Testing multiple fluid samples with multiple biopolymer arrays

• US 6,399,394 B1
• Filed: 06/30/1999
• Issued: 06/04/2002
• Est. Priority Date: 06/30/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Dahm, SueAnn C., Schleifer, Arthur, Schembri, Carol T., Amorese, Douglas A.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Gordon, Brian R.
• Application Number:
  US09/343,645
• Time in Patent Office: 1,070 Days
• Field of Search: 422/100, 422/102, 422/99, 422/68.1, 422/104, 422/105, 436/172, 436/180, 436/63, 435/305.1, 435/305.2, 435/305.3, 435/305.4
• US Class Current: 436/180
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A method of testing multiple fluid samples with multiple biopolymer arrays. A cover is assembled to a contiguous substrate carrying on a first side, multiple arrays each with multiple regions of biopolymers linked to the substrate, such that the cover and the substrate together form a plurality of chambers each containing a biopolymer array and each being accessible through its own port. Multiple fluid samples are introduced into respective chambers through a port of each such that the fluid samples contact respective arrays. A binding pattern of the arrays is observed. An apparatus and kit useful in such methods, are also provided.

Claims

1. A method of testing multiple fluid samples with multiple biopolymer arrays to detect a binding pattern between the multiple fluid samples and the arrays, comprising:

(a) assembling a cover to a one-piece substrate carrying on a first side, multiple arrays each with multiple regions of biopolymers linked to the substrate, such that the cover an the substrate together form a plurality of chambers each containing a biopolymer array and each being accessible through its own port which includes a resilient self-sealing portion;

(b) introducing the multiple fluid samples into respective chambers through a port of each such that the fluid samples contact respective arrays; and

(c) observing a binding pattern on the arrays;

wherein each chamber is accessible through a first and a second port each of which includes a resilient self-sealing portion, the method additionally comprising inserting a first set of conduits through the resilient members of respective first ports, and inserting a second set of conduits through the self-sealing portion of respective second ports, and wherein the multiple fluid samples are introduced into each chamber through the first set of conduits while venting occurs through the second set of conduits.

2. A method according to claim 1 wherein the assembling includes applying an external force to urge the cover toward the substrate and which remains applied to retain them in the assembled position.

3. A method according to claim 1 wherein fluid samples are simultaneously introduced into each chamber through the first set of conduits.

4. A method according to claim 2 wherein the force is applied from a coupler extending between the cover and the substrate to urge the cover toward the substrate and retain them in the assembled position.

5. A method according to claim 4 wherein the coupler includes a plate with at least one view opening and includes an adjustable interconnect member, and wherein the coupler application comprises:

positioning the plate facing a second side of the substrate with the at least one view opening in alignment with the arrays such that the arrays can be observed from the second side of the substrate through the at least one plate view opening;

extending the adjustable interconnect member between the cover and the plate; and

adjusting the interconnect member to urge the cover toward the substrate.

6. A method according to claim 4 additionally comprising, after applying the coupler, heating the chambers.

7. A method of testing multiple fluid samples with multiple biopolymer arrays to detect a binding pattern between the multiple fluid samples and the arrays, comprising:

(a) assembling a cover to a contiguous substrate carrying on a first side, multiple arrays each with multiple regions of biopolymers linked to the substrate, such that the cover and the substrate together form a plurality of chambers each containing a biopolymer array and each being accessible through its own port;

(b) introducing the multiple fluid samples into respective chambers through a port of each such that the fluid samples contact respective arrays; and

(c) observing a binding pattern of the arrays;

wherein each chamber is accessible through a first and a second port, and wherein fluid samples are introduced into respective chambers through respective first ports while venting through respective second ports.

8. A method according to claim 7 wherein the maximum distance between the substrate and the cover in the chambers is no greater than 2 mm.

9. A method according to claim 7 wherein each of the chambers has a volume no greater than 1000 μ

l.

10. A method according to claim 7 wherein the multiple fluid samples are different fluid samples.

11. A method of testing multiple fluid samples with multiple biopolymer arrays to detect a binding pattern between the multiple fluid samples and the arrays, using a cover which includes a cover member and a resilient gasket with multiple openings, the method comprising:

(a) assembling the cover to a contiguous substrate carrying on a first side multiple arrays each with multiple regions of biopolymers linked to the substrate, with the gasket sandwiched between the substrate and cover member and the gasket openings aligned with respective arrays, such that the cover and the substrate together form a plurality of chambers each containing a biopolymer array and being accessible through a port comprising respective port portions of the resilient gasket which normally close the port;

(b) penetrating gasket port portions with at least one conduit and introducing fluid samples into respective chambers through the at least one conduit and chamber ports such that the fluid samples contact respective arrays; and

(c) observing a binding pattern of the arrays.

