Measuring device using biological cells or chemical biologically active substances contained in an analyte

• US 6,280,586 B1
• Filed: 10/06/1997
• Issued: 08/28/2001
• Est. Priority Date: 04/04/1995
• Status: Expired due to Fees

• Current Assignee: Micronas Gmbh (TDK Corporation)
• Original Assignee: Micronas Gmbh (TDK Corporation)
• Inventors: Ehret, Ralf, Sieben, Ulrich, Baumann, Werner, Wolf, Bernhard
• Primary Examiner(s): Warden, Sr., Robert J.
• Assistant Examiner(s): Olsen, Kaj K.
• Application Number:
  US08/930,657
• Time in Patent Office: 1,422 Days
• Field of Search: 204/403, 204/406, 257/253, 435/817
• US Class Current: 257/253
• CPC Class Codes: G01N 27/3276 being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A measuring device (1) for measuring or investigating physiological parameters using biological cells or chemical and biologically active substances contained in an analyte (2). The measuring device comprises a sensor (4) with an electronic measurement structure (6) located on a substrate (5). Function-specific receptor cells and/or target cells (7) form part of the sensor (4) and are in direct contact with the measurement structure (6). For measurement, the medium under investigation can be brought into contact with the target cells or receptor cells (7). The measuring device (1) is especially compact in its design and facilitates largely feedback-free investigation of biological or chemical components contained in the analyte.

Claims

1. A measuring device (1) for measuring the presence of at least one component (3) contained in an analyte (2), said device comprising a plurality of sensors including at least one reference sensor and at least one electrical sensor (4) each having a measurement output connectable to an evaluating device, wherein the electrical sensor (4) and the reference sensor each have an electrical measurement structure (6) located on a common substrate (5), the measurement structure (6) of the electrical sensor is connected to at least one function-specific plant or animal receptor cell (7) serving as a biological sensor, wherein each electrical sensor measures the analyte (2) under investigation by measuring a morphologic or physiologic property of the receptor cell (7), wherein provided between the receptor cell and the measurement structure (6) is a structured, biocompatible micro porous interlayer (13) to which the receptor cell at least partially adheres, the measurement structure of the reference sensor being free of connections to function-specific receptor cells (7), the reference sensor and the at least one electrical sensor being arranged on the common substrate (5) to form a sensor array (22), whereby a change of the property is indicative of the presence of the component in the analyte.

2. A measuring device as claimed in claim 1, wherein the measurement outputs of the sensors (4) arranged on a common substrate (5) are connected to a control and evaluating device that is integrated on the common substrate (5).

3. A measuring device as claimed in claim 2, wherein on the substrate (5) with the sensor array (22) are a multiplexer (23), an AD/DA converter (24) with sensor control, a microprocessor (26) and an IO unit (25) as a control and evaluating device.

4. A measuring device as claimed in claim 1, wherein at least one stimulating electrode (19) for the receptor cell is arranged on the substrate (5) within or adjacent to a measurement area of a corresponding measurement structure (6).

5. A measuring device as claimed in claim 1, wherein the substrate (5) is a semiconductor substrate and wherein the measurement structure is provided in the form of at least one ISFET (11) whose gate (12) is adjacent to the interlayer (13) opposite from the receptor cell (7).

6. A measuring device as claimed in claim 1, wherein the measurement structure (6) is provided in the form of at least one interdigital capacitor (9) exhibiting electrodes (10) that are interleaved in pairs.

7. A measuring device as claimed in claim 6, wherein a plurality of interdigital capacitors (9) varying in size are provided.

8. A measuring device as claimed in claim 6, wherein the plurality of sensors that are reactive to at least one component that the analyte is being investigated for is provided in at least one insulated interspace of the electrodes (10) of the interdigital capacitor (9).

9. A measuring device as claimed in claim 6, wherein light guides are provided between the electrodes (10) of the interdigital capacitor (9) and that light detectors for the reception and detection of the light passing through the respective light guide are arranged in the substrate (5).

10. A measuring device as claimed in claim 1, wherein CCD sensors, in particular in the form of a CCD line or CCD array, are integrated in the substrate (5).

11. A measuring device as claimed in claim 1, wherein the at least one reference sensor (20) comprises a field effect transistor disposed on the substrate (5) outside a substrate area designated for the measurement.

12. A measuring device as claimed in claim 1, wherein at least one temperature measuring diode is arranged on the substrate (5) supporting the measurement structure (6).

13. A measuring device as claimed in claim 1, wherein the receptor cells (7) are arranged in a gel structure (15) that is permeable to the specific component being tested for and that provides a nutritional reservoir for the receptor cell (7).

14. A measuring device as claimed in claim 1, wherein the electrical measurement structure (6) is part of a wall (16) of a receptacle (17) for the analyte.

15. A measuring device as claimed in claim 14, wherein the measurement structure (6) is situated on the bottom of the receptacle (17) and that a plurality of side walls are formed by an encapsulation bounding a measurement area of the measurement structure (6).

16. A measuring device as claimed in any one of claims 1 to 19, wherein a plurality of measurement structures (6) are arranged side by side.

17. A measuring device as claimed in claim 1, wherein the electrical contact points and/or the structured biocompatible interlayers (13) of at least two measurement structures (6) have different electrical properties.