Method for carrying out a biochemical protocol in continuous flow in a microreactor

• US 20050282224A1
• Filed: 08/04/2005
• Published: 12/22/2005
• Est. Priority Date: 07/28/1999
• Status: Abandoned Application

• Current Assignee: Commissariat a L'Energie Atomique (AES Corporation), Serono Genetics Institute S.A. (Merck & Co., Inc.)
• Original Assignee: Commissariat a L'Energie Atomique (AES Corporation), Serono Genetics Institute S.A. (Merck & Co., Inc.)
• Inventors: Claustre, Patricia, Vauchier, Claude, Peponnet, Christine, Sarrut, Nicolas, Fouillet, Yves, Charles, Raymond, Clerc, Jean-Frederic
• Application Number:
  US11/197,040
• Publication Number:
  US 20050282224A1
• Time in Patent Office: Days
• US Class Current: 435/6.19
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• 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 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0845 Filaments, strings, fibres, i.e. not hollow
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2300/1883 using thermal insulation
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• 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 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B01L 7/02 Water baths; Sand baths; Air baths
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: B01L 7/5255 : by moving sample containers
• CPC Class Codes: F28F 2260/02 : having microchannels
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis

Abstract

Devices and methods for carrying out a chemical or biochemical protocol are disclosed. In one embodiment, the chemical or biochemical protocol is performed by cycling at least one thermal transfer member between at least two temperatures while liquid samples on which the chemical or biochemical protocol is to be performed are continuously moving through at least one temperature regulated zone upon which the at least one thermal transfer member acts. In some embodiments, the device comprises a sample transport member that comprises liquid samples in sample receiving regions. The sample transport member moves the samples continuously through a temperature regulated zone which cycles between at least two temperatures while the liquid samples are moving through a temperature regulated zone on which at least one thermal transfer member acts. In some embodiments, the sample receiving regions comprise wells, hydrophillic films or hydrophillic filaments.

Claims

1. A method of performing a chemical or biochemical protocol comprising:

cycling at least one thermal transfer member between at least two temperatures while liquid samples on which said chemical or biochemical protocol is to be performed are continuously moving through at least one temperature regulated zone upon which said at least one thermal transfer member acts.

2. The method of claim 1, wherein said liquid samples move through the temperature regulated zone in sample receiving regions selected from the group consisting of wells, hydrophilic films and hydrophilic filaments.

3. The method of claim 1, wherein said chemical or biochemical protocol comprises adding at least one reagent to the liquid samples.

4. The method of claim 1, wherein said cycling between at least two temperatures is repeated 1 to 35 times while said liquid samples are moving through the temperature regulated zone.

5. The method of claim 1, wherein said chemical or biochemical protocol comprises a nucleic acid amplification procedure.

6. The method of claim 1, wherein said chemical or biochemical protocol is performed on a plurality of liquid samples arranged in parallel.

7. The method of claim 1, further comprising detecting the result of said protocol.

8. The method of claim 1, wherein said chemical or biochemical protocol comprises determining the identity of at least one polymorphic nucleotide.

9. A method for carrying out a chemical or biochemical protocol comprising:

depositing liquid sample volumes into a plurality of sample receiving regions on at least one mobile sample transport member; and

moving the sample transport member along a pathway such that said sample receiving regions move through at least one temperature regulated zone upon which a thermal transfer member acts, wherein said thermal transfer member is capable of cycling between at least two temperatures while said sample receiving regions are moving through said at least one temperature regulated zone.

10. A device comprising:

a substrate comprising regions for receiving liquid samples wherein said liquid samples move along at least one sample pathway; and

at least one thermal transfer member which is capable of cycling between at least two temperatures, said at least one thermal transfer member being adapted to bring at least a portion of said sample pathway to said at least two temperatures while a sample is continuously moving along said at least a portion of said sample pathway.

11. The device of claim 10, wherein said substrate comprising regions for receiving liquid samples is selected from the group consisting of substrates comprising a plurality of wells, hydrophilic films and hydrophilic filaments.

12. The device of claim 10, further comprising at least one reagent supplier.

13. The device of claim 10, further comprising a detector for determining the result of said protocol.

14. A device comprising at least one mobile sample transport member having sample receiving regions thereon and at least one thermal transfer member which is capable of cycling between at least two temperatures, said at least one thermal transfer member being adapted to allow said sample receiving regions to cycle between at least two temperatures while said sample receiving regions are moving through at least one temperature regulated zone upon which said at least one thermal transfer member acts.

15. The device of claim 14, further comprising reagent addition members.

16. The device of claim 14, wherein the sample receiving regions comprise wells.

17. The device of claim 16, wherein the sample receiving regions comprise a plate, having a plurality of wells therein, said wells having a thin film on their bottom surfaces.

18. The device of claim 17, wherein the plate is made of a material selected from the group consisting of plastic, silicon and glass.

19. The device of claim 14, wherein the sample receiving regions comprise a film.

20. The device of claim 19, wherein a surface of the film is sufficiently hydrophilic to allow adherence of individual liquid sample volumes in the form of droplets on the surface.

21. The device of claim 19, wherein said film comprises a matrix of hydrophilic areas surrounded by a hydrophobic region, said hydrophilic areas being sufficiently hydrophilic to allow adherence of individual liquid samples in the form of droplets on said hydrophilic areas.

22. The device of claim 19, wherein the film is made of a material selected from the group consisting of polyimide, kapton, polycarbonate, PDMS and aluminum.

23. The device of claim 19, wherein the film has anisotropic thermal conductivity such that the thermal conductivity through a cross section of the film is greater than the thermal conductivity within a plane of the film.

24. The device of claim 14, wherein said sample receiving regions comprise a filament.

25. The device of claim 24, wherein the filament is sufficiently hydrophilic to allow adherence of individual liquid sample volumes in the form of droplets on the filament.

26. The device of claim 25, wherein the filament is electrically conductive, and the liquid sample volumes are heated by passing electric current through said filament.

27. The device of claim 14, further comprising reels, which move said sample transport member along said pathway by frictionally engaging the sample transport member.