Method and apparatus for biosensor spectral shift detection

• US 8,247,240 B2
• Filed: 05/18/2010
• Issued: 08/21/2012
• Est. Priority Date: 10/30/2000
• Status: Expired due to Term

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Inventors: Pien, Homer Paul, Karl, William C., Puff, Derek, Li, Peter, Cunningham, Brian
• Primary Examiner(s): Chin, Chris L
• Application Number:
  US12/782,630
• Publication Number:
  US 20100231907A1
• Time in Patent Office: 826 Days
• Field of Search: None
• US Class Current: 436/518
• 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 resonance peak shifts, comprising the steps of:

(i) obtaining a reference spectrum for the biosensor and a sample spectrum from the biosensor;

(ii) determining an initial offset estimate from the reference spectrum and the sample spectrum, the initial offset estimate being an estimate of the amount of resonance peak shift in the sample spectrum;

(iii) determining an incremental offset (shift) value; and

(iv) updating the initial offset estimate in response to the incremental offset (shift) value, the updated initial offset estimate representing an updated estimate of the amount of resonance peak shift.

2. The method of claim 1 wherein steps (iii) and (iv) are repeated until a determined incremental offset (shift) value is below a predetermined threshold.

3. The method of claim 1 wherein the step of determining an initial offset is performed by one of the following steps:

(a) determining an offset corresponding to a peak resonance value;

(b) determining an offset corresponding to a peak correlation value;

or

(c) determining an offset corresponding to a difference between measured band edges and reference band edges.

4. The method of claim 1 wherein the incremental offset (shift) value is determined using the derivative of the reference spectrum.

5. The method of claim 1 wherein the incremental offset (shift) value is determined using a least squares criterion.

6. The method of claim 1 wherein the incremental offset (shift) value is determined using a criterion based on maximal likelihood estimation.