TR202013687A2 - Non-Interventional Mobile Blood Glucose Meter - Google Patents

Abstract

The invention relates to an improved device for measuring mobile bedside blood glucose used for periodically measuring blood glucose of type-1 and / or type-2 diabetics. Thanks to this invention, instead of blood glucose measurement devices, which are used today to measure the blood glucose levels of patients themselves in the medical and biomedical industry branches and which are made with blood (interventional-invasive) and disposable test kits, without bleeding the fingertip. (non-invasive-noninvasive) Using customized Raman spectrometry, hemoglobin and blood glucose levels are measured.

Description

DESCRIPTION Non-Interference Mobile Blood Glucose Meter The invention is suitable for mobile use, which type-1 and/or type-2 diabetes patients can carry with them. It relates to a device developed to measure blood sugar periodically.

State of the art Invasive blood glucose meters and kits available today, o-toluidine by measuring the color change caused by the reaction or by glucose oxidation to gluconic acid and blood sugar by measuring the conductivity level that changes as a result of hydrogen peroxide formation measuring levels. However, all of these devices are interfering, that is, invasive. These are single-use kits that are used with fingertip blood and device. can measure with. By measuring the color change caused by the reaction to o-toluidine, used in the prior art, or Changed conductivity as a result of glucose oxidation and formation of gluconic acid and hydrogen peroxide fingertip blood and device for measurement of blood sugar levels by measuring blood sugar level A single-use kit is required to be used with called Interventional (Invasive Disadvantages of these devices (used) are that they need to measure blood sugar 4 to 8 times a day. Infection in the fingertips, numbness, long-term bleeding etc. cause problems in blood glucose measurements of children, they are quite uncomfortable to use. In addition, intrusive and devices based on the aforementioned glucose oxidation and o-toluidine reaction. Calibrations should be done every 3 months with a reference biochemistry laboratory equipment.

For the device developed with the invention, this period may extend up to 1 year.

In the table below, various features of some conventional blood glucose meters specified. In the table, conventional blood glucose measurement devices are developed with the invention. The comparison with the blood glucose measurement system is also given (Table 1).

Table 1. Comparison of blood glucose measurement systems Technicial Specifications With Invention developed Spectroscopy Based Device Strip-Based Entrepreneurial House Type Devices (Bayer Contour TSE, Accucheck®, OneTouch Ultrasound Interfering N lR absorbance Measurement Devices (Cnoga®, GIuco-wise®, DiaMonTeCE] Being movable movable movable movable Instant/Continuous Measurement Instantaneous Instantaneous Consumables _ job job _ _ None Strip for interference measurement at each measurement Usage _ work _ I and interference measurement 10-50 at first use with interference measurement Calibration Frequency Once a year 6 months to 1 year _ _ calibration, followed by Measurement Method _ Glucose Oxidation NIR Spectrometry spectrometry Device measurement Your measurements Coefficient of Variation - - - Smart phone Yes Some brands have yes Application Support Commercial Sales in the Market and Widely Used No Yes No It also includes patent scans on blood glucose measurement devices and measurement techniques. Research has also been done and a patent application containing the scope of this invention has been submitted. not found.

Patent application number U810299706 is a non-invasive method of blood glucose concentrations. It concerns the measurement method and the apparatus required for its implementation. mentioned method polarized infrared light of glucose in human blood again polarizing to a specific angle is based on. Incoming polarizer with a given angular position of a polarization plane Glucose in blood exposed to infrared radiation, first polarization and second polarization separation and the angular polarization state of both light beams. The determination of the polarization planes by a polarizer-analyzer measuring process such as measuring an angle shift between their angular positions and the transmitted radiation includes steps.

Patent application numbered USlO209192 is used to detect glucose levels in hemoglobin. describes an invasive method for According to this; passing through a sample of hemoglobin a second correlation matrix using a second light beam at a second wavelength is created. First correlation matrix, second correlation to get a third matrix multiplied by the inverse of the matrix. A fourth matrix is formed by taking the singular value decomposition of the third matrix. is created. The fourth matrix is a unique one for the glycation level in the hemoglobin sample. Contains biomarker. The level of glycation in the hemoglobin sample corresponds to the fourth matrix. determined as a response and output as an indicator describing the determined glycation level. Patent application numbered US9885698, glucose, ketones, HbAlC and other blood components Near-infrared lasers are used for monitoring with non-invasive infrared absorption method. It relates to a wearable device for use with a smartphone or tablet that it receives.

