Integrated biological neural electrode, preparation method and neural signal detection device

Abstract

The application discloses an integrated biological nerve electrode, a preparation method and a nerve signal detection device, and is applied to the technical field of nerve signal detection. The integrated biological nerve electrode comprises a substrate and a heterojunction ISHFET, the heterojunction ISHFET comprises a heterojunction and source-drain electrodes arranged on the heterojunction, a two-dimensional electron gas is formed in the heterojunction, the source-drain electrodes comprise a source ohmic contact and a drain ohmic contact which are arranged at intervals, and the source ohmic contact and the drain ohmic contact are electrically connected with the two-dimensional electron gas; nerve signals on the gate surface of the heterojunction ISHFET regulate the conductivity of the two-dimensional electron gas, the source-drain current output of the heterojunction ISHFET changes, and the detection of biological nerve signals is realized. The integrated biological nerve electrode provided by the application utilizes the transconductance amplification effect of the two-dimensional electron gas to detect biological nerve signals, and can perform differential processing through the heterojunction REHFET, so that the collection efficiency and collection quality of the biological nerve signals are improved.

Description

Technical Field

[0001] This invention relates to the field of neural signal detection technology, and in particular to an integrated biological neural electrode, its preparation method, and a neural signal detection device. Background Technology

[0002] Neuroelectrophysiological techniques are crucial for detecting electrical signals in the brain and are essential for a deeper understanding of the nervous system's function under normal and pathological conditions. These techniques provide a foundation for the early diagnosis, effective intervention, and treatment of neurological diseases. However, current neuroelectrophysiological techniques still face several problems and challenges, particularly in terms of signal acquisition speed, stability, and spatial resolution.

[0003] Current neurophysiological techniques primarily rely on neural electrodes, which can be categorized into passive and active types based on signal detection methods. Passive neural electrodes detect bioelectrical signals through the electrochemical impedance spectroscopy of microelectrodes. While their structure is simple, signal acquisition is slow and they are susceptible to interference from electric fields and electromagnetic radiation, resulting in poor signal stability. Active neural electrodes, such as silicon-based field-effect transistor (ISFET) electrodes, enhance signal acquisition stability by modulating the conductivity of the ISFET channel through bioelectrical signals. However, their acquisition speed remains slow, and these electrodes have complex structures and large sizes, thus limiting their spatial resolution and application flexibility. Summary of the Invention

[0004] This invention proposes an integrated biological neural electrode, its preparation method, and a biological signal detection device, aiming to improve the acquisition efficiency and quality of biological neural signals.

[0005] The present invention proposes an integrated bio-neural electrode, comprising:

[0006] Substrate;

[0007] A heterojunction ISHFET, disposed on the substrate, includes a heterojunction and source / drain electrodes disposed on the heterojunction;

[0008] The heterojunction includes a buffer layer disposed on the substrate and a barrier layer disposed on the buffer layer; a two-dimensional electron gas is formed in the buffer layer near the interface with the barrier layer; the source and drain electrodes include source ohmic contacts and drain ohmic contacts disposed at intervals, and the source ohmic contacts and drain ohmic contacts are electrically connected to the two-dimensional electron gas.

[0009] Optionally, the heterojunction includes a GaN buffer layer, an AlN insertion layer, and an AlGaN barrier layer stacked sequentially from bottom to top; the two-dimensional electron gas is formed in the GaN buffer layer near the interface with the AlN insertion layer.

[0010] Optionally, an ISHFET recessed gate is etched on the AlGaN barrier layer.

[0011] Optionally, the integrated bioneural electrode further includes:

[0012] ISHFET leads and ISHFET pads are disposed on the GaN buffer layer, and a first insulating passivation layer covers the heterojunction ISHFET and the ISHFET leads;

[0013] The ISHFET leads are wired parallel to the longitudinal axis of the integrated biological neural electrode, including ISHFET source leads and ISHFET drain leads.

[0014] The ISHFET pads include ISHFET source pads and ISHFET drain pads;

[0015] One end of the ISHFET source lead is electrically connected to the source ohmic contact, and the other end is electrically connected to the ISHFET source pad; one end of the ISHFET drain lead is electrically connected to the drain ohmic contact, and the other end is electrically connected to the ISHFET drain pad.

[0016] The first insulating passivation layer has an ISHFET gate window and an ISHFET pad window.

[0017] Optionally, the integrated bioneural electrode includes a plurality of heterojunction ISHFETs arranged at intervals, and further includes:

[0018] Multiple microelectrodes are spaced apart from the heterojunction ISHFET. The microelectrodes are connected to the microelectrode pads via microelectrode leads, and the microelectrode leads are wired parallel to the longitudinal axis of the integrated biological neural electrode.

[0019] The microelectrode is disposed on the GaN buffer layer, and the first insulating passivation layer also has a microelectrode window and a microelectrode pad window; or, the microelectrode is disposed on the first passivation layer, and the microelectrode and the microelectrode lead are covered by a second insulating passivation layer, and the second insulating passivation layer has an ISHFET gate window, an ISHFET pad window, a microelectrode window and a microelectrode pad window.

[0020] Optionally, the integrated bio-neural electrode includes a heterojunction ISHFET disposed at the test end, a heterojunction REHFET adjacent to the heterojunction ISHFET, and at least one heterojunction REHFET located away from the test end.

[0021] Wherein, the first insulating passivation layer has an ISHFET gate window on the heterojunction REHFET far from the test end, and no ISHFET gate window is formed on the heterojunction REHFET adjacent to the heterojunction ISHFET.

[0022] The heterojunction REHFET is used for differential applications, and its material and structure are the same as those of the heterojunction ISHFET.

[0023] Optionally, the microelectrode includes a first microelectrode and a second microelectrode, wherein the first microelectrode is used to acquire biological signals and the second microelectrode is used for differential analysis.

[0024] Both the first and second microelectrodes have microelectrode windows in their insulating passivation layers.

[0025] Alternatively, any second microelectrode may be disposed adjacent to the first microelectrode, wherein the insulating passivation layer on the first microelectrode has a microelectrode window, and the insulating passivation layer on the second microelectrode does not have a microelectrode window, and a differential microelectrode solution contact window is provided on the microelectrode lead connected to the second microelectrode.

[0026] Optionally, the integrated bio-neural electrode further includes: a metal shielding layer and a third insulating passivation layer stacked on the integrated bio-neural electrode; the metal shielding layer and the third insulating passivation layer have windows corresponding to the windows of the lower insulating passivation layer, and the third insulating passivation layer also has a metal shielding layer grounding window. The present invention proposes a method for preparing an integrated bio-neural electrode, comprising the following steps:

[0027] S1, Fabrication of AlGaN / GaN ISHFET epitaxial wafer: GaN buffer layer, AlN insertion layer and AlGaN barrier layer are sequentially deposited on the substrate;

[0028] S2, Fabrication of AlGaN / GaN ISHFET: The AlGaN / GaN ISHFET epitaxial wafer is etched to the GaN buffer layer under the conditions of Cl2 and BCl3 gas environment by photolithography and dry etching process to form multiple AlGaN / GaN ISHFETs spaced apart.

[0029] S3, Fabrication of source / drain electrodes: Ti / Al / Ni / Au metal thin films are deposited in a high vacuum environment by photolithography and electron beam evaporation, and the Ti / Al / Ni / Au metal thin films are patterned using a lift-off process to obtain source / drain electrodes disposed on the AlGaN barrier layer;

[0030] S4, Perform rapid thermal annealing on the device prepared in step S3;

[0031] S5, Etching the ISHFET recessed gate: The surface of the AlGaN barrier layer is shallowly etched with a recessed gate through photolithography and photoelectrochemical oxidation processes under ultraviolet light irradiation and deionized water environment.

[0032] S6, fabricate ISHFET leads, ISHFET pads, microelectrodes, microelectrode leads and microelectrode pads, and then deposit a first insulating passivation layer to cover them; or, fabricate ISHFET leads and ISHFET pads, deposit a first insulating passivation layer to cover them, fabricate microelectrodes, microelectrode leads and microelectrode pads on the first insulating passivation layer, and then deposit a second insulating passivation layer to cover them.

