Spectroscopy with correlation matrices, ratios and glycation

• US 10,209,192 B2
• Filed: 06/12/2018
• Issued: 02/19/2019
• Est. Priority Date: 10/05/2015
• Status: Active Grant

• Current Assignee: Nxgen Partners Ip, LLC (NxGen Partners LLC)
• Original Assignee: Nxgen Partners Ip, LLC (NxGen Partners LLC)
• Inventors: Ashrafi, Solyman
• Primary Examiner(s): Nur, Abdullahi
• Application Number:
  US16/006,090
• Publication Number:
  US 20180306723A1
• Time in Patent Office: 252 Days
• CPC Class Codes: G01N 2021/655 Stimulated Raman
• CPC Class Codes: G01N 21/17 Systems in which incident light is modified in accordance with the properties of the material investigated where the material investigated is optically excited causing a change in wavelength of the incident light G01N21/63
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/55 Specular reflectivity
• 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 21/65 Raman scattering
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80

Abstract

A system and method for detecting glycation levels within hemoglobin generates a first correlation matrix using a first light beam at a first wavelength passing through a hemoglobin sample. A second correlation matrix is generated using a second light beam at a second wavelength passing through the hemoglobin sample. The first correlation matrix is multiplied by an inverse of the second correlation matrix to obtain a third matrix. A fourth matrix is generated by taking a singular value decomposition of the third matrix. The fourth matrix comprises a unique biomarker for a level of glycation within the hemoglobin sample. The level of glycation within the hemoglobin sample is determined responsive to the fourth matrix and an indicator identifying the determined level of glycation is output.

Claims

1. A method for detecting glycation levels within hemoglobin, comprising:

generating a first correlation matrix using a first light beam at a first wavelength passing through a hemoglobin sample;

generating a second correlation matrix using a second light beam at a second wavelength passing through the hemoglobin sample;

multiplying the first correlation matrix by an inverse of the second correlation matrix to obtain a third matrix;

generating a fourth matrix by taking a singular value decomposition of the third matrix, wherein the fourth matrix comprises a unique biomarker for a level of glycation within the hemoglobin sample;

determining the level of glycation within the hemoglobin sample responsive to the fourth matrix; and

outputting an indicator identifying the determined level of glycation.

2. The method of claim 1, wherein the step of determining the level of glycation further comprises:

comparing the fourth matrix to a plurality of matrices stored within a database, each of the plurality of matrices associated with a particular level of glycation within hemoglobin;

determining a stored matrix of the plurality of matrices that matches the fourth matrix; and

identifying the level of glycation within the hemoglobin sample based upon the level of glycation associated with the determined stored matrix that matches the fourth matrix.

3. The method of claim 1, wherein the step of generating the first correlation matrix further comprise the steps of:

generating the first light beam at the first wavelength;

applying each of a plurality of different orthogonal functions to the first light beam;

shining the first light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a third light beam exiting the hemoglobin sample;

measuring an intensity value of the third light beam exiting the hemoglobin sample for each of the plurality of different orthogonal functions; and

storing the measured intensity values of the third light beam for each of the different orthogonal functions within the first correlation matrix.

4. The method of claim 3, wherein the step of generating the second correlation matrix further comprise the steps of:

generating the second light beam at the second wavelength;

applying each of the plurality of different orthogonal functions to the second light beam;

shining the second light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a fourth light beam exiting the hemoglobin sample;

measuring an intensity value of the fourth light beam exiting the hemoglobin sample for each of the plurality of different orthogonal functions; and

storing the measured intensity values of the fourth light beam for each of the different orthogonal functions within the second correlation matrix.

5. The method of claim 4, wherein the plurality of different orthogonal functions comprise a plurality of different Hermite-Gaussian functions for applying a different helicity to the first and the second light beams.

6. The method of claim 1, wherein the step of multiplying further comprises the step of inverting the second correlation matrix to create the inverse of the second correlation matrix.