Patent application US9937293 describes a glucose solution for the monitoring and treatment of diabetes. to receive glucose concentration data from the sensor and monitor the glucose concentration continuously. relates to a device configured to monitor

US l 0 l 368 l 9 patent application short wave infrared for imaging applications It relates to an imaging device comprising supercontinuous lasers and similar light sources.

Said device; Laser diodes (LDs) that produce light near infrared wavelengths a primary lens with one or more detectors configured to transmit the receiver and at least one LD impact piece.

Patent application U88583204 nuinarali is an invasive continuous treatment of an analyte concentrate SVO. It is a device designed for measuring membrane (here the membrane contains a polyurethane and a hydrophilic part).

Patent application U810006859 relates to a multi-parameter spectroscopy system.

An apparatus for detecting material in a sample, at least one light through the sample. It contains a light emitting unit to direct its beam. Multiple units from sample receives the passing light beam and, depending on the received light beam, the spectroscopic performs the analysis. Each of the many units defines a different parameter according to the sample. analyzes and provides a separate output signal according to the analysis. One processor, discrete output provided detects the material according to each of its signals.

US9759714 nuinarali patent application for a non-invasive glucose concentration It relates to methods and apparatus for normalizing the path length in the optical system.

The mentioned method is based on light absorption and a detection from the first photo-detector providing a source of optical energy spaced by the field; first from the optical energy source of energy transmitting it to the photo detector; to the light intensity observed by the first photo-detector. storing a corresponding first reading; then an optically active substance delivering a solution containing a solution to the sampling area of the cabinet; optical energy in the sampling area transmitting energy from the source and onto the first photodetector; first photo-detector storing a second reading corresponding to the light intensity observed by; It includes the steps of determining the ratio of the first reading to the second reading.

Patent application USlOZ13 l 13, a light with LEDs for measuring physiological parameters a wearable measurement with a source, adapted to be placed on the wrist or ear It's about the device. The meter modulates the LEDs between 700-2500 nanometers. produces an optical beam of near-infrared wavelength, and lenses to transmit the beam to the tissue, have spectral filters in front of spatially separated detectors connected to the analog it reflects on a receiver and works on an absorption basis. Signal-noise of heat reflected from tissue ratio, by comparing the receiver outputs and increasing the light intensity from the LEDs. is improved. The receiver is synchronized to the modulation of the LEDs and changes the modulation frequency. It uses a sensing locking technique. Measuring device invasive on blood in tissue produces an output signal that represents a measurement that is not

Patent application number U810201283, Close-up used in Imaging applications It relates to infrared laser diodes. A series of pulsed laser diodes between 700-2500 nanometers. produces light with near-infrared wavelengths. Second lenses, array to texture generates light to directed points. An infrared camera synchronized with laser diodes and The array generates data based on the light reflected from the tissue. Smartphone or tablet, infrared creates a two-dimensional or three-dimensional image using the data from the camera. Clever The phone or tablet consists of a wireless receiver, a wireless transmitter, a display, an audio input module, and includes a speaker.

Patent application U8102785 80, continuous analyte for monitoring and treating diabetes relates to an integrated drug delivery device for use with a sensor. According to this; amount of drug a drug injection pen, configured and arranged for injecting into the host, configured and arranged to receive sensor data from a continuous glucose sensor an integrated receiver, configured at least for input of host information, and Contains a customizable user interface.

Patent application U810188325 describes an ultrasound for noninvasive glucose detection. generator, an ultrasound detector, a non-invasive glucose sensor, and a feedback unit. relates to a wearable device containing

USlOlSS299 patent application for measuring physiological parameters It relates to a structured wearable device system. Accordingly, its physiological parameters multiple halves, each configured to generate an output optical beam, to measure contains a light source with conductive light-emitting diodes (LEDs), where one or more At least part of the wavelength of excess optical light is near infrared. Light by increasing the light intensity for at least one of the LEDs and at least one of the LEDs It is configured to increase the signal-to-noise ratio by increasing the pulse rate. Output optical heat A lens is configured to receive and send output heat to the tissue. a detection system, generates an output signal in response to the lens output beam reflected from the tissue; don't detect here system is configured to be synchronized to the light source and from the first of the LEDs located at a different distance from the second one.

