KR20210055983A - Invasive Brain Pressure System - Google Patents

Abstract

Disclosed is an invasive brain pressure measurement system. According to the present invention, the invasive brain pressure measurement system comprises: an invasive brain pressure meter detecting displacement of a diaphragm of a micro semiconductor pressure sensor to invasively measure the brain pressure at each position in the cranial cavity of the head, generating an electric signal by V = Ed according to a change in the capacitance of an LC resonator, and including one or more micro semiconductor pressure sensors including the LC resonator to measure the brain pressure corresponding to the electric signal; and a user terminal displaying the brain pressure for each specific position in the cranial cavity of the one or more micro semiconductor pressure sensors received through wired/wireless communications from the invasive brain pressure sensor. A normal range of pseudotumor cerebri of the brain cerebrospinal fluid space of the head is 0 to 15 mmHg in the case of an adult, and the user terminal displays a portion having a brain pressure equal to or greater than a predetermined value exceeding the range for each measurement position by brain pressure measurement and analysis software thereof and visualizes the same in a two-dimensional (2D) or three-dimensional (3D) brain map.

Description

Invasive Brain Pressure System

)를 측정하고, 전기 신호에 상응하는 두개강 내 측정 위치별 뇌압을 측정하여 사용자 단말로 전송하며, 사용자 단말은 측정 위치별 뇌압을 표시하고, 정상 뇌압/비정상 뇌압 부위를 표시하며, 일정치 이상의 비정상 뇌압을 2D 뇌지도 또는 3D 뇌지도에 비주얼하게 데이터 시각화하여 출력하는, 침습적 뇌압 측정 시스템에 관한 것이다.The present invention relates to an invasive brain pressure measurement system, and more particularly, to open the cranial cavity of the head by surgery to measure the brain pressure, and invasively measure the brain pressure at each measurement location in the cranial cavity of the head ( capacitance type), displacement of the upper and lower plates of the diaphragm of one or more micro semiconductor pressure sensors equipped with LC resonators, the capacitance of the LC resonator is changed, and the electric signal and the LC resonator of the micro semiconductor pressure sensor by V=Ed Resonant frequency of (

), and measures the brain pressure for each measurement location in the cranial cavity corresponding to the electrical signal and transmits it to the user terminal, and the user terminal displays the brain pressure by measurement location, displays the normal brain pressure/abnormal brain pressure, and displays abnormalities above a certain value. It relates to an invasive brain pressure measurement system that visually visualizes and outputs brain pressure on a 2D brain map or a 3D brain map.

The human brain is occupied by the cerebral parenchyma (about 1400 g, 80%), cerebral spinal fluid (150 mL, 10%), and blood (150 mL, 10%) within the solid bones of the skull, and cerebrospinal fluid (CSF) within the skull. ), the brain and the spine are connected, and the cerebrospinal fluid (CSF) is created on the one hand and absorbed by the blood vessels on the other, forming a constant pressure. The brain and spinal cord are immersed in a clean fluid called cerebrospinal fluid (CSF).

The cranial cavity has a volume of about 1,400 cc and is occupied by the brain parenchyma (about 1400 g, 80%), cerebral spinal fluid (150 mL, 10%) and blood (150 mL, 10%) in normal cases. The brain does not decrease in volume and maintains constant intracranial pressure (pseudotumor cerebri), and blood and cerebral spinal fluid (CSF) serve as the main buffer.

Cerebral spinal fluid (CSF) is a fluid that fills the central canal of the ventricle and spine in the cranial cavity of the head, and serves to supply oxygen and nutrients to brain tissues that cannot receive blood supply. It also serves to protect against traumatic shock. Cerebrospinal fluid (CSF) is made from blood that passes through the choroidal plexus in the ventricles (open spaces inside the brain). This fluid is ultimately returned to the heart through the superior sagittal sinus, which collects venous blood at the top of the two cavities.

Cerebrospinal fluid (CSF) protects the brain and spinal cord in the cranial cavity from changes in the external environment or shock, and at the same time maintains the shape of the brain. The composition of cerebral spinal fluid is similar to that of plasma other than protein, but there is a difference in sodium ion (Na+) or chloride ion (Cl-) concentration and low glucose concentration compared to plasma.

Brain pressure is the pressure of the cerebrospinal fluid (CSF) in the cranial cavity of the head. In addition, the brain pressure can be directly measured when the cerebrospinal fluid (CSF) is removed from the spine and examined.

또는 0~15 mmHg가 정상 범위이다.Brain pressure is 60-180

Or 0-15 mmHg is the normal range.

), 또는 0~15 수은주밀리미터(mmHg)의 범위를 갖는다.Medically, cerebral pressure is the intracranial pressure (pseudotumor cerebri) of the cerebrospinal fluid space in the cranial cavity of the head, and in the normal range, usually 120 to 180 several millimeters in adults (

), or 0-15 millimeters of mercury (mmHg).

Physically, pressure is P = F/A, which is the force (F) acting vertically per unit area (A).

In the normal range, intracranial pressure increases in the brain volume, increases in cerebral spinal fluid (in case of excessive production of cerebral spinal fluid), blood volume in the cranial cavity increases when excessive production of cerebral spinal fluid is generated. It becomes a state of abnormal brain pressure.

는 그에 상응하는 뇌혈관의 확장을 일으켜 혈관저항이 최소로 되며, 이에 따라 뇌혈류량이 증가하여 뇌압의 상승된다. 이는 이산화탄소의 혈관에 대한 직접적인 작용으로 생각되어지나 Reilly 등은 이러한 변화가 체내 pH나

에 의한 것이라기 보다 뇌 척수액의 pH의 변화에 의한 것이라고 보고하고 있다.`Brain pressure is determined by the cerebral parenchyma, blood volume and cerebral spinal fluid within the defined cranial cavity. Acutely increased

The vascular resistance is minimized by causing the corresponding expansion of cerebrovascular blood vessels, and accordingly, the amount of blood flow to the brain increases, resulting in an increase in brain pressure. This is thought to be a direct action of carbon dioxide on blood vessels, but Reilly et al.

It is reported that it is not caused by a change in the pH of the cerebrospinal fluid.