[0033] Among them, one or more of the ISHFET leads, ISHFET pads, microelectrodes, microelectrode leads and microelectrode pads are prepared by the following method: a Ti / Au seed layer is deposited in a high vacuum environment by photolithography and electron beam evaporation, a thick gold film is electroplated by secondary photolithography and electroplating, and the thick gold film is patterned by a lift-off process.

[0034] The first insulating passivation layer and / or the second insulating passivation layer are prepared by the following method: a silicon dioxide isolation layer is prepared in a high vacuum and 350°C environment with SiH4 and N2O gas environment by photolithography and plasma-enhanced chemical vapor deposition process to obtain the insulating passivation layer; the insulating passivation layer is patterned with buffer oxide etchant using a wet etching process to prepare one or more of the following: ISHFET gate window, ISHFET pad window, microelectrode window, microelectrode pad window and differential microelectrode solution contact window;

[0035] S7, Preparation of metal shielding layer: A metal thin film is prepared in a high vacuum environment by photolithography and electron beam evaporation to obtain a metal shielding layer; and the metal shielding layer is patterned by a lift-off process to prepare each window corresponding to the underlying insulating passivation layer.

[0036] S8, Preparation of the third insulating passivation layer: A silicon dioxide passivation layer is prepared in a high vacuum and 350°C environment with SiH4 and N2O gas environment by photolithography and plasma-enhanced chemical vapor deposition process to obtain the third insulating passivation layer. The third insulating passivation layer is then patterned using a dry etching process to prepare the metal shielding layer grounding window and other windows corresponding to the metal shielding layer.

[0037] This invention also proposes a neural signal detection device, characterized in that the device comprises the integrated biological neural electrode described above or the integrated biological neural electrode prepared by the above preparation method, and:

[0038] The back-end circuit is electrically connected to the integrated bio-neural electrode and is used to power the integrated bio-neural electrode and process the bio-neural signals collected by the integrated bio-neural electrode.

[0039] A computer device, electrically connected to the back-end circuit, is used to receive the biological neural signals processed by the back-end circuit, and to perform computational analysis and visualization display.

[0040] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0041] Heterojunction ISHFETs (such as AlGaN / GaNISHFETs) with high-mobility, high-concentration two-dimensional electron gas are used for active detection of biological neural signals. The two-dimensional electron gas structure is highly sensitive to gate voltage control. Since the electron mobility in the two-dimensional electron gas structure is orders of magnitude higher than the charge mobility on the gate surface, subtle fluctuations in the charge on the gate surface of the heterojunction ISHFET can be quickly reflected in changes in the conductivity of the two-dimensional electron gas and amplified, thus manifesting as changes in source-drain current, which is the detection of biological neural signals. Therefore, using this heterojunction ISHFET for the detection of biological neural signals has the advantages of being label-free, fast, and stable, improving the acquisition efficiency and quality of biological neural signals. Attached Figure Description

[0042] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0043] Figure 1 This is a three-dimensional structural diagram of the substrate and epitaxial wafer of some embodiments of the integrated bioneural electrode of the present invention;

[0044] Figure 2 The following are three-dimensional structural diagrams of AlGaN / GaN ISHFET after mesa device isolation and fabrication of source-drain electrode ohmic contacts in some embodiments of the integrated bioneural electrode of the present invention.

[0045] Figure 3 This is a three-dimensional structural diagram of some embodiments of the integrated bio-neural electrode of the present invention after fabrication of ISHFET leads and ISHFET pads;

[0046] Figure 4 This is a schematic diagram of the three-dimensional structure of some embodiments of the integrated bio-neural electrode of the present invention after the preparation of the first insulating passivation layer;

[0047] Figure 5 The following are three-dimensional structural diagrams of some embodiments of the integrated bioneural electrode of the present invention after fabrication of microelectrodes, microelectrode leads and microelectrode pads;

[0048] Figure 6 This is a schematic diagram of the three-dimensional structure of some embodiments of the integrated bio-neural electrode of the present invention after the fabrication of the second insulating passivation layer;

[0049] Figure 7 This is a three-dimensional structural diagram of some embodiments of the integrated bio-neural electrode of the present invention after the preparation of the metal shielding layer;

[0050] Figure 8 This is a schematic diagram of the three-dimensional structure of some embodiments of the integrated bio-neural electrode of the present invention after the preparation of the third insulating passivation layer;

[0051] Figure 9 These are side views of some embodiments of the integrated bioneural electrode of the present invention after each layer has been peeled off;

[0052] Figure 10 These are three-dimensional structural diagrams of the integrated bio-neural electrode of the present invention after each layer has been peeled off, representing some embodiments.

[0053] Figure 11 This is a top view of some embodiments of the integrated bioneural electrode of the present invention;

[0054] Figure 12 This is a three-dimensional structural diagram of some other embodiments of the integrated bioneural electrode of the present invention after mesa device isolation;

[0055] Figure 13 The following are three-dimensional structural diagrams of AlGaN / GaN ISHFETs after fabrication of source-drain electrode ohmic contacts, representing some other embodiments of the integrated bioneural electrode of the present invention.

[0056] Figure 14 This is a three-dimensional structural diagram of some other embodiments of the integrated bioneural electrode of the present invention after fabrication of the ISHFET recessed gate;

[0057] Figure 15 Enlarged detail of the ISHFET recessed gate fabricated for some other embodiments of the integrated bioneural electrode of the present invention;

[0058] Figure 16 This is a three-dimensional structural diagram of the integrated bioneural electrode of the present invention after fabrication of ISHFET leads, ISHFET pads, microelectrodes, microelectrode leads, and microelectrode pads in other embodiments of the present invention.

[0059] Figure 17 Three-dimensional structural diagram of the integrated bio-neural electrode of the present invention after the preparation of the first insulating passivation layer;

[0060] Figure 18 Three-dimensional structural diagrams of the integrated bioneural electrode of the present invention after fabrication of the metal shielding layer;

[0061] Figure 19 Three-dimensional structural diagram of the integrated bioneural electrode of the present invention after the preparation of the third insulating passivation layer in other embodiments;

[0062] Figure 20 This is a side view of each layer after peeling off in some other embodiments of the integrated bioneural electrode of the present invention;

[0063] Figure 21 These are three-dimensional structural diagrams of the integrated bioneural electrode of the present invention after the layers have been peeled off in some other embodiments;

[0064] Figure 22 This is a top view of some other embodiments of the integrated bioneural electrode of the present invention;

[0065] Figure 23 This is a flowchart of the integrated bio-neural electrode fabrication method of the present invention.

[0066] Explanation of reference numerals in the attached figures:

[0067] 1. Substrate; 2. AlGaN / GaN ISHFET; 2', Near-end AlGaN / GaN REHFET; 2'', Far-end AlGaN / GaN REHFET; 21. GaN buffer layer; 22. AlN insertion layer; 23. AlGaN barrier layer; 24. Source / drain electrodes; 31. ISHFET lead; 31-1: ISHFET source lead; 31-2: ISHFET drain lead; 32. ISHFET pad; 4. First insulating passivation layer; 51. First microelectrode; 51', Second microelectrode; 52. Microelectrode lead; 53. Microelectrode pad; 6. Second insulating passivation layer; 7. Metal shielding layer; 8. Third insulating passivation layer;

[0068] W1, ISHFET gate window; W2, ISHFET pad window; W3, microelectrode window; W4, microelectrode pad window; W5, metal shielding layer ground window; W6, differential microelectrode solution contact window; W7, metal shielding layer window; B, ISHFET recessed gate; L1~L7: layer numbering after stripping. Detailed Implementation

[0069] To make the objectives, features, and advantages of this invention more apparent and understandable, the technical solutions of the embodiments of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the embodiments described below are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0070] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0071] In the description of this specification, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0072] The following is a description of the technical terms used in the embodiments of the present invention:

[0073] ISHFET: Ion-sensitive high electron mobility field-effect transistor. The gate of an ISHFET structure is composed of an electrolyte solution on top of the gate region, also known as a "solution gate".

