Flexible hybrid electronic system for intraoperative intracranial monitoring

Abstract

Provided in the present invention is a flexible hybrid electronic system for intraoperative intracranial monitoring. The system comprises a flexible front-end signal collection module, a rear-end signal processing module and an upper computer system, wherein the flexible front-end signal collection module comprises a flexible framework body, which is formed by a top encapsulation layer, an intermediate encapsulation layer and a bottom substrate layer from top to bottom, an electroencephalogram layer and a flexible sensor array, which are arranged in the flexible framework body, and a temperature-controlled hydrogel interface layer and an electrothermal film, which are respectively integrated above and below the flexible framework body, the flexible sensor array being used for collecting pressure, temperature and brain tissue oxygen saturation signals, and the electrothermal film regulating the adhesion and peeling of the temperature-controlled hydrogel interface layer and brain tissue; and the rear-end signal processing module is electrically connected to the flexible front-end signal collection module, so as to receive signals collected by the flexible sensor array and the electroencephalogram layer, analyze and process the signals, and then transmit the signals to the upper computer system. The flexible hybrid electronic system can both replace traditional brain patties and monitor the state of brain tissue throughout the process, thereby ensuring intraoperative safety.

Description

A flexible hybrid electronic system for intracranial monitoring during surgery

Technical field

[0001] The present invention relates to the technical field of biomedical instruments, and in particular to a flexible hybrid electronic system for intracranial monitoring during surgery. [Background Technology]

[0002] The brain, as part of the human body's higher central nervous system, is one of its most important organs. Its structure is highly complex, encompassing multiple functional areas. According to data from the International Agency for Research on Cancer, in 2020, there were 308,102 new cases of central nervous system brain cancer and 25,139 deaths from brain tumors. China has among the highest morbidity and mortality rates for brain tumors in the world. Furthermore, the mortality rate for patients with severe craniocerebral trauma exceeds 20%, and the severe disability rate exceeds 50%. Neurosurgery, including craniotomy, is an important treatment for brain tumors and trauma, and a necessary intervention when conventional treatments are ineffective. Due to the complex structure of the brain, which includes numerous central nervous systems, arteries and veins, and speech and motor function areas, as well as the relative fragility of brain tissue, craniotomy is one of the most difficult and complex surgeries performed clinically.

[0003] Craniotomy involves opening the patient's skull using specialized medical equipment and surgical instruments to remove diseased tissue. Craniotomy can be performed through a bone window or a bone flap, and is a common neurosurgery procedure. The success rate of craniotomy varies depending on the condition. Data show that the success rate of craniotomy for brain tumor removal is over 90%, while the success rate for cerebrovascular disease is generally between 90% and 95%. The success rate for functional systemic diseases may be lower. One of the most common causes of surgical failure during intracranial surgery is cerebral contusion and hemorrhage caused by traction on the brain tissue. To provide an adequate field of view, craniotomy requires traction on the brain tissue. Improper traction during surgery, such as improper technique or timing, can lead to bleeding in the brain tissue, potentially resulting in contusion and hemorrhage. In severe cases, complications such as hypothalamic dysfunction may occur. Because the brain tissue structure is very fragile, it should be protected as much as possible during craniotomy. Therefore, when necessary traction is performed, brain cotton pads should be placed on the traction area.

[0004] Existing brain cotton pads are primarily made of medical absorbent cotton or spunlace nonwovens. These thin, soft cushions cushion the pressure of surgical instruments on surrounding intracranial tissue during surgery, protecting the nerves in the surgical area and minimizing the risk of postoperative bleeding, brain contusions, and other complications. Direct contact between surgical instruments and brain tissue can easily lead to damage due to the significant mechanical differences between traditional surgical instruments such as retractors and electrodes and brain tissue. Improper handling can significantly increase the risk of postoperative complications, death, and disability.

[0005] Due to the difficulty and complexity of neurosurgery craniotomy, surgeons must constantly ensure that the ongoing surgical steps will not cause neurological damage to the patient, confirm the patient's vital signs, and ensure the accuracy of key brain parameters to prevent postoperative complications. In addition to microscopic observation, intraoperative electrophysiological monitoring (IONM) can perceive information that is not visually perceptible, thereby reflecting various physiological indicators of the human body. Therefore, during surgery, data monitoring and timely feedback of intracranial physiological parameters, including brain tissue oxygen saturation, EEG signals, temperature, and the pressure of surgical instruments on surrounding tissues, are essential. Traditional brain cotton pads generally lack transparency and physical monitoring feedback, and the limited space in the craniotomy makes it difficult to perform intraoperative physiological monitoring while protecting the brain, making continuous electrophysiological monitoring difficult. Typically, the surgeon performs electrophysiological monitoring at intervals during brain protection. This makes it difficult to obtain a complete picture of the patient's brain status throughout the hours-long surgery.

