Nanoliter array loading

• US 8,105,554 B2
• Filed: 03/11/2005
• Issued: 01/31/2012
• Est. Priority Date: 03/12/2004
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Smith, Steve, Linton, John, Hess, Robert, Yoder, Karl, Brennan, Colin, Kanigan, Tanya S.
• Primary Examiner(s): Bullock, In Suk
• Assistant Examiner(s): Kingan, Timothy G
• Application Number:
  US11/078,196
• Publication Number:
  US 20070003448A1
• Time in Patent Office: 2,517 Days
• Field of Search: None
• US Class Current: 422/504
• CPC Class Codes: B01L 2200/021 Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/50857 using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: B01L 3/563 Joints or fittings in general F16L; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/1624 Destructible or deformable element controlled
• CPC Class Codes: Y10T 137/206 : Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
• CPC Class Codes: Y10T 436/2525 : Stabilizing or preserving

Abstract

An interface is provided for storing microfluidic samples in a nanoliter sample chip. A fluid access structure provides a fluid access region to a selected subset of sample wells from an array of sample wells. A fluid introduction mechanism introduces a sample fluid to the fluid access region so that the sample wells in the selected subset are populated with the sample fluid without the unselected sample wells being populated with the sample fluid.

Claims

1. A method of storing microfluidic samples, the method comprising:

providing an array of sample wells for storing microfluidic samples, the sample wells disposed along and open to at least one planar surface;

positioning a fluid access structure adjacent to one of the at least one planar surfaces, the fluid access structure comprising a microfluidic circuit for distributing the sample fluid to a fluid access region encompassing a subset of the sample wells from the array of sample wells, wherein the microfluidic circuit includes one or more microfluidic channels adapted to overlay openings of the subset of the sample wells, wherein two or more channels of the one or more microfluidic channels span at least two openings of the subset; and

introducing a sample fluid through the microfluidic circuit to the fluid access region so that the sample wells in the fluid access region are populated with the sample fluid.

2. A method according to claim 1, further comprising providing a fluid access region encompassing the subset of sample wells, wherein the fluid access structure includes a mask to create a barrier between the fluid access region and other regions of the one planar surface.

3. A method according to claim 1, wherein the fluid access structure includes a printing plate.

4. A method according to claim 1, further comprising:

providing a fluid access region encompassing the subset of sample wells; and

dragging a drop of the sample fluid over the fluid access region.

5. The method of claim 1, wherein the sample wells are through-holes.

6. The method of claim 1, further comprising flowing fluid from the one channel into the at least two openings.

7. An interface device for storing microfluidic samples in a chip having an array of sample wells, the interface device comprising:

a fluid access structure comprising a microfluidic circuit for distributing the sample fluid to a subset of sample wells of the array of sample wells, wherein the microfluidic circuit includes microfluidic channels, wherein two or more of the microfluidic channels are adapted to overlay at least two sample wells of the subset of the sample wells.

8. An interface device according to claim 7, wherein the fluid access structure includes a mask to create a barrier between the fluid access region and other regions of the array.

9. An interface device according to claim 7, further comprising:

a fluid access region encompassing the subset of sample wells; and

means for dragging a drop of the sample fluid over the fluid access region.

10. An interface device according to claim 7, further comprising a fluid access region encompassing the subset of sample wells, wherein a pipette is provided for introducing a sample fluid to the fluid access region.

11. An interface device according to claim 7, further comprising a fluid access region encompassing the subset of sample wells, wherein the fluid access structure includes a membrane for providing the fluid access region and the means for introducing a sample fluid.

12. An interface device according to claim 11, wherein the membrane includes an outer surface having patterned hydrophobic and hydrophilic regions.

13. The device of claim 7, further comprising means for introducing a sample fluid through the microfluidic circuit to the fluid access region so that the subset of sample wells are populated with the sample fluid.

14. The device of claim 7, wherein the sample wells are through-holes.

15. The device of claim 7, further comprising a chip including the array of sample wells.

16. The device of claim 7, further comprising an array of sample wells disposed along and open to a planar surface, the fluid access structure configured to be positioned adjacent the planar surface such that the one channel overlays at least two of the sample wells.

17. The device of claim 7, wherein the one channel is configured to flow fluid within the channel into the at least two sample wells.

18. A kit for storing microfluidic samples comprising:

the interface device of claim 7; and

a chip containing the array of sample wells.

