WO2023048681A1

WO2023048681A1 - High precision noninvasive blood glucose measurement sensor and system with microstrip technology

Info

Publication number: WO2023048681A1
Application number: PCT/TR2022/050991
Authority: WO
Inventors: Ali Kara; Pejman MOHAMMADI; Ali MOHAMMADI; Simsek Demir
Original assignee: Gazi Universitesi Rektorlugu
Priority date: 2021-09-24
Filing date: 2022-09-15
Publication date: 2023-03-30

Abstract

The subject of the invention is a high precision non-invasive blood glucose measurement sensor and system with microstrip technology providing high precision and accuracy by minimizing environmental impact and noise level, reducing the error rates in the system measurement process and the time to get results, which enables the sensor size to be reduced and the dielectric coefficient to be determined non-invasively, eliminating finger positioning problems, is low cost and requires no investment, and consisting of the parts of BLC sensor with 4 ports, including input port, two output ports and isolated port, connected to each other by transmission lines, SRR sensor, which reduces the size of the sensor by positioning it in the space above the BLC, which is connected to the system with microstrip lines in series, and the glass layer that is positioned to cover the SRR, on which the finger is positioned to take the measurement, preventing the electrical contact between the finger and the sensor.

Description

HIGH PRECISION NONINVASIVE BLOOD GLUCOSE MEASUREMENT SENSOR AND SYSTEM WITH MICROSTRIP TECHNOLOGY

Technical field of the invention:

The invention relates to a blood glucose measurement sensor and system that are developed using low-cost printed circuit method and microstrip technology, which can measure blood sugar level in a non-invasive manner with high precision and continuous monitoring.

In particular, the invention relates to a non-invasive blood glucose measurement sensor and system based on the use of a branch line coupler (BLC), split-ring resonators (SRRs) and a glass layer placed in between the finger to be measured and the sensor.

State of the Art:

Diabetes mellitus, or diabetes as known among people, is a metabolic disease-that disables the human body’s natural mechanism to regulate the Blood Glucose Levels (BGLs).

The aim of diabetes treatment is to regulate blood glucose, in other words, to prevent blood glucose spikes and blood glucose drops. Ensuring this adjustment is extremely important to prevent the development of complications or slow the course of advanced complications. While mentioned blood glucose exceeding 230 mg/dL, causes serious health problems, especially related to the heart and eyes, the decrease in blood glucose (typically 65 mg/dl) can lead to fatal consequences, especially brain damage.

Regular monitoring of the blood glucose of diabetic patients not only increases the quality of life but also reduces the burden of the health system. These diabetes patients need to measure their BGLs regularly, every day or even more than once a day in order to monitor and control diabetes successfully. Advanced diabetes patients (using insulin) determine their insulin dosages according to the measured BGL values and nutritional diets. Existing blood glucose measurements currently used by patients are based on the procedure of, in an invasive manner, taking a capillary blood sample with a needle, applying it to the test strip, and reaching the BGL value as a result of placing the test strip on the measuring device (Glucometers). However, this method is quite troublesome for patients who require continuous measurement for diagnostic and therapeutic purposes. For this reason, methods are being developed rapidly to measure blood glucose level in a non-invasive manner.

Enzyme-based electrochemical methods are methods used to detect glucose level by measuring sweat and interstitial fluid (ISF) and correlating them with glycemia in the bloodstream. Non-invasive methods of monitoring glucose in the interstitial fluid through the skin have been widely used in recent years due to increasing patient compliance. The micro-invasive sensing of interstitial fluid by micro-needles and microneedle arrays has been used by Jina et al. in the development of glucose-sensing patches. Micro-needle patches ensure that the device is in continuous contact with the skin, permanently reaching the interstitial fluid and continuously monitoring the glucose level. The short length of the micro-needles provides optimal penetration for interstitial fluid samples.

Using hydrogel glucose-sensing micro-spheres, Russell et al. developed, for the first time, 'tattoo' type glucose sensors. By advancing this technology, Zhive et al. have placed the sensors in a thin film layer and achieves faster analysis of solutes.

Another non-invasive method is a group of devices that perform sweat analysis. In 2010, Heikenfeld et al. developed sweat detection patches that can wirelessly measure solution concentrations in sweat, triggering sweat production, and transmitting this information to a smart phone. In addition, Wang et al's work on detecting specific solutions in sweat continuously and in a non-invasive manner by electrochemical analysis led to creative sensors such as wrist-worn bands, glasses, and adhesive flexible sensors. However, in systems regarding glucose analysis conducted with sweat, the delay between ISF and physical glucose changes in the blood remains a problem.