[0006] Brain tissue oxygen saturation can usually reflect the balance between brain oxygen supply and demand. Brain tissue has a high metabolic rate and is more sensitive to hypoxic environments. Short-term hypoxia can cause irreversible damage to the central nervous system. Brain oxygen saturation is mainly used to monitor the patient's brain oxygen balance. Monitoring brain oxygen saturation during surgery helps to promptly detect hypoxia and ischemia in the patient's brain. Brain protection is very important in important neurosurgery, major vascular surgery, rescue of critically ill patients, and cardiopulmonary resuscitation after cardiac arrest. Anesthesia during surgery can easily disrupt the brain's oxygen balance and increase the incidence of postoperative brain nerve dysfunction. EEG monitoring mainly monitors the presence of the patient's brain waves. Intracranial EEG is not interfered by the scalp and skull and can be placed deep in the brain, allowing doctors to obtain richer EEG information.

[0007] In recent years, flexible electronics technology has been increasingly used in brain physiological monitoring. It can be used for intraoperative recording in neurosurgery, postoperative rehabilitation monitoring, and nerve stimulation. Compared with traditional silicon-based electronics, flexible electronics, with its advantages such as good ductility, stretchability, and biocompatibility, partially solves the above-mentioned continuous monitoring problem. It can conformally contact with brain tissue, effectively reducing damage to brain tissue. The damage to brain tissue caused by neurosurgery is mainly due to the pulling, displacement, and bending of surgical instruments, and these forces are converted into pressure on brain tissue. Therefore, it is very necessary to develop a device that can measure brain pressure. [Summary of the invention]

[0008] In order to solve the problems existing in the background technology, the present invention provides a flexible hybrid electronic system for intracranial EEG monitoring during surgery. This flexible hybrid electronic system can not only replace the traditional brain cotton pad to pull the brain tissue and expose the lesion area, but also monitor the state of brain tissue throughout the process to protect intraoperative safety.

[0009] The technical solution of the present invention to solve the above technical problems is as follows:

[0010] The present invention provides a flexible hybrid electronic system for intracranial monitoring during surgery, comprising a flexible front-end signal acquisition module, a back-end signal processing module and a host computer system;

[0011] The flexible front-end signal acquisition module includes a flexible frame body formed by a top packaging layer, an intermediate packaging layer and a bottom base layer arranged from top to bottom, an EEG layer arranged between the intermediate packaging layer and the top packaging layer, a flexible sensor array arranged on the upper surface of the bottom base layer, a temperature-controlled hydrogel interface layer integrated above the top packaging layer and an electric heating film integrated below the bottom base layer; the EEG layer includes a top base layer and an EEG electrode array and an internal circuit arranged on the top base layer, the EEG electrode array passes through the flexible frame body and is connected to the temperature-controlled hydrogel interface layer; the flexible sensor array is connected to the EEG layer through the intermediate packaging layer, and the flexible sensor array is used to detect pressure, temperature and brain tissue oxygen saturation signals; the electric heating film regulates the adhesion of the temperature-controlled hydrogel interface layer by temperature to achieve adhesion and peeling of the temperature-controlled hydrogel interface layer to the brain tissue.

[0012] The back-end signal processing module is electrically connected to the flexible front-end signal acquisition module to receive pressure signals, temperature signals, EEG signals and brain tissue oxygen saturation signals, and transmits them to the host computer system through wireless or wired transmission after analysis and processing.

[0013] According to the above solution, the flexible sensor array includes a pressure sensor array, a temperature sensor array and a brain tissue oxygen sensor, which are electrically connected to the back-end signal processing module respectively.

[0014] According to the above solution, the multiple pressure sensors in the pressure sensor array are all flexible pressure sensors.

[0015] According to the above scheme, the back-end signal processing module includes an acquisition circuit, a core processing module, a multiplexing switch, a flexible battery, a power management chip and a wireless transmission module. The flexible battery supplies power to the wireless flexible hybrid electronic system through the power management chip. The acquisition circuit is electrically connected to the flexible sensor array and the EEG electrode array respectively, and is used to receive pressure signals, temperature signals, EEG signals and brain tissue oxygen saturation signals and transmit them to the core processing module through the multiplexing switch. The core processing module is used to process the signals transmitted by the acquisition circuit and send them to the host computer system.

[0016] According to the above scheme, the acquisition circuit includes an operational amplifier, an EEG acquisition front end and a brain oxygen acquisition front end. The operational amplifier is electrically connected to the pressure sensor array and the temperature sensor array, the EEG acquisition front end is electrically connected to the EEG electrodes, and the brain oxygen acquisition front end is electrically connected to the brain tissue oxygen sensor.

[0017] According to the above solution, the core processing module transmits the processed signal to the host computer system through the wireless transmission module or through the serial port.

[0018] According to the above scheme, the materials of the top packaging layer, the middle packaging layer, the bottom base layer and the top base layer in the flexible front-end signal acquisition module are all polydimethylsiloxane, and the EEG electrode array, the internal circuit, and the wires connecting the various components of the wireless flexible hybrid electronic system are all made of flexible composite conductive materials.

[0019] According to the above scheme, the temperature-controlled hydrogel interface layer includes multiple temperature-controlled hydrogel sheets corresponding one by one to the EEG electrodes in the EEG electrode array, and the multiple temperature-controlled hydrogel sheets are respectively covered on the corresponding EEG electrodes. The temperature-controlled hydrogel sheets are formed by photoinitiated polymerization with poly (ethylene glycol) diacrylate as an initiator and poly (3,4-ethylenedioxythiophene) and poly (styrene sulfonic acid) as blended components.