7. The method of claim 1, wherein the unique biomarker comprises at least one of fluorescence lifetimes of native fluorophores, Raman vibrational modes of Amide 1 and 3 bands;

florescence Stokes Δ

λ

(excitation-emission) differences and Raman vibrational modes of amino acids residues.

8. A system for detecting glycation levels within hemoglobin, comprising:

a database containing a plurality of matrices, each of the plurality of matrices associated with a particular level of glycation within hemoglobin;

a processor;

a memory coupled to the processor, the memory storing a plurality of instructions for execution by the processor, the plurality of instructions including;

instructions for generating a first correlation matrix using a first light beam at a first wavelength passing through a hemoglobin sample;

instructions for generating a second correlation matrix using a second light beam at a second wavelength passing through the hemoglobin sample;

instructions for multiplying the first correlation matrix by an inverse of the second correlation matrix to obtain a third matrix;

instructions for generating a fourth matrix by taking a singular value decomposition of the third matrix, wherein the fourth matrix comprises a unique biomarker for a level of glycation within the hemoglobin sample;

instructions for determining the level of glycation within the hemoglobin sample responsive to the fourth matrix; and

instructions for outputting an indicator identifying the determined level of glycation.

9. The system of claim 8, wherein the instructions for determining the level of glycation further include:

instructions for comparing the fourth matrix to a plurality of matrices stored within a database, each of the plurality of matrices associated with a particular level of glycation within hemoglobin;

instructions for determining a stored matrix of the plurality of matrices that matches the fourth matrix; and

instructions for identifying the level of glycation within the hemoglobin sample based upon the level of glycation associated with the determined stored matrix that matches the fourth matrix.

10. The system of claim 8, wherein the instructions for generating the first correlation matrix further include:

instructions for generating the first light beam at the first wavelength;

instructions for applying each of a plurality of different orthogonal functions to the first light beam;

instructions for shining the first light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a third light beam exiting the hemoglobin sample;

instructions for measuring an intensity value of the third light beam exiting the hemoglobin sample for each of the plurality of different orthogonal functions; and

instructions for storing the measured intensity values of the third light beam for each of the different orthogonal functions within the first correlation matrix.

11. The system of claim 10, wherein the instructions for generating the second correlation matrix further include:

instructions for generating the second light beam at the second wavelength;

instructions for applying each of the plurality of different orthogonal functions to the second light beam;

instructions for shining the second light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a fourth light beam exiting the hemoglobin sample;

instructions for measuring an intensity value of the fourth light beam exiting the hemoglobin sample for each of the plurality of different orthogonal functions; and

instructions for storing the measured intensity values of the fourth light beam for each of the plurality of different orthogonal functions within the second correlation matrix.

12. The system of claim 11, wherein the plurality of different orthogonal functions comprise a plurality of different Hermite-Gaussian functions for applying a different helicity to the first and the second light beams.

13. The system of claim 8, wherein the instructions for multiplying further comprise instructions for inverting the second correlation matrix to create the inverse of the second correlation matrix.

14. The system of claim 8, wherein the unique biomarker comprises at least one of fluorescence lifetimes of native fluorophores, Raman vibrational modes of Amide 1 and 3 bands;

florescence Stokes Δ

λ

(excitation-emission) differences and Raman vibrational modes of amino acids residues.

15. A system for detecting glycation levels within hemoglobin, comprising:

a database containing a plurality of matrices, each of the plurality of matrices associated with a particular level of glycation within hemoglobin;

a beam generator for generating a light beam at a first wavelength and a second wavelength having one of a plurality of orthogonal functions applied thereto and directing the light beam through a hemoglobin sample;

a correlation matrix generator for generating a first correlation matrix using a first light beam from the beam generator at the first wavelength passing through the hemoglobin sample and for generating a second correlation matrix using a second light beam at the second wavelength passing through the hemoglobin sample; and

a glycation detection system for multiplying the first correlation matrix by an inverse of the second correlation matrix to obtain a third matrix, for generating a fourth matrix by taking a singular value decomposition of the third matrix, wherein the fourth matrix comprises a unique biomarker for a level of glycation within the hemoglobin sample, for determining the level of glycation within the hemoglobin sample responsive to the fourth matrix and the plurality of matrices within the database and for outputting an indicator identifying the determined level of glycation of the hemoglobin sample.

