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

Abstract

The invention discloses an integrated biological neural electrode, a preparation method and neural signal detection equipment, and is applied to the technical field of neural signal detection. The integrated biological neural electrode comprises a substrate and a heterojunction ISHFET, the heterojunction ISHFET comprises a heterojunction and a source and drain electrode arranged on the heterojunction, two-dimensional electron gas is formed in the heterojunction, the source and drain electrode comprises a source ohmic contact and a drain ohmic contact which are arranged at an interval, and the source ohmic contact and the drain ohmic contact are electrically connected with the two-dimensional electron gas; the neural signal on the surface of the heterojunction ISHFET gate regulates and controls the conductivity of the two-dimensional electron gas, so that the source and drain current output of the heterojunction ISHFET is changed, and the detection of the biological neural signal is realized. According to the integrated biological neural electrode provided by the invention, the transconductance amplification effect of the two-dimensional electron gas is utilized to perform biological neural signal detection, and differential processing can be performed through the heterojunction REHFET, so that the collection efficiency and the collection quality of the biological neural signal are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of neural signal detection, and in particular to an integrated biological neural electrode, a preparation method and a neural signal detection device. Background Art

[0002] Neuroelectrophysiology is one of the important methods for detecting brain neural electrical signals. It is crucial to gain a deeper understanding of the functions of the nervous system in normal and pathological states. These technologies provide a basis for early diagnosis, effective intervention and treatment of neurological diseases. However, current neuroelectrophysiology still faces several problems and challenges, especially in terms of signal acquisition speed, stability and spatial resolution.

[0003] Existing neuroelectrophysiological technologies mainly rely on neural electrodes, which can be divided into passive and active types according to the signal detection method. Passive neural electrodes detect bioelectric signals through the electrochemical impedance spectroscopy of microelectrodes. Although their structure is simple, the signal acquisition speed is slow and they are easily interfered by 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 regulating the channel conductivity of field-effect transistors through bioelectric signals, but the acquisition speed is still slow, and the structure of this type of electrode is relatively complex and large in size, which limits its spatial resolution and application flexibility. Summary of the invention

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

[0005] The present invention provides an integrated biological neural electrode, comprising:

[0006] substrate;

[0007] A heterojunction ISHFET is provided on the substrate and comprises a heterojunction and a source-drain electrode provided on the heterojunction;

[0008] The heterojunction includes a buffer layer arranged on the substrate and a barrier layer arranged 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 electrode includes 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 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 in sequence 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 biological neural electrode further comprises:

[0012] An ISHFET lead and an ISHFET pad disposed on the GaN buffer layer, and a first insulating passivation layer covering the heterojunction ISHFET and the ISHFET lead;

[0013] The ISHFET leads are arranged in parallel along the longitudinal axis of the integrated biological neural electrode, and include an ISHFET source lead and an ISHFET drain lead;

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

[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 is provided with an ISHFET gate window and an ISHFET pad window.

[0017] Optionally, the integrated biological neural electrode comprises a plurality of the heterojunction ISHFETs arranged at intervals, and further comprises:

[0018] A plurality of microelectrodes spaced apart from the heterojunction ISHFET, the microelectrodes being connected to the microelectrode pads via microelectrode leads, the microelectrode leads being arranged parallel to the longitudinal axis of the integrated biological neural electrode;

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

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

[0021] Wherein, the first insulating passivation layer is provided with an ISHFET gate window on the heterojunction REHFET far away from the test end, and no ISHFET gate window is provided on the heterojunction REHFET adjacent to the heterojunction ISHFET;

[0022] The heterojunction REHFET is used for differential, 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, the first microelectrode is used for collecting biological signals, and the second microelectrode is used for differential;

[0024] The insulating passivation layers on the first microelectrode and the second microelectrode are both provided with microelectrode windows;

[0025] Alternatively, any of the second microelectrodes is arranged adjacent to the first microelectrode, 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 biological neural electrode further comprises: a metal shielding layer and a third insulating passivation layer stacked on the integrated biological neural electrode; the metal shielding layer and the third insulating passivation layer are provided with windows corresponding to the windows of the lower insulating passivation layer, and the third insulating passivation layer is also provided with a metal shielding layer grounding window. The present invention proposes a method for preparing an integrated biological neural electrode, comprising the following steps:

[0027] S1, preparing AlGaN / GaN ISHFET epitaxial wafer: depositing GaN buffer layer, AlN insertion layer and AlGaN barrier layer on the substrate in sequence;

[0028] S2, preparing AlGaN / GaN ISHFET: etching the AlGaN / GaN ISHFET epitaxial wafer to the GaN buffer layer in a gas environment of Cl2 and BCl3 by photolithography and dry etching process to form a plurality of spaced AlGaN / GaNISHFETs;

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

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

[0031] S5, etching ISHFET recessed gate: shallowly etching the recessed gate on the surface of the AlGaN barrier layer in an environment of ultraviolet light irradiation and deionized water solution by photolithography and photoelectrochemical oxidation process;

[0032] S6, preparing ISHFET leads, ISHFET pads, microelectrodes, microelectrode leads and microelectrode pads, and then depositing and covering a first insulating passivation layer; or, preparing ISHFET leads and ISHFET pads, depositing and covering a first insulating passivation layer, preparing microelectrodes, microelectrode leads and microelectrode pads on the first insulating passivation layer, and then depositing and covering a second insulating passivation layer;

[0033] Wherein, one or more of the ISHFET lead, the ISHFET pad, the microelectrode, the microelectrode lead and the microelectrode pad are prepared by the following method: evaporating a Ti / Au seed layer in a high vacuum environment by photolithography and electron beam evaporation process, electroplating a thick gold film by secondary photolithography and electroplating process, and patterning the thick gold film by 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 by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment to obtain an insulating passivation layer; a buffered oxide etching solution is used to pattern the insulating passivation layer by a wet etching process to prepare one or more of an ISHFET gate window, an ISHFET pad window, a microelectrode window, a microelectrode pad window and a differential microelectrode solution contact window;

[0035] S7, preparing a metal shielding layer: preparing a metal film in a high vacuum environment by photolithography and electron beam evaporation process to obtain a metal shielding layer; and patterning the metal shielding layer by a lift-off process to prepare windows corresponding to the lower insulating passivation layer;

[0036] S8, preparing a third insulating passivation layer: preparing a silicon dioxide passivation layer by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment to obtain a third insulating passivation layer, and patterning the third insulating passivation layer by a dry etching process to prepare a metal shielding layer grounding window and other windows corresponding to the metal shielding layer.

