CN107485385B - Ultrahigh-flux high-space-time-resolution living body neuron activity detection system - Google Patents
Ultrahigh-flux high-space-time-resolution living body neuron activity detection system Download PDFInfo
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Abstract
The invention discloses a system for detecting the activity of living neurons with ultrahigh flux and high space-time resolution, which comprises: the nerve probe array is used as a collecting tool of nerve signals; the signal acquisition module is used for acquiring and reading the neural signals acquired by the neural probe array; the signal processing module is used for sequentially amplifying, filtering and carrying out analog-to-digital conversion on the neural signals read out by the signal acquisition module; the data storage and transmission module is used for transmitting and storing the neural signal data processed by the signal processing module; and the control and display system is used for controlling the operation of each module of the system and displaying the relevant working process. The system breaks through the limitation that the existing detection system is smaller than 1000 channels, can detect biological cranial nerve signals in multiple directions and multiple levels aiming at the acquisition and processing of ultra-high flux nerve signals, can meet the increasing research requirements of researchers, and provides hardware support for realizing the plan of recognizing and researching the brain of human beings.
Description
Technical Field
The invention relates to the technical field of neuron detection, in particular to an ultrahigh-flux high-space-time-resolution living body neuron activity detection system.
Background
The neural signal detection is the most critical and indispensable part for human brain research, and the next research can be carried out only if the accurate and reliable neural signal is obtained. With the deeper and deeper cognition of the brain, the requirements on the quantity, resolution, signal to noise ratio and the like of the acquired cranial nerve signals are higher and higher. How to develop a high-channel, high-resolution, reliable and high-reliability neural signal acquisition system has been a goal pursued by those skilled in the art.
The basic functional unit of the brain is a neuron. When a neuron is active, it undergoes an all-or-nothing short-lived change in its membrane potential, called the action potential, and the signal recorded extracellularly is of the order of 80-200 microvolts for a duration of about 1 millisecond. The amplitude of the action potential is fixed and unchanged, like a digital signal in a modern computer, and is characterized as 1 when a neuron is active and 0 when the neuron is inactive. To reveal the mechanism of brain function and decipher the information coding principle of its neuron network, it is necessary to observe and record the action potential signals of the individual neurons in the complex neuron network of the brain as many as possible at the same time. While the conventional acquisition systems currently in wide use are generally in the 128-channel 256 channels, the highest acquisition system currently in the experimental stage is also in the vicinity of 1000 channels, such as Scholvin.J. et al, Close-Packed Silicon Microelectrodes for scalable spatial iterative Neural Recording, IEEE Transactions on biological Engineering, Vol.63(2016), pp.120-130, and the existing way of connecting the electrodes to the acquisition system defines this upper limit. Recording the Activity of a large number of neurons simultaneously is one of the main targets of the american brain program "dynamic brain Map Project": namely, by developing a new technology, the method obtains the action potential (Every action potential) of each Neuron in the brain Neuron network as much as possible. Moreover, the new generation of technology can only maximize its value by collecting the activities of large-scale neurons when conscious animals are behaving and further analyzing the neural circuit mechanisms that derive the behaviour. Therefore, the research and development of a new generation of large-scale neuron activity recording technology can simultaneously observe the action potentials of a large number of neurons in the brain of an animal in the waking behavior, and is a huge challenge facing the advanced technology research of the international brain science at present.
The existing technologies for observing and recording brain activity signals mainly include: functional magnetic resonance imaging, electroencephalogram recording, two-photon calcium imaging, voltage sensitive imaging, multi-channel in-vivo recording and the like. Signals recorded by functional magnetic resonance imaging and electroencephalogram are from macroscopic activity of neuron clusters, and single neuron activity signals cannot be distinguished, such as Lolothetis.N.K, Whatwe can do and what we can do with fMRI.Nature, Vol.453(2008), pp.869-878, doi:10.1038/nature06976(2008). The two-photon calcium imaging technology can distinguish the activity signal of a single neuron, but the sampling frequency can only reach about 30Hz at present, and the principle of calcium imaging is that the concentration of intracellular calcium is changed due to electrical activity, and further the change of a calcium-sensitive fluorescent signal is caused, which is equivalent to the convolution of the electrical activity of the neuron and a function of about one hundred milliseconds, so that the time resolution of the fine time sequence of the neuron activity, the high-frequency discharge activity and the functional connection strength among the neurons is not high, such as Scanziani.M,
m, Electrophysiology in the age of light, Nature, Vol.461(2009), pp.930-939. Voltage sensitive imaging although the rate of fluorescence signals can reflect millisecond-scale electrical activity of neurons, the signals are too low and single cell accuracy is not readily achieved, as in deisseoth.k, chnitzer.m.j, Engineering approaches to illuninating tissue structures and dynamics, Neuron, vol.80(2013), pp.568-577. Currently, only multi-channel in-vivo recording technology can directly detect extracellular action potential signals of group neurons and meet the precision requirement of the activity level of single neurons, such as Buzs & ki.G, Neural syntax: cell assays, synapses, and readers, Neuron, Vol.68(2010), pp.362-385. On the basis, how to break through the limit of the number of the existing channels is also a problem which is continuously addressed by researchers, and the realization of high channels involves high passThe method comprises the steps of manufacturing a neural probe, acquiring data with high flux, and communicating and storing data at high speed.