[0074] HEMT: High Electron Mobility Transistor. The gate of a HEMT structure is made of metal deposited on top of the gate region, also known as a "metal gate".

[0075] REHFET: Reference High Mobility Field-Effect Transistor (In this embodiment of the invention, the REHFET uses the same materials and structure as the ISHFET. To distinguish it from the working ISHFET used for detecting biological neural signals, it is named REHFET).

[0076] Current neurophysiological techniques still face several problems and challenges, especially in terms of signal acquisition speed, stability, and spatial resolution. Existing neurophysiological techniques mainly rely on neural electrodes, which can be divided into two categories according to the area of ​​use: non-invasive external electrodes (such as electroencephalography, EEG) and invasive internal electrodes (such as electrocorticography, ECoG, and multichannel electrode, MEA). According to the signal detection method, neural electrodes can also be divided into passive and active electrodes.

[0077] Passive neural electrodes employ microelectrode structures made of metal or glass materials to acquire biological neural signals via electrochemical impedance spectroscopy. Although their structure is simple, the signal acquisition quality depends on the interfacial impedance. When the interfacial impedance of the microelectrode is low, no signal can be detected, while when the impedance is high, it is easily affected by noise interference. Furthermore, the signal acquisition speed is slow, and it is also susceptible to interference from electric fields and electromagnetic radiation, resulting in poor signal stability. In addition, the biocompatibility of metallic materials also affects their effectiveness.

[0078] Active neural electrodes typically employ field-effect transistors, such as silicon-based field-effect transistors (ISFETs), which regulate the channel conductance by changing the potential on the gate, thereby altering the source-drain current and detecting neural signals. Active detection offers advantages in signal acquisition stability, signal-to-noise ratio, and acquisition speed, with signal acquisition quality dependent on the device's electrical characteristics. However, silicon-based field-effect transistors still have a relatively slow acquisition speed and are structurally complex and large in size, thus limiting their spatial resolution and application flexibility.

[0079] Currently, researchers are attempting to fabricate field-effect transistors with excellent electrical properties using different materials, aiming to acquire neural signals more accurately, faster, and more stably, but the results have been limited. Therefore, developing a neural electrode that can provide both high-speed, stable signal acquisition and meet the requirements of high spatial resolution is an important direction for current research.

[0080] Through dedicated research, the applicant discovered that heterojunction ion-sensitive high electron mobility field-effect transistors (hereinafter referred to as heterojunction ISHFETs), such as AlGaN / GaN ISHFETs, possess unique advantages in the field of biochemical detection. The high-concentration, high-mobility two-dimensional electron gas structure at the AlGaN / GaN interface enables ISHFETs to exhibit label-free, rapid, and stable response characteristics when detecting charged biochemical molecules. Considering that the essence of biological neural signals is the inflow and outflow of charged ions in neurons, the applicant, after long-term research and development, has improved the acquisition of biological neural signals by adopting the AlGaN / GaN ISHFET structure, hoping to further promote the development of the field of neuroscience.

[0081] To address the problems existing in current neural electrodes, this invention proposes an integrated biological neural electrode by leveraging the unique advantages of heterojunction ISHFETs.

[0082] In some embodiments, the integrated bioneural electrode proposed in this invention includes:

[0083] Substrate;

[0084] A heterojunction ISHFET is disposed on a substrate and includes a heterojunction and source / drain electrodes disposed on the heterojunction. The heterojunction includes a buffer layer disposed on the substrate and a barrier layer disposed on the buffer layer. A two-dimensional electron gas is formed in the buffer layer near the interface with the barrier layer. The source / drain electrodes include source ohmic contacts and drain ohmic contacts disposed at intervals, and the source ohmic contacts and drain ohmic contacts are electrically connected to the two-dimensional electron gas.

[0085] When the integrated biological neural electrode is working, the gate of the heterojunction ISHFET is an electrolyte solution on the upper part of the gate region. The electrolyte solution regulates the conductivity of the two-dimensional electron gas by changing the surface charge of the gate, thereby causing the source and drain current output of the heterojunction ISHFET to change.

[0086] In these embodiments, the heterojunction ISHFET uses a heterojunction with a high concentration and high mobility of two-dimensional electron gas, such as AlGaN / GaN, AlGaAs / InGaAs / GaAs, SiC / Si and other semiconductor material heterojunctions from the third to the fifth group. Alternatively, other novel metal oxide semiconductor heterojunctions or novel two-dimensional material heterojunctions with two-dimensional electron gas formed at the interface between the barrier layer and the channel layer can be used. The specific material and stack-up structure design of the heterojunction can be selected according to the actual application scenario requirements and relevant research progress, and are not limited here.

[0087] The formation principle of two-dimensional electron gas is as follows: When two different semiconductor materials form a heterojunction, if there is a large difference in their conduction band edge energy, a conduction band discontinuity will be formed at the interface. This conduction band discontinuity will form a potential well on one side of the channel layer, and electrons will accumulate in this potential well, thus forming a two-dimensional electron gas. In some material systems, due to the spontaneous polarization and piezoelectric polarization of the material, an additional electric field will be generated at the heterojunction interface. This electric field will further change the band structure, causing electrons to accumulate in a specific region and forming a high-concentration two-dimensional electron gas. In other cases, valence band discontinuity and band bending will also form a two-dimensional electron gas.

[0088] In these embodiments, a heterojunction ISHFET is used to detect the biological neural signals of the test subject. The gate of the ISHFET structure is composed of an electrolyte solution on the top of the gate region, also known as a "solution gate". The two-dimensional electron gas structure in the heterojunction can be very sensitively controlled by the gate voltage. Any positive or negative ion adsorbed on the surface of the gate region corresponds to the gain or loss of an electron in the two-dimensional electron gas structure of the channel. Since the electron mobility in the two-dimensional electron gas structure has an order of magnitude higher advantage than the charge mobility on the surface of the gate region, the slight fluctuation of the charge on the sensing area surface of the ISHFET device can be quickly reflected in the change of conductivity of the two-dimensional electron gas and "amplified", thus manifesting as a change in source and drain current.

[0089] In these embodiments, the object of study is a biological neuron or neural tissue.

[0090] In the specific application scenarios of these embodiments, an integrated bio-neural electrode is inserted into biological neural tissue. The electrode is immersed in a biological solution, and the gate region of the heterojunction ISHFET is in contact with the neuron. When the organism receives stimulation, the neuron generates an action potential (mainly manifested as sodium ion influx and potassium ion efflux). This causes a potential change in the electrolyte solution between the heterojunction ISHFET and the neuron. This potential change (i.e., the extracellular potential of the neuron) rapidly and sensitively modulates the conductivity of the two-dimensional electron gas structure, causing a change in the source and drain current of the heterojunction ISHFET, which is the detection of biological neural signals.

[0091] Therefore, the changes in the source and drain current of a heterojunction ISHFET reflect the changes in the neural signals of biological neurons, and the extracellular potential V of the neuron can be calculated using the following formula. G Size:

[0092]

[0093] In the formula, I ds For source and drain current, μ n C represents the electron mobility of a two-dimensional electron gas. ox V is the capacitance of the two-dimensional electron gas to the surface of the heterojunction barrier layer, W is the width of the heterojunction ISHFET, L is the channel length of the heterojunction ISHFET, and V is the capacitance of the two-dimensional electron gas to the surface of the heterojunction barrier layer. G Extracellular potential (nerve signal), V TH V is the threshold voltage of the heterojunction ISHFET. DS This represents the source-drain voltage.

[0094] As can be seen from the above, the embodiments of the present invention use a heterojunction ISHFET with a high-mobility and high-concentration two-dimensional electron gas to actively detect biological neural signals. The two-dimensional electron gas structure is very sensitive to gate voltage control. Since the electron mobility in the two-dimensional electron gas structure is orders of magnitude higher than the charge mobility on the gate surface, the slight fluctuations in the surface charge of the sensing region of the heterojunction ISHFET can be quickly reflected in the change of conductivity of the two-dimensional electron gas and amplified, and then manifested as a change in source-drain current, which is the detection of biological neural signals.

