WO2022113060A1 - Portable, quantitative and non-invasive measuring instrument of laser spectroscopy-based urine glucose levels for early detection of diabetes mellitus - Google Patents

Portable, quantitative and non-invasive measuring instrument of laser spectroscopy-based urine glucose levels for early detection of diabetes mellitus Download PDF

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WO2022113060A1
WO2022113060A1 PCT/ID2021/000001 ID2021000001W WO2022113060A1 WO 2022113060 A1 WO2022113060 A1 WO 2022113060A1 ID 2021000001 W ID2021000001 W ID 2021000001W WO 2022113060 A1 WO2022113060 A1 WO 2022113060A1
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glucose levels
urine
portable
quantitative
measuring instrument
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PCT/ID2021/000001
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French (fr)
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Retna Apsari
Moh. YASIN
Riky Tri YUNARDI
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Universitas Airlangga
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3577Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing liquids, e.g. polluted water
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/359Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/12Circuits of general importance; Signal processing
    • G01N2201/126Microprocessor processing

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  • Spectroscopy & Molecular Physics (AREA)
  • Health & Medical Sciences (AREA)
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Abstract

This Invention relates to the development of portable, quantitative and non-invasive measuring instrument of laser spectroscopy-based urine glucose levels. The non-invasive measurement of glucose levels is carried out by utilizing the intensity absorbance and laser transmittance by glucose molecules in the urine. This invention instrument consist of infrared diode laser, photodiode detector, voltage amplifier circuit, microcontroller, digital display device, cuvette container in which the microcontroller in the instrument contains a program for converting analog voltage data into digital data by comparing the intensity before the sample is inserted and the Intensity after the sample is inserted into the cuvette. Further, the light intensity is converted into voltage input data to obtain accuracy value by comparing the voltage input data to reference urine glucose level sample. The calculation results are displayed through a digital display device in the form of LCD in which the glucose levels are expressed in mg/dL in fasting, postprandial or temporary urine samples.