Significant work has been performed to develop alternative non-invasive glucose measurement techniques. These studies are on optical methods using optical parameters such as optical coherence tomography (OCT), fluorescence spectroscopy of glucose concentrations. However, bulky and costly instruments are often required for such measurements at short wavelengths. Absorption spectroscopy techniques such as red/near-infrared and mid-infrared work on the principle of scattering light on biological tissue to detect optical signs of glucose in the blood. However, the high cost of implementation, and high precision to changes in physiological and environmental parameters are general shortcomings for these approaches.

One of the non-invasive glucose measurement methods being developed is devices that measure by emitting high-frequency radio waves. In said technique, electromagnetic (EM) waves provide solid penetration in biological tissues, unlike ionizing radiation (eg X-rays) which can cause dangerous effects. Such techniques are mainly based on material characterization theory, in which a correlation model is applied successfully since the EM properties (dielectric permittivity and conductivity) of a person's blood are significantly affected by glucose content. For material characterization in said microwave/RF ranges, dielectric permittivity measurement is provided by transmission and reflection techniques.

Microwave biosensors are Printed Circuit Board (PCB) based sensors compared to other thermal, optical and micro electro-mechanical (MEMS) based sensor types. These sensors are preferred because of their low cost, easy fabrication and design flexibility, and they offer much more efficient real-time responses for on-site applications compared to expensive and labour-intensive chemical procedures.

Split ring resonators (SRR), which are excited with normal magnetic field show meta material properties (positive si negative z) with induced resonating current in the loop. These small electrical size resonators are preferable in detection and characterization applications due to their accuracy, small size, simple fabrication, easy integration and high precision. In said systems, device precisions are higly dependent on the planar resonators connected to transmission lines. Particularly split ring resonators (SRRs) and microstrip lines have potentials to improve precision by localizing the electric field in a small sensing area. However, the resulting instrument precisions are determined by the coupling level between the resonator arms and the transmission lines, and by the structure of the resonator. The branch line coupler (BLC) is one of the most common microwave components in many radio frequency (RF) applications for design simplification and system integration. The branch line coupler (BLC) is a type of directional coupler that divides the incoming power equally into two output power channels with a phase difference of 90°. Branch line coupler (BLC) phase difference between connected and open ports is odd multiples of 90°. Furthermore, the traditional branch line coupler (BLC) has been developed in the form of two crossover transmission lines and two vertical branches with quarter wavelength transmission lines. The most common application of branch line couplers (BLC) has been quarter wavelength where all branches are designed in the centre of the frequency band of interest.

Accurate and precise continuous monitoring of blood glucose is critical for patients both in hospitals and at home for diagnostic and therapeutic purposes. The performance of the proposed methods can generally be evaluated by criteria such as accuracy, precision, size and cost. The most critical component in non-invasive blood glucose measurement systems is the sensor component that detects the level of glucose in the blood. The working principle of non-invasive sensors is based on the electromagnetic interaction of the part of the body to be measured with the sensor. This method requires a very precise measurement and, environmental effects and noise appear to be the most important parameters.

Patent document no “US2008/ 0200790A1” in the state of the art is reviewed. In the abstract of the invention that is the subject of the application, the statements that read "There is provided an apparatus for measuring a blood sugar by using a microwave without withdrawing any blood while enhancing the reliability of measurement. The apparatus for measuring the blood sugar according to the present invention has a main body having a measurement surface configured to contact a measurement portion of a user, a probe part having a contact member exposed on the measurement surface” is given. In said document, microwave-based non-invasive blood glucose measurement apparatus is explained with the help of a probe, and environmental noise is reduced by means of the probe. However, humidity and temperature in the environment still affect the precision and accuracy of the system. Patent document no “LIS2012/0150000 A1” in the state of the art is reviewed. In the abstract of the invention that is the subject of the application, the statements that read “The invention concerns a device for non-invasive monitoring of the concentration of a constituent of a human or animal bloodstream, the device comprising drive circuitry for provision of an alternating current at a microwave frequency. The device has a sensor adapted to be placed in proximity to the body of the human or animal. The sensor is electrically connected to said drive circuitry to receive said alternating current and is adapted to project microwave energy into the said body. Detector circuitry is provided for detecting a signal transmitted and/or reflected by the sensor, the detected signal properties being dependent on the concentration of the said blood constituent” are given. Said invention is a device that uses a non-invasive sensor with the help of a ring resonator on a waveguide (CPW-coplanar waveguide) operating in the 1-6 GHz band. The fact that the operational band in said system is very wide requires a license, and it does not take into account environmental factors which is resulted in a precision problem.