[0020] According to the above solution, a thermoelectric generator is provided in the electrothermal film, and the heating sites of the thermoelectric generator correspond one-to-one to the positions of the temperature-controlled hydrogel sheet.

[0021] According to the above solution, the flexible front-end signal acquisition module and the back-end signal processing module are connected via FPC.

[0022] The host computer system is provided with an alarm module, and when the pressure data received in the host computer system is higher than the preset normal pressure, the alarm module activates an alarm.

[0023] The beneficial effects of the present invention are: the flexible hybrid electronic system of the present invention can not only replace the traditional brain cotton pad to pull the brain tissue and expose the lesion area, but also monitor the EEG, pressure, temperature and brain tissue oxygen saturation data in the brain tissue throughout the process, and provide an alarm when necessary, which helps to improve the success rate of open surgery.

Brief Description of the Drawings

[0024] FIG1 is a schematic structural diagram of a flexible hybrid electronic system for intracranial monitoring during surgery according to the present invention;

[0025] FIG2 is a diagram showing the manufacturing process of the electroencephalogram layer and the underlying basal layer of the flexible hybrid electronic system for intracranial monitoring during surgery according to the present invention;

[0026] FIG3 is a system integration process diagram of a flexible hybrid electronic system for intracranial monitoring during surgery according to the present invention;

[0027] FIG4 is a circuit schematic diagram of a flexible hybrid electronic system for intracranial monitoring during surgery according to the present invention;

[0028] FIG5 is a diagram of the host computer software of the flexible hybrid electronic system for intracranial monitoring during surgery according to the present invention;

[0029] FIG6 is a data playback interface of the flexible hybrid electronic system for intracranial monitoring during surgery according to the present invention;

[0030] FIG7 is a diagram showing a method of using the flexible hybrid electronic system for intracranial monitoring during surgery according to the present invention.

[0031] In all the drawings, the same reference numerals are used to represent the same elements or structures, wherein: 1-top encapsulation layer; 2-EEG layer; 2-1-top substrate layer; 2-2-polydimethylsiloxane (PDMS); 2-3-mask; 2-4-laser cutter; 2-5-conductive composite material; 2-6-cured conductive composite material; 3-middle encapsulation layer; 4-back-end processing module; 5-flexible sensor array; 5-1 bottom substrate layer; 5-2-polydimethylsiloxane (PDMS); 5-3-mask; 5-4-conductive composite material; 5-5-cured conductive composite material; 6-electrical heating film; 7-pressure sensor; 8-diode ;9-temperature sensor; 10-temperature-controlled hydrogel interface layer; 11-flexible circuit board FPC; 12-mobile terminal APP; 13-host computer software; 14-perception algorithm; 15-program burning; 16-RF antenna; 17-serial port; 18-core processing module; 19-multiplexing switch; 20-operational amplifier; 21-pressure sensor array; 22-temperature sensor array; 23-EEG acquisition front end; 24-EEG electrode array; 25-brain oxygen acquisition front end; 26-photodiode; 27-light-emitting diode; 28-flexible battery; 29-power management chip; 30-thermoelectric transmitter; 31-flexible front-end signal acquisition module. [Specific implementation method]

[0032] The principles and features of the present invention are described below with reference to the accompanying drawings and specific embodiments. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0033] The present invention provides a flexible hybrid electronic system for intracranial monitoring during surgery, the structure of which is shown in Figure 1, including a flexible front-end signal acquisition module 31 and a back-end signal processing module 4; the flexible front-end signal acquisition module 31 includes a flexible frame body formed by a top packaging layer 1, an intermediate packaging layer 3 and a bottom base layer 5-1 arranged from top to bottom, an EEG layer 2 arranged between the intermediate packaging layer 3 and the top packaging layer 1, a flexible sensor array 5 arranged on the upper surface of the bottom base layer 5-1, a temperature-controlled hydrogel interface layer 10 integrated above the top packaging layer 1 and an electric heating film 6 integrated below the bottom base layer 5-1; the EEG layer 2 includes a top base layer 2-1 and an EEG electrode array 24 arranged on the top base layer 2-1 and an internal electric The EEG electrode array 24 extends out of the flexible frame body through the window on the top packaging layer 1 and is connected to the temperature-controlled hydrogel interface layer 10; the flexible sensor array 5 passes through the window of the middle packaging layer 3 and is connected to the EEG layer 2, and the flexible sensor array 5 is used to detect pressure, temperature and brain tissue oxygen saturation signals; the electric heating film 6 regulates the adhesion of the temperature-controlled hydrogel interface layer 10 by temperature to achieve adhesion and peeling of the temperature-controlled hydrogel interface layer 10 to the brain tissue, and the back-end signal processing module 4 is electrically connected to the flexible front-end signal acquisition module 31 to receive pressure signals, temperature signals, EEG signals and brain tissue oxygen saturation signals, and transmits them to the host computer system through wireless or wired transmission after analysis and processing.

[0034] According to the above solution, the flexible sensor array 5 includes a pressure sensor array 21 , a temperature sensor array 22 and a brain tissue oxygen sensor, which are electrically connected to the back-end signal processing module 44 respectively.

