CN115886827A - Neural microelectrode with temperature regulation and temperature measurement functions and preparation method thereof - Google Patents

Abstract

The disclosure provides a neural microelectrode with the functions of temperature regulation and temperature measurement, which can be applied in the technical field of microelectromechanical system biosensors. The neural microelectrode includes: a substrate, including a detection area; a microfluidic channel, which is arranged inside the substrate and has an overlapping portion with the detection area, and the microfluidic channel is used to transmit liquid; a microelectrode array, which is arranged on the substrate and has an overlap with the detection area In the part, the microelectrode array is used to measure the electrical signal of the detection area; the temperature measurement element is arranged on the substrate and has an overlapping part with the detection area, and the temperature measurement element is used to measure the temperature of the detection area; the insulating layer is arranged on the microelectrode array and On the temperature measuring element, the microelectrode array and the temperature measuring element are covered. The disclosure integrates the functions of temperature regulation and temperature measurement with the microelectrode, realizes the recording of neuron electrical signals while controlling the temperature of neurons, and realizes the real-time measurement of the temperature of neurons.

Description

Neural microelectrode with temperature regulation and temperature measurement functions and preparation method thereof

technical field

The disclosure relates to the technical field of MEMS biosensors, in particular to a neural microelectrode with temperature regulation and temperature measurement functions and a preparation method thereof.

Background technique

Neuronal electrical signals are the most fundamental information transmission and processing method of brain activity. By recording neuron electrical signals, the real-time physiological state of the brain can be understood. Neuronal microelectrodes can record the action potentials of brain regions, and conduct long-term, multi- Object detection is a major tool for studying neuronal activity.

Understanding the causality of neuronal networks and the relationship between patterns of neuronal activity, brain function, and behavior is important for elucidating the inner workings of the brain. Gain- and loss-of-function neural circuits can be studied by using electrical, optogenetic, and/or pharmacological stimulation with simultaneous electrophysiological recordings, which has driven the development of multifunctional neural probes. Specifically, stimulating electrodes, light-emitting diodes (LEDs), and optical fibers can be integrated into existing neural recording probe architectures. For example, the publication number CN114520070A provides a nerve electrical stimulation electrode and its preparation method, through electrical stimulation and synchronously recording the corresponding neuron activity to analyze the brain cognition causality; The photoelectrode for stimulation and electrophysiological recording and its preparation method integrates LED in the monolithic electrode, and adds a metal shielding layer to reduce the influence of LED power supply line on the recording signal, and uses optogenetics technology to achieve precise regulation of specific target neurons , to study neural circuits and systems.

Since temperature is also an important factor in neuronal function and synaptic integration, each neuron has many different kinds of ion channels. Among them, each neuron has a different temperature dependence on conductance, activation, and inactivation, and small temperature changes can also disturb the balance of biological parameters, such as ion channel dynamics, maximum conductance, and Ca2 ⁺ buffer. However, there is a lack of neural microelectrodes that can achieve temperature control in the current related art.

Contents of the invention

In view of the above problems, the present disclosure provides a neural microelectrode with temperature regulation and temperature measurement functions and a preparation method.

According to a first aspect of the present disclosure, a neural microelectrode with temperature regulation and temperature measurement functions is provided, including:

the substrate, including the detection area;

The microfluidic channel is arranged inside the substrate and has an overlapping portion with the detection area, and the microfluidic channel is used to transmit various temperature liquids to control the temperature of the detection area;

The microelectrode array is arranged on the substrate and has an overlapping portion with the detection area, and the microelectrode array is used to measure the electrical signal of the detection area;

A temperature measuring element is arranged on the substrate and has an overlapping portion with the detection area, and the temperature measurement element is used to measure the temperature of the detection area;

The insulating layer is arranged on the microelectrode array and the temperature measuring element, and covers the microelectrode array and the temperature measuring element.

According to an embodiment of the present disclosure, wherein the substrate further includes a non-detection area, the liquid inlet and the liquid outlet of the microfluidic channel are arranged in the non-detection area, the liquid inlet is used for circulating the input liquid, and the liquid outlet is used for circulating the output liquid .

According to an embodiment of the present disclosure, the neural microelectrode also includes:

a substrate disposed on the base and not in contact with the microfluidic channel;

The microelectrode array and the temperature measuring element are arranged between the substrate and the insulating layer, and the microelectrode array and the temperature measuring element are arranged on the same layer on the substrate.

According to an embodiment of the present disclosure, wherein the temperature measuring element is disposed outside the microelectrode array, and the outside of the microelectrode array is separated from the inside of the temperature measuring element by a predetermined distance.

