Thermo-controllable high-density chips for multiplex analyses

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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the priority benefit of U.S. Provisional Application Ser. No. 60 / 630,789 filed Nov. 24, 2004, and U.S. Patent Application Ser. No. 10 / 857,552 filed May 28, 2004, all of which are hereby incorporated herein by reference in their entirety.TECHNICAL FIELD [0002] This invention relates to miniaturized instruments for conducting chemical reactions where control of the reaction temperature is desired or required. Specifically, the invention relates to chips and optical systems for performing 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. BACKGROUND OF THE INVENTION [0003] The advent of Polymerase Chain Reaction (PCR) since 1983 has revolutionized molecular biology through vastly extending the capability to identify, manipulate, and reproduce DNA. Nowadays PCR is routinely pract...

AI Technical Summary

Benefits of technology

[0007] A principal aspect of the present invention is the design of miniaturized devices applicable for multiplex analyses of individual molecules, and / or simultaneous performance of a vast number of chemical reactions. The devices and methods of the present invention simplify the laborious and expensive procedures of performing chemical reactions where a control of the reaction temperature is desired or required.

[0014] In other aspects, the thermo-controllable units of the subject chips can be arranged in different temperature zones, each of which can be separately controlled. In general, the micro well within each unit is in thermal contact with a heating element that can be made of metal or semi-conducting material. Preferred heating element is an indium-tin-oxide (ITO) heater. Heating element can be located within the micro well, or can be attached to the upper or bottom, or both surfaces of the micro well. To prevent evaporation and condensation of the reaction sample on the upper surface of the well, the upper surface can be maintained at a higher temperature than the bottom surface. In preferred embodiments, a plurality of grooves is fabricated to the bottom surface of the chip. The presence of the grooves greatly facilitates passive heat dissipation during thermal cycling. In other embodiments, the subject chips have a ramp temperature time about 10° C. or higher per second, preferably about 25° C. or higher per second. In other preferred embodiments, the subject chips may comprise temperature sensors in thermal contact with the micro wells.

Problems solved by technology

Performing a large quantity of PCR with the conventional thermal cycler has been rather expensive.

This is partly due to the intrinsic limitations of the conventional instrument.

Because the instrument has a large thermal mass and the plastic tubes have low heat conductivity, high level of electrical power is required to operate the instrument.

While the channel- or chamber-based design in principle reduces the thermal mass and the reaction volume, it still suffers from other practical drawbacks.

In particular, the channels or chambers by design are not amenable to automated sealing that prevents evaporation and / or cross contamination of the reaction samples.

Images