Biopolymer arrays and their fabrication

• US 6,900,048 B2
• Filed: 06/29/2001
• Issued: 05/31/2005
• Est. Priority Date: 07/16/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Perbost, Michel G. M.
• Primary Examiner(s): JONES, WILLIAM G
• Application Number:
  US09/895,050
• Publication Number:
  US 20010044115A1
• Time in Patent Office: 1,432 Days
• Field of Search: 422/100, 435/287.1, 435/287.3, 435/6, 435/91.1, 427/333, 427/340, 427/385.5
• US Class Current: 435/287.3
• 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 2219/00617 by chemical means
• 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 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries

Abstract

A method of fabricating an addressable array of biopolymers on a substrate using a biomonomer with a first linking group which must be activated for linking to a substrate bound moiety, and apparatus and computer program products for executing the method. The method includes forming on a region of the substrate carrying the substrate bound moiety, a solid activator composition. A biomonomer containing fluid composition is deposited on the region so that the solid activator activates the first linking group and the biomonomer links to the substrate bound moiety. The foregoing steps may be repeated, wherein a biomonomer deposited and linked to the substrate bound moiety in one cycle is the substrate bound moiety for the next cycle, so as to form the biopolymer.

Claims

1. An apparatus for fabricating an addressable array of biopolymers on a substrate according to a target pattern, comprising:

(a) a deposition system which can separately dispense onto a substrate, fluid compositions of different biomonomers each with a first linking group which must be activated for linking to a substrate bound moiety, and a fluid composition of a solid activator;

(b) a processor to operate the deposition system, which processor derives from the target array pattern a target drive pattern for operating the deposition system to form the array, the target drive pattern comprising instructions to the deposition system to perform the following at each of multiple regions at which a biomonomer is to be deposited;

(i) deposit the fluid composition of solid activator separate from and preceding deposition of the biomonomer;

(ii) allow sufficient time for evaporation to leave solid activator at the region; and

(iii) then deposit the biomonomer.

2. An apparatus according to claim 1 wherein the deposition system comprises multiple pulse jets which can dispense droplets of the different biomonomer fluid compositions and at least one pulse jet which can separately dispense the activator fluid composition, each jet comprising:

a chamber with an orifice; and

an ejector which, when activated, causes a droplet to be ejected from the orifice.

3. An apparatus according to claim 1 wherein the processor derives a target drive pattern which repeats (i) to (iii) at each of multiple features.

4. An apparatus according to claim 1 wherein the deposition system comprises a head having multiple pulse jets which can dispense droplets of the different biomonomer fluid compositions.

5. An apparatus for fabricating an addressable array of biopolymers on a substrate according to a target pattern, comprising:

(a) a deposition system which can separately dispense onto a substrate, fluid compositions of different biomonomers each with a first linking group which must be activated for linking to a substrate bound moiety, and a fluid composition of a solid activator; and

(b) a processor to operate the deposition system, which processor derives from the target array pattern a target drive pattern for operating the deposition system to form the array, the target drive pattern comprising instructions to the deposition system to deposit the fluid composition of solid activator at each region at which a biomonomer is to be deposited, separate from and preceding deposition of the biomonomer;

wherein the deposition system comprises multiple pulse jets which can dispense droplets of the different biomonomer fluid compositions and at least one pulse jet which can separately dispense the activator fluid compositions, each jet comprising;

a chamber with an orifice; and

an ejector which, when activated, causes a droplet to be ejected from the orifice; and

wherein the target drive pattern comprises ejector instructions such that a droplet of biomonomer fluid composition deposited at a region will cover an area greater than that covered by a preceding droplet of activator fluid composition at the same region.