[0037] The present invention also provides a neural signal detection device, characterized in that the device comprises the above-mentioned integrated biological neural electrode or the integrated biological neural electrode prepared by the above preparation method, and:

[0038] A back-end circuit, electrically connected to the integrated biological neural electrode, for supplying power to the integrated biological neural electrode and processing biological neural signals collected by the integrated biological neural electrode;

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

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] A heterojunction ISHFET (such as AlGaN / GaNISHFET) with a high-mobility and high-concentration two-dimensional electron gas is used to actively detect biological neural signals. The two-dimensional electron gas structure of this layer is very sensitive to gate voltage control. Since the electron mobility in the two-dimensional electron gas structure is an order of magnitude higher than the charge mobility on the gate surface, the slight fluctuation of the charge on the gate surface of the heterojunction ISHFET can be quickly reflected in the conductivity change of the two-dimensional electron gas and amplified, and then manifested as a change in source-drain current, that is, the detection of biological neural signals. Therefore, the use of this heterojunction ISHFET to detect biological neural signals has the advantages of being label-free, fast, and stable, which improves the collection efficiency and quality of biological neural signals. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0043] Figure 1 A three-dimensional structural diagram of the substrate and epitaxial wafer of some embodiments of the integrated biological neural electrode of the present invention;

[0044] Figure 2 This is a three-dimensional structure diagram of an AlGaN / GaN ISHFET after the mesa device isolation and the preparation of the source-drain electrode ohmic contact in some embodiments of the integrated biological neural electrode of the present invention;

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

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

[0047] Figure 5 It is a three-dimensional structural diagram of some embodiments of the integrated biological neural electrode of the present invention after preparing microelectrodes, microelectrode leads and microelectrode pads;

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

[0049] Figure 7 Schematic diagram of the three-dimensional structure of some embodiments of the integrated biological neural electrode of the present invention after the metal shielding layer is prepared;

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

[0051] Fig. 9 It is a side view of some embodiments of the integrated biological neural electrode of the present invention after each layer is peeled off;

[0052] Fig.10 It is a three-dimensional structural diagram of some embodiments of the integrated biological neural electrode of the present invention after each layer is peeled off;

[0053] Fig.11 The top views of some embodiments of the integrated biological neural electrode of the present invention are shown;

[0054] Fig.12 Schematic diagram of the three-dimensional structure of some other embodiments of the integrated biological neural electrode of the present invention after the table device is isolated;

[0055] Fig.13 The three-dimensional structure diagram of AlGaN / GaN ISHFET after preparing the source-drain electrode ohmic contact of some other embodiments of the integrated biological neural electrode of the present invention;

[0056] Fig.14 Schematic diagram of the three-dimensional structure of some other embodiments of the integrated biological neural electrode of the present invention after preparing the ISHFET recessed gate;

[0057] Fig.15 A magnified view of the details of the ISHFET recessed gate prepared for some other embodiments of the integrated biological neural electrode of the present invention;

[0058] Fig.16 Schematic diagram of the three-dimensional structure after preparing ISHFET leads, ISHFET pads, microelectrodes, microelectrode leads, and microelectrode pads for other embodiments of the integrated biological neural electrode of the present invention;

[0059] Fig.17 A three-dimensional structural diagram of some other embodiments of the integrated biological neural electrode of the present invention after the first insulating passivation layer is prepared;

[0060] Fig.18 A three-dimensional structural diagram of some other embodiments of the integrated biological neural electrode of the present invention after the metal shielding layer is prepared;

[0061] Fig.19 A three-dimensional structural diagram of some other embodiments of the integrated biological neural electrode of the present invention after preparing the third insulating passivation layer;

[0062] Fig. 20 It is a side view of other embodiments of the integrated biological neural electrode of the present invention after each layer is peeled off;

[0063] Fig.21 It is a three-dimensional structural diagram of other embodiments of the integrated biological neural electrode of the present invention after each layer is peeled off;

[0064] Fig. 22 1. The top views of some other embodiments of the integrated biological neural electrode of the present invention;

[0065] Fig.23 It is a flowchart of the method for preparing the integrated biological neural electrode of the present invention.

[0066] Description of reference numerals:

[0067] 1. Substrate; 2. AlGaN / GaN ISHFET; 2', proximal AlGaN / GaN REHFET; 2'', distal AlGaN / GaNREHFET; 21, GaN buffer layer; 22, AlN insertion layer; 23, AlGaN barrier layer; 24, source and 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 grounding window; W6, differential microelectrode solution contact window W6; W7, metal shielding layer window; B, ISHFET recessed gate; L1~L7: layer number label after each layer is peeled off. DETAILED DESCRIPTION

[0069] In order to make the purpose, features and advantages of the present invention more obvious and easy to understand, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the embodiments described below are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

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

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

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

[0073] ISHFET: Ion-sensitive high electron mobility field effect transistor. 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".

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

[0075] REHFET: Reference high mobility field effect transistor (in the embodiment of the present invention, the material and structure of REHFET are the same as those of ISHFET. In order to distinguish it from the working ISHFET used for detecting biological neural signals, REHFET is named).

