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

Abstract

This disclosure provides a neural microelectrode with temperature regulation and temperature measurement functions, which can be applied in the field of microelectromechanical systems (MEMS) biosensor technology. The neural microelectrode includes: a substrate including a detection region; a microfluidic channel disposed within the substrate and overlapping with the detection region, the microfluidic channel being used to transport liquid; a microelectrode array disposed on the substrate and overlapping with the detection region, the microelectrode array being used to measure the electrical signal of the detection region; a temperature measuring element disposed on the substrate and overlapping with the detection region, the temperature measuring element being used to measure the temperature of the detection region; and an insulating layer disposed on the microelectrode array and the temperature measuring element, covering the microelectrode array and the temperature measuring element. This disclosure integrates temperature regulation and temperature measurement functions into a single microelectrode, enabling simultaneous temperature control of neurons and recording of neuronal electrical signals, as well as real-time measurement of neuronal temperature.

Description

Technical Field

[0001] This disclosure relates to the field of microelectromechanical systems (MEMS) biosensor technology, specifically to a neural microelectrode with temperature regulation and temperature measurement functions and its preparation method. Background Technology

[0002] Neuronal electrical signals are the most fundamental way of information transmission and processing in brain activity. By recording neuronal electrical signals, we can understand the real-time physiological state of the brain. Neuromicroelectrodes can record action potentials in brain regions and perform long-term, multi-target detection of a large number of neurons, making them the main tool for studying neuronal activity.

[0003] Understanding the causal relationships within neural networks and the connections between neuronal activity patterns, brain function, and behavior is crucial for elucidating the brain's internal workings. The use of electro- and optogenetic, and / or pharmacological, stimulation, along with simultaneous electrophysiological recording, allows for the study of neural circuits that gain or lose function, driving 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, CN114520070A discloses a neural electrostimulation electrode and its fabrication method, which analyzes cognitive causal relationships through electrical stimulation and simultaneous recording of corresponding neuronal activity; CN111613700A discloses an optogenetic electrode for optogenetic stimulation and electrophysiological recording, and its fabrication method, which integrates an LED into a monolithic electrode and adds a metal shielding layer to reduce the influence of the LED power supply line on the recording signal, utilizing optogenetic technology to achieve precise control of specific target neurons and study neural circuits and systems.

[0004] Since temperature is a crucial factor influencing neuronal function and synaptic integration, each neuron possesses numerous different types of ion channels. Each neuron exhibits varying temperature dependencies on conductance, activation, and inactivation; even minute temperature changes can disrupt the balance of biological parameters, such as ion channel kinetics, maximum conductance, and Ca2+. 2+ Buffers, etc. However, current technologies lack neural microelectrodes that can achieve temperature control. Summary of the Invention

[0005] In view of the above problems, this disclosure provides a neural microelectrode with temperature regulation and temperature measurement functions and a method for its preparation.

[0006] According to a first aspect of this disclosure, a neural microelectrode with temperature regulation and temperature measurement functions is provided, comprising:

[0007] The substrate, including the detection area;

[0008] Microfluidic channels are located inside the substrate and overlap with the detection area. These channels are used to transport liquids of various temperatures to control the temperature of the detection area.

[0009] A microelectrode array, disposed on a substrate and overlapping with the detection area, is used to measure the electrical signal in the detection area.

[0010] A temperature measuring element is disposed on a substrate and overlaps with the detection area; the temperature measuring element is used to measure the temperature of the detection area.

[0011] An insulating layer is disposed on the microelectrode array and the temperature measuring element, covering the microelectrode array and the temperature measuring element.

[0012] According to an embodiment of this disclosure, the substrate further includes a non-detection area, and the inlet and outlet of the microfluidic channel are disposed in the non-detection area. The inlet is used for cyclic input of liquid, and the outlet is used for cyclic output of liquid.

[0013] According to embodiments of this disclosure, the neural microelectrode further includes:

[0014] The substrate is disposed on the base and does not contact the microfluidic channel;

[0015] The microelectrode array and temperature measuring element are disposed between the substrate and the insulating layer, and the microelectrode array and temperature measuring element are disposed on the same layer on the substrate.

[0016] According to an embodiment of this disclosure, the temperature measuring element is disposed on the outside of the microelectrode array, and the outside of the microelectrode array is spaced apart from the inside of the temperature measuring element by a predetermined distance.

[0017] According to embodiments of this disclosure, the temperature measuring element includes a temperature-sensing resistor for measuring the temperature at the end of the detection area.

