Device and method for detecting cellular processes by means of luminescence measurements

• US 7,767,443 B2
• Filed: 03/05/2003
• Issued: 08/03/2010
• Est. Priority Date: 03/27/2002
• Status: Expired due to Fees

• Current Assignee: Endress+Hauser Conducta Gesellschaft FUER Mess- und Regeltechnik mbH+Company KG
• Original Assignee: Micronas Gmbh (TDK Corporation)
• Inventors: Lehmann, Mirko, Klapproth, Holger
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): Doe; Shanta G
• Application Number:
  US10/509,040
• Publication Number:
  US 20050153387A1
• Time in Patent Office: 2,708 Days
• Field of Search: 435/288.7, 435/808, 435/40.5, 4352871-2873, 422/52
• US Class Current: 435/288.7
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability

Abstract

A device includes a carrier element with a surface prepared for direct or indirect coupling or receiving of cells, at least one optical detector to receive a luminescence signal, the detector being integrated into the carrier element below the prepared surface, a cover covering the prepared surface to form a cavity, the cover having an inlet opening and an outlet opening, and an excitation source connected to the inlet opening. The excitation source constitutes a reservoir for a chemical or biological excitation substance or medium that influences the metabolism of the cell, with metabolic processes being made visible by luminescence and detected by at the least one optical detector.

Claims

1. A device for detecting a cellular metabolic process associated with a cell by detecting a luminescence event in, at, or in the immediate vicinity of the cell, the device comprising:

a carrier element with a surface prepared for coupling of the cell thereto;

a detector for receiving a luminescence signal indicative of the luminescent event through the prepared surface, where the detector is integrated into the carrier element below the prepared surface;

a cover covering the prepared surface to form a cavity, the cover having an inlet and an outlet; and

a metabolically-influencing cell excitation reservoir connected to the inlet and containing a biological or chemical excitation medium that includes a luminophore, where the excitation medium influences the metabolism of the cell during excitation thereof by the medium, and where the luminophore reacts with a metabolic product of the cell during the excitation thereof to thereby provide the luminescence signal.

2. The device of claim 1, further comprising an optical filter located between the prepared surface and the optical detector.

3. The device of claim 1, where the carrier element is a semiconductor body.

4. The device of claim 1, where a plurality of optical detectors are integrated into the carrier element below the prepared surface.

5. The device of claim 1, where the optical detector comprises a photodiode.

6. The device of claim 1, further comprising an evaluation circuit connected to the detector.

7. The device of claim 1, further comprising an evaluation circuit integrated into the carrier element.

8. The device of claim 1, further comprising an evaluation circuit that controls the excitation reservoir to send the chemical or biological excitation medium to the inlet opening.

9. The device of claim 1, further comprising a valve disposed in an inlet line between the excitation reservoir and the inlet to control a supply of the excitation medium to the inlet.

10. The device of claim 1, where the prepared surface includes an adhesion matrix and/or a growth substrate for the cell coupled thereto.

11. The device of claim 10, where the growth substrate comprises gelatin.

12. The device of claim 1, where the prepared surface has a cell-immobilizing medium applied thereto.

13. The device of claim 12, where the cell-immobilizing medium comprises negatively charged polystyrene.

14. The device of claim 1, where the cell is immobilized at the prepared surface.

15. The device of claim 1, where a depression is created in at least a portion of the prepared surface.

16. A device for detecting a cellular metabolic process associated with a cell by detecting a luminescence event in, at, or in the immediate vicinity of the cell, the device comprising:

a semiconductive device with a surface prepared for coupling of the cell thereto;

a detector for receiving a luminescence signal indicative of the luminescent event through the prepared surface, where the detector is integrated into the semiconductive device below the cell;

a cover that covers the prepared surface to forth a cavity, the cover having an inlet and an outlet; and

a metabolically-influencing cell excitation reservoir that provides to the cavity via the inlet a biological or chemical excitation medium that includes a luminophore, where the excitation medium influences the metabolism of the cell during excitation thereof by the medium, and where the luminophore reacts with a metabolic product of the cell during the excitation thereof to provide luminescence detected by the detector.

17. The device of claim 16, further comprising an optical filter located between the prepared surface and the optical detector, and where a plurality of optical detectors are integrated into the semiconductive substrate below the prepared surface.

18. The device of claim 16, further comprising an evaluation circuit semiconductive that controls the excitation reservoir to send the chemical or biological excitation medium to the inlet opening.

19. The device of claim 16, where the prepared surface has a cell-immobilizing medium applied thereto.

20. A device for detecting a cellular metabolic process associated with a cell by detecting a luminescence event, the device comprising:

a semiconductive device with a surface prepared with a cell-immobilizing medium for coupling and immobilizing of the cell thereto;

a detector for receiving a luminescence signal indicative of the luminescent event through the prepared surface, where the detector is integrated into the semiconductive device below the cell and prepared surface;

a housing that in cooperation with the prepared surface forms a cavity having an inlet and an outlet; and

one of a metabolically-influencing cell excitation reservoir that provides to the cavity via the inlet a biological or chemical excitation medium that includes a luminophore, where the excitation medium influences the metabolism of the cell and the luminophore reacts with a metabolic product of the cell to provide luminescence detected by the detector.