Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2000-08-29
2001-09-04
Beisner, William H. (Department: 1744)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S286100, C435S303100, C204S601000, C204S604000, C204S605000
Reexamination Certificate
active
06284525
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention generally relates to miniaturized devices for carrying out and controlling chemical reactions and analyses. In particular, the present invention provides devices which have miniature temperature controlled reaction chambers for carrying out a variety of synthetic and diagnostic applications, such as PCR amplification, nucleic acid hybridization, chemical labeling, thermal cycling, nucleic acid fragmentation, transcription, sequencing and the like.
A large number of diagnostic and synthetic chemical reactions require precise monitoring and control of reaction parameters. For example, in nucleic acid based diagnostic applications, it is generally desirable to maintain optimal temperature controls for a number of specific operations in the overall process. In particular, PCR amplification requires repeated cycling through a number of specific temperatures to carry out the melting, annealing, and ligation steps which are part of the process. By reducing reaction volumes, the amount of time required for thermal cycling may also be reduced, thereby accelerating the amplification process. Further, this reduction in volume also results in a reduction of the amounts of reagents and sample used, thereby decreasing costs and facilitating analyses of small amounts of material. Similarly, in hybridization applications, precise temperature controls are used to obtain optimal hybridization conditions. Finally, a number of other pre-and post-hybridization treatments also favor precise temperature control, such as fragmentation, transcription, chain extension for sequencing, labeling, ligation reactions, and the like.
A number of researchers have attempted to miniaturize and integrate reaction vessels for carrying out a variety of chemical reactions, including nucleic acid manipulation. For example, published PCT Application No. WO 94/05414, to Northrup and White reports an integrated micro-PCR apparatus fabricated from thin silicon wafers, for collection and amplification of nucleic acids from a specimen. Similarly, U.S. Pat. No. 5,304,487 to Wilding, et al., and U.S. Pat. No. 5,296,375 to Kricka, et al. discuss chambers and flow channels micromachined from silicon substrates for use in collection and analysis of cell samples.
The increased desire for automated chemical processes in both analytical and synthetic applications has led to a need for miniaturization and integration of existing processes and equipment for carrying out these chemical processes. The present invention meets these and other needs.
SUMMARY OF THE INVENTION
The present invention generally provides miniature temperature controlled reaction chambers and devices which incorporate them. In a first aspect, the present invention provides a miniature temperature controlled reaction chamber, which comprises a body having a cavity disposed therein. A resistive heater is disposed in the cavity, and is electrically connected to a power source for delivering a voltage across the resistive heater. The reaction chamber also includes a temperature sensor disposed on a surface of the body adjacent to or within the cavity, for determining the temperature within the cavity.
In a preferred aspect, the reaction chamber is used as an amplification chamber and comprises an effective amount of each of the four deoxynucleoside triphosphates, a nucleic acid polymerase and amplification primer sequences disposed therein.
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Mathies Richard A.
Woolley Adam T.
Affymetrix Inc.
Beisner William H.
McGarrigle Philip L.
Sherr Alan B.
Zitkovsky Ivan D.
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