High-density reaction chambers and methods of use

• US 20050277125A1
• Filed: 10/27/2004
• Published: 12/15/2005
• Est. Priority Date: 10/27/2003
• Status: Abandoned Application

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Cooper, Mats, Benn, James A., Thorsen, Todd
• Application Number:
  US10/976,168
• Publication Number:
  US 20050277125A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00563 Magnetic means
• CPC Class Codes: B01J 2219/00574 radioactive
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• 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 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 : centrifugal forces
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/021 : Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0293 : for liquids
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: B01L 9/543 : for disposable pipette tips, e.g. racks or cassettes
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 35/1011 : Control of the position or alignment of the transfer device

Abstract

Methods and devices for performing multiple simultaneous reactions on a reaction surface are disclosed. Methods and devices for simultaneously interrogating multiple patient samples with multiple diagnostic reagents are disclosed.

Claims

1. A method of forming a line of sample on a surface, the method comprising the steps of:

(a) forming a contact between a reaction surface on a reaction substrate and an open microfluidic channel on a channel substrate;

(b) introducing a sample solution into the microfluidic channel, wherein the sample solution contacts the reaction surface along a contact line formed by the contact between the reaction surface and the open microfluidic channel; and

,

(c) disrupting the contact between the reaction surface and the microfluidic channel, thereby forming a line of sample on the reaction surface, wherein the line corresponds to the contact line.

5. The method of claim 1, wherein the contact line of the microfluidic channel is between 1 micron and 500 microns wide.

6. The method of claim 1, wherein the contact line of the microfluidic channel is between 1 um and 500 um deep.

12. The method of claim 1, wherein the channel substrate comprises a plurality of open microfluidic channels, and a plurality of sample solutions are introduced into the microfluidic channels.

16. The method of claim 12, wherein the microfluidic channels are separated by a plurality of channel walls each having a thickness of between 5 and 50 microns.

17. The method of claim 12, wherein said plurality consists of between 10 and 2000 microfluidic channels.

35. A reaction surface array comprising a plurality of lines of biological samples, wherein the array is produced according to the method of claim 1.

36. A reaction surface array comprising a plurality of lines of reagent, wherein the array is produced according to the method of claim 1.

37. The surface array of claim 35, wherein the array comprises about 2000 lines of biological samples.

38. The surface array of claim 36, wherein the array comprises between 10 and 400,000 lines of reagents.

2. -4. (canceled)

7. -11. (canceled)

13. -15. (canceled)

18. -34. (canceled)

39. An array of target samples with a density of at least 50 sample lines per linear centimeter.

40. A method of contacting each member of a first plurality of samples with each member of a second plurality of samples, the method comprising the steps of:

(a) forming a contact between a reaction surface on a reaction substrate and an array of open microfluidic channels on a channel substrate, wherein the reaction surface comprises an array of lines of a first plurality of samples; and

,

(b) introducing a second plurality of sample solutions into the microfluidic channels, wherein a sample solution contacts the reaction surface along a contact line formed between the reaction surface and each microfluidic channel, and wherein each contact line intersects each line of the first plurality of samples on the reaction surface, thereby contacting each member of the first plurality of samples with each member of the second plurality of samples.

41. -43. (canceled)

44. A method of connecting a matrix of sample wells to an array of microfluidic channels, the method comprising the step of:

a) contacting a first surface of a matrix of sample wells to a first surface of a transfer plate, wherein a plurality of wells of said matrix is in fluid connection with a plurality of first channels on said transfer plate; and

,

b) contacting a second surface of the transfer plate to a first surface of an array of microfluidic channels, wherein a plurality of microfluidic channels of said array is in fluid connection with a plurality of second channels on said transfer plate, and wherein said plurality of first channels is in fluid connection with said plurality of second channels.

45. -53. (canceled)

54. An interface comprising:

a guide adapted to align a tip of a pipette toward a target within a well of a multi-well array; and

a retainer adapted to hold the tip of the pipette in alignment with the target.

55. -68. (canceled)

69. A method of placing solution from a pipette tip into a target within a well of a multi-well plate, the method comprising:

guiding the pipette tip toward a position of alignment with the target with a guide mated with the multi-well array;

retaining the pipette tip in the position of alignment with a retainer; and

flowing the solution from the pipette tip and into the target.

70. The method of claim 69, wherein guiding comprises guiding the pipette tip with a funnel shaped portion of a guide plate.

71. The method of claim 70, wherein the guide plate is adapted to mate with the multi-well array and has a plurality of funnel shaped portions each to guide a pipette tip toward a corresponding target.

72. The method of claim 71, wherein the guide plate has a funnel shaped portion corresponding to each well of the multi-well array.

73. The method of claim 72, wherein the target includes an aperture disposed within each well of the multi-well array.

74. -115. (canceled)