Tip design and random access array for microfluidic transfer

• US 6,551,557 B1
• Filed: 12/10/1999
• Issued: 04/22/2003
• Est. Priority Date: 07/07/1998
• Status: Expired due to Fees

• Current Assignee: Digilab, Inc.
• Original Assignee: Cartesian Technologies, Inc. (Harvard Bioscience, Inc.)
• Inventors: Tisone, Thomas C., Rose, Don
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Gordon, Brian R.
• Application Number:
  US09/459,245
• Time in Patent Office: 1,229 Days
• Field of Search: 422/100, 436/180, 738/633.1, 738/633.2, 738/635.4, 738/64, 738/640.1, 738/641.1, 738/641.3, 738/642.4, 738/642.5, 738/643.1, 738/643.4, 738/643.5
• US Class Current: 422/502
• 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 2219/00367 capillary
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/0265 using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 35/10 Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices G01N35/0099 takes precedence
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention relates to a ceramic tip and a random access print head for the transfer of microfluidic quantities of fluid. The print head can randomly collect and deposit fluid samples to transfer the samples from a source plate to a target. The print head can also be programmed to create a direct map of the fluid samples from the source plate on the target or to create any desired pattern or print on the target. The tip and print head can be used for a wide variety of applications such as DNA microarraying and compound reformatting. In one preferred embodiment, the tip is used as a capillary or “gravity” pin to draw or collect source fluid and “spot” or deposit the fluid onto the target via physical contact (touch-off). In another preferred embodiment, the tip is used in conjunction with an aspirate-dispense system to actively aspirate source fluid and deposit the fluid via a contact or non-contact approach. The tip provides improved, accurate and repeatable microfluidic transfer.

Claims

1. A random access contact-transfer dispensing system for selectively transferring microfluidic quantities of at least one fluid from a source to at least one predetermined position of a target, comprising:

a plurality of contact transfer pins arranged in a predetermined manner, each said contact transfer pin being adapted to collect fluid when dipped in said source and to deposit a quantity of said fluid when contacted with said target;

a mount in which said contact transfer pins are slidingly mounted;

a plurality of actuators each being associated with a respective one of said contact transfer pins for selectively raising or lowering each said contact transfer pin relative to said target and/or said source to independently operate each contact transfer tip;

each said contact transfer pin being connected to a respective base with each said base positioned above said mount; and

each said base comprising a magnetic material and each said actuator comprising a solenoid responsive to an actuation signal and mounted above a respective one of each said base for selectively raising or lowering each said base, thereby independently raising or lowering each said contact transfer pin.

2. The contact-transfer dispensing system of claim 1 wherein said mount comprises a plurality of holes with each said contact transfer pin precisely fitted and movable through a respective one of each hole.

3. The contact-transfer dispensing system of claim 1 wherein said contact transfer pins are arranged in an array.

4. The contact-transfer dispensing system of claim 3 wherein said contact transfer pins are arranged in a one-dimensional array.

5. The contact-transfer dispensing system of claim 3 wherein said contact transfer pins are arranged in a two-dimensional array.

6. The contact-transfer dispensing system of claim 3 wherein said array comprises 96 of said contact transfer pins.

7. The contact-transfer dispensing system of claim 3 wherein said array comprises 384 of said contact transfer pins.

8. The contact-transfer dispensing system of claim 3 wherein said array comprises 1536 of said contact transfer pins.

9. The contact-transfer dispensing system of claim 1 further comprising a robot arm for providing relative motion between said contact transfer pins and said target and/or said source.

10. The contact-transfer dispensing system of claim 1 further comprising an X, X-Y or X-Y-Z platform for providing relative motion between said contact transfer pins and said target and/or said source.

11. The contact-transfer dispensing system of claim 1 in combination with a controller for coordinating the actuations of said actuators and the positioning of said contact transfer pins relative to said target and/or said source.

12. The contact-transfer dispensing system of claim 1 wherein said target comprises one or more glass slides, substrates, membranes and microtiter plates.

13. The contact-transfer dispensing system of claim 1 wherein said source comprises one or more microtiter plates containing one or more liquids.

14. The contact-transfer dispensing system of claim 1 wherein said contact transfer pins comprise capillary tips.

15. The contact-transfer dispensing system of claim 1 wherein said contact transfer pins comprise pins having a sharp point at their lower-most ends.

16. The contact-transfer dispensing system of claim 1 wherein each said contact transfer pin has a lumen extending generally therethrough and has an orifice at a lower-most end thereof adapted to admit a quantity of fluid into said lumen by capillary action when said contact transfer pin is dipped into said source and further adapted to dispense a spot or dot of said fluid when said lower-most end is contacted with said target.

17. The contact-transfer dispensing system of claim 16 wherein each said lumen has a portion adjacent a respective one of each said orifice which is tapered in the direction of a respective one of each said orifice.

18. The contact-transfer dispensing system of claim 16 wherein each said contact transfer pin has a substantially cylindrical upper body portion and a substantially tapered lower body portion which is tapered inwardly in the direction of a respective one of each said lower-most end.

19. The contact-transfer dispensing system of claim 16 in combination with a wash station which comprises a vacuum system.

20. The contact-transfer dispensing system of claim 19 wherein said vacuum system comprises a plurality of cavities connected to a pump and adapted to receive said contact transfer pins.