Cerebral spinal fluid test can be used to diagnose the cause of brain disease and at the time of examination, and in some cases, it is necessary to perform brain CT, MRI, or PET before the cerebrospinal fluid test. Although the type of meningitis can be estimated by the number of white blood cells in the brain spinal fluid, the concentration of protein and sugar, etc., cerebral spinal fluid culture tests and molecular genetics tests (PCR) are required to find the exact cause.

1 is a brain MRI image taken at a neurology department at a university hospital in Seoul, and is a brain MRI image comparing normal pressure hydrocephalus (NPH) on the left with the normal brain on the right.

Typically, excessive exercise increases heart blood pressure and brain pressure.

For reference, if the cerebrovascular vessels are expanded due to extreme stress, and the brain pressure is increased, headache, vomiting, dizziness, movement disorders, and visual field defects occur.In severe cases, a cerebral aneurysm bursts and serious bleeding in the brain causes nerve paralysis or coma. It may even come to a state.

In particular, when the brain is severely impacted by a traffic accident or bruise or the head is damaged, oxygen deficiency in the brain and swelling of the brain occur, and even if the skull is protected, the swollen brain is pressed inside the sealed skull to increase brain pressure. And the patient dies.

According to the Department of Neurosurgery at a university hospital in Seoul, the intracranial pressure measurement device has been continuously studied for the past 30 years since Lundberg4 measured ventricular pressure in 1960, and has been widely implemented in the neurosurgery field. have.

With the recent development of cranial perfusion pressure therapy, etc., intracranial pressure measurement is classified into epidural and intrathecal measurement according to its measurement location, and intrathecal measurement is again classified into subarachnoid measurement, intraventricular measurement, and intraventricular measurement. Among the various measurement methods, the intraventricular measurement method is recognized as the standard method of measuring intracranial pressure because its measured value is the most accurate, and is most commonly used. However, the intraventricular measurement method also requires the setting of a reference point at all times, and it is not easy to install it when the location of the ventricle is changed or the size of the ventricle is small, and there are disadvantages that infection or bleeding may occur during installation in some cases . Recently, an epidural measuring device that is relatively safe and easy to install has been developed that does not require setting of a reference point and is used in clinical practice in view of the risk of infection, epilepsy, bleeding, and the like. However, the epidural measuring device is located in the epidural to reduce brain damage, but according to several studies, it is higher than the measured value in the ventricle, and its accuracy is questioned. The most commonly used non-invasive measurement method using fibroptic transducer is easy to measure at the ventricle, cerebral parenchyma, and subdural locations, and has the advantage that the transducer is located close to the measurement unit. It is recognized as a reliable method. It is reported that the method using a lumbar spine and a non-invasive measurement method that can be limitedly applied to newborns is a measure that reflects changes in brain pressure, and numerical measurements are not reliable.

[Brain pressure measurement sensor, brain pressure measurement method]

For reference, the intracranial pressure sensor is a sensor for measuring brain pressure used for postoperative management of patients in the field of brain and surgery. There are three methods of measuring intracranial pressure. First, a tube is inserted directly into the ventricle to measure the pressure in the ventricle, and the second is a method to measure the pressure of the balloon from the outside by inserting a balloon between the base of the skull and the dura. Third, it is a method of measuring the internal pressure of the skull by pushing the sensor on the dura. The first and second measurement methods are to measure pressure with a pressure gauge installed outside the body, and a general pressure gauge is used.

The sensor used in the third measurement method is collectively referred to as the brain pressure sensor. Since this method can measure intracranial pressure without damaging the dura, it can be monitored for a long time without fear of bacterial infection. The brain pressure sensor should measure the pressure accurately by reducing the effect of the tension on the dura.

In addition, a team of professors at the Department of Materials Science and Engineering at the University of Illinois, USA, has developed a sensor that can measure pressure and temperature in the brain in collaboration with Washington Medical University, reported in the scientific journal Nature. Researchers in the US have developed an implantable wireless sensor that can measure pressure and temperature in the brain, and the implantable sensor for measuring brain pressure using biodegradable polymers is inserted into the brain and dissolves on its own after a few days. It is smaller than a pencil lead and less than a grain of rice. It's a lightweight sensor, and the sensor has a thin wire that's about a tenth the thickness of a hair. This wire connects the wireless transmission device attached to the outside of the skull and the sensor. Brain pressure and temperature data measured by sensors can be wirelessly transmitted in real time.

All the materials used in the sensor will melt and be absorbed in the body within a few days. The research team observed that the device was immersed in a saline solution with a concentration similar to that of the cerebrospinal fluid and found that the shape began to soften after 30 hours.

In addition, it was confirmed that the sensor could be inserted into the brain of mice to observe the condition for 3 days. It is said that so far, inflammation, which was pointed out as a problem with other implantable devices, has not occurred.

For reference, an invasive blood pressure measurement sensor is a contact between blood pressure and blood pressure when measuring blood pressure, and is called a direct method. In this method, an injection needle or catheter is inserted into a blood vessel, and blood pressure is measured by connecting an electric blood pressure meter through a connector filled with heparin reproductive water. Alternatively, blood pressure can be measured by inserting a catheter tip type pressure gauge directly into a blood vessel, and high-precision blood pressure can be measured. In this method, because the pressure gauge and blood are in contact, it is necessary to consider disinfection or electrical safety.

2 is a photograph showing an invasive brain pressure measurement method (left) and a non-invasive brain pressure measurement method (right).

The brain pressure meter is an invasive brain pressure meter that measures intracranial pressure by inserting a probe that measures brain pressure of a person's head into the skull of a person, and a ratio that measures intracranial pressure indirectly without inserting the probe into the skull. Non-invasive brain pressure meters exist.

; 1 mm Hg = 136

)를 갖는다. 정상 범위를 초과하는 뇌압은 뇌조직에 이차적인 손상을 가져올 수 있는데, 뇌압 상승에 의해 뇌관류압이 감소하면서 뇌허혈이 초래되거나, 뇌압의 압력경사에 의해 뇌탈출이 일어나면서 이차적인 뇌손상이 발생한다.According to "Brain Pressure and Hematology (J Neurocrit Care 2011;4:35-41)" of the Seoul National University Medical School Department of Neurology, the range of normal brain pressure and normal brain pressure in adults ranged from 5 mm Hg to 15 mm Hg (75-20

; 1 mm Hg = 136

). Brain pressure that exceeds the normal range can cause secondary damage to brain tissue.Cerebral ischemia is caused by a decrease in cerebral perfusion pressure due to an increase in brain pressure, or secondary brain damage occurs as a brain escape occurs due to a pressure gradient of the brain pressure.

