CN108389931B - Biological nerve chip integrating photoelectrode and microelectrode and preparation method thereof - Google Patents
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Classifications
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L31/00—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
- H01L31/12—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof structurally associated with, e.g. formed in or on a common substrate with, one or more electric light sources, e.g. electroluminescent light sources, and electrically or optically coupled thereto
- H01L31/14—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof structurally associated with, e.g. formed in or on a common substrate with, one or more electric light sources, e.g. electroluminescent light sources, and electrically or optically coupled thereto the light source or sources being controlled by the semiconductor device sensitive to radiation, e.g. image converters, image amplifiers or image storage devices
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L23/00—Details of semiconductor or other solid state devices
- H01L23/28—Encapsulations, e.g. encapsulating layers, coatings, e.g. for protection
- H01L23/31—Encapsulations, e.g. encapsulating layers, coatings, e.g. for protection characterised by the arrangement or shape
- H01L23/3107—Encapsulations, e.g. encapsulating layers, coatings, e.g. for protection characterised by the arrangement or shape the device being completely enclosed
- H01L23/3121—Encapsulations, e.g. encapsulating layers, coatings, e.g. for protection characterised by the arrangement or shape the device being completely enclosed a substrate forming part of the encapsulation
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L25/00—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof
- H01L25/03—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof all the devices being of a type provided for in the same subgroup of groups H01L27/00 - H01L33/00, or in a single subclass of H10K, H10N, e.g. assemblies of rectifier diodes
- H01L25/04—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof all the devices being of a type provided for in the same subgroup of groups H01L27/00 - H01L33/00, or in a single subclass of H10K, H10N, e.g. assemblies of rectifier diodes the devices not having separate containers
- H01L25/075—Assemblies consisting of a plurality of individual semiconductor or other solid state devices ; Multistep manufacturing processes thereof all the devices being of a type provided for in the same subgroup of groups H01L27/00 - H01L33/00, or in a single subclass of H10K, H10N, e.g. assemblies of rectifier diodes the devices not having separate containers the devices being of a type provided for in group H01L33/00
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- Condensed Matter Physics & Semiconductors (AREA)
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- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
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Abstract
The invention relates to the technical field of semiconductor devices, in particular to a biological nerve chip integrating a photoelectrode and a microelectrode and a preparation method thereof. The specific structure of the chip comprises a photoelectrode part and a microelectrode part, wherein the photoelectrode part utilizes a light-emitting diode to emit light of 470nm to stimulate nerve cells to generate nerve current signals, and the microelectrode part near the photoelectrode is used for receiving the potential change of the nerve signals, so that the influence of the external signals on the nerve cells is detected, and the biological behavior is further studied. The photoelectrode part comprises a gallium nitride-based light emitting diode, a metal electrode, a transparent conducting layer, a temperature sensor, a metal circuit and a PAD electrode; the microelectrode part comprises a transparent film electrode or a metal electrode, a metal line and a PAD electrode. The invention integrates the photoelectrode and the microelectrode, has the characteristics of small size, high test precision, high conversion efficiency, easy implantation into organisms and the like, and realizes the measurement of nerve potential while carrying out optical stimulation on nerve cells.
Description
Technical Field
The invention relates to the technical field of semiconductor devices, in particular to a biological nerve chip integrating a photoelectrode and a microelectrode and a preparation method thereof.
Background
Since the 20 th century, human studies on living cells have progressed rapidly, and electrophysiological studies have greatly facilitated human studies on the functional activities of individual single nerve cells, the physiological and physical properties of neuronal membranes, and the location and role of individual neurons in neuronal circuits. The awareness of the nervous system is continually perfecting and addressing neurological disorders through electrical activity of the nerve. Conventional electrophysiological experiments all require the use of electrical stimulation of the neurons. The electrical stimulation has the defects that the intensity is too high, the temperature of local nerve tissues is easily caused to be too high, and the damage to a nervous system is caused; in addition, electrical stimulation generally has a large scope of application and is difficult to control with accuracy, and attempts have been made to find alternative techniques.
The optogenetic technology is a rapidly developing multidisciplinary crossing biotechnology, and utilizes the optical-stabbed laser sense genes to realize writing of external information, and utilizes the photoelectrode array technology to realize electrophysiological information reading under specific behaviors so as to analyze the functional characteristics of a certain nerve region and the relation with biological expression behaviors. The light stimulus adopted by the optogenetic technology can effectively act on specific individual neurons, and the speed of the light pulse can reach the sub-millisecond level, which is similar to that of the electric pulse.
