Fabricating biopolymer arrays

• US 6,323,043 B1
• Filed: 04/30/1999
• Issued: 11/27/2001
• 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): Horlick, Kenneth R.
• Assistant Examiner(s): Siew, Jeffrey
• Application Number:
  US09/302,922
• Time in Patent Office: 942 Days
• Field of Search: 435/6, 435/91.2, 435/518, 435/283.1, 435/285.2, 435/287.2, 536/22.1, 536/24.3, 536/24.31, 536/24.32, 536/24.33, 346/140.1, 436/518, 436/180
• US Class Current: 436/518
• 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 fabricating an array of biopolymers on a substrate using a biopolymer or biomonomer fluid, and using a dispensing head having:

a reservoir chamber;

at least one jet which can dispense droplets 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;

the method comprising;

(a) loading the head by positioning the head with the orifice adjacent and facing a biomonomer or biopolymer containing fluid, and providing a load pressure to the reservoir chamber which is sufficient 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;

(b) positioning the head with the orifice facing the substrate; and

(c) dispensing multiple droplets from the head so as to form an array of droplets on the substrate.

2. A method according to claim 1 wherein the load pressure is a negative pressure.

3. A method according to claim 1 wherein, during the dispensing, a spotting pressure is provided to the reservoir chamber which is higher than the load pressure.

4. A method according to claim 3 wherein the spotting pressure is a negative pressure.

5. A method according to claim 1 additionally comprising:

positioning the head with the orifice facing a cleaning station which is spaced from the substrate;

exposing the head about the orifice to a cleaning fluid from the cleaning station while providing a holdoff pressure to the reservoir chamber which is sufficiently positive to prevent cleaning fluid entering the delivery chamber.

6. A method according to claim 5 wherein the holdoff pressure is provided in the form of gas pressure to the reservoir.

7. A method according to claim 5 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.

8. A method according to claim 7 wherein the head has multiple jets with respective orifices on a common front face of the head.

9. A method according to claim 1 additionally comprising:

positioning the head with the orifice facing a purge station which is spaced from the substrate; and

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.

10. A method according to claim 5 additionally comprising:

positioning the head with the orifice facing a purge station which is spaced from the substrate; and

providing a purge pressure to the reservoir chamber which is greater than the holdoff pressure, so as to expel fluid remaining in the delivery chamber through the orifice thereof.

11. A method of fabricating an array of biopolymers on a substrate using a fluid dispensing head and a biopolymer or biomonomer containing fluid, the dispensing head having:

a reservoir chamber;

at least one jet which can dispense droplets 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;

the method comprising;

(a) loading the head by positioning the head with the orifice adjacent and facing a biomonomer or biopolymer containing fluid, and providing a load pressure to the reservoir chamber which is sufficient 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;

(b) positioning the head with the orifice facing the substrate and moving at least one of the head and the substrate with respect to the other while dispensing multiple droplets from the head, so as to form an array of droplets on the substrate; and

(c) positioning the head with the orifice facing a cleaning station which is spaced from the substrate, and exposing the head about the orifice to a cleaning fluid from the cleaning station while providing a gas holdoff pressure to the reservoir chamber which is sufficiently positive to prevent cleaning fluid entering the delivery chamber.

12. A method according to claim 11 wherein the load pressure is a negative pressure.

13. A method according to claim 11 wherein a spotting pressure is provided during the dispensing of step (b) which is higher than the load pressure.

14. A method according to claim 11 additionally comprising:

(b1) positioning the head with the orifice facing a purge station which is spaced from the substrate, and 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.

15. A method according to claim 14 wherein the purge pressure is greater than the holdoff pressure.

16. A method according to claim 14 additionally comprising, following step (b) and prior to step (b1), loading the reservoir chamber with a cleaning fluid.

17. A method of fabricating an array of biopolymers on a substrate using a dispensing head with a biopolymer or biomonomer fluid, the fluid dispensing head having:

a reservoir chamber;

at least one jet which can dispense droplets onto a substrate, the jet including a capillary delivery chamber communicating with the reservoir chamber, and which capillary chamber has 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 orifice facing the substrate;

(b) dispensing multiple droplets from the head orifice so as to form an array of droplets on the substrate;

(c) positioning the head with the orifice facing a cleaning station which is spaced from the substrate; and

(d) exposing the head about the orifice to a cleaning fluid from the cleaning station while providing a holdoff gas pressure to the reservoir chamber which is sufficiently positive to prevent cleaning fluid entering the delivery chamber.