Recently, a non-invasive method of measuring brain pressure has been studied a lot, but since it measures brain pressure outside the brain, there is no fear of bacterial infection, but the measurement of brain pressure is inaccurate and there are few medical devices that can be applied clinically. In order to measure accurately, an invasive method of measuring brain pressure is mainly used.

Two invasive methods of measuring brain pressure are commonly used, such as measuring ventricular pressure using an extraventricular drainage catheter or directly measuring brain tissue pressure by inserting a pressure monitor into the ventricle. When using an extraventricular drainage catheter, since intraventricular pressure is measured, a value reflecting the overall pressure in the cranial cavity can be obtained. However, when there is a localized mass, the brain pressure around the mass increases, but the pressure in the area far from the brain lesion is normal. When the brain pressure is compartmentalized in this way, since the overall intraventricular pressure is measured lower than the local tissue pressure, the actual elevated brain pressure may be underestimated. The advantage is that it can be used for therapeutic purposes such as draining cerebrospinal fluid or injecting drugs through a drainage catheter, and it is possible to zero the brain pressure whenever there is doubt about the reliability of the pressure measurement. The disadvantage is that since the catheter must be closed to measure the brain pressure, it is impossible to measure the brain pressure continuously for a long period of time, and complications of bleeding or infection are higher than the method of inserting the intraventricular monitor. In order to reduce the complications of infection, a catheter made of a new material coated with antibiotics or particles having an antibacterial effect is being used.

The method of measuring brain pressure using an intraventricular monitor is mainly to measure the pressure using fiberoptics, and fix it to the skull using bolts. The Camino® monitor commonly used in Korea uses this method. The downside is that the monitor shows a tendency to deviate from the true value as the time passes after inserting, so there may be a problem in the reliability of the measured value when used for a long period of time, and once inserted, the pressure gauge can be zeroed. none. However, in patients with localized brain lesions, local brain tissue pressure can be directly measured, and brain pressure can be continuously monitored, so a method of measuring brain pressure using an intracranial parenchyma monitor is widely used.

As a related prior art, a non-invasive brain pressure meter is a brain blood flow measurement device using ultrasound, and the existing devices use a wire-type controller (Special 2003-0081346: Doppler ultrasound method for blood flow monitoring and embolism detection) And apparatus, JP 2003-0036137: Method and apparatus for combining diagnostic ultrasound and therapeutic ultrasound for enhancing blood clot dissolution, US005348015A: Method and apparatus for ultrasonically detecting, counting and/or characterizing emboli, US006196972B1: Doppler ultrasound method and apparatus for monitoring blood flow).

In general, in the brain blood flow measurement device using wired ultrasound, the ultrasound probe head is placed on a specific part (window) of the patient's head, and the window depth, scale, sample volume, etc. are adjusted by pressing buttons on the controller panel with the other hand. It is adjusted to obtain the desired optimal output, but there are restrictions on the overlapping and distance of cables during work, and restrictions on movement.

Referring to FIG. 3, a non-invasive brain pressure meter that communicates ergonomically with a measuring device and a controller wirelessly is disclosed in Korean Patent Publication No. 10-2005-0056100, an ultrasonic brain blood flow measuring device using a wireless charging controller. I'm doing it.

The way to measure brain pressure and perfusion pressure is to insert a pressure transducer, a pressure measuring transducer into the brain. However, inserting a pressure transducer for measuring brain pressure may cause intracranial bleeding as a complication, and thus cannot be performed in all patients.

Therefore, the control unit used in the non-invasive ultrasonic brain blood flow measurement device [ultrasonic TCD (Transcranial Doppler) apparatus] provides a method of driving with a rechargeable infrared remote controller. As a pulsed ultrasound probe of 2 MHz, by using a wireless controller to measure and position the blood flow rate of cerebrovascular vessels through a window, it is non-invasively accurate and quick to detect cerebrovascular stenosis and obstruction when diagnosing stroke, a cerebrovascular disease. Not only can it be diagnosed correctly, but also the result values can be viewed in detail.

The conventional cerebral blood flow measurement apparatus calculates brain pressure by analyzing a waveform returned by mainly firing an ultrasound at the middle cerebral artery cerebrovascular.

The operation principle of the entire ultrasonic brain blood flow measurement device will be described with reference to the block diagram of FIG. 3. By controller, Direction is set to the forward/reverse direction of blood flow, Probe is 2MHz PW probe selection, Delete is modified, Sample is the size of Sample volume is adjusted, Zero is the zero position is adjusted, Amplitude is the amplitude of the signal is increased or decreased, Sweep is repeated constant. Set the output time of the received signal waveform of the period, Depth adjusts the size of the window depth, Scale adjusts the size of the scale when displaying the output waveform, and the Window selects one of the windows (MCA, ACA, PCA, VA). Provides the ability to choose.

Transmitter and Receiver is a device that sends a 2MHz PW signal to the skull through a probe and receives the returned Doppler signal. The received signal goes to the TGC AMP. TGC AMP is a TGC (Time Gain Control) Amplifier that amplifies the reflected wave received through Pre-Amp. The next step is Quadrature Detection. Quadrature Detection is a demodulation circuit for detecting the direction of blood flow, and passes the cutoff frequency through the LPF by multiplying the received signal and the two signals, which are 90° phase difference signals, using an analog multiplier. After that, it enters the S/H (Sample and Hold) circuit. Sample and Hold detects the Doppler frequency displacement of the sample volume as Sample & Hold (S/H) of the two demodulated In-Phase and Quadrature-Phase signals, respectively. After that, the Stationary Canceler removes the 50~150Hz components of the signal by harmonics caused by unwanted Clutter and sampling frequency among the signals detected by S/H with HPF having a cutoff frequency of 200Hz. Here, it goes through the filter. As an option, the Nyquist Filter removes the PRF/2 or higher signal among the harmonics of the signal sampled by PRF so that the audible frequency can be heard by the diagnosis through the amplifier and speaker. In the next step, the Comparator compares the phases of the two signals of the Quadrature and In-Phase in the conversion of the Doppler frequency to the frequency band voltage proportional to the velocity of the sample volume, and leads or follows a zero-crossing detector. Makes a positive or negative pulse at. Finally, Integral integrates the pulse trains of different polarities in both directions, and the LPF outputs the integrating circuit through an LPF having a cutoff frequency, and the average speed signal is output and displayed on the TFT-LCD display.

