An optical device for diagnosing and monitoring microcirculation disorders.

Abstract

The invention is a portable, patient bedside monitor consisting of LEDs and photodiodes, usable in the diagnosis and monitoring of diseases, operating independently of user experience, and providing information about the microcirculation of tissues. This monitor incorporates sensors designed to be functionally attached to the patient, enabling the acquisition of information about the microcirculation metabolism of the tissue beneath the sensors. The invention also includes the measurement of quantitative tissue oxygen saturation values ​​using information obtained from light-tissue interaction.

Description

1 TARIFF AN OPTICAL DEVICE FOR DIAGNOSIS AND MONITORING OF MICROCIRCULATORY DISORDERS. TECHNICAL FIELD The invention, developed in the biomedical field, is used in the diagnosis and monitoring of 5 diseases. It is a patient bedside monitor that can be used. This monitor provides the patient with functional benefits. sensors designed to be attached to the tissue beneath the sensor monitor microcirculation. It involves obtaining information about metabolism. The invention is obtained as a result of light-tissue interaction. Using the information obtained, quantitative measurement of tissue oxygen saturation values ​​is performed. It is related. 10 STATE OF THE ART Doppler ultrasound; Doppler ultrasound is a non-invasive surgical technique used in many clinical applications. It is an invasive and real-time bit technique. In this technique, the speed and direction of my blood flow are monitored. It can be calculated from reflected ultrasound waves. However, quantitative analysis is only possible with Doppler ultrasound. Measurements cannot be made, and the results reflect large vessels rather than microcirculation. Also, it is not very suitable for making local measurements, and for evaluating the results. This requires considerable experience, continuous monitoring is not possible, and the ultrasound device... Due to its high cost, it cannot be used as a patient monitor. Photoplethysmography (PPG); Blood volume in the area of ​​the body close to the skin 20 It is a non-invasive, electro-optical method that provides information about the relevant area of ​​the body. Light is sent through and the intensity of the light reflected or passing through this area is measured. These signals are converted into electrical signals. There are many studies on PPG signals in the literature. These are available. The best known of these are blood oxygen saturation (SpO2) measurement and pulse rate. It is a pulse oximeter device that calculates the number of pulses in the arterioles. With a pulse oximeter, the 25 The signal resulting from pulsation is measured. That is, SpO2 is the oxygen level of arterial blood. It corresponds to saturation and is a systemic value. Microcirculation measurements are pulse measurements. This is quite different from SpO2 measurements made with an oximeter. Microcirculation average tissue oxygen saturation over a volume of tissue in measurements It is measured and therefore is a local measurement. Therefore, the supply of oxygen in the tissue and 30 It can provide information about changes in local conditions (microcirculation) in its consumption. Transcutaneous Partial Oxygen Pressure (TcPO2) is the partial oxygen pressure in the tissue. It is a method of directly measuring blood pressure. TcPO2 is measured in tissue at a specific time. It shows the balance between perfusion and oxygen consumption in the tissue. TcPO2 measurement. 2 The principle is via a metal cathode coated with an oxygen-permeable hydrophobic membrane. It is based on the principle of electrochemical reduction of oxygen. During application... Heating the probe to 43-45°C is the biggest disadvantage of the method. Necrotic and viable It cannot distinguish between tissues, acute and chronic hypoxia. Furthermore, arterial blood gas pressure... It is similar to and correlated with 5. InSpectra Model 325 (Hutchinson Technology Inc., USA); NIR region tissue It is a spectrometer. In this system, tissue oxygen saturation is measured using a spectrometer. The aim is to take measurements. The most significant disadvantage of the system is the lack of a spectrometer. Due to its usage, it can be used as a bedside monitor for many patients. The cost is high. 10 OXY-2 (ViOptix, Inc. The ODIS Technology) tissue oximeter; device 690-830nm It contains a laser light source at a specific wavelength. THE PURPOSE OF THE INVENTION The purpose of the invention is to provide tissue oxygen information that indicates the microcirculation of tissues. saturation value, quantitatively, in real time, without causing any harm to the patient. The goal is to offer a medical device that can determine this. In the clinic, after tissue transplants... Follow-ups are carried out through clinical observations. However, clinical observation requires considerable experience. It requires, is not objective, and therefore contributes little to early diagnosis. The purpose of this