[0076] Current neuroelectrophysiology technology still faces several problems and challenges, especially in terms of signal acquisition speed, stability and spatial resolution. Existing neuroelectrophysiology technology mainly relies on neural electrodes, which can be divided into two categories according to the area of ​​use: in vitro non-invasive (such as electroencephalogram (EEG)) and in vivo invasive (such as electrocorticogram (ECoG) and multi-channel electrodes (MEA). According to the signal detection method, neural electrodes can be divided into passive and active types.

[0077] Among them, passive neural electrodes use a microelectrode structure made of metal or glass materials to collect biological neural signals through electrochemical impedance spectroscopy. Although its structure is simple, the quality of signal acquisition depends on the interface impedance. When the microelectrode interface impedance is low, no signal can be detected, and when the impedance is high, it will be easily interfered by noise. The signal acquisition speed is slow and it is easily interfered by electric fields and electromagnetic radiation, resulting in poor signal stability. In addition, the biocompatibility of metal materials also affects its use effect.

[0078] Active neural electrodes usually use field effect transistors such as silicon-based field effect transistors (ISFETs), which control channel conductance by changing the potential on the gate, causing the source-drain current to change, thereby detecting neural signals. Active detection has advantages in signal acquisition stability, signal-to-noise ratio, and acquisition speed, and the signal acquisition quality depends on the electrical characteristics of the device. However, silicon-based field effect transistors still have a slow acquisition speed, a complex structure, and a large size, which limits their spatial resolution and application flexibility.

[0079] Currently, researchers have tried to use different materials to prepare field-effect transistors with excellent electrical properties, aiming to collect neural signals more accurately, faster and more stably, but the results have been mediocre. Therefore, how to develop a neural electrode that can provide high-speed and stable signal acquisition while meeting the requirements of high spatial resolution is an important direction of current research.

[0080] The applicant has found through intensive research that heterojunction ion-sensitive high electron mobility field effect transistors (hereinafter referred to as heterojunction ISHFETs) such as AlGaN / GaN ISHFETs have 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, fast, 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 has improved the collection of biological neural signals by using the AlGaN / GaN ISHFET structure after long-term research and development, hoping to promote further development in the field of neuroscience.

[0081] In view of the problems existing in current neural electrodes, the present invention proposes an integrated biological neural electrode by utilizing the unique advantages of heterojunction ISHFET.

[0082] In some embodiments, the integrated biological neural electrode proposed by the present invention includes:

[0083] substrate;

[0084] A heterojunction ISHFET is provided on a substrate, comprising a heterojunction and a source-drain electrode provided on the heterojunction; the heterojunction comprises a buffer layer provided on the substrate and a barrier layer provided on the buffer layer; a two-dimensional electron gas is formed in the buffer layer near an interface with the barrier layer; the source-drain electrode comprises a source ohmic contact and a drain ohmic contact provided at intervals, and the source ohmic contact and the drain ohmic contact are electrically connected to the two-dimensional electron gas;

[0085] Among them, when the integrated biological neural electrode is working, the gate of the heterojunction ISHFET is the electrolyte solution on the upper part of the gate region. The electrolyte solution regulates the conductivity of the two-dimensional electron gas through the change of the surface charge of the gate, thereby changing the source-drain current output of the heterojunction ISHFET.

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

[0087] Among them, 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 energies, 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 to form 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 energy band structure, causing electrons to accumulate in a specific area to form a high-concentration two-dimensional electron gas; in other cases, valence band discontinuity and band bending can also form a two-dimensional electron gas.

[0088] In these embodiments, a heterojunction ISHFET is used to detect biological neural signals of the object to be tested. The gate of the ISHFET structure is composed of an electrolyte solution on the upper part 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, and any positive ion or negative ion adsorbed on the surface of the gate region will correspond to the gain or disappearance of an electron in the channel two-dimensional electron gas structure. Since the electron mobility in the two-dimensional electron gas structure is an order of magnitude higher than the charge mobility on the surface of the gate region, the slight fluctuation of the charge on the surface of the sensing area of ​​the ISHFET device can be quickly manifested in the conductivity change of the two-dimensional electron gas and "amplified", and then manifested as a change in the source-drain current.

[0089] In these embodiments, the object to be detected is a biological neuron or neural tissue.

[0090] In the specific application scenarios of these embodiments, an integrated biological 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 is stimulated and the neuron generates an action potential (mainly manifested as an influx of sodium ions and an outflow of potassium ions), it will cause a change in the potential in the electrolyte solution between the heterojunction ISHFET and the neuron. The change in this potential (i.e., the extracellular potential of the neuron) will quickly and sensitively regulate the conductivity of the two-dimensional electron gas structure, causing the source-drain current of the heterojunction ISHFET to change, which is the detection of biological neural signals.

[0091] It can be seen that the change of the source-drain current of the heterojunction ISHFET reflects the change of the biological neuron neural signal. The extracellular potential V of the neuron can be calculated by the following formula: G Size:

[0092]

[0093] In the formula, I ds is the source-drain current, μ n is the electron mobility of the two-dimensional electron gas, C ox is the capacitance from 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, V G is the extracellular potential (neural signal), V TH is the threshold voltage of heterojunction ISHFET, V DS is the source-drain voltage.

[0094] From the above, it can be seen that the embodiment of the present invention uses a heterojunction ISHFET with a high-mobility and high-concentration two-dimensional electron gas to actively detect biological neural signals. This layer of two-dimensional electron gas structure is very sensitive to gate voltage control. Since the electron mobility in the two-dimensional electron gas structure is an order of magnitude higher than the charge mobility on the gate surface, the slight fluctuation of the surface charge in the heterojunction ISHFET sensing area can be quickly manifested in the conductivity change of the two-dimensional electron gas and amplified, and then manifested as a change in source-drain current, that is, the detection of biological neural signals.

[0095] Compared with the neural electrodes in existing electrophysiological technologies, such as passive neural electrodes and active silicon-based neural electrodes, the heterojunction ISHFET of the present application can detect biological neural signals more quickly and stably; the biological neural signals collected by the heterojunction ISHFET are signals after transconductance amplification, rather than the original weak signals, so it can also reduce the difficulty of back-end circuit design.