Conventional cerebral blood flow measurement devices have to measure the patient's brain pressure by contacting the head of a person while holding the measurement device directly by a skilled operator, and calculate the patient's brain pressure based only on information obtained from cerebrovascular blood vessels. It is not possible to calculate an accurate brain pressure value.

In addition, as the population ages, the number of elderly patients suffering from central nervous system diseases is increasing, and they suffer from diseases such as degenerative brain diseases such as Alzheimer's disease and Parkinson's disease, epilepsy, and blood circulation disorders such as stroke.

In the case of the elderly over 65 years old, it is called normal pressure hydrocephalus (NPH), in which brain pressure does not rise, but abnormal brain function occurs as the cerebrospinal fluid increases, and it is known that 2 out of 100 people develop a relatively common disease. have. In addition, in the case of elderly patients, there are more than 30% of cases where ultrasound does not pass through the skull. Brain pressure cannot be measured in patients whose skull has been destroyed by damage to the skull.

In recent years, research and development of an implantable brain pressure meter for invasive brain pressure measurement rather than non-invasive in vitro measurement to measure vital signs of brain pressure and brain temperature have been conducted.

Figure 1b is a low-resistance silicon wafer substrate (0001 ~ 0005 Ωcm) using conventional poly silicon, a capacitive brain pressure sensor on the lower electrode, and a resistive temperature sensor using a temperature coefficient resistance (TCR). It is a cross-sectional view of a brain pressure/temperature sensor device implemented in one semiconductor chip through a MEMS process.

The lightning pressure measurement sensor deposits a silicon-nitride film (2000 Å) on a low resistance (silicon wafer: 0001~0005Ωcm) using an LPCVD equipment, and then uses a LPCVD process on the poly-silicon. A sacrificial layer was deposited to a thickness of 1 μm using the film, and boron doping was performed during the deposition. In the poly-silicon film, the pressure sensor unit acts as a sacrificial layer, and the temperature sensor unit acts as a resistance-type temperature sensor that detects changes in surrounding temperature.

The deposited poly-silicon film was etched (1 µm) using patterning and deep-RIE processes to form the cavity of the pressure sensor and the resistor of the temperature sensor.

On the formed sacrificial layer (poly-silicon), low stress silicon nitride was deposited (1 µm) again to form a support layer of the upper electrode, and then a thin film was deposited using a sputter process (Ti/Au 200/2000). Å) and then an upper electrode was formed using an exposure process.

Thereafter, for etching of the sacrificial layer, silicon nitride, which is a support layer of the upper electrode, was partially removed through a patterning process, and isotropy etching of the silicon of XeF2 was performed to remove the sacrificial layer. In addition, a SU-8 2000 photo resist was used to maintain the pressure of the capacitive pressure sensor (2 μm).

Recently, wireless brain pressure/brain temperature measurement sensors are harmless to the human body, and a bio-insertable electronic device composed of a material that can be decomposed and absorbed by the cerebral spinal fluid within the skull to measure brain pressure and brain temperature in a wireless form for a certain period in the body. A wireless type of brain pressure/brain temperature measurement sensor using (implantable electronic device) is being studied.

Korea University has developed a'wireless brain pressure/brain temperature sensor' that melts into the body by Professor Hwang's team at the KU-KIST Graduate School of Convergence. This sensor, which is harmless to the human body, melts after a certain period of time after transmitting data related to brain pressure and brain temperature wirelessly. It is absorbed by the human body and disappears.

The research results were published in the world-renowned scientific journal'Nature'.

Professor Hwang's team emphasized, "The existing sensors for measuring brain pressure and brain temperature have to be inserted into the brain and then taken out again, so re-operation is required, but this sensor eliminates the risk of reoperation to remove the sensor."

The electronic device that can be inserted into a living body is composed/designed of a material that is completely decomposed and reabsorbed in the body within the cranial cavity, and is an ultra-thin semiconductor, silicon (Si), an insulator, silicon oxide (SiO2), and a metallic material, magnesium (Mg). , Molybdenum (Mo), and biodegradable polymer (PLGA; poly(lactic-co-glycolic acid)).

However, a non-invasive method for measuring brain pressure has been studied a lot, but since it measures brain pressure from the outside of the head, there is no fear of bacterial infection, but the measurement of brain pressure is inaccurate and there are few medical devices that can be applied clinically.

On the other hand, in an invasive method of measuring the cranial cavity of the head by surgery to measure the brain pressure, bleeding occurs and there is a concern of bacterial infection, but the measurement of the brain pressure is relatively accurate.

Patent Publication No. 10-2005-0056100 (published date June 14, 2005), "Ultrasonic brain blood flow measurement device using wireless controller for charging", B.M. Tech 21, Inc.

)를 측정하고 전기 신호에 상응하는 두개강 내 측정 위치별 뇌압을 측정하여 사용자 단말로 전송하며, 사용자 단말은 측정 위치별 뇌압을 표시하고, 정상 뇌압/비정상 뇌압 부위를 표시하며, 일정치 이상의 비정상 뇌압을 2D 뇌지도 또는 3D 뇌지도에 비주얼하게 데이터 시각화하여 출력하는, 침습적 뇌압 측정 시스템을 제공한다. An object of the present invention for solving the above problem is to open the cranial cavity of the head by surgery to measure the brain pressure, and invasively measure the brain pressure at each measurement location in the cranial cavity of the head. The displacement of the upper and lower plates of the diaphragm of one or more micro semiconductor pressure sensors equipped with an LC resonator occurs, the capacitance of the LC resonator is changed, and V=Ed causes the electric signal and the resonance frequency of the LC resonator of the micro semiconductor pressure sensor (

) And measure the brain pressure for each measurement location in the cranial cavity corresponding to the electrical signal and transmit it to the user terminal, the user terminal displays the brain pressure by measurement location, displays the normal brain pressure/abnormal brain pressure, and abnormal brain pressure above a certain value It provides an invasive brain pressure measurement system that visualizes and outputs data visually on a 2D brain map or a 3D brain map.