[0018] According to embodiments of this disclosure, the material of the temperature-sensing resistor includes a metal whose resistivity changes stably with temperature.

[0019] According to embodiments of this disclosure, the temperature range of the liquid is 0°C to 60°C.

[0020] According to an embodiment of this disclosure, in the neural microelectrode of claim 1, a probe is disposed in the detection region, and the substrate material of the probe is silicon.

[0021] A second aspect of this disclosure provides a method for fabricating a neural microelectrode with temperature regulation and temperature measurement functions, comprising:

[0022] After thermal oxidation of the substrate, trenches of a predetermined size are etched out.

[0023] Microfluidic channels are etched at the bottom of the trench to obtain a substrate including the microfluidic channels, the width of which is greater than the width of the trench.

[0024] Using low-pressure chemical vapor deposition, polycrystalline silicon of a predetermined thickness is deposited on a substrate including microfluidic channels to obtain a substrate that seals the microfluidic channels, with the polycrystalline silicon located above the microfluidic channels.

[0025] A substrate is grown on a substrate with a sealed microfluidic channel;

[0026] A microelectrode array is deposited on a substrate to obtain a substrate including the microelectrode array;

[0027] Deposit temperature measuring elements on a substrate;

[0028] An insulating layer is deposited on a temperature measuring element and a microelectrode array to obtain a neural microelectrode to be etched;

[0029] The neural microelectrode to be etched is etched from the direction of the insulating layer to obtain the front structure of the neural microelectrode to be etched.

[0030] The neural microelectrode to be etched is etched from the direction of the substrate to obtain the back structure of the neural microelectrode to be etched.

[0031] A third aspect of this disclosure provides a method for fabricating a neural microelectrode with temperature regulation and temperature measurement functions, comprising:

[0032] Trenches of a predetermined size are etched on the substrate using photoresist;

[0033] Microfluidic channels are etched at the bottom of the trench to obtain a substrate including the microfluidic channels;

[0034] A second substrate of the same material as the substrate is wafer-bonded to the substrate containing the microfluidic channels from the direction of the microfluidic channels, and the second substrate is thinned by chemical mechanical polishing to obtain a substrate that seals the microfluidic channels.

[0035] A substrate is grown on a substrate with a sealed microfluidic channel;

[0036] A microelectrode array is deposited on a substrate to obtain a substrate including the microelectrode array;

[0037] Deposit temperature measuring elements on a substrate;

[0038] An insulating layer is deposited on a temperature measuring element and a microelectrode array to obtain a neural microelectrode to be etched;

[0039] The neural microelectrode to be etched is etched from the direction of the insulating layer to obtain the front structure of the neural microelectrode to be etched.

[0040] The neural microelectrode to be etched is etched from the direction of the substrate to obtain the back structure of the neural microelectrode to be etched.

[0041] This disclosure provides a neural microelectrode with temperature regulation and measurement functions. By introducing liquids of different temperatures into a microfluidic channel, the temperature of the microelectrode tip is altered. This allows for simultaneous recording of neuronal electrical signals and measurement of the neuronal temperature in the detection area, thereby studying the effects of temperature on the nervous system. The neural microelectrode provided in this disclosure requires only a single device to study the effects of temperature on the nervous system, simplifying the research process and eliminating the influence of other factors. Attached Figure Description

[0042] The foregoing contents, as well as other objects, features, and advantages of this disclosure, will become clearer from the following description of embodiments with reference to the accompanying drawings, in which: Figure 1 An explosion diagram of a neural microelectrode according to an embodiment of the present disclosure is shown schematically;

[0043] Figure 2 A schematic diagram of the structure of a neural microelectrode according to an embodiment of the present disclosure is shown.

[0044] Figure 3 A schematic diagram of the structure of a substrate according to an embodiment of the present disclosure is shown.

[0045] Figure 4 Schematic illustration Figure 3 AB cross-sectional view of the microelectrode of the central nervous system;

[0046] Figure 5 A schematic diagram of a temperature measuring element according to an embodiment of the present disclosure is shown;

[0047] Figure 6A A schematic diagram of a substrate in a preparation method according to the present disclosure is shown;

[0048] Figure 6B A schematic diagram is shown after etching trenches on a substrate according to the preparation method of this disclosure;

[0049] Figure 6C A schematic diagram illustrating the etching of microfluidic channels on a substrate according to the preparation method of this disclosure is shown.