According to an embodiment of the present disclosure, the temperature measuring element includes a temperature measuring resistor for measuring the temperature at the end of the detection area.

According to an embodiment of the present disclosure, the material of the temperature measuring resistor includes a metal whose resistivity changes stably with temperature.

According to an embodiment of the present disclosure, the temperature of the liquid ranges from 0°C to 60°C.

According to an embodiment of the present disclosure, the neural microelectrode according to claim 1, wherein probes are arranged in the detection area, and the base material of the probes is silicon.

The second aspect of the present disclosure provides a method for preparing a neural microelectrode with temperature regulation and temperature measurement functions, including:

After thermally oxidizing the substrate, etching a trench with a preset size;

Etching a microfluidic channel at the bottom of the groove to obtain a substrate including a microfluidic channel, the width of the microfluidic channel is greater than the width of the groove;

Using low-pressure chemical vapor deposition, depositing polysilicon with a predetermined thickness on the substrate including the microfluidic channel to obtain a substrate for sealing the microfluidic channel, the polysilicon is located above the microfluidic channel;

growing substrates on substrates that seal microfluidic channels;

Depositing the microelectrode array on the substrate to obtain a substrate comprising the microelectrode array;

Depositing a temperature measuring element on a substrate;

Deposit an insulating layer on the temperature measuring element and the microelectrode array to obtain the neural microelectrode to be etched;

Etching the nerve microelectrode to be etched from the direction of the insulating layer to obtain the front structure of the nerve microelectrode to be etched;

The nerve microelectrode to be etched is etched from the direction of the substrate to obtain the back structure of the nerve microelectrode to be etched.

The third aspect of the present disclosure provides a method for preparing a neural microelectrode with temperature regulation and temperature measurement functions, including:

Etching a groove with a preset size on the substrate by using photoresist;

Etching a microfluidic channel at the bottom of the trench to obtain a substrate including the microfluidic channel;

A second substrate made of the same material as the substrate is wafer bonded to the substrate including the microfluidic channel from the direction of the microfluidic channel, and the second substrate is thinned using a chemical mechanical polishing process to obtain a sealed microfluidic channel. base;

growing substrates on substrates that seal microfluidic channels;

Depositing the microelectrode array on the substrate to obtain a substrate comprising the microelectrode array;

Depositing a temperature measuring element on a substrate;

Deposit an insulating layer on the temperature measuring element and the microelectrode array to obtain the neural microelectrode to be etched;

Etching the nerve microelectrode to be etched from the direction of the insulating layer to obtain the front structure of the nerve microelectrode to be etched;

The nerve microelectrode to be etched is etched from the direction of the substrate to obtain the back structure of the nerve microelectrode to be etched.

The present disclosure provides a neural microelectrode with the functions of temperature regulation and temperature measurement. By feeding different temperature liquids into the microfluidic channel, the temperature of the needle tip part of the microelectrode can be changed. Simultaneously with the signal recording, the temperature of the neurons in the probe area is changed and measured to study the influence of temperature on the nervous system. The neural microelectrode provided by the present disclosure can study the influence of temperature on the nervous system with only one device of the neural microelectrode, which helps to simplify the process of studying the influence of temperature on the nervous system and excludes the influence of other factors on the nervous system.

Description of drawings

Through the following description of the embodiments of the present disclosure with reference to the accompanying drawings, the above content and other objects, features and advantages of the present disclosure will be more clear. In the accompanying drawings: Fig. 1 schematically shows a neural microelectrode according to an embodiment of the present disclosure Explosion schematic diagram;

Fig. 2 schematically shows a schematic structural diagram of a neural microelectrode according to an embodiment of the present disclosure;

Fig. 3 schematically shows a schematic structural view of a substrate according to an embodiment of the present disclosure;

Fig. 4 schematically shows the A-B sectional view of the neural microelectrode in Fig. 3;

Fig. 5 schematically shows a schematic diagram of a temperature measuring element according to an embodiment of the present disclosure;

Fig. 6A schematically shows a schematic diagram of a substrate in a preparation method according to the present disclosure;

FIG. 6B schematically shows a schematic diagram after etching a trench on a substrate according to the preparation method of the present disclosure;

Fig. 6C schematically shows a schematic diagram after etching a microfluidic channel on a substrate according to the preparation method of the present disclosure;

Figure 6D schematically shows a schematic diagram after sealing the microfluidic channel in the preparation method according to the present disclosure;

FIG. 6E schematically shows a schematic diagram after depositing a substrate in the preparation method according to the present disclosure;

Fig. 6F schematically shows a schematic diagram after growing a microelectrode array according to the preparation method of the present disclosure;

FIG. 6G schematically shows a schematic diagram after growing a temperature measuring element in the preparation method according to the present disclosure;

FIG. 6H schematically shows a schematic diagram after growing an insulating layer in the preparation method according to the present disclosure;

Fig. 6I schematically shows a schematic diagram after etching the front structure of a neural microelectrode according to the preparation method of the present disclosure;

FIG. 6J schematically shows a schematic diagram after etching the back structure of a neural microelectrode according to the preparation method of the present disclosure.

