Optical system for parameter characterization of an element of body fluid or tissue

• US 10,209,178 B2
• Filed: 01/31/2014
• Issued: 02/19/2019
• Est. Priority Date: 01/31/2013
• Status: Active Grant

• Current Assignee: Universidade do Minho
• Original Assignee: Nuno Jorge Sousa, Rui Miguel Da Costa Martins, Universidade do Minho
• Inventors: Carvalho Sousa, Nuno Jorge, Da Costa Martins, Rui Miguel, Alvarez Osorio, Ricardo Alberto
• Primary Examiner(s): Bologna, Dominic J
• Application Number:
  US14/765,242
• Publication Number:
  US 20150369725A1
• Time in Patent Office: 1,845 Days
• CPC Class Codes: A61B 2503/40 Animals
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2560/0285 Apparatus for single use
• CPC Class Codes: A61B 2560/045 with a separable interface unit, e.g. for communication
• CPC Class Codes: A61B 2562/0238 Optical sensor arrangements for performing transmission measurements on body tissue
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/6824 Arm or wrist
• CPC Class Codes: A61B 5/7246 using correlation, e.g. template matching or determination of similarity
• CPC Class Codes: G01N 21/255 Details, e.g. use of specially adapted sources, lighting or optical systems
• 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 21/65 Raman scattering
• CPC Class Codes: G01N 2201/0221 Portable; cableless; compact; hand-held
• CPC Class Codes: G01N 2201/0612 Laser diodes
• CPC Class Codes: G01N 2201/062 LED's
• CPC Class Codes: G01N 2201/12 Circuits of general importance; Signal processing
• CPC Class Codes: G01N 33/4833 of solid biological material, e.g. tissue samples, cell cultures tissue in vivo A61B5/00; cell suspensions G01N33/48735

Abstract

Biophotonic device for the point-of-care, real-time, non-invasive determination of parameters with diagnostic relevance, in particular an optical system for parameter characterization of an element of body fluid or tissue comprising an optical device which comprises: a light source for emitting light onto the element; and a spectrometer for recording the spectrum of light from the element, said light from the element being of transmittance, reflectance or Raman scattering of the emitted light by said element; the optical system further comprising a data processing module configured to: convert the recorded spectrum by a conversion matrix into a standardized spectrum, wherein said conversion matrix has been obtained by calibrating the optical system spectrum response against a spectrum reference; pre-process the converted spectrum; correlate, for parameter quantification, the converted pre-processed spectrum with pre-obtained spectral bands for each parameter; said spectrum being contained within uv-vis-nir wavelengths. Also methods of operating said system.

Claims

1. An optical system for parameter characterization of an element of body fluid or tissue comprising an optical device which comprises:

a light source for emitting light onto the element;

a chamber for holding an element of body fluid or tissue, wherein the chamber includes a reference sample;

a sample spectrometer for recording the spectrum of light from the element of body fluid or tissue, said light from the element being of transmittance, reflectance or Raman scattering of the emitted light by said element and the spectrum of light from the reference sample;

the optical system further comprising a processor having a memory and configured

to compare the recorded spectrum of the reference sample to a stored value within the memory, by obtaining a higher spectral full width at half maximum (FWHM) than that of an optical limit of the spectrometer by;

(1) calculating an interpolation model of the higher pixel resolution by local regression, and interpolating the obtained reference spectral measurements;

(2) performing deconvolution of the interpolated spectral measurements by an apodization function of the optical device to resolve convolved information below optical resolution; and

(3) comparing the convoluted spectral measurements to a stored reference spectral measurement of the reference sample,

where the convoluted spectral measurement of the reference sample is substantially similar to the stored reference measurement, convert the recorded spectrum of the element of body fluid or tissue using a conversion matrix into a standardized spectrum, wherein said conversion matrix has been obtained by calibrating the optical system spectrum response against a spectrum reference previously measured by a reference spectrometer;

pre-process the converted spectrum by correcting the standardized spectrum for at least scattering;

correlate, for parameter quantification, the converted pre-processed spectrum with pre-obtained spectral bands for each parameter previously measured by the reference spectrometer;

wherein said the recorded spectrum is within the ultraviolet—

visible—

near infrared wavelengths.

2. An optical system according to claim 1 wherein the spectral bands for each parameter were pre-obtained by:

obtaining sample spectra with the reference spectrometer for known parameter values;

pre-processing the obtained sample spectra;

correlating the pre-processed spectra with the known parameter values in order to obtain the spectral bands for each parameter.