[0050] Figure 6D A schematic diagram of the microfluidic channel after sealing according to the preparation method of this disclosure is shown.

[0051] Figure 6E A schematic diagram of the substrate deposition process according to the preparation method of this disclosure is shown.

[0052] Figure 6F A schematic diagram of the fabrication method according to this disclosure after growing a microelectrode array is shown.

[0053] Figure 6G A schematic diagram is shown after the growth temperature measuring element in the preparation method according to this disclosure;

[0054] Figure 6H A schematic diagram is shown after the growth of the insulating layer according to the preparation method of this disclosure;

[0055] Figure 6I A schematic diagram of the front structure of the neural microelectrode after etching according to the fabrication method of this disclosure is shown.

[0056] Figure 6J A schematic diagram of the back structure of a neural microelectrode after etching according to the fabrication method of this disclosure is shown.

[0057] Figure 7A A schematic diagram of a substrate in a preparation method according to the present disclosure is shown;

[0058] Figure 7B A schematic diagram illustrating the etching of microfluidic channels on a substrate according to the preparation method of this disclosure is shown.

[0059] Figure 7C A schematic diagram of the microfluidic channel after sealing according to the preparation method of this disclosure is shown.

[0060] Figure 7D A schematic diagram of the substrate deposition process according to the preparation method of this disclosure is shown.

[0061] Figure 7E A schematic diagram of the fabrication method according to this disclosure after growing a microelectrode array is shown.

[0062] Figure 7F A schematic diagram is shown after the growth temperature measuring element in the preparation method according to this disclosure;

[0063] Figure 7G A schematic diagram is shown after the growth of the insulating layer according to the preparation method of this disclosure;

[0064] Figure 7H A schematic diagram of the front structure of the neural microelectrode after etching according to the fabrication method of this disclosure is shown.

[0065] Figure 7I A schematic diagram of the back structure of a neural microelectrode after etching according to the fabrication method of this disclosure is shown. Detailed Implementation

[0066] The embodiments of the present disclosure will now be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the disclosure. In the following detailed description, numerous specific details are set forth to provide a thorough understanding of the embodiments of the present disclosure for ease of explanation. However, it will be apparent that one or more embodiments may be practiced without these specific details. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concepts of the present disclosure.

[0067] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit this disclosure. The terms “comprising,” “including,” etc., as used herein indicate the presence of the 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.

[0068] All terms used herein (including technical and scientific terms) have the meanings commonly understood by those skilled in the art, unless otherwise defined. It should be noted that the terms used herein are to be interpreted in a manner consistent with the context of this specification, and not in an idealized or overly rigid way.

[0069] When using expressions such as "at least one of A, B and C", they should generally be interpreted in accordance with the meaning that is commonly understood by those skilled in the art (e.g., "a system having at least one of A, B and C" should include, but is not limited to, a system having A alone, a system having B alone, a system having C alone, a system having A and B, a system having A and C, a system having B and C, and / or a system having A, B and C, etc.).

[0070] Figure 1 An exploded view of a neural microelectrode according to an embodiment of the present disclosure is shown schematically.

[0071] According to embodiments of this disclosure, such as Figure 1 As shown, a neural microelectrode with temperature regulation and temperature measurement functions includes: a substrate 1, a microelectrode array 3, a temperature measuring element 4, and an insulating layer 5. The substrate 1 contains a microfluidic channel 11.

[0072] According to embodiments of this disclosure, the test object includes neurons.

[0073] According to embodiments of this disclosure, substrate 1 includes a detection region and a non-detection region. For example... Figure 1 As shown, the cone-shaped region in front of basal 1 is the probe region, which measures the electrical signals generated by the neuron in response to temperature changes by contacting the neuron. The other regions on basal 1 are non-probe regions.

[0074] The microelectrode array 3 is disposed on the substrate 1, and the microelectrode array 3 and the substrate 1 have an overlapping portion, which is used to measure the electrical signal of the test object.

[0075] The microfluidic channel 11 is disposed inside the substrate 1 and has an overlapping portion with the detection area. The microfluidic channel is used to transport liquid.

[0076] According to embodiments of this disclosure, such as Figure 1 As shown, the microfluidic channel 11 flows through the detection area to control the temperature of the detection area through the transported liquid.

[0077] Temperature measuring element 4 is disposed on substrate 1 and overlaps with the detection area. Temperature measuring element 4 can measure the temperature of the detection area through the construction of the overlapping portion with the detection area.