In order to achieve the object of the present invention, the invasive brain pressure measurement system detects the displacement amount of the diaphragm of the micro-semiconductor pressure sensor so as to invasively measure the brain pressure for each measurement position in the cranial cavity of the head, and V=Ed according to the change of the capacitance of the LC resonator. An invasive brain pressure meter having at least one micro-semiconductor pressure sensor including an LC resonator for generating an electrical signal and measuring a brain pressure corresponding to the electrical signal; And a user terminal displaying the brain pressure for each specific location within the cranial cavity of the micro semiconductor pressure sensor received through wired/wireless communication from the invasive brain pressure meter.

)를 측정하고 전기 신호에 상응하는 두개강 내 측정 위치별 뇌압을 측정하여 사용자 단말로 전송하며, 사용자 단말은 측정 위치별 뇌압을 표시하고, 정상 뇌압/비정상 뇌압 부위를 표시하며, 일정치 이상의 비정상 뇌압을 2D 뇌지도 또는 3D 뇌지도에 비주얼하게 데이터 시각화하여 출력하는 효과가 있다. The invasive brain pressure measurement system of the present invention opens the cranial cavity of the head by surgery to measure the brain pressure, and uses a capacitive type LC resonator to measure the brain pressure at each measurement location in the cranial cavity of the head in an invasive manner. One or more micro-semiconductor pressure sensors are located, and the displacement of the upper and lower plates of the diaphragm of the micro-semiconductor pressure sensor occurs according to the pressure of each measurement location in the cranial cavity, the capacitance of the LC resonator is changed, and electricity is generated by V=Ed. Signal and the resonance frequency of the LC resonator of the micro semiconductor pressure sensor (

) And measure the brain pressure of each measurement location in the cranial cavity corresponding to the electrical signal and transmit it to the user terminal, the user terminal displays the brain pressure by measurement location, displays the normal brain pressure/abnormal brain pressure, and abnormal brain pressure above a certain value It has the effect of visualizing and outputting data visually on a 2D brain map or a 3D brain map.

As a medical device, one or more micro-semiconductor pressure sensors equipped with a living body-insertable LC resonator for each measurement location in the cranial cavity of the head are medical devices and can be used to diagnose brain disease patients, head injuries, cerebral hemorrhage, cerebral infarction, meningitis, and brain tumors.

FIG. 1A is a brain MRI image taken at a neurology department at a university hospital in Seoul, and is a brain MRI image comparing normal pressure hydrocephalus (NPH) on the left and normal brain on the right.
Figure 1b is a low-resistance silicon wafer substrate (0001 ~ 0005 Ωcm) using conventional poly silicon, a capacitive brain pressure sensor on the lower electrode, and a resistive temperature sensor using a temperature coefficient resistance (TCR). It is a cross-sectional view of a brain pressure/temperature sensor device implemented in one semiconductor chip through a MEMS process.
2 is a photograph showing an invasive brain pressure measurement method (left) and a non-invasive brain pressure measurement method (right).
3 is a block diagram of a conventional whole ultrasound brain blood flow measurement equipment and a diagram showing a measurement principle.
Figure 4 is a configuration diagram of the brain pressure measurement system according to the present invention.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

)를 측정하고 전기 신호에 상응하는 두개강 내 측정 위치별 뇌압을 측정하여 사용자 단말로 전송하며, 사용자 단말은 측정 위치별 뇌압을 표시하고, 정상 뇌압/비정상 뇌압 부위를 표시하며, 일정치 이상의 비정상 뇌압을 2D 뇌지도 또는 3D 뇌지도에 비주얼하게 데이터 시각화하여 출력한다. The invasive brain pressure measurement system of the present invention opens the cranial cavity of the head by surgery to measure the brain pressure, and invasively measures the brain pressure at each measurement location in the cranial cavity of the head. The displacement of the upper and lower plates of the diaphragm of one or more micro semiconductor pressure sensors with (capacitance type) LC resonators occurs, the capacitance of the LC resonator is changed, and the electric signal and the LC of the micro semiconductor pressure sensor are changed by V=Ed. The resonant frequency of the resonator (

) And measure the brain pressure for each measurement location in the cranial cavity corresponding to the electrical signal and transmit it to the user terminal, the user terminal displays the brain pressure by measurement location, displays the normal brain pressure/abnormal brain pressure, and abnormal brain pressure above a certain value Visualize and output data visually on a 2D brain map or a 3D brain map.

For reference, in the EEG test using 32 to 128 EEG electrodes, an EEG test device outside the head can be used to determine the local location of the brain lesion where abnormal EEG is generated.

)의 변화에 상응하는 뇌압[뇌 척수액 공간의 두개강 내압(pseudotumor cerebri)]을 측정한다. Opens the cranial cavity of the head by surgery, and has a number of microscopic semiconductor pressure sensors of the bio-insertion type capacitance type at the local location of the brain lesion in the cranial cavity of the head, and the micro-semiconductor pressure of the bio-insertion type capacitive type The sensor measures the change in the capacitance of the LC resonator of the micro semiconductor pressure sensor according to the concentration of the cerebrospinal fluid at each measurement location, and measures the resonant frequency of the LC resonator (

) Corresponding to the change in the brain pressure [intracranial pressure (pseudotumor cerebri) of the cerebral spinal fluid space] is measured.

)의 변화에 상응하는 뇌압[뇌 척수액 공간의 두개강 내압(pseudotumor cerebri)]을 측정한다.The ultra-compact semiconductor pressure sensor of the bio-inserted capacitive type is a micro-pressure sensor composed of an LC resonator, a micro-pressure sensor chip made with MEMS technology on a glass substrate or a flexible polyimide substrate, measuring position within the cranial cavity of the head. The characteristic impedance is changed by measuring the change in the capacitance of the LC resonator of the micro semiconductor pressure sensor of the star, and the resonant frequency of the LC resonator (

) Corresponding to the change in the brain pressure [intracranial pressure (pseudotumor cerebri) of the cerebral spinal fluid space] is measured.