The optogenetic technology is controlled mainly by stimulating two photosensitive proteins, namely photosensitive channel protein (ChR 2) and halophilic rhodopsin (NpHR). Wherein, the photosensitive channel protein (ChR 2) is most sensitive to 470nm optical stimulus and can cause nerve excitation; halophilic rhodopsin (NpHR) is most sensitive to 580nm light stimulus and can inhibit nerve excitation. The invention mainly adopts the control of the light sensitive channel protein, namely, a blue light device near 470nm is adopted.
At present, most of semiconductor nerve chips developed in the background of optogenetic technology only can realize a recording function, and most of optical stimulation is provided by optical fiber conduction near a recording position. The light stimulus transmitted by the method has low conversion efficiency and insufficient accuracy of the action position.
Disclosure of Invention
The present invention provides a biological nerve chip integrating photoelectrode and microelectrode and its preparation method, which combines the luminous signal and the receiving electric signal required in the optogenetic technology.
The technical scheme of the invention is as follows: the biological nerve chip integrating the photoelectrode and the microelectrode comprises a photoelectrode part and a microelectrode part, wherein the photoelectrode part utilizes a light-emitting diode to emit light of 470nm to stimulate nerve cells to generate nerve current signals, and the microelectrode part near the photoelectrode is used for receiving the potential change of the nerve signals, so that the influence of the external signals on the nerve cells is detected, and the biological behavior is studied. The photoelectrode part comprises a gallium nitride-based light emitting diode, a metal electrode, a transparent conducting layer, a temperature sensor, a metal circuit and a PAD electrode; the microelectrode part comprises a transparent film electrode or a metal electrode, a metal line and a PAD electrode.
Furthermore, the material of the epitaxial lamination used by the photoelectrode can be gallium nitride, indium aluminum gallium nitride and other materials, and is suitable for emitting 470nm optical signals; the transparent thin film conducting layer on the epitaxial lamination can be any transparent conducting material such as indium tin oxide, indium gallium zinc oxide, iridium oxide, thin Ni/Au and the like; the n-pole and p-pole metal electrodes used for the photoelectrode can be Ni/Au, ti/Al/Ni/Au or other alloys.
Further, the material used for the microelectrode may be transparent or opaque according to the relative position between the microelectrode and the microelectrode; the metal material adopted by the transparent microelectrode can be ITO, IGZO, znO, irO, thin Ni/Au and other transparent materials; the metal material used for the opaque microelectrode can be thick Ni/Au, ti/Au, cr/Au and other alloys. The growth method comprises electron beam evaporation, metal organic chemical vapor deposition, magnetron sputtering and the like;
Further, the microelectrode and the photoelectrode part are isolated by adopting a transparent medium layer, so that the interference of nerve current to photoelectrode current and noise generated by receiving nerve current signals from the photoelectrode optical signals to the microelectrode are avoided; the dielectric layer can be a transparent non-conductive layer such as silicon dioxide, silicon nitride and the like.
Further, the microelectrode may be in the same position as the transparent conductive layer of the photoelectrode, and in different layers isolated from each other; or may be in the vicinity of the light-emitting position of the photoelectrode portion; the microelectrodes may be arranged in a linear array or in a rectangular mesh.
Further, the material of the temperature sensor may be any metal whose resistivity is stable with temperature change. Such as platinum, copper, etc., are suitable for operation at different temperatures.
In the invention, the chip has small volume, thin thickness, easy implantation into organism, less damage to the tissue and repeated use. The photoelectrode and the microelectrode are combined at the same position, so that accurate nerve potential recording can be performed while the light-sensitive channel protein is subjected to light stimulation, and the resolution ratio is high. Unlike traditional optical stimulation by optical fiber conduction, the photoelectrode adopts a micro light emitting diode, and the miniaturization in size enables the experimental mouse to freely move, so that more biological reactions can be observed. In order to realize the integration of the photoelectrode and the microelectrode at the same position of the chip,
The preparation method of the biological nerve chip integrating the photoelectrode and the microelectrode comprises the following steps:
s1, etching a P-type platform on an epitaxial lamination layer on which a gallium nitride luminescent layer is grown by using a plasma etching method;
s2, depositing an ITO transparent conductive film on the whole surface, and carrying out wet etching to only leave an ITO conductive layer on the p-type platform with a p-type window;
s3, depositing a mask dielectric layer by utilizing PECVD, and etching p-type and n-type windows on the dielectric layer;
S4, respectively obtaining a p-type electrode, an n-type electrode, a microelectrode, a metal circuit, a PAD electrode part and a temperature sensor on the dielectric layer by photoetching, whole surface vapor plating metal, stripping or corrosion;
S5, depositing a mask dielectric layer by PECVD, and etching a PAD window and a microelectrode window on the dielectric layer.
