Device for performing timed assay by electrical resistance change

• US 5,554,531 A
• Filed: 08/07/1995
• Issued: 09/10/1996
• Est. Priority Date: 01/13/1993
• Status: Expired due to Term

• Current Assignee: Beckman Coulter Incorporated (Danaher Corporation)
• Original Assignee: Avocet Medical, Inc. (Danaher Corporation)
• Inventors: Zweig, Stephen E.
• Primary Examiner(s): Kepplinger, Esther
• Assistant Examiner(s): Cano, Milton I.
• Application Number:
  US08/512,134
• Time in Patent Office: 400 Days
• Field of Search: 435/4, 435/817, 435/286.1, 435/287.1, 435/287.7, 435/287.9, 435/288.7, 436/46, 436/805, 436/806, 436/808, 422/56, 204/513.12
• US Class Current: 435/286.1
• CPC Class Codes: C12Q 1/00 Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: C12Q 1/56 involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
• CPC Class Codes: G01N 27/041 of a solid body
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10T 436/112499 with sample on test slide

Abstract

Assays for liquid analytes are performed on a bibulous matrix containing dried reagents which produce a visibly detectable reaction product. Application of liquid sample to the bibulous matrix is detected by measuring a drop in resistance across the matrix. A preferred test article for performing the method includes the matrix and a pair of spaced-apart electrodes in electrical contact with a reaction zone on the matrix. The test article is used in combination with a detection unit having means for probing the electrodes to determine when electrical resistance in the matrix has decreased. The assay methods and apparatus are particularly useful for performing enzyme assays where signal developed as a function of time is critical.

Claims

1. A detection unit comprising:

a support stage for receiving a test article, the test article having spaced-apart electrodes in electrical contact with a reaction zone, wherein the reaction zone on the test article is disposed at a viewing location;

a heater attached to the support stage for heating the test article in the region of the reaction zone;

means attached to the support stage for detecting electrical resistance across the test article;

means attached to the support stage for optically viewing the reaction zone when disposed at the viewing location;

means in communication with the electrical resistance detecting means for initiating a timing cycle when the electrical resistance detecting means detects a lowering of electrical resistance across the test article upon application of a fluid sample having an amount of analyte therein to the test article;

means for actuating the optical viewing means and the electrical resistance detecting means at one or more times during the timing cycle to measure one or more optically detectable signals and electrical resistance values at known times during the timing cycle; and

means for correlating the measured signals and values from the optical viewing means and the electrical resistance detecting means with the known times at which the signals and values are measured so that the amount of analyte initially present in the sample may be determined.

2. A detection unit as in claim 1, further comprising an input/output interface for connecting at least one of the heater, electrical resistance detection means, and the optical viewing means to a digital controller.

3. A detection unit as in claim 1, wherein the heater comprises an upper heated surface and a lower heated surface, which surfaces are disposed to contact a top and a bottom side of the test article around the reaction zone.

4. A detection unit as in claim 1, wherein the electrical resistance detecting means includes a pair of spaced-apart plates which contact the test article on opposite sides of the reaction zone when the test article is in place in the support stage.

5. A detection unit as in claim 1, wherein the optically viewing means comprises a light source which directs light at the reaction zone and a light detector which detects light from the reaction zone.

6. A detection unit as in claim 5, wherein the light source emits light at a wavelength selected to induce fluorescence in a particular reaction product and the light detector detects light at the fluorescent wavelength.

7. A detection unit for use in combination with a test article comprising:

(a) a bibulous matrix;

(b) one or more dried reagents which are present within the matrix and which, when wetted by a liquid sample, initiate an optically detectable chemical reaction with an analyte present in the sample;

(c) a pair of spaced-apart metal strips proximate a sample target location of the matrix, wherein the metal strips are disposed so that application of the liquid sample to the target location will lower electrical resistance between the electrode

wherein the detection unit comprises;

a support stage for receiving the test article, where a reaction zone on the test article is disposed at a viewing location;

a heater attached to the support stage for heating the test article in the region of the reaction zone;

means attached to the support stage for detecting electrical resistance across the test article;

means attached to the support stage for optically viewing the reaction zone when disposed at the viewing location;

means in communication with the electrical resistance means for initiating a timing cycle when the electrical resistance detecting means detects a lowering of electrical resistance between the electrodes upon application the sample to the test article;

means for actuating the optical viewing means and the electrical resistance detecting means at one or more times during the timing cycle to measure one or more optically detectable signals and electrical resistance values at known times during the timing cycle; and

means for correlating the measured signals and value from the optical viewing means and the electrical resistance detecting means with the known times at which the signals and values are measured so that the amount of analyte initially present in the sample may be determined.

8. A detection unit as in claim 7, further comprising an input/output interface for connecting at least one of the heater, electrical resistance detection means, and the optical viewing means to a digital controller.

9. A detection unit as in claim 7, wherein the heater comprises a pair of metal plates and means for heating said plates, wherein said plates contact the metal strips on the test article and said metal strips conduct heat to the reaction zone.

10. A detection unit as in claim 7, the electrical resistance detecting means includes the same metal plates which comprise the heater, whereby electrical resistance is measured across the gap between the metal strips on the test article.

11. A detection unit as in claim 7, wherein the optically viewing means comprises a light source which directs light at the reaction zone and a light detector which detects light from the reaction zone.

12. A detection unit as in claim 11, wherein the light source emits light at a wavelength selected to induce fluorescence in a particular reaction product and the light detector detects light at the fluorescent wavelength.