Chemistry: molecular biology and microbiology – Apparatus
Reexamination Certificate
2001-02-08
2004-01-06
Redding, David A. (Department: 1744)
Chemistry: molecular biology and microbiology
Apparatus
C435S287200, C435S288300, C435S303100, C204S451000, C366S341000, C422S105000
Reexamination Certificate
active
06673593
ABSTRACT:
TECHNICAL FIELD
The present invention refers to an integrated device for microfluid thermoregulation and a manufacturing process thereof.
BACKGROUND OF THE INVENTION
As is known, the treatment of some fluids involves an increasingly precise temperature regulation, in particular when chemical or biochemical reactions are involved. Furthermore frequently the need is felt of using very small amounts of fluid since the fluid is costly or not readily available.
For example, in the DNA amplification process (Polymerase Chain Reaction process, or PCR process) in which precise temperature control in the various steps (it is necessary to perform repeated preset thermal cycles), there is a need to avoid as far as possible thermal gradients in the fluid reaction areas (so that in these areas there may be a uniform temperature), and also the quantity of fluid used (which is very costly) is of crucial importance for obtaining a good reaction efficiency or even for obtaining the reaction itself.
Other examples of fluid treatment having the above characteristics are, for example, linked to the performance of chemical and/or pharmacological analyses, biological tests, etc.
At present, various techniques are available that enable thermal control of chemical or biochemical reagents. A first technique uses a reactor including a glass or plastic base on which a biological fluid is deposited by a pipette. The base rests on a hotplate called “thermo-chuck”, which is controlled by external instrumentation.
Another known reactor includes a heater, which is controlled by appropriate instrumentation and on which a biological fluid to be examined is deposited. The heater is supported by a base also carrying a sensor set in the immediate vicinity of the heater and is also connected to the temperature regulation instrumentation, so as to enable precise temperature control.
Both types of reactors are often enclosed in a protective casing.
A common disadvantage of the above known reactors lies in the large thermal mass of the system; consequently, they are slow and have high power absorption. For example, in case of the PCR process mentioned above, times of the order of 6-8 hours are required.
Another disadvantage of known solutions is linked to the fact that they are able to treat only relatively high volumes of fluids (i.e., minimum volumes of the order of milliliters) because of the macroscopic dimensions of the reactors.
The above disadvantages result in very high treatment costs (in the case of the aforementioned PCR process, the cost can amount to several hundreds of dollars); in addition, they restrict the application of known reactors to test laboratories alone.
A recent solution (see, for example, U.S. Pat. No. 5,858,195) describes a microchip laboratory system and method that enable manipulation of a fluid for a plurality of applications including injection of samples for chemical separation. The microchip is manufactured using standard photolithographic procedures and by etching a substrate, preferably of glass, on which surface channels are made and which is bonded directly on a covering plate. Also envisaged is the use of a silicon substrate. However, there is a need to furnish precise thermoregulation.
SUMMARY OF THE INVENTION
According to the embodiments of the present invention, an integrated device for microfluid thermoregulation and a manufacturing process thereof are provided. The integrated device included a semiconductor material body having a surface; at least one buried channel extending in the semiconductor material body, arranged at a distance from the surface, and having a first and a second end; at least one port and a second port extending from the surface, respectively, as far as the first end and the second end of the buried channel, and being in fluid connection with the buried channel; and at least one heating element arranged on the semiconductor material body.
In accordance with another aspect of the foregoing embodiment of the invention, the heating element is arranged to be positioned over the at least one buried channel.
In accordance with another aspect of the invention, a temperature sensing element is arranged adjacent the at least one heating element, or where there are multiple heating elements, between pairs of adjacent heating elements. Ideally the temperature sensing element is configured to maintain the temperature of the heating element so as to maintain the temperature of fluid in the at least one buried channel at a predetermined temperature.
In practice, an integrated microreactor is provided that exploits the mechanical properties of semiconductor materials, and in particular of silicon. The microreactor can be manufactured using steps that are standard in microelectronics, and enables fluids to be contained and/or circulated in microchannels, if necessary mixed with appropriate reagents, as well as treated with heat, possibly repeated according to preset cycles, at precisely controlled temperature and duration.
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Kopp, Martin U. et al., “Chemical Amplification: Continous-Flow PCR on a Chip,” Science, vol. 280, pp. 1046-1048: May 15, 1998.
Barlocchi Gabriele
Mastromatteo Ubaldo
Villa Flavio
Jorgenson Lisa K.
Redding David A.
Seed IP Law Group PLLC
STMicroelectronics S.r.l.
Tarleton E. Russell
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