[0078] The temperature measuring element 4 is made of a material that is sensitive to temperature changes. The temperature measuring element 4 includes a resistor, for example, the resistance of the temperature measuring element 4 increases as the temperature increases, in order to measure the temperature of the detection area.

[0079] An insulating layer 5 is disposed on the microelectrode array 3 and the temperature measuring element 4, covering the microelectrode array 3 and the temperature measuring element 4.

[0080] Figure 2 A schematic diagram of the structure of a neural microelectrode according to an embodiment of the present disclosure is shown.

[0081] According to embodiments of this disclosure, the substrate includes a detection region and a non-detection region, such as... Figure 2 As shown, the area below the needle tip of the neural microelectrode is the detection area, while the area above the needle handle is the non-detection area.

[0082] The inlet 12 and outlet 13 of the microfluidic channel are located in the non-detection area. The inlet 12 is used for cyclic input of liquid, and the outlet is used for cyclic output of liquid.

[0083] like Figure 2 As shown, the microfluidic channel flows through the tip region of substrate 1.

[0084] According to embodiments of this disclosure, the temperature range of the liquid transported through the microfluidic channel is 0°C to 60°C, which alters the temperature of the brain region being tested while ensuring no damage to neurons in the brain. Specifically, during temperature control, the temperature of the input liquid can be changed according to actual needs. For example, a liquid with a temperature higher than the brain region temperature can be introduced into the microfluidic channel through the inlet to achieve a warming stimulation; a liquid with a temperature lower than the brain region temperature can be introduced into the microfluidic channel through the inlet to achieve a cooling stimulation.

[0085] According to embodiments of this disclosure, the liquid transported through the microfluidic channel can be water. For example, water at 2°C can be circulated into the microfluidic channel to record electrical signals of living neurons while lowering the temperature of the brain region being tested.

[0086] 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.

[0087] The microelectrode array 3 and the temperature measuring element 4 are disposed between the substrate 2 and the insulating layer 5, and the microelectrode array 3 and the temperature measuring element 4 are disposed on the same layer on the substrate 2.

[0088] According to embodiments of this disclosure, the microfluidic channel 11 is sealed inside the substrate 1 and does not contact the substrate 2. An electrode array 3 and a temperature measuring element 4 are disposed on the upper surface of the substrate 2. Either the electrode array 3 or the temperature measuring element 4 can be disposed directly above the microfluidic channel 11 or on the outside of the microfluidic channel 11, respectively for measuring the electrical signal of the neuron and the temperature of the detection area.

[0089] According to embodiments of this 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. The microelectrode array 3 and the temperature measuring element 4 do not contact 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 may be disposed outside the microelectrode array 3, surrounding the microelectrode array 3; or the temperature measuring element 4 may be disposed inside the microelectrode array 3; or the temperature measuring element 4 may be located to the left or right of the microelectrode array 3.

[0090] In one specific embodiment, the temperature measuring element 4 is disposed on the outer side of the microelectrode array 3, and the outer side of the microelectrode array 3 is spaced apart from the inner side of the temperature measuring element 4 by a preset distance. The preset distance can be 5 to 20 micrometers to ensure that the outer side of the microelectrode array 3 and the inner side of the temperature measuring element 4 do not come into contact with each other, and both are disposed on the substrate 2.

[0091] According to an embodiment of this disclosure, the temperature measuring element 4 includes a resistor disposed at the end of the detection area for measuring the temperature at the end of the detection area.

[0092] According to another embodiment of this disclosure, the temperature measuring element 4 as a whole can be used as a thermal resistor to measure the temperature at the end of the detection area.

[0093] According to embodiments of this disclosure, the resistance value of the resistor in the temperature measuring element 4 increases with increasing temperature, so as to measure the temperature of the neural microelectrode tip in real time.

[0094] According to embodiments of this disclosure, the resistor in the temperature measuring element 4 can be a metallic conductor. For example, the metallic conductor can be platinum, copper, nickel, etc.

[0095] Figure 3 A schematic diagram of the structure of a substrate according to an embodiment of the present disclosure is shown. Figure 4 Schematic illustration Figure 3 AB cross-sectional view of the microelectrode of the central nervous system.

[0096] like Figure 3 As shown, microfluidic channels 11 are disposed inside the substrate 1 for transporting fluids at different temperatures. Figure 4 As shown, the microfluidic channel 11 is not in contact with the outside world. Therefore, during the process of using the microfluidic channel 11 to transport 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.