[0095] Compared with existing nerve electrodes in electrophysiological techniques, such as passive nerve electrodes and active silicon-based nerve electrodes, the heterojunction ISHFET of this application can detect biological nerve signals more quickly and stably. The biological nerve signals acquired by the heterojunction ISHFET are signals amplified by transconductance, rather than the original weak signals, which can also reduce the difficulty of back-end circuit design.

[0096] Compared to the metal gate of HEMT structure, the "solution gate" of ISHFET is in direct contact with the solution to be tested, and can directly sense changes in ion concentration in the solution. The detection of changes in ion concentration is faster and more sensitive. In addition, the metal gate of HEMT usually does not have the characteristic of good compatibility with biological systems and is difficult to be directly applied to detection in biological bodies. ISHFET, on the other hand, can modify the surface of the barrier layer by selecting appropriate biochemical materials, so that the biological neural electrode has better biocompatibility and adaptability.

[0097] Therefore, the integrated bioelectrode proposed in this application has the advantages of being label-free, rapid, and stable.

[0098] Based on the above embodiments, see Figures 1-22 In some specific embodiments, the heterojunction ISHFET is an AlGaN / GaN ISHFET (reference numeral 2 in the figure), wherein the heterojunction is an AlGaN / GaN heterojunction.

[0099] Specifically, in these embodiments, an AlGaN / GaN heterojunction is disposed on a substrate 1, and a GaN buffer layer 21, an AlN insertion layer 22, and an AlGaN barrier layer 23 are stacked sequentially from bottom to top in the AlGaN / GaN heterojunction. A two-dimensional electron gas is formed in the GaN buffer layer 21 near the interface with the AlN insertion layer 22.

[0100] In one preferred embodiment, the substrate 1 is made of Sapphire material (sapphire, the main component of which is Al2O3). Sapphire substrates have good insulation, thermal stability and chemical stability.

[0101] In these embodiments, both AlGaN and GaN belong to the wurtzite structure. Their low symmetry gives AlGaN and GaN the characteristic of spontaneous polarization. When AlGaN and GaN come into contact, the lattice is deformed by external stress, resulting in piezoelectric polarization. Spontaneous polarization and piezoelectric polarization will simultaneously cause a high-mobility, high-concentration two-dimensional electron gas structure to form on the AlGaN / GaN contact surface near GaN. This two-dimensional electron gas structure can be very sensitively controlled by the gate voltage. Any positive or negative ion adsorbed on the gate surface will correspond to the gain or loss of an electron in the channel two-dimensional electron gas structure.

[0102] The AlN insertion layer is used to reduce interface defects between GaN and AlGaN and improve carrier mobility. In addition, by adjusting the thickness and quality of the AlN insertion layer, the density of the two-dimensional electron gas generated by the polarization effect can be controlled, which is beneficial to optimizing the threshold voltage and conductivity of the device.

[0103] In these embodiments, GaN exhibits superior biocompatibility compared to AlGaN materials and metal- and silicon-based materials, enabling longer-term in vivo biological neural signal acquisition.

[0104] In these embodiments, the spacing between AlGaN / GaN ISHFETs can be adjusted according to the actual situation to reduce signal crosstalk.

[0105] In a preferred embodiment, the source / drain electrodes 24 may be Ti / Al / Ni / Au metal electrodes, which can form an ohmic contact with the AlGaN barrier layer 23 through thermal annealing.

[0106] It should be noted that there can be one or more AlGaN / GaN ISHFETs. The arrangement of multiple AlGaN / GaN ISHFETs can be linear or other array distribution methods, depending on the actual needs of signal acquisition.

[0107] See Figures 1-22 Based on the above embodiments of AlGaN / GaN ISHFET, in some specific embodiments, the integrated bio-neural electrode further includes:

[0108] ISHFET lead 31 and ISHFET pad 32 are disposed on GaN buffer layer 21, and a first insulating passivation layer covers AlGaN / GaNISHFET and ISHFET lead 31.

[0109] ISHFET lead 31 is wired parallel to the longitudinal axis of the integrated biological neural electrode, including ISHFET source lead 31-1 and ISHFET drain lead 31-2.

[0110] ISHFET pad 32 includes ISHFET source pad and ISHFET drain pad;

[0111] One end of the ISHFET source lead 31-1 is electrically connected to the source ohmic contact, and the other end is electrically connected to the ISHFET source pad; one end of the ISHFET drain lead 31-2 is electrically connected to the drain ohmic contact, and the other end is electrically connected to the ISHFET drain pad.

[0112] The first insulating passivation layer has an ISHFET gate window W1 and an ISHFET pad window W2.

[0113] In these embodiments, the ISHFET leads 31 are wired parallel to the longitudinal axis, so that the noise is the same between different AlGaN / GaN ISHFETs, which helps to improve the uniformity of the signal and ensure a high signal-to-noise ratio in signal acquisition.

[0114] In these embodiments, the AlGaN / GaN ISHFET is connected to the back-end circuit via source / drain electrodes 24, ISHFET leads 31, and ISHFET pads 32; wherein the back-end circuit is used to power the bio-neural electrode and to receive and process the bio-neural signals acquired by the bio-neural electrode.

[0115] In a preferred embodiment, both the ISHFET lead 31 and the ISHFET pad 32 can be made of Ti / Au metal.

[0116] In these embodiments, a first insulating passivation layer 4 covers the AlGaN / GaN ISHFET and ISHFET leads 31 to prevent unintended electrical contact between the conductive material and surrounding tissue, ensuring that electrical signals are exchanged only through designed contact points. This also ensures the functional independence of each ISHFET, avoids electrical signal crosstalk, and guarantees a high signal-to-noise ratio during signal acquisition. Furthermore, the first insulating passivation layer protects the biological neural electrodes from corrosive substances in the test object, maintains the long-term stability of device performance, and reduces the release of harmful substances from the dissolution or corrosion of conductive materials into the body, ensuring biocompatibility and safety.

[0117] In a preferred embodiment, the first insulating passivation layer is made of silicon dioxide.

[0118] In these embodiments, the AlGaN / GaN ISHFET contacts the electrolyte solution of the test object through the ISHFET gate window W1. The ISHFET gate window W1 is opened between the source ohmic contact and the drain ohmic contact on the top of the AlGaN / GaN ISHFET, so that the source and drain electrodes 24 are completely covered by the first insulating passivation layer. Correspondingly, the exposed part of the AlGaN barrier layer 23 is the ISHFET open gate region. The ISHFET open gate region serves as the acquisition area for neural signals, and its shape and area can be set according to the actual signal acquisition requirements and process conditions. The first insulating passivation layer has an ISHFET pad window W2, and the ISHFET pad 32 is connected to the back-end circuit through the ISHFET pad window W2.

[0119] See Figure 14 and Figure 15 Based on the above AlGaN / GaN ISHFET embodiments, in some other embodiments, the surface of the AlGaN barrier layer 23 at the ISHFET open gate region is formed with an ISHFET recessed gate B by shallow etching.

[0120] In these embodiments, the ISHFET recessed gate reduces the polarization effect of the AlGaN / GaN heterojunction by thinning the AlGaN barrier layer, thereby reducing the two-dimensional electron gas concentration and shifting the threshold voltage in the positive direction. This allows the AlGaN / GaN ISHFET to achieve a maximum transconductance value near Vg=0V without adjusting the device operating point using a metal gate or reference electrode. This improves device sensitivity and also reduces device size, making integration easier.

[0121] In addition, adjusting the shape of the ISHFET gate can also improve the signal-to-noise ratio of signal acquisition to some extent.