Patent application US10098546 describes wearables that use near-infrared light sources. relates to the device. Here, the wearable device is a light-emitting device that measures a physiological parameter. It contains a measuring device with diodes (LEDs). Measuring device, 700-2500 nanometers modulate the LEDs to produce an optical beam with a near-infrared wavelength between it does. The lenses are analog-to-digital, configured to generate the optical beam, receiver outputs. reflecting on a receiver with spatially separated detectors coupled to the converters receives the optical heat and transmits it to the tissue. The receiver catches the light when the LEDs are off and when the LEDs are on captures the light reflected from the tissue to generate the first and second signals, respectively. Signal- noise ratio, differentiation of first and second signals and receiver outputs improved by differentiation. The meter can also be adjusted according to an initial light intensity. It improves the signal-to-noise ratio of reflected optical light by increasing the light intensity of the LEDs. Measuring device representing a non-invasive measurement on blood contained within tissue generates an output signal. This paper relates to the use of Raman spectroscopy for non-transcutaneous measurement. Raman spectroscopy for transcutaneous glucose measurement in patients with blood glucose levels monitored used. Raman spectra, glucose reference provided by standard capillary blood analysis were collected through the skin along with their values. Some of the data from each subject small squares calibration created and cross-validation leaving one out validated using

Patent application EP2528505 was found in the interstitial fluid in the skin of a subject. Apparatus for non-invasive in vivo measurement of glucose by Raman spectroscopy.

Accordingly, said apparatus includes a light source, the first optical components are from said light. defines a light path. A light to a measurement location below the source skin surface Raman scattered from the measurement location to the sensing unit, the second optical components, said light sensing unit defining a return path to the light and said first and to define the position of the second optical components relative to the surface of the coating in use It consists of a skin-attached element with a distal surface.

In the patent application numbered USZOl60354015, skin thickness was determined by Raman spectroscopy. and non-invasive measurement of glucose concentration and calibration method is explained. In said application, the glucose concentration in the blood of a subject for the purpose of operating a physiological measurement system to measure; the subject mentioned receiving a Raman signal from a predetermined area of his skin; the aforementioned Raman A second data related to the glucose concentration in the second layer based on the signal taking the data and based on the first data and the second data, the blood of the said subject It consists of processing steps, including determination of glucose concentration.

In practice in medicine and bioinedical industry, patients' self-blood sugar To measure the levels of blood (interventional- invasive) and disposable test kits are used. In this invention, type-1 and/or type-2 mobile patient used to measure blood sugars of diabetic patients periodically. that is, it is designed to measure blood sugar without intervention (non-invasive).

Technical problems that the invention aims to solve The blood glucose measurement system designed with the invention can measure blood glucose from the fingertip to the skin. By measuring the blood in the capillaries under the Raman spectrometry method, it is possible to determine the blood sugar level. based on the measurement principle. However, Raman spectrometry technique generally electro-optical, which gives the relevant specific peaks of all the molecular components in its content. It is a technique that requires the use of expensive CCD optical sensors. In this aspect, meet; CCD that is expensive and requires high hardware and software performance to operate instead of the sensor, it only measures the specific peak intensities of molecules required for blood glucose measurement. comparatively to conventional systems by using a specialized optical detector that can measure It is a system that measures mobile blood sugar at similar costs. In this way, the invention developed The device allows patients who need frequent blood glucose measurements, bloodless and much more comfortably. It will allow them to measure their blood sugar without interference. Similarly, children needle, kit, etc. in blood sugar measurements. as medical consumables, without bleeding It will allow blood sugar to be measured.

Description of the invention The invention demonstrates the hardware analysis of a blood glucose measurement method using Raman spectroscopy. mobile in the size and weight of cheaper, effective and conventional blood glucose meters It is based on the electro-optical design that will enable it to be developed as a device.

Description of Figures Figure 1: Raman energy levels diagram Figure 2: Raman detector optical components specialized for glucose measurement Figure 3: Raman detector and peaks specialized for glucose measurement Figure 4 : The Specialized Raman Detector Subject to the Invention Figure 5 : Mask placed in front of the Detector Subject to the Invention Detailed description of the invention: Diabetes is among the most common diseases in the world and is incurable but appropriate. control with exercise and nutrition programs and regular monitoring of the amount of glucose in the blood It is an incurable disease. Some patients can use fingertips 8 or more times a day. It is necessary to measure sugar with the blood taken and it is painful every time while making these measurements. In addition to feeling, the patient's skin weakens, the blood flow cannot be stopped, risk of infection, complications such as numbness and the use of these methods in daily life The lack of practical methods that can be applied also means that blood sugar levels can be adjusted without intervention. There is a need to develop new methods that will allow the measurement of shows. In addition, the latest technology such as measuring stick, finger piercing needle, continuous tracking sensor. Consumables that are out of date and easily affected by ambient temperature and humidity extra cost is also an important parameter. However, the existing The consumable costs of the devices are also quite high.