[0097] None of the related technologies start from the device for measuring electrical signals and combine temperature regulation and temperature measurement on the neural microelectrode for measuring electrical signals, so as to simultaneously realize temperature regulation, temperature measurement and electrophysiological recording.

[0098] This disclosure provides a neural microelectrode with temperature regulation and measurement functions. By integrating microfluidic channels and temperature measurement elements onto the neural microelectrode, it enables simultaneous temperature regulation, temperature measurement, and electrophysiological recording from the measurement device, thereby studying the effects of temperature on the nervous system. Furthermore, the neural microelectrode provided in this disclosure requires only a single device to study the effects of temperature on the nervous system, simplifying the research process and eliminating the influence of other factors on the nervous system.

[0099] Furthermore, in situations where the ambient temperature of the analyte cannot be changed, such as with living analytes, existing techniques are generally unable to study the effects of temperature on neurons. In contrast, the neural microelectrode with temperature regulation and measurement functions provided in this disclosure can simultaneously achieve temperature regulation, temperature measurement, and electrical signal recording of the analyte.

[0100] Figure 5 A schematic diagram of a temperature measuring element according to an embodiment of the present disclosure is shown.

[0101] like Figure 5 As shown, the temperature measuring element 4 is used as a measuring resistor. The temperature measuring element 4 is folded multiple times and distributed at the end of the detection area, i.e., the tip of the needle, to increase the resistance of the temperature measuring element 4 at the tip of the needle, thereby increasing the sensitivity and accuracy of the temperature measurement at the tip of the needle, so as to control the flow rate and temperature of the liquid in the microfluidic channel in real time.

[0102] According to an embodiment of this disclosure, a probe is also provided in the detection area, and the probe substrate is made of silicon.

[0103] Figures 6A-6J The schematic diagram illustrates the process flow for fabricating neural microelectrodes with temperature regulation and temperature measurement functions.

[0104] Figure 6A A schematic diagram of the substrate in the preparation method according to the present disclosure is shown.

[0105] like Figure 6A As shown, the substrate for fabricating the neural microelectrode is a silicon substrate. Specifically, a 400-micrometer-thick double-polished silicon wafer can be selected as substrate 1.

[0106] Figure 6B The schematic diagram illustrates a post-etching of trenches on a substrate according to the preparation method of this disclosure.

[0107] like Figure 6B As shown, after thermal oxidation of the substrate 1, trenches 14 of a predetermined size are etched. The trenches 14 are used to determine the position and depth of the microfluidic channel 11.

[0108] Specifically, 1000 nm silicon oxide can be thermally oxidized on substrate 1. Then, the location of trenches is patterned on the thermally oxidized silicon oxide using reactive ion etching, and trenches 14 are obtained using the Bosch deep silicon etching process. Trench 14 is 2 μm wide and 35 μm deep.

[0109] Figure 6C A schematic diagram is shown after etching microfluidic channels on a substrate according to the preparation method of this disclosure.

[0110] like Figure 6C As shown, after etching trenches 14 on substrate 1, microfluidic channels are etched on the bottom of trenches 14 to obtain a substrate including microfluidic channels, and the width of microfluidic channels 11 is greater than the width of trenches 14.

[0111] Specifically, 200 nm silicon oxide is thermally oxidized on the surface of trench 14 as a mask, and the silicon oxide layer at the bottom of trench 14 is removed using reactive ion etching. The silicon substrate is then etched using isotropic etching to obtain microfluidic channels 11. The diameter of the microfluidic channels 11 can be 40 μm.

[0112] Figure 6D A schematic diagram of the microfluidic channel after sealing in the preparation method according to this disclosure is shown.

[0113] like Figure 6DAs shown, polycrystalline silicon of a predetermined thickness is deposited on a substrate 1, including microfluidic channels 11, using low-pressure chemical vapor deposition to obtain a substrate that seals the microfluidic channels. The deposited polycrystalline silicon is located above the microfluidic channels.

[0114] Specifically, buffered oxide etchant (BOE) can be used to remove all silicon oxide mask layers on substrate 1, and then 1.5-micron polycrystalline silicon can be grown using low-pressure chemical vapor deposition (LPCVD) to fill the top of trench 14, sealing the microfluidic channel 11 to obtain a silicon substrate with microfluidic channel 11.

[0115] Figure 6E A schematic diagram of the substrate after deposition is shown in the preparation method according to this disclosure.