Disclosure of Invention
The invention aims to provide an ultrahigh-flux high-space-time-resolution living body neuron activity detection system, breaks through the limitation that the existing detection system is smaller than 1000 channels, can detect biological cranial nerve signals in multiple directions and multiple levels aiming at the acquisition and processing of ultrahigh-flux nerve signals, can meet the increasing research requirements of researchers, and provides hardware support for realizing the plan of recognizing and researching the brain of human beings.
The purpose of the invention is realized by the following technical scheme:
an ultra-high flux high spatial-temporal resolution in vivo neuron activity detection system, comprising: the device comprises a nerve probe array, a control and display system, a signal acquisition module, a signal processing module and a data storage and transmission module; the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module are sequentially connected, and the control and display system is respectively connected with the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module; wherein:
the nerve probe array is used as a collecting tool of nerve signals;
the signal acquisition module is used for acquiring and reading the neural signals acquired by the neural probe array;
the signal processing module is used for sequentially amplifying, filtering and carrying out analog-to-digital conversion on the neural signals read out by the signal acquisition module;
the data storage and transmission module is used for transmitting and storing the neural signal data processed by the signal processing module;
and the control and display system is used for controlling the work of the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module and displaying the related work process.
The nerve probe array is a three-dimensional nerve probe array with the total channel quantity of 10000 formed by vertically assembling a plurality of probes on a connector through a reverse welding process or a connector assembly according to a certain arrangement sequence, and the number of channels of a single probe is 500-1000; one side of the connector is the socket or pad for the probe and the other side is a 100 x 100 array of pads.
The surface electrode array nerve probe is manufactured by adopting a micro-nano processing technology, wherein a substrate adopts silicon, and a layer of 0.1-1 micron silicon oxide or silicon nitride film is grown by low-pressure chemical vapor deposition to serve as an electrode substrate isolation layer; the electrodes and the internal connecting wires adopt Au/Ti or Pt/Ti, and pattern exposure is carried out by using electron beam lithography or electron beam lithography-ultraviolet lithography mixed technology; then, a single-layer or composite film of silicon oxide and silicon nitride is grown by using a plasma chemical vapor deposition or low-pressure chemical vapor deposition technology to serve as a passivation layer, the electrodes are exposed by adopting reactive ion etching or ion beam etching, and finally, the formation of the nerve probe outline is completed by adopting a wet etching technology.
The infrared focal plane array of the CMOS circuit chip is used as a signal acquisition module, the infrared focal plane array of the CMOS circuit chip is connected with a connector of the nerve probe array in a reverse welding mode, and a read-out circuit ROIC of the signal acquisition module is connected with a signal processing module through a specific circuit interface.
In the signal processing module, the amplification processing of the neural signals is realized through a differential amplifier, noise signals in the neural signals are filtered through a filter, the denoised signals are converted into digital signals through an analog-to-digital converter, the sampling frequency of the analog-to-digital converter is greater than 20kHz, the resolution is 12bits, and the high-fidelity sampling quantification of the neural signals is realized.
The data storage and transmission module adopts a Camera Link protocol, the storage capacity is TB magnitude, the transmission rate is Gb/s magnitude, the time resolution is 1ms, and data which is output by the signal processing module and is converted into a specific format through the FPGA is transmitted and stored.