Fig. 7A schematically shows a schematic diagram of a substrate in a preparation method according to the present disclosure;

Fig. 7B schematically shows a schematic diagram after etching a microfluidic channel on a substrate according to the preparation method of the present disclosure;

Figure 7C schematically shows a schematic diagram after sealing the microfluidic channel in the preparation method according to the present disclosure;

Fig. 7D schematically shows a schematic diagram after depositing a substrate in the preparation method according to the present disclosure;

Fig. 7E schematically shows a schematic diagram after growing a microelectrode array in the preparation method according to the present disclosure;

FIG. 7F schematically shows a schematic diagram after growing a temperature measuring element in the preparation method according to the present disclosure;

FIG. 7G schematically shows a schematic diagram after growing an insulating layer in the preparation method according to the present disclosure;

FIG. 7H schematically shows a schematic diagram after etching the front structure of the neural microelectrode in the preparation method according to the present disclosure;

FIG. 7I schematically shows a schematic diagram after etching the back structure of a neural microelectrode according to the preparation method of the present disclosure.

Detailed ways

Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. It should be understood, however, that these descriptions are exemplary only, and are not intended to limit the scope of the present disclosure. In the following detailed description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the present disclosure. It may be evident, however, that one or more embodiments may be practiced without these specific details. Also, in the following description, descriptions of well-known structures and techniques are omitted to avoid unnecessarily obscuring the concept of the present disclosure.

The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting of the present disclosure. The terms "comprising", "comprising", etc. used herein indicate the presence of stated features, steps, operations and/or components, but do not exclude the presence or addition of one or more other features, steps, operations or components.

All terms (including technical and scientific terms) used herein have the meaning commonly understood by one of ordinary skill in the art, unless otherwise defined. It should be noted that the terms used herein should be interpreted to have a meaning consistent with the context of this specification, and not be interpreted in an idealized or overly rigid manner.

Where expressions such as "at least one of A, B, and C, etc." are used, they should generally be interpreted as those skilled in the art would normally understand the expression (for example, "having A, B, and C A system of at least one of "shall include, but not be limited to, systems with A alone, B alone, C alone, A and B, A and C, B and C, and/or A, B, C, etc. ).

FIG. 1 schematically shows an exploded view of a neural microelectrode according to an embodiment of the present disclosure.

According to an embodiment of the present disclosure, as shown in FIG. 1 , a neural microelectrode with temperature regulation and temperature measurement functions includes: a substrate 1 , a microelectrode array 3 , a temperature measurement element 4 and an insulating layer 5 . Wherein, a microfluidic channel 11 is arranged inside the substrate 1 .

According to an embodiment of the present disclosure, the analytes include neurons.

According to an embodiment of the present disclosure, the substrate 1 includes a detection area and a non-detection area. As shown in FIG. 1 , the cone-shaped area in front of the substrate 1 is the detection area, and the electrical signal generated by the neuron according to the temperature change is measured by contacting with the neuron. Other areas on the substrate 1 are non-detection areas.

The micro-electrode array 3 is disposed on the base 1, and the micro-electrode array 3 and the base 1 have overlapping portions, and is used for measuring electrical signals of the object to be tested.

The microfluidic channel 11 is arranged inside the substrate 1 and overlaps with the detection area, and the microfluidic channel is used for transporting liquid.

According to an embodiment of the present disclosure, as shown in FIG. 1 , the microfluidic channel 11 flows through the detection area for controlling the temperature of the detection area through the transported liquid.

The temperature measuring element 4 is arranged on the substrate 1 and overlaps with the detection area. The temperature measuring element 4 can measure the temperature of the detection area by the configuration of the overlapping portion with the detection area.

The material of the temperature measuring element 4 includes materials sensitive to temperature changes. The temperature measuring element 4 includes a resistance, for example, the resistance value of the temperature measuring element 4 increases as the temperature rises, so as to measure the temperature of the detection area.

