Preparation of biopolymer arrays

• US 6,242,266 B1
• Filed: 04/30/1999
• Issued: 06/05/2001
• Est. Priority Date: 04/30/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Schleifer, Arthur, Caren, Michael P., Schembri, Carol T.
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): Siew, Jeffrey
• Application Number:
  US09/302,899
• Time in Patent Office: 767 Days
• Field of Search: 435/518, 435/6, 435/7.1, 435/91.1, 435/91.2, 435/257.2, 346/140.1, 346/141, 536/22.1, 536/23.1, 536/25.32, 536/24.1, 536/24.2, 536/24.3, 536/24.31, 536/24.32, 536/24.33
• 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 2219/0036 Nozzles
• 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 2219/0061 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 2219/00689 using computers
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00729 Peptide nucleic acids [PNA]
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• 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 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/1041 : Ink-jet like dispensers
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array

Abstract

A method and apparatus for fabricating an array of biopolymers on a substrate using a biopolymer or biomonomer fluid, and using a fluid dispensing head. The head has at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including an ejector which, when activated, causes a droplet to be ejected from the orifice. The method includes positioning the head with the orifice facing the substrate. Multiple droplets of the biopolymer or biomonomer fluid are dispensed from the head orifice so as to form an array of droplets on the substrate. A gas flow is directed through a venturi which has a throat opening communicating with the dispensing head chamber. A venturi control valve which particularly communicate with an outlet of the venturi, is adjusted to alter the chamber pressure. The venturi may be driven by a source of inert anhydrous compressed gas which assists in maintaining fluid in the head isolated from moisture.

Claims

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

at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including 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 of the biopolymer or biomonomer fluid from the head so as to form an array of droplets on the substrate;

(c) directing a gas flow through a venturi which has a throat opening communicating with the dispensing head chamber;

(d) varying gas flow resistance on an outlet side of the venturi, to alter the chamber pressure.

2. A method according to claim 1 wherein gas flow resistance on the venturi outlet side is adjusted to alter the chamber pressure before or after step (b).

3. A method according to claim 1 wherein a negative spotting pressure is provided from the venturi throat opening to the head chamber during dispensing of the droplets, and wherein the gas flow resistance of the venturi outlet side is adjusted to provide a positive chamber pressure.

4. A method according to claim 1 additionally comprising loading the chamber with fluid from a direction behind the orifice and wherein, following loading, the gas flow resistance of the venturi outlet side is increased to provide a positive priming pressure to the chamber so as to assist in priming the at least one jet.

5. A method according to claim 1 wherein the gas flow resistance of the venturi outlet side is increased to provide a positive purging pressure to the chamber so as to purge any fluid remaining in the chamber through the orifice.

6. A method according to claim 3 additionally comprising adding a purge fluid to the chamber prior to providing the purging pressure to the chamber.

7. A method according to claim 1 wherein the gas directed through the venturi is an anhydrous compressed gas.

8. A method according to claim 1 wherein each fluid droplet has a volume of from 0.1 to 1000 pL .

9. A method according to claim 1 additionally comprising altering the gas flow rate through the venturi by adjusting a valve on an inlet side of the venturi.

10. A method according to claim 1 additionally comprising:

providing a spotting pressure in the chamber from the venturi throat opening while the head is facing the substrate so as to retain fluid in the chamber in the absence of the ejector being activated;

and wherein the venturi outlet side gas flow resistance is increased to provide a purging pressure which is greater than the spotting pressure and sufficiently positive so as to purge fluid remaining in the chamber through the orifice.

11. A method according to claim 10 additionally comprising adding a purge fluid to the head prior to providing the purging pressure to the head.

12. A method according to claim 1 additionally comprising, prior to step (a):

positioning the head facing a load station spaced from the substrate, with the orifice adjacent and facing the biomonomer or biopolymer fluid, and

providing a loading pressure in the chamber from the venturi throat opening while the head is facing the load station, which is sufficiently negative such that the fluid is drawn into the chamber through the orifice;

and wherein the gas flow rate through the venturi is adjusted to provide a spotting pressure while dispensing droplets from the head, which spotting pressure is higher than the loading pressure.

13. A method according to claim 12 wherein the gas flow rate is adjusted to provide the spotting pressure by adjusting a valve on an inlet side of the venturi.

14. A method according to claim 1 additionally comprising:

positioning the head facing a load station with the orifice adjacent and facing the biomonomer or biopolymer fluid;

providing a loading pressure in the chamber from the venturi throat opening while the head is facing the load station, which is sufficiently negative such that the fluid is drawn into the chamber through the orifice;

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

and wherein;

the gas flow rate through the venturi is adjusted by adjusting a valve on an inlet side of the venturi to provide a spotting pressure while dispensing droplets from the head, which spotting pressure is higher than the loading pressure; and

following dispensing of droplets, the venturi outlet side gas flow resistance is increased to provide a purging pressure in the chamber while the head is facing the purge station which is sufficiently positive such that fluid in the chamber is purged through the orifice.

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

at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including 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 of the biopolymer or biomonomer fluid from the head so as to form an array of droplets on the substrate;

(c) directing a flow of anhydrous gas through a venturi which has a throat opening communicating with the dispensing head chamber.

16. A method according to claim 15 additionally comprising providing a spotting pressure in the chamber from the venturi throat opening while the head is facing the substrate so as to retain fluid in the chamber in the absence of the ejector being activated.

17. A method according to claim 15 additionally comprising:

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

providing a purging pressure in the chamber from the venturi throat opening so as to purge fluid remaining in the chamber through the orifice.

18. A method according to claim 15 additionally comprising, prior to step (a):

positioning the head facing a load station which is spaced from the substrate, with the orifice adjacent and facing the biomonomer or biopolymer fluid, and

providing a loading pressure in the chamber from the venturi throat opening while the head is facing the load station, which is sufficiently negative such that the fluid is drawn into the chamber through the orifice.

19. A method according to claim 15 wherein the head has multiple pulse jets with orifices on a common front face of the head.

20. A method according to claim 18 wherein fluid is simultaneously drawn in through the orifice of the multiple jets when the head is facing the loading station.