For reference, pressure sensors are classified into mechanical pressure sensors and semiconductor pressure sensors. The mechanical pressure sensor uses a Bourdon tube, a metal plate diaphragm, etc., and the size of the device of the pressure sensor is large, and the semiconductor pressure sensor uses a silicon diaphragm, and the size of the device is made using MEMS (Micro Electro Mechanical Systems) technology. Can be made small. Silicon diaphragm type pressure sensors using MEMS technology are classified into piezo-resistive type and capacitive type semiconductor pressure sensors according to the detection method.

The capacitive semiconductor pressure sensor can use a flat diaphragm or ring diaphragm having a thickness of 200 to 300 μm, and when the pressure changes, the capacitance changes and the electrical signal changes accordingly to measure the pressure.

에 의해 커패시턴스(capacitance)가 변화되며, V = Ed [v] 식에 전기 신호를 측정한다. That is, when pressure is applied to the upper plate, the distance d between the upper and lower plates changes in proportion to the magnitude of the force due to the piezoelectric phenomenon (pressure -> electrical signal).

The capacitance is changed by, and the electric signal is measured according to the equation V = Ed [v].

For reference, in order to invasively measure the brain pressure in the cranial cavity of the head, the invasive pressure sensor changes the piezo-resistance value of the semiconductor when a force is applied to the semiconductor pressure sensor, and measures the electrical signal by the piezoelectric effect (pressure -> electrical signal). Without using a piezo resistance type pressure sensor that measures

에 의해 커패시턴스 값이 측정된다.

는 진공의 유전율(permittivity of vacuum), ε는 물질의 비유전율(relative permittivity), A는 평행판 콘덴서 면적(sensing area)이며, d는 감지층의 두께(thickness of the sensing layer)이다.The micro pressure sensor of the present invention uses a micro semiconductor pressure sensor using an electrostatic capacitance type LC resonator. As a basic concept, the capacitance between the two electrodes, which is the cross-sectional area of the parallel plate capacitor A and the distance d between the upper and lower plates of the parallel plate capacitor, is

The capacitance value is measured by

Is the permittivity of vacuum, ε is the relative permittivity of the material, A is the sensing area of the parallel plate, and d is the thickness of the sensing layer.

V is the potential difference between the two conductor plates of the upper and lower plates, E is the intensity of the uniform magnetic field generated between the two conductor plates, and d is the distance between the two conductor plates of the upper and lower plates.

4 is a block diagram of an invasive brain pressure measurement system according to the present invention.

The invasive brain pressure measurement system of the present invention

The brain pressure measurement system of the present invention,

In order to measure the brain pressure invasively for each measurement location in the head's cranial cavity, the displacement amount of the diaphragm of several μm to several tens of μm thick of the micro semiconductor pressure sensor 11 at each measurement location is detected, and V= according to the change of the capacitance of the LC resonator. An invasive brain pressure meter 10 having at least one micro semiconductor pressure sensor having an LC resonator for generating an electrical signal by Ed and measuring a brain pressure corresponding to the electrical signal; And

Including a user terminal 20 (PC, smartphone/tablet PC) 20 for displaying the brain pressure for each specific location within the cranial cavity of the micro semiconductor pressure sensor received through wired/wireless communication from the invasive brain pressure meter 10, and ,

The user terminal displays the brain pressure for each measurement location in the cranial cavity on the display, displays abnormal brain pressure above a certain value, and visually visualizes and outputs it on a 2D brain map or a 3D brain map.

The invasive brain pressure meter 10 may further include a separate pressure gauge connected to the micro semiconductor pressure sensor 11 on the outside of the head.

The micro-semiconductor pressure sensor 11 equipped with an invasive living body-insertable LC resonator in the cranial cavity of the head uses MEMS (micro electro mechanical system) technology on a glass substrate or a flexible flexible substrate. Inductor) is designed/manufactured using MEMS technology and manufactured by semiconductor packaging. The ultra-miniature semiconductor pressure sensor 11 equipped with a tube-type capacitance type LC resonator is used.

Pressure sensors that measure brain pressure are classified into intrathecal measurements (subarachnoid measurement, intraventricular measurement, and intraventricular measurement), and the intraventricular measurement method, which is mainly used among various measurement methods, can use a pressure sensor of the intracranial pressure measurement method whose measurement is accurate. have.

The intracranial pressure sensor used as a brain pressure measurement sensor is

i) Measuring the pressure in the ventricle by inserting a tube directly into the ventricle, and measuring it with a pressure gauge from the outside of the head, or

ii) The pressure of the balloon is measured from the outside of the head by inserting a balloon between the base of the skull and the dura, and measured with a pressure gauge from the outside of the head.

iii) Third, the brain pressure sensor used in the method of measuring the intracranial pressure by pushing the brain pressure sensor on the dura can measure the intracranial pressure without damaging the dura, so it can be monitored for a long time without fear of bacterial infection. have. The brain pressure measurement sensor should measure accurate pressure by reducing the influence of the dura mater tension.

In the embodiment, a micro semiconductor pressure sensor 11 provided with an LC resonator of a capacitance type will be described as an example.

[Example]

For example, as an RF Bio Sensor for measuring brain pressure, the ultra-compact semiconductor pressure sensor 11 equipped with a capacitive type LC resonator 11 is symmetrical on a glass substrate or a flexible polyimid flexible substrate. It may be implemented as a BPF of an octagonal structure (helical structure) that is provided with an LC resonator and is cross-connected by an air bridge structure.

Cuc = Cg + Cs

Here, Cuc is the unit cell capacitance constituting each turn of the octagonal resonator, Cg is the gap capacitance, and Cs is the substrate mapping capacitance.

The capacitance of the LC resonator changes according to the displacement amount of the diaphragm for each measurement position in the two cavity of the head, and the resonant frequency change, reflection coefficient, and gap capacitance due to the spiral-coupled BPF capacitance having two symmetrical resonators capacitance) and complex permittivity, and measure the capacitance,

The octagonal structure BPF is

Two symmetrical LC resonators cross the lower part of the air-bridge structure and form an LC resonator having a plurality of turns of an symmetrical octagonal structure, and induction between mutually wound resonators each having an inductance of L/2. Inductive coupling (Lm),

Capacitive coupling between gaps of two open-ended interwound resonators (Cg) and fringe capacitance (Cs) developed through flexible substrates. ),

The resistance characteristic of an LC resonator is modeled as Rs, and the unit cell capacitance Cuc of each turn of the octagonal structure is the capacitance value obtained by adding the gap capacitance (Cg) and the substrate mapping capacitance (Cs). ,

)는

에 의해 계산된다.The basic resonance frequency of the octagonal BPF (

) Is

Is calculated by

Here, Leq is the inductance of the equivalent circuit, and Ceq is the capacitance of the equivalent circuit.

