Apparatus for high throughput chemical reactions

• US 9,132,427 B2
• Filed: 08/24/2012
• Issued: 09/15/2015
• Est. Priority Date: 01/22/2007
• Status: Active Grant

• Current Assignee: Takara Bio Usa, Inc. (Ningbo Junsheng Investment Group Co., Ltd.)
• Original Assignee: WaferGen, Inc.
• Inventors: Joseph, Victor, Huda, Amjad, Shivji, Alnoor
• Primary Examiner(s): Boyer, Randy
• Application Number:
  US13/594,562
• Publication Number:
  US 20130053272A1
• Time in Patent Office: 1,117 Days
• US Class Current: 1/1
• 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 2200/147 Employing temperature sensors
• 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 2300/0893 having a very large number of wells, microfabricated wells
• 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 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2300/1894 Cooling means; Cryo cooling
• 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: B01L 7/54 using spatial temperature gradients
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 21/0332 with temperature control control of temperature G05D23/00; cryostats F17C3/08
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00

Abstract

Apparatus, systems, chips, and methods of performing a large number of simultaneous chemical reactions are provided herein. The chips of the invention comprise addressable units that can be addressed according to the temperature of the reaction to be run. The subject apparatus, systems, and chips are particularly suited for performing polymerase chain reactions on thousands of nucleic acid sequences, up to and including sequences of an entire genome of an organism of interest.

Claims

1. A method of conducting a chemical reaction in a chip while avoiding condensation comprising:

a) providing;

i) a chip configured to receive a reaction sample wherein the chip comprises a substrate and an array of addressable units; and

ii) an apparatus for conducting chemical reactions in said chip comprising;

A) a first heater configured to be in thermal contact with the bottom of said chip such that said array of wells can be cycled between a nucleic acid denaturation temperature and a primer annealing temperature; and

B) a second heater configured to be in thermal contact with said top of said chip, wherein said second heater provides a temperature at the surface of said chip such that condensation is avoided at said surface of said chip when said array of wells are cycled between said nucleic acid denaturation temperature and said primer annealing temperature; and

b) conducting a chemical reaction in the reaction sample by cycling the temperature of the chip between said nucleic acid denaturation temperature and said primer annealing temperature.

2. The method of claim 1, wherein the chemical reaction is a nucleic acid amplification reaction.

3. The method of claim 2, wherein said apparatus further comprises an optical system, wherein the reaction sample is capable of producing an optical signal, and, wherein the chip is operatively coupled to said optical system which is configured to detect optical signals emitted from the reaction sample.

4. The method of claim 3, wherein the optical signals are proportional to the amount of product of the chemical reaction.

5. The method of claim 1, wherein said array comprises 25,000 to 200,000 addressable units.

6. The method of claim 1, wherein said first heater comprises 6 distinct temperature zones.

7. The method of claim 1, wherein said addressable units are sealed with a radiation-curable adhesive.

8. The method of claim 1, wherein said first heater provides a plurality of temperature zones, and said second heater provides a uniform temperature.