The insulating layer 5 is arranged on the microelectrode array 3 and the temperature measuring element 4 , covering the microelectrode array 3 and the temperature measuring element 4 .

Fig. 2 schematically shows a structural diagram of a neural microelectrode according to an embodiment of the present disclosure.

According to an embodiment of the present disclosure, the substrate includes a detection area and a non-detection area. As shown in FIG. 2 , the needle tip area below the neural microelectrode is the detection area, and the needle handle area above is the non-detection area.

The liquid inlet 12 and the liquid outlet 13 of the microfluidic channel are arranged in the non-detection area, the liquid inlet 12 is used for circulating the input liquid, and the liquid outlet is used for circulating the output liquid.

As shown in FIG. 2 , the microfluidic channel flows through the tip region of the substrate 1 .

According to an embodiment of the present disclosure, the temperature range of the liquid transported by the microfluidic channel is 0° C. to 60° C., and the temperature of the tested brain region can be changed while ensuring that neurons in the brain region are not damaged. Specifically, during the process of temperature regulation, the temperature of the input liquid can be changed according to actual needs. For example, a liquid whose temperature is higher than that of the brain region is injected into the microfluidic channel through the liquid inlet to realize heating stimulation; a liquid whose temperature is lower than that of the brain region is injected into the microfluidic channel through the liquid inlet to realize cooling stimulation.

According to an embodiment of the present disclosure, the liquid transported by the microfluidic channel may be water. For example, water at 2°C is circulated through microfluidic channels to complete electrical signal recordings from living neurons while lowering the temperature of the tested brain region.

According to an embodiment of the present disclosure, the neural microelectrode further includes: a substrate 2 disposed on the substrate 1 and not in contact with the microfluidic channel 11 .

The microelectrode array 3 and the temperature measuring element 4 are arranged between the substrate 2 and the insulating layer 5 , and the microelectrode array 3 and the temperature measuring element 4 are arranged on the same layer on the substrate 2 .

According to an embodiment of the present disclosure, the microfluidic channel 11 is hermetically disposed inside the substrate 1 and not in contact with the substrate 2 . The electrode array 3 and the temperature measuring element 4 are arranged on the upper surface of the substrate 2 . Wherein, the electrode array 3 or the temperature measuring element 4 can be arranged directly above the microfluidic channel 11, or can be arranged outside the microfluidic channel 11, respectively for measuring the electrical signal of neurons and the temperature of the detection area.

According to an embodiment of the present disclosure, the microelectrode array 3 and the temperature measuring element 4 are disposed on the same layer on the upper surface of the substrate 2 . Wherein, the microelectrode array 3 and the temperature measuring element 4 are not in contact with each other. Various positional relationships can exist between the microelectrode array 3 and the temperature measuring element 4, for example, the temperature measuring element 4 is arranged on the outside of the microelectrode array 3, and the temperature measuring element 4 surrounds the microelectrode array 3; or the temperature measuring element 4 is arranged on The inner side of the microelectrode array 3 ; or the temperature measuring element 4 is located on the left or right side of the microelectrode array 3 .

As a specific embodiment, the temperature measuring element 4 is arranged on the outside of the microelectrode array 3 , and the outside of the microelectrode array 3 is separated from the inside of the temperature measuring element 4 by a preset distance. The preset distance can be 5-20 micrometers, so as to ensure that the outside of the microelectrode array 3 and the inside of the temperature measuring element 4 are not in contact with each other, and both can be arranged on the substrate 2 .

According to an embodiment of the present disclosure, the temperature measuring element 4 includes a resistor, and the resistor is arranged at the end of the detection area for measuring the temperature at the end of the detection area.

According to another embodiment of the present disclosure, the temperature measuring element 4 as a whole can be used as a thermal resistor for measuring the temperature at the end of the detection area.

According to the embodiment of the present disclosure, the resistance value of the resistor in the temperature measuring element 4 increases with the increase of temperature, so as to measure the temperature of the needle tip of the nerve microelectrode in real time.

According to an embodiment of the present disclosure, the resistor in the temperature measuring element 4 may be a metal conductor. For example, the metallic conductor may be metallic platinum, metallic copper, metallic nickel, and the like.

Fig. 3 schematically shows a schematic structural diagram of a substrate according to an embodiment of the present disclosure. Fig. 4 schematically shows the A-B sectional view of the neural microelectrode in Fig. 3 .

