METHOD AND MULTIPLE RESERVOIR APPARATUS FOR FABRICATION OF BIOMOLECULAR ARRAYS

• US 20010051334A1
• Filed: 09/09/1998
• Published: 12/13/2001
• Est. Priority Date: 09/09/1998
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: BARTH, PHILLIP W., MCALLISTER, WILLIAM H., SCHLEIFER, ARTHUR, SCHEMBRI, CAROL T., CAREN, MICHAEL P.
• Granted Patent: US 6,461,812 B2
• Time in Patent Office: Days
• US Class Current: 435/6.1
• 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 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B41J 2/14145 Structure of the manifold
• CPC Class Codes: B41J 2002/14387 Front shooter
• 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

Apparatus for delivering a plurality of different biological materials onto discrete locations on a receiving surface, as for example to fabricate an array of different biological materials, includes a plurality of orifices in an orifice member, at least six delivery chambers each in fluid conducting relationship with at least one of the orifices, a plurality of reservoirs each in fluid communication with at least one of the delivery chambers, means associated with each orifice for propelling fluid through the associated orifice from the delivery chamber that is in fluid conducting relationship with the orifice, and a vent for commonly venting at least two of the reservoirs. In some embodiments the chambers and reservoirs are loaded with fluids containing selected biomolecules by drawing the selected fluids into the chambers through the orifices; in other embodiments the fluids are introduced into the reservoirs. Also, methods for depositing biological materials onto a surface, as for example to fabricate a biomolecular array, employ the apparatus.

Claims

1. Apparatus for delivering a plurality of different biological materials onto discrete locations on a receiving surface, the apparatus comprising:

a plurality of orifices in an orifice member;

a plurality of delivery chambers each in fluid conducting relationship with at least one of said orifices;

a plurality of reservoirs each in fluid conducting relationship with at least one of said delivery chambers;

means associated with each orifice for propelling fluid through the associated orifice from the delivery chamber that is in fluid conducting relationship with the orifice; and

a vent for commonly venting at least two of said reservoirs.

2. The apparatus of

claim 1

wherein the combined capacity of each said reservoir and delivery chamber in fluid conducting relationship therewith is less than 100 microliters.

3. The apparatus of

claim 2

wherein the combined capacity of each said reservoir and delivery chamber in fluid conducting relationship therewith is less than 10 microliters.

4. The apparatus of

claim 2

wherein the combined capacity of each said reservoir and delivery chamber in fluid conducting relationship therewith is less than 1 microliter.

5. The apparatus of

claim 1

, comprising at least six said reservoirs.

6. The apparatus of

claim 5

, comprising at least sixteen said reservoirs.

7. The apparatus of

claim 5

, comprising at least fifty said reservoirs.

8. The apparatus of

claim 5

, comprising at least one hundred said reservoirs.

9. The apparatus of

claim 1

, further comprising means operatively connected with said vent for commonly changing the pressure within said at least two reservoirs.

10. The apparatus of

claim 1

, further comprising means for contacting at least one of said orifices with a fluid outside said delivery chamber.

11. The apparatus of

claim 9

wherein said pressure changing means comprises means for reducing pressure within said at least two reservoirs.

12. The apparatus of

claim 11

, further comprising means for contacting at least one of said orifices with a fluid outside said delivery chamber, whereby operating said pressure reducing means results in drawing the fluid through said orifice into said delivery chamber.

13. The apparatus of

claim 9

wherein said pressure changing means comprises means for increasing pressure within said at least two reservoirs.

14. The apparatus of

claim 13

wherein said pressure increasing means comprises means for introducing a fluid into said at least two reservoirs, whereby operating said pressure increasing means results in expelling fluid out from said at least one delivery chamber in fluid communication with said reservoir by way of said orifices.

15. The apparatus of

claim 1

wherein said propelling means comprises a source of heat.

16. The apparatus of

claim 15

wherein said source of heat comprises an electrical heater, said heater being operative when activated to heat fluid within the delivery chamber to a degree sufficient to propel a quantity of fluid out from the delivery chamber through the associated orifice.

17. The apparatus of

claim 1

wherein said propelling means comprises a piezoelectric device.