[0035] The EEG electrode array 24 includes a plurality of EEG electrodes, which are electrically connected via an internal circuit and electrically connected to the back-end signal processing module 44 via the internal circuit.

[0036] According to the above scheme, the multiple pressure sensors 7 in the pressure sensor array 21 are all flexible pressure sensors. The pressure sensors 7 use medical cotton pads as the framework and the polymer material PEDOT:PSS as the conductive channel of the piezoresistive material, resulting in a high-performance piezoresistive pressure sensor 7. In addition to excellent flexibility and biocompatibility, the pressure sensor 7 also has a high pressure range and a fast response speed. Signals are acquired and transmitted between the multiple pressure sensors 7 using wires made of a flexible composite conductive material.

[0037] In some specific embodiments, the temperature sensor array 22 includes multiple temperature sensors 9, which are thermistor-type temperature sensors. The thermistors are negative temperature coefficient thermistors (NTC) or positive temperature coefficient thermistors (PTC), whose resistance changes with temperature. A standard platinum resistance (SPR) is used to perform a temperature comparison between the temperature sensors 9 and the interface in a constant temperature water bath to verify the temperature accuracy and phase change characteristics of the interface under elevated temperature conditions.

[0038] Thermistors have high sensitivity, small size, easy use and good stability. For the temperature sensor 9 and the interface, a standard platinum resistor is used in a constant temperature water bath to perform a temperature increase comparison to verify the temperature accuracy under the temperature increase condition and the phase change characteristics of the interface. The resistance-temperature characteristics of the negative temperature coefficient thermistor can be approximated by The resistance-temperature characteristic of the positive temperature coefficient thermistor can be approximated by where T1 and T2 are Kelvin temperatures, R t is the resistance of the thermistor at temperature T1, R is the nominal resistance of the thermistor at room temperature T2, which generally refers to the actual resistance of the thermistor when the ambient temperature is 25 degrees Celsius, and B p and B n Is the material constant of the thermistor, which is also the sensitivity index, B p and B n The larger the value, the higher the sensitivity of the thermistor. p and B n The value is not constant and varies depending on the material composition.

[0039] In some specific embodiments, the brain tissue oxygen sensor includes a photoelectric converter and a light source. The light source uses two light-emitting diodes 27LED with different specific wavelengths that are selective for oxyhemoglobin and deoxyhemoglobin. The photoelectric conversion device uses a photodiode 26PD to receive light reflected and absorbed by the brain tissue, convert and amplify the photoelectric signal, and finally process the data according to the Lambert-Beer law to obtain the brain tissue oxygen saturation at the corresponding moment. The incident light source and the receiving light source need to be unobstructed or made of transparent materials.

[0040] In some specific embodiments, the back-end signal processing module 4 converts the brain tissue oxygen near-infrared spectra of red light and infrared light collected by the flexible front-end signal acquisition module 31 into brain oxygen saturation output using a specific brain oxygen saturation algorithm. The process of the specific brain tissue oxygen algorithm is as follows:

[0041] Step 1: Set the sampling rate of the acquisition front-end detection circuit to 150Hz and the sampling time length to 2s; the acquisition back-end circuit detection module starts running when it detects power-on, and controls the light-emitting diode 27 to emit red light and infrared light; the optical signal is received by the photodiode 26 at the receiving end; when the data reaches a certain time length, it starts processing and performs a 0.5Hz low-pass filter on the waveform. After the signal passes through the data acquisition front-end, the DC components of the red light and infrared light are obtained; the two DC components are respectively subjected to a 0.5Hz-5Hz band-pass filter to obtain the required raw data.

[0042] Step 2: Use the Lambert-Beer theorem formula OD(λ,t)=-ln(I t (λ) / I0(λ)) can be used to obtain the density of red light and infrared light, respectively, and then the amount of red light and infrared light absorbed into hemoglobin Hb(t) and HbO2(t) can be obtained.

[0043] Step 3: Calculate the concentration ratio of hemoglobin and oxyhemoglobin in the blood to obtain tissue oxygen saturation. The formula is: Where rStO2 is the value of tissue oxygen saturation.

[0044] Step 4: The calculated tissue oxygen saturation signal is transmitted via the Bluetooth radio frequency module to the mobile terminal App 12 and the host computer software 13. When the data length received by the back-end signal processing module 4 reaches 0.5 seconds, the 2-second window is shifted back by 0.5 seconds and the above steps are repeated to calculate the brain oxygen saturation signal.

[0045] The preparation of the flexible front-end signal acquisition module 31 combines flexible electronic manufacturing technology and micro-nano processing technology, and the layers of materials are connected by oxygen plasma bonding.

[0046] According to the above scheme, the materials of the top encapsulation layer 1, the middle encapsulation layer 3, the bottom substrate layer 5-1, and the top substrate layer 2-1 in the flexible front-end signal acquisition module 31 are all polydimethylsiloxane (PDMS), and the mass ratio of the PDMS prepolymer and the curing agent is 10:1. They are added to the plastic cup in sequence and stirred for 5 minutes to ensure that the curing agent and the prepolymer are evenly mixed to prepare the top encapsulation layer 1, the middle encapsulation layer 3, the bottom substrate layer 5-1, and the top substrate layer 2-1.

