Devices and methods for biological sample-to-answer and analysis

• US 9,518,291 B2
• Filed: 11/01/2013
• Issued: 12/13/2016
• Est. Priority Date: 12/23/2011
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Malik, Imran R., Garcia, Erika F., Madero, Xiomara Linnette, Scherer, Axel
• Primary Examiner(s): Kim, Young J
• Application Number:
  US14/070,466
• Publication Number:
  US 20140057279A1
• Time in Patent Office: 1,138 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• 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 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: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: F17D 3/00 Arrangements for supervising or controlling working operations
• CPC Class Codes: G01N 1/286 involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising microtomes G01N1/06; pulverising in general B02C; mixing in general B01F
• CPC Class Codes: G01N 2001/2866 Grinding or homogeneising
• CPC Class Codes: G01N 2001/4061 Solvent extraction
• CPC Class Codes: G01N 2021/0325 Cells for testing reactions, e.g. containing reagents
• CPC Class Codes: G01N 2035/00326 Analysers with modular structure
• CPC Class Codes: G01N 2035/00465 Separating and mixing arrangements
• CPC Class Codes: G01N 2035/0446 Combinations of the above
• CPC Class Codes: G01N 2035/1048 using the transfer device for another function
• CPC Class Codes: G01N 2035/1058 for mixing
• CPC Class Codes: G01N 21/03 : Cuvette constructions
• CPC Class Codes: G01N 21/552 : Attenuated total reflection
• CPC Class Codes: G01N 21/648 : using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 2201/0221 : Portable; cableless; compact; hand-held
• CPC Class Codes: G01N 35/04 : Details of the conveyor system G01N35/021 - G01N35/028 take precedence

Abstract

Methods and devices for biological sample preparation and analysis are disclosed. A device may have a linear or circular arrangement of containers, with a connecting structure such as a bar or disk. Fluidics channels between containers allow the performance of different techniques for sample preparation, such as lysing, washing and elution. Different functional elements, such as grinders or mixers, may be attached to the containers. The device may have a reaction cartridge with a reaction chamber to perform techniques such as polymerase chain reaction.

Claims

1. A device comprising:

a top structure;

a bottom structure;

a connecting structure, wherein the connecting structure connects the top structure to the bottom structure; and

a cartridge comprising;

a first part, wherein the first part is transparent to electromagnetic waves of a desired wavelength range and has an inner surface defining a first surface of at least one reaction chamber;

a central part, attached to the first part, wherein the central part has an inner surface defining sidewalls of the at least one reaction chamber; and

a metal back plate, attached to the central part, wherein the metal back plate has an inner surface defining a second surface of the at least one reaction chamber,

wherein the first part comprises;

a transparent top layer configured to act as a waveguide and focus or direct electromagnetic waves onto the at least one reaction chamber;

at least one prism, attached to a side of the transparent top layer and configured to focus or direct electromagnetic waves onto the transparent top layer;

at least one handle;

at least one opening in the transparent top layer; and

at least one fluidics channel connecting the at least one opening to the at least one reaction chamber, the cartridge attached to the top structure or the bottom structure;

wherein the top structure comprises

a first plurality of containers, each container of the first plurality of containers having;

a top opening, wherein the top opening has a sealing element which can slide inside the container while substantially maintaining a seal;

a central part;

a bottom opening;

at least two ports in at least one container of the first plurality of containers, the at least two ports comprising

a first port configured for air venting;

a second port configured for fluid insertion;

a sealing cap for each port;

the bottom structure comprises

a second plurality of containers, each container of the second plurality of containers having;

a top opening;

a central part;

a bottom opening, wherein the bottom opening has a sealing element;

the connecting structure comprises

at least one fluidics channel;

a supporting element which can slide, rotate or move within a plane, thereby establishing a fluidics connection, through the at least one fluidics channel, between;

i) the bottom opening of at least one container of the first plurality of containers and the top opening of at least one container of the second plurality of containers, while substantially sealing other bottom openings of the first plurality of containers and other top openings of the second plurality of containers;

ii) the bottom opening of at least one container of the first plurality of containers and the at least one opening of the cartridge, while substantially sealing other bottom openings of the first plurality of containers and the top openings of the second plurality of containers;

or

iii) the top opening of at least one container of the second plurality of containers and the at least one opening of the cartridge, while substantially sealing the bottom openings of the first plurality of containers and other top openings of the second plurality of containers.

2. The device of claim 1, wherein the at least one opening comprises an insertion port and a venting port.

3. The device of claim 1, wherein the metal back plate is made of aluminum and the first and central parts are made of polymeric material, and wherein the cartridge further comprises an adhesive layer between the central part and the metal back plate.

4. The device of claim 1, wherein the at least one reaction chamber comprises three reaction chambers, each reaction chamber having a venting port and an insertion port.

5. The device of claim 1, wherein the at least one reaction chamber comprises

three reaction chambers;

one insertion port;

fluidics channels connecting the insertion port to each of the three reaction chambers; and

a venting port for each reaction chamber.

6. The device of claim 1, wherein the at least one prism extends onto an outer surface of the central part and is configured to focus or direct light onto the at least one reaction chamber.