16. The system of claim 15, wherein the glycation detection system further compares the fourth matrix to the plurality of matrices stored within the database, determines a stored matrix of the plurality of matrices that matches the fourth matrix and identifies the level of glycation within the hemoglobin sample based upon the level of glycation associated with the determined stored matrix that matches the fourth matrix.

17. The system of claim 15, wherein the correlation matrix generator further generates the first light beam at the first wavelength, applies each of a plurality of different orthogonal functions to the first light beam and shines the first light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a third light beam exiting the hemoglobin sample, further wherein the correlation matrix generator measures an intensity value of the third light beam exiting the hemoglobin sample for each of the plurality of different orthogonal functions and stores the measured intensity values of the third light beam for each of the different orthogonal functions within the first correlation matrix.

18. The system of claim 17, wherein the correlation matrix generator further generates the second light beam at the second wavelength, applies each of the plurality of different orthogonal functions to the second light beam and shines the second light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a fourth light beam exiting the hemoglobin sample, further wherein the correlation matrix generator generates an intensity value of the fourth light beam exiting the hemoglobin sample for each of the plurality of different orthogonal functions and stores the measured intensity values of the fourth light beam for each of the different orthogonal functions within the second correlation matrix.

19. The system of claim 18, wherein the plurality of different orthogonal functions comprise a plurality of different Hermite-Gaussian functions for applying a different helicity to the first and the second light beams.

20. The system of claim 15, wherein the correlation matrix generator further inverts the second correlation matrix to create the inverse of the second correlation matrix.

21. The system of claim 15, wherein the unique biomarker comprises at least one of fluorescence lifetimes of native fluorophores, Raman vibrational modes of Amide 1 and 3 bands;

florescence Stokes Δ

λ

(excitation-emission) differences and Raman vibrational modes of amino acids residues.

22. A method for detecting glycation levels within hemoglobin, comprising:

generating a first correlation matrix using a first light beam at a first wavelength passing through a hemoglobin sample;

generating a second correlation matrix using a second light beam at a second wavelength passing through the hemoglobin sample;

multiplying the first correlation matrix by an inverse of the second correlation matrix to obtain a third matrix;

generating a fourth matrix by taking a singular value decomposition of the third matrix, wherein the fourth matrix comprises a unique biomarker for a level of glycation within the hemoglobin sample;

comparing the fourth matrix to a plurality of matrices stored within a database, each of the plurality of matrices associated with a particular level of glycation within hemoglobin;

determining a stored matrix of the plurality of matrices that matches the fourth matrix;

identifying the level of glycation within the hemoglobin sample based upon the level of glycation associated with the determined stored matrix that matches the fourth matrix; and

outputting an indicator identifying the level of glycation.

23. The method of claim 22, wherein the step of generating the first correlation matrix further comprise the steps of:

generating the first light beam at the first wavelength;

applying each of a plurality of different orthogonal functions to the first light beam;

shining the first light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a third light beam exiting the hemoglobin sample;

measuring an intensity value of the third light beam exiting the hemoglobin sample for each of the plurality of different orthogonal functions; and

storing the measured intensity values of the third light beam for each of the different orthogonal functions within the first correlation matrix;

wherein the step of generating the second correlation matrix further comprise the steps of;

generating the second light beam at the second wavelength;

applying each of the plurality of different orthogonal functions to the second light beam; and

shining the second light beam through the hemoglobin sample as each of the plurality of different orthogonal functions is applied thereto to generate a fourth light beam exiting the hemoglobin sample.