[0047] The EEG electrode array 24, the internal circuit, and the wires connecting the various components of the wireless flexible hybrid electronic system are all made of flexible composite conductive materials.

[0048] In some specific embodiments, a mask is prepared by laser cutting on the bottom substrate layer 5-1 and the top substrate layer 2-1. A flexible composite conductive material (ECC) is applied to the printed circuit board using a doctor blade. The printed circuit board is then placed on a controllable hot plate at 160 degrees Celsius for 30 minutes. The flexible composite conductive material (ECC) can be prepared by mixing PDMS and silver powder in a mass ratio of 1:3.

[0049] When using the above-mentioned flexible composite conductive material to prepare EEG electrodes, in order to ensure that the material has reliable biocompatibility, gold is sputtered on the surface of the EEG electrode as a protective layer and an adhesion layer for the interface material.

[0050] According to the above scheme, the temperature-controlled hydrogel interface layer 10 includes a plurality of temperature-controlled hydrogel sheets corresponding one to one with the EEG electrodes, and the plurality of temperature-controlled hydrogel sheets are respectively covered on the corresponding EEG electrodes. The temperature-controlled hydrogel sheets are formed by photoinitiated polymerization with poly(ethylene glycol) diacrylate as an initiator and poly(3,4-ethylenedioxythiophene) and poly(styrenesulfonic acid) as blended components.

[0051] The collection of EEG signals often occurs during the measurement of neural evoked potentials during surgery. Therefore, the interface has high viscosity during surgery and adheres firmly to the brain, effectively reducing the generation of stimulation artifacts. When the position needs to be changed or the brain protection device needs to be moved after the operation, the electric heating film 6 is started and the temperature is set above the phase transition temperature. The hydrogel microspheres are dehydrated and quickly debonded. The system can be removed without adhering to the brain tissue. The phase transition temperature of the interface is lower than the brain temperature.

[0052] Specifically, gold is sputtered on the EEG electrode to facilitate interface grafting, and hydrogel is cast on the EEG electrode. When the temperature is low, the surface of the temperature-controlled hydrogel sheet becomes sticky and conformally adheres to the brain tissue to achieve stable transmission of EEG signals. After the operation is completed, the electric heating film 6 is started to generate heat to increase the temperature, debond the interface, and remove the flexible hybrid electronic system without the temperature-controlled hydrogel sheet adhering to the brain tissue.

[0053] According to the above scheme, a thermoelectric transmitter 30 is provided in the electric heating film 6, and the thermoelectric transmitter 30 is powered by a flexible battery 28. The heating position of the thermoelectric transmitter 30 corresponds one-to-one with the position of the temperature-controlled hydrogel sheet. The temperature of the temperature-controlled hydrogel sheet is adhered or debonded by changing the temperature of the thermoelectric transmitter 30.

[0054] In some specific embodiments, the thermoelectric generator 30 is a resistance wire, which is laid flat in a circuitous manner within the electrothermal film. When the operator needs to change positions or move the brain protection device after surgery, the electrothermal film 6 is activated, raising the temperature above the phase transition temperature. This dehydrates the microspheres in the temperature-controlled hydrogel interface and rapidly debonds them, allowing the system to be removed without adhering to brain tissue. An infrared camera can be used to capture the heating process of the heater to test the heating uniformity and the system's temperature rise curve characteristics.

[0055] The host computer system is provided with an alarm module, and when the pressure data received in the host computer system is higher than the preset normal pressure, the alarm module activates an alarm.

[0056] The preparation process of the flexible hybrid electronic system for intracranial monitoring during surgery of the present invention is shown in FIG2 and FIG3 .

[0057] (1) Preparation of EEG layer 2

[0058] S1: Spin-coat PDMS 2-2 on a glass plate 2-1 to form a top substrate layer 2-1, wherein the mass ratio of PDMS prepolymer and curing agent is 10:1. After mixing evenly, cure in an oven at 90 degrees Celsius for 30 minutes. After curing, peel off the PDMS layer from the glass plate and paste mask material 2-3 on both sides of the PDMS layer.

[0059] S2: Use a laser cutting machine 2-4 to laser cut the mask to cut out the required EEG electrode pattern and internal circuit pattern. After cutting, apply a conductive composite material (ECC) 2-5 on the mask, where ECC is a mixture of PDMS and silver powder in a mass ratio of 1:3. After the coating is completed, a solidified conductive composite material 2-6 is formed.

[0060] S3: Sputter gold on the solidified EEG electrodes, and finally peel the mask off the base layer to obtain EEG layer 2.

[0061] (2) Preparation of base layer 5-1

[0062] S1: Spin-coat PDMS 5-2 on a glass plate 5-1 to form a bottom substrate layer 5-1, wherein the mass ratio of PDMS prepolymer and curing agent is 10:1. After mixing evenly, cure in an oven at a temperature of 90 degrees Celsius for 30 minutes. After curing, peel off the PDMS layer from the glass plate and stick masks 5-3 on both sides of the PDMS layer.