The technical scheme provided by the invention can be seen that aiming at the urgent need of neuroscience for disclosing the large-scale neural cyclic coding behavior rule, the invention aims to break through the limitation that the existing detection system is smaller than 1000 channels, innovatively complete the high-precision acquisition and measurement of ultrahigh channels by an ROIC circuit of a CMOS image sensor, and innovatively realize an electrode array of 10000 channels by an integrated silicon chip electrode cluster.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on the drawings without creative efforts.
FIG. 1 is a schematic diagram of an ultra-high flux high spatial-temporal resolution in vivo neuron activity detection system according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of an overall structure of an ultra-high-throughput high-spatial-temporal-resolution in-vivo neuron activity detection system according to an embodiment of the present invention;
FIG. 3 is a flowchart of the operation of an ultra-high flux high spatial-temporal resolution in vivo neuron activity detection system according to an embodiment of the present invention;
FIG. 4 is a schematic diagram of a silicon-based surface electrode array neuroprobe provided by an embodiment of the present invention;
FIG. 5 is a schematic diagram of an electrode interface provided in an embodiment of the invention;
fig. 6 is an overall block diagram of a signal acquisition module and a signal processing module according to an embodiment of the present invention;
fig. 7 is an overall block diagram of a data storage transmission module according to an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the present invention without making any creative effort, shall fall within the protection scope of the present invention.
The embodiment of the invention provides an ultra-high flux high space-time resolution living body neuron activity detection system, as shown in figure 1, which mainly comprises: the device comprises a nerve probe array, a control and display system, a signal acquisition module, a signal processing module and a data storage and transmission module; the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module are sequentially connected, and the control and display system is respectively connected with the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module; wherein:
the nerve probe array is used as a collecting tool of nerve signals;
the signal acquisition module is used for acquiring and reading the neural signals acquired by the neural probe array;
the signal processing module is used for sequentially amplifying, filtering and carrying out analog-to-digital conversion on the neural signals read out by the signal acquisition module;
the data storage and transmission module is used for transmitting and storing the neural signal data processed by the signal processing module;
and the control and display system is used for controlling the work of the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module and displaying the related work process.
The structure of the system is shown in fig. 2, which is a nerve probe array 1, a cover plate 2, a probe adapter 3, a signal acquisition and processing module 4 (including the aforementioned signal acquisition module and signal processing module), a circuit interface 5, a data storage module 6, and a housing 7. The nerve probe array 1 is connected with a connector (the connector comprises a cover plate 2 and a probe adapter interface 3) through a flip-chip welding process or a connector assembly mode. One side of the connector is provided with silicon probes arranged in an array, the spacing of the probes can be designed according to the customization of the distribution of brain areas, and the other side of the connector is provided with 100-by-100 electrode pads. And indium balls are placed on electrode pads of the connector by using a flip chip bonding technology and are connected with the ROIC on the signal acquisition and processing module 4, and finally, the indium balls are connected with the data storage module by using a circuit interface 5.
The working flow of the system provided by the invention is shown in figure 3. The solid line is the data flow and the dashed line is the control flow. The whole system is divided into five blocks according to the flow of data, 1 is a nerve probe array, the number of channels reaches 10000, firstly, the nerve probe is inserted into a designated animal brain area, and at the moment, the control end of the system confirms the conduction rate of electrode connection in a software mode and marks the conduction rate. The 2 is an electrode interface to realize the connection and detection of the electrode and a reading circuit, the neuron signals detected by the 1 are transmitted to a reading circuit (ROIC) of a CMOS through a silicon probe and a connector, then reach a signal acquisition and processing module 3, are amplified, filtered and subjected to analog-to-digital conversion by the part and then are transmitted to a module 4 to be converted into a corresponding data format, and the 4 is a data interface which comprises an FPGA and a Camera Link and is used for converting a digital signal communication protocol and further leading the digital signal communication protocol into a data storage and transmission module 5 to perform high-speed transmission and storage of data. All the above 5 modules are monitored and displayed in real time by the control and display system.
For ease of understanding, the various components of the system are described in further detail below.
1. An array of nerve probes.
The nerve probe array is a three-dimensional nerve probe array with the total channel quantity of 10000, which is formed by vertically assembling a plurality of probes on a connector through a reverse welding process or a connector assembly according to a certain arrangement sequence, and can be manufactured into an ultrahigh-channel, expandable and multi-layer 3D high-precision nerve probe array by adopting a traditional planar silicon probe process, wherein the number of channels of a single probe is 500-1000; one side of the connector is the socket or pad for the probe and the other side is a 100 x 100 array of pads. The indium balls may be placed on the electrodes of the connector and connected to the ROIC on the signal acquisition module using flip chip technology.
