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CN-122028842-A - Generation and testing of multivariate analysis models using spectroscopic techniques to measure in analytes

CN122028842ACN 122028842 ACN122028842 ACN 122028842ACN-122028842-A

Abstract

A method and apparatus for testing a multivariate model for generating values of analyte concentration using spectroscopic techniques, the method comprising a) providing a multivariate model for generating output values of analyte concentration based on spectroscopic measurements, b) inputting spectra of analytes to be measured of known concentration to the model, c) inputting spectra of interferents, and d) processing the received spectra of analytes to be measured and interferents and generating output values of analytes to be measured using the model. A method for generating such a multivariate analysis model is also described, the method comprising spectral doping of an input spectrum of the model.

Inventors

  • Anders Yoslev Boer
  • Caspar Gotthardt Rasmussen
  • Rooney Englev
  • Anders Webb

Assignees

  • RSP系统公司

Dates

Publication Date
20260512
Application Date
20240620
Priority Date
20230714

Claims (13)

  1. 1. A method of testing a multivariate model for generating values of analyte concentrations using spectroscopic techniques, the method comprising: a spectrum of the interferent is input and processed in combination with a spectrum of the analyte to be measured to generate an output value of the analyte to be measured using the model.
  2. 2. The method according to claim 1, comprising: (a) Providing a multivariate model for generating output values of analyte concentrations based on the spectral measurements; (b) Inputting a spectrum of an analyte to be measured of known concentration into the model; (c) The received spectra of the analyte to be measured and the interferent are processed to generate an output value for the analyte to be measured.
  3. 3. The method of claim 2, comprising repeating steps (a) to (c) to generate an indication of the effect of the spectrum of the interferent on the determined value of the analyte to be measured.
  4. 4. A method according to any one of claims 1 to 3, wherein the analyte to be measured is glucose.
  5. 5. The method of any one of claims 1 to 4, wherein the interferent is a topical substance on the exterior of the user's skin.
  6. 6. The method of any one of claims 1 to 5, wherein the interferent is an interstitial substance found in interstitial fluid of the user.
  7. 7. The method of claim 5, wherein the interfering substance is an interstitial substance that is a compound that originates outside of the user's body.
  8. 8. The method according to any one of claims 1 to 7, comprising updating the model according to the generated output value of the analyte to be measured.
  9. 9. A method for generating a multivariate analysis model for use in an apparatus for non-invasive measurement of analytes using spectroscopic techniques, the method comprising: spectrally doping the input spectrum of the model during testing of the model; an output from the model is determined in response to the spectrally doped input.
  10. 10. The method according to any one of claims 1 to 9, wherein the spectrum of the analyte to be measured and the spectrum of the interferent of known concentration are provided as a single superimposed spectrum to the model to be tested.
  11. 11. A device for non-invasive measurement of analyte concentration using spectroscopic techniques, the device having: A light source; a spectrometer for receiving the generated spectrum for making a measurement of the analyte concentration, and The device receives the spectrum and inputs the spectrum to a measurement model, wherein the model has been tested using the method according to any of claims 1 to 10.
  12. 12. A device for testing a model for non-invasive measurement of analyte concentration using spectroscopic techniques, the device being arranged to: (a) Receiving a spectrum of an analyte to be measured and a spectrum of an interferent at known concentrations; (b) The received spectra of the analyte to be measured and the interferent are processed and the model is used to generate an output value for the analyte to be measured.
  13. 13. A method of testing a multivariate model for generating analyte concentration values using spectroscopic techniques, the method comprising: (a) Providing a multivariate model for generating output values of analyte concentrations based on the spectral measurements; (b) Inputting a spectrum of an analyte to be measured of known concentration into the model; (c) Inputting the spectrum of the interfering substance, and (D) The received spectra of the analyte to be measured and the interferent are processed and the model is used to generate an output value of the analyte to be measured.

Description

Generation and testing of multivariate analysis models using spectroscopic techniques to measure in analytes Technical Field The present invention relates to a method and apparatus for testing a multivariate model for use in non-invasive measurement of analyte concentration using spectroscopic techniques. In embodiments, the method may be used to study the effect of the presence of certain substances on the performance of a model in quantifying analytes. A multivariate model herein may be defined as a processing tool that establishes a relationship between a plurality of input variables and output variables. For example, the model may be arranged to receive as input a plurality of variables that may be measured or determined, and then process these variables and produce as output a value of the blood glucose concentration or the glucose concentration of interstitial fluid. Background Different forms of diabetes are affecting more and more individuals and putting undue stress on the national health care budget. Estimates (from 2015) indicate that 41500 ten thousand people worldwide suffer from diabetes, and this number is expected to increase to 64200 ten thousand in 2040. To control the treatment, self-monitoring of blood glucose is recommended, which is typically done with invasive finger prick methods. In type 1 diabetics, insulin administration is typically based on 4 to 6 blood glucose determinations per day. For these reasons, a long-felt goal is to develop truly non-invasive techniques to measure blood glucose levels in diabetics. The current clinical trend supports indwelling electrochemical sensors that allow continuous glucose monitoring in a minimally invasive manner. However, there is still a need for skin penetration, with attendant discomfort and increased risk of infection for the user. These sensors also suffer from biocompatibility problems that limit their lifetime to a few weeks. For decades, the goal has been to develop non-invasive techniques to measure blood glucose levels in diabetics, but no practical solution for general use has been developed so far. Most methods have been based on optical measurement of glucose in tissue such as skin. Among these, spectroscopic techniques such as fluorescence, absorbance and raman have attracted considerable attention. Despite the fact that inelastic raman scattering is a weak process and thus leads to a weak signal, many factors make it an attractive choice as a spectroscopic technique for measuring glucose concentration in the user's skin and indeed other analyte concentrations. They include high chemical specificity, minimal interference from tissue water content, and only modest fluorescent background. These make this technique one of the most promising candidates for non-invasive glucose monitoring. Since the first feasibility study of measuring blood glucose using near infrared raman spectroscopy in 1997, several groups have demonstrated the basic effectiveness of this technique by quantitative measurement of glucose levels in vivo. However, these reports may be considered proof of concept only, as all measurements are performed in a controlled environment, whereas the predictive ability of the calibration model is only assessed by cross-validation. In previous publications and patent applications, the inventors have described the design and development of bench-top confocal near-infrared raman instruments for intermittent glucose determination. The instrument uses the principle of critical depth raman spectroscopy, where measurements are made from interstitial fluid within a defined area of the skin. Notably, in contrast to the prior art that also utilizes confocal settings for detection in living parts of the skin, the inventors work to systematically investigate the first time among this type of relationship between the detection depth and the expected performance of a raman-based glucometer, allowing to define the critical depth from which raman signals should be acquired. In the present inventors' international application number WO2011/83111 (in many jurisdictions) a method and apparatus for non-invasive in vivo measurement of glucose present in interstitial fluid of the skin by raman spectroscopy is described. In other aspects, an apparatus for non-invasive in vivo measurement of glucose present in interstitial fluid in the skin of a subject by raman spectroscopy is described, the apparatus comprising a light source, an optical component defining an optical path from the light source to a measurement location, a light detection unit, an optical component defining a return path for raman scattered light from the measurement location to the light detection unit, and a skin engaging member having a distal surface for defining a position of the optical component defining a return path relative to a surface of the skin in use, and wherein the optical component defining a return path for raman scattered light selectively transmits light scat