[0063] S2: Use a laser cutting machine to laser cut the mask 5-3 to cut out the required conductive layer pattern. After cutting, apply a conductive composite material (ECC) 5-4 on the mask, wherein the ECC is a mixture of PDMS and silver powder in a mass ratio of 1:3. After the application, a solidified conductive composite material 5-5 is formed.

[0064] S3: Finally, the mask is peeled off from the base layer to obtain the bottom base layer 5-1 having a conductive layer.

[0065] (3) Integration of flexible hybrid electronic systems

[0066] S1: Multiple pressure sensors 7, temperature sensors 9, and diodes 8 (including photodiodes 26 and light-emitting diodes 27) for measuring brain tissue oxygen are integrated on the above-mentioned bottom base layer 5-1 with a conductive layer. After the integration, the intermediate packaging layer 3 is integrated. The intermediate packaging layer 3 has windows for the pressure sensors 7, temperature sensors 9, and photodiodes 26 and light-emitting diodes 27 to extend out, which protect the flexible sensor array 5.

[0067] S2: The EEG layer 2 and the top packaging layer 1 are sequentially integrated on the upper end of the middle packaging layer 3.

[0068] S3: A temperature-controlled hydrogel interface layer 10 is integrated on top of the top encapsulation layer 1 , and the layers are bonded by plasma. After all the bonding is completed, a flexible front-end signal acquisition module 31 of the system is obtained.

[0069] S4: The flexible front-end signal acquisition module 31 is connected to the back-end signal processing module 4 .

[0070] According to the above scheme, the back-end signal processing module 4 includes a hardware acquisition circuit board and an acquisition circuit, a flexible battery 28, a power management chip 29, a core processing module 18, a multiplexing switch 19 and a wireless transmission module arranged on the hardware acquisition circuit board. The flexible battery 28 powers the wireless flexible hybrid electronic system through the power management chip 29. The acquisition circuit is electrically connected to the flexible sensor array 5 and the EEG electrode array 24, and is used to receive pressure signals, temperature signals, EEG signals and brain tissue oxygen saturation signals and transmit them to the core processing module 18 through the multiplexing switch 19. The core processing module 18 is used to process the signals transmitted by the acquisition circuit 4 and send them to the host computer system. The hardware acquisition circuit board adopts a flexible circuit board FPC 11.

[0071] According to the above scheme, the acquisition circuit includes an operational amplifier 20, an EEG acquisition front end 23 and a brain oxygen acquisition front end 25. The operational amplifier 20 is electrically connected to the pressure sensor array 21 and the temperature sensor array 22, the EEG acquisition front end 23 is electrically connected to the EEG electrode array 24, and the brain oxygen acquisition front end 25 is electrically connected to the brain tissue oxygen sensor.

[0072] The core processing module 18 MCU main control chip is a CY8CKIT-062-BLE chip, which is internally integrated with a clock management module, Bluetooth SoC, multi-channel ADC and rich interfaces such as SPI and I2C. The clock crystal oscillator module includes a 32.768KHz timer clock circuit and a 32KHz high-speed clock. The MCU main control chip is directly connected to the signal input terminal of the Bluetooth antenna in the Bluetooth radio frequency module, sends the signal outward through the antenna, and adopts a symmetric encryption protocol to ensure the security of data transmission. The MCU main control chip can also use the serial port UART17 to send raw data to the host computer software 13. In one embodiment, the program on the computer can be burned into the chip in advance, and then the chip can be integrated into the circuit.

[0073] According to the above solution, the core processing module 18 transmits the processed signal to the host computer system through the wireless transmission module or through the serial port 17.

[0074] In some specific embodiments, the flexible circuit board FPC 11 and the front-end interface of the acquisition circuit are connected together by snapping.

[0075] In some specific embodiments, the hardware acquisition circuit board of the back-end signal processing module 4 adopts a modular design, consisting of multiple acquisition boards, enabling modular combination of acquisition parameters. The boards are divided into a power management area, a main control area, a data acquisition area, a signal storage area, and a communication area. The back-end of the acquisition circuit transmits the data to the hardware board. The modular board transmits the raw data to the host computer system via Bluetooth, Wi-Fi, or a serial port for analysis, displaying the current brain tissue status in real time and providing safety monitoring for the operating physician and anesthesiologist. The front-end of the acquisition circuit generally uses analog signals, utilizing the principle of voltage divider resistors to obtain signals such as pressure and temperature through analog-to-digital conversion (ADC). Its load capacity is increased by a follower operational amplifier 20. The signals from the EEG electrode array 24 are acquired using a dedicated chip ADS1299 with a multi-channel 16k sampling rate, and are transmitted to the host computer system via wireless communication and serial port transmission. The power management chip 29 uses a DC-DC and LDO approach to ensure the stability of data acquisition and transmission.