Preferably, a gallium nitride-based sapphire substrate is preferred in the present invention; the n and p-pole metals are preferably Ti/Al/Ni/Au and Ni/Au respectively; the transparent conductive layer is preferably ITO; the microelectrode material is preferably ITO; the circuit and the PAD part are preferably Ni/Au and Ti/Au; the temperature sensor is preferably Pt metal; the dielectric layer material is preferably silicon dioxide (SiO 2). The size of the whole device is preferably long x width = 1.0cm x 0.30mm; the p-type electrode and the n-type electrode are preferably rectangular, the transparent conductive layer is preferably rectangular, and the microelectrode is preferably circular. The front process is completed, the substrate can be thinned properly, and the damage when the biological nerve tissue is implanted is reduced.
Compared with the prior art, the beneficial effects are that: the invention integrates the photoelectrode and the microelectrode at the same position, has the effect of simulating nerve stimulation, and can record nerve potential change generated during stimulation. The heights of the photoelectrodes and the microelectrodes are close, and the accuracy of the stimulation signals can be improved better. In addition, the chip has the characteristics of small size, high conversion efficiency, easiness in implantation into organisms and the like, and has wide prospect in future optogenetic research.
Drawings
Fig. 1 is a front perspective view of embodiment 1.
Fig. 2 is a top view of embodiment 1.
FIG. 3 is a schematic view of a partial device implanted in a living body at a detection site in example 1.
Fig. 4 is a first schematic view of a partial device implanted in a detection site portion in a living body according to example 2.
Fig. 5 is a second schematic view of a partial device implanted in a detection site portion in a living body according to example 2.
Fig. 6 is a cross-sectional view of the device of example 1 at the tip of the photoelectrode and microelectrode integration.
Fig. 7 is a schematic diagram of a window position of the encapsulation layer in embodiment 1 (the dotted line part is an opening in the figure).
Fig. 8 is a top view of the front surface photoelectrode of example 3.
Fig. 9 is a cross-sectional view of example 3 taken along the vertical direction of the photoelectrode-microelectrode.
Detailed Description
The drawings are for illustrative purposes only and are not to be construed as limiting the present patent; for the purpose of better illustrating the embodiments, certain elements of the drawings may be omitted, enlarged or reduced and do not represent the actual product dimensions; it will be appreciated by those skilled in the art that certain well-known structures in the drawings and descriptions thereof may be omitted. The positional relationship depicted in the drawings is for illustrative purposes only and is not to be construed as limiting the present patent.
Example 1
As shown in fig. 1, 2, 3,6, and 7, this example integrates microelectrodes and photoelectrodes at the same location at the tip of the probe chip. The photoelectrode part is formed by sequentially growing a buffer layer, an n-GaN layer, a quantum well luminescent layer and a p-GaN layer on a sapphire substrate. And after the original sheet is cleaned, photoetching and developing are carried out, and plasma etching is utilized for a certain depth to form a p-type platform. And then depositing an ITO conductive film on the whole surface, etching and removing the parts except the p-type platform, and exposing the p-type window on the p-type platform. And then depositing a mask layer and corroding to expose n and p electrode windows, and sequentially evaporating n and p electrodes, metal lines and PAD electrode metals. Thus, the photoelectrode is manufactured. The electrode part is continuously manufactured on the basis, firstly, in order to prevent the microelectrode part from being interfered by the current of the electrode circuit, a dielectric layer deposited on the device is required to play a role of protection and isolation, and then one end of a metal circuit connected with the microelectrode on the transparent conductive layer is windowed. And then depositing an ITO transparent conductive film on the whole surface, and corroding the round tip. Thus, the microelectrode part is manufactured. Finally, the entire device is encapsulated, leaving only the microelectrode, PAD electrode window exposed, as shown by the shading in fig. 7.
Example two
As shown in fig. 4 and 5, the device structure is similar to the embodiment, except that the arrangement of the microelectrodes is changed, and a metal material is used as the microelectrodes, i.e. the microelectrodes are opaque. Since the photoelectrode used in the present invention has sufficiently high optical power, it is possible to receive a nerve potential signal from a neuron cell stimulated by light emitted from the photoelectrode even if the microelectrode itself is not located on the photoelectrode portion. Since the microelectrode can be made of the same metal material as the metal circuit, the process steps can be saved. Meanwhile, the microelectrodes are arranged outside the light-emitting area, so that the change of the switching potential caused by direct irradiation of light can be avoided.