As shown in FIG. 3 , a microfluidic channel 11 is disposed inside the substrate 1 for transmitting fluids of different temperatures. As shown in FIG. 4 , the microfluidic channel 11 is not in contact with the outside world. Therefore, during the process of using the microfluidic channel 11 to transport the liquid, the temperature of the liquid will not change drastically, which can ensure that the temperature of the detection area is in a stable state.

In the related art, starting from the device for measuring electrical signals, temperature regulation and temperature measurement are combined on the nerve microelectrode for measuring electrical signals, so as to realize temperature regulation, temperature measurement and electrophysiological recording at the same time.

The present disclosure provides a neural microelectrode with the functions of temperature regulation and temperature measurement. By integrating microfluidic channels and temperature measurement elements on the neural microelectrode, it is possible to realize simultaneous temperature regulation, temperature measurement and temperature measurement starting from the measurement device. Electrophysiological recordings to study the effects of temperature on the nervous system. Moreover, the neural microelectrode provided by the present disclosure can study the influence of temperature on the nervous system with only one device of the neural microelectrode, which helps to simplify the process of studying the influence of temperature on the nervous system and excludes the influence of other factors on the nervous system.

In addition, for situations where the ambient temperature of the analyte cannot be changed, such as a living analyte, related techniques are usually unable to study the influence of temperature on neurons. On the contrary, the neural microelectrode provided by the present disclosure has the functions of temperature regulation and temperature measurement, which can simultaneously realize the temperature regulation, temperature measurement and electrical signal recording of the object to be tested.

Fig. 5 schematically shows a schematic diagram of a temperature measuring element according to an embodiment of the disclosure.

As shown in FIG. 5 , the temperature measuring element 4 as a whole serves as a measuring resistance. The temperature measuring element 4 is folded multiple times and distributed at the end of the detection area, that is, the end of the needle tip, increasing the resistance of the temperature measuring element 4 at the end of the needle tip, thereby increasing the sensitivity and accuracy of temperature measurement at the end of the needle tip, so as to control the liquid in the microfluidic channel in real time flow rate and temperature.

According to an embodiment of the present disclosure, probes are also disposed in the detection area, and the material of the probe base is silicon.

6A to 6J schematically show the process flow of preparing a neural microelectrode with temperature regulation and temperature measurement functions.

Fig. 6A schematically shows a schematic diagram of a substrate in a preparation method according to the present disclosure.

As shown in FIG. 6A , the substrate for preparing neural microelectrodes is a silicon substrate. Specifically, a double-polished silicon wafer with a thickness of 400 microns can be selected as the substrate 1 .

FIG. 6B schematically shows a schematic diagram after etching trenches on the substrate in the preparation method according to the present disclosure.

As shown in FIG. 6B , after the substrate 1 is thermally oxidized, a trench 14 with a predetermined size is etched. Among them, the groove 14 is used to determine the position and depth of the microfluidic channel 11 .

Specifically, 1000 nanometers of silicon oxide can be thermally oxidized on the substrate 1 . Then, the location of the patterned trench is masked on the thermally oxidized silicon oxide by reactive ion etching, and the deep silicon etching Bosch process is used to etch to obtain the trench 14 . Wherein, the groove 14 is 2 microns wide and 35 microns deep.

FIG. 6C schematically shows a schematic diagram after etching microfluidic channels on a substrate in the preparation method according to the present disclosure.

As shown in Figure 6C, after the groove 14 is etched on the substrate 1, the microfluidic channel is continuously etched on the bottom of the groove 14 to obtain a substrate comprising a microfluidic channel, and the width of the microfluidic channel 11 is greater than that of the groove 14 in width.

Specifically, 200 nanometers of silicon oxide is thermally oxidized on the surface of the trench 14 as a mask, and the silicon oxide layer at the bottom of the trench 14 is removed by reactive ion etching. The silicon substrate is etched using the principle of isotropic etching to obtain the microfluidic channel 11 . Wherein, the diameter of the microfluidic channel 11 may be 40 microns.

FIG. 6D schematically shows a schematic view after sealing the microfluidic channel in the preparation method according to the present disclosure.

As shown in FIG. 6D , by using low-pressure chemical vapor deposition, polysilicon with a predetermined thickness is deposited on the substrate 1 including the microfluidic channel 11 to obtain a substrate that seals the microfluidic channel. The deposited polysilicon is located over the microfluidic channels.

Specifically, buffered oxide etchant (BOE) can be used to remove all silicon oxide mask layers on the substrate 1, and then low-pressure chemical vapor deposition (LPCVD) is used to grow 1.5 micron polysilicon to fill the top of the trench 14, and the microfluidic The channels 11 are sealed, resulting in a silicon substrate with microfluidic channels 11 .