Raman technology, which is one of the optical methods without interference in the literature, levels can be measured reliably. In determining blood sugar level currently used devices, fingertip puncture blood and o-toluidine by measuring the color change caused by the reaction or by glucose oxidation to gluconic acid and blood sugar by measuring the conductivity level, which changes as a result of the formation of hydrogen peroxide measuring levels.

There are many cases where Raman spectroscopy can be used to measure blood sugar without interference. It has been dealt with in many scientific studies and experimental data have been obtained. Raman spectroscopy has advantages over other blood glucose measurement methods.

Having relatively low cost and high quality optical components in today's technology, The use of excitation light at a single wavelength, specific to each molecule, has a signature quality. generation of spectrum peaks, non-invasive (non-invasive) and non-destructive measurement can be obtained. and any disposable test kit etc. for measurement. not need are some of these advantages. However, Raman spectroscopy technique is better than existing systems. hardware and software that require cost and high analytical performance as disadvantages. Requirement Need can be shown.

Based on international standards in this field, for conventional interference systems specified sensitivity, reliability, etc. properties can also be determined by interference-free Raman spectroscopy. It has been proven by scientific studies that it can be provided.

This invention demonstrates the hardware analysis of the blood glucose measurement method using Raman spectroscopy. mobile in the size and weight of cheaper, effective and conventional blood glucose meters It is based on the electro-optical design that will enable it to be developed as a device.

Raman spectroscopy systems are generally mentioned in the figure below and are used by an Indian physicist. Observed by Chandrashekhara Venkata Raman in 1928 and awarded the Nobel Prize in 1930. It is an important analysis tool in the field of science and technology with its research that enables it to work.

This phenomenon, also known as the Raman effect, is caused by the vibration, rotation and other low As a result of the change in molecular energy levels in frequency resonance modes, 0 molecules The radiations observed in the specific fingerprint selectivity and the radiations that stimulate the molecule of these radiations. can be defined as the relationship between

The energy levels seen in Figure 1 are the quantum values in the bond energies of any molecule. are jumps. The molecule is removed from the sample by excitation with an inochromatic light source (Laser). scattered names are observed. The measured rays are different from the Rayleight scattering in the figure. passes to a lower or higher quantum level, and in this process the excited monochromatic light A release of energy occurs, either less (Stokes) or more (Anti-Stokes) energy.

Raman spectroscopy, mining, pharmaceutical industry, chemical industry, biology/microbiology It is used extensively in many technological fields such as the petrochemical industry.

Figure 2 shows the general optical components of the Raman spectrometer. of the system in order of work; Laser diode with a monochromatic light source (830 nm laser diode) (a) the incoming excitation light is first filtered through an IR filter (b) which filters out the IR radiation emitted from the source. is passed. Then, a light beam is formed with a lens (C) and with the help of the light splitter mirror (d). 50% of the name is directed to the sample. Laser light with the help of focusing lens (e) focuses on the sample. Raman rays scattered from excited molecules pass through the same optical path. it reaches the light divider (d) again and again 50% of it passes directly across. On the optical path Rayleight with only the stokes and anti-stokes rays and the laser light itself The light from the sample is filtered by the single-proof filter (f) (notch), which filters the radiation. Just After the Raman rays pass through the notch filter, they are focused by a lens (9) into the optical half (h).

Raman rays passing through the slit are observed in the optical grid (I) at different angles according to their wavelengths. It is conditioned and specific for optical glucose measurement with lens (k) after deflection with a flat mirror (D). focuses on the mask (I) located at the locations of the peaks. passing through the slits on the mask Raman rays reach the photodiodes (m) located behind the mask and each Raman name The invention is based on the cheap and small size of the system, the optical and electronic components of which are described above. optimized for measuring blood sugar only It is based on the development of a non-invasive blood sugar measuring device. 3) cheaper, analysis power with an electro-optical detector to be placed at optical locations a Raman glucose that can work with relatively lower computer hardware and software detector development. For this purpose, a detector shown in Figure 4 has been designed. Shape PIN diodes (3) seen in Fig. 4, optically blood glucose and associated reference (Hemoglobin) A circuit (1} is located at the points where the peaks are observed and with micro wire connections. They are connected to the board (5] and from there to the conductor pins (2) via signal transitions (4]. with a mask (Figure 2/I and Figure 5) to be positioned in front of the detector Intensities of molecular peaks can be measured with a simpler and more economical detector.