[0122] It should be noted that the recessed gate of the ISHFET is a preferred embodiment of the present invention and is not a limitation thereof. In other embodiments, AlGaN / GaN ISHFETs with non-recessed gate structures can also be used to acquire neural signals, for example, by using fluorine ion implantation, adding a P-type GaN cap, introducing a reference electrode for modulation, or using a metal gate for modulation.

[0123] Based on the above-described AlGaN / GaN ISHFET embodiments, see [link / reference]. Figures 1-22 To further improve the spatial resolution of signal acquisition in integrated bioneural electrodes, in some embodiments, the integrated bioneural electrode includes multiple spaced AlGaN / GaN ISHFETs, and further includes:

[0124] Multiple microelectrodes (including a first microelectrode 51 and a second microelectrode 51') are spaced apart from the AlGaN / GaN ISHFET. The microelectrodes are connected to the microelectrode pads 53 via microelectrode leads 52, which are wired parallel to the longitudinal axis of the integrated bioneural electrode.

[0125] Among them, the microelectrode detects bioelectric signals through electrochemical impedance spectroscopy; specifically, the top of the microelectrode that collects biosignals is in contact with the electrolyte solution of the neuron. When the neuron receives stimulation, it generates an action potential, and the impedance between the microelectrode and the electrolyte solution changes. The bioneural signal can be obtained based on the electrochemical impedance spectroscopy.

[0126] See Figure 5 In some embodiments, each AlGaN / GaN ISHFET is connected to the ISHFET source pad via a corresponding ISHFET source lead 31-1; the microelectrode, microelectrode lead 52 and microelectrode pad 53 are disposed on the first insulating passivation layer 4, and the microelectrode and microelectrode lead 52 are covered with a second insulating passivation layer 6, and the second insulating passivation layer 6 has corresponding ISHFET gate window W1, ISHFET pad window W2, microelectrode window W3 and microelectrode pad window W4.

[0127] Among them, the microelectrode, microelectrode lead and microelectrode pad can be made of Ti / Au metal thin film, and the second insulating passivation layer can be made of silicon dioxide.

[0128] See Figure 16 In some other implementations, all AlGaN / GaN ISHFETs are connected to the ISHFET pad 32 via an ISHFET source lead 31-1, that is, the sources of all AlGaN / GaN ISHFETs are collinear, in order to reduce the number of ISHFET leads and the area occupied, so that the microelectrode can be placed on the GaN buffer layer 21.

[0129] In the AlGaN / GaN ISHFET source-line collinearity implementation, the microelectrode, microelectrode lead 52, and microelectrode pad 53 can be fabricated together with the ISHFET lead 31 and ISHFET pad 32 on the GaN buffer layer 21 to reduce process steps; correspondingly, the first insulating passivation layer also has a microelectrode window W3 and a microelectrode pad window W4; the materials of the microelectrode, microelectrode lead, microelectrode pad, as well as the ISHFET lead and ISHFET pad, can all be Ti / Au metal thin film.

[0130] Based on the above-described AlGaN / GaN ISHFET embodiments, in order to improve the signal-to-noise ratio of integrated biological neural electrodes, the present invention also proposes the following embodiments.

[0131] See Figures 12-22 In some embodiments, the integrated bioneural electrode further includes an AlGaN / GaN ISHFET (reference numeral 2) disposed at the test end, an AlGaN / GaN REHFET adjacent to the AlGaN / GaN ISHFET (i.e., the proximal AlGaN / GaN REHFET, reference numeral 2'), and at least one AlGaN / GaN REHFET remote from the test end (i.e., the distal AlGaN / GaN REHFET, reference numeral 2'').

[0132] Among them, AlGaN / GaN REHFET is used for differential applications, and its materials and structure are the same as those of AlGaN / GaN ISHFET.

[0133] The first insulating passivation layer has an ISHFET gate window on the far-end AlGaN / GaN REHFET, but no ISHFET gate window on the near-end AlGaN / GaN REHFET.

[0134] Specifically, the gate surface of the near-end AlGaN / GaN REHFET used for differential is covered by a first insulating layer material, making it insensitive to changes in neural signals, but still able to collect ambient noise and device background noise of the AlGaN / GaN REHFET to a certain extent.

[0135] It should be noted that the quantity relationship between AlGaN / GaN ISHFET and near-end AlGaN / GaN REHFET can be one-to-one, or one near-end AlGaN / GaN REHFET can correspond to multiple AlGaN / GaN ISHFETs. Their arrangement can be linear or other array distribution methods.

[0136] The gate window of the far-end AlGaN / GaN REHFET used for differential is opened after the first insulating passivation layer is prepared. However, the arrangement of the far-end AlGaN / GaN REHFET needs to be set outside the neural discharge region so that only ambient noise is collected.

[0137] In a preferred embodiment, after the first insulating passivation layer is prepared, a gate window for the near-end AlGaN / GaN REHFET for differential is opened. A material that is insensitive to neural signals, remains sensitive to environmental signals, and does not change the electrical characteristics of the original device is used to modify the surface of the AlGaN barrier layer in the gate region to achieve better differential performance. The specific modification material can be reasonably selected according to the actual test conditions.

[0138] In these embodiments, subtracting the signal acquired by the AlGaN / GaN REHFET from the signal acquired by the AlGaN / GaN ISHFET and performing differential sampling yields a purer neural signal, improving the signal-to-noise ratio of the acquired signal.

[0139] Based on the aforementioned AlGaN / GaN ISHFET embodiment with microelectrodes, to further improve the signal-to-noise ratio of integrated biological neural electrodes, see [reference needed]. Figures 1-22 In some embodiments, the microelectrode includes a first microelectrode 51 and a second microelectrode 51'. The first microelectrode 51 is used to collect biological signals, and the second microelectrode 51' is used for differential analysis. That is, the in vivo biological environmental noise collected by the second microelectrode 51' is normalized and then the difference is made with the biological neural signal collected by the first microelectrode 51 to achieve the differential function.

[0140] See Figures 5-11In some embodiments, the second microelectrode 51' is disposed outside the nerve discharge area for collecting environmental noise, and the insulating passivation layer on the second microelectrode 51' has a microelectrode window W3 (for embodiments where the microelectrode is disposed on the GaN buffer layer, the insulating passivation layer there is the first insulating passivation layer; for embodiments where the microelectrode is disposed on the first insulating passivation layer, the insulating passivation layer there is the second insulating passivation layer).

[0141] In these embodiments, the area of ​​the second microelectrode 51' can be set to be larger than the area of ​​the first microelectrode 51, so as to collect more uniform environmental noise over a larger area.

[0142] In these embodiments, the second microelectrode 51' can also serve as a stimulation electrode, providing electrical stimulation to biological neurons via a power supply from a back-end circuit.

[0143] See Figures 16-22 In some other embodiments, the second microelectrode 51' is disposed adjacent to the first microelectrode 51, and the insulating passivation layer on the second microelectrode 51' does not have a microelectrode window, while the microelectrode lead 52 connected to the second microelectrode 51' has a differential microelectrode solution contact window.

[0144] Specifically, in these embodiments, the second microelectrode 51' is completely covered by an insulating passivation layer, making it insensitive to changes in neural signals, but still able to collect environmental noise and the device background noise of the first microelectrode 51 to a certain extent.

[0145] In these embodiments, in order to avoid the second microelectrode 51' from becoming suspended and causing increased noise, a window of a certain length that comes into contact with the ambient solution must be opened at the corresponding microelectrode lead 52 to eliminate suspension, that is, a differential microelectrode solution contact window is set.

[0146] Based on the above-described AlGaN / GaN ISHFET embodiments, see [link / reference]. Figures 1-22 To effectively reduce electroinduced noise, in some embodiments, the integrated bio-neural electrode further includes:

[0147] A metal shielding layer 7 and a third insulating layer 8 are stacked on the integrated bio-neural electrode; the metal shielding layer 7 and the third insulating layer 8 have windows corresponding to the windows of the lower insulating passivation layer.