As shown in fig. 4, the surface electrode array nerve probe can be manufactured by a micro-nano processing technology, wherein the substrate is made of silicon, and a layer of 0.1-1 micron silicon oxide or silicon nitride film is grown by low-pressure chemical vapor deposition to serve as an electrode substrate isolation layer; the electrodes and the internal connecting wires adopt Au/Ti or Pt/Ti, and pattern exposure is carried out by using electron beam lithography or electron beam lithography-ultraviolet lithography mixed technology; then, a single-layer or composite film of silicon oxide and silicon nitride is grown by using a plasma chemical vapor deposition or low-pressure chemical vapor deposition technology to serve as a passivation layer, the electrodes are exposed by adopting reactive ion etching or ion beam etching, and finally, the formation of the nerve probe outline is completed by adopting a wet etching technology.
Fig. 5 is a schematic diagram of an electrode interface. Fig. 5(a) is an overall view of an electrode interface, and fig. 5(b) is a front view of a plurality of probe slots for integrally arranging nerve probes to assemble a three-dimensional probe array; fig. 5(c) is a back view of an array of 10000 pads connected to a readout circuit interface in a signal acquisition module.
2. Signal acquisition module and signal processing module
The CMOS circuit chip infrared focal plane array is used as a signal acquisition module and is connected with a connector of the nerve probe array in a reverse welding mode. In the embodiment of the invention, a novel design idea of a multichannel neural signal acquisition circuit based on a CMOS infrared focal plane array reading circuit is adopted, 10000 signals detected by probes are connected to a pixel array of the CMOS infrared focal plane array, one or more pixel points are an acquisition channel, and thus, ten thousand neural signal acquisition circuits can be integrated through a modified CMOS infrared focal plane array. The reading circuit of the infrared focal plane is connected with the next stage signal preprocessing circuit, and the reading circuit is used for reading and transmitting signals to the next stage circuit.
In the signal processing module, the amplification processing of the neural signals is realized through a differential amplifier, noise signals in the neural signals are filtered through a filter, the denoised signals are converted into digital signals through an analog-to-digital converter, the sampling frequency of the analog-to-digital converter is greater than 20kHz, the resolution is 12bits, and the high-fidelity sampling quantification of the neural signals is realized.
In the embodiment of the present invention, the signal acquisition module and the signal processing module may be integrated together, as shown in fig. 6, which is a general frame schematic diagram of the signal acquisition module and the signal processing module, and mainly includes a voltage reference, a timing generation circuit, an analog signal processing circuit, an a/D conversion circuit, a row selection circuit, a column selection circuit, and a sensor readout circuit array (ROIC). The amplifying circuit can adopt a pixel level operational amplifier or an array level operational amplifier, and the A/D converting circuit can use an on-chip ADC or an array level ADC.
3. Data storage transmission module
The data storage and transmission module adopts a Camera Link protocol, the storage capacity is TB magnitude, the transmission rate is Gb/s magnitude, the time resolution is 1ms, and data which is output by the signal processing module and is converted into a specific format through the FPGA is transmitted and stored. For example, the storage capacity can be 4-10TB, the data transmission rate can be 3.6Gb/s, the time resolution can be 1ms, and the communication distance can be 50 m.
Fig. 7 shows a general framework diagram of the data storage and transmission module, which may be divided into two layers according to hardware functions, namely a link layer and a master layer. The link layer comprises a data transmission link and a control link, the data transmission link comprises an FPGA (field programmable gate array), a CameraLink cable and a high-speed image acquisition card supporting the CameraLink, and the data transmission link is responsible for transmitting data to the main control layer safely at a high speed; the control link consists of an RAM, an Ethernet and a host or a server which are integrated in the FPGA and is responsible for configuring and controlling a register of the acquisition layer, monitoring the working state of the system and the like. The main control layer is built in a small server containing RAID (redundant array of independent disks), is provided with a plurality of PCIe (peripheral component interface express) card slots, can support an image acquisition card and a GPU (graphics processing unit) card, and is responsible for storing data, displaying images in real time and controlling/monitoring the whole system.