[0076] Figure 4 shows the circuit schematic of a wireless flexible hybrid electronic system for intracranial monitoring during neurosurgery. First, the pressure and temperature signals collected by the pressure sensor array 21 and temperature sensor array 22 are passed through the operational amplifier 20, which acts as a follower to increase the signal's load capacity. The EEG signals and brain tissue oxygen saturation signals collected by the EEG electrode array 24, photodiode 26, and light-emitting diode 27 are transmitted to the EEG acquisition front end 23 and brain oxygen acquisition front end 25, respectively. Next, the signals obtained by the operational amplifier 20, EEG acquisition front end 23, and brain oxygen acquisition front end 25 are transmitted to the core processing module 18 via the multiplexer 19. The multiplexer 19 can output the input EEG signals, brain oxygen saturation signals, temperature signals, and pressure signals to the same output line. Then, the core processing module 18 performs digital filtering, 50Hz notch filtering and wavelet transformation on the existing data, and can transmit the processed signal to the mobile terminal APP 12 via Bluetooth, NFC or WIFI radio frequency antenna 16. The core processing module 18 can also transmit multimodal data to the host computer software 13 through the serial port 17, use MATLAB for algorithm processing, and embed the state perception algorithm 14 into the host computer software 13. It can display various data of the flexible front-end signal acquisition module 31 and the brain tissue status of the current operation process, display the measured data waveform and the current safety status, and ensure the safe conduct of neurosurgery.

[0077] In some embodiments, the chip can be integrated into the circuit after a computer program is burned into it via programming 15. Finally, the acquisition circuit, core processing module 18, and thermoelectric generator 30 are powered by a flexible battery 28 through a power management chip 29. The power management chip 29 includes multiple DC-DC converters and LDOs to ensure stable data transmission.

[0078] The host computer system can be a mobile terminal APP 12 or a host computer software 13. The host computer software 13 is designed to be displayed in the form of a visual interface. After the multimodal data is transmitted to the host computer system, MATLAB is first used for algorithm processing. The state perception algorithm is embedded in the host computer display software to identify and warn of possible damage to brain tissue caused by improper operation during surgery. The host computer system can display various data of the flexible front-end signal acquisition module 31 and the state of brain tissue during the current operation to ensure the safety of neurosurgery. After digital filtering, 50Hz notch and wavelet transformation of the existing data, combined with the optical processing method of Lambert-Beer law, the current intraoperative brain tissue state is judged in real time and sent to the host computer visualization interface written in Python to display the measured data waveform and the current safety status.

[0079] Figures 5 and 6 show the display interface of the host computer software 13. Figure 5 shows the software interface when no signal is being transmitted. EEG signals are recorded through six channels: channel_1, channel_2, channel_3, channel_4, channel_5, and channel_6. Temperature signals are recorded through channel_7, brain oxygen signals through channel_8, and pressure signals through channel_9. The maximum value of the six-channel pressure signal is taken and displayed on the host computer. The upper left corner of the host computer software interface displays the current status of the measured object, which is divided into three states: safe, warning, and dangerous. When the doctor's handheld instrument applies excessive pressure to the surrounding brain tissue, the device enters a warning state, prompting the doctor to reduce the pressure on the surrounding brain tissue. All raw data is stored on the host computer and can be viewed through the data review window. Figure 6 shows an example of EEG monitoring in a flexible hybrid electronic system used for intraoperative intracranial monitoring. The left side shows the signal graphs of the six EEG channels, and the upper left corner on the right shows a graph of the frequency variation over time. In the lower right corner, you can select the power supply, signal graph playback settings, and the number of channels for the time-frequency graph.

[0080] The mobile terminal APP 12 is used on a mobile phone or PC. The mobile terminal APP 12 can display the subject's brain tissue oxygen saturation, pressure, temperature, and EEG signals in real time. When the subject's pressure exceeds the preset normal pressure, an alarm function within the APP is activated, and the surgeon can control the pressure applied by the surgical instrument to the brain tissue through the mobile terminal human-computer interaction APP. The mobile terminal interactive APP can store the received brain tissue oxygen saturation, temperature, pressure, and EEG signals in real time on the mobile terminal platform in a time series.

[0081] Figure 7 shows how to use a flexible hybrid electronic system for intraoperative intracranial monitoring. During surgery, the structure is slowly placed into the skull using surgical tools such as forceps. After adjusting the position, the surgeon performs the procedure on the flexible front-end signal acquisition module 31. This not only reduces the pressure of surgical instruments on surrounding brain tissue but also enables real-time monitoring of brain tissue oxygen, EEG, pressure, and temperature signals during surgery.

[0082] Because the present invention utilizes printed circuit board technology, it is easy to achieve large-scale batch production. A printed circuit board based on the flexible material PDMS is used, and the surface is covered with hydrogel adhesive, thereby ensuring that the device can be adhered to the skin of the subject for a long time and maintains conformal conformity, providing excellent wear comfort. The system's flexible front-end signal acquisition module 31 is designed to consist of a plurality of sensor unit arrays, which can detect parameters such as EEG, pressure, temperature, and brain tissue oxygen in real time. For sensors of multiple parameters for intracranial monitoring during surgery, high sensitivity, wide linear range, and stable data acquisition capabilities are required. The back-end signal processing module 4 adopts a modular design and consists of multiple acquisition boards, which can modularly combine the acquisition parameters. The front-end sensor detection module and the back-end signal processing module are connected using FPC. The acquisition circuit back-end transmits the data to the hardware board. The modular board sends the raw data to the host computer system via Bluetooth, Wi-Fi, and serial port for analysis, and displays the current brain tissue status in real time. The host software design is demonstrated in the form of Python plus MATLAB host computer. Although the success rate of craniotomy has reached over 90% in recent years, the brain tissue is very fragile and needs to be protected as much as possible during the operation. In addition, due to the complexity and difficulty of the operation, the patient's physiological state needs to be monitored at all times. Doctors usually use brain cotton pads to protect the brain tissue, but the brain cotton pads block the corresponding monitoring parts. The present invention can quantitatively display the oxygen, pressure, temperature and EEG signals of brain tissue during the operation. When the data is abnormal, the mobile terminal APP will issue an alarm and synchronously inform the surgeon of the data, and the surgeon will take corresponding measures for emergency treatment. The present invention can not only protect the brain tissue during craniotomy, but also continuously monitor the patient's physiological state during the operation and provide an alarm when necessary, which helps to improve the success rate of craniotomy and has far-reaching significance.