[0096] Compared with the metal gate of the HEMT structure, the "solution gate" of the ISHFET is in direct contact with the solution to be tested, and can directly sense the changes in ion concentration in the solution. The detection of changes in ion concentration is more rapid and sensitive. The metal gate of the HEMT usually does not have the characteristics of direct good compatibility with the biological system and is difficult to be directly applied to detection in vivo. The ISHFET can modify the surface of the barrier layer by selecting suitable 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 Figure 1-Figure 22 In some specific embodiments, the heterojunction ISHFET is an AlGaN / GaN ISHFET (reference numeral 2 ), wherein the heterojunction is an AlGaN / GaN heterojunction.

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

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

[0101] In these embodiments, both AlGaN and GaN materials belong to the wurtzite structure, and their low symmetry makes AlGaN and GaN have the characteristics of spontaneous polarization. When AlGaN and GaN come into contact, the lattice is deformed by the external stress and piezoelectric polarization occurs. The spontaneous polarization and piezoelectric polarization will simultaneously form a layer of high-mobility and high-concentration two-dimensional electron gas structure on the contact surface of AlGaN / GaN close to the GaN side. This layer of two-dimensional electron gas structure can be very sensitively controlled by the gate voltage. Any positive or negative ion adsorbed on the surface of the gate region will correspond to the gain or disappearance of an electron in the channel two-dimensional electron gas structure.

[0102] Among them, the AlN insertion layer is used to reduce the interface defects between GaN and AlGaN and improve the 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 optimize the threshold voltage and conductivity of the device.

[0103] In these embodiments, GaN and AlGaN materials have superior biocompatibility compared to metal and silicon-based materials, and can perform in vivo biological neural signal acquisition work for a longer period of time.

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

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

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

[0107] See also Figure 1-Figure 22 Based on the above AlGaN / GaN ISHFET embodiment, in some specific embodiments, the integrated biological neural electrode further includes:

[0108] An ISHFET lead 31 and an ISHFET pad 32 disposed on the GaN buffer layer 21, and a first insulating passivation layer covering the AlGaN / GaNISHFET and the ISHFET lead 31;

[0109] The ISHFET leads 31 are arranged in parallel along the longitudinal direction of the integrated biological neural electrode, and include an ISHFET source lead 31 - 1 and an ISHFET drain lead 31 - 2 ;

[0110] The ISHFET pads 32 include an ISHFET source pad and an 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 is provided with an ISHFET gate window W1 and an ISHFET pad window W2.

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

[0114] In these embodiments, the AlGaN / GaN ISHFET is connected to the back-end circuit through the source-drain electrode 24, the ISHFET lead 31 and the ISHFET pad 32; wherein the back-end circuit is used to power the biological neural electrode and receive and process the biological neural signal collected by the biological neural electrode.

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

[0116] In these embodiments, the first insulating passivation layer 4 covers the AlGaN / GaN ISHFET and the ISHFET lead 31, and is used to prevent unexpected electrical contact between the conductive material and the surrounding tissue, ensuring that electrical signals are exchanged only through the designed contact points, while ensuring the functional independence of each ISHFET, avoiding electrical signal crosstalk, and ensuring a high signal-to-noise ratio in signal acquisition; in addition, the first insulating passivation layer can protect the biological neural electrode from being corroded by corrosive substances in the object to be tested, maintain the long-term stability of the device performance, and reduce the release of harmful substances produced by the dissolution or corrosion of the conductive material into the organism, thereby ensuring biocompatibility and safety.

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

[0118] In these embodiments, the AlGaN / GaN ISHFET contacts the electrolyte solution of the object to be tested 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. Accordingly, the exposed portion of the AlGaN barrier layer 23 is the ISHFET gate open region. The ISHFET gate open region serves as a neural signal collection area, and its shape and area can be set according to actual signal collection requirements and process conditions; the first insulating passivation layer is provided with 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 also Fig.14 and Fig.15 Based on the above-mentioned AlGaN / GaN ISHFET embodiments, in some other embodiments, an ISHFET recessed gate B is formed on the surface of the AlGaN barrier layer 23 at the ISHFET gate region by shallow etching.

[0120] In these embodiments, the ISHFET recessed gate reduces the polarization effect of the AlGaN / GaN heterojunction by thinning the thickness of the AlGaN barrier layer, thereby reducing the concentration of the two-dimensional electron gas and shifting the threshold voltage positively, so that the AlGaN / GaN ISHFET has a maximum transconductance point near Vg=0V in the absence of a metal gate or a reference electrode to adjust the device operating point, thereby improving the device sensitivity and reducing the device size for easy integration.

[0121] In addition, the signal-to-noise ratio of signal acquisition can be improved to a certain extent by adjusting the shape of the ISHFET recessed gate.

[0122] It should be noted that the ISHFET recessed gate is a preferred embodiment of the present invention and is not a limitation of the present invention. In other embodiments, an AlGaN / GaN ISHFET with a non-recessed gate structure may also be used to collect neural signals, for example: using a fluorine ion implantation process, adding a P-type GaN cap, introducing reference electrode control, using metal gate control, etc.

[0123] Based on the above AlGaN / GaN ISHFET embodiments, see Figure 1-Figure 22 In order to further improve the spatial resolution of the integrated biological neural electrode signal acquisition, in some embodiments, the integrated biological neural electrode includes a plurality of spaced AlGaN / GaN ISHFETs, and further includes:

[0124] A plurality of microelectrodes (including a first microelectrode 51 and a second microelectrode 51') are spaced apart from the AlGaN / GaN ISHFET, and the microelectrodes are connected to the microelectrode pad 53 via microelectrode leads 52, which are arranged parallel to the longitudinal axis of the integrated biological neural 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 neuron electrolyte solution. When the neuron is stimulated to generate an action potential, the impedance between the microelectrode and the electrolyte solution changes, and the bioneural signal can be obtained based on the electrochemical impedance spectroscopy.

