Apparatus and method for multiplex analysis

• US 20060073491A1
• Filed: 05/24/2005
• Published: 04/06/2006
• 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 7,622,296 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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. An apparatus for multiplexed analysis comprising:

an array of micro wells for containing and confining reaction samples, wherein the array is optically linked to

(a) an optical multiplexer adapted for receiving and multiplexing a plurality of incoming beams of one or more different wavelengths;

(b) an optical switch adapted for redirecting the multiplexed wavelengths of (a) to individual output fibers, wherein each of the individual output fibers optically linked to a micro well of the array, said micro well being coupled to a spectrum analyzer that spectrally analyzes optical signals coming -from the micro well.

2. The apparatus of claim 1, wherein the optical multiplexer is an arrayed waveguide grating (AWG).

3. The apparatus of claim 1, wherein the spectrum analyzer comprises an optical transmission element and a photon-sensing element.

4. The apparatus of claim 3, wherein the optical transmission element is selected from the group consisting of multi-mode fibers (MMF), single-mode fibers (SMF) and a waveguide.

5. The apparatus of claim 3, wherein the photon-sensing element is selected from the group consisting of photo multiplier tube, charge coupled device, avalanche photo diode, gate sensitive FET'"'"'s and nano-tube FET'"'"'s, and P-I-N diode.

6. The apparatus of claim 1, wherein the array of micro wells contains biological molecules.

7. The apparatus of claim 1, wherein the multiplexed analysis comprises chemical reaction.

8. The apparatus of claim 1, wherein the multiplexed analysis reaction is nucleic acid amplification.

9. The apparatus of claim 7, wherein the chemical reaction takes place in a cell contained in the micro well.

10. A method of varying and/or maintaining a temperature of a reaction sample comprising:

placing the reaction sample into a micro well fabricated in a chip, said micro well 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 the micro well receives and confines the reaction sample, and is sealed when ;

filled with the reaction sample;

applying a voltage to the heating element thereby varying and/or maintaining the temperature of the reaction sample.

11. The method of claim 10 further comprising cycling the applying step to raise and lower the temperature of the reaction sample.

12. The method of claim 10, 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.

13. The method of claim 10, wherein the micro well has a volume of from about 100 μ

l to about 0.001 μ

l.

14. The method of claim 10, wherein the heating element is an indium-tin-oxide (ITO) heater.

15. The method of claim 10, wherein the well has an upper and a bottom surface, and wherein the heating element is attached to the bottom surface or the upper surface but not both.

16. The method of claim 10, wherein the well has an upper and a bottom surface, and wherein the heating element is attached to both the upper and the bottom surfaces.

17. The method of claim 10, wherein the well is operatively coupled to an optical system that detects optical signals emitted from the reaction sample.

18. The method of claim 10, wherein the well further comprises a plurality of grooves at the bottom surface.

19. The method of claim 10, wherein the chip is in thermal contact with a temperature sensor.

20. The method of claim 10, wherein the step of applying a voltage is effected by processing a predetermined algorithm stored on a computer readable media operatively linked to the heating element.