Dual manifold system and method for fluid transfer

• US 20010053337A1
• Filed: 12/15/2000
• Published: 12/20/2001
• Est. Priority Date: 03/04/1999
• Status: Active Grant

• Current Assignee: Mitchel J. Doktycz, Reid Kress, William Louis Bryan
• Original Assignee: Mitchel J. Doktycz, Reid Kress, William Louis Bryan
• Inventors: Kress, Reid, Bryan, William Louis, Doktycz, Mitchel J.
• Granted Patent: US 6,569,687 B2
• Time in Patent Office: Days
• US Class Current: 422/503
• 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 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A dual-manifold assembly is provided for the rapid, parallel transfer of liquid reagents from a microtiter plate to a solid state microelectronic device having biological sensors integrated thereon. The assembly includes aspiration and dispense manifolds connected by a plurality of conduits. In operation, the aspiration manifold is actuated such that the aspiration manifold is seated onto an array of reagent-filled wells of the microtiter plate. The wells are pressurized to force reagent through conduits toward the dispense manifold. A pressure pulse provided by a standard ink-jet printhead ejects nanoliter-to-picoliter droplets of reagent through an array of printhead orifices and onto test sites on the surface of the microelectronic device.

Claims

1. A dual-manifold assembly for transferring liquid from an array of reservoirs to an array of test sites on a target substrate, comprising:

a liquid aspiration manifold;

a liquid dispense manifold having a plurality of orifices;

a plurality of conduits for providing fluid connection between said aspiration manifold and said dispense manifold;

a controllable pneumatic pressure source for urging the liquid from said reservoirs through said plurality of conduits toward said dispense manifold; and

,

a means for effecting the ejection of at least one droplet of said liquid through at least one of said plurality of orifices and onto at least one of said test sites.

2. A dual-manifold assembly as recited in

claim 1

, further comprising a switching valve integrated into said liquid dispense manifold.

3. A dual-manifold assembly as recited in

claim 1

, wherein said ejection means is integrated into said liquid dispense manifold.

4. A dual-manifold assembly as recited in

claim 1

, further comprising at least one modular connector for providing fluid connection between lengths of said plurality of conduits.

5. A dual-manifold assembly as recited in

claim 1

, wherein said ejection means comprises an ink-jet printing valve incorporating drop-on-demand technology.

6. A dual-manifold assembly as recited in

claim 5

, wherein said ink-jet valve is one of a thermal ink-jet valve, a solenoid ink-jet valve, and a piezoelectric ink-jet valve.

7. A dual-manifold assembly as recited in

claim 5

, wherein said ink jet valve is adapted for delivering a pressure pulse having a pressure of about 6.9(10)³ N/m² to about 138(10)³ N/m², and having a pulse duration ranging from about (10)⁻

6 seconds to about (10)<sup>−

2</sup> seconds.

8. A dual-manifold assembly as recited in

claim 1

, wherein said plurality of conduits comprise plastic tubing.

9. A dual-manifold assembly as recited in

claim 1

, wherein said plurality of conduits comprise at least one of metal and glass tubing.

10. A dual-manifold assembly as recited in

claim 1

, wherein said array of reservoirs comprise microtiter plate wells and said liquid comprises a reagent.

11. A dual-manifold assembly as recited in

claim 1

, wherein said array of test sites comprise biological sensors integrated on a microelectronic device.

12. A dual-manifold assembly as recited in

claim 1

, wherein the minimum distance between adjacent test sites on said target substrate is in the range of about 1 micron (μ

m) to about 10,000 microns (μ

m).

13. A dual-manifold assembly as recited in

claim 1

, wherein said liquid dispense manifold is adapted for dispensing volumes of liquid in the range of about (10)⁻

12 to about (10)<sup>−

6</sup> liters.

14. A dual-manifold assembly as recited in

claim 1

, further comprising a conduit cleaning and purging apparatus.

15. A dual-manifold assembly as recited in

claim 1

, further comprising a means for detecting the passage of a droplet of liquid from a dispense manifold orifice.

16. A dual-manifold assembly as recited in

claim 15

, wherein said detection means comprise optoelectronic devices.

17. A dual-manifold assembly as recited in

claim 15

, wherein said detection means comprise electronic conduction-based sensors integrated into said dispense manifold.

18. A dual-manifold assembly as recited in

claim 1

, wherein said aspiration manifold includes an array of aspiration subassemblies extending from a base plate and adapted for being received by said array of liquid-filled reservoirs, each subassembly comprising:

a guide member having a first end adapted for being mechanically fastened to said base plate and having a second flanged end extending away from said base plate;

a cap member having a first end adapted for engaging the flanged end of said guide member and a second end having a tapered outer surface for engaging the perimeter of one of said liquid-filled reservoirs; and

,

first and second conduits each extending through aligned apertures in each of said base plate, said guide member and said cap member;

wherein said first conduit terminates at a position above a liquid level of the reservoir and said second conduit terminates at a position below a liquid level of the reservoir, said first conduit providing a means for pressurizing said reservoir to urge liquid through said second conduit toward said dispense manifold.

19. A dual-manifold assembly as recited in

claim 18

, wherein each of said guide member, said cap member and said base plate are integrated to form a unitary structure.

20. A dual-manifold assembly as recited in

claim 1

, wherein said aspiration manifold assembly is adapted for being seated upon a source plate having an array of liquid-filled reservoirs, said aspiration manifold assembly comprising:

a base plate;

a gasket member disposed along the periphery of a lower surface of said base plate, said gasket dimensioned for sealing against a periphery of said source plate;

a pressure conduit extending through said base plate for pressurizing said array of liquid-filled reservoirs; and

,

a plurality of aspiration conduits extending through said base plate and into said liquid-filled reservoirs for aspirating said liquid from said reservoirs.

21. A method for transferring liquid reagent from an array of source plate reservoirs to an array of test sites on a target substrate using a dual-manifold assembly, comprising the steps of:

positioning said source plate below an aspiration manifold;

positioning said target substrate below a dispense manifold having a plurality of channels each terminating at an orifice;

seating said aspiration manifold onto said source plate;

pressurizing said source plate reservoirs through at least one pressure conduit to effect the aspiration of reagent from said reservoirs via a plurality of aspiration conduits to said dispense manifold; and

,

communicating a force to reagent in said dispense manifold channels for a period of time, wherein said force effects the ejection of a desired volume of said reagent to each of the test sites.

22. A method as recited in

claim 21

, further comprising the step of checking the alignment of said target substrate prior to said step of communicating a force.

23. A method as recited in

claim 21

, further comprising the step of detecting the passage of a volume of reagent from each said orifice to each said test site after the step of communicating a force.

24. A method as recited in

claim 21

, further comprising the step of purging said dual-manifold system.

25. A method as recited in

claim 21

, wherein the step of communicating a force comprises communicating a pressure pulse in the range of about 6.9(10)³ N/m² to about 138(10)³ N/m², for a period of time in the range of about (10)⁻

6 seconds to about (10)<sup>−

2</sup> seconds.