Method and apparatus for biosensor spectral shift detection

• US 7,718,440 B2
• Filed: 05/15/2007
• Issued: 05/18/2010
• Est. Priority Date: 10/30/2000
• Status: Expired due to Fees

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Cunningham, Brian, Puff, Derek, Pien, Homer Paul, Li, Peter, Karl, William C.
• Primary Examiner(s): Chin; Christopher L
• Application Number:
  US11/749,073
• Publication Number:
  US 20080052006A1
• Time in Patent Office: 1,099 Days
• Field of Search: None
• US Class Current: 436/164
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/0218 using optical fibers
• CPC Class Codes: G01J 3/0224 using polarising or depolarising elements
• CPC Class Codes: G01J 3/1804 Plane gratings
• CPC Class Codes: G01J 3/42 Absorption spectrometry; Double beam spectrometry; Flicker spectrometry; Reflection spectrometry beam switching arrangements G01J3/08
• CPC Class Codes: G01N 2021/3196 Correlating located peaks in spectrum with reference data, e.g. fingerprint data
• CPC Class Codes: G01N 2021/7773 Reflection
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G02B 5/1809 with pitch less than or comparable to the wavelength
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

Performing high-resolution determination of the relative shift of the spectral properties of a biosensor. The shift in the resonance peak of the biosensor is indicative of the amount of material bound to the surface of the biosensor. A preferred biosensor is a Guided Mode Resonant Filter Biosensor (GMRFB). In one aspect of the invention, curve fitting is used to determine the relative location of the spectrum of the unexposed biosensor with respect to those spectra that are altered (e.g., shifted) by the presence of materials bound to the surface of the biosensor. In an alternative embodiment, the cross correlation function is used to detect spectral peak offsets between a reference spectrum and a spectrum measured from an exposed biosensor. In yet another alternative, maximal likelihood estimation techniques are used to determine the spectral shift or offs.

Claims

1. A method for determining biosensor spectral resonance offsets comprising the steps:

determining reference band edges of a biosensor reference spectrum;

measuring a sample spectrum from a biosensor;

determining sample band edges of the sample spectrum;

determining a spectral resonance offset in response to reference band edges and the sample band edges.

2. The method of claim 1, wherein the step of determining sample band edges comprises determining an upper and lower maximum of the derivative of the measured sample spectrum.

3. The method of claim 2, wherein the derivative values are weighted by a scaling factor.

4. The method of claim 3, wherein the scaling factor is one of the following:

(i) the signal amplitude;

or

(ii) the square of the signal amplitude.

5. The method of claim 1 wherein the step of determining sample band edges comprises determining an upper and lower wavelength where the spectrum values are a predetermined proportion of a maximum spectral value.

6. The method of claim 5 wherein the predetermined proportion of the maximum spectral value is one of the following:

(i) one half the maximum spectral value;

(ii) three-quarters the maximum spectral value;

or

(iii) one-quarter the maximum spectral value.

7. The method of claim 1 wherein the step of determining sample band edges comprises determining an upper and lower turning point.

8. The method of claim 7, wherein the step of determining an upper and lower turning point includes determining a point where the slope of the spectral response is zero.

9. The method of claim 1 wherein the reference band edges comprise a lower reference band edge and an upper reference band edge, and the sample band edges comprise a lower sample band edge and an upper sample band edge, and the step of determining a spectral resonance offset comprises averaging the difference between the lower reference band edge and the lower sample band edge and the difference between the upper reference band edge and the upper sample band edge.

10. The method of claim 1, wherein the reference band edges comprise a lower reference band edge and an upper reference band edge, and the sample band edges comprise a lower sample band edge and an upper sample band edge, and the step of determining a spectral resonance offset comprises averaging the absolute value of the difference between the lower reference band edge and the lower sample band edge and the absolute value of the difference between the upper reference band edge and the upper sample band edge.

11. The method of claim 1, wherein the step of determining sample band edges comprises interpolation to provide linearized data samples.