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

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

[0128] See also Fig.16 In some other embodiments, all AlGaN / GaN ISHFETs are connected to the ISHFET pad 32 via an ISHFET source lead 31 - 1 , i.e., the sources of all AlGaN / GaN ISHFETs are in the same line, so as to reduce the number of ISHFET leads and the occupied area, so that the microelectrodes can be arranged on the GaN buffer layer 21 .

[0129] In the implementation of the AlGaN / GaN ISHFET source co-linear implementation, the microelectrode, microelectrode lead 52 and microelectrode pad 53 can be prepared together with the ISHFET lead 31 and ISHFET pad 32 on the GaN buffer layer 21 to reduce the number of process steps; accordingly, the first insulating passivation layer is also provided with a microelectrode window W3 and a microelectrode pad window W4; the microelectrode, microelectrode lead and microelectrode pad, as well as the ISHFET lead and ISHFET pad can be made of Ti / Au metal film.

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

[0131] See also Figure 12-Figure 22 In some embodiments, the integrated biological neural 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., a proximal AlGaN / GaN REHFET, reference numeral 2'), and at least one AlGaN / GaN REHFET far from the test end (i.e., a distal AlGaN / GaN REHFET, reference numeral 2'').

[0132] Among them, AlGaN / GaN REHFET is used for differential, and its material 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 does not have an ISHFET gate window on the near-end AlGaN / GaN REHFET.

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

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

[0136] The gate window of the remote AlGaN / GaN REHFET used for differential is opened after the first insulating passivation layer is prepared, but the arrangement position of the remote AlGaN / GaN REHFET needs to be set outside the neural discharge area, so that only environmental noise is collected.

[0137] In a preferred embodiment, after preparing the first insulating passivation layer, a gate window of a proximal AlGaN / GaN REHFET for differential is opened, and the surface of the AlGaN barrier layer in the gate region is modified with a material that is insensitive to neural signals, remains sensitive to environmental signals, and does not change the electrical characteristics of the original device, so as to achieve a better differential effect; the specific modified material can be reasonably selected according to the actual test conditions.

[0138] In these embodiments, by subtracting the signal collected by the AlGaN / GaN ISHFET from the signal collected by the AlGaN / GaN REHFET and performing differentiation, a purer neural signal can be obtained, thereby improving the signal-to-noise ratio of signal collection.

[0139] Based on the aforementioned AlGaN / GaN ISHFET embodiment with microelectrodes, in order to further improve the signal-to-noise ratio of the integrated biological neural electrode, refer to Figure 1-Figure 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 differentiation; that is, the in vivo biological environmental noise collected by the second microelectrode 51' is normalized and then subtracted from the biological neural signal collected by the first microelectrode 51 to achieve the differential function.

[0140] See also Figure 5-Figure 11In some embodiments, the second microelectrode 51' is arranged outside the neural discharge area for collecting environmental noise, and the insulating passivation layer on the second microelectrode 51' is provided with a microelectrode window W3 (for an embodiment in which the microelectrode is arranged on the GaN buffer layer, the insulating passivation layer there is the first insulating passivation layer; for an embodiment in which the microelectrode is arranged 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 ′ may 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 be used as a stimulation electrode to electrically stimulate biological neurons through power supplied by a back-end circuit.

[0143] See also Figure 16-Figure 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, and a differential microelectrode solution contact window is provided on the microelectrode lead 52 connected to the second microelectrode 51'.

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

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

[0146] Based on the above AlGaN / GaN ISHFET embodiments, see Figure 1-Figure 22 In order to effectively reduce electrically induced noise, in some embodiments, the integrated biological neural electrode further comprises:

[0147] The metal shielding layer 7 and the third insulating layer 8 are stacked on the integrated biological neural electrode; the metal shielding layer 7 and the third insulating layer 8 are provided with windows corresponding to the windows of the lower insulating passivation layer.

[0148] Specifically, for an embodiment in which the microelectrode is disposed on the GaN buffer layer, the metal shielding layer is disposed on the first insulating passivation layer; for an embodiment in which 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 corresponding one to one with the first insulating passivation layer or the second insulating passivation layer.

[0150] In some other embodiments, see Fig.18 The metal shielding layer can directly be provided with a metal shielding layer window W7 with a larger area, and the metal shielding layer window W7 includes one or more lower layer windows within its range.

[0151] The third insulating passivation layer is used to prevent unexpected electrical contact between the conductive material and the surrounding tissue, ensuring a high signal-to-noise ratio in signal acquisition. It can also protect the biological neural electrodes from being corroded by corrosive substances in the object to be tested, maintain the long-term stability of the device performance, and reduce the release of harmful substances produced by the dissolution or corrosion of the conductive material into the body, thereby ensuring biocompatibility and safety.

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

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

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

[0155] It can be seen from the above embodiments that the present invention designs an integrated bio-neural electrode for collecting bio-neural signals based on the sensitive response of the two-dimensional electron gas structure in the heterojunction ISHFET to the change of the gate potential. Since the electron mobility in the two-dimensional electron gas structure is an order of magnitude higher than the charge mobility on the gate surface, the slight fluctuation of the surface charge in the sensing area of ​​the heterojunction ISHFET can be quickly manifested in the change of the conductivity of the two-dimensional electron gas and amplified, and then manifested as a change in the source-drain current, thereby realizing the rapid and stable collection of bio-neural signals.

[0156] At the same time, the present application adopts AlGaN / GaN ISHFET as a preferred embodiment to carry out a specific design of the integrated biological neural electrode, and provides a new design idea for biological neural electrodes based on heterojunctions of other materials; in the 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 and GaN materials have better biocompatibility than metal and silicon-based materials, and can perform signal acquisition work for a longer time.