invention... Consisting of LEDs and photodiodes, easily portable and user-experience dependent 20 The goal is to produce a patient monitor that can function without needing one. This is crucial for tissue transplants worldwide. There is currently no objective gold standard method used in monitoring. Currently, Doppler ultrasound, photoplethysmography, and transcutaneous oxygen pressure are used. Although techniques such as measurement are being used, most physicians are currently adapting to these changes. It relies on clinical experience to evaluate these methods. Because these methods have clinical 25 They require experience for implementation and continuous monitoring, they are expensive, and they are impractical. They have limitations such as not being present. Therefore, microcirculation in tissue transplants Reliable monitoring would be a valuable and practical tool for clinicians. An ideal system, Non-invasive, reliable, objective, repeatable, immediate response to changes in blood flow. 30 that determine, require no experience, are economically feasible and real-time. It should be suitable for continuous monitoring. Blood supply to all tissues consists of macrocirculation and microcirculation elements. This occurs. These can be affected by many factors, and these influences affect perfusion, that is... They can dramatically affect the viability of the tissue. Therefore, monitoring tissues is crucial for the tissue's survival. 3 This can be done by monitoring blood flow. Microcirculation, microvascular geometry and tissue It is controlled by oxygen saturation. Tissue oxygen saturation is measured by the light emitted. oxygenated hemoglobin in microcirculation in tissue volume to total hemoglobin It is a measure of the ratio and is an absolute value. Changes in oxygen saturation affect the blood. Light absorption varies considerably. Therefore, 5 of the light reflected back from the tissue... Tissue oxygen saturation can be determined by analyzing the absorption component. In recent years, optical methods have been increasingly used in the diagnosis of diseases. It is used. The aim of these studies is to treat the disease in a painless, non-invasive way. The goal is to diagnose it in a way that is effective and at an early stage. Also, the results are available in real time. Developing practical systems for evaluation using optical methods 10 These are other objectives of the research. In the world, tissue oxygen saturation measurement A standard method for using this method is not yet available. Therefore, reliable tissue analysis is not possible. Monitoring will be a valuable and practical tool for clinicians. Currently, as mentioned above... Although the techniques described are used in some cases, they are not suitable for continuous monitoring of tissues. Most physicians rely on their clinical experience. Because these methods require experience of 15 years. They require, are expensive for clinical application, and are also impractical. They have limitations, such as not being able to see tissue. Near infrared spectroscopy (NIR) It is used to measure oxygen saturation. Oxyhemoglobin is used for measurement. The difference between the absorption spectra of (HbO2) and deoxyhemoglobin (Hb) It is used. This invention involves a patient monitor designed for clinical use, 20 The sensor has an LED that emits at 760 nm and 800 nm and reflects light from the tissue. It consists of a photodiode that measures the intensity of light. It emits 760 nm and 790 nm wavelengths of light into the tissue. A light is shone on the neck, and the intensity of the light returning from the tissue is measured and averaged. This information is received by embedded software in the electronic hardware. It is then measured. Tissue oxygen saturation in embedded software using average light intensities 25 It is calculated. The goal of this invention is to monitor the microcirculation of tissues. It is an optical patient monitor that provides quantitative and real-time assessment. In conclusion, tissue circulation disorders can be diagnosed early and tissues can be monitored. a patient 30 that causes no harm to the patient and can be used without requiring any experience This can be done with the monitor. 4 DESCRIPTION OF THE FIGURES Figure 1: Main body of the device and input / output sockets. Figure 2. Schematic and PCB views of the measurement probe. Figure 3. Components located on the front layer of the main control board (PCB). Figure 4. Components located on the front layer of the main control board (PCB) 5 Figure 5. HX3242 DC / DC step-up converter circuits. Figure 6. LM1117IMP-3.3 volt regulator circuit. Figure 7. TP4056 charging circuit and battery with Micro USB charging socket. Figure 8. TP4056 charging circuit and battery. Figure 9. Digital-to-Analog Converter (DAC) module control circuit 10 Figure 10. Bridge-type LED switching circuit. Figure 11. An op-amp circuit with a photodiode. Figure 12. Schematic of the OPA4350UA Op-amp used on the main control board. Figure 13. Measurement Diagram Explanation of the references in the figures. 