Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor

• US 20100329933A1
• Filed: 07/22/2010
• Published: 12/30/2010
• Est. Priority Date: 08/11/2005
• Status: Abandoned Application

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Borsody, Alex, Li, Peter Y., Binder, Brant, Jogikalmath, Gangadhar, Cunningham, Brian T., Laing, Lance G., Schulz, Stephen C.
• Application Number:
  US12/804,525
• Publication Number:
  US 20100329933A1
• Time in Patent Office: Days
• US Class Current: 422/82.05
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. Some embodiments are disclosed which are optimized for ER detection in an air mode, in which the sample is dry. Other embodiments are optimized for ER detection in liquid mode, in which the sample is suspended in liquid medium such as water. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. One embodiment includes a first light source optimized for collecting label-free detection data, a second light source optimized for collecting ER fluorescence amplification data, and at least one detector. In one embodiment, the detector is in the form of an imaging system and includes a CCD camera for collecting both ER and label-free data. In other embodiments, the at least one detector takes the form of a spectrometer for collection of label-free data and a photomultiplier for collecting ER data. In other embodiments, a single light source such as a tunable laser or broad band light source is used.

Claims

1. A readout detection instrument for a sensor having a periodic grating pattern constructed in a manner designed for both evanescent resonance (ER) and label-free detection of a sample placed on the sensor, comprising:

a first light source adapted for obtaining ER data from the sensor;

a second light source adapted for obtaining label-free detection data from the sensor;

an optical system combining the light from the first and second light sources into an illuminating beam for illuminating the sensor;

at least one detector for detecting reflected light from the sensor; and

an analysis module using data from the at least one detector and obtaining ER and label-free data from the sample.

2. The instrument of claim 1, wherein the at least one detector comprises a spectrometer for obtaining label-free data and a photodetector for obtaining ER data.

3. The instrument of claim 1, further comprising a means for polarizing light from the first and second light sources.

4. The instrument of claim 1, further comprising an X-Y motion stage receiving the sensor and for moving the sensor relative to the illuminating beam.

5. The instrument of claim 1, wherein the optical system further comprising a set of optical filters and a beam splitting and combining assembly.

6. A readout detection instrument for a sensor having a periodic grating pattern constructed in a manner designed for both evanescent resonance (ER) and label-free detection of a sample placed on the sensor, comprising:

a first light source adapted for obtaining ER data from the sensor;

a second light source adapted for obtaining label-free detection data;

an optical system selectively illuminating the sensor with light from the first and second light sources;

at least one detector for detecting reflected light from the sensor; and

an analytical instrument obtaining ER and label-free data from the at least one detector.

7. The instrument of claim 6, wherein the at least one detector comprises a spectrometer for obtaining label-free data and a photodetector for obtaining ER data.

8. The instrument of claim 6, further comprising a means for polarizing light from the first and second light sources.

9. The instrument of claim 6, further comprising an X-Y motion stage receiving the sensor and for moving the biosensor relative to the optical system.

10. The instrument of claim 6, wherein the optical system further comprising a set of optical filters and a beam splitting and combining assembly.

11. A readout detection instrument and sensor combination, comprising:

a sensor having a periodic grating pattern constructed in a manner designed for both evanescent resonance (ER) and label-free detection of a sample placed on the sensor, and

an instrument for acquiring data from the sensor, the instrument comprising;

a light source adapted for obtaining both ER and label free data from the sensor;

an optical system illuminating the sensor with light from the light source;

at least one detector for detecting reflected light from the biosensor; and

an analytical instrument obtaining ER and label-free data from the at least one detector.

12. The apparatus of claim 11, wherein the light source comprises a broad band light source.

13. The apparatus of claim 11, wherein the light source comprises a tunable laser.

14. The apparatus of claim 11, wherein the light source is activated in succession in a first activation and a second activation, the at least one detector acquiring label-free data from the sensor in the first activation and acquiring ER data from the sensor in the second activation.

15. The apparatus of claim 11, wherein the at least one detector acquires label-free data and ER data from a single activation of the light source.

16. The apparatus of claim 11, wherein the at least one detector comprises an imaging detector.

17. The apparatus of claim 11, wherein the at least one detector comprises a photodetector and a spectrometer.

18. The apparatus of claim 13, wherein the instrument further comprises a beam expander.

19. The apparatus of claim 12, wherein the instrument further comprises a monochromator receiving light from the broad band light source.

20. The apparatus of claim 12, wherein the instrument further comprises a filter stage receiving light from the broad band light source.