3. An optical system according to claim 2 wherein the spectral bands for each parameter were pre-obtained, explicitly or implicitly, by correlation through multivariate regression, latent variable model, partial least squares, two-step partial least squares, sparse partial least squares, canonical correlation, artificial neural network or support vector machines.

4. An optical system according to claim 1 wherein the spectrum calibrating for obtaining said conversion matrix comprises computing the warping of a conversion matrix function to match both the frequency and intensity of the spectra of the optical device spectrum response against the frequency and intensity of the spectrum reference previously measured by the reference spectrometer.

5. An optical system according to claim 4 wherein the spectrum calibrating for obtaining said conversion matrix comprises:

recording a spectrum of a spectrum reference of the same light emitting, reflecting, absorbing or scattering material of the previously recorded spectrum reference by the reference spectrometer;

pre-processing the recorded spectrum;

computing the warping of said conversion matrix function such that the pre-processed recorded spectrum converted by said matrix matches the frequency and intensity of the previously recorded spectrum reference.

6. An optical system according to claim 5 wherein the pre-processing of a spectrum further comprises correcting the spectrum for Mie and Rayleigh scattering, and correcting for baseline-stray light.

7. An optical system according to claim 1 wherein the processor is configured to operate the spectrometer when recording a spectrum in piecewise measurement in a plurality of overlapping intervals covering the wavelength range to be recorded of the spectrometer, each interval optimized in both integration time and light intensity for being substantially within the optimum sensitivity and linear region of the spectrometer.

8. An optical system according to claim 1 wherein the processor is configured such that the spectrum recording comprises interpolation of the received spectra to a resolution at least three (3) times higher than the original spectra.

9. An optical system according to claim 1 wherein processor is configured such that spectrum recording comprises the steps of:

recording a sample spectrum without the element of body fluid or tissue to be characterized; and

linearly calibrating the spectrometer for each frequency such that the sample spectrum matches a previously obtained reference spectrum.

10. The optical system according to claim 9 wherein the element of body fluid or tissue to be characterized is a sample of a body fluid.

11. An optical system according to claim 10 wherein the chamber comprises one or more mirrors for reflecting the light from the light source through the element of body fluid or tissue to be characterized to the spectrometer, wherein at least one of the mirror or mirrors is attached to the chamber lid.

12. The optical system according to claim 11 comprising one mirror in the chamber, said mirror being arranged distal to the optical device to reflect light back to the optical device, and comprising one mirror coupled to the optical device said mirror being arranged to reflect light back to the element of body fluid or tissue to be characterized.

13. An optical system according to claim 1 wherein the chamber has a lid for receiving the sample.

14. An optical system according to claim 13 wherein the chamber is attachable to the optical device for characterization of the element of body fluid or tissue by magnets, mechanical pressure or mechanical fasteners.

15. An optical system according to claim 1 wherein the element of body fluid or tissue to be characterized is a body in-vivo element, and the optical system is arranged for parameter characterization of the body element by skin contact of the optical device, to a blood vessel or to adipose tissue body element.

16. An Optical system according to claim 1 comprising a plurality of light sources for emitting light onto the element of body fluid or tissue, a plurality of spectrometer inputs for recording the spectrum of light, and the processor is configured to select for the spectrometer, among the plurality of spectrometer inputs, the input or inputs which maximize the parameter quantification correlation with the pre-obtained spectral bands.

17. An optical system according to claim 16 wherein the optical device is a bracelet.

18. An optical system according to claim 1 wherein the parameter is one or more of the following:

in urine, saliva, whole blood or blood serum sample, or in non-invasive in-vivo skin-contact to blood vessel or adipose tissue;

glucose, urea, creatinine, ALT, AST, cholesterol, triglycerides, uric acid, ALP, K, Na, Cl, Ca, amylase, total protein, micro-albumin, hemoglobin, erythrocytes, mean corpuscular volume, leukocytes, platelets, troponin, and/or myoglobin.

19. An optical system according to claim 1 wherein the parameter is one or more of the following:

probabilistic findings of intermediate diagnostic relevance of diabetes mellitus, renal insufficiency;

hyperuricemia;

hepatic insufficiency;

inflammation; and

/or dyslipidemia.

20. An optical system according to claim 1 wherein said recorded spectrum, is contained in the 200-2500 nm wavelengths.