JP2006230955A - Nerve implant apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a measuring sensor for clarifying brain function under a natural environment. <P>SOLUTION: A needle array provided with a plurality of electrodes made of Si is equipped with an LED on one of its centers, and photo-diodes are arranged around it as a research tool for cranial nerve science. Infrared light emitted from the LED passes through brain tissues with being absorbed by the tissues, and the blood volume can be measured based on the amount of the absorption. Such system configuration enables nerve potential and metabolic amount to be observed simultaneously, and micro-amount of metabolic blood to be measured. Observing a brain surface with the infrared light is widely employed to obtain the metabolic amount. The infrared light LED is brought into the tissues, observed with transmitted light, and combined with the array with the electrodes made of Si. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a measurement sensor for elucidating brain functions.

  In order to develop a new field of neuroscience using multiple sensors in a multidimensional / stereoscopic manner, this project aims to develop an unprecedented new multifunctional integrated neural implant based on chip bonding technology. With this integrated nerve implant, it is possible to measure the electroencephalogram in the depth direction of a very small region of the cortex and perform three-dimensional observation. This integrated implant is equipped with a blood flow sensor using an infrared LED, enabling metabolic measurement and electroencephalogram measurement based on blood flow in a three-dimensional manner. Furthermore, it becomes possible to mount various chemical sensors and to electrically stimulate nerve cells. In addition, the animal implanted with the integrated nerve implant and the extracorporeal measurement unit can be connected wirelessly, so that the inside of the freely active animal's brain can be observed in multiple ways using various sensors. In the future, this integrated nerve implant can be transplanted into the brain of patients with Parkinson's disease, hemorrhoids, and half-body, and can be used to treat the disease and improve the patient's quality of life (QOL).

  As the 21st century is called the century of the brain, social attention is focused on brain and neuroscience. This is thought to be due to the strong demand for the elucidation of information processing in the brain due to the increasing demand for advanced information processing that accompanies an increase in brain diseases accompanying the progress of an aging society and the arrival of a ubiquitous society. In recent years, measurement methods for elucidating new brain functions, such as PET and fMRI, have been invented and have greatly contributed to the development of brain and neuroscience. However, a conventional technique for observing deep brain waves by inserting a measurement probe into the brain has been used to elucidate finer and more detailed phenomena. This measuring probe is made of a tungsten rod or the like by a researcher who manually machines the tip by mechanical polishing and electropolishing, which is a major cause of impairing the efficiency and reproducibility of the experiment. In order to observe more detailed phenomena, it is strongly desired to manufacture a measurement probe having a plurality of measurement units at a desired position in one measurement probe. Furthermore, in the prior art, there is a problem that, in the measurement, laboratory animals such as monkeys are restricted by restraints to fix the electrodes, are only painful, or are difficult to observe in a natural environment. .

  Against this backdrop, this research project has developed a “highly functional integrated neural implant” that uses multi-chip bonding technology to open up new areas of neuroscience by using various sensors in multiple and three-dimensional ways. suggest. Research representatives have been active in the Tohoku University Venture Business Laboratory, and have been conducting research on ultra-fine processing technology for semiconductors and MEMS for many years. By using the ultrafine processing technology that the research representatives are good at, it is possible to easily produce a measurement probe for electroencephalogram measurement, or it is possible to produce a nerve probe having many unprecedented functions. In particular, research representatives have been researching new unprecedented LSI integration / implementation techniques called three-dimensional integration technology and artificial eyes for treating blind patients. For this reason, we have already gained knowledge about the effects of integrated devices such as LSIs on living organisms.

  Figure 1 shows a conceptual diagram of a multifunctional integrated neural implant using the multichip bonding technology proposed in this research project. A nerve implant (block diagram in Fig. 2) with an LSI and an LSI formed with an amplifier and a nerve stimulation pulse generator, etc., bonded to a Si measurement probe array is transplanted into the monkey's brain to send and receive signals and supply power wirelessly. Done, brain waves are collected by the extracorporeal unit. By using such an implant, it is possible to observe the inside of the animal's brain in a free environment while minimizing the pain given to the experimental animal. In this multifunctional integrated nerve implant, all control LSIs and sensors are connected to the measuring probe by bonding. Therefore, various sensors can be easily mounted.