Patent document no “WO2014/ 048799A2” in the state of the art is reviewed. In the abstract of the invention that is the subject of the application, the statements that read “A sensor arrangement for non-invasive measurements of dielectric permittivity of liquids comprises a signal splitter comprising a reference path coupled to said signal splitter, a reference fluid container containing a reference fluid, and a reference sensor with a measurement path. A processor determines a change in amplitude and/or phase of said sensor signal compared to one or more reference signals obtained in reference measurements using reference fluids and determines the dielectric permittivity of the measurement fluid from said determined change in amplitude and/or phase of said sensor signal. The reference sensor and the measurement sensor each comprises two or more coupled microstrip lines” are given. The present invention is based on the non- invasive measurement of the dielectric constant of fluids. The fact that the reference and measurement sensors have two or more microstrip coupling lines increases the size of the structure and therefore increases the environmental effects. This situation requires more calibration during measurements.

Patent document no “US2014/0213870” in the state of the art is reviewed. Said patent document is described as “The present invention describes a system comprising a substrate, a first metal layer, a second metal layer, and a blood glucose sensing unit. The first metal layer is formed on the one surface of the substrate and has a microstrip antenna in the internal thereof, the second metal layer is formed on the other surface of the substrate, and the blood glucose sensing unit is electrically connected to the first metal layer and the second metal layer. In the present invention, the non-invasive blood glucose sensor can be used to measure a numerical value of the blood glucose in a human body by way of disposing the non-invasive blood glucose sensor near the human body, without using any body-invading ways.” The invention is based on accuracy and precision values that are not very realistic for practical use. It is also exposed to a much higher amount of environmental effects than the previously described solutions.

As a result, due to the weaknesses and disadvantages along with the inadequacy of the existing solutions on the subject, it was necessary to make a development in the relevant technical field.

The aim of the invention

The most important aim of the invention is to provide high precision and accuracy by minimizing environmental effects and noise level by developing a sensor based on microstrip technology with a new sensing technique provided by branch line coupler (BLC) as the main transmission line and split ring resonators (SRRs) as the sensing area.

Said invention is based on the use of a branch line coupler (BLC) and split ring resonator (SRR) together and the use of a glass layer between the finger to be measured and the sensor. The SRRs are located in the free space of the BLC and are connected in series to the serial branches of the BLC by two thin microstrip lines.

In existing sensors, transmission lines and sensing fields are not directly connected. In the developed sensor, the sensing area SRR is directly coupled to the BLC and therefore, the effect of leakage fields in existing sensors is reduced by the proposed technique. In addition, the direct and coupled arms of the BLC provide two output lines symmetrical in differential form to the proposed sensor. These symmetrical outputs make it easy to balance the finger position. The technique is based on the system of lowering the frequency in the transmission line in the coupled arm of the BLC due to the glucose concentration on the SRR. The change in dielectric coefficient (dielectric permittivity) is measured by looking at the change of transmission zeros (TZs).

Said invention has been developed in a structure where the finger position can be adjusted according to the transmission zeros values of the BLC sensor at the outputs. By using a glass interface between the finger and the sensor, any electrical contact between the finger and the sensor is avoided.

The sensors described in the state of the art are systems with two sensing parts. This situation causes a sensor system configuration with a large transducer structure. On the other hand, there is one sensing part in the developed sensor. Therefore, it can be produced in a smaller size compared to existing sensors. In addition, adding capacitive and inductive elements on the empty space of the BLC can cause the size to be reduced even more.

The sensor design based on microstrip technology used in the present invention provides high precision and accuracy by minimizing environmental effects and noise level due to the same TZs at two outputs simultaneously. The system has been developed in a structure that enables lower errors in the measurement process and shorter time to get results as well as reduced sensor size.

Said invention provides superiority to the known state of the art by its properties of non- invasively determining the dielectric coefficients of materials, especially blood glucose, providing high precision compared to the sensors described in the state of the art, minimizing noise and ambient effects, having a smaller structure compared to similar sensors, eliminating finger positioning problems in the measurement process, being low cost and not requiring much investment in production.