Thanks to this invention, the blood sugar that diabetics have to measure constantly It is the greatest advantage to measure the value without pain, blood and intervention. In addition, As a result of measuring with the spectrometry technique, which is the subject of the invention, no consumables use is not required. Average lifetime of conventional systems and consumables equal to operating costs that will last for many years, given the material requirements. It is important that it is a cost-free system and does not require any consumables. is an advantage.

Raman spectroscopy technique, which is the working principle of the developed product, has been scientifically proven. It is an analysis and measurement technique that has been used in related industries for many years. known. However, using this technique, a specialized instrument that can only measure blood glucose a sensor application is designed for the first time in the world within the scope of this invention.

Regarding the invention, the preliminary studies mentioned in scientific publications and articles are standard. It was tested using a Raman spectrometer. In these trials, standard Raman Fingertip measurements were made using the fiber optic probe of the spectrometer. Invention subject glucose and reference Raman radiation spectra of molecules (hemoglobin, etc.) were investigated.

In order to measure blood sugar without intervention, which is the subject of the invention, Raman spectrometers for use in the detection of a single molecule or component Customization is an innovative approach. The sensors developed by this method are Instead of the entire spectrum that can be obtained from a Raman spectrometer, only the selected molecule will be able to measure Raman radiation intensities that can be used in the detection of compounds or compounds. This The non-invasive blood glucose measurement system, which will be developed with the invention, will only be used for blood glucose. It will be a detection and measurement system. In a standard spectrometer intended by the invention high sensitivity near infrared (NIR) CCD detector and this due to the hardware and software required for the detector to be operated and analyzed. It is to prevent the high cost and complexity of the system. To be obtained with the invention non-interference blood glucose measurement system will not use the above mentioned CCD sensor and all corresponds to the wavelengths of the predetermined desired Raman radiations instead of the spectrum. Photodiodes at the incoming optical positions will be used. Thus, the cost of NlR CCD It will not be, and in parallel, the required for CCD with 1024 or 2048 pixel elements. Computing performance will not be required either. Uninterrupted blood sugar with the invention To measure it, only 6-10 photodiode measurements will be sufficient. Similarly, with the invention The proposed method is inexpensive, reliable and reliable for the detection of many other inolecules or compounds. It uses a simpler electronic infrastructure than a standard Raman spectrometer. systems can be realized. The invention, apart from measuring blood sugar without intervention, Molecule or component-specific Raman detector with mobile speed in other areas It can be used as a detection device.

The non-invasive blood glucose measurement system developed with this invention offers its users a conventional the problem of puncturing the fingertip with a needle, which they live with, from the blood taken. It will solve it without the need to measure sugar. In this way, certain group infection, fingertip numbness, which cause important health problems in patients, conditions such as bleeding problems, difficulty in administration in elderly or pediatric patients will not happen. In addition, no consumable parts of the system offered with the invention It is also an important benefit to measure blood sugar without intervention. Invention& additional Widespread use of Raman spectroscopy technique in blood glucose measurement A specialized electro-optical detector whose high cost and complexity hinders operating costs of conventional blood glucose measurement systems using equates. In this way, the same costs, the same reliability and standards without interference. blood sugar can be measured.

Claims (5)

REQUESTS . It is a non-invasive blood glucose meter, and its feature is; For blood glucose measurement, it is characterized by a specialized optical detector that can measure the peak Intensities of hemoglobin and determinant and specific molecules such as glucose in the blood. . It is a device according to claim 1 and its feature is; PIN diodes (3) are optically positioned at the points where the glucose and related reference (Hemoglobin) peaks in the blood are observed, and they are transmitted to a circuit board (5) and from there to a circuit board (with micro wire connections). 4) and a mask positioned in front of the detector, connected to the conductive pins (2) (Fig. 5) is characterized only by measuring the intensities of the respective molecular peaks with an electro-optical detector. . It is a device according to claim 2 and its feature is; It has a detector design suitable for mobile use. . It is a device according to claim 1 and its feature is; It is suitable for use by type 1 or type 2 diabetes patients. . It is a device according to claim 2, its feature is; is the use of photodiodes at optical positions corresponding to the wavelengths of the predetermined desired Raman radiations. . It is a device according to claim 5, its feature is; 6 to 10 photodiode measurements are sufficient. . It is a device according to the request and its feature is; It is suitable for periodic use.