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

[0158] Furthermore, by introducing the proximal and distal AlGaN / GaN REHFETs as differentials, the influence of environmental noise and device background noise is reduced, and the signal acquisition signal-to-noise ratio of the AlGaN / GaN ISHFET can be further improved.

[0159] The integrated biological neural electrode based on AlGaN / GaN ISHFET integrates the first microelectrode at intervals in the AlGaN / GaN ISHFET array, 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, and improve the signal-to-noise ratio of the signal collection of the first microelectrode.

[0161] The present invention also designs an ISHFET recessed gate to adjust the device operating point, which is beneficial to reducing the size of the device; by sharing the source lead of the AlGaN / GaN ISHFET, the wiring is optimized, and the device size can be further reduced, and the microelectrode can be prepared on the GaN buffer layer at the same time as the ISHFET lead and the ISHFET pad, reducing the process steps; therefore, the integrated biological neural electrode proposed by the present invention is also a small-sized implantable neural electrode.

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

[0163] Therefore, the integrated bio-neural electrode proposed in the present invention realizes the rapid and stable acquisition of bio-neural signals, and can also acquire bio-neural signals with high resolution, and greatly improves the signal-to-noise ratio of the acquired signals, thereby ensuring the high quality of signal acquisition.

[0164] The present invention overcomes the limitations of the prior art, significantly improves the efficiency, accuracy and quality of biological neural signal acquisition, and is expected to promote further development in the field of neuroscience.

[0165] See also Fig.23 The present invention also proposes the following specific embodiments for preparing an integrated biological neural electrode based on AlGaN / GaN ISHFET.

[0166] Example 1

[0167] See also Figure 1 , prepare AlGaN / GaN ISHFET epitaxial wafer: deposit GaN buffer layer 21, AlN insertion layer 22 and AlGaN barrier layer 23 in sequence on Sapphire (i.e. Al2O3) substrate.

[0168] See also Figure 2 , prepare AlGaN / GaN ISHFET: etch the AlGaN / GaN ISHFET epitaxial wafer to the GaN buffer layer 21 through photolithography and dry etching processes in a gas environment of Cl2 and BCl3 to form a plurality of spaced AlGaN / GaN ISHFET terraces with an etching depth of about 200nm.

[0169] See also Figure 2 , prepare source-drain electrodes 24: evaporate Ti / Al / Ni / Au metal film in a high vacuum environment through photolithography and electron beam evaporation, and pattern the Ti / Al / Ni / Au metal film using a lift-off process to obtain source-drain electrodes arranged on the AlGaN barrier layer, and the thickness parameters of the Ti / Al / Ni / Au metal film are 150 / 800 / 200 / 600nm.

[0170] The device is subjected to rapid thermal annealing to form a good ohmic contact between the metal film at the source and drain and the AlGaN barrier layer.

[0171] Etching ISHFET recessed gate: Through photolithography and photoelectrochemical oxidation processes, the surface of the AlGaN barrier layer is shallowly etched for recessed gate under ultraviolet light irradiation and deionized water solution environment.

[0172] The recessed gate shallow etching is performed in a deionized water solution environment because the etching rate in this environment is relatively slow, which facilitates the control of the recessed gate etching depth.

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

[0174] See also Figure 4 , prepare the first insulating passivation layer 4: prepare a silicon dioxide passivation layer by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment; use a wet etching process to pattern the insulating passivation layer with a buffered oxide etching solution to prepare an ISHFET gate window W1 and an ISHFET pad window W2.

[0175] See also Figure 5 , prepare microelectrodes 51, microelectrode leads 52 and microelectrode pads 53: evaporate a Ti / Au (15 / 100 nm) seed layer in a high vacuum environment through photolithography and electron beam evaporation processes, electroplate a thick gold film using secondary photolithography and electroplating processes, and pattern the thick gold film using a lift-off process.

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

[0177] See also Figure 6 , prepare the second insulating passivation layer 6: prepare a silicon dioxide passivation layer by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment, and pattern the insulating passivation layer by dry etching process to prepare ISHFET gate window W1, ISHFET pad window W2, microelectrode window W3, and microelectrode pad window W4.

[0178] See also Figure 7 , preparing a metal shielding layer 7: preparing a metal film in a high vacuum environment through photolithography and electron beam evaporation processes to obtain a metal shielding layer; and patterning the metal shielding layer through a lift-off process to prepare windows corresponding to the first insulating passivation layer and the second insulating passivation layer.

[0179] See also Figure 8 , prepare a third insulating passivation layer 8: prepare a silicon dioxide passivation layer by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment to obtain a third insulating passivation layer, and pattern the third insulating passivation layer by a dry etching process to prepare a 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 biological neural electrode prepared in Example 1 after each layer is peeled off are shown in Figures 1 and 2. Fig. 9 , Fig.10 and Fig.11 shown.

[0181] Example 2

[0182] See also Fig.12 , prepare AlGaN / GaN ISHFET epitaxial wafer: deposit GaN buffer layer 21, AlN insertion layer 22 and AlGaN barrier layer 23 in sequence on Sapphire (i.e. Al2O3) substrate.

[0183] Preparation of AlGaN / GaN ISHFET and AlGaN / GaN REHFET: Through photolithography and dry etching processes, the AlGaN / GaN ISHFET epitaxial wafer is etched to the GaN buffer layer 21 in a gas environment of Cl2 and BCl3 to form a plurality of spaced AlGaN / GaN ISHFET mesas (including AlGaN / GaN REHFET mesas for differentiation), with an etching depth of about 200nm.

[0184] See also Fig.13 , prepare source-drain electrodes 24: evaporate Ti / Al / Ni / Au metal film in a high vacuum environment through photolithography and electron beam evaporation, and pattern the Ti / Al / Ni / Au metal film using a lift-off process to obtain source-drain electrodes arranged on the AlGaN barrier layer, and the thickness parameters of the Ti / Al / Ni / Au metal film are 150 / 800 / 200 / 600nm.

[0185] The device is subjected to rapid thermal annealing to form a good ohmic contact between the metal film at the source and drain and the AlGaN barrier layer.