Description

Description
PORTABLE, QUANTITATIVE AND NON-INVASIVE MEASURING INSTRUMENT
OF LASER SPECTROSCOPY-BASED URINE GLUCOSE LEVELS FOR EARLY
DETECTION OF DIABETES MELLITUS
Field of the Invention
This invention relates to the quantitative and non-invasive measuring instrument of laser spectroscopy-based urine glucose levels . Further, the instrument is portable that operates on the basis of non-invasive measurement of glucose levels by utilizing the intensity absorbance and laser transmittance by glucose molecules in the urine . This measurement method is called the spectroscopic method.
Invention Background
The non-invasive measuring instrument of glucose levels needs to be developed in the market for being able to improve the quality of life of the Diabetics, enabling better regulation for any hyper-hypoglycemia events and avoiding from any psychological complications . Non-invasive measurement of glucose levels is carried out by utilizing the laser light absorbing process with the spectroscopic method. The advantages of this method are it measures glucose levels non-invasively and is portable in nature so it does not injure patients and it can also quantitatively measure urine glucose levels as well show the detection results of diabetes mellitus or normal results based on the measurement results of urine glucose levels .
Several previous inventions have disclosed non-invasive measurements of glucose levels, such as US 2005/0203358A1, however the invention does not use urine samples but the measurement is carried out by reflecting a specific spectral source on the tissue of the skin surface at the fingertips or wrists .
In the US 5, 876, 952 glucose sensors that use urine sample, the urine glucose sensor operates on the basis of redox mediator and bio enzyme system-based amperometric measurements to measure glucose levels. so that the disclosure in the patent document is different from the invention submitted. Therefore, applicants still require a qualitative and non-invasive urine glucose detector that is reliable and portable.
This non-invasive measuring instrument of infrared laserbased urine glucose levels plays its roles as an early detector for diabetes mellitus in the community so that patients should not necessarily go to the laboratory to check their urine glucose levels .
Short Description of the Invention The embodiment of this invention relates to a portable. quantitative and non-invasive measuring instrument of laser spectroscopy-based urine glucose levels consisting of : infrared diode laser; photodiode detector; voltage amplifier circuit; microcontroller; digital display device; sample container; characterized by a microcontroller that processes input data from the amplified photodiode detector voltage rate by using a voltage amplifier circuit where the voltage rate is in proportion to the infrared laser light intensity captured by the photodiode detector and the voltage is converted in digital form.
Non-invasive measuring instrument of laser spectroscopybased urine glucose levels uses infrared laser equipped with the display features on the LCD. With the features of selection of urine samples used, this device can automatically measure the glucose levels of the urine sample of the patients in fasting and postprandial conditions . The level written is the result of calibrated signal processing from the microcontroller . In addition, microcontroller also functions to converse analogous signal to digital one using Analog to Digital Converters (ADC) .
Analogous signal originates from the photodetector of changes in light intensity received . The change originates from the infrared laser light source Infrared experiencing absorption by urine glucose molecules in a cuvette container.
Short Description of the Image
Image 1A, shows the circuit of the components of the instrument, consisting of ( 1) LCD, (2 ) microcontroller, (3) AC Adapter, (4) transparent plastic cuvette, (5) voltage amplifier,
(6) Laser IR, (7 ) urine sample, (8) photodetector, and (9) cuvette holder
Image IB, shows the display of non-invasive measuring instrument of laser spectroscopy-based urine glucose levels according to the invention, with the following information : (10) unit value in mg/dl, (11) fasting urine program button, (12) postprandial urine program button, (13) IR Laser running button,
(14) urine glucose level, (15) laser indicator on LCD, (16) fasting indicator on LCD, (17) Power
Image 2, is regression graph of the ADC readings to Beer- Lambert law-based concentrations .
Image 3, is Hardware Diagram Block Design of the invention instrument Full Description of the Invention
This invention relates to the non-invasive instrument used for measuring glucose levels of urine samples by using infrared laser with measurement unit in mg/dL. The measuring Instrument of glucose levels has a laser spectroscopy-based innovative technology used as an early detector for the diabetics . The advantage of this invention is the development of non-invasive measuring instrument of glucose levels in fasting and postprandial conditions on a small and portable as well as light
LCD display.
This invention uses laser as a light source as it is monochromatic, coherent, and directional in nature with high brightness . Laser characterization is required to know the character and behaviour of the laser to use for optimum operation . Laser characterization is made by observing the effects of the distance between the laser as a light source and the photodetector to the light intensity received by the photodetector. The absorbance of the laser wavelength used has to match that of the urine sample wavelength.
Further, this instrument consists of infrared laser, photodiode, voltage amplifier circuit, microcontroller, 16x2 cm
LCD display module (preferable) and cuvette as a sample container. The invention of this non-invasive measuring instrument of glucose levels uses a diode laser at a wavelength range of 830 nm. Component of photodiode used for measuring light intensity is placed in parallel to and in opposite to diode laser at a distance of 4 cm. A 250 ml transparent cuvette
(preferable) is placed between laser diode and photodiode as a sample urine container . This invention works by using laser light absorbing process (absorption intensity) by glucose molecules in the urine and transmitted light intensity rate
(laser transmission) is detected.
The program works by using software on the microcontroller by using language C. Microcontroller functions to process input data of the amplified photodiode voltage rate using a voltage amplifier circuit . The voltage rate is in proportion to that of the captured infrared laser light intensity . The voltage rate is then converted to digital form for simple data processing and calibration. The calibration process is made in the program to compare the voltage input data to the sample glucose levels of the reference urine for the best accuracy rate.
Data that has been processed by the microcontroller is then displayed through the display unit of the measurement results of the urine glucose levels in the form of a 16x2 cm LCD. The benefits of this invention can be used as an alternative early detection for the diabetes meliitus that is non-invasive nature .
Example of the Implementation of the Invention
The laser wavelength of this instrument is 850 nm. The laser is used as a light source to illuminate the urine . Glucose will not appear in the urine as long as the concentration of glucose in the blood does not exceed the renal reabsorption threshold for glucose of 160-180 mg/dL. The normal urine glucose concentration is ± 0.55 mol /L in the fasting condition and ± 4.4 mol/L after having meals for non-diabetic people .
The design of this instrument uses a different power supply between Arduino uno and infrared laser. The power supply for the laser has a voltage specification of 3.3-5 volts with a current of <100 mA, while that for the Arduino Uno requires 5- 12 volts .
Arduino Uno in this study is used for controlling the output given by the photodetector to display the measurement results of urine glucose levels on the LCD and for controlling the push button for urine sample selection .
The measurement results of glucose levels are displayed on the LCD. Laser characterization results indicate that the maximum laser intensity at a distance of 0.5 cm is 31.44 mW with an energy dose of 0.16765 J/cm2. The measurement results of glucose levels indicate that the quantity of glucose levels in the urine or Diabetes detection result is normal . The calibration of the instrument already designed with dipstick reagents indicates that the accuracy of the designed instrument is 90% . This indicates that the design of this instrument can be used as an alternative for detecting Diabetes Mellitus .
The Beer-Lambert law can be expressed in equation 1 :
Figure imgf000009_0001
remark ;
10 :s: initial light intensity
It - intensity of light transmitted by molecules in the sample ε = molar absorption coefficient in units of 1 mol / c concentration of molecules in mole unit/1 d = length of sample passed by the light in cm
The values of 10 and It cannot be measured in absolute terms, so the measurement thereof is assumed as a percentage of the so- called Transmittance (T) Percentage . Transmittance (T)
Percentage indicates a linear relationship with the concentration of molecules if the inverse of the logarithm is used, as shown in equation 2 :
Figure imgf000009_0002
So that the following result is obtained,
Figure imgf000009_0003
Remark:
A = molecular absorbance
10 initial light intensity I = intensity of light transmitted by molecules in the sample T transmittance percentage ε - molar absorption coefficient in units of 1 mol-1 cm-1 c concentration of molecules in mole unit/1 d length of sample passed by the light in cm
The Beer Lambert equation indicates a linear relationship between the sample concentration and the absorbance value thereof . Basic assumption that the dif ference between 10 and I is a measurement of absorbance radiation . However, chis is not completely true because ID may not be measurable, so the actual number of 10 is as described in equations (5) , (6) and (7) .
10 ~ absorbed + I + lost intensity (5)
The transmission radiation is obtained by measuring the empty samples by placing effective 10, so that equation (6) is obtained
Empty sample = 10 - lost intensity (6)
Therefore, absorbed = 10 I (5)
Maximum transmittance can be obtained by using an empty sample to obtain 100% transmittance and 0 absorbance . Ready to test urine samples are placed on the instrument as in the Image 2.
The test is conducted to know the amount of light intensity received by the detector that is converted to voltage in digital form by using ADC. The first s tep of resting the instrument is to determine the comparison curve between the ADC readings and the D (+) Glucose levels with different levels . The realization of the software design requires a comparison curve Of D ( +)
Glucose levels with different levels . The realization of the software design requires a comparison curve between the ADC readings and the amount of glucose concentration in pm units .
The purpose is to convert the value of the ADC readings to the concentration of D (+) Glucose in Ppm units and then convert the same to urine glucose levels namely mmol/L . The measurement of the ADC values for each different glucose concentration is presented in Table 1. From the results of ADC readings of glucose samples with different concentrations, a regression value can be determined to determine equation in determining the amount of glucose concentration in the urine . The regression graph of the reading of ADC values of different concentrations is presented in Image 2. Instrument block data is presented in
Image 3.
Table 1. ADC Reading Results from Different Concentrations of
D (+) Glucose
Figure imgf000011_0001
Figure imgf000012_0002
From the Image 2, we know that the linearity relationship between the ADC values and glucose concentration with the linear regression equation thereof is
Y - 0, 126x + 277.2 (8)
So that Equation (9) is obtained to determine glucose levels .
Figure imgf000012_0001

