Device for thermal cycling

• US 6,990,290 B2
• Filed: 11/23/2001
• Issued: 01/24/2006
• Est. Priority Date: 11/23/2000
• Status: Expired due to Fees

• Current Assignee: Gyros Patent AB (Mesa Laboratories Inc.)
• Original Assignee: Gyros AB (Mesa Laboratories Inc.)
• Inventors: Kylberg, Gunnar, Andersson, Per, Salven, Owe
• Primary Examiner(s): Campbell, Thor S.
• Application Number:
  US10/432,107
• Publication Number:
  US 20040131345A1
• Time in Patent Office: 1,523 Days
• Field of Search: 392/465, 392/479, 435/1, 422/50, 422/58, 422/72, 422/82.12, 422/186.2
• US Class Current: 392/465
• 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 7/54 using spatial temperature gradients

Abstract

An apparatus for performing temperature cycling, comprising a micro channel reactor structure (46, 48, 50), and having a heating structure (b1, b2, B1, B2) defining a desired temperature profile. A preferred embodiment of a heating element structure comprises a pattern of areas of a material capable of providing heat when energized, disposed over said micro channel reactor structure.

Claims

1. A microchannel reactor apparatus for performing temperature cycling, comprising a substrate having at least one microchannel structure, the microchannel structure comprising one or more microchannels wherein

(a) at least a portion of at least one of said microchannels constitutes a reaction volume for performing said temperature cycling;

and

(b) there is provided a heating structure defining

i) a selected area on said substrate, including said reaction volume in which said temperature cycling is to be performed; and

ii) a temperature profile in said reaction volume such that an essentially uniform temperature is obtainable and maintained in said reaction volume,

said heating structure comprises a material capable of transferring heat into said selected area when energized, and said material is laid out in a pattern that causes heating and cooling to balance each other so as to create said uniform temperature in the reaction volume.

2. The microchannel reactor apparatus of claim 1 wherein said heating structure defines a continuous layer covering said selected area.

3. The reactor apparatus as claimed in claim 1 wherein the microchannel structure comprises at least one channel exhibiting a U turn, defining said reaction volume.

4. The reactor apparatus as claimed in claim 1 wherein the reaction volume is defined in a straight channel provided with a valve to prevent a sample from being moved in the channel beyond the reaction volume, said valve comprising a plug of a material that is capable of changing its volume in response to an external stimulus, wherein the external stimulus is light, heat, radiation, or magnetism.

5. The reactor apparatus as claimed in claim 4 wherein said plug material is selected from the group consisting of polymers, waxes and metals having low melting temperature.

6. The reactor apparatus as claimed in claim 1 wherein said material is capable of absorbing electromagnetic energy, and said electromagnetic energy is light.

7. The reactor apparatus as claimed in claim 1 wherein said heating structure comprises a separate member disposed so as to mask electromagnetic radiation directed towards the surface of the substrate, and having openings defining said pattern, and wherein the material capable of transferring heat into said selected area when energized is provided as a continuous layer covering said reaction volume.

8. The reactor apparatus as claimed in claim 1 wherein the material capable of transferring heat into said selected area when energized comprises a pattern of areas of a resistive material capable of generating heat when an electric current is passed therethrough.

9. The reactor apparatus as claimed in claim 1 wherein the portion constituting said reaction volume has an inlet end and an outlet end, and said reaction volume has the same cross section as the portions of said microchannel connecting to said reaction volume at both the inlet and the outlet end thereof.

10. The reactor apparatus as claimed in claim 1 wherein the substrate is a rotatable disc.

11. The reactor apparatus as claimed in claim 1 wherein the substrate is a stationary, non-rotary member.

12. A system for performing temperature cycling, comprising

(a) a reactor apparatus as claimed in claim 1 having a substrate that is rotatable;

(b) a motor coupled to the reactor apparatus to enable rotation of the apparatus;

(c) a source of energy for heating said reactor apparatus; and

(d) a control unit for controlling heating power and rotation of said reactor apparatus in accordance with a desired temperature cycling operation.

13. The system as claimed in claim 12, adapted for PCR.

14. A method for temperature cycling of a sample in a microchannel between a lower and a uniform elevated temperature, comprising the steps of

(i) providing a microchannel reactor apparatus as defined in claim 1,

(ii) filling at least one of said one or more reactor volumes with a liquid aliquot to be temperature cycled,

(iii) supplying energy to the heating structure of the apparatus to reach said uniform elevated temperature,

(iv) reducing the energy supply so as to reach said lower temperature, and

(v) repeating steps ii) and iii) a desired number of times.

15. The method as claimed in claim 14, wherein the substrate is a disc and the disc is spun during temperature cycling, with an increased spinning speed during step (iv).

16. A method for temperature cycling of a sample in a microchannel between a lower and a uniform elevated temperature, comprising the steps of(i) providing a microchannel reactor apparatus as defined in claim 1, (ii) filling at least one of said one or more reactor volumes with a liquid aliquot to be temperature cycled, (iii) supplying energy to the heating structure of the apparatus to reach said uniform elevated temperature, (iv) reducing the energy supply so as to reach said lower temperature, and (v) repeating steps ii) and iii) a desired number of times a system for performing temperature cycling, comprising (a) a reactor apparatus as claimed in claim 1 having a substrate that is rotatable, (b) a motor coupled to the reactor apparatus to enable rotation of the apparatus;

(c) a source of energy for heating said reactor apparatus; and

(d) a control unit for controlling heating power and rotation of said reactor apparatus in accordance with a desired temperature cycling operation, wherein the apparatus provided in step (i) is part of a system for performing temperature cycling, comprising (a) a reactor apparatus having a substrate that is rotatable, (b) a motor coupled to the reactor apparatus to enable rotation of the apparatus;

(c) a source of energy for heating said reactor apparatus; and

(d) a control unit for controlling heating power and rotation of said reactor apparatus in accordance with a desired temperature cycling operation.

18. The reactor apparatus as claimed in claim 1, wherein the pattern is annular.

17. A microchannel PCR reactor apparatus, comprising:

(a) a substrate in the form of a transparent, rotatable disc, having a microchannel structure comprising a plurality of microchannels, provided therein, wherein at least a portion of one of said microchannels constitutes a reaction volume for performing PCR;

(b) a layer of a material capable of absorbing electromagnetic energy and capable of transferring heat into said selected area when energized, said layer provided so as to cover at least an area within which said reaction volume is confined;

wherein

said portion of one of said microchannels that constitutes a reactor volume is shaped as a U having an inlet end and an outlet end, and said material is laid out in a pattern of coated and intermediate non-coated areas over said reaction volume, said pattern defining a desired and uniform temperature in the reaction volume.