Fabricating biopolymer arrays

• US 7,282,332 B2
• Filed: 09/01/2004
• Issued: 10/16/2007
• Est. Priority Date: 04/30/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Caren, Michael P., Schembri, Carol T., Webb, Peter G.
• Primary Examiner(s): Kim; Young J.
• Application Number:
  US10/932,886
• Publication Number:
  US 20050106754A1
• Time in Patent Office: 1,140 Days
• Field of Search: None
• US Class Current: 435/6.11
• 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 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• 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: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A method and apparatus for fabricating an array of biopolymers on a substrate using a biopolymer or biomonomer fluid, and using a dispensing head. The head has a reservoir chamber and at least one jet which can dispense droplets onto a substrate. The jet includes a capillary delivery chamber communicating with the reservoir chamber, which delivery chamber has an orifice. The jet further includes an ejector which, when activated, causes a droplet to be ejected from the orifice. The method includes loading the head by positioning the head with the orifice adjacent and facing a biomonomer or biopolymer fluid, and providing a load pressure to the reservoir chamber. The load pressure is sufficiently negative such that the fluid is drawn into the reservoir chamber through the orifice and delivery chamber, while simultaneously being insufficient to result in ambient atmosphere entering the delivery chamber through the orifice once the head has been loaded and no further fluid is facing and adjacent the orifice. The head is positioned with the orifice facing the substrate and multiple droplets are dispensed from the head orifice so as to form an array of droplets on the substrate.

Claims

1. A method of synthesizing or depositing a biopolymer on a substrate using a dispensing head with biopolymer or biomonomer fluids, the fluid dispensing head having:

a reservoir chamber;

multiple jets which can dispense droplets of biopolymer or biomonomer fluids onto a substrate, each jet including a delivery chamber communicating with the reservoir chamber, and including an orifice and an ejector which, when activated, causes a droplet to be ejected from the orifice;

the method comprising;

(a) positioning the head with the orifices facing the substrate;

(b) dispensing at least one droplet from an orifice of said orifices on the substrate;

(c) positioning the head with the orifices facing a cleaning station; and

(d) exposing the head about the orifices to a cleaning fluid from the cleaning station.

4. The method of claim 1, further comprising repeating (a) to (d) as needed to form an array of biopolymers.

6. The method according to claim 1 wherein the cleaning station comprises a pad carrying cleaning fluid and the head is exposed to the cleaning fluid by wiping at least one of the head and pad across the other.

19. The method of claim 1, further comprising providing a holdoff pressure when said head is facing said cleaning station and prior to exposing the head to a cleaning fluid.

21. The method of claim 1, wherein said exposing of the head about the orifices to a cleaning fluid results in said delivery and reservoir chambers being filled with a quantity of said cleaning fluid.

2. A method of synthesizing or depositing a biopolymer on a substrate using a dispensing head with biopolymer or biomonomer fluids, the fluid dispensing head having:

a reservoir chamber;

multiple jets which can dispense droplets of biopolymer or biomonomer fluids onto a substrate, each jet including a delivery chamber communicating with the reservoir chamber, and including an orifice and an ejector which, when activated, causes a droplet to be ejected from the orifice;

the method comprising;

(a) loading the head with a biopolymer or biomonomer fluid;

(b) positioning the head with the orifices facing the substrate;

(c) dispensing at least one droplet from an orifice of said orifices on the substrate;

(d) positioning the head with the orifices facing a cleaning station; and

(e) exposing the head about the orifices to a cleaning fluid from the cleaning station.

3. The method of claim 2, wherein the head is loaded through the orifices.

5. The method of claim 2, further comprising repeating (a) to (e) as needed to form an array of biopolymers.

7. The method according to claim 2 wherein the fluid is a polynucleotide-containing fluid.

8. The method according to claim 2, wherein the fluid comprises a polymer of amino acids.

20. The method of claim 2, further comprising providing a holdoff pressure when said head is facing said cleaning station and prior to exposing the head to a cleaning fluid.

22. The method of claim 2, wherein said exposing of the head about the orifices to a cleaning fluid results in said delivery and reservoir chambers being filled with a quantity of said cleaning fluid.

9. An apparatus for synthesizing or depositing a biopolymer on a substrate, comprising:

(a) a dispensing head having;

a reservoir chamber;

at least one jet which can dispense droplets of a biomonomer or biopolymer onto a substrate, the jet including a capillary delivery chamber communicating with the reservoir chamber, and which capillary delivery chamber has an orifice and an ejector which, when activated, causes a droplet to be ejected from the orifice;

(b) a cleaning station which provides a cleaning fluid for the head; and

(c) a pressure source to provide to the reservoir chamber, when the head is facing the cleaning station, a pressure which is sufficiently positive to prevent cleaning fluid contacting the orifice from entering the delivery chamber, wherein the pressure source also provides a holdoff pressure when the head is facing the cleaning station.

10. The apparatus of claim 9, wherein the apparatus further comprises a substrate station on which the substrate can be mounted.

11. The apparatus of claim 9, wherein the apparatus further comprises a positioning station to selectively position the head facing the cleaning station.

12. The apparatus of claim 10, wherein the apparatus further comprises a positioning station to selectively position the head facing the substrate station or the cleaning station.

13. The apparatus of claim 9, wherein the cleaning station comprises a pad comprising cleaning fluid.

14. The apparatus of claim 12, wherein when the head is facing the substrate station, the positioning system moves at least one of the head and a mounted substrate with respect to the other while multiple droplets are dispensed from the loaded head, so as to form an array of drops on the substrate.

15. The apparatus of claim 9, further comprising a processor which controls pressure provided to the reservoir chamber.

16. The apparatus of claim 14, further comprising a load station to receive at least one fluid sample for loading into the head.

17. The apparatus of claim 9, wherein the pressure source is capable of providing a purge pressure to the reservoir chamber which is sufficiently positive so as to purge fluid remaining in the delivery chamber through the orifice at selected times.

18. An apparatus according to claim 16 additionally comprising a processor which directs the pressure source to provide the load pressure when the head is facing the load station, provide the holdoff pressure when the head is facing the cleaning station, and provide the spotting pressure when the head is facing the substrate station.