[0083] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A flexible hybrid electronic system for intraoperative intracranial monitoring, characterized in that, It includes a flexible front-end signal acquisition module, a back-end signal processing module, and a host computer system; The flexible front-end signal acquisition module includes a flexible frame body formed by arranging a top encapsulation layer, a middle encapsulation layer, and a bottom base layer from top to bottom, an electroencephalogram layer arranged between the middle encapsulation layer and the top encapsulation layer, a flexible sensor array arranged on the upper surface of the bottom base layer, a temperature-controlled hydrogel interface layer integrated above the top encapsulation layer, and a heating film integrated below the bottom base layer; the electroencephalogram layer includes a top base layer and an electroencephalogram electrode array and an internal circuit arranged on the top base layer, and the electroencephalogram electrode array passes through the flexible frame body and is connected to the temperature-controlled hydrogel interface layer; the flexible sensor array passes through the middle encapsulation layer and is connected to the electroencephalogram layer, and the flexible sensor array is used to detect pressure, temperature, and cerebral tissue oxygen saturation signals, and the heating film adjusts the adhesiveness of the temperature-controlled hydrogel interface layer through temperature to realize the adhesion and peeling of the temperature-controlled hydrogel interface layer and the cerebral tissue; The back-end signal processing module is electrically connected to the flexible front-end signal acquisition module to receive pressure, temperature, electroencephalogram, and cerebral tissue oxygen saturation signals, and after analyzing and processing them, transmits them to the host computer system through wireless or wired transmission methods.

2. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 1, wherein The flexible sensor array includes a pressure sensor array, a temperature sensor array, and a cerebral tissue oxygen sensor, which are respectively electrically connected to the back-end signal processing module.

3. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 2, wherein Multiple pressure sensors in the pressure sensor array are all flexible pressure sensors.

4. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 2, wherein The back-end signal processing module includes an acquisition circuit, a core processing module, a multiplexer switch, a flexible battery, a power management chip, and a wireless transmission module. The flexible battery realizes the power supply of the wireless flexible hybrid electronic system through the power management chip. The flexible sensor array and the electroencephalogram electrode array are respectively connected to the acquisition circuit. The acquisition circuit is connected to the core processing module through the multiplexer switch. The acquisition circuit is used to receive pressure signals, temperature signals, electroencephalogram signals, and cerebral tissue oxygen saturation signals, and transmits them to the core processing module through the multiplexer switch. The core processing module is used to process the signals transmitted by the acquisition circuit and send them to the host computer system.

5. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 4, characterized in that, The acquisition circuit includes an operational amplifier, an electroencephalogram acquisition front-end, and a cerebral oxygen acquisition front-end. The operational amplifier is electrically connected to the pressure sensor array and the temperature sensor array. The electroencephalogram acquisition front-end is electrically connected to the electroencephalogram electrode array. The cerebral oxygen acquisition front-end is electrically connected to the cerebral tissue oxygen sensor.

6. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 4, wherein The core processing module transmits the processed signals to the host computer system through the wireless transmission module or the serial port.

7. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 1, wherein The materials of the top encapsulation layer, the middle encapsulation layer, the bottom base layer, and the top base layer in the flexible front-end signal acquisition module are all polydimethylsiloxane. The electroencephalogram electrode array, the internal circuit, and the wires connecting the components of the wireless flexible hybrid electronic system are all prepared from flexible composite conductive materials.

8. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 1, characterized in that, The temperature-controlled hydrogel interface layer includes a plurality of temperature-controlled hydrogel sheets corresponding one by one to the electroencephalogram electrodes in the electroencephalogram electrode array. The plurality of temperature-controlled hydrogel sheets respectively cover the corresponding electroencephalogram electrodes. The temperature-controlled hydrogel sheets are formed by photoinitiated polymerization using poly(ethylene glycol) diacrylate as an initiator and poly(3,4-ethylenedioxythiophene) and poly(styrenesulfonic acid) as blend components.

9. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claim 8, characterized in that, A thermogenic actuator is provided in the electrothermal film, and the heat generation sites of the thermogenic actuator correspond one by one to the positions of the temperature-controlled hydrogel sheets.

10. The flexible hybrid electronic system for intraoperative intracranial monitoring according to claims 1-9, characterized in that, An alarm module is provided in the host computer system. When the pressure data received in the host computer system is higher than the preset normal pressure, the alarm module starts to alarm.

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