[0186] See also Fig.14 and Fig.15 , Etching ISHFET recessed gate B: Through photolithography and photoelectrochemical oxidation processes, the surface of the AlGaN barrier layer is shallowly etched for recessed gate under ultraviolet light irradiation and deionized water solution environment.

[0187] The recessed gate shallow etching is performed in a deionized water solution environment because the etching rate in this environment is relatively slow, which facilitates the control of the recessed gate etching depth.

[0188] See also Fig.16 , prepare ISHFET leads 31 and ISHFET pads 32 (not shown in the figure, refer to Fig.21 ), microelectrodes, microelectrode leads 52 and microelectrode pads 53 (not shown in the figure, see Fig.21): A Ti / Au (15 / 100 nm) seed layer is evaporated in a high vacuum environment through photolithography and electron beam evaporation processes, a thick gold film is electroplated using secondary photolithography and electroplating processes, and the thick gold film is patterned using a lift-off process.

[0189] The ISHFET lead 31 includes an ISHFET source lead 31 - 1 and an ISHFET drain lead 31 - 2 , and the ISHFET sources share one 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 also Fig.17 and Fig. 22 , prepare the first insulating passivation layer 4: prepare a silicon dioxide passivation layer by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment; use a wet etching process to pattern the insulating passivation layer with a buffered oxide etching solution to prepare an ISHFET gate window W1, an ISHFET pad window W2, a microelectrode window W3, a differential microelectrode solution contact window W6, and a microelectrode pad window W4.

[0192] The first insulating passivation layer 4 on the first microelectrode 51 is provided with a microelectrode window W3, while the second microelectrode 51' is not provided with 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 also Fig.18 , prepare a metal shielding layer 7: prepare a metal film in a high vacuum environment through photolithography and electron beam evaporation processes to obtain a metal shielding layer; and pattern the metal shielding layer using a lift-off process to prepare metal shielding layer windows W7 corresponding to the windows of the first insulating passivation layer.

[0194] See also Fig.19 and Fig. 22 , prepare a third insulating passivation layer 8: prepare a silicon dioxide passivation layer by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment to obtain a third insulating passivation layer, and pattern the third insulating passivation layer by a dry etching process to prepare a metal shielding layer grounding window W5 and other windows corresponding to the metal shielding layer.

[0195] The side view, three-dimensional structure diagram and top view of the integrated biological neural electrode prepared in Example 2 after each layer is peeled off are shown in Figures 1 and 2. Fig. 20 , Fig.21 and Fig. 22 shown.

[0196] It should be understood that the above specific embodiments are not limitations of the present invention. Based on the above specific embodiments, those skilled in the art can obtain more embodiments according to the actual application scenario requirements and related research progress, and these embodiments do not deviate from the spirit and scope of the technical solution of the present invention. For example, other heterojunctions with two-dimensional electron gas can be used to replace AlGaN / GaN, such as AlGaAs / InGaAs / GaAs, SiC / Si and other heterojunctions; suitable ISHFETs, microelectrode numbers and arrangements can also be selected; the various preparation steps do not necessarily have to be performed in sequence, these steps can be performed in other orders, and different combinations of the various steps can also be performed.

[0197] The present invention further provides a neural signal detection device. In some embodiments, the device includes the integrated biological neural electrode provided in the above embodiments, and:

[0198] A back-end circuit is electrically connected to the integrated biological neural electrode, and is used to supply power to the integrated biological neural electrode, and to receive and process biological neural signals collected by the integrated biological neural electrode;

[0199] The computer device is electrically connected to the back-end circuit and is used to receive the biological neural signals processed by the back-end circuit and perform computational analysis and visual display.

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

[0201] The back-end circuit mainly processes the collected biological neural signals through functions such as amplification, filtering and conversion, including: amplifying the biological neural signals through a preamplifier; removing unnecessary signal components such as high-frequency noise and low-frequency drift through a filter; converting the amplified and filtered analog neural signals into digital signals through an analog-to-digital converter. Since the biological neural signals collected by the heterojunction ISHFET are signals amplified by two-dimensional electron gas transconductance rather than the original weak signals, the integrated biological neural electrodes provided by the aforementioned embodiments can reduce the design difficulty of the back-end circuit.

[0202] The computer device is electrically connected to the back-end circuit through a special acquisition card, receives the biological neural signals processed by the back-end circuit, and stores them in a storage medium; researchers can set the acquisition parameters, such as sampling frequency, sampling time, etc., through the acquisition software; further, run relevant calculation and analysis software on the computer device to perform various analyses on the collected biological neural signals, including calculating the amplitude, frequency, latency and other parameters of the action potential; spectrum analysis can also be performed to understand the energy distribution of neural signals at different frequencies. For example, the characteristic frequency components of a certain neurological disease attack can be found by analyzing the spectral characteristics of the signal; in addition, the computer device also includes a visualization unit to display the biological neural signals in the form of intuitive graphics or images, which is convenient for researchers to observe and understand.

[0203] It can be understood that the integrated biological neural electrode is a key component of the neural signal detection device. The technical effects that can be achieved by the integrated biological neural electrode provided in the aforementioned embodiments can also be achieved by the neural signal detection device, which will not be elaborated here.

[0204] The embodiments described above are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. An integrated biological neural electrode, characterized in that: include: substrate; A heterojunction ISHFET is provided on the substrate and comprises a heterojunction and a source-drain electrode provided on the heterojunction; The heterojunction includes a buffer layer arranged on the substrate and a barrier layer arranged 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 electrode includes 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 to the two-dimensional electron gas.

2. The integrated biological neural electrode according to claim 1, characterized in that: The heterojunction includes a GaN buffer layer, an AlN insertion layer and an AlGaN barrier layer stacked in sequence from bottom to top; the two-dimensional electron gas is formed in the GaN buffer layer near the interface with the AlN insertion layer.