[0116] like Figure 6E As shown, a substrate 2 is grown on a substrate 1 of a sealed microfluidic channel 11. Specifically, a 500 nm silicon oxide and a 500 nm silicon nitride mixed film can be grown sequentially as the substrate 2 using plasma chemical vapor deposition.

[0117] Figure 6F A schematic diagram of the fabrication method according to this disclosure after growing a microelectrode array is shown.

[0118] like Figure 6F As shown, a microelectrode array 3 is patterned and deposited on substrate 2 to obtain a substrate including the microelectrode array 3. Specifically, 10 nm chromium and 200 nm gold can be deposited by magnetron sputtering as the microelectrode array 3.

[0119] Wherein, 31 is the lead window end of the microelectrode array and 32 is the recording electrode end of the microelectrode array.

[0120] Figure 6G A schematic diagram is shown after the growth temperature measuring element in the preparation method according to this disclosure.

[0121] like Figure 6G As shown, a temperature measuring element 4 is patterned and deposited on substrate 2. Specifically, 10 nm chromium and 200 nm platinum are sequentially deposited on substrate 2 using magnetron sputtering as the temperature measuring element 4.

[0122] Figure 6H A schematic diagram of the preparation method according to this disclosure after the growth of the insulating layer is shown.

[0123] like Figure 6H As shown, 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 the neural microelectrode to be etched.

[0124] Specifically, a 300-nanometer silicon oxide layer 5 can be grown using plasma chemical vapor deposition.

[0125] Figure 6I A schematic diagram of the front structure of the neural microelectrode after etching according to the fabrication method of this disclosure is shown.

[0126] like Figure 6I As shown, after depositing the insulating layer 5, the neural microelectrode to be etched is etched from the direction of the insulating layer 5 to obtain the front structure of the neural microelectrode to be etched.

[0127] Specifically, reactive ion etching exposes the electrode leads 16 and the test window formed by the two leads 16 by etching a 300 nm silicon oxide insulating material layer. Then, reactive ion etching is used to sequentially etch 300 nm silicon oxide, 500 nm silicon nitride, and 500 nm silicon oxide, followed by deep silicon etching using the Bosch process to etch 10 μm silicon to obtain trench 15, forming the front structure of the neural microelectrode.

[0128] Figure 6J A schematic diagram of the back structure of a neural microelectrode after etching according to the fabrication method of this disclosure is shown.

[0129] According to an embodiment of the present disclosure, the neural microelectrode to be etched is etched from the direction of the substrate 1 to obtain the back structure of the neural microelectrode to be etched.

[0130] Specifically, such as Figure 6J As shown, 300 micrometers of silicon were etched from the substrate direction of the neural microelectrode using the Bosch deep silicon etching process. During the etching of the substrate 1 from the back side, a 100-micrometer-thick tip portion 17 was retained to form the back side structure of the neural microelectrode.

[0131] Figures 7A to 7I This schematically illustrates another process flow for fabricating neural microelectrodes with temperature regulation and temperature measurement functions.

[0132] Figure 7A A schematic diagram of the substrate in the preparation method according to the present disclosure is shown.

[0133] like Figure 7A As shown, the substrate for fabricating the neural microelectrode is a silicon substrate. Specifically, a 400-micrometer-thick double-polished silicon wafer can be selected as substrate 1.

[0134] Figure 7B A schematic diagram is shown after etching microfluidic channels on a substrate according to the preparation method of this disclosure.

[0135] like Figure 7BAs shown, AZ4620 photoresist was specifically selected as the mask, and the morphology of the microfluidic channel 11 was etched using the Bosch process. The microfluidic channel 11 is 50 micrometers wide and 50 micrometers deep.

[0136] Figure 7C A schematic diagram of the microfluidic channel after sealing in the preparation method according to this disclosure is shown.

[0137] After etching microfluidic channels 11 on substrate 1, a second substrate of the same material as substrate 1 is wafer-bonded to substrate 1 containing microfluidic channels 11 from the direction of microfluidic channels 11, and the second substrate is thinned by chemical mechanical polishing process to obtain a substrate that seals the microfluidic channels.

[0138] Specifically, a second 400-micron thick double-polished silicon wafer is selected and wafer-bonded with the silicon wafer etched with microfluidic channels 11. The excess silicon on the second silicon wafer is removed using a chemical mechanical polishing (CMP) process, leaving 20 microns thick silicon for sealing the microfluidic channels 11.