12. A method according to claim 11 wherein, following assembly, the gasket has a first side facing the substrate and a second side facing the cover member, and has port portions positioned transversely beyond the substrate, and wherein the ports further comprise respective fluid ducts in the cover member communicating between respective chambers and respective port portions of the gasket such that the chambers can be accessed by conduits which have penetrated from the first side of the gasket through the port portions to the ducts.

13. A method according to claim 12 wherein the ducts are channels in a first side of the cover member which faces the gasket.

14. A method according to claim 12 wherein each chamber has a first and a second port, the method additionally comprising inserting a first set of conduits through the gasket port portions of respective first ports, and inserting a second set of conduits through the gasket port portions of respective second ports, and wherein the multiple fluid samples are introduced into each chamber through the first set of conduits while venting occurs through the second set of conduits.

15. A method according to claim 13 additionally comprising applying a coupler extending between the cover and the substrate to urge the cover toward the substrate and retain them in the assembled position, the coupler including a first member which is positioned adjacent a second side of the substrate and an adjustable interconnect member extending between the first member and the substrate.

16. A method according to claim 15 wherein the first member comprises a plate having guide openings which, following application of the coupler, are aligned with respective port portions of the gasket.

17. A method according to claim 16 wherein the plate has at least one view opening and wherein the coupler member application comprises positioning the plate facing a second side of the substrate with the at least one view opening in alignment with the arrays such that the arrays can be observed from the second side of the substrate through the at least one view opening.

18. An apparatus for testing multiple fluid samples with multiple biopolymer arrays, comprising:

(a) a cover defining multiple cavities on a first side and with respective ports communicating with the cavities, the ports including respective resilient self-sealing portions normally closing the ports, which cover can be assembled to a one-piece planar substrate carrying on a first side, multiple arrays each with multiple regions of biopolymers linked to the substrate, such that the cover and the substrate together form a plurality of chambers each containing a biopolymer array;

wherein the cover has a first and a second set of ports such that each chamber is accessible through a first and a second port so that fluid samples can be introduced into respective chambers through respective first ports while venting through respective second ports.

19. An apparatus according to claim 18 additionally comprising the planar substrate attached to the cover.

20. An apparatus for testing multiple fluid samples with multiple biopolymer arrays, comprising:

a cover including;

a resilient gasket with multiple openings and port portions; and

a cover member

wherein the gasket and cover member are dimensioned so that the cover can be assembled to a contiguous planar substrate carrying on a first side multiple arrays each with multiple regions of biopolymers linked to the substrate, with the gasket sandwiched between the substrate and cover member and with the gasket openings aligned with respective arrays, such that the cover and the substrate together form a plurality of chambers each containing a biopolymer array and each accessible through a port which includes the gasket port portions normally closing the port, upon penetration of a conduit through respective port portions of the resilient gasket.

21. An apparatus according to claim 20 wherein:

the gasket is dimensioned such that, following assembly, a first side of the gasket faces the substrate and a second side of the gasket faces the cover member, and the port portions are positioned transversely beyond the substrate;

and wherein the ports further comprise respective fluid ducts in the cover member which, following assembly, communicate between respective chambers and respective port portions of the gasket such that the chambers can be accessed by conduits which have penetrated from the first side of the gasket through the port portions thereof to the ducts.

22. An apparatus according to claim 21 wherein the ducts are channels in a first side of the cover member which faces the gasket following assembly.

23. An apparatus according to claim 21 wherein the cover member and gasket have ducts and port portions, respectively, such that following assembly each chamber has a first and a second port both normally closed by a gasket port portion.

24. An apparatus according to claim 21 additionally comprising a coupler to extend between the assembled cover and substrate to urge the cover toward the substrate and retain them in the assembled position, the coupler including a first member positionable adjacent a second side of the substrate and an adjustable interconnect member extendable between the first member and the substrate.

25. An apparatus according to claim 24 wherein the first member comprises a plate having guide openings alignable with respective port portions of the gasket.

26. An apparatus according to claim 24 wherein the plate has at least one view opening through which the arrays can be observed when the plate faces a second side of the substrate with the coupler retaining the cover and substrate in the assembled position.