18. A method according to claim 17 wherein the head has multiple pulse jets with respective orifices on the front face of the head.

19. A method according to claim 17 wherein the cleaning station comprises a pad carrying a cleaning fluid and the head is exposed to the cleaning fluid by wiping at least one of the head and pad across the other.

20. An apparatus for fabricating an array of biopolymers on a substrate, comprising:

(a) a substrate station on which the substrate can be mounted;

(b) a dispensing head having;

a reservoir chamber;

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

(c) a load station spaced from the substrate station to receive at least one fluid sample for loading into the head;

(d) a positioning system to selectively position the head facing any one of the stations; and

(e) a pressure source which provides a gas load pressure valve to the reservoir chamber which is sufficiently negative such that fluid adjacent and facing the orifice is loaded into the head by being 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.

21. An apparatus according to claim 20 additionally comprising a processor which directs the positioning system to selectively position the head, and which directs the pressure source to provide the load pressure when the head is facing the load station.

22. An apparatus according to claim 21 wherein the pressure source is a selectable pressure source, and the processor directs the pressure source to provide a spotting pressure to the reservoir chamber which is higher than the load pressure when the head is facing the substrate station.

23. An apparatus according to claim 22 wherein the spotting pressure is a negative pressure.

24. An apparatus according to claim 20 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 a pulse jet of the loaded head, so as to form an array of drops on the substrate.

25. An apparatus according to claim 20 additionally comprising:

a cleaning station which is spaced from the substrate and load stations, and which provides a cleaning fluid for the head; and

a processor, wherein when the head is positioned at the cleaning station the processor directs the pressure source to provide a holdoff pressure to the reservoir chamber which is sufficiently positive to prevent cleaning fluid entering the delivery chamber.

26. An apparatus according to claim 25 wherein, when the head is facing the cleaning station, the positioning system moves at least one of head and cleaning station across the other so that the head can be cleaned by wiping.

27. An apparatus according to claim 20 wherein the head has multiple pulse jets with orifices on a common front face of the head.

28. An apparatus according to claim 25 additionally comprising a purge station which is spaced from the substrate and load stations;

and wherein, when the head is facing the purge station, the pressure source provides a purge pressure to the reservoir chamber which is sufficiently positive so as to purge fluid remaining in the delivery chamber through the orifice, and which is greater than the holdoff pressure.

29. An apparatus for fabricating an array of biopolymers on a substrate, comprising:

(a) a substrate station on which the substrate can be mounted;

(b) a dispensing head having;

a reservoir chamber;

at least one jet which can dispense droplets 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;

(c) a load station spaced from the substrate station to receive at least one fluid sample for loading into the head;

(d) a cleaning station which is spaced from the substrate station, and which provides a cleaning fluid for the head;

(e) a positioning system to selectively position the head facing any one of the stations; and

(f) a pressure source which provide to the reservoir chamber;

when the head is facing the load station, a load pressure valve which is sufficiently negative such that the fluid adjacent and facing the orifice is loaded into the head by being 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; and

when the head is facing the cleaning station, a holdoff pressure which is sufficiently positive to prevent cleaning fluid contacting the orifice from entering the delivery chamber.

30. An apparatus according to claim 29 wherein the holdoff pressure is provided in the form of gas pressure to the reservoir.

31. An apparatus according to claim 29 wherein the pressure source provides a spotting pressure to the reservoir chamber when the head is facing the substrate station, which spotting pressure is higher than the load pressure.

32. An apparatus according to claim 31 wherein the spotting pressure is a negative pressure.

33. An apparatus according to claim 29 additionally comprising a purge station which is spaced from the substrate and load stations;

and wherein, when the head is facing the purge station, the pressure source provide s a purge pressure to the reservoir chamber which is sufficiently positive so as to purge fluid remaining in the delivery chamber through the orifice, and which is greater than the holdoff pressure.

34. An apparatus according to claim 29 additionally comprising a processor which directs the pressure source to provide the load pressure when the head is facing the load station and provide the holdoff pressure when the head is facing the cleaning station.

35. An apparatus according to claim 31 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.