[0139] Figure 7D A schematic diagram of the substrate after deposition is shown in the preparation method according to this disclosure.

[0140] like Figure 7D As shown, a substrate 2 is grown on a substrate 1 of a sealed microfluidic channel 11. Specifically, a 500 nm silicon oxide and a 500 nm silicon nitride mixed film can be grown sequentially as the substrate 2 using plasma chemical vapor deposition.

[0141] Figure 7E A schematic diagram of the fabrication method according to this disclosure after growing a microelectrode array is shown.

[0142] like Figure 7E As shown, a microelectrode array 3 is patterned and deposited on substrate 2 to obtain a substrate including the microelectrode array 3. Specifically, 10 nm chromium and 200 nm gold can be deposited by magnetron sputtering as the microelectrode array 3.

[0143] Wherein, 31 is the lead window end of the microelectrode array and 32 is the recording electrode end of the microelectrode array.

[0144] Figure 7F A schematic diagram is shown after the growth temperature measuring element in the preparation method according to this disclosure.

[0145] like Figure 7F As shown, a temperature measuring element 4 is patterned and deposited on substrate 2. Specifically, 10 nm chromium and 200 nm platinum are sequentially deposited on substrate 2 using magnetron sputtering as the temperature measuring element 4.

[0146] Figure 7G A schematic diagram of the preparation method according to this disclosure after the growth of the insulating layer is shown.

[0147] like Figure 7G As shown, 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 the neural microelectrode to be etched.

[0148] Specifically, a 300-nanometer silicon oxide layer 5 can be grown using plasma chemical vapor deposition.

[0149] Figure 7H A schematic diagram of the front structure of the neural microelectrode after etching according to the fabrication method of this disclosure is shown.

[0150] like Figure 7H As shown, after depositing the insulating layer 5, the neural microelectrode to be etched is etched from the direction of the insulating layer 5 to obtain the front structure of the neural microelectrode to be etched.

[0151] Specifically, reactive ion etching exposes the electrode leads 16 and the test window formed by the two leads 16 by etching a 300 nm silicon oxide insulating material layer. Then, reactive ion etching is used to sequentially etch 300 nm silicon oxide, 500 nm silicon nitride, and 500 nm silicon oxide, followed by deep silicon etching using the Bosch process to etch 10 μm silicon to obtain trench 15, forming the front structure of the neural microelectrode.

[0152] Figure 7I A schematic diagram of the back structure of a neural microelectrode after etching according to the fabrication method of this disclosure is shown.

[0153] According to an embodiment of the present disclosure, the neural microelectrode to be etched is etched from the direction of the substrate 1 to obtain the back structure of the neural microelectrode to be etched.

[0154] Specifically, such as Figure 7I As shown, 300 micrometers of silicon were etched from the substrate direction of the neural microelectrode using the Bosch deep silicon etching process. During the etching of the substrate 1 from the back side, a 100-micrometer-thick tip portion 17 was retained to form the back side structure of the neural microelectrode.

[0155] It should be noted that the microelectrode array 3 and the temperature control element 4 of this disclosure have various positional relationships on the substrate 2. Figures 6A-6J , Figures 7A to 7I The process flow diagram is only used as an example to illustrate the hierarchical relationship within the neural microelectrode.

[0156] The method for fabricating a neural microelectrode with temperature regulation and temperature measurement functions disclosed herein is fully compatible with micro-electro-mechanical system (MEMS) processes, reducing the cost of fabricating neural microelectrodes with temperature control and temperature measurement functions.

[0157] This disclosure provides a neural microelectrode with temperature regulation and temperature measurement functions. By introducing a low-temperature liquid into a microfluidic channel, the brain region at the tip of the microelectrode is cooled. While recording the electrical signals of neurons, the temperature of the brain test area can be changed and measured, thereby studying the effect of temperature on the nervous system.

[0158] Those skilled in the art will understand that the features described in the various embodiments and / or claims of this disclosure can be combined or combined in various ways, even if such combinations or combinations are not explicitly described in this disclosure. In particular, the features described in the various embodiments and / or claims of this disclosure can be combined or combined in various ways without departing from the spirit and teachings of this disclosure. All such combinations and / or combinations fall within the scope of this disclosure.

[0159] The specific embodiments described above further illustrate the purpose, technical solutions, and beneficial effects of this disclosure. It should be understood that the above descriptions are merely specific embodiments of this disclosure and are not intended to limit this disclosure. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this disclosure should be included within the protection scope of this disclosure.