  Research representatives have already made a prototype of a Si measurement probe, and Fig. 13 shows a photograph of the prototype measurement probe. FIG. 15 shows the results of measuring the electroencephalogram from the Japanese monkey motor cortex using such a measurement probe. Although there was room for improvement in the impedance of the measuring probe, the brain waves were successfully observed.

  Wise et al. From the University of Minggan aim to create a system that forms a circuit on the same silicon substrate as the measurement probe, processes it, and transmits it wirelessly. However, it is impossible to easily mount sensors manufactured by different processes on the same silicon substrate. On the other hand, since the research representatives mount everything on the measurement probe by bonding, they can also produce a blood flow sensor using a light emitting element that Wise et al. Cannot. Fig. 3 shows how LSI is mounted on a measurement probe using biocompatible resin developed by research representatives. As can be seen from the figure, it is confirmed that the connection is good and the connection is good electrically.

  Fig. 5 shows a conceptual diagram of the blood flow sensor mounted on the neural implant proposed in this project. As shown in the figure, an infrared LED is mounted on the center needle of the measurement probe array, and a light receiving element is formed on the surrounding needle. Since the transmitted infrared light intensity is inversely proportional to the oxygen concentration of the transmitted tissue, the amount of blood in the tissue can be observed by observing the light emission intensity of the central LED with a surrounding light receiving element. Fig. 6 shows a photograph of an LED mounted with a biocompatible resin developed by the research representatives. FIG. 8 shows the light emission characteristics of this LED. From the figure, it can be seen that uniform light can be irradiated in a range of ± 40 degrees.

  It is possible to obtain a three-dimensional and three-dimensional brain wave distribution including the depth direction of the brain cortex, which could not be obtained in the case where the highly functional integrated neural implant proposed in this project was put into practical use. become. Furthermore, by installing the blood flow sensor described in this plan, it will be possible to obtain data for brain function elucidation from a new angle, and it can be expected that research in neuroscience will accelerate. . In the experiment, it becomes possible to remove the restraint from the experimental animal, and it becomes possible to elucidate the brain function of the experimental animal in a free environment that was not possible in the past. I believe that this is not a little, and that it is also true to the spirit of animal welfare.

  A highly integrated neural implant having a blood flow measurement function based on the multichip bonding technology will be described.

  Many research programs for expressing the nervous system of the brain are being developed around the world, with the goal of developing new information processing systems and healing brain diseases. Currently, most neurophysiologists use a single electro-etched tungsten wire electrode for neurorecording technology. Therefore, simultaneous multi-point recording within the neuronal unit of the brain has attracted considerable interest in neurophysiology due to its high measurement efficiency. As an opportunity for a more thorough investigation of increased cellular function in the nerve, a further functional system (we termed a highly integrated neuronal implant) is needed. Using this system, neurophysiologists can always record electrical response responses accurately from individual neuronal units without causing pain in laboratory animals.

  In order to realize highly functional neural implants with multi-chip bonding technology, we have developed multi-chip bonding technology consisting of a novel multi-point recording Si microelectrode, biocompatible resin and flexible cable. In addition, we attempted to construct a photodiode and LED on a neural implant to obtain microscopic tomographic images of blood flow.

  The concept of a highly integrated neural implant with blood flow measurement based on multi-chip bonding technology will be described.

  1 shows multiple electrodes, blood flow detector, on-electrode circuit (stimulation circuit, MUX, amplifier and DA converter), flexible cable with secondary coil for inductive link, main control circuit and external unit The structure of the highly functional integrated nerve implant which consists of is shown. FIG. 2 shows a block diagram of our highly integrated neural implant.

  In highly integrated neural implants, the SNR of nerve signals, signals and noise is as low as 10 microV, so multiplex transmission and DA converters must be mounted directly on a multi-electrode array. Therefore, we developed multi-chip bonding technology using biocompatible resin.

  As shown in FIG. 3, in the LSI chip, the microelectrodes and the bumps are connected by a very accurate alignment technique. As shown in FIG. 4, good IV characteristics were obtained, and the resistance value of one bump was 0.6Ω.

  In addition, using this multi-chip bonding technique, we attempted to mount an infrared LED on a nerve implant in order to obtain a tomographic image of micro blood flow at the same time as recording electrical signals with multiple electrodes. The absorption of infrared light by the tissue depends on the amount of oxygen in the blood. Therefore, as shown in FIG. 5, the intensity of light that has penetrated the tissue is measured with a photodiode.

