Sample preparation module with stepwise pressurization mechanism

• US 10,252,264 B2
• Filed: 02/05/2015
• Issued: 04/09/2019
• Est. Priority Date: 02/05/2014
• Status: Active Grant

• Current Assignee: Talis Biomedical Corporation (Baker Bros. Advisors LP)
• Original Assignee: Talis Biomedical Corporation (Baker Bros. Advisors LP)
• Inventors: Shen, Feng, Da Costa, Chris, Maamar, Hedia
• Primary Examiner(s): Warden, Jill A
• Assistant Examiner(s): Brazin, Jacqueline
• Application Number:
  US15/117,156
• Publication Number:
  US 20160346781A1
• Time in Patent Office: 1,524 Days
• Field of Search: 422527
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0631 Purification arrangements, e.g. solid phase extraction [SPE]
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/027 Digital display, e.g. LCD, LED
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0832 cylindrical, tube shaped
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0475 specific mechanical means and fluid pressure
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: C12N 15/1006 by means of a solid support carrier, e.g. particles, polymers
• CPC Class Codes: G01N 1/405 by adsorption or absorption
• CPC Class Codes: G01N 2035/00881 network configurations

Abstract

The present invention relates to fluidic systems for controlling one or more fluids or reagents. These systems can be used in combination with one or more devices for assaying, processing, or storing samples. In particular, the systems and related methods can allow for controlled pressure and actuation of fluids.

Claims

1. A sample preparation module comprising:

a housing having an interior surface;

a central shaft comprising a threaded section;

a pressure cap comprising;

a gasket engaged with the interior surface of the housing to create an airtight seal;

a central column extending centrally from the inner surface of the pressure cap, wherein the central column comprises threads configured to engage the threaded section of the central shaft such that rotation of the central shaft relative to the central column results in movement of said pressure cap linearly along the length of said central shaft;

a plurality of coaxially arranged layers engaged with the central shaft, at least one being a rotor and one being a stator, said coaxially arranged layers having complementary facing surfaces assembled in a frictional, sealed engagement, each layer having at least one passageway with an upstream entry and a downstream outlet capable for successive selective placement in communication to establish plural dedicated flow paths within the assembly, wherein the central shaft extends through the plurality of coaxially arranged layers, and wherein a first coaxially arranged layer engages with the interior surface of the housing to create an airtight seal; and

an airtight compartment formed by the interior surface of the housing engaged in said airtight seal with the gasket of the pressure cap and the interior surface of the housing engaged in the airtight seal with the first coaxially arranged layer,

wherein rotation of the central column relative to the central shaft slidably moves the gasket of the pressure cap or the first coaxially arranged layer along the interior surface of the housing such that the compartment is compressed, thereby generating pressure against the upstream surface of the first coaxially arranged layer, and

wherein rotation of said rotor around said central shaft selectively connects passageways of different coaxial layers thereby serially forming and disrupting a plurality of fluid paths.

2. The sample preparation module of claim 1, wherein the rotor is engaged directly or indirectly with the central shaft and the stator is engaged directly or indirectly with the housing.

3. The sample preparation module of claim 1, wherein the stator is engaged directly or indirectly with the central shaft and the rotor is engaged directly or indirectly with the housing.

4. The sample preparation module of claim 1, wherein the central shaft engages with a drive.

5. The sample preparation module of claim 4, wherein the coaxially arranged layer most proximal to the drive is transparent.

6. The sample preparation module of claim 1, wherein the pressure cap further comprises a key or keyseat that engages with a complementary keyseat or key in the housing thereby inhibiting rotation of the pressure cap relative to the housing.

7. The sample preparation device of claim 1, wherein the pressure cap further comprises a manual grip.

8. The sample preparation module of claim 1, wherein the threads of the central column have a different pitch than the threaded section of the central shaft.

9. The sample preparation module of claim 1, wherein the threaded section of the central shaft is externally threaded and the central column of the pressure cap is internally threaded.

10. The sample preparation module of claim 1, wherein the threaded section of the central shaft is internally threaded and the central column of the pressure cap is externally threaded.

11. The sample preparation module of claim 1, wherein the central shaft comprises a plurality of linked sections, each section engaged with adjacent sections.

12. The sample preparation module of claim 1, wherein the housing is permanently affixed to a coaxially arranged layer.

13. The sample preparation module of claim 1, wherein the housing is comprised of two or more segments that when assembled form airtight junctions.

14. The sample preparation module of claim 13, wherein each of the two or more segments of the housing are permanently affixed to a coaxially arranged layer.

15. The sample preparation device of claim 1, wherein the coaxially arranged layers comprise a reagent layer, a separation layer, and a receiving layer.

16. The sample preparation module of claim 15, wherein the reagent layer receives a sample in a first fluid path that is open to the upstream and downstream surfaces.

17. The sample preparation module of claim 16, wherein the reagent layer comprises a second fluid path that is open to the upstream and downstream surfaces.

18. The sample preparation module of claim 15, wherein the separation layer comprises a separation material occluding the at least one passageway between the upstream and downstream surfaces, said separation material capable of reversibly binding a molecule of interest.

