1, wherein said first layer, said second layer, or said intermediate layer is planar or non-planar.

5. The device of claim 1, wherein said first layer, said second layer, or said intermediate layer, or a portion thereof, is differentially wetted.

6. The device of claim 1, further comprising a deformable layer between said first layer and said intermediate layer and/or between said second layer and said intermediate layer.

7. The device of claim 6, further comprising a coating on one or more of said first layer, said intermediate layer, said second layer, or said deformable layer.

8. The device of claim 7, wherein said coating comprises a fluoropolymer.

9. The device of claim 1, wherein said first layer, said second layer, and/or said intermediate layer translates longitudinally.

10. The device of claim 1, wherein said first layer, said second layer, and/or said intermediate layer rotates axially.

11. The device of claim 1, further comprising a third layer comprising one or more third chambers, wherein said third layer is disposed beneath said second layer, and wherein at least one of said plurality of first chambers, at least one of said one or more second chambers, at least one of said one or more third chambers, and membrane matrix are able to be connected by relative movement.

12. The device of claim 11, further comprising a lubricant between said first layer and said intermediate layer and/or between said second layer and said intermediate layer and/or between said second layer and said third layer.

13. The device of claim 1, wherein one or more of said plurality of first chambers or at least one of said one or more second chambers is a well, a microchannel, or a duct.

14. The device of claim 1, further comprising an injection port for serial and/or sequential filling of said plurality of first chambers or at least one of said one or more second chambers.

15. The device of claim 1, further comprising a receiving chamber for controlling the volume of one or more fluids in said plurality of first chambers or at least one of said one or more second chambers.

16. The device of claim 1, wherein said first layer and said intermediate layer are fabricated as a single layer or wherein said intermediate layer and said second layer are fabricated as a single layer.

17. The device of claim 1, wherein said first layer further comprises a through-hole that connects to at least one of said plurality of first chambers and the intermediate layer disposed beneath said first layer;

and

wherein said device further comprises a lid that encloses a cavity having volume V₁ and surrounds said through-hole, wherein closure of said lid encloses said cavity and exerts a pressure commensurate with a volume difference between said volume V₁ and an open system having volume V₀.

18. The device of claim 17, wherein said lid further comprises a buckle pump, a flexible membrane, or a pumping cup that interfaces with said through-hole.

19. The device of claim 17, wherein said through-hole is configured to interface with a modified pipette tip, a modified syringe, or a porous sponge for filling at least one of said plurality of first chambers or at least one of said one or more second chambers.

20. The device of claim 1, wherein said first layer further comprises a through-hole that connects to at least one of said plurality of first chambers and the intermediate layer disposed beneath said first layer;

and wherein said device further comprises;

(iv) a housing system surrounding said device, wherein said housing system comprises an access port that connects to said through-hole for inserting a sample; and

(v) a cap for enclosing said housing system, wherein closing said cap results in introducing said sample into said through-hole and/or results in relatively moving said first layer and/or said intermediate layers.

21. The device of claim 20, wherein closing said cap results in introducing said sample and results in relatively moving said first layer and/or said intermediate layer.

22. The device of claim 20, wherein said cap encloses a cavity having volume V₁ and surrounds said through-hole, wherein closure of said cap encloses said cavity and exerts a pressure commensurate with a volume difference between said volume V₁ and an open system having volume V₀.

23. The device of claim 20, further comprising a spring mechanism or a rail system configured to move said cap within said housing.

24. The device of claim 1, wherein the intermediate layer comprises a first material and a second material different than the first material, wherein the membrane matrix comprises the second material.

25. A method of preparing and/or analyzing a sample, said method

comprising:

(i) providing a sample preparation device of claim 1;

(ii) introducing a test sample to said device; and

(iii) moving said first layer, said intermediate layer, and/or said second layer, if present, thereby resulting in sample preparation.

26. The method of claim 25, further comprising capturing one or more analytes from said sample with said membrane matrix.

27. The method of claim 26, further comprising moving said intermediate layer to be connected by relative movement to at least one of said plurality of first chambers or at least one of said one or more second chambers.

28. The method of claim 27, further comprising eluting said one or more analytes into at least one of said one or more second chambers using an elution buffer from the elution chamber.

29. The method of claim 25, wherein said sample preparation comprises one or more of the following steps:

partitioning said test sample into separate aliquots, filtering said one or more of said aliquots, washing said one or more of said aliquots, and/or quantifying the volume of said one or more aliquots after partitioning, after filtering, or after washing.

30. The method of claim 25, wherein said sample preparation comprises filtering, lysing, binding, washing, eluting, assaying, and/or detecting said test sample.

31. The method of claim 25, wherein said sample preparation comprises nucleic acid extraction, nucleic acid purification, nucleic acid enrichment, concentrating of a nucleic acid, protein extraction, protein purification, protein enrichment, concentrating of a protein, cell separation, sample enrichment, nucleic acid amplification, nucleic acid detection, and/or protein detection.

32. The method of claim 25, wherein step (iii) results in autonomous analysis of said sample.

33. The method of claim 25, wherein said test sample comprises blood, plasma, serum, sputum, urine, fecal matter, sweat, spinal fluid, amniotic fluid, interstitial fluid, tear fluid, bone marrow, a swab, a tissue sample, a buccal mouthwash sample, an aerosol, a nucleic acid, a cell, a protein, and/or an enzyme.

34. A kit comprising:

(i) a sample preparation device of claim 1; and

(ii) a collector for collecting a sample for use with said device.