The capacitive type micro-semiconductor pressure sensor 11 may be provided in the invasive brain pressure meter 10 having a control unit, a storage unit, and a communication unit through an amplifier and an ADC.

The invasive brain pressure meter 10

In order to open the cranial cavity of the head by surgery and measure the brain pressure invasively, a micro semiconductor pressure sensor 11 equipped with a bio-inserted capacitive LC resonator at one or more specific locations of the brain in the cranial cavity is provided. It is located, detects the displacement of the diaphragm according to the intracranial pressure of each measurement location in the cranial cavity, and measures the change in the capacitance of the LC resonator of the micro semiconductor pressure sensor, and an electrical signal is detected by V = Ed, and the brain pressure corresponding to the electrical signal A micro semiconductor pressure sensor 11 having at least one LC resonator measuring

A control unit 12 connected to the micro semiconductor pressure sensor 11 having the at least one LC resonator;

A storage unit 13 connected to the control unit and configured to store brain pressure information measured for each measurement position in the cranial cavity of the head; And a battery 19.

Additionally, the invasive brain pressure meter 10 is connected to the control unit 12 and further includes a display unit (not shown) for displaying brain pressure information measured for each measurement location in the cranial cavity of the head.

In addition, the invasive brain pressure meter 10 is connected to the control unit 12, and provides wired and wireless communication (USB cable, Bluetooth, Wi-Fi, etc.) It further includes a communication unit for transmitting to the user terminal 20 through.

The ultra-compact semiconductor pressure sensor equipped with the capacitive LC resonator is a bio-insertable RF biosensor in the two cavity of the head,

After opening the cranial cavity of the head by surgery, a micro-semiconductor pressure sensor is provided to measure the brain pressure invasively at one or more specific locations of the brain, and a bio-insertable capacitance in the cranial spinal fluid (CSF) in the cranial cavity It uses an ultra-compact semiconductor pressure sensor equipped with a capacitance type LC resonator, and the displacement of the diaphragm with a thickness of several μm to several tens of μm occurs depending on the pressure at each measurement location in the two cavity, and changes in the capacitance of the LC resonator are detected. By measuring, an electric signal is generated by V=Ed, and the resonant frequency of the LC resonator is measured, and the corresponding brain pressure (pseudotumor cerebri) is measured.

The micro semiconductor pressure sensor 11 equipped with the LC resonator is

A substrate;

A bottom electrode provided on the substrate;

)의 변화를 측정하고 상기 전기 신호에 상응하는 뇌압을 측정하는 생체삽입형 정전용량 방식(capacitance type)의 LC 공진기를 구비한 초소형 압력 센서; 및Formed on the lower electrode, for example, a first metal line and a first stub using gold (Au) and a second metal line and a second stub using gold (Au) facing each other, the A first stub and an input/output port respectively connected to the second stub; The displacement of the diaphragm (thickness d of the upper and lower plates) is sensed according to the pressure of each measurement position in the cranial cavity of the head, and the electrical signal is measured by V=Ed. Additionally, the resonance frequency of the LC resonator of the micro semiconductor pressure sensor (

) To measure the change and to measure the brain pressure corresponding to the electrical signal, a microscopic pressure sensor equipped with an LC resonator of the bioinsertion type capacitance type (capacitance type); And

It includes an upper electrode (top electrode) provided on the pressure sensor,

The substrate is a glass substrate or a flexible flexible substrate,

The flexible substrate is made of polyimide or polysilicon.

The ultra-compact semiconductor pressure sensor equipped with the bio-insertable capacitive type LC resonator is the three materials SU-8, silicon nitride, and Au, which are exposed to the biological tissue in the cranial cavity of the head, and the chip is inserted into the living body. However, a material that is stable and excellent in biocompatibility was used.

The user terminal 20 uses a PC, a smartphone, or a tablet PC, and a brain pressure measurement and analysis SW is installed, and brain pressure for each measurement location in the cranial cavity of the head is displayed.

The user terminal 20 is the resonant frequency information of the LC resonator measured according to the change in the capacitance of the LC resonator according to the displacement amount of the diaphragm of the micro semiconductor pressure sensor 11 equipped with the LC resonator for each measurement position in the cranial cavity of the head. A communication unit 21 received through wired/wireless communication (USB cable, Bluetooth, Wi-Fi, etc.); A control unit 22 connected to the communication unit 21 and controlling the brain pressure for each measurement position in the cranial cavity to be displayed on the display unit 27; It is connected to the control unit 22, stores brain pressure measurement and analysis software, and is measured according to a change in the capacitance of the LC resonator of the micro semiconductor pressure sensor 11 equipped with the LC resonator. A storage unit 23 for storing the measured electrical signal (additionally, the resonance frequency of the LC resonator) and brain pressure information corresponding thereto; And a display unit 27 connected to the control unit 22 and displaying the measured brain pressure for each measurement position in the cranial cavity of the head of the micro semiconductor pressure sensor 11 using a living body implantable LC resonator.

When a person's head is scanned using a 3D scanner, it is possible to create a 3D brain map that is modeled and rendered in 3D, and the 3D brain map can display abnormal brain waves and abnormal brain pressure areas on the coordinates in a 3D space.

For adults, the normal range of intracranial pressure (pseudotumor cerebri) in the cerebrospinal fluid space within the cranial cavity has a range of 0 to 15 mmHg, and the brain pressure of the user terminal 20 is measured and analyzed for areas of brain pressure exceeding the normal range of brain pressure. The brain pressure for each measurement location in the cranial cavity is displayed by software, and visualized on a 2D brain map or a 3D brain map and output.

In adults, the normal range of intracranial pressure (pseudotumor cerebri) ranges from 0 to 15 mmHg.

