Research And Design Of CMOS Microelectrode Array Chip For Neural Signal Extraction

The brain is the "leadership center" of the organism and governs various activities of the body.The reason why the brain receives and processes complex information is the connection and coordinated electrical activity between the network of neurons.In order to master the brain's process of processing information and sending instructions,high-resolution technology is needed to monitor the electrical activity of neurons.The traditional methods of measuring the electrical activity of neurons are:voltage clamp technology,current clamp technology and patch clamp technology.The specific method is to use glass capillary to draw electrodes,penetrate the cell membrane to obtain the electrophysiological characteristics of neurons,and understand the mechanism of their action potentials.There are hundreds of billions of neurons in the brain.The disadvantage of using the above traditional methods is that the number of cells to be monitored at the same time is small,and the intrusion of electrodes into the cells shortens the survival time of the cells.With the development of technology,extracellular recording microelectrode array technology is used to study the network activity of neurons,replacing traditional techniques such as patch clamp for intracellular recording.The extracellular recording method is to culture neuron tissue in a microelectrode array.On the surface of the Array(MEA),when an action potential occurs on a neuron,the flow of ions inside and outside the cell and the membrane resistance form an electric field,and the induced charges are recorded by the microelectrode array.Compared with the traditional method,the extracellular recording method is non-invasive to the cells,the cell survival time is long,and it can be recorded for a long time;and the microelectrodes are small in area,large in number,with high resolution,and can simultaneously monitor a large number of neurons.The traditional microelectrode array requires an external device to amplify the electrical signal of the cell,which will weaken the signal and limit the size of the microelectrode array.In recent years,with the rapid development of Complementary Metal Oxide Semiconductor,microelectrode arrays and amplifier circuits can be integrated on the same chip to improve position resolution and reduce noise,and enhance the ability to collect signals.The Topmetal series of pixel chips independently developed by our laboratory uses bare top metal as the signal collection electrode for each pixel.At the same time each nixel integrates signal processing circuits such as amplifiers,which can be used to extract neuronal signals in the brain.This paper uses the existing pixel chip Topmetal_?-test in the laboratory to verify the feasibility of Topmetal series pixel chips to extract neuron signals,and on the basis of the test results,a microelectrode array pixel chip Topmetal-MEA is designed.The specific work and innovations of this paper are as follows:1.Use Topmetal_?-pixel chip to test analog neurons:Topmetal_?_the overall area is 8×9mm2,including 72 rows×72 columns of pixels,analog readout and digital readout units;single pixel size 83.2?m×83.2?m,including electrodes inside,Analog front end,source follower,comparator,DAC,5-bit SRAM and priority logic control module,the electrode area for collecting charge is 15×15?m2;the electrical performance of this chip is well tested.A gold-plated tungsten wire is used to simulate a neuron,and the signal that generates an action potential from the neuron is simulated by a signal source and input to the tungsten wire.The chip can detect this signal.The amplitude of neuron action potential signals varies from organism to organism.Therefore,the signal source provides a large range of signal amplitude during the experiment,and signals as low as 20mV can be detected.2.Topmetal-MEA pixel chip circuit design:Topmetal-MEA includes 128 rows×128 columns of pixels and analog readout channels.A single pixel contains electrodes,charge sensitive amplifier(CSA),two-stage source follower,2bit SRAM,OR gate and stimulation circuit;the analog readout channel includes scan module,voltage conversion module and analog buffer.The charge collected by the electrode is injected into the CSA and converted into an analog voltage,which is sent to the outside of the array through the column switch through the two-stage source follower drive,and is output to the outside of the chip through the analog buffer.The source follower circuit ensures the stability of the output signal;the output signal of the 2bit SRAM and OR gate can control the transmission gate in the circuit to convert the circuit into a stimulation mode and stimulate the tested neuron tissue with voltage;the Scan module is used to control each For signal output within the pixel,Buffer can increase the driving capability of the output signal.3.Topmetal-MEA pixel chip layout design:The overall area of the chip is 5.8×4.2mm2,including 181 pins distributed around the chip.The size of a single pixel is 36.5?m×25.5?m and the electrode area is 17.4×6.3?m2.On the left and bottom of the 128 rows×128 columns is an"L"-shaped digital scanning module,the left side is 4777?m,and the bottom is 3343?m..After the row output and column output of the Scan module are connected to the layout of the level conversion module,the layout of the analog buffer is placed at the bottom right of the array.In order to reduce the value of the equivalent charge noise ENC,the layout of a single pixel must be continuously optimized to reduce the parasitic capacitance on the feedback capacitor and the input and output connection traces of the CSA.The area of a single pixel is reduced,and neuron signals can be detected more accurately.4.The simulation results after Topmetal-MEA pixel chip:the rise time of CSA in the pixel is 1.12?s,the fall time is 1.26ms,the equivalent charge noise ENC is 21.24e-;the operational amplifier gain used is 71.1dB,and the gain bandwidth product is 2.008 MHz;When the input charge is 1K,the calculation of the theoretical value is 16mV,and the output amplitude is 13.07mV.Compared with the existing chip,this chip has made improvements in the four aspects of equivalent charge noise,stimulation circuit,electrode area and array size.The ENC is reduced,so that the circuit can detect weaker neuron signals;the stimulation circuit uses 2-The transmission gate in the output signal control circuit of bit SRAM and OR gate is obtained in a fully closed state;the electrode area is 1 7.4×6.3?m2,which is smaller than the existing domestic electrode area;the array size is increased to 128 rows×128 columns,The above are the four innovations of the chip made in this article.The chip has been delivered to the factory and successfully taped out,and the related external circuits have been made on the board.The electrical test and functional experiment of the chip will be arranged in the future.