1. On / off button on the device's outer protective casing. 2. Software update socket on the device's outer protective casing. 3. Micro SD memory card slot on the device's outer protective case. 4. Microphone input socket (measurement channels) 20 on the device's outer protective case. 5. Micro SD memory card for screen software updates in the device's outer protective case. card slot 6. Micro USB power input on the device's outer protective case. 7. Reset button on the device's outer protective casing. 8. Measurement probe: SMT760 LED1 25 9. SMT800 LED2 on the measuring probe. 10. VEMD6060x01 photodiode in the measurement probe. 11. Battery charge control circuit 12. Battery socket 13. On / off switch 30 on the main control board. 14. Display socket 15. Step-up converter circuit (for display power supply) 16. Step-up converter circuit (for main control power supply) 17. LED current control DAC transistor 18. Microcontroller 19.8 MHz Crystal component 20. Regulator component 21. LED control circuits (8 channels) 22. Measurement sockets (8 channels) 5 23. ADC Circuits (2x4) 24. Reset button on the Main Control Board 25. Micro USB power input on the main control board. 26. Micro SD card slot on the main control board. 27. Software update socket 10 on the main control board. 28. A bridge-type transistor LED switching circuit. 29. Current protection resistor 30. Measurement is taken with the DAC value kept at zero, i.e., without sending light to the tissue. 31. Collection of light intensity using a photodiode on the measuring probe. The Background Value is obtained by averaging 32,200 ADC samples. to be done 33. Sending light to the tissue with LED1. 34. Collection of LED1 light reflected back from the tissue by photodiode. 35. Obtaining the value of LED1 light intensity. 36. Sending light to the tissue with LED2 20 37. Collection of LED2 light reflected back from the tissue using a photodiode. 38. Obtaining the value of LED2 light intensity. DETAILED DESCRIPTION OF THE INVENTION The probe of the invention device uses LEDs emitting at both wavelengths to draw 25 millimeters from the tissue. It consists of a photodiode that measures the intensity of the returning light. Through the photodiode... The measured light intensity can be processed by embedded software in the electronic hardware. These signals are converted into electronic signals. These signals regulate tissue oxygen saturation. The results are calculated using (%StO2) and displayed on a 7-inch, touch-screen LCD display. This is reflected in the device developed with this invention, which consists of three main parts. 30 The first of these is the main body of the device, on which the screen and main controls are located. with parts designed and produced with a 3D printer, which includes the circuit board and battery The first part is the enclosed body section. The second part is the socket located on the device's body. attached, an LED that sends light to the tissue and a photodiode that measures the intensity of the reflected light. 6 This is the measuring probe that is formed. The third and final part is the battery located inside the device. This is a charging adapter used for charging, with a DC 5 volt 2A output power. The device's body has a flip-up switch that allows the device to be turned on and off. There is a power button (1). There is no other switch on the device besides this switch. There are no mechanical switches or buttons. Therefore, all users 5 Operations are performed using a capacitive touch-sensitive LCD screen. The device on the body, on the side where the on / off button is located, in the device's software There is a software update socket that is used to perform updates (2). Also to record patient information and measurements so that they can be analyzed later, There is one Micro SD memory card slot where data is stored (3). 10 To take measurements from 8 different areas of the patient's body, the device requires 8 measurements. 8 channels have been designed. To use these channels, there are a total of 8 channels on the right side of the device. There are 4 pole 3.5mm female microphone input sockets (4). The device's body has a port used to update the LCD screen software. There is a micro SD memory card slot (5). The LCD screen software update is also 15 This is done from here. Also, micro USB power input (6) and reset button (7) is located Measurement Probe Features: The device has a probe that sends light to the tissue and back again. It has a measuring probe that measures the value of the reflected light (Figure 2). Probe PCB It is a flexible PCB with a thickness of 0.1mm. The developed device has a measurement probe of 20 Two LEDs emitting different wavelengths are used to direct light to the tissue. and a photodiode that measures the intensity of the light reflected back from the tissue. The designed On this probe, there is an SMT760 (8) to send 2 different wavelengths to the tissue and There are two SMT800 (9) LEDs. The light sent to the tissue with these LEDs, After interacting with the tissue, it is reflected back, with a