FIG. 6E schematically shows a schematic diagram after depositing a substrate in the manufacturing method according to the present disclosure.

As shown in FIG. 6E , a substrate 2 is grown on a substrate 1 sealing a microfluidic channel 11 . Specifically, a mixed film of 500 nm silicon oxide and 500 nm silicon nitride can be sequentially grown by plasma chemical vapor deposition as the substrate 2 .

FIG. 6F schematically shows a schematic view after growing a microelectrode array in the preparation method according to the present disclosure.

As shown in FIG. 6F , the microelectrode array 3 is patterned and deposited on the substrate 2 to obtain a substrate including the microelectrode array 3 . Specifically, magnetron sputtering coating (Sputtering) of 10 nanometers of chromium and 200 nanometers of gold can be used as the microelectrode array 3 .

Wherein, 31 is the lead window end of the microelectrode array, and 32 is the recording electrode end of the microelectrode array.

FIG. 6G schematically shows a schematic diagram after growing a temperature measuring element in the manufacturing method according to the present disclosure.

As shown in FIG. 6G , the temperature measuring element 4 is patterned and deposited on the substrate 2 . Specifically, 10 nanometers of chromium and 200 nanometers of platinum are sequentially deposited on the substrate 2 as the temperature measuring element 4 by using the magnetron sputtering method.

FIG. 6H schematically shows a schematic diagram after growing an insulating layer in the manufacturing method according to the present disclosure.

As shown in FIG. 6H , an insulating layer 5 is deposited on the blank area of the temperature measuring element 4 , the microelectrode array 3 and the substrate 2 to obtain a nerve microelectrode to be etched.

Specifically, silicon oxide with a thickness of 300 nanometers can be grown as the insulating material layer 5 by using a plasma chemical vapor deposition method.

FIG. 6I schematically shows a schematic diagram after etching the front structure of a neural microelectrode in the preparation method according to the present disclosure.

As shown in FIG. 6I , after the insulating layer 5 is deposited, the nerve microelectrode to be etched is etched from the direction of the insulating layer 5 to obtain the front structure of the nerve microelectrode to be etched.

Specifically, the lead wire 16 of the electrode and the test window formed by the two lead wires 16 are exposed by reactive ion etching of the 300 nm silicon oxide insulating material layer. Using reactive ions to sequentially etch 300nm silicon oxide, 500nm silicon nitride and 500nm silicon oxide, and then use deep silicon etching Bosch process to etch 10 micron silicon to obtain groove 15, forming the front structure of neural microelectrodes.

FIG. 6J schematically shows a schematic diagram after etching the back structure of a neural microelectrode according to the preparation method of the present disclosure.

According to an embodiment of the present disclosure, the nerve microelectrode to be etched is etched from the direction of the substrate 1 to obtain the back structure of the nerve microelectrode to be etched.

Specifically, as shown in FIG. 6J , 300 microns of silicon were etched from the direction of the base of the neural microelectrode using a deep silicon etching Bosch process. In the process of etching the substrate 1 from the back side, the needle tip portion 17 with a thickness of 100 micrometers remains to form the back structure of the neural microelectrodes.

7A to 7I schematically show another process flow for preparing a neural microelectrode with temperature regulation and temperature measurement functions.

Fig. 7A schematically shows a schematic diagram of a substrate in a preparation method according to the present disclosure.

As shown in FIG. 7A , the substrate for preparing neural microelectrodes is a silicon substrate. Specifically, a double-polished silicon wafer with a thickness of 400 microns can be selected as the substrate 1 .

Fig. 7B schematically shows a schematic diagram after etching microfluidic channels on a substrate in the preparation method according to the present disclosure.

As shown in FIG. 7B , the photoresist of AZ4620 is specifically selected as a mask, and the morphology of the microfluidic channel 11 is etched by Bosch process. Wherein, the microfluidic channel 11 is 50 microns wide and 50 microns deep.

FIG. 7C schematically shows a schematic diagram after sealing the microfluidic channel in the preparation method according to the present disclosure.

After the microfluidic channel 11 is etched on the substrate 1, a second substrate made of the same material as the substrate 1 is wafer bonded to the substrate 1 including the microfluidic channel 11 from the direction of the microfluidic channel 11, and chemical mechanical The polishing process thins the second substrate to obtain a substrate that seals the microfluidic channels.

Specifically, the second 400-micron thick double-thrown silicon wafer is selected for wafer bonding with the silicon wafer etched with the microfluidic channel 11, and the excess silicon on the second silicon wafer is removed using a chemical mechanical polishing (CMP) process. 20 μm thick silicon is reserved for sealing the microfluidic channels 11 .