[0148] Specifically, in the embodiment where the microelectrode is disposed on the GaN buffer layer, the metal shielding layer is disposed on the first insulating passivation layer; in the embodiment where the microelectrode is disposed on the first insulating passivation layer, the metal shielding layer is disposed on the second insulating passivation layer.

[0149] In some embodiments, the metal shielding layer is provided with an ISHFET gate window, an ISHFET pad window, a microelectrode window, a microelectrode pad window, and a differential microelectrode solution contact window that correspond one-to-one with the first insulating passivation layer or the second insulating passivation layer.

[0150] In other embodiments, see Figure 18 The metal shielding layer can be directly set with a large metal shielding layer window W7, and the area of ​​the metal shielding layer window W7 includes one or more lower layer windows.

[0151] The third insulating passivation layer is used to prevent unintended electrical contact between conductive materials and surrounding tissues, ensuring a high signal-to-noise ratio in signal acquisition. It also protects the biological neural electrodes from corrosive substances in the test object, maintains the long-term stability of device performance, and reduces the release of harmful substances from the dissolution or corrosion of conductive materials into the biological body, ensuring biocompatibility and safety.

[0152] The third insulating passivation layer has a metal shielding grounding window W5 and various windows corresponding to the metal shielding layer.

[0153] In these embodiments, the internal electrical noise of the integrated bio-neural electrode is mainly caused by the source potential of the AlGaN / GaN ISHFET and the microelectrode potential. By setting a metal shielding layer and grounding it through the metal shielding layer window, the electric field and electromagnetic interference signals inside the device can be further shielded, effectively reducing electro-induced noise.

[0154] In these embodiments, the metal shielding layer can be made of metals or alloys such as Au, Cu, Ag, Al, Ni, and can be a thin layer or mesh structure. The third insulating passivation layer can be made of silicon dioxide.

[0155] As can be seen from the above embodiments, this invention designs an integrated bio-neural electrode for acquiring bio-neural signals based on the sensitive response of the two-dimensional electron gas structure in the heterojunction ISHFET to changes in the gate potential. Since the electron mobility in the two-dimensional electron gas structure is orders of magnitude higher than the charge mobility on the gate surface, subtle fluctuations in the surface charge of the sensing region of the heterojunction ISHFET can be rapidly reflected in and amplified by changes in the conductivity of the two-dimensional electron gas, thus manifesting as changes in the source-drain current, achieving rapid and stable acquisition of bio-neural signals.

[0156] Meanwhile, this application uses AlGaN / GaN ISHFET as a preferred embodiment to specifically design the integrated biological neural electrode, and provides a new design idea for biological neural electrodes based on heterojunctions of other materials; in AlGaN / GaN ISHFET, a two-dimensional electron gas structure with high mobility and high concentration is formed due to the spontaneous polarization and piezoelectric polarization of AlGaN and GaN, and AlGaN has better biocompatibility than metal and silicon-based materials compared with GaN materials, and can perform signal acquisition for a longer period of time.

[0157] AlGaN / GaN ISHFETs inherently possess low background noise and low gate input noise due to the high sensitivity of the two-dimensional electron gas and the distribution of the device surface states.

[0158] Furthermore, by introducing near-end and far-end AlGaN / GaN REHFETs as differential pairs, the influence of environmental noise and device background noise can be reduced, thereby further improving the signal-to-noise ratio of AlGaN / GaN ISHFETs.

[0159] The integrated bio-neural electrode based on AlGaN / GaN ISHFET integrates the first microelectrode at intervals in the AlGaN / GaN ISHFET array, which increases the signal detection channel and improves the spatial resolution of signal acquisition.

[0160] Furthermore, adding a second microelectrode as a differential electrode can reduce the influence of environmental noise and device background noise, thereby improving the signal-to-noise ratio of the first microelectrode.

[0161] This invention also designs an ISHFET recessed gate to adjust the operating point of the device, which is beneficial to reducing the device size; by sharing the source leads of AlGaN / GaN ISHFET, the wiring is optimized, which can further reduce the device size, and the microelectrode can be fabricated on the GaN buffer layer simultaneously with the ISHFET leads and ISHFET pads, reducing the number of process steps; therefore, the integrated biological neural electrode proposed in this invention is also a small-sized implantable neural electrode.

[0162] In addition, the present invention introduces a metal shielding layer, which can further reduce the radiation interference of electric fields and electromagnetic waves. Furthermore, this application also improves the signal-to-noise ratio of signal acquisition and the stability of device use through the overall device structure design, including the axial parallel wiring of ISHFET leads and pads, microelectrode leads and pads, the equidistant one-to-one arrangement of ISHFET array and microelectrodes, and the use of an insulating passivation layer to isolate and protect the ISHFET part, microelectrode part and metal shielding layer part.

[0163] Therefore, the integrated bio-neural electrode proposed in this invention achieves rapid and stable acquisition of bio-neural signals, while also acquiring bio-neural signals at high resolution and greatly improving the signal-to-noise ratio of the acquired signals, thus ensuring high-quality signal acquisition.

[0164] This invention overcomes the limitations of existing technologies and significantly improves the efficiency, accuracy, and quality of biological neural signal acquisition, and is expected to promote the further development of the field of neuroscience.

[0165] See Figure 23 The present invention also proposes the following specific embodiments for fabricating integrated bio-neural electrodes based on AlGaN / GaN ISHFET.

[0166] Example 1

[0167] See Figure 1 Preparation of AlGaN / GaN ISHFET epitaxial wafers: GaN buffer layer 21, AlN insertion layer 22 and AlGaN barrier layer 23 are sequentially deposited on a Sapphire (Al2O3) substrate.

[0168] See Figure 2 Fabrication of AlGaN / GaN ISHFET: The AlGaN / GaN ISHFET epitaxial wafer is etched to the GaN buffer layer 21 through photolithography and dry etching processes under the conditions of Cl2 and BCl3 gas environment to form multiple spaced AlGaN / GaN ISHFET mesa, with an etching depth of about 200nm.

[0169] See Figure 2 Source / drain electrodes 24 are prepared by photolithography and electron beam evaporation in a high vacuum environment to deposit Ti / Al / Ni / Au metal thin films, and then patterning the Ti / Al / Ni / Au metal thin films using a lift-off process to obtain source / drain electrodes disposed on the AlGaN barrier layer. The thickness parameters of the Ti / Al / Ni / Au metal thin films are 150 / 800 / 200 / 600 nm.

[0170] Rapid thermal annealing is performed on the device to ensure good ohmic contact between the metal thin film at the source and drain and the AlGaN barrier layer.

[0171] Etching the recessed gate of an ISHFET: The surface of the AlGaN barrier layer is shallowly etched with a recessed gate through photolithography and photoelectrochemical oxidation processes under ultraviolet light irradiation and deionized water environment.

[0172] The reason for performing shallow etching of the gate in a deionized aqueous solution environment is that the etching rate is slower in this environment, which makes it easier to control the etching depth of the gate.

[0173] See Figure 3 ISHFET leads 31 and ISHFET pads 32 are prepared by depositing a Ti / Au (15 / 100nm) seed layer in a high vacuum environment through photolithography and electron beam evaporation processes, electroplating a thick gold film using secondary photolithography and electroplating processes, and patterning the thick gold film using a lift-off process.

[0174] See Figure 4 The first insulating passivation layer 4 is prepared by photolithography and plasma-enhanced chemical vapor deposition in a gas environment of SiH4 and N2O, high vacuum and 350℃. The insulating passivation layer is patterned with buffer oxide etchant using wet etching process to prepare ISHFET gate window W1 and ISHFET pad window W2.

[0175] See Figure 5 Microelectrode 51, microelectrode lead 52 and microelectrode pad 53 are prepared by depositing a Ti / Au (15 / 100nm) seed layer in a high vacuum environment through photolithography and electron beam evaporation process, electroplating a thick gold film using secondary photolithography and electroplating process, and patterning the thick gold film using a lift-off process.

[0176] The microelectrode includes a first microelectrode 51 and a second microelectrode 51'.