21. The contact-transfer dispensing system of claim 20 wherein each said vacuum cavity has means adapted to substantially sealingly contact an upper body portion of each said contact transfer pin and/or a lower tapered body portion of each said contact transfer pin.

22. The contact-transfer dispensing system of claim 1 wherein said mount has a low friction surface finish.

23. A method of using the contact-transfer dispensing system of claim 1, comprising the steps:

selectively and independently dipping one or more of said contact transfer pins in said source to collect a quantity of one or more liquids; and

selectively and independently contacting one or more of said contact transfer pins with said target to deposit one or more of said liquids in a predetermined arrangement.

24. The method of claim 23 further comprising providing relative motion between said contact transfer tips and said source and/or said target.

25. The contact-transfer dispensing system of claim 1 wherein at least one of said contact transfer pins comprises a substantially V-shaped groove or notch adapted to provide an easy break point in the event of accidental hard jarring or excessive contact forces.

26. The contact-transfer dispensing system of claim 1 wherein at least one of said contact transfer pins is fabricated from a ceramic.

27. The contact-transfer dispensing system of claim 26 wherein at least one of said contact transfer pins is fabricated from alumina.

28. The contact-transfer dispensing system of claim 1 wherein at least one of said contact transfer pins is coated with a film or coating of hydrophobic material.

29. The contact-transfer dispensing system of claim 28 wherein said hydrophobic material is selected from the group:

silicon nitride, silicon carbide and titanium nitride.

30. The contact-transfer dispensing system of claim 16 wherein each said lower-most end of each said contact transfer pin has an outer diameter of about 50 μ

m to about 400 μ

m.

31. The contact-transfer dispensing system of claim 16 wherein each said lower-most end of each said contact transfer pin has an outer diameter of about 400 μ

m to about 900 μ

m.

32. The contact-transfer dispensing system of claim 1 wherein at least one of said bases is removably attached to a respective one of said contact transfer pins.

33. The contact-transfer dispensing system of claim 1 wherein said mount comprises a bearing alignment sleeve and has a plurality of through holes arranged in a predetermined manner through which said contact transfer pins are slidingly fitted to align said contact transfer pins in a precise predetermined manner.

34. The contact-transfer dispensing system of claim 1 wherein said mount comprises brass with a low friction surface finish.

35. The contact-transfer dispensing system of claim 1 wherein the spacing between adjacent contact transfer pins is about 2.5 mm.

36. The contact-transfer dispensing system of claim 1 wherein the spacing between adjacent contact transfer pins is about 4.5 mm.

37. The contact-transfer dispensing system of claim 1 wherein the spacing between adjacent contact transfer pins is about 9 mm.

38. A random access contact-transfer dispensing system for selectively transferring microfluidic quantities of at least one fluid from a source to at least one predetermined position of a target, comprising:

a plurality of contact transfer pins arranged in a predetermined manner, each said contact transfer pin being adapted to collect fluid when dipped in said source and to deposit a quantity of said fluid when contacted with said target;

a mount in which said contact transfer pins are slidingly mounted; and

a plurality of actuators each being associated with a respective one of said contact transfer pins for selectively raising or lowering each said contact transfer pin relative to said target and/or said source to independently operate each contact transfer tip;

each said contact transfer pin having a lumen extending generally therethrough and an orifice at a lower-most end thereof adapted to admit a quantity of fluid into said lumen by capillary action when said contact transfer pin is dipped into said source and further adapted to dispense a spot or dot of said fluid when said lower-most end is contacted with said target;

the contact-transfer dispensing system in combination with a wash station comprising a vacuum system; and

said vacuum system comprising a plurality of cavities connected to a pump and adapted to receive said contact transfer pins.

39. The contact-transfer dispensing system of claim 38 wherein said wash station further comprises a wash bath.

40. The contact-transfer dispensing system of claim 38 wherein said wash station further comprises an ultrasonic bath.

41. The contact-transfer dispensing system of claim 38 wherein at least one of said cavities has means adapted to substantially sealingly contact an upper body portion of at least one of said contact transfer pins and/or a lower tapered body portion of at least one of said contact transfer pins.

42. The contact-transfer dispensing system of claim 38 wherein at least one of said cavities has a shoulder adapted to substantially sealingly contact a tapered lower portion of at least one of said contact transfer pins.

43. The contact-transfer dispensing system of claim 42 wherein the shoulder comprises a resilient material.

44. The contact-transfer dispensing system of claim 38 wherein at least one of said cavities houses an O-ring adapted to substantially sealingly contact a preselected exterior surface of at least one of said contact transfer pins.

45. The contact-transfer dispensing system of claim 44 wherein the preselected exterior surface comprises a tapered surface of a lower body portion of at least one of said contact transfer pins.

46. The contact-transfer dispensing system of claim 44 wherein the preselected exterior surface comprises a cylindrical surface of an upper body portion of at least one of said contact transfer pins.

47. The contact-transfer dispensing system of claim 38 wherein said contact transfer pins are arranged in an array.

48. The contact-transfer dispensing system of claim 47 wherein said array comprises a generally rectangular array having 96 of said contact transfer pins.

49. The contact-transfer dispensing system of claim 47 wherein said array comprises a generally rectangular array having 384 of said contact transfer pins.

50. The contact-transfer dispensing system of claim 47 wherein said array comprises a generally rectangular array having 1536 of said contact transfer, pins.

51. The contact-transfer dispensing system of claim 47 wherein said array comprises a generally linear array of said contact transfer pins.