System and cartridge for processing a biological sample

• US 20040141880A1
• Filed: 07/22/2003
• Published: 07/22/2004
• Est. Priority Date: 07/24/2002
• Status: Abandoned Application

• Current Assignee: CombiMatrix Corporation, Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Degenhardt, Volker, Prokop, Sara Akiko, Slota, Michael William, Handler, Erich
• Application Number:
  US10/624,827
• Publication Number:
  US 20040141880A1
• Time in Patent Office: Days
• US Class Current: 422/58
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• 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 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• 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 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 35/00029 : provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/10 : Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices G01N35/0099 takes precedence

Abstract

There is disclosed a sample processing system for processing a sample contained in a liquid. Specifically, there is disclosed a sample processing system comprising a pipettor, and a cartridge. The cartridge comprises a chamber which has an inlet and an outlet. The chamber contains a microarray device having an active surface. The active surface is accessible to liquid contained in the chamber. The cartridge further comprises an optical interface that provides optical access to the active surface of the microarray device, an inlet port and an outlet port. The inlet port is so configured and dimensioned that it forms an air-tight connection with a pipette tip when the pipette tip is inserted into the inlet port.

Claims

1. A sample processing system for processing a sample contained in a liquid, said system comprising:

a) a pipettor having a pipette tip for dispensing liquids, and

b) a cartridge comprising;

(b.1) a chamber which has an inlet and an outlet, said chamber containing a microarray device having an active surface which is formed by an array of different oligomers at known locations, said active surface being accessible to liquid contained in the chamber,

(b.2) an optical interface which provides optical access to said active surface of said microarray device, and

(b.3) an inlet port and an outlet port, said inlet port being so configured and dimensioned that it forms an air-tight connection with the pipette tip when said pipette tip is inserted into said inlet port.

2. The sample processing system according to claim 1, wherein a first channel connects said inlet port with said chamber inlet, a second channel connects said chamber outlet with said outlet port, and said chamber inlet lies at a lower height than said chamber outlet, whereby liquid supplied to the chamber through said chamber inlet displaces air contained in said chamber and enables a complete and bubble free filling of said chamber with liquid, any excess of liquid leaving said chamber through said chamber outlet.

3. The sample processing system according to claim 1, wherein said inlet port is an inlet channel having an inner surface which fits the outer surface of said pipettor end part, said inlet port and said pipettor end part being thereby adapted to form an air-tight connection.

4. The sample processing system according to claim 1, wherein said inlet port is closed by a closure which is adapted to be pierced by said pipette tip, whereby said inlet port and said pipette tip being so configured and dimensioned that they form an air-tight connection when that closure is pierced by said pipettor end part.

5. The sample processing system according to claim 1, further comprising a thermal interface, whereby the thermal interface allows heating or cooling said microarray device by heat exchange with a heat transfer means.

6. The sample processing system according to claims 1, wherein said inlet port is adapted for receiving said pipette tip inserted in the inlet port coming from a position located above said port.

7. A cartridge for processing a sample contained in a liquid, said cartridge comprising:

(a) a flow-cell having a chamber which has an inlet and an outlet, said flow-cell containing a microarray device having an active surface, said active surface being accessible to liquid contained in that chamber, and

(b) a housing containing said flow-cell, said housing comprising;

(b.1) an optical interface which provides optical access to said active surface of said microarray device;

(b.2) an inlet port and an outlet port;

(b.3) a first conduit connecting said inlet port of said housing with said inlet of the flow-cell; and

(b.4) a second conduit connecting said outlet of said flow cell with said outlet port of said housing.

8. The cartridge according to claim 7, wherein said inlet port is an inlet channel having an inner surface which fits the outer surface of a pipette tip, whereby said inlet port and said pipette tip being thereby adapted to form an air-tight connection.

9. The cartridge according to claim 7, wherein said inlet port of said housing is closed by a closure which is adapted to be pierced by a pipette tip, whereby said inlet port and said pipette tip being so configured and dimensioned that it forms an air-tight connection when that closure is pierced by said pipette tip.

10. The cartridge according to claim 7, wherein said housing has a thermal interface that provides access to an outer surface of said flow-cell so that the active surface of the microarray device can be heated or cooled by putting it in contact with an outer surface of a heat transfer element.

11. The cartridge according to claim 7, wherein said flow cell comprises:

(a) a microarray device having a first surface that is an active surface, a second surface on a second side opposite to said first side, and an edge having a peripheral outer surface which extends between said first surface and said second surface,

(b) a base plate having a depression for receiving said microarray device, said depression having a bottom surface such that at least part of said second surface of said microarray device being attached to said bottom surface of the base plate, and

(c) a cover plate having a transparent or a translucent region,

said base plate and said cover plate being so configured, dimensioned and assembled to form a chamber, wherein the chamber has an inlet and an outlet, whereby when the chamber is filled with a liquid sample the active surface of said microarray device is in contact with the liquid.