Specific examples of the various parts of the system described above are given below.
In the present example, it is shown that,
a nerve probe array: the high flux silicon probe array with the total channel number reaching 10000 is used for being inserted into different brain areas to detect neuron signals, the traditional plane silicon probe process is adopted, electron beam lithography and ultraviolet lithography are adopted to manufacture electrodes and internal connecting wires, the electrode size is 20um to 30um, the bonding pad is 50um to 100um, the connecting wire width is 800nm to 1um, sputtering coating is adopted to deposit metal, PECVD or LPCVD is adopted to manufacture silicon oxide and silicon nitride films, reactive ion etching is adopted to etch the silicon oxide and silicon nitride films, and bulk silicon etching technology is adopted to etch redundant silicon substrates, so that the ultrahigh channel, expandable and multilevel 3D high-precision nerve probe array is manufactured. The number of single probe channels is 1000. The 10 silicon probe arrays are connected with the connector by a flip-chip bonding process or a connector assembly. One side of the connector is provided with silicon probes arranged according to a certain mode, the spacing of the probes can be designed according to the distribution customization of the brain area, and the other side of the connector is provided with 100-by-100 electrode pads. Indium balls are placed on the electrodes of the connector and connected to the ROIC on the CMOS circuit chip using flip chip technology.
Or, the high flux silicon probe array with the total channel number reaching 10000 is used for inserting into different brain areas for neuron signal detection, the traditional plane silicon probe process is adopted, the electron beam lithography and the ultraviolet lithography are adopted for manufacturing electrodes and internal connecting wires, the electrode size is 20um to 30um, the bonding pad is 50um to 100um, the connecting wire width is 800nm to 1um, the sputtering coating is adopted for metal deposition, the PECVD or LPCVD is adopted for manufacturing silicon oxide and silicon nitride films, the reactive ion etching is adopted for etching the silicon oxide and silicon nitride films, the bulk silicon etching technology is adopted for etching redundant silicon substrates, and the ultrahigh channel, expandable and multilevel 3D high-precision nerve probe array is manufactured. The number of single probe channels is 500. The 20 silicon probe arrays are connected with the connector by means of a flip-chip bonding process or a connector assembly. One side of the connector is provided with silicon probes arranged according to a certain mode, the spacing of the probes can be designed according to the distribution customization of the brain area, and the other side of the connector is provided with 100-by-100 electrode pads. Indium balls are placed on the electrodes of the connector and connected to the ROIC on the CMOS circuit chip using flip chip technology.
The signal acquisition module: the novel design idea of the multichannel neural signal acquisition circuit based on the CMOS infrared focal plane array reading circuit is adopted, 10000 signals detected by the probe are connected to a pixel array of the CMOS infrared focal plane array, one or more pixel points are acquisition channels, and therefore tens of thousands of neural signal acquisition circuits can be integrated through a modified CMOS infrared focal plane array. The reading circuit of the infrared focal plane is connected with the next stage signal preprocessing circuit, and the reading circuit is used for reading and transmitting signals to the next stage circuit.
The signal processing module: the high-efficiency analog filter circuit is adopted to realize the enhancement processing of weak electroencephalogram signals, high-precision digital-to-analog conversion is carried out on the electroencephalogram signals with ultrahigh density, high-fidelity sampling quantification of neuron electrical signals is realized, the sampling frequency is 20kHZ, and the sampling precision is 12 bits.
The data storage and transmission module: and a special transmission, storage and processing module is designed to realize real-time multi-channel high-speed acquisition, transmission and management of mass data generated by high-resolution imaging, and provide low-delay data reading capability to greatly improve the data reconstruction speed. The system can utilize protocols such as CameraLink and the like to realize the rapid storage of the high-flux neuron data converted by the CMOS circuit. The data volume is 4-10TB, the data transmission rate is 3.6Gb/s, the time resolution is 1ms, and the communication distance is 50 m.
The invention provides an ultra-high flux high space-time resolution live body neuron activity detection system, which mainly has the following characteristics:
1. the electrode array with 1 ten thousand channels is realized by the integrated silicon chip electrode cluster, the number of the channels is large, and the neural signals of different brain areas can be collected in an omnibearing and multilevel manner. The manufactured electrode interface has strong expansibility, and can be applied to the neural signal acquisition of different animals by slightly modifying the design.