FIG. 7D schematically shows a schematic diagram after depositing a substrate in the manufacturing method according to the present disclosure.

As shown in FIG. 7D , a substrate 2 is grown on a substrate 1 sealing a microfluidic channel 11 . Specifically, a mixed film of 500 nanometers of silicon oxide and 500 nanometers of silicon nitride can be sequentially grown by plasma chemical vapor deposition as the substrate 2 .

FIG. 7E schematically shows a schematic diagram after growing a microelectrode array in the preparation method according to the present disclosure.

As shown in FIG. 7E , the microelectrode array 3 is patterned and deposited on the substrate 2 to obtain a substrate including the microelectrode array 3 . Specifically, magnetron sputtering coating (Sputtering) of 10 nanometers of chromium and 200 nanometers of gold can be used as the microelectrode array 3 .

Wherein, 31 is the lead window end of the microelectrode array, and 32 is the recording electrode end of the microelectrode array.

FIG. 7F schematically shows a schematic diagram after growing a temperature measuring element in the preparation method according to the present disclosure.

As shown in FIG. 7F , the temperature measuring element 4 is patterned and deposited on the substrate 2 . Specifically, 10 nanometers of chromium and 200 nanometers of platinum are sequentially deposited on the substrate 2 as the temperature measuring element 4 by using the magnetron sputtering method.

FIG. 7G schematically shows a schematic diagram after growing an insulating layer in the preparation method according to the present disclosure.

As shown in FIG. 7G , an insulating layer 5 is deposited on the blank area of the temperature measuring element 4 , the microelectrode array 3 and the substrate 2 to obtain a nerve microelectrode to be etched.

Specifically, silicon oxide with a thickness of 300 nanometers can be grown as the insulating material layer 5 by using a plasma chemical vapor deposition method.

FIG. 7H schematically shows a schematic diagram after etching the front structure of a neural microelectrode in the preparation method according to the present disclosure.

As shown in FIG. 7H , after the insulating layer 5 is deposited, the nerve microelectrodes to be etched are etched from the direction of the insulating layer 5 to obtain the front structure of the nerve microelectrodes to be etched.

Specifically, the lead wire 16 of the electrode and the test window formed by the two lead wires 16 are exposed by reactive ion etching of the 300 nm silicon oxide insulating material layer. Using reactive ions to sequentially etch 300nm silicon oxide, 500nm silicon nitride and 500nm silicon oxide, and then use deep silicon etching Bosch process to etch 10 micron silicon to obtain groove 15, forming the front structure of neural microelectrodes.

FIG. 7I schematically shows a schematic diagram after etching the back structure of a neural microelectrode according to the preparation method of the present disclosure.

According to an embodiment of the present disclosure, the nerve microelectrode to be etched is etched from the direction of the substrate 1 to obtain the back structure of the nerve microelectrode to be etched.

Specifically, as shown in FIG. 7J , 300 microns of silicon were etched from the direction of the base of the neural microelectrode using a deep silicon etching Bosch process. In the process of etching the substrate 1 from the back side, the needle tip portion 17 with a thickness of 100 micrometers remains to form the back structure of the neural microelectrodes.

It should be noted that there are various positional relationships between the microelectrode array 3 and the temperature control element 4 in the present disclosure on the substrate 2 . The process flow charts in FIGS. 6A-6J and 7A-7I are only used as an example, reflecting the upper and lower hierarchical relationships in the neural microelectrodes.

The preparation method of a nerve microelectrode with temperature control and temperature measurement functions provided by the present disclosure can be completely compatible with the micro-electromechanical system (MEMS, Micro-Electro-Mechanical System) process, reducing the cost of preparing nerve microelectrodes with temperature control and temperature measurement functions. The cost of microelectrodes.

The present disclosure provides a neural microelectrode with the functions of temperature regulation and temperature measurement, which cools the brain region of the needle tip part of the microelectrode by passing low-temperature liquid into the microfluidic channel, and realizes the recording of neuron electrical signals at the same time. The temperature of the test area of the brain can be varied and measured to study the effects of temperature on the nervous system.

Those skilled in the art can understand that various combinations and/or combinations of the features described in the various embodiments and/or claims of the present disclosure can be made, even if such combinations or combinations are not explicitly recorded in the present disclosure. In particular, without departing from the spirit and teaching of the present disclosure, the various embodiments of the present disclosure and/or the features described in the claims can be combined and/or combined in various ways. All such combinations and/or combinations fall within the scope of the present disclosure.

