Chemistry: electrical and wave energy – Apparatus – Electrolytic
Patent
1996-10-08
1998-12-08
Bell, Bruce F.
Chemistry: electrical and wave energy
Apparatus
Electrolytic
204409, 422 8202, 422 8203, G01N 2726
Patent
active
058463925
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/DE95/00339 filed on Mar. 10, 1995.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a miniaturized circulatory measuring chamber with integrated chemo- and biosensor elements, to a method for its production and to its utilization.
2. Discussion of Background
It is known that chemo- and biosensor elements are integrated in circulatory systems. The best known example is flow injection analysis (FIA) (e.g.: G. Schwedt: Taschenatlas der Analytik, Georg Thieme Verlag Stuttgart, 1992).
Similar devices are used as microdialysis systems for determining the glucose concentration in human tissue (e.g.: F. J. Schmidt et al.: Calibration of a wearable glucose sensor, The International Journal of Artificial Organs, Vol. 15, No. 1, 1992, Pages 055-061).
It is likewise known that chemo- and biosensor elements which operate with polymeric membranes and gel layers for substance recognition, can be produced in silicon technology according to the containment principle (DE 41 15 414 A1). In this respect the polymeric membranes and gel layers are not produced on the surface of silicon chips but in the interior of the chip. Compared to planar structures, this has considerable advantages as regards simplicity of manufacture and long-term stability.
These sensors can also be incorporated in silicon technology in prefabricated circulatory measuring cells.
A disadvantage of the described prior art is that until now no sensors have been described which operate on the containment principle and are incorporated in common with a circulatory measurement chamber on a chip.
SUMMARY OF THE INVENTION
Therefore the object underlying the invention is to integrate chemo- and biosensor elements according to the containment principle in common with a circulatory measurement chamber on a chip. The measuring chamber with the integrated sensors is to be produceable preferably in silicon technology, but also in other technology. In addition the sensors are to be capable of integration with the circulatory measuring chamber, e.g. in common with pumps, reaction paths, valves, etc. in microsystems.
Thus it is proposed according to the invention to dispose a duct-shaped cavity in a chip in such a way that it is contact with the smaller opening of the containment. Then the substance-recognition material inserted in the containment forms in the area of the small containment opening the active sensor surface, to which the liquid measuring medium is brought to the duct, and thus can come into contact with the sensor surface.
Preferably, in the circulatory measuring chamber, a Si substrate is used as a carrier. The invention however includes all other appropriate materials. The substance-recognition membrane materials usable for the sensor arrangement and the design of the containment and of the preferred Si carrier itself are known from DE 41 15 414. Therefore reference is made expressly to the disclosed content of this document.
There are preferably used as substance-recognition membrane materials those which, due to their flow behaviour through one of the openings, preferably the large opening, can be brought in on the front-side surface into the containment. Filling may for example be effected by means of an automatic dispenser device according to the ink jet principle, or also according to the method described in DE 41 15 414.
All the immobilizing materials previously known from prior art can be used for potentiometric and in particular amperometric biosensors. Examples of these are gelatin, collagen, alginate, agar, cellulose. triacetate, silicon rubber, polyvinyl alcohol, polyurethane, HEMA and all other known materials. Photolinkable materials can be cross-linked by UV radiation after filling through the upper or lower containment opening.
The active substance-recognition components such as enzymes or antibodies are immobilised in these materials. This may be effected according to known methods, such for example as F. Scheller, F. Schubert: Biosensors, Birkhauser Verlag, Berlin, 198
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Shuiji Shoji et al., "Micro Flow Cell for Blood Gas Analysis Realizing Very Small Sample Volume", Sensors and Actuators B, vol. B08, No. 2, pp. 205-208, XP 000286957, May 1, 1992.
Van Der Schoot et al., "An ISFET-Based microlitre titrator: Integration of a chemical sensor-actuator system", Third International Conference on Solid-State Sensors and Actuators (Transducers '85), Philadelphia, PA USA, 11-14 Jun. 1985, vol. 8, No. 1, ISSN 0250-6874, Sensors and Actuators, Sep., 1985, Switzerland, pp. 11-22.
Van Der Shoot et al., "Modular setup for a miniaturized chemical analysis system", Eurosensors VI, San Sebastian, Spain, 5-7, Oct. 1992, vol. B15, No. 1-3, ISSN 0925-4005, Sensors and Actuators B (Chemical), Aug. 1993, Switzerland, pp. 211-213.
Schwedt, Taschentlas de Analytik (1992), pp. IV and V, no month available.
Schmidt et al., "Calibration of a Wearable Glucose Sensor," The International Journal of Artificial Organs, 15, pp. 55-61 (1992), no month available.
Scheller et al., Biosensoren (1989), pp. V-VII, no month available.
Schwedt, Taschentlas de Analytik (1992), pp. IV, V, and 190-195.
Scheller et al., Biosensoren (1989), pp. V and 48-67.
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