VEMD6060x01(10) photodiode 25 The reflected light is measured. The measurement data from the photodiode is transmitted through a wired headphone jack. Using a (3.5mm, 4-pole) cable, connect the female headphone socket on the main control board to the headphone jack. The values ​​received from the photodiode are transmitted to the microcontroller via software. After processing, the values ​​are displayed on the screen. Microcontroller and its features: The device's main control board contains a 30 microcontroller manufactured by ST. STM32F407VGT6 microcontroller with 32-bit ARM-M4 Cortex architecture. This microcontroller has a low power supply thanks to its ARM-based architecture. some advantages such as low power consumption, high operating speed, and high Analog-Digital resolution It has another advantage; peripheral equipment and other electronic circuits. 7 for controlling its components, within the necessary modules operating at high speed. It has a single microcontroller. Therefore, only one microcontroller was used in the system. The Digital-to-Analog Converter (DAC) module located inside the microcontroller, To control the brightness of the LEDs located on the measuring probe. This module allows the LEDs to be set to the desired light intensity via software. It is easily adjustable. Another module used in the microcontroller is Analog. It is a Digital Converter (ADC) module. The measurement is obtained via the photodiode in the measurement probe. The low signals obtained are processed by the op-amp integrated circuit located on the main control board. The signal can be processed electronically using an Impedance Amplifier (TIA). is converted. The TIA module converts the signal received as analog current from the photodiode into 10¹³ ... It performs the voltage conversion process. At the output of the op-amp integrated circuit. These resulting analog voltage values ​​are stored within the microcontroller's 12-bit Analog Processing Unit (AAS). The data is converted to digital format using a Digital Converter (ADC) module. Another module used in the microcontroller is USART serial communication. This is the communication module. Using this communication module, a 15-inch connection is established between the device and the LCD screen. Communication is established. Finally, another method we use in the microcontroller... The module in question is the SDIO communication module. This module is used to transfer information to a Micro SD memory card. Writing and reading information from a memory card are performed. Main Control Board (PCB) Layout Architecture: Electronic circuit design of the device. It was made using Altium Designer18 program. PCB 20, which forms the main board of the circuit. The circuit board measures 181mm x 108mm x 1mm and has a double-layered structure. On the PCB... A total of 211, 64 on the upper layer and 147 on the lower layer. It contains electronic components. Figure 3 shows the front of the main control board (PCB). in the layer; battery charge control circuit (11), battery socket (12), on / off switch (13), display socket (14), step-up converter circuit (for display power supply) 25 (15), step-up converter circuit (for main control supply) (16), LED current control DAC transistor (17), microcontroller (18), 8 MHz crystal (19), regulator (20) It contains components. Figure 4 shows the back of the main control board (PCB). in the layer; LED control circuits (8 channels) (21), measurement sockets (8 channels) (22), ADC Circuits (2x4) (23), reset button (24), micro USB power input (25), micro SD card slot 30 (26), software update socket (27) components are included. Battery Charge Control Circuit and Supply Voltage: Microvoltage used in the device. The controller, STM32F407VGT6 (U5), operates with a voltage of 3.3 volts. The system The operating voltage has therefore been selected according to the microcontroller and the electronic circuit. 8 The design was made accordingly. The LCD screen (LCD1) used in the device is powered by a 5-volt voltage. It is working. The voltage of the battery, which enables the device to be portable, is... The voltage is 3.7 volts. Since the circuit requires 5 volts for the display, the HX3242 (U1) stepper motor... The 5 volts DC required for the LCD screen is obtained by using the up dc / dc converter integrated circuit (15). The voltage is supplied in this way. With this integrated circuit, the voltage in the battery is 5 volts DC. The voltage is fixed (Figure 5). For the voltage required for the microcontroller, A second HX3242 (U2) integrated circuit is used. This second 5 volt DC is obtained. The voltage is then converted to 3.3 DC volts by the LM117IMP3.3 (U3) regulator integrated circuit. by reducing the supply voltage of the circuit and the microcontroller in this way. This is provided (Figure 6). The reason for using two HX3242 integrated circuits is the screen and 10 The goal is to separate the supply voltages of the circuit from each other. This allows them to remain separate. This prevents it from affecting the circuit. The OPA4350UA (U6-U7) op-amp used in