The specific embodiments described above have further described the purpose, technical solutions and beneficial effects of the present disclosure in detail. It should be understood that the above descriptions are only specific embodiments of the present disclosure, and are not intended to limit the present disclosure. Within the spirit and principles of the present disclosure, any modifications, equivalent replacements, improvements, etc., shall be included in the protection scope of the present disclosure.

Claims (10)

1. A neural microelectrode with temperature regulation and temperature measurement functions, comprising: the substrate, including the detection area; A microfluidic channel is arranged inside the substrate and has an overlapping portion with the detection area, and the microfluidic channel is used to transmit liquids of various temperatures to regulate the temperature of the detection area; a microelectrode array, arranged on the substrate and having an overlapping portion with the detection area, the microelectrode array is used to measure the electrical signal of the detection area; a temperature measuring element, disposed on the substrate and having an overlapping portion with the detection area, the temperature measuring element is used to measure the temperature of the detection area; The insulating layer is arranged on the microelectrode array and the temperature measuring element, and covers the microelectrode array and the temperature measuring element. 2. The neural microelectrode according to claim 1, wherein the substrate also includes a non-detection area, the liquid inlet and the liquid outlet of the microfluidic channel are arranged in the non-detection area, and the liquid inlet It is used for circulating input liquid, and the liquid outlet is used for circulating output liquid. 3. The neural microelectrode according to claim 1, further comprising: a substrate disposed on the base and not in contact with the microfluidic channel; The microelectrode array and the temperature measuring element are arranged between the substrate and the insulating layer, and the microelectrode array and the temperature measuring element are arranged on the same layer on the substrate. 4. The nerve microelectrode according to claim 3, wherein the temperature measuring element is arranged on the outside of the microelectrode array, and the outside of the microelectrode array is spaced a preset distance from the inside of the temperature measuring element . 5. The neural microelectrode according to claim 1, the temperature measuring element comprises a temperature measuring resistor for measuring the temperature at the end of the detection area. 6. The neural microelectrode according to claim 5, wherein the material of the temperature measuring resistor comprises a metal whose resistivity changes stably with temperature. 7. The neural microelectrode according to claim 1, wherein the temperature of the liquid ranges from 0°C to 60°C. 8. The nerve microelectrode according to claim 1, wherein a probe is arranged in the detection area, and the base material of the probe is silicon. 9. A method for preparing a neural microelectrode with temperature regulation and temperature measurement functions, comprising: After thermally oxidizing the substrate, etching a trench with a preset size; Etching a microfluidic channel at the bottom of the groove to obtain a substrate comprising a microfluidic channel, the width of the microfluidic channel is greater than the width of the groove; Depositing polysilicon with a predetermined thickness on the substrate including the microfluidic channel by low-pressure chemical vapor deposition to obtain a substrate sealing the microfluidic channel, the polysilicon being located above the microfluidic channel; growing a substrate on said substrate sealing said microfluidic channel; Depositing a microelectrode array on the substrate to obtain a substrate comprising the microelectrode array; depositing a temperature measuring element on said substrate; Depositing an insulating layer on the temperature measuring element and the microelectrode array to obtain a neural microelectrode to be etched; Etching the nerve microelectrode to be etched from the direction of the insulating layer to obtain the front structure of the nerve microelectrode to be etched; Etching the nerve microelectrode to be etched from the direction of the substrate to obtain the back structure of the nerve microelectrode to be etched. 10. A method for preparing a neural microelectrode with temperature regulation and temperature measurement functions, comprising: Etching a groove with a preset size on the substrate by using photoresist; Etching a microfluidic channel at the bottom of the groove to obtain a substrate including a microfluidic channel; A second substrate made of the same material as the substrate is wafer-bonded to the substrate including the microfluidic channel from the direction of the microfluidic channel, and a chemical mechanical polishing process is used to reduce the thickness of the second substrate. thin, resulting in a substrate that seals the microfluidic channel; growing a substrate on said substrate sealing said microfluidic channel; Depositing a microelectrode array on the substrate to obtain a substrate comprising the microelectrode array; depositing a temperature measuring element on said substrate; Depositing an insulating layer on the temperature measuring element and the microelectrode array to obtain a neural microelectrode to be etched; Etching the nerve microelectrode to be etched from the direction of the insulating layer to obtain the front structure of the nerve microelectrode to be etched; Etching the nerve microelectrode to be etched from the direction of the substrate to obtain the back structure of the nerve microelectrode to be etched.

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