Claims

Claims
1. A Portable and non-invasive measuring instrument of laser spectroscopy-based urine glucose levels comprising of : infrared diode laser; photodiode detector; voltage amplifier circuit; microcontroller ; digital display device; sample container; characterized by a microcontroller that processes input data from the ampli fied photodiode detector voltage rate by using a voltage amplifier circuit where the voltage rate is in proportion to the infrared laser light, intensity captured by the photodiode detector and the voltage is converted in digital form.
2. A portable, quantitative and non-invasive measuring instrument of urine glucose levels as in the claim 1, where the infrared laser diode being a light source is placed in parallel to and in opposite to the photodiode detector used for measuring the light intensity that passes the cuvette as a sample urine container .
3. A portable. quantitative and non-invasive measuring instrument of urine glucose levels as in the claim 1 -2, where the microcontroller contains a program for converting analog voltage data into digital data that compares the Intensity before the sample is inserted and the Intensity after the sample is inserted into the cuvette .
4. A portable, quantitative and non- invasive measuring instrument of urine glucose levels as in the claim 1-3, where the light intensity is then converted to voltage input data to obtain accuracy level by comparing the voltage input data to the reference urine glucose level sample.
5. A portable, quantitative and non-invasive jmeasur ing instrument of urine glucose levels as in the claim 1-4, where the program on the microcontrol ler using language C is preferable .
6. portable, quantitative and non-invasive measuring instrument of urine glucose levels as in the claim 1-5, where the LCD display screen, is preferable.
7. A portable quantitative measuring instrument of non- invasive urine glucose levels as in the claim 1-5, where the glucose level display on LCD screen is mg/dL .
8. A portable, quantitative and non-invasive measuring instrument of urine glucose levels as in the claim 1-6, where the urine samples in fasting, postprandial or temporary condition are preferable .
PCT/ID2021/000001 2020-11-26 2021-11-26 Portable, quantitative and non-invasive measuring instrument of laser spectroscopy-based urine glucose levels for early detection of diabetes mellitus WO2022113060A1 (en)

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Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ALI HAIDER ET AL: "Novel Approach to Non-Invasive Blood Glucose Monitoring Based on Transmittance and Refraction of Visible Laser Light", IEEE ACCESS, vol. 5, 23 May 2017 (2017-05-23) - 28 June 2017 (2017-06-28), pages 9163 - 9174, XP011653609, DOI: 10.1109/ACCESS.2017.2707384 *
LEE YI-HSIUNG ET AL: "The noninvasive and optical only glucose monitoring investigation and analysis", 2021 IEEE INTERNATIONAL INSTRUMENTATION AND MEASUREMENT TECHNOLOGY CONFERENCE (I2MTC), IEEE, 17 May 2021 (2021-05-17), pages 1 - 5, XP033934991, DOI: 10.1109/I2MTC50364.2021.9459869 *
REICH ET AL: "Near-infrared spectroscopy and imaging: Basic principles and pharmaceutical applications", ADVANCED DRUG DELIVERY REVIEWS, ELSEVIER, AMSTERDAM , NL, vol. 57, no. 8, 15 June 2005 (2005-06-15), pages 1109 - 1143, XP025283939, ISSN: 0169-409X, [retrieved on 20050615], DOI: 10.1016/J.ADDR.2005.01.020 *

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