Detection method

• US 6,818,886 B2
• Filed: 02/07/2003
• Issued: 11/16/2004
• Est. Priority Date: 08/09/2000
• Status: Active Grant

• Current Assignee: Artificial Sensing Instruments ASI AG
• Original Assignee: Artificial Sensing Instruments ASI AG
• Inventors: Tiefenthaler, Kurt
• Primary Examiner(s): Lee, John R.
• Assistant Examiner(s): Gill, Erin-Michael
• Application Number:
  US10/344,186
• Publication Number:
  US 20030168587A1
• Time in Patent Office: 648 Days
• Field of Search: 250/282, 356/128
• US Class Current: 250/282
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: G01N 21/7746 the waveguide coupled to a cavity resonator
• CPC Class Codes: H01J 49/164 Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI] sample holders H01J49/0418

Abstract

A method for detecting a substance or substances in a sample or in a matrix of samples combining detection methods that are, on the one hand, based on direct detection with integrated optical (bio)chemo-sensitive waveguide grating structures and, on the other hand, based on a mass-spectrometric detection effected by way of a desorption process. The method permits an increase in detection security and/or detection sensitivity.

Claims

1. A method for detecting a substance or substances in a sample or in a matrix of samples, comprising the steps of:

(a) separating the substance or substances to be detected from the sample or matrix of samples with one of an integrated optical (bio)chemo-sensitive sensor-chip plate, of an integrated optical (bio)chemo-sensitive micro-array and of an integrated optical (bio)chemo-sensitive lab-on-chip, wherein each of said integrated optical (bio)chemo-sensitive sensor-chip plate, of said integrated optical (bio)chemo-sensitive micro-array and of said integrated optical (bio)chemo-sensitive lab-on-chip comprises at least one (bio)chemo-sensitive waveguide grating structure unit or (bio)chemo-sensitive sensor location;

(b) detecting during or after the separation the substance or the substances with the help of a light wave, said light wave having an evanescent field and being at least partly guided in a waveguide structure;

(c) detecting the substance or the substances or substance parts on selected (biochemo-sensitive waveguide grating structure units or on selected (bio)chemo-sensitive sensor locations by desorption and ionization of the substance or the substances or the substance parts with the help of a mass spectrometer.

2. The method according to claim 1, wherein a (bio)chemo-sensitive layer at least partly covers the waveguide grating structure unit or the sensor location of a waveguide grating.

3. The method according to claim 1, wherein a (bio)chemo-sensitive layer covers a diffracting part of the waveguide grating structure unit.

4. The method according to claim 1, wherein a (bio)chemo-sensitive layer covers a non-diffracting part of the waveguide grating structure unit.

5. The method according to claim 1, wherein at least one of a waveguide grating and the waveguide grating structure unit contains a uni-diffractive waveguide grating.

6. The method according to claim 1, wherein at least one of a waveguide grating and the waveguide grating structure unit contains a multi-diffractive waveguide grating.

7. The method according to claim 1, wherein the waveguide grating structure unit consists of two waveguide gratings lying next to one another, both waveguide gratings belong to the same waveguide grating structure unit and the non-diffracting distance between the two waveguide gratings is part of the waveguide grating structure unit.

8. The method according to claim 1, wherein the waveguide grating structure unit consists of two part-waveguide grating structures lying next to one another and the non-diffracting distance between the two part-waveguide grating structures is part of the waveguide grating structure.

9. The method according to claim 1, wherein at least one of a waveguide grating and the waveguide grating structure contains a one-dimensional or two-dimensional array of sensor locations.

10. The method according to claim 1, wherein the sensor chip plate is a micro-plate.

11. The method according to claim 1, wherein at least one of the sensor chip plate, a micro-array, and the lab-on-chip comprises a glass substrate.

12. The method according to claim 1, wherein at least one of the sensor chip plate, a micro-array, and the lab-on-chip comprises a polymer substrate.

13. The method according to claim 1, wherein at least one of the sensor chip plate, a micro-array, and the lab-on-chip comprises a removable sample accommodating device or sample holder device.

14. The method according to claim 1, wherein at least one of the sensor chip plate, a micro-array, and the lab-on-chip comprises a sample accommodating device or a sample holding device of glass.

15. The method according to claim 1, wherein at least one of the sensor chip plate, a micro-array, and the lab-on-chip comprises a sample accommodating device or a sample holder device of polymer.

16. The method according to claim 1, wherein desorption and ionisation is effected by shooting with a pulsed laser.

17. The method according to claim 1, wherein a (bio)chemo-sensitive waveguide grating structure unit with accumulated analyte or a (bio)chemo-sensitive sensor location of a waveguide grating with accumulated analyte is provided with a MALDI matrix.

18. The method according to claim 1, wherein desorption and ionisation is effected via a MALDI step.

19. The method according to claim 1, wherein the mass spectrometer is a time-of flight (TOF) mass spectrometer or a quadrupole mass spectrometer.