the circuit. for the flawless operation of integrated circuits and Analog-to-Digital conversion in microcontrollers The supply voltages must be extremely stable because the operations will be performed. It is required. A 3.7 volt 4000 mAh Li-15 battery is used to power the device. To charge the ion battery (BAT1), there is one female microcontroller on the main control board. There is a USB (USB1) socket (Figure 7). A DC 5 Volt 2 Ampere charger is connected to this socket. The battery is charged in a controlled manner using a charger adapter. The device... The charge control of the battery used is done using the TP4056 (U4) integrated circuit. This is provided (Figure 8). These integrated Li-ion batteries require a special 20-inch charging cable. It is designed and is extremely useful. Whether the battery is charging or fully charged... This situation is indicated by two LEDs (red and green LEDs) by the user. It is seen. Switching and current control of LEDs: For taking measurements with the measuring probe. The light intensity of the two LEDs used is controlled by the Digital 25 located in the microcontroller. This is done using an Analog Converter (DAC) module located in the microcontroller. The light intensity of these LEDs can be precisely adjusted using software. Micro The BCP56HX (Q1) DAC transistor is driven by the DAC_OUT voltage output of the controller. The light intensity of the LEDs is being controlled (Figure 9). The LEDs on the measuring probe... A bridge-type transistor LED switching circuit is used to drive the LED on the main control board. The circuit (28) is used. With this circuit, two different waveforms can be produced using only two pins. The LEDs on the neck are controlled by a microcontroller. Each channel Thanks to the existing LED control circuit (total 8 channels) in the circuit, measurement is possible. Fewer cables are used in the connection between the probe and the device. Micro 9 Only when the K1_L1 pin (1st LED for channel 1) is activated by the controller, the probe... LED1 (8) lights up according to the DAC_OUT value from the microcontroller. The bridge-type switching system contains four transistors (Q6, Q10, Q14, Q18). (28). Transistor Q2, Q6 and Q18 triggered by the signal from pin K1_L1 It switches its transistors. All other transistors remain in cutoff. 5 Thus, the K1_LED1 pin at the circuit output becomes positive and the K1_LED2 pin becomes negative, and Only LED1 (8) lights up. Triggered by the signal from the K1_L2 pin using the same logic. Transistor Q22 switches transistors Q14 and Q10, and the output of the circuit... Make the K1_LED2 pin positive and the K1_LED1 pin negative, so that only LED2 (9) It emits light. The 22 Ohm resistor shown in the circuit diagram in Figure 10 is 10 Ohms. It acts as a maximum current protection resistor and protects the LEDs. (29). Both LEDs can withstand a voltage of up to 2.5 volts. This voltage They are damaged when the value is exceeded. The circuit's supply voltage is 3.3 volts. The LEDs are protected by adjusting the settings. Photodiode, Op-amp Circuit and Analog-to-Digital Converter (ADC) Unit: Device 15 In the electronic circuit, since an 8-channel design was used, it contains 4 op-amps. It features two high-speed, single-supply OPA4350UA op-amp integrated circuits. The light reflected back from the tissue at the measurement probe is detected by the VEMD6060x01 located on the probe. The signals obtained from the light on the photodiode are collected by the photodiode (10). The signal is transmitted to the corresponding op-amp integrated circuit located on the main control board. This 20 The op-amp integrated circuit converts the signals received from the photodiode as analog current into voltage. It performs the conversion process to its value. Figure 11 shows an op-amp with a photodiode. The integrated circuit schematic, shown in Figure 12, contains 4 channels of the OPA4350UA (U6). The circuit diagram of the integrated circuit is shown. The analog output of the op-amp integrated circuit is shown. The signal is sent to the microcontroller for processing by the Analog Digital Converter (ADC) 25 is being sent. The Analog-to-Digital Converter (ADC) transmits the analog signal electronically. circuit that converts data into digital form that software can understand It is a component. The analog voltage value generated at the output of the OPA4350UA Op-amp integrated circuit is: the 12-bit Analog-to-Digital Converter (ADC) module inside the microcontroller These are converted into numerical data using software. This resulting numerical data is then processed using software in 30... by analyzing the oxygen saturation of the tissue where the measurement probe is located. It calculates. Measurement Taking: The light intensity of the LEDs used in the measurement probe is measured by the microcontroller. This is provided by a DAC module controlled by embedded software. Figure 13 The measurement diagram is shown. The measurement probe is connected to the measurement device. When the Measurement button for the channel to be measured is