19. The sample preparation module of claim 15, further comprising an analytic layer.

20. The sample preparation module of claim 19, wherein the analytic layer comprises a microfluidic device.

21. The sample preparation module of claim 1, wherein at least one coaxially arranged layer comprises a waste chamber, said waste chamber being a dead end path open only to the upstream surface of the layer.

22. The sample preparation module of claim 1, further comprising a re-sealable sample inlet.

30. The sample preparation module of claim 1, wherein the gasket of the pressure cap or the first coaxially arranged layer is slidably engaged with the interior surface of the housing.

23. A method of isolating a molecule of interest from a sample, the method comprising:

a) providing a device comprising a pressure cap, a central shaft, and a plurality of coaxially arranged layers, including a reagent layer, a separation layer and a receiving layer;

b) loading the reagent layer with a lysis solution, a wash solution and an elution solution, each solution occupying a separate passageway having an upstream entry and downstream outlet, wherein each of the downstream outlets of the passageways is occluded in a first position of the device;

c) combining a sample with the lysis solution in the reagent layer to form a lysed mixture;

d) rotating the central shaft to a second position, thereby

1) rotating the reagent layer relative to the separation layer to align the outlet of the passageway holding the lysed mixture with the upstream entry of a passageway in the separation layer, said passageway in the separation layer being occluded by a separation material capable of binding the molecule of interest; and

2) moving the pressure cap toward the plurality of coaxially arranged layers, thereby applying positive pressure to the lysed mixture and forcing the lysed mixture onto and through the separation material;

e) rotating the central shaft to a third position, thereby

1) rotating the reagent layer relative to the separation layer to align the outlet of the passageway holding the wash solution with the upstream entry of the passageway in the separation layer occluded by the separation material; and

2) moving the pressure cap further toward the plurality of coaxially arranged layers, thereby applying additional positive pressure to force the wash solution through the separation material; and

f) rotating the central shaft to a fourth position, thereby

1) rotating the reagent layer relative to the separation layer to align the outlet of the passageway holding the elution solution with the upstream entry of the passageway in the separation layer occluded by the separation material;

2) rotating the separation layer relative to the receiving layer to align the outlet of the passageway occluded with the separation material with the upstream entry of a first passageway in the receiving layer; and

3) moving the pressure cap further toward the plurality of coaxially arranged layers, thereby applying additional positive pressure to force the elution solution through the separation material to detach the molecule of interest from the separation material and collect the elution solution and molecule of interest in the passageway of the receiving layer.

24. The method of claim 23, wherein rotating the central shaft to the second position further comprises rotating the separation layer relative to the receiving layer to align the outlet of the passageway occluded with the separation material with the upstream entry of a second passageway in the receiving layer, said second passageway configured to capture waste liquids.

25. The method of claim 24, wherein the waste liquids are captured in an absorbent housed in the second passageway of the receiving layer.

26. The method of claim 23, wherein the plurality of coaxially arranged layers includes an analytic layer and the method further comprises the step of:

g) rotating the central shaft to a fifth position, thereby

1) rotating the receiving layer relative to the analytic layer to align the outlet of the passageway holding the elution solution and the molecule of interest with the upstream entry of a passageway in the analytic layer; and

2) moving the pressure cap further toward the plurality of coaxially arranged layers, thereby applying additional positive pressure to force the elution solution and molecule of interest into the passageway of the analytic layer.

27. The method of claim 26, wherein the molecule of interest is a nucleic acid and the analytic layer is configured to amplify the nucleic acid.

28. The method of claim 23, wherein the sample is provided through a re-sealable sample inlet.

29. The method of claim 23, wherein the molecule of interest is a nucleic acid.

31. A sample preparation module comprising:

a housing having an interior surface;

a central shaft comprising a threaded section;

a pressure cap comprising;

a gasket engaged with the interior surface of the housing to create an airtight seal;

a central column extending centrally from the inner surface of the pressure cap, wherein the central column comprises threads configured to engage the threaded section of the central shaft such that rotation of the central shaft relative to the central column results in movement of said pressure cap linearly along the length of said central shaft;

a plurality of coaxially arranged layers engaged with the central shaft, at least one being a rotor and one being a stator, said coaxially arranged layers having complementary facing surfaces assembled in a frictional, sealed engagement, each layer having at least one passageway with an upstream entry and a downstream outlet capable for successive selective placement in communication to establish plural dedicated flow paths within the assembly, wherein the central shaft extends through the plurality of coaxially arranged layers, and wherein a first coaxially arranged layer engages with the interior surface of the housing to create an airtight seal; and

an airtight compartment formed by the interior surface of the housing engaged in said airtight seal with the gasket of the pressure cap and the airtight seal with the first coaxially arranged layer,

wherein rotation of the central column relative to the central shaft slidably moves the gasket of the pressure cap or the first coaxially arranged layer along the interior surface of the housing such that the compartment is compressed, thereby generating pressure against the upstream surface of the first coaxially arranged layer, and

wherein rotation of the central shaft relative to the central column simultaneously

i) slidably moves the pressure cap or the first layer along the interior surface of the housing such that the compartment is compressed, thereby generating pressure against the upstream surface of the first coaxially arranged layer, and

ii) rotates the rotor relative to the stator to selectively connect passageways of different coaxial layers thereby serially forming and disrupting a plurality of fluid paths.