Method and apparatus for liquid dispensing

• US 7,736,591 B2
• Filed: 04/22/2003
• Issued: 06/15/2010
• Est. Priority Date: 07/07/1998
• Status: Expired due to Term

• Current Assignee: BioDot, Inc. (ATS Corp.)
• Original Assignee: BioDot, Inc. (ATS Corp.)
• Inventors: Tisone, Thomas C., Rose, Don
• Primary Examiner(s): Gordon; Brian R
• Application Number:
  US10/421,636
• Publication Number:
  US 20040072365A1
• Time in Patent Office: 2,611 Days
• Field of Search: 422 99-100, 738/633.2, 738/64, 738/640.1, 738/640.2, 738/641.1
• 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. An apparatus for aspirating and dispensing predetermined microfluidic quantities of a fluid, comprising:

a ceramic tip including a nozzle with an inner taper to provide improved and generally laminar flow, at least a portion of said tip comprising a hydrophobic coating;

a drop-on-demand valve adapted to be opened and closed at a predetermined frequency and/or duty cycle to permit intermittent hydraulic coupling with said tip; and

a positive displacement pump hydraulically coupled with said valve for metering predetermined quantities of fluid to or from said tip.

2. A method for using the apparatus of claim 1 to dispense a fluid from a fluid source onto a desired target substrate, comprising the following steps:

operating said pump in a reverse direction to draw a small quantity of air into said tip and thereby form an air bubble within system fluid present in said tip;

dipping said nozzle in said fluid source;

operating said pump in the reverse direction to create a reduced pressure to thereby allow a quantity of fluid from said fluid source to be aspirated into said tip; and

operating said pump in a forward direction to dispense a predetermined quantity of fluid onto said target substrate.

3. The apparatus of claim 1, wherein said tip comprises a lumen that extends substantially completely through said tip to form an orifice at a lower-most end of said nozzle.

4. The apparatus of claim 3, wherein said lumen comprises a substantially cylindrical upper portion and a substantially tapered lower portion.

5. The apparatus of claim 4, wherein said upper and lower portions are coaxially aligned relative to one another about a central axis and said lower-most end is substantially flat and lies in a plane substantially normal to said ventral axis.

6. The apparatus of claim 5, wherein said nozzle comprises at least a portion of said tapered lower portion adjacent said orifice and has an inner diameter adjacent said orifice.

7. The apparatus of claim 6, wherein said upper portion has a first inner diameter and said lower portion has a second inner diameter and wherein said second inner diameter is smaller than said first inner diameter.

8. The apparatus of claim 6, wherein the inner diameter of said nozzle adjacent said orifice is about 20 microns (μ

m) to about 180 microns (μ

m).

9. The apparatus of claim 7, wherein said tip comprises a substantially cylindrical upper body portion having a first outside diameter and a substantially tapered lower body portion having a second outside diameter at a transition portion thereof which is substantially equal to said first outside diameter of said upper body portion and a third outer diameter at said lower-most end thereof which is smaller than said first or second outside diameters.

10. The apparatus of claim 9, wherein said upper and lower body portions are coaxially aligned relative to one another about said central axis.

11. The apparatus of claim 9, wherein said ceramic tip comprises alumina.

12. The apparatus of claim 9, wherein at least said lower body portion is coated on the outside with a hydrophobic coating.

13. The apparatus of claim 9, wherein at least said lower body portion is coated on the outside with a film or coating of material selected from the group:

silicon nitride, silicon carbide or titanium nitride.

14. The apparatus of claim 1, wherein said apparatus further comprises a vacuum dry system including at least one vacuum cavity to facilitate in cleaning said tip.

15. The apparatus of claim 14, wherein said vacuum cavity comprises at least one seal and/or step that engages at least one outer surface of said tip to facilitate removal or clearing of fluid from inside said tip.

16. The apparatus of claim 14, wherein said vacuum dry system further comprises a pump to remove excess fluid from an outer surface of said tip.

17. The apparatus of claim 16, wherein said pump is configured such that it removes excess fluid from said outer surface of said tip without disturbing fluid present inside said tip.

18. The apparatus of claim 5, wherein said lower-most end of said nozzle has an outer diameter greater than the effective diameter of a drop dispensed by said apparatus.

19. The apparatus of claim 18, wherein said apparatus is operable to dispense a drop having a volume less than about 100 nanoliters (nL).

20. The apparatus of claim 18, wherein said outer diameter of said lower-most end is about 400 microns (μ

m) to about 900 microns (μ

m).

21. The apparatus of claim 20, wherein said apparatus is operable to dispense a drop having a volume less than about 100 nanoliters (nL).

22. The apparatus of claim 21, wherein said drop has a volume of about 10 nanoliters (nL).

23. The apparatus of claim 21, wherein said drop has a volume of about 1 nanoliter (nL).

24. A method for using the apparatus of claim 1 to dispense a first fluid from a source onto or into a target, comprising:

operating said pump to draw a quantity of a second fluid into said tip such that said second fluid does not substantially mix with system fluid present in said tip and forms a discrete volume in said tip;

dipping said nozzle in said source;

operating said pump to aspirate a quantity of said first fluid from said source into said tip;

whereby, presence of said second fluid in said tip allows the flow profile during aspiration of said first fluid to be substantially laminar and mitigates or substantially prevents mixing and dilution of said aspirated first fluid with said system fluid.

25. The method of claim 24, wherein said method further comprises operating said pump to dispense a quantity of said first fluid onto or into said target.

26. The method of claim 24, wherein said second fluid comprises a gas.

27. The method of claim 26, wherein said gas comprises air and forms an air bubble within said tip.