Chemistry: electrical and wave energy – Apparatus – Electrophoretic or electro-osmotic apparatus
Reexamination Certificate
2000-06-22
2004-11-09
Bell, Mark L. (Department: 1755)
Chemistry: electrical and wave energy
Apparatus
Electrophoretic or electro-osmotic apparatus
Reexamination Certificate
active
06814846
ABSTRACT:
In general, the present invention concerns microchip laboratory systems that carry out chemical and chemical-physical, physical, biochemical and/or biological processes, especially for analyzing or synthesizing substances on a substrate with a microfluid structure electrically, electronically, electromagnetically, mechanically or controlled in a similar manner. In particular, the invention concerns a device to operate such a laboratory microchip where a supply unit provides the potential necessary for moving the substance along the microfluid structure, and supply lines are provided to transmit the potential to the microchip.
The continuous development in this area is best illustrated by a comparison with corresponding developments in the field of microelectronics. In the field of chemical analysis as well, there is a substantial need (not least in the area of dinical diagnosis) to integrate existing stationary laboratory devices into portable systems and correspondingly miniaturize them. An overview of the most recent developments in this field of microchip technology is found in a collection of relevant professional publications published by Kluwer Academic Publishers (Holland, 1995) by A. van den Berg and P. Bergveld with the title,
Micro Total Analysis Systems
. The takeoff point for these developments was the established method of capillary electrophoresis; efforts had been made in the past to implement this method on a planar glass microstructure.
The basic required components for such a microchip system are shown in FIG.
1
. They are basically divided into systems that have a material flow
1
, and systems that represent an information flow
2
that occurs during an experiment. In the area of the material flow
1
, means are necessary to supply
3
and transport
4
substances on the chip, and means are required to treat e.g. pretreat
5
the investigated substances. Furthermore, sensors
6
are required to detect the results of an experiment. The arising flow of information is essentially for controlling the transport of substance on the chip using e.g. control electronics
7
. In addition, a flow of information occurs while processing in the signals
8
of the detected measured results, and especially while evaluating them
9
.
Another motivation for miniaturization in the field of chemical analysis is to minimize the transport paths of the substances, especially between the substance supply and the respective detection point of a chemical reaction (see FIG.
2
). In the fields of liquid chromatography and electrophoresis, it is understood that substances can be separated more quickly in such systems (test results are therefore available more quickly), and individual components can be separated with a higher resolution than is possible with conventional systems. In addition, the amount of substances (especially reagents) that micro-miniaturized laboratory systems use is greatly reduced, and the substance components are mixed much more efficiently.
The above-mentioned background is discussed in detail in an article by Andreas Manz et al. on page 5 ff. of the cited collection. The article also states that the authors have already manufactured a microchip consisting of a layer system of individual substrates that permits a three-dimensional transport of substances.
In contrast to creating a micro-laboratory system on a glass or plastic substrate, systems are mentioned in above-cited article that are based on a silicon-based microstructure. On this basis, apparently already-integrated enzyme reactors (e.g. for a glucose test), micro-reactors for immunoassays, and miniaturized reaction vessels for DNA quick assays have been created using the method of polymerase chain reaction.
A microchip laboratory system of the initially-cited type is also discussed in U.S. Pat. No. 5,858,195 where the relevant substances are moved by a system of connected channels integrated in a microchip. The movement of these substances in these channels can be precisely controlled using electrical fields that are applied along the transport channels. Given the highly-precise control of substance movement that this allows as well as the very precise dosing of the moved substances, the substances can be precisely mixed and separated, and/or chemical or physical-chemical reactions can be induced with the desired stochiometry. In this laboratory system, the integrated channels also have numerous substance reservoirs that contain the necessary substances for chemical analysis or synthesis. These substances are also moved out of the reservoirs along the transport channels by means of electrical differences in potential. The substances moved along the transport channels therefore contact different chemical or physical environments that allow the necessary chemical or chemical-physical reactions to take place between the respective substances. In particular, the prior-art substrate has one or more transport channel intersections at which these substances are mixed. By simultaneously using different electrical potentials at different substance reservoirs, the volumetric flows of the various substances through one or more intersections can be selectively controlled; a precise stochiometric template is therefore possible based just on the applied electrical potentials.
By means of the cited technology, complete chemical or biochemical experiments can be carried out using microchips tailored to the respective application. In handling microchips in measurement setups for experiments, the chips of the measuring system must be easily exchangeable, and the measuring setup must be easily adaptable to different microchip layouts. On the one hand, this adaptability is related to the respective arrangement of the substance reservoirs, the high voltage necessary for moving the substances on the chips, and the corresponding application of the voltage to the microchips. For such a measuring setup, you therefore need to run electrodes to the contact surfaces correspondingly provided on the microchip, and you need devices to supply the substances to the cited reservoirs. In particular, the microchips dimensions can only range from a few millimeters to approximately 1centimeter which makes the chips relatively difficult to handle.
A relevant arrangement for handling the microchip described at the onset is described in a prior publication, intentional patent application WO 9 8/05424. This has a base unit with a seat to receive an adapter that in turn receives a removable microchip. Corresponding counterelectrodes are provided on the adapter for the electrodes required to move the substances on the microchip. An electrical contact between the electrodes and the corresponding counterelectrodes is automatically created when the microchip is introduced into the adapter. Furthermore, the adapter itself contains devices that are required for evaluating the experimental measuring results such as a laser source and an associated photocell. In particular, the advantage of the adapter is that the base unit can work with numerous different microchips without having to adapt or even exchange the base unit. The disadvantage of this prior-art system is that the adapter is relatively involved since it e.g. contains the cited optical measuring devices. In particular, there are no devices in this arrangement for supplying the investigated substances and/or the reagents required for the experiment.
Moving substances by high voltage is, however only one variation among other conceivable solutions. For example, the difference in potential necessary to move the substances can also be created by applying a pressurized medium, preferably an inert gas, or another suitable gas medium or a liquid. Of course, when the microchip is subjected to a pressurized medium via a supply line, suitable seals must be supplied at the connecting site between the supply line and the microchip to prevent the pressurized medium from exiting at this connecting site. Alternatively, the movement of the substances can be generated by using a suitable temperature grid w
Bell Mark L.
Brown Jennine
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