[0177] See Figure 6 The second insulating passivation layer 6 is prepared by photolithography and plasma-enhanced chemical vapor deposition in a SiH4 and N2O gas environment, high vacuum and 350℃ high temperature environment. The insulating passivation layer is then patterned using a dry etching process to prepare the ISHFET gate window W1, ISHFET pad window W2, microelectrode window W3 and microelectrode pad window W4.

[0178] See Figure 7 7. Preparation of metal shielding layer: A metal thin film is prepared in a high vacuum environment by photolithography and electron beam evaporation process to obtain a metal shielding layer; and the metal shielding layer is patterned by a lift-off process to prepare each window corresponding to the first insulating passivation layer and the second insulating passivation layer.

[0179] See Figure 8 Preparation of the third insulating passivation layer 8: A silicon dioxide passivation layer is prepared in a high vacuum and 350°C environment with SiH4 and N2O gas environment by photolithography and plasma-enhanced chemical vapor deposition process to obtain the third insulating passivation layer. The third insulating passivation layer is then patterned using a dry etching process to prepare the metal shielding layer grounding window and other windows corresponding to the metal shielding layer.

[0180] The side view, three-dimensional structure diagram, and top view of the integrated bio-neural electrode prepared in Example 1 after each layer was peeled off are shown below. Figure 9 , Figure 10 and Figure 11 As shown.

[0181] Example 2

[0182] See Figure 12 Preparation of AlGaN / GaN ISHFET epitaxial wafers: GaN buffer layer 21, AlN insertion layer 22 and AlGaN barrier layer 23 are sequentially deposited on a Sapphire (Al2O3) substrate.

[0183] Fabrication of AlGaN / GaN ISHFET and AlGaN / GaN REHFET: The AlGaN / GaN ISHFET epitaxial wafer is etched to the GaN buffer layer 21 under the conditions of Cl2 and BCl3 gas environment by photolithography and dry etching process to form multiple spaced AlGaN / GaN ISHFET mesa (including AlGaN / GaN REHFET mesa for differential), with an etching depth of about 200nm.

[0184] See Figure 13 Source / drain electrodes 24 are prepared by photolithography and electron beam evaporation in a high vacuum environment to deposit Ti / Al / Ni / Au metal thin films, and then patterning the Ti / Al / Ni / Au metal thin films using a lift-off process to obtain source / drain electrodes disposed on the AlGaN barrier layer. The thickness parameters of the Ti / Al / Ni / Au metal thin films are 150 / 800 / 200 / 600 nm.

[0185] Rapid thermal annealing is performed on the device to ensure good ohmic contact between the metal thin film at the source and drain and the AlGaN barrier layer.

[0186] See Figure 14 and Figure 15 Etching the ISHFET recessed gate B: Shallow etching of the AlGaN barrier layer surface is performed by photolithography and photoelectrochemical oxidation processes under ultraviolet light irradiation and deionized water environment.

[0187] The reason for performing shallow etching of the gate in a deionized aqueous solution environment is that the etching rate is slower in this environment, which makes it easier to control the etching depth of the gate.

[0188] See Figure 16 Fabricate ISHFET lead 31 and ISHFET pad 32 (not shown in the figure, please refer to the reference). Figure 21 ), microelectrode, microelectrode lead 52 and microelectrode pad 53 (not shown in the figure, please refer to the reference). Figure 21): A Ti / Au (15 / 100nm) seed layer is deposited in a high vacuum environment by photolithography and electron beam evaporation. A thick gold film is then electroplated using secondary photolithography and electroplating. Finally, the thick gold film is patterned using a lift-off process.

[0189] ISHFET lead 31 includes ISHFET source lead 31-1 and ISHFET drain lead 31-2, and the ISHFET source and ISHFET share a single ISHFET source lead.

[0190] The microelectrode includes a first microelectrode 51 and a second microelectrode 51' disposed adjacent to the first microelectrode 51.

[0191] See Figure 17 and Figure 22 The first insulating passivation layer 4 is prepared by photolithography and plasma-enhanced chemical vapor deposition in a gas environment of SiH4 and N2O, high vacuum and 350℃. The insulating passivation layer is patterned with buffer oxide etchant using a wet etching process to prepare ISHFET gate window W1, ISHFET pad window W2, microelectrode window W3, differential microelectrode solution contact window W6 and microelectrode pad window W4.

[0192] The first insulating passivation layer 4 on the first microelectrode 51 has a microelectrode window W3, while the second microelectrode 51' does not have a corresponding window. A differential microelectrode solution contact window W6 of a certain length is provided at the microelectrode lead connected to the second microelectrode 51'.

[0193] See Figure 18 Preparation of metal shielding layer 7: A metal thin film is prepared in a high vacuum environment by photolithography and electron beam evaporation to obtain a metal shielding layer; and the metal shielding layer is patterned by a lift-off process to prepare metal shielding layer windows W7 that correspond to each window of the first insulating passivation layer.

[0194] See Figure 19 and Figure 22 Preparation of the third insulating passivation layer 8: A silicon dioxide passivation layer is prepared in a high vacuum and 350°C environment with SiH4 and N2O gas environment by photolithography and plasma-enhanced chemical vapor deposition process to obtain the third insulating passivation layer. The third insulating passivation layer is then patterned using a dry etching process to prepare the metal shielding layer grounding window W5, as well as other windows corresponding to the metal shielding layer.

[0195] The side view, three-dimensional structure diagram, and top view of the integrated bio-neural electrode prepared in Example 2 after each layer was peeled off are shown below. Figure 20 , Figure 21 and Figure 22 As shown.

[0196] It should be understood that the above specific embodiments are not intended to limit the present invention. Those skilled in the art can obtain more embodiments based on the above specific embodiments, according to actual application requirements and relevant research progress. These embodiments do not depart from the spirit and scope of the present invention. For example, other heterojunctions forming two-dimensional electron gases can be used instead of AlGaN / GaN, such as AlGaAs / InGaAs / GaAs, SiC / Si, etc.; suitable ISHFETs, the number of microelectrodes, and their arrangement can also be selected; the various preparation steps are not necessarily performed in a specific order, these steps can be performed in other orders, or different combinations of the steps can be made.

[0197] The present invention also proposes a neural signal detection device, which in some embodiments includes the integrated bio-neural electrode provided in the foregoing embodiments, and:

[0198] The back-end circuit is electrically connected to the integrated bio-neural electrode and is used to power the integrated bio-neural electrode and to receive and process the bio-neural signals collected by the integrated bio-neural electrode.

[0199] Computer equipment, electrically connected to back-end circuitry, is used to receive biological neural signals processed by the back-end circuitry and to perform computational analysis and visualization.

[0200] In these embodiments, the back-end circuit is electrically connected to the heterojunction ISHFET via ISHFET pads and to the first or second microelectrode via microelectrode pads. The change in the source-drain current of the ISHFET is the biological neural signal acquired by the ISHFET, and the electrical signal acquired by the microelectrode through electrochemical impedance spectroscopy is the biological neural signal acquired by the microelectrode.

[0201] The back-end circuitry primarily processes the acquired biological neural signals through amplification, filtering, and conversion. Specifically, this includes: amplifying the biological neural signals using a preamplifier; removing unwanted signal components such as high-frequency noise and low-frequency drift using a filter; and converting the amplified and filtered analog neural signals into digital signals using an analog-to-digital converter. Since the biological neural signals acquired by the heterojunction ISHFET are amplified signals through two-dimensional electron gas transconductance rather than the original weak signals, using the integrated biological neural electrode provided in the aforementioned embodiment can reduce the design complexity of this back-end circuitry.

[0202] The computer device is electrically connected to the back-end circuitry via a dedicated acquisition card, receiving the processed biological neural signals and storing them in a storage medium. Researchers can set acquisition parameters, such as sampling frequency and sampling time, through acquisition software. Furthermore, relevant computational analysis software is run on the computer device to perform various analyses on the acquired biological neural signals, including calculating parameters such as the amplitude, frequency, and latency of action potentials. Spectral analysis can also be performed to understand the energy distribution of neural signals at different frequencies; for example, the characteristic frequency components of a neurological disease attack can be identified by analyzing the spectral characteristics of the signal. In addition, the computer device includes a visualization unit to display the biological neural signals in intuitive graphical or image form, facilitating observation and understanding by researchers.