Description of drawings:

FIGURE -1 ; Exploded view of sensor elements

FIGURE -2; Individual drawing of sensor elements Reference numbers:

100. BLC (Branch line coupler)

110. Transmission line

111. Input port

112. Output port

113. Output port

114. Isolated port

200. SRR (Split Ring Resonator)

210. Microstrip line

300. Glass layer

Description of the invention

High precision non-invasive blood glucose measurement sensor and system with microstrip technology, which is the subject of the invention, consists of branch line coupler (BLC) (100), split ring resonator (SRR) (200) and glass layer (300) used between the finger to be measured and the sensor, which minimizes environmental effects and noise level and so provides high precision and accuracy.

Said invention is based on the use of a branch line coupler (BLC) (100) and a split ring resonators (SRR) (200) to measure the dielectric coefficient in blood, and the use of a glass layer (300) between the finger to be measured and the sensor. As shown in Figure 1 , the SRR (200) is located in the free space of the BLC (100) and is connected to the transmission lines (110) of the BLC by two thin microstrip lines (210). By this way, it provides higher accuracy and precision by reducing the effect of fringing fields.

In the present invention, the blood measurement system is based on the variation of the frequency (110) occurring in the transmission line in the combined arm of the BLC (100). The change in dielectric coefficient (dielectric permittivity) is measured by looking at the change of transmission zeros.

In addition, the transmission lines of the BLC (100) provide two output lines (112, 113) symmetrical in differential form to the proposed sensor. These symmetrical outputs (112,113) easily compensate for finger positions. In said system, the transmission zeros of the two outputs (112,113) must have the same values, so that the correct position of the finger can be adjusted by observing the two outputs (112,113) at the same time. By using a glass layer (300) between the user's finger and the sensor, any electrical contact between the finger and the sensor is avoided. Also, the operation of the BLC (100) can be simulated by varying the dielectric permittivity of the glass layer (300).

Said invention is connected in series so that the sensing area SRR (200) of the high precision non-invasive blood glucose measurement sensor with microstrip technology can be loaded symmetrically to the two outputs of the BLC (100). The application of SRRs (200) in the empty space of the BLC (100) provides inductance and capacitance effects on the BLC (100), and the phase velocity and wavelength are reduced to increase the inductive and capacitive effect. This leads to a reduction in the operating frequency and therefore in the sensor size.

Said invention uses a high precision non-invasive blood glucose measurement sensor and system with microstrip technology, and two separate sensor systems to detect the dielectric coefficient to measure blood glucose with high precision and accuracy. The first of the said sensors has 4 ports: BLC (100), input port (111), output ports (112,113) and isolated port (114) and they are connected to each other by transmission lines (110). The second sensor SRR (200), which is positioned in the space above the BLC (110), is connected to the system with microstrip lines (210) in series. The glass layer (300) on which the said measurement is made is also positioned on it to cover the SRR (200).

Claims

1. Non-invasive blood glucose measurement sensor and system with microstrip technology that allows the dielectric coefficient to be determined in a non- invasive manner, comprising

• BLC (100) sensor, measuring the dielectric coefficient change by looking at the change of transmission zeros based on the change in the frequency (110) occurring in the transmission line in its combined branch, connected by transmission lines (110) with at least one port, and providing two output lines (112,113) symmetrical in differential form for output, with transmission lines (110),

• SRR (200), which is connected in series with two thin microstrip lines (210) to the transmission lines (110) of the BLC, to be loaded symmetrically to the two outputs of the BLC (100), reducing the sensor size by being positioned in the space above the BLC (110), and

• Glass layer (300) positioned to cover the SRR (200), on which the finger is positioned to take the measurement, preventing electrical contact between the finger and the sensor.

2. Blood glucose measurement sensor and system according to claim 1 , comprising 4 ports of BLC (100) sensor, as input port (111), output ports (112,113) and isolated port (114).

3. Blood glucose measurement sensor and system according to claim 1 , comprising SRR (200), which provides increased precision by reducing the effect of fringing fields by connecting two thin microstrip lines (210), and BLC in series with the transmission lines (110).

4. Blood glucose measurement sensor and system according to claim 1 , comprising symmetric outputs (112,113) that allow the correct positioning of the finger to be set by observing that the transmission zeros have the same values for finger position compensation. Blood glucose measurement sensor and system according to claim 1 , comprising glass layer (300) simulating the operation of the BLC (100) by varying the dielectric permittivity. Blood glucose measurement sensor and system according to claim 1 , comprising SRR (200) which, by connecting directly to the BLC (100), reduces the effect of fringing fields on the sensors. Blood glucose measurement sensor and system according to claim 1 , comprising SRR (200) reducing the phase velocity and wavelength to increase the inductive and capacitive effects, providing inductance and capacitance effects on the BLC (100), by being applied to the empty spaces of the BLC (100).