  FIG. 6 shows an LED mounted on a neural implant using this multi-chip bonding technique. FIG. 7 shows the IV characteristics of LEDs mounted on a neural implant. The far-field image and the angular distribution of the light emitted from the LED mounted on the neural implant are shown in FIG. The light emitted from the LED spread widely between ± 40 degrees.

  In addition, the highly integrated neural implant can stimulate nerves with stimulation current pulses of both positive and negative polarities. FIGS. 9 and 10 show the measurement results of the circuit for the stimulation current generator and the test chip, respectively. With an appropriate frequency, it was possible to generate a pulse of a positive and negative stimulation current.

  The production of the multi-electrode array will be described. The overall structure of the microelectrode used for the test is shown in FIG. FIG. 12 shows a photograph of an 8-channel pattern of microelectrodes covered with a stainless steel pipe to penetrate the microelectrodes into the closed brain membrane. Also shown in FIG. 13 is a biocompatible flexible cable that has 200 recording sites (5 × 5 electrodes are 8 channels) and is connected to a completely parallel microelectrode array and electrodes. developed.

  The results will be described. A photograph of an assembled microelectrode test system consisting of a stainless steel pipe for piercing through the brain membrane, a manipulator for position control, and a stainless steel lead for connection to an amplifier. 14 shows. We used this microelectrode to monitor the neural response from the motor area of the brain that controls the lower limbs of monkeys under ketamine anesthesia. As shown in FIG. 15, we successfully observed the neural signal with our manufactured microelectrode system and the noise amplitude was approximately 10 microV.

  We have proposed and developed these highly integrated neural implants with blood flow measurement consisting of multi-microelectrodes, blood flow detectors, electrical circuits and flexible cables connected by multi-chip bonding technology. The microelectrode array was successfully manufactured and clearly detected the neural response.

  Although the embodiments of the present invention have been described with reference to the drawings, the specific configuration is not limited to these embodiments, and modifications and additions within the scope of the present invention are included in the present invention. It is.

  As an application example of the present invention, the highly functional integrated nerve implant can be used for the treatment of patients with brain diseases such as Parkinson's disease and hemorrhoids and those who are not half-body. As soon as the nerve implant detects a seizure, such as a sputum, it generates a stimulus signal and suppresses the seizure. Furthermore, for patients who are not half-body, the patient's thoughts can be interpreted with neural implants, and artificial hands, artificial legs, and computers can be operated. The present invention is considered to contribute not only to the development of brain science but also to greatly improve the quality of life of patients with brain diseases.

The conceptual diagram of a multifunctional integrated nerve implant. 1 is a block diagram of an integrated nerve implant. Bonding to a measurement probe of LSI using biocompatible resin. The graph which shows IV characteristic. The conceptual diagram of the blood flow rate sensor mounted in a nerve implant. LED mounted on the measurement probe. The graph which shows the IV characteristic of LED on a nerve implant. Light emission from the mounted LED. Bipolar current stimulation circuit. Dual current for nerve cell stimulation generated in the prototype circuit. Overall structure of the microelectrode used in the test. A picture of a microelectrode. Prototype Si measuring probe Photo of assembled microelectrode. An electroencephalogram from the Japanese monkey's motor cortex measured using a prototype measuring probe.

Claims (5)

  A nerve implant device in which a minute probe is embedded in a cranial nerve in order to elucidate a brain function, and a control LSI, sensors, and the like are mounted on the probe by bonding.   The nerve implant device according to claim 1, wherein the bonding is performed using a biocompatible resin.   2. The blood flow rate in the tissue is measured by mounting an LED and a photodiode on the probe by the bonding, and detecting the light emitted from the LED by the photodiode. 2. The nerve implant device according to 2.   4. The nerve implant device according to claim 1, wherein the nerve implant device includes a flexible cable extending from the probe.   The nerve implant device is composed of an in-vivo unit that is transplanted into the body equipped with the probe, and an in-vitro unit that collects data from the in-vivo unit, and exchanges signals between the in-vivo unit and the in-vitro unit. The nerve implant device according to any one of claims 1 to 4, wherein power is supplied to the internal unit wirelessly.