3. The integrated biological neural electrode according to claim 2, characterized in that: An ISHFET recessed gate is etched on the AlGaN barrier layer.

4. The integrated biological neural electrode according to claim 2, characterized in that: Also includes: An ISHFET lead and an ISHFET pad disposed on the GaN buffer layer, and a first insulating passivation layer covering the heterojunction ISHFET and the ISHFET lead; The ISHFET leads are arranged in parallel along the longitudinal axis of the integrated biological neural electrode, and include an ISHFET source lead and an ISHFET drain lead; The ISHFET pads include an ISHFET source pad and an ISHFET drain pad; 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; The first insulating passivation layer is provided with an ISHFET gate window and an ISHFET pad window.

5. The integrated biological neural electrode according to claim 4, characterized in that: The method comprises a plurality of the heterojunction ISHFETs arranged at intervals, and further comprises: A plurality of microelectrodes spaced apart from the heterojunction ISHFET, the microelectrodes being electrically connected to the microelectrode pads via microelectrode leads, the microelectrode leads being wired in parallel along the longitudinal axis of the integrated biological neural electrode; The microelectrode, microelectrode lead and microelectrode pad are arranged on the GaN buffer layer, and the first insulating passivation layer is also provided with a microelectrode window and a microelectrode pad window; or, the microelectrode, microelectrode lead and microelectrode pad are arranged on the first passivation layer, the microelectrode and microelectrode lead are covered with a second insulating passivation layer, and the second insulating passivation layer is provided with an ISHFET gate window, an ISHFET pad window, a microelectrode window and a microelectrode pad window.

6. The integrated biological neural electrode according to claim 4, characterized in that: It includes a heterojunction ISHFET disposed at a test end, a heterojunction REHFET adjacent to the heterojunction ISHFET, and at least one heterojunction REHFET away from the test end; Wherein, the first insulating passivation layer is provided with an ISHFET gate window on the heterojunction REHFET far away from the test end, and no ISHFET gate window is provided on the heterojunction REHFET adjacent to the heterojunction ISHFET; The heterojunction REHFET is used for differential, and its material and structure are the same as those of the heterojunction ISHFET.

7. The integrated biological neural electrode according to claim 5, characterized in that: 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 differentiation; The insulating passivation layers on the first microelectrode and the second microelectrode are both provided with microelectrode windows; Alternatively, any of the second microelectrodes is arranged adjacent to the first microelectrode, 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.

8. The integrated biological neural electrode according to any one of claims 4 to 7, characterized in that: Also includes: 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 windows corresponding to the lower insulating passivation layer, and the third insulating passivation layer is also provided with a metal shielding layer grounding window.

9. A method for preparing an integrated biological neural electrode, characterized in that: The method comprises the following steps: S1, preparing AlGaN / GaN ISHFET epitaxial wafer: depositing GaN buffer layer, AlN insertion layer and AlGaN barrier layer on the substrate in sequence; S2, preparing AlGaN / GaN ISHFET: etching the AlGaN / GaN ISHFET epitaxial wafer to the GaN buffer layer in a gas environment of Cl2 and BCl3 by photolithography and dry etching process to form a plurality of spaced AlGaN / GaNISHFETs; S3, preparing source and drain electrodes: evaporating Ti / Al / Ni / Au metal films in a high vacuum environment by photolithography and electron beam evaporation, and patterning the Ti / Al / Ni / Au metal films by a lift-off process to obtain source and drain electrodes disposed on the AlGaN barrier layer; S4, performing rapid thermal annealing on the device prepared in step S3; S5, etching ISHFET recessed gate: shallowly etching the recessed gate on the surface of the AlGaN barrier layer in an environment of ultraviolet light irradiation and deionized water solution by photolithography and photoelectrochemical oxidation process; S6, preparing ISHFET leads, ISHFET pads, microelectrodes, microelectrode leads and microelectrode pads, and then depositing and covering a first insulating passivation layer; or, preparing ISHFET leads and ISHFET pads, depositing and covering a first insulating passivation layer, preparing microelectrodes, microelectrode leads and microelectrode pads on the first insulating passivation layer, and then depositing and covering a second insulating passivation layer; Wherein, one or more of the ISHFET lead, the ISHFET pad, the microelectrode, the microelectrode lead and the microelectrode pad are prepared by the following method: evaporating a Ti / Au seed layer in a high vacuum environment by photolithography and electron beam evaporation process, electroplating a thick gold film by secondary photolithography and electroplating process, and patterning the thick gold film by lift-off 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 photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment to obtain an insulating passivation layer; a buffered oxide etching solution is used to pattern the insulating passivation layer by a wet etching process to prepare one or more of an ISHFET gate window, an ISHFET pad window, a microelectrode window, a microelectrode pad window and a differential microelectrode solution contact window; S7, preparing a metal shielding layer: preparing a metal film in a high vacuum environment by photolithography and electron beam evaporation process to obtain a metal shielding layer; and patterning the metal shielding layer by a lift-off process to prepare windows corresponding to the lower insulating passivation layer; S8, preparing a third insulating passivation layer: preparing a silicon dioxide passivation layer by photolithography and plasma enhanced chemical vapor deposition process in a gas environment of SiH4 and N2O, high vacuum and 350°C high temperature environment to obtain a third insulating passivation layer, and patterning the third insulating passivation layer by a dry etching process to prepare a metal shielding layer grounding window and other windows corresponding to the metal shielding layer.

10. A neural signal detection device, characterized in that: The device comprises the integrated biological neural electrode according to any one of claims 1 to 8 or the integrated biological neural electrode prepared by the preparation method according to claim 9, and: A back-end circuit, electrically connected to the integrated biological neural electrode, for supplying power to the integrated biological neural electrode, and receiving and processing biological neural signals collected by the integrated biological neural electrode; The computer device is electrically connected to the back-end circuit, and is used to receive the biological neural signals processed by the back-end circuit, and perform computational analysis and visual display.

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