7. The device of claim 1, wherein reagents are coated to the first surface, the second surface or the sidewalls of the at least one reaction chamber.

8. The device of claim 1, wherein the first surface, second surface, or sidewalls of the at least one reaction chamber are nanopatterned.

9. The device of claim 1, wherein the transparent top layer is configured for total internal reflection detection.

10. The device of claim 1, wherein the at least one opening is attached to a capillary.

11. The device of claim 10, wherein the capillary is configured for capillary electrophoresis.

12. The device of claim 11, wherein the capillary is configured for optical detection.

13. The device of claim 1, further comprising a waveguide layer between the metal back plate and the central part, wherein the waveguide layer is configured to focus or direct an evanescent field of electromagnetic waves onto the second surface of the at least one reaction chamber.

14. The device of claim 1, wherein the central part and the metal back plate have a mechanically complementary shape configured to allow a mechanical lock.

15. The device of claim 1, wherein the at least one opening comprises an insertion port and a venting port located on a same side of the cartridge.

16. The device of claim 1, wherein the at least one reaction chamber comprises a plurality of reaction chambers, arranged in a substantially circular pattern, and wherein the transparent top layer is configured to focus or direct electromagnetic waves onto the plurality of reaction chambers.

17. The device of claim 1, wherein the first and second plurality of containers are arranged in a circular pattern and the connecting structure is a disk.

18. The device of claim 17, wherein the sealing element of the first plurality of containers is a plunger or a piston.

19. The device of claim 1, wherein at least one container of the first plurality of containers further comprises an additional container attached on the central part of the at least one container, the additional container comprising

a top opening, wherein the top opening has a sealing element which can slide inside the additional container while substantially maintaining a seal;

a central part;

a bottom opening attached to the at least one container of the first plurality of containers; and

at least two ports in the additional container, the at least two ports comprising

a first port configured for air venting;

a second port configured for fluid insertion;

a sealing cap for each port.

20. The device of claim 19, wherein the additional container further comprises one or more of a mixer element, a pump element, a lysing element, and a filter element.

21. The device of claim 19, wherein the additional container further comprises a grinder element.

22. The device of claim 1, wherein the bottom opening of the first plurality of containers and the top opening of the second plurality of containers comprises a sealing element configured to

substantially seal a container against the connecting structure;

or

allow a fluidics connection between the top structure and the bottom structure, depending on a position of the connecting structure.

23. The device of claim 1, wherein the connecting structure further comprises at least one functional element selected from the group consisting of:

a nucleic acid binding membrane, a mixer, a sonicating element, and a filter.

24. The device of claim 1, wherein the sealing element of the second plurality of containers comprises a springed seal, a plunger, a piston, or a rubber pouch.

25. The device of claim 1, wherein at least one container of the second plurality of containers further comprises an additional container attached on the central part of the at least one container, the additional container comprising

a top opening, wherein the top opening has a sealing element which can slide inside the additional container while substantially maintaining a seal;

a central part; and

a bottom opening attached to the at least one container of the first plurality of containers.

26. The device of claim 1, wherein the second port comprises a supporting element configured to support a tip of a pipette.

27. The device of claim 1, wherein the device comprises a material selected from a cyclic olefin copolymer or cyclic olefin polymer, thermoplastic materials, metal, glass or elastomers.

28. The device of claim 1, wherein at least one of the first plurality of containers contains one or more of an elute solution, a washing solution, and a lysing solution.

29. The device of claim 1, wherein at least one container of the first or second plurality of containers has a flattened cylindrical structure.

30. The device of claim 1, wherein at least one container of the first or second plurality of containers has a heater element attached to an outer surface of the at least one container.

31. The device of claim 1, wherein the second port is attached to a capillary.

32. The device of claim 1, further comprising:

an elution container in the top or bottom structure;

a master mix container in the top or bottom structure, wherein the master mix container contains a master mix solution and has a desired fraction of volume of the elution container;

a plunger configured to operate the elution container and the maxter mix container simultaneously;

a mixer element in the top, bottom, or connecting structure;

a fluidics channel in the top, bottom or connecting structure, connecting the elution container to the mixer element;

a fluidics channel in the top, bottom or connecting structure, connecting the master mix container to the mixer element;

a fluidics channel in the top, bottom or connecting structure, connecting the mixer element to the at least one opening of the cartridge.

33. A method comprising:

providing the device of claim 1;

inserting a sample analyte in a first container of the first plurality of containers;

operating the connecting structure and the sealing elements of the first and second plurality of containers, based on a desired movement of fluids between the first and second plurality of containers, thereby obtaining a prepared sample; and

operating the connecting structure and the sealing elements of the first or second plurality of containers, thereby moving the prepared sample to the at least one reaction chamber, thereby obtaining a target analyte.

34. The method of claim 33, wherein the desired movement of fluids comprises:

a lysing step;

at least one washing step;

an elution step;

and wherein a reaction is carried out in the reaction chamber.

35. The method of claim 34, wherein the reaction in the reaction chamber is polymerase chain reaction.