Device and method for detecting analytes

• US 6,548,311 B1
• Filed: 06/15/2000
• Issued: 04/15/2003
• Est. Priority Date: 11/21/1997
• Status: Expired due to Fees

• Current Assignee: Meinhard Knoll
• Original Assignee: Meinhard Knoll
• Inventors: Knoll, Meinhard
• Primary Examiner(s): Le, Long V.
• Assistant Examiner(s): COUNTS, GARY W
• Application Number:
  US09/554,845
• Time in Patent Office: 1,034 Days
• Field of Search: 422/82.01, 422/82.02, 422/82.03, 422/98, 422/101, 422/186.01, 422/186.03, 422/186.04, 422/186.13, 422/58, 204/450, 204/516, 204/518, 204/400, 204/403, 204/411, 204/415, 435/7.1, 435/285.2, 436/518, 436/524, 436/525
• US Class Current: 436/524
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00614 Delimitation of the attachment areas
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/587 Nanoparticles

Abstract

The invention relates to a method for detecting analytes and to a device for carrying out the method, for use for analysis or diagnosis in the fields of chemistry, biochemistry, molecular genetics, food chemistry, biotechnology, the environment and medicine. Marker particles (5) with different electrical properties or a different relative permeability to those of the measuring solution (3) surrounding them are used to detect the analytes (8). The marker particles (5) either bond specifically to the analytes (8) or to a base (2) in competition with the analyte. The analytes (8) are detected by the changes in an electrical field or an electrical current generated by electrodes (2) or in an electrical voltage applied to an electrode or in a magnetic field, said changes being caused by marker particles which have bonded with the analytes or by marker particles which have instead bonded to the base in an electrical field.

Claims

1. A process for detection of analytes in a measuring solution comprising the steps of:

providing marker particles for binding specifically to the analytes, the particles having electrical properties which are different from the measuring solution;

arranging an electrode so that an electric field and an electric current are produced in the solution; and

determining changes in the electric current caused by the marker particles, wherein the electrode arrangement produces an inhomogeneous electric field and the marker particles are electrically insulating.

2. Process according to claim 1, wherein at least two electrodes are used as the electrode arrangement, wherein at least one of the electrodes is a microelectrode and the surface area of the at least one microelectrode is approximately equal to the cross-sectional surface area of one of the marker particles, wherein the marker particles have a diameter less than about 10 μ

m.

3. Process according to claim 1, wherein the different electrical properties is dielectric constant.

4. Process according to claim 1, wherein the analytes specifically bound to marker particles bind in turn specifically to a substrate.

5. Process according to claim 1, wherein free analytes with marker particles or with marker particles to which the analytes are bound, compete around binding sites specific to the free analytes on a substrate which is the electrode used for producing an electric field.

6. Process according to claim 1, comprising providing a second electrode, wherein the measuring solution with marker particles which bind specifically to the analytes flows between the two electrodes, by means of which the electric field is produced.

7. Process according to claim 1, comprising producing a magnetic field which exerts a force on the marker particles before determining the change in electric current due to the marker particles.

8. Process according to claim 7, wherein an alternating voltage and/or a magnetic field alternating its direction is produced in the measuring solution.

9. Process according to claim 7, wherein the electric and/or magnetic field is designed such that it exerts a force in the direction of a substrate provided with binding sites for the marker particles, on the marker particles towards and/or away from the substrate.

10. Process according to claim 1, wherein at least two electrodes are used as the electrode arrangement, wherein a diaphragm with an opening for the passage of electric field is arranged in front of at least one of the electrodes, and the marker particles are bound on or in the vicinity of a surface of the diaphragm.

11. A device for determination of analytes in a measuring solution, comprising:

marker particles which specifically bind to the analytes and have electrical properties which are different from the measuring solution;

an electrode for producing an electric field and an electric current in the measuring solution; and

a measuring device for recording the electric current, wherein an inhomogeneous electric field is produced by arrangement of the electrode and the marker particles are electrically insulating.

12. Device according to claim 11, comprising a second electrode for producing the electric field and the electric current resulting therefrom, wherein at least one of the electrodes is a microelectrode and the surface area of the at least one microelectrode is approximately equal to the cross-sectional surface area of one of the marker particles, wherein the marker particles have a diameter less than about 10 μ

m.

13. Device according to claim 11, comprising a support on which a substrate having specific binding sites of the analytes is arranged and wherein the marker particles have specific binding sites for the analytes or the substrate, wherein marker particles are arranged on the support or a covering.

14. Device according to claim 13, wherein the substrate is a microelectrode.

15. Device according to claim 11, comprising a second electrode for producing the electric field and the electric current resulting therefrom and wherein the first and second electrodes are components of a through-flow cell, wherein an opening for the passage of the measuring solution exists between the two electrodes.

16. Device according to claim 11, comprising a covering, which covering is sealed externally by a membrane containing a marker particle which is permeable to the analytes and to the measuring solution.

17. Device according to claim 11, wherein the inhomogeneous electric field has a magnetic element of reversible polarity.

18. Device according to claim 14, comprising a diaphragm which is connected to the measuring solution and which has one small opening and which serves as binding element for the marker particles, the diaphragm is arranged in front of the electrode for producing the electric field and the current resulting therefrom.

19. Device according to claim 18, wherein the space between the diaphragm and the electrode is filled with an electrolyte which is in contact with the measuring solution.

20. Device according to claim 19, comprising a flat support which supports the electrode, and a spacer element, wherein the spacer element is provided with at least one perforation to receive the electrolyte, and is connected to the flat support, and the perforation is covered by a covering serving as the diaphragm, in which at least one diaphragm opening is provided.