pressed, the DAC value is measured first. Measurement is taken by keeping it at zero, that is, without sending light to the tissue (30). The light intensity collected by the photodiode on the probe (31) is measured by the ADC of the microcontroller With this module, 84 sampling times and 15 analog-to-digital conversion periods. is being converted. To obtain accurate measurements, there should be a 1-minute interval between each sample collection. There is a millisecond waiting time. In this way, a total of 200 ADCs will be used. By averaging the sample size, approximately 200 milliseconds of background information is obtained. The value is obtained (32). Then light was sent to the tissue with LED1 (8) (33), 10 reflected back from the tissue LED1 light was collected by photodiode (34). Background Value was obtained by The process was repeated in the same way. A total of 200 ADCs were used for 200 milliseconds. By taking the average of the samples, the LED1 light intensity value is obtained (35). After this value is obtained, the light of LED1 is completely switched off. With LED2... Before starting the measurement, LED1 was switched off for 200 milliseconds. There is a waiting period. After this waiting period, light is emitted via LED2. (36), the LED2 light reflected back from the tissue is collected by the photodiode (37) and with the same processes The light intensity value of LED2 is obtained (38). Then LED2 is completely The measurement process is completed by extinguishing the light source. The obtained light intensity is... Background value, LED1 and LED2 20 before the values ​​are displayed on the LCD screen Their values ​​are extracted individually. Then, these values ​​are used in embedded software. Tissue oxygen saturation (%StO2) values ​​are calculated and displayed on the screen. is displayed. If the user wishes, they can use these values ​​displayed on the screen via a microSD card. It can store it on its card. HOW THE INVENTION WAS APPLIED TO INDUSTRY The patient monitor developed with this invention is geared towards practical purposes and goals. a technologically unique device with the potential for widespread use in our country This will happen. Tissue oxygen saturation measurement devices have not been developed in our country. There are no studies on this subject, and such a method is not used in the monitoring of other diseases. 30 It is not used. Tissue oxygen saturation measurement is used in cancer diagnosis, diabetes, and thyroid problems. and vital in many medical applications, such as determining ischemia / reperfusion injury. It is an important parameter. This discovery will be used in hospitals, in patients' tissues, all conditions requiring early diagnosis and monitoring of microcirculation disorders 11 In some cases, it has the potential to be used as a bedside monitor. Tissue Flap transplants (flap surgeries) are very common surgeries in plastic surgery and worldwide. It affects millions of people worldwide. Development of post-operative follow-up methods. It is a fact that this will improve the quality of treatment decisions. Physicians' understanding of the disease Quantitative data such as tissue oxygenation, which is needed to evaluate, are among these 5. The invention can be used to calculate the risk of unnecessary surgical intervention or delay. It is thought that it will also provide solutions to problems such as these. Furthermore, dentistry... It can be used in treatment monitoring in various applications. 15 25

Claims

12 REQUESTS 1- The actual oxygen saturation of the tissue is measured using a photodiode. Optical imaging for the diagnosis and monitoring of microcirculation disorders through timed and continuous measurement. It is a device, and its feature is; 5 - LEDs that send light at 760 nm and 800 nm wavelengths to the tissue and back A measuring probe consisting of a photodiode that measures the intensity of reflected light, - one or more to take measurements from different areas of the tissue measurement channel (4), - Light intensity measured via photodiode can be processed electronically. 10 converting signals into measured signals and determining tissue oxygen saturation. software that includes a calculation algorithm, - Ensuring the LEDs illuminate at the desired light intensity for a total of 200 milliseconds. during this period, the average of 200 ADC samples was taken to obtain the result. Based on the light intensity value of LED1 and for a total duration of 200 milliseconds, 200 units of 15 LED2 light intensity obtained by averaging the ADC sampling. From that value, with the ADC module, 84 samples and 15 analog-to-digital samplings. conversion during the conversion period and 200 ADC samples obtained by averaging the time, approximately in 200 milliseconds. Extraction of background values ​​separately and tissue oxygen 20 with software The values ​​obtained by calculating the saturation (%StO2) values by including a microcontroller (18) that enables it to be displayed on the screen It is characteristic. 30

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