Claims

1. A neural microelectrode with temperature regulation and temperature measurement functions, comprising: The substrate, including the detection area; A microfluidic channel is disposed within the substrate and overlaps with the detection area. The microfluidic channel is used to transport liquids of various temperatures to regulate the temperature of the detection area. The substrate also includes a non-detection area, where the inlet and outlet of the microfluidic channel are located. The inlet is used for circulating liquid input, and the outlet is used for circulating liquid output. The temperature range of the liquid is 0°C to 60°C, which is used to change the temperature of the brain region being tested without damaging neurons in the brain. A microelectrode array is disposed on the substrate and overlaps with the detection area; the microelectrode array is used to measure the electrical signal in the detection area. A temperature measuring element is disposed on the substrate and overlaps with the detection area; the temperature measuring element is used to measure the temperature of the detection area. The temperature measuring element includes a temperature-sensing resistor, which is folded multiple times and distributed at the end of the detection area to measure the temperature at the end of the detection area. An insulating layer is disposed on the microelectrode array and the temperature measuring element, covering the microelectrode array and the temperature measuring element; A substrate is disposed on the base and does not contact the microfluidic channel. The microelectrode array and the temperature measuring element are disposed between the substrate and the insulating layer, and the microelectrode array and the temperature measuring element are disposed on the same layer on the substrate. The temperature measuring element is disposed on the outside of the microelectrode array, and the outside of the microelectrode array is spaced at a predetermined distance from the inside of the temperature measuring element.

2. The neural microelectrode according to claim 1, wherein, The temperature measuring resistor is made of a metal whose resistivity changes stably with temperature.

3. The neural microelectrode according to claim 1, wherein, A probe is provided in the detection area, and the substrate material of the probe is silicon.

4. A method for preparing a neural microelectrode with temperature regulation and temperature measurement functions as described in claim 1, comprising: After thermal oxidation of the substrate, trenches of a predetermined size are etched out. Microfluidic channels are etched at the bottom of the trench to obtain a substrate including microfluidic channels. The width of the microfluidic channels is greater than the width of the trench. The substrate also includes a non-detection area. The inlet and outlet of the microfluidic channels are located in the non-detection area. The inlet is used for circulating liquid input, and the outlet is used for circulating liquid output. Using low-pressure chemical vapor deposition, polycrystalline silicon of a predetermined thickness is deposited on the substrate including the microfluidic channels to obtain a substrate that seals the microfluidic channels, wherein the polycrystalline silicon is located above the microfluidic channels; A substrate is grown on the substrate that seals the microfluidic channel; A microelectrode array is deposited on the substrate to obtain a substrate including the microelectrode array; A temperature measuring element is deposited on the substrate; the temperature measuring element includes a temperature sensing resistor, which is folded multiple times and distributed at the end of the detection region for measuring the temperature at the end of the detection region. An insulating layer is deposited on the temperature measuring element and the microelectrode array to obtain the neural microelectrode to be etched; The neural microelectrode to be etched is etched from the direction of the insulating layer to obtain the front structure of the neural microelectrode to be etched. The neural microelectrode to be etched is etched from the direction of the substrate to obtain the back structure of the neural microelectrode to be etched.

5. A method for fabricating a neural microelectrode with temperature regulation and temperature measurement functions as described in claim 1, comprising: Trenches of a predetermined size are etched on the substrate using photoresist; Microfluidic channels are etched at the bottom of the trench to obtain a substrate including the microfluidic channels; The substrate also includes a non-detection area, and the inlet and outlet of the microfluidic channel are located in the non-detection area. The inlet is used for circulating liquid input, and the outlet is used for circulating liquid output. A second substrate 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 by chemical mechanical polishing to obtain a substrate that seals the microfluidic channel. A substrate is grown on the substrate that seals the microfluidic channel; A microelectrode array is deposited on the substrate to obtain a substrate including the microelectrode array; A temperature measuring element is deposited on the substrate; the temperature measuring element includes a temperature sensing resistor, which is folded multiple times and distributed at the end of the detection region for measuring the temperature at the end of the detection region. An insulating layer is deposited on the temperature measuring element and the microelectrode array to obtain the neural microelectrode to be etched; The neural microelectrode to be etched is etched from the direction of the insulating layer to obtain the front structure of the neural microelectrode to be etched. The neural microelectrode to be etched is etched from the direction of the substrate to obtain the back structure of the neural microelectrode to be etched.

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