[0203] It is understandable that integrated biological neural electrodes are key components of neural signal detection devices. The neural signal detection devices can achieve the same technical effects as the integrated biological neural electrodes provided in the aforementioned embodiments, and will not be elaborated here.

[0204] The above-described embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application.

Claims

1. An integrated bio-neural electrode, comprising: The application relates to an integrated biological nerve electrode, which comprises the following parts: a substrate; a plurality of first field effect transistors arranged at intervals on the substrate, wherein the first field effect transistors comprise a heterojunction and a source-drain electrode arranged on the heterojunction; the heterojunction comprises a GaN buffer layer, an AlN insertion layer and an AlGaN barrier layer arranged in sequence from bottom to top; a two-dimensional electron gas is formed in the GaN buffer layer close to the interface with the AlN insertion layer; the source-drain electrode comprises a source ohmic contact and a drain ohmic contact arranged at intervals, and the source ohmic contact and the drain ohmic contact are electrically connected with the two-dimensional electron gas; a first lead and a first pad arranged on the GaN buffer layer; the first lead comprises a first source lead and a first drain lead, and the first pad comprises a first source pad and a first drain pad; one end of the first source lead is electrically connected with the source ohmic contact, and the other end is electrically connected with the first source pad; one end of the first drain lead is electrically connected with the drain ohmic contact, and the other end is electrically connected with the first drain pad; a first insulating passivation layer covering the first field effect transistors and the first lead; the first insulating passivation layer is provided with a first gate window and a first pad window; the first gate window is arranged between the source ohmic contact and the drain ohmic contact, and the first pad window is arranged above the first pad; a plurality of microelectrodes arranged on the GaN buffer layer or the first insulating passivation layer and arranged at intervals with the first field effect transistors; a microelectrode lead and a microelectrode pad; the microelectrode lead is connected with the microelectrode and the microelectrode pad; when the microelectrode is arranged on the GaN buffer layer, the microelectrode lead and the microelectrode pad are arranged on the GaN buffer layer, the first insulating passivation layer is provided with a microelectrode window above the microelectrode and a microelectrode pad window above the microelectrode pad; when the microelectrode is arranged on the first insulating passivation layer, the microelectrode lead and the microelectrode pad are arranged on the first insulating passivation layer, the microelectrode and the microelectrode lead are covered with a second insulating passivation layer, the second insulating passivation layer is provided with a first gate window between the source ohmic contact and the drain ohmic contact, a first pad window above the first pad, a microelectrode window above the microelectrode and a microelectrode pad window above the microelectrode pad.

2. The integrated bio-neural electrode of claim 1, wherein, A recessed gate is etched on the AlGaN barrier layer.

3. The integrated bioelectrode of claim 1, wherein, The first lead is arranged in parallel along the longitudinal axis direction of the integrated biological nerve electrode.

4. The integrated bioelectrode of claim 3, wherein, The microelectrode lead is arranged in parallel along the longitudinal axis direction of the integrated biological nerve electrode.

5. The integrated bioelectrode of claim 3, wherein, The integrated biological nerve electrode comprises a first field effect transistor arranged on a test end, a second field effect transistor adjacent to the first field effect transistor and at least one second field effect transistor away from the test end; the second field effect transistor is used for differential and has the same material and structure as the first field effect transistor. The first insulating passivation layer is provided with a second gate window on the second field effect transistor away from the test end, and the second gate window is located between the source ohmic contact and the drain ohmic contact of the second field effect transistor.

6. The integrated bioelectrode of claim 4, wherein, The microelectrode comprises a first microelectrode and a second microelectrode, the first microelectrode is used for collecting biological signals, and the second microelectrode is used for differential; The insulating passivation layer on the first microelectrode and the second microelectrode is provided with a microelectrode window; or, any one of the second microelectrode and the first microelectrode is provided adjacent to each other, the insulating passivation layer on the first microelectrode is provided with a microelectrode window, the insulating passivation layer on the second microelectrode is not provided with a microelectrode window, and a differential microelectrode solution contact window is provided on the microelectrode lead connected to the second microelectrode.

7. The integrated bio-neural electrode of any of claims 3-6, wherein, Further comprising: A metal shielding layer and a third insulating passivation layer are stacked on the integrated biological neural electrode; the metal shielding layer and the third insulating passivation layer are provided with respective windows corresponding to the underlying insulating passivation layer, and the third insulating passivation layer is further provided with a metal shielding layer grounding window.

8. A method of fabricating an integrated bio-neural electrode, comprising: The method comprises the following steps: S1, preparing an AlGaN / GaN first field effect transistor epitaxial wafer: sequentially depositing a GaN buffer layer, an AlN insertion layer and an AlGaN barrier layer on a substrate; S2, preparing an AlGaN / GaN first field effect transistor: etching the AlGaN / GaN first field effect transistor epitaxial wafer to the GaN buffer layer under the condition that the gas environment is Cl2 and BCl3 through a photolithography and dry etching process, to form a plurality of spaced AlGaN / GaN first field effect transistors; S3, preparing a source-drain electrode: through photolithography and electron beam evaporation, Ti / Al / Ni / Au metal thin film is evaporated in a high vacuum environment, and the Ti / Al / Ni / Au metal thin film is patterned using a stripping process to obtain a source-drain electrode arranged on the AlGaN barrier layer; S4, rapidly thermally annealing the device prepared in step S3; S5, etching a recessed gate: through photolithography and photoelectrochemical oxidation process, the surface of the AlGaN barrier layer is subjected to recessed gate shallow etching in the environment of ultraviolet lamp irradiation and deionized water solution; S6, preparing a first lead, a first pad, a microelectrode, a microelectrode lead and a microelectrode pad, and then depositing a first insulating passivation layer; or, preparing a first lead, a first pad, depositing a first insulating passivation layer, preparing a microelectrode, a microelectrode lead and a microelectrode pad on the first insulating passivation layer, and then depositing a second insulating passivation layer; One or more of the first lead, the first pad, the microelectrode, the microelectrode lead and the microelectrode pad are prepared by the following method: Ti / Au seed layer is evaporated in a high vacuum environment through photolithography and electron beam evaporation process, thick gold film is electroplated by using secondary lithography and electroplating process, and the thick gold film is patterned using a stripping process. The first insulating passivation layer and / or the second insulating passivation layer are prepared by the following method: a silicon dioxide isolation layer is prepared by a photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, a high vacuum and a high temperature environment of 350 DEG C, to obtain an insulating passivation layer; a wet etching process is used to pattern the insulating passivation layer with a buffer oxide etching solution, to obtain one or more of the first gate window, the first pad window, the microelectrode window, the microelectrode pad window and the differential microelectrode solution contact window; S7, preparing a metal shielding layer: a metal thin film is prepared by a photolithography and electron beam evaporation process in a high vacuum environment, to obtain a metal shielding layer; and a stripping process is used to pattern the metal shielding layer, to obtain each window corresponding to the underlying insulating passivation layer; S8, preparing a third insulating passivation layer: a silicon dioxide passivation layer is prepared by a photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, a high vacuum and a high temperature environment of 350 DEG C, to obtain a third insulating passivation layer, and a dry etching process is used to pattern the third insulating passivation layer, to obtain a metal shielding layer grounding window and each other window corresponding to the metal shielding layer.

9. A neural signal detection device, characterized by, The device comprises the integrated biological neural electrode of any one of claims 1-7 or the integrated biological neural electrode prepared by the preparation method of claim 8, and: a backend circuit electrically connected to the integrated biological neural electrode, for powering the integrated biological neural electrode, and receiving and processing biological neural signals collected by the integrated biological neural electrode; a computer device electrically connected to the backend circuit, for receiving biological neural signals processed by the backend circuit, and performing calculation analysis and visual display.

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