Thermo-controllable chips for multiplex analyses

• US 20060030035A1
• Filed: 05/24/2005
• Published: 02/09/2006
• Est. Priority Date: 05/28/2004
• Status: Active Grant

• Current Assignee: Takara Bio Usa, Inc. (Ningbo Junsheng Investment Group Co., Ltd.)
• Original Assignee: WaferGen, Inc.
• Inventors: Zhou, Jie, Joseph, Victor, Huda, Amjad, Shivji, Alnoor
• Granted Patent: US 7,833,709 B2
• Time in Patent Office: Days
• US Class Current: 435/288.400
• 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 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/50853 with covers or lids
• 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
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6844 Nucleic acid amplification reactions
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2035/0405 : manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
• CPC Class Codes: G01N 21/01 : Arrangements or apparatus for facilitating the optical investigation
• CPC Class Codes: G01N 21/0332 : with temperature control control of temperature G05D23/00; cryostats F17C3/08
• CPC Class Codes: G01N 21/6408 : with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/76 : Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2201/0231 : Thermostating
• CPC Class Codes: G01N 35/0099 : comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: H01L 27/1443 : with at least one potential jump or surface barrier
• CPC Class Codes: H01L 31/0203 : Containers; Encapsulations , e.g. encapsulation of photodiodesfor photovoltaic devices H01L31/048; for organic photosensitive devices H10K30/80
• CPC Class Codes: H01L 31/02325 : the optical elements not being integrated nor being directly associated with the device
• CPC Class Codes: H01L 31/024 : Arrangements for cooling, heating, ventilating or temperature compensation for photovoltaic devices H01L31/052
• CPC Class Codes: H01L 31/105 : the potential barrier being of the PIN type
• CPC Class Codes: H01L 31/18 : Processes or apparatus specially adapted for the manufacture or treatment of these devices or of parts thereof

Abstract

The present invention provides miniaturized instruments for conducting chemical reactions where control of the reaction temperature is desired or required. Specifically, this invention provides chips and optical systems for performing and monitoring temperature-dependent chemical reactions. The apparatus and methods embodied in the present invention are particularly useful for high-throughput and low-cost amplification of nucleic acids.

Claims

1. A chip for varying and/or maintaining temperature of a reaction sample comprising:

an array of thermo-controllable units, said array being in thermal contact with a heating element, wherein the varying and/or maintaining of temperature is achieved by controlling the heating element alone, and wherein individual unit within the array comprises a micro well for receiving and confining the reaction sample, said well being sealed when filled with the reaction sample.

2. The chip of claim 1, wherein the micro well is sealed by (a) applying a radiation-curable adhesive along peripheral dimensions defining an open surface of the micro well;

(b) placing a cover to encompass the peripheral dimensions that define the open surface of the micro well; and

(c) exposing the micro well to a radiation beam to effect the sealing.

3. The chip of claim 2, wherein the radiation-curable adhesive is UV-curable adhesive.

4. The chip of claim 1, wherein the well has a dimension of about 10 mm to about 100 μ

m in length, about 100 mm to about 100 μ

m in width, and about 10 mm to about 100 μ

m in depth.

5. The chip of claim 1, wherein the micro well has a volume of from about 100 μ

l to about 0.001 μ

l.

6. The chip of claim 1, wherein the chip comprises a photon-sensing element.

7. The chip of claim 1, wherein the chip is operatively coupled to an optical system that detects optical signals emitted from the reaction sample.

8. The chip of claim 1, wherein the chip has a ramp temperature time about 25°

C. or higher per second.

9. The chip of claim 1, wherein each unit further comprises a temperature sensor in thermal contact with the micro well.

10. The chip of claim 1, wherein the heating element is located within the micro well.

11. The chip of claim 1 comprising an upper surface and a bottom surface, and two arrays of thermo-controllable units, wherein one array is arranged in one orientation along the upper surface, and wherein the other array is arranged in an opposite orientation along the bottom surface.

12. An apparatus for conducting a chemical reaction requiring cycling at least two temperature levels, comprising:

(a) a chip for cycling at least two temperature levels, said array comprising;

an array of thermo-controllable units, said array being in thermal contact with a heating element, wherein the varying and/or maintaining of temperature is achieved by controlling the heating element alone, and wherein individual unit within the array comprises a micro well for receiving and confining a reaction sample, said well being sealed upon filling the reaction sample;

(b) an optical system operatively coupled to the chip of (a), wherein the optical system detects an optical signal coming from the micro well.

13. The apparatus of claim 12, wherein the micro well is sealed by (a) applying a radiation-curable adhesive along peripheral dimensions defining an open surface of the micro well;

(b) placing a cover to encompass the peripheral dimensions that define the open surface of the micro well; and

(c) exposing the micro well to a radiation beam to effect the sealing.

14. The apparatus of claim 12, wherein the chemical reaction is nucleic acid amplification reaction.

15. The apparatus of claim 12, wherein the optical system comprises a spectrum analyzer.

16. The apparatus of claim 15, wherein the spectrum analyzer comprises an optical transmission element and a photon-sensing element.

17. A method of conducting a chemical reaction that involves a plurality of reaction samples and requires cycling at least two temperature levels, comprising:

(a) providing a chip comprising;

an array of thermo-controllable units, said array being in thermal contact with a heating element, wherein the cycling of at least two temperature levels is achieved by controlling the heating element alone, and wherein individual unit within the array comprises a micro well for receiving and confining a reaction sample, said micro well being sealed when filled with the reaction sample;

(b) placing the plurality of reaction samples into the thermo-controllable units; and

(c) controlling the heating element to effect cycling at least two temperature levels.

18. The method of claim 17, wherein the controlling step comprises processing sensor signals retrieved from a temperature sensor operatively linked to a thermo-controllable unit based on protocol stored on a computer readable medium.

19. The method of claim 17, wherein the chip is operatively coupled to an optical system that detects optical signals emitted from the reaction sample.

20. The method of claim 17, wherein the optical signals are proportional to the amount of product of the chemical reaction.