12. The cartridge according to claim 11, wherein said depression of said base plate has a predetermined depth.

13. The cartridge according to claim 7, further comprising a frame plate having an opening that defines a cavity above said active surface of said microarray device.

14. The cartridge according to claim 7, wherein said flow-cell chamber has a depth comprised between 0.2 and 1 millimeter.

15. The cartridge according to claim 11, wherein said base plate is made of machinable glass ceramic.

16. The cartridge according to claim 11, wherein said base plate is made of aluminum oxide.

17. A sample processing system for processing a sample contained in a liquid, said system comprising:

(a) a cartridge having

(a.

     1) a chamber which has an inlet and an outlet, said chamber containing a microarray device having an active surface which is formed by an array of different oligomers at known locations, said active surface being accessible to liquid contained in the chamber,

(a.2) an optical interface which provides optical access to said active surface of said microarray device, and

(a.3) an inlet port and an outlet port, said inlet port being so configured and dimensioned that it forms an air-tight connection with a pipette tip when said pipette tip is inserted into said inlet port; and

(b) an optical means for performing a optical fluorescence or chemiluminescence scanning of said active surface of said microarray device.

18. The sample processing system according to claim 17, wherein said optical scanning means comprises:

(a) a light source for irradiating said active surface of said microarray device with excitation light,

(b) first light filter means arranged between said light source and said active surface for irradiating said active surface with light having a wave length lying in a first wave length range,

(c) a light receiving element for acquiring an image of said active surface or a portion thereof, and

(d) second light filter means arranged between said light receiving element and said active surface so that the latter element receives from said active surface light having a wave length lying in a second wave length range.

19. The sample processing system according to claim 17, further comprising means for drying the active surface of said microarray device.

20. The sample processing system according to claim 19, wherein said drying means comprises a membrane pump.

21. A sample processing system for processing a sample contained in a liquid, said system comprising:

(a) a cartridge having;

(a.1) a chamber which has an inlet and an outlet, said chamber containing a microarray device having an active surface which is formed by an array of different oligomers at known locations, said active surface being accessible to liquid contained in the chamber,

(a.2) an optical interface which provides optical access to said active surface of said microarray device, and

(a.3) an inlet port and an outlet port, said inlet port being so configured and dimensioned that it forms an air-tight connection with a pipette tip when said pipette tip is inserted into said inlet port;

(b) a cartridge holder adapted for holding said cartridge in such a position that the flow-cell inlet lies at a lower height than the flow-cell outlet, whereby liquid supplied to the flow-cell chamber through said inlet displaces air contained in said chamber and enables a complete and bubble free filling of said chamber with liquid, any excess of liquid leaving said chamber through said flow-cell outlet; and

(c) a waste container for receiving excess liquid flowing out of the flow-cell outlet.

22. The sample processing system according to claim 21, wherein the amount of liquid supplied to the flow-cell chamber is larger than the volume of the flow-cell chamber, so that excess liquid flows out of said flow-cell outlet.

23. The sample processing system according to claim 21, further comprising:

(a) an automatic pipetting system,

(b) a set of pipetting tips,

(c) a control system which operates said automatic pipetting system for performing pipetting operations, said operations including picking up a pipetting tip, loading a liquid sample taken from a sample container into said pipetting tip, inserting said tip into said inlet port of said housing, transferring said liquid sample from the inserted tip to said flow-cell chamber.

24. The sample processing system according to claim 23, wherein each of said pipetting tips is adapted to form an air-tight connection with the inlet port of said cartridge.

25. The sample processing system according to claim 23, wherein said automatic pipetting system and said pipetting tip are also used for applying air flow to said flow-cell chamber for expelling liquid contained therein.

26. The sample processing system according to claim 23, wherein said air flow is used for drying the active surface of said microarray device.

27. The sample processing system according to claim 23, wherein said inlet port of said housing is adapted for receiving a pipetting tip inserted in that inlet port coming from a position located above said port.

28. A sample processing system for processing a sample contained in a liquid, said system comprising

(a) a plurality of cartridges, wherein each cartridge comprises:

(b.

     1) a chamber which has an inlet and an outlet, said chamber containing a microarray device having an active surface which is formed by an array of different oligomers at known locations, said active surface being accessible to liquid contained in the chamber,

(b.2) an optical interface which provides optical access to said active surface of said microarray device, and

(b.3) an inlet port and an outlet port, said inlet port being so configured and dimensioned that it forms an air-tight connection with a pipette tip when said pipette tip is inserted into said inlet port;

(b) a cartridge holder for holding said plurality of cartridges; and

(c) a waste container for receiving excess liquid flowing out from any and all of the outlet ports of said plurality of cartridges