19. A kit according to claim 18, wherein the interface device further contains a reagent for the wells in the selected subset of sample wells.

20. A kit according to claim 19, wherein the reagent is a dye for staining the sample fluid populated into the subset of wells.

21. An interface device for storing microfluidic samples in a chip having an array of sample wells, the interface device comprising:

a fluid access structure configured to define a fluid access region encompassing a subset of at least two sample wells of an array of sample wells, the fluid access structure adapted for positioning next to a planar surface of the array and including a microfluidic circuit for distributing a sample fluid to the fluid access region, wherein the microfluidic circuit includes microfluidic channels, wherein two or more of the microfluidic channels are adapted to overlay at least two of the sample wells.

22. An interface device according to claim 21, wherein the fluid access structure includes a mask to create a barrier between the fluid access region and the rest of the array.

23. An interface device according to claim 21, wherein the fluid introduction mechanism is adapted for dragging a drop of the sample fluid over the fluid access region.

24. The device of claim 21, further comprising a fluid introduction mechanism for introducing a sample fluid through the microfluidic circuit to the fluid access region so that the subset of sample wells are populated with the sample.

25. The device of claim 21, wherein the sample wells are through-holes.

26. The device of claim 21, further comprising a chip including the array of sample wells.

27. The device of claim 21, further comprising an array of sample wells disposed along and open to a planar surface, the fluid access structure configured to be positioned adjacent the planar surface such that the one channel overlays at least two of the sample wells.

28. The device of claim 21, wherein each channel is configured to flow fluid within the channel into the at least two sample wells.

29. A kit for storing microfluidic samples comprising:

the interface of claim 21; and

a chip containing the array of sample wells.

30. A kit according to claim 29, wherein the interface device further contains a reagent for the wells in the selected subset of sample wells.

31. A kit according to claim 30, wherein the reagent is a dye for staining the sample fluid populated into the subset of wells.

32. A method of storing microfluidic samples, the method comprising:

providing a chip having an array of sample wells for storing microfluidic samples, the sample wells open to at least one planar surface;

positioning a fluid access structure adjacent to one of the at least one planar surfaces of the chip, the fluid access structure configured to define a fluid access region encompassing a subset of sample wells, and facilitate providing a fluid access region to a selected subset of sample wells;

and introducing a sample fluid to the fluid access region so that the sample wells are populated with the sample fluid;

wherein providing a fluid access region includes folding a portion of the chip.

33. An interface for storing microfluidic samples in a chip having an array of sample wells, the interface comprising:

a fluid access structure configured to define a fluid access region encompassing a subset of the sample wells; and

means for introducing a sample fluid to the fluid access region so that the sample wells in the selected subset are populated with the sample fluid;

wherein the means for providing a fluid access region includes means for folding a portion of the array.

34. An interface for storing microfluidic samples in a chip having an array of sample wells, the interface comprising:

a fluid access structure configured to define a fluid access region encompassing a subset of sample wells; and

a fluid introduction mechanism for introducing a sample fluid to the fluid access region so that the sample wells in the selected subset are populated with the sample fluid;

wherein the fluid access structure is adapted for positioning next to a planar surface of the array to provide the fluid access region; and

wherein the fluid access structure is adapted to fold a portion of the array to provide the fluid access region.

35. A through-hole array comprising:

a plurality of sub-array nodes, each sub-array node including a sub-array of through-holes; and

a plurality of foldable arms connecting adjacent sub-array nodes.

36. The through-hole array of claim 35, wherein the plurality of sub-array nodes and the plurality of foldable arms are formed from a single sheet of material.

37. The through-hole array of claim 36, wherein the material is a metal.

38. The through-hole array of claim 35, wherein the plurality of sub-array nodes is sized for insertion into a microtiter plate.

39. The through-hole array of claim 38, wherein the microtiter plate is a 96-well microtiter plate.

40. A method of transferring one or more liquid samples residing in one or more wells of a microtiter plate to a through-hole array, the method comprising:

providing a through-hole array including;

a plurality of sub-array nodes, each sub-array node including a sub-array of through-holes; and

a plurality of foldable arms connecting adjacent sub-array nodes;

folding one or more of the plurality of foldable arms to produce a three-dimensional structure wherein the inter-node spacing substantially matches the inter-well spacing of the microtiter plate; and

dipping the sub-array nodes in the wells of the microtiter plate;

thereby transferring one or more liquid samples residing in a microtiter plate to a through-hole array.