Method and apparatus for biosensor spectral shift detection

• US 20030077660A1
• Filed: 09/25/2002
• Published: 04/24/2003
• Est. Priority Date: 10/30/2000
• Status: Active Grant

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Li, Peter, Cunningham, Brian, Karl, William C., Pien, Homer, Puff, Derek
• Granted Patent: US 7,217,574 B2
• Time in Patent Office: Days
• US Class Current: 435/7.1
• 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 offsets comprising the steps:

determining a reference spectrum;

measuring a sample spectrum from a biosensor;

correlating the reference spectrum and the sampled spectrum;

determining an offset in response to a maximum correlation value.

2. The method of claim 1 wherein the step of measuring a sample spectrum includes interpolating spectral data to obtain a sample spectrum having linearly spaced measurements.

3. The method of claim 1 wherein the step of correlating includes digitally filtering the measured sample spectrum with an FIR filter whose coefficients are determined in response to the reference spectrum.

4. The method of claim 1 wherein the step of determining a reference spectrum comprises selecting a mid-point spectrum from a plurality of measured spectra, and further comprising the step of correlating the reference spectrum and a second sampled spectrum, and wherein the step of determining an offset in response to a maximum correlation value comprises summing the maximum correlations from the two correlating steps.

5. The method of claim 1 wherein the step of determining an offset in response to a maximum correlation comprises determining a lag parameter.

6. The method of claim 1 wherein the step of correlating includes determining a window of the reference spectrum and a window of the measured spectrum to use in the correlation.

7. A method for determining biosensor resonance peak 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 an offset in response to reference band edges and the sample band edges.

8. The method of claim 7, wherein the step of determining sample band edges comprises determining an upper and lower maximum of the derivative of the measured sample spectrum.

9. The method of claim 7 wherein the step of determining sample band edges comprises determining an upper and lower wavelength where the spectrum values are one half the maximum spectral value.

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

11. The method of claim 7 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 an offset comprises averaging the difference between a lower reference band edge and a lower sample band edge and the difference between an upper lower reference band edge and an upper sample band edge.

12. A method for determining biosensor resonance peak offsets comprising the steps:

(i) determining a reference spectrum and a sample spectrum;

(ii) determining an initial offset estimate;

(iii) determining an incremental offset value;

(iv) updating the initial offset estimate in response to the incremental offset value.

13. The method of claim 12 wherein steps (iii) and (iv) are repeated until a determined incremental offset value is below a predetermined threshold.

14. The method of claim 12 wherein the step of determining an initial offset value 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;

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

15. The method of claim 12 wherein the incremental offset value is responsive to the derivative of the reference spectrum.

16. The method of claim 12 wherein the incremental offset value is determined using a least squares criterion.

17. The method of claim 12 wherein the incremental offset value is determined using a criterion based on maximal likelihood estimation.

18. A method for determining biosensor resonance peak offsets comprising the steps:

(i) providing a peak value of a reference spectrum;

(ii) measuring a sample spectrum;

(iii) determining a peak value of the sample spectrum by fitting a curve to the measured sample spectrum;

(iv) determining a spectral resonance offset in response to the peak value of a reference spectrum and the peak value of the sample spectrum.

19. The method of claim 18 wherein the step of providing a peak value comprises the steps:

(i) measuring a reference spectrum;

(iii) determining a peak value of the reference spectrum by fitting a curve to the measured reference spectrum.

20. The method of claim 18 further comprising the step of determining a window of the measured spectrum to use when fitting a curve to the measured sample spectrum.

21. The method of claim 18 wherein the step of determining a peak value of the sample spectrum by fitting a curve to the measured sample spectrum includes determining the point at which the derivative of the fitted curve is zero.

22. A method for determining biosensor resonance peak offsets comprising the steps:

(i) determining a reference spectrum and a sample spectrum;

(ii) performing an interative calculation to estimate spectral offset of the sample spectrum based on a maximal likelihood estimation, wherein each iteration is performed in response to the signal amplitude values of the reference spectrum and the sample spectrum and signal slope values of at least one of the reference spectrum and the measured spectrum.

23. The method of claim 22 wherein the iterative calculation is performed until the spectral offset estimate has converged.

24. The method of claim 22 wherein the iterative calculation uses signal values of one the reference spectrum and the sample spectrum as estimates of noise values.

25. A method for determining biosensor resonance peak offsets comprising the steps:

(i) determining a reference spectrum and a sample spectrum;

(ii) determining a peak resonance offset in response to the slope of the reference spectrum weighted by the signal amplitudes of the reference spectrum.

26. The method of claim 25 wherein the step of determining a peak resonance offset comprises determining an offset that minimizes a set of linear equations, wherein the linear equations include terms dependent upon the slope of the reference spectrum.

27. The, method of claim 25 wherein the step of determining a peak resonance offset comprises determining reference band edges in response to the slope of the reference spectrum weighted by the signal amplitudes of the reference spectrum, determining sample band edges in response to the slope of the sample spectrum weighted by the signal amplitudes of the sample spectrum, and determining a relative change in band edges between the reference spectrum and the sample spectrum.