18. The apparatus of

claim 1

wherein said orifice member is a generally planar orifice plate having an inner surface and an exit surface, said orifices providing openings through said plate from said inner surface to said outer surface.

19. The apparatus of

claim 1

, comprising a plurality of said orifice members.

22. A method for delivering a plurality of different biological materials onto discrete locations on a receiving surface, the method comprising:

loading a fluid medium containing one of said different biological materials into one of said delivery chambers of the apparatus of

claim 1

, each said propelling means when activated propelling a quantity of said fluid medium along a delivery path away from said associated orifice member;

positioning the apparatus of

claim 1

in relation to the receiving surface so that said orifice member is proximate the receiving surface and the delivery path for at least one selected said fluid medium intersects said receiving surface at a locus of intersection;

moving the apparatus of

claim 1

in relation to the receiving surface so that locus of intersection moves on said receiving surface;

activating the propelling means associated with said orifice when the locus of intersection is at a first location on said surface onto which delivery of the selected said fluid medium is desired; and

repeating the moving and activating steps to deliver the plurality of different biological materials onto discrete locations on the surface.

24. An array of biological materials made according to the method of

claim 22

.

26. The method of

claim 22

wherein said fluid medium loading step results in each said delivery chamber being loaded with a fluid containing a different biological material.

27. The method of

claim 22

wherein said plurality of different biological materials comprises a plurality of nucleic acids.

28. The method of

claim 27

wherein said plurality of nucleic acids comprises a plurality of nucleic acids selected from the group consisting of DNAs, RNAs and synthetic derivatives thereof.

20. Apparatus for depositing a plurality of different biological materials onto discrete locations on a receiving surface, the apparatus comprising:

an orifice plate defining a plurality of orifices;

a substrate connected to said orifice plate, said substrate defining a plurality of delivery chambers and a plurality of reservoirs, each of said orifices being in fluid communication with one of said reservoirs by way of one of said delivery chambers;

means adjacent each said orifice for propelling fluid through the orifice from the delivery chamber providing fluid communication with the orifice; and

a vent for commonly venting at least two of said reservoirs to ambient pressure.

21. Apparatus for depositing a plurality of different biological materials onto discrete locations on a receiving surface, the apparatus comprising:

an orifice member defining a plurality of orifices therethrough from a first surface to a second surface thereof;

a barrier affixed to said first surface of said orifice member, said barrier and said orifice member together defining a plurality of delivery chambers, each said delivery chamber being in fluid communication with one of said orifices, and said barrier and said orifice member together defining a plurality of fluid reservoirs;

said orifice member further having a plurality of channels, each said channel having an opening in said first surface to one of said delivery chambers and an opening in said first surface to one of said reservoirs, each said channel providing fluid communication between one of said delivery chambers and one of said fluid reservoirs; and

means associated with each said orifice for propelling fluid through the associated orifice from the reservoir that is in fluid communication with the orifice.

23. A method for loading a plurality of different fluids into printing apparatus having a plurality of orifices in an orifice member, a plurality of delivery chambers each in fluid conducting relationship with at least one of the orifices, a plurality of reservoirs each in fluid communication with at least one of said delivery chambers, and means associated with each orifice for propelling fluid through the associated orifice from the delivery chamber that is in fluid conducting relationship with the orifice, and a vent for commonly venting at least two of said reservoirs, the method comprising contacting said orifices with a fluid outside said delivery chamber and permitting said outside fluid to flow through said orifices into said delivery chambers.

29. The method of

claim 23

, said apparatus further comprising means for reducing the pressure upstream from said delivery chambers, wherein said fluid flow permitting step comprises activating said pressure lowering means, whereby said fluid is drawn through said orifices into said delivery chambers.

25. Apparatus for delivering a plurality of different biological materials onto discrete locations on a surface, the apparatus comprising:

a generally planar substrate having a thickness and a contoured first surface and an edge, and a generally planar cover affixed to said first surface, said contoured first surface and said cover together defining a plurality of enclosed deposition chambers, a plurality of orifices on said edge, and a channel providing fluid communication between each said chamber and at least one said orifice; and

a vent for commonly venting at least two of the delivery chambers below ambient pressure.