2. The electrode interface is connected with the infrared focal plane array through the reading circuit interface, so that the connection between brain and the machine is easily realized, and the trouble of connecting the traditional implanted nerve signal acquisition probe with an external instrument is overcome.
3. The system realizes the acquisition and transmission of the neural signals by combining the CMOS image sensor infrared focal plane array and the reading circuit, breaks through the limitation on the number of the neural signal channels, and realizes the acquisition of the neural signals with ultra-high flux.
4. The high-efficiency analog amplification filter circuit adopted by the signal acquisition and processing module of the system realizes the enhancement processing of weak electroencephalogram signals. The high-precision analog-to-digital converter realizes high-fidelity sampling quantification of the neuron electric signals.
5. The system adopts protocols such as Camera Link and the like, and realizes the rapid transmission and storage of the ultra-large amount of neural signal data. In conclusion, the system for detecting the activity of the living body neurons with the ultrahigh flux and the high space-time resolution mainly realizes the omnibearing and multi-level acquisition, the quick processing, the quick transmission and the quick storage of a large number of neural signals.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (4)
1. An ultra-high-throughput high-spatial-temporal-resolution in vivo neuron activity detection system, comprising: the device comprises a nerve probe array, a control and display system, a signal acquisition module, a signal processing module and a data storage and transmission module; the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module are sequentially connected, and the control and display system is respectively connected with the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module; wherein:
the nerve probe array is used as a collecting tool of nerve signals;
the signal acquisition module is used for acquiring and reading the neural signals acquired by the neural probe array;
the signal processing module is used for sequentially amplifying, filtering and carrying out analog-to-digital conversion on the neural signals read out by the signal acquisition module;
the data storage and transmission module is used for transmitting and storing the neural signal data processed by the signal processing module;
the control and display system is used for controlling the work of the nerve probe array, the signal acquisition module, the signal processing module and the data storage and transmission module and displaying the related work process;
the nerve probe array is a three-dimensional nerve probe array with the total channel quantity of 10000, wherein a plurality of probes are vertically assembled on a connector through a reverse welding process or a connector assembly according to a certain arrangement sequence, and the number of channels of a single probe is 500-1000; one side of the connector is a slot or a bonding pad of a probe, and the other side is a 100 multiplied by 100 bonding pad array;
the infrared focal plane array of the CMOS circuit chip is used as a signal acquisition module, the infrared focal plane array of the CMOS circuit chip is connected with a connector of the nerve probe array in a reverse welding mode, and a read-out circuit ROIC of the signal acquisition module is connected with a signal processing module through a specific circuit interface.
2. The system for detecting the activity of the living body neurons with the ultrahigh flux and the high space-time resolution according to claim 1 is characterized in that a micro-nano processing technology is adopted to manufacture a surface electrode array nerve probe, wherein a substrate adopts silicon, and a layer of 0.1-1 micron silicon oxide or silicon nitride film is grown by low-pressure chemical vapor deposition to serve as an electrode substrate isolation layer; the electrodes and the internal connecting wires adopt Au and Ti or Pt and Ti, and pattern exposure is carried out by using electron beam lithography or electron beam lithography-ultraviolet lithography mixed technology; then growing a silicon oxide single layer, a silicon nitride single layer or a silicon oxide and silicon nitride composite film as a passivation layer by using a plasma chemical vapor deposition or low-pressure chemical vapor deposition technology, exposing the electrode by adopting reactive ion etching or ion beam etching, and finally finishing the formation of the nerve probe outline by adopting a wet etching technology.
3. The system for detecting the activity of the living body neurons with the ultra-high flux and the high space-time resolution as claimed in claim 1, wherein in the signal processing module, the amplification processing of the neural signals is realized through a differential amplifier, the noise signals in the neural signals are filtered through a filter, the denoised signals are converted into digital signals through an analog-to-digital converter, the sampling frequency of the analog-to-digital converter is greater than 20kHz, the resolution is 12bits, and the high-fidelity sampling quantification of the neural signals is realized.
4. The system for detecting the activity of the living body neurons with the ultra-high throughput and the high spatial-temporal resolution as claimed in claim 1, wherein the data storage and transmission module adopts a Camera Link protocol, the storage capacity is TB magnitude, the transmission rate is Gb/s magnitude, the time resolution is 1ms, and the data which is output by the signal processing module and is converted into a specific format by the FPGA is transmitted and stored.
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