Carrier matrix for integrated microanalysis systems, method...

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Reexamination Certificate

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C428S172000, C428S188000, C428S318600, C216S056000, C216S079000, C073S019020, C073S023350, C073S061520

Reexamination Certificate

active

06187446

ABSTRACT:

The present invention relates to a carrier matrix for integrated microanalysis systems, a method for the production thereof as well as the use of the same.
In the field of micromechanical technology and sensor construction, a rapid development of miniaturised chemical analysis systems is at present taking place, the aim being to totally integrate an analysis system on microscale. By “total integration” is here meant that pumps, flow ducts, flow valves, physical and chemical sensors, detectors etc. are produced on microscale on an underlying structure or as a composite unit consisting of several microcomponents made of different materials.
Several of the part components required to produce Micro Total Analysis Systems (&mgr;TAS) are easily available on today's market. Silicon-integrated micropumps for liquids can be obtained from a number of manufacturers (see, for instance, Büstgens B., Bacher W., Ehnes R., Maas D., Ruprecht R., Schomburg W. K., Keydel L., Micro-membrane Pump Manufactured by Molding, Proceedings of the 4th International Conference on New Actuators, Actuator '94, Bremen, 1994, 86-90, and van der Schoot B. H., Jeanneret S., van den Berg A. and de Rooij N. F., Micro-systems for Flow Injection Analysis, Analytical Methods and Instrumentation, 1993, 1 No. 1 (1993) 38-42), as is the case with silicon-integrated microvalves (see, for instance, Shoji S., van der Schoot B., de Rooij N. and Esashi M., Smallest Dead Volume Microvalves for Integrated Chemical Analyzing Systems, Proceedings, Transducers 1991, San Fransisco, USA, 1991, 1052-1055, and Fahrenberg J., Maas D., Menz W., Schomburg W. K., Active Microvalve System Manufactured by the LIGA Process, Proceedings of the 4th International Conference on New Actuators, Actuator '94, Bremen, 1994, 71-74).
The chemical sensor element of the microanalysis systems is a key component and still is the factor checking the development of these systems.
The most common parameters studied in integrated analysis systems are the pH value and the dissolved gases, such as O
2
and CO
2
(Arquint P., Integrated Blood Gas Sensor for pO
2
, pCO
2
and pH based on the Silicon Technology, PhD Thesis, 1994). If more complex compounds are to be studied, an enzymatic detection has to be included in, or associated with, the sensors in order to result in selective detection, which in turn increases the complexity of the systems.
Enzyme reactors (ER) are frequently used as detector units for complex analytes in the analysis in biological systems, one reason being their prolonged stability due to the excess of enzyme present. The sensor connected to the reactor usually measures basic parameters. Examples of such sensors are the Clark electrode and pH electrodes. The sensor may also measure any other parameter that the enzyme-catalysed reaction gives rise to.
As mentioned in the foregoing, the chemical sensor element is a factor checking the development of microanalysis systems. To enable a rapid and reproducible analysis in a flow, the carrier matrix for the chemical sensor has to have a high ratio of surface area to volume.
Silicon is the material most commonly used in micro-structure technology. Also, silicon may advantageously be used in integrated enzyme reactors, since there exist standard methods for immobilising chemical reagents, for instance enzymes, by coupling to silicon-dioxide gels.
By integrating the chemical sensor element in microanalysis systems, large amounts of reagent in the reactor structures may be expected to prolong the life span of the sensor, whereas microbiosensors based on layered reagents with protecting membranes often have limited life spans owing to the gradual loss of chemical activity, for instance enzyme activity.
Previous efforts to achieve sufficient enzyme activity in integrated microreactors for measurement applications have been based on fairly simple flow cells. As carrier matrix in silicon-integrated enzyme reactors, use has been made of anisotropically-etched reactor structures, which have been designed as one long V-shaped channel (Murakami Y., Toshifumi T., Yokoyama K., Tamiya E., Karube I. and Suda M., Integration of Enzyme-Immobilized Column with Electrochemical Flow Cell Using Micromachining Techniques for a Glucose Detection System, Anal. Chem., 65, 1993, 2731-2735), several parallel V-shaped channels (Bin Xie, Bengt Danielsson, Petronella Norberg, Fredrik Winquist and Ingemar Lundström, Development of a Thermal Micro-Biosensor Fabricated on a Silicon Chip., Sensors and Actuators B, 6, 1992, 127-130) or several parallel, deep and vertical channels (Laurell T., Rosengren L. and Drott J., Silicon Wafer Integrated Enzyme Reactors., Biosensors & Bioelectronics, 1995, in press). The latter method involving the etching of deep vertical grooves in <110>-oriented silicon increases the available surface on the silicon wafer by a factor of at least 5 in relation to a smooth silicon surface.
As a result of the rapid development towards smaller and smaller components in the integrated microanalysis systems, there is today a considerable demand for a further increase in the ratio of surface area to volume in carrier matrices intended for use in such integrated microanalysis systems. This would enable smaller systems, which at the same time would remain active for a long period of time owing to a high capacity of chemical reagent.
Porous silicon is a well-known material which has long been used as electrically insulating material in semi-conductor technology or as luminescent material in optronics research. Porous silicon has also been employed in micromechanics as sacrificial material in etching processes in micromechanical processing.
In analytical chromatography, silicon-dioxide-based microporous powder matrices (for instance controlled porous glass, CPG) are commonly used as carrier material for separation columns. The carrier material (the matrix) may either have a chemically-activated surface for the separation, or the microporous structure may in itself constitute a molecular separating medium.
Microporous pulverulent silicon dioxide is also to a large extent used as carrier matrix in enzyme reactors and systems for various sorts of chromatography, the surface-enlarging capacity of the matrix being used for connecting a large amount of an active chemical component to a fairly small carrier (Unger, Klaus K., 1979, Porous Silica, its Properties and Use as Support in Column Liquid Chromatography, Journal of Chromatography Library—Volume 16, ISBNO-44-41683-8, Elsevier Scientific Publishing Company, the Netherlands).
The size of the micropores in such microporous pulverulent matrices is of decisive importance for the properties of the carrier matrix. By checking the size of the micropores of the matrix, one obtains a defined carrier having well-characterised properties as regards capacity, separating capacity, surface enlargement, catalytic action, and so forth.
It has now been found that porous silicon is an excellent material for use as carrier matrix for integrated microanalysis systems where a high ratio of surface area to volume is aimed at.
One object of this invention is, therefore, to provide a silicon-based carrier matrix having a high ratio of surface area to volume for integrated microanalysis systems, said carrier matrix being characterised in that it comprises at least one layer of microporous silicon on a body of monocrystalline silicon.
Another object of the invention is to provide a method for producing a silicon-based carrier matrix having a high ratio of surface area to volume for integrated microanalysis systems, said method being characterised by electrochemical etching of a body of monocrystalline silicon for forming at least one layer of microporous silicon on said body.
A further object of the invention is to enable the use of said carrier matrix for chemical sensors in integrated microanalysis systems, in particular biochemical sensors, and especially as carrier matrix in enzyme reactors.
Yet other objects of the invention bear upon the use of said carrier matrix i

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