In the invasive brain pressure measurement system of the present invention, the cranial cavity of the head is opened by surgery, and at least one micro-semiconductor pressure sensor equipped with a capacitive LC resonator for each measurement location in the cranial cavity of the head is located, and the diaphragm for each measurement location in the cranial cavity It detects the displacement and measures the change in capacitance of the LC resonator of the micro semiconductor pressure sensor, generates an electrical signal by V=Ed, measures the brain pressure for each measurement location in the cranial cavity corresponding to this electrical signal, and transmits it to the user terminal. The terminal displays the brain pressure for each measurement location in the cranial cavity on the display unit, and visually visualizes and outputs abnormal brain pressure above a certain value on a 2D brain map or a 3D brain map.

As a medical device, one or more micro semiconductor pressure sensors equipped with a living body-insertable LC resonator for each measurement location in the cranial cavity of the head are medical devices and can be used to diagnose brain disease patients, head injuries, cerebral hemorrhage, cerebral infarction, meningitis, and brain tumors.

Although it has been described with reference to the preferred embodiments of the present invention, various modifications or variations of the present invention within the scope not departing from the spirit and scope of the present invention described in the following claims by those of ordinary skill in the relevant technical field It will be understood that this can be done.

10: brain pressure meter
11: Ultra-compact semiconductor pressure sensor using LC resonator
12: control unit 13: storage unit
17: communication unit 19: battery
20: user terminal 21: communication unit
22: control unit 23: storage unit
27: display

Claims (9)

The displacement of the diaphragm of the micro-semiconductor pressure sensor is sensed to measure the brain pressure by invasive measurement position in the cranial cavity of the head, and an electrical signal is generated by V=Ed according to the change in the capacitance of the LC resonator, and the brain pressure corresponding to the electrical signal An invasive brain pressure meter having at least one micro-semiconductor pressure sensor having an LC resonator for measuring the measurement; And
A user terminal that displays brain pressure for each specific location in the cranial cavity of the at least one micro semiconductor pressure sensor received through wired or wireless communication from the invasive brain pressure meter;
Invasive brain pressure measurement system comprising a. The method of claim 1,
The ultra-compact semiconductor pressure sensor with the LC resonator
After the cranial cavity of the head is opened by surgery, it is equipped to invasively measure the brain pressure at one or more specific locations, and uses a micro semiconductor pressure sensor equipped with a capacitance type LC resonator in the cranial cavity of the head. By measuring the brain pressure, an invasive brain pressure measurement system. The method of claim 1,
The ultra-compact semiconductor pressure sensor with the LC resonator
Board;
A lower electrode provided on the substrate;
Formed on the lower electrode, for example, a first metal line and a first stub using gold (Au) and a second metal line and a second stub using gold (Au) facing each other, the A first stub and an input/output port respectively connected to the second stub; The displacement of the diaphragm (thickness d of the upper and lower plates) is sensed according to the pressure of each measurement position in the cranial cavity of the head, and the electrical signal is measured by V=Ed. Additionally, the resonance frequency of the LC resonator of the micro semiconductor pressure sensor (

) To measure the change and to measure the brain pressure corresponding to the electrical signal, a microscopic pressure sensor equipped with an LC resonator of the bioinsertion type capacitance type (capacitance type); And
It includes an upper electrode provided on the pressure sensor,
The substrate is a glass substrate or a flexible substrate with flexibility,
The flexible substrate is a polyimide (polyimid) or polysilicon (polysilicon) using, invasive brain pressure measurement system. The method of claim 1,
The invasive brain pressure meter
In order to open the cranial cavity of the head by surgery and measure the brain pressure invasively, a micro semiconductor pressure sensor 11 equipped with a bio-inserted capacitive LC resonator at one or more specific locations of the brain in the cranial cavity is provided. It is located, detects the displacement of the diaphragm according to the intracranial pressure of each measurement location in the cranial cavity, and measures the change in the capacitance of the LC resonator of the micro semiconductor pressure sensor, and an electrical signal is detected by V = Ed, and the brain pressure corresponding to the electrical signal A micro semiconductor pressure sensor having at least one LC resonator for measuring
A control unit connected to the micro semiconductor pressure sensor 11 having the at least one LC resonator;
A storage unit connected to the control unit and configured to store brain pressure information measured for each measurement position in the cranial cavity of the head; And
Invasive brain pressure measurement system including batteries. The method of claim 4,
The invasive brain pressure measurement system is connected to the control unit and further comprises a display unit for displaying brain pressure information measured for each measurement location in the cranial cavity of the head. The method of claim 4,
The invasive brain pressure measurement system is connected to the control unit, further comprising a communication unit for transmitting the measured location and measured brain pressure information for each measurement location in the cranial cavity of the head to the user terminal through wired or wireless communication. The method of claim 1,
The invasive brain pressure measurement system further includes a separate pressure gauge connected to one or more micro semiconductor pressure sensors on the outside of the head. The method of claim 1,
The user terminal transmits the resonant frequency information of the LC resonator measured according to the change in the capacitance of the LC resonator according to the displacement amount of the diaphragm of the micro semiconductor pressure sensor equipped with the LC resonator for each measurement position in the cranial cavity of the head. A communication unit received through a USB cable, Bluetooth, Wi-Fi, etc.);
A control unit connected to the communication unit and controlling the brain pressure to be displayed on the display unit 27 by analyzing the brain pressure for each measurement position in the cranial cavity;
It is connected to the control unit, stores the brain pressure measurement and analysis software, and the electrical signal measured by V = Ed measured according to the change in the capacitance of the LC resonator of the micro semiconductor pressure sensor equipped with the LC resonator (in addition, the LC resonator A resonant frequency) and a storage unit for storing brain pressure information corresponding thereto; And
An invasive brain pressure measurement system comprising a display unit connected to the control unit and configured to display the measured brain pressure for each measurement position in the cranial cavity of the head of the micro-semiconductor pressure sensor using a living body-insertable LC resonator. The method of claim 8,
In the case of an adult, the intracranial pressure (pseudotumor cerebri) of the normal range of the cerebral spinal fluid space in the cranial cavity of the head has a range of 0 to 15 mmHg, and a region of brain pressure above a certain value exceeding this is determined by the brain pressure measurement and analysis software of the user terminal. Invasive brain pressure measurement system that displays brain pressure by measurement location and visually visualizes it on a 2D brain map or a 3D brain map

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