Example III
As shown in fig. 8 and 9, the device incorporates a Pt temperature sensor to monitor the heating condition of the photoelectrode, and a microelectrode portion is provided on the back of the substrate. The device adopts a sapphire transparent substrate, light emitted by the photoelectrode can penetrate through the substrate to irradiate on a neuron cell where the microelectrode is positioned, and the microelectrode receives nerve potential change. The shape of the photoelectrode n and the photoelectrode p can be a ring electrode and a rectangular electrode as shown in fig. 6.
It is to be understood that the above examples of the present invention are provided by way of illustration only and not by way of limitation of the embodiments of the present invention. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. Any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the invention are desired to be protected by the following claims.
Claims (7)
1. The biological nerve chip integrating the photoelectrode and the microelectrode is characterized by comprising a photoelectrode unit and a microelectrode unit, wherein the photoelectrode unit comprises a gallium nitride luminous layer, a p-type electrode, an n-type electrode, a transparent conducting layer, a temperature sensor, a metal circuit and a PAD electrode; the microelectrode unit comprises four microelectrodes, four metal lines and four PAD electrodes; the microelectrode is a transparent film electrode or a metal electrode;
The photoelectric electrode unit and the microelectrode unit are positioned on the same side of the substrate, in the photoelectric electrode unit, a gallium nitride light-emitting layer is connected with a PAD electrode through a p-type electrode, an n-type electrode and a metal circuit, a transparent conductive layer covers part of the gallium nitride light-emitting layer, a mask medium layer covers the top of the gallium nitride light-emitting layer and the top of the transparent conductive layer, a transparent medium layer covers the top of the mask medium layer, and the p-type electrode, the n-type electrode, the microelectrode, the metal circuit, the PAD electrode part and the temperature sensor are respectively obtained on the mask medium layer by photoetching, whole-surface metal evaporation, stripping or corrosion methods;
The microelectrode unit is positioned on the upper layer which is mutually isolated from the photoelectrode unit and the temperature sensor, wherein the four microelectrodes are respectively connected with the four PAD electrodes through four metal lines;
the microelectrode is positioned at the same position as the transparent conducting layer of the photoelectrode unit and is in different layers isolated from each other;
The microelectrode and the photoelectrode unit are isolated by a transparent dielectric layer.
2. The photoelectrode and microelectrode integrated biochip according to claim 1, wherein: the material of the epitaxial lamination used by the photoelectrode unit is gallium nitride, and the epitaxial lamination is suitable for emitting 470nm optical signals; the transparent conductive layer on the epitaxial lamination is made of transparent conductive material and comprises indium tin oxide, indium gallium zinc oxide, iridium oxide or thin nickel-gold alloy; the n-pole and p-pole metal electrodes adopted by the photoelectrode unit comprise nickel-gold alloy, titanium-gold alloy or titanium-aluminum-nickel-gold alloy.
3. The photoelectrode and microelectrode integrated biochip according to claim 1, wherein: the microelectrode is made of transparent or opaque materials according to the relative positions of the microelectrode and the gallium nitride light-emitting layer; materials adopted by the transparent microelectrode comprise ITO, IGZO, znO, irO or thin nickel-gold alloy; materials used for the opaque microelectrode include thick nickel-gold alloy, titanium-gold alloy or chrome-gold alloy.
4. The photoelectrode and microelectrode integrated biochip according to claim 1, wherein: the transparent dielectric layer is a transparent non-conductive layer comprising silicon dioxide or silicon nitride.
5. The photoelectrode and microelectrode integrated biochip according to claim 1, wherein: the microelectrodes are arranged in a linear array or in a rectangular mesh.
6. The photoelectrode and microelectrode integrated biochip according to claim 1, wherein: the material of the temperature sensor is metal with stable resistivity along with temperature change.
7. The method for manufacturing a photoelectrode and microelectrode integrated biological neural chip according to claim 1, comprising the steps of:
s1, etching a P-type platform on an epitaxial lamination layer on which a gallium nitride luminescent layer is grown by using a plasma etching method;
S2, depositing an ITO transparent conductive film on the whole surface, and carrying out wet etching to only leave the ITO transparent conductive film on the p-type platform to form a transparent conductive layer with a p-type window;
S3, depositing a mask dielectric layer by utilizing PECVD, and etching p-type and n-type windows on the mask dielectric layer;
s4, respectively obtaining a p-type electrode, an n-type electrode, a microelectrode, a metal circuit, a PAD electrode part and a temperature sensor on the mask dielectric layer by photoetching, whole-surface vapor plating metal, stripping or corrosion;
S5, depositing a mask dielectric layer by PECVD, and etching a PAD window and a microelectrode window on the mask dielectric layer.
Priority Applications (1)
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CN201810332745.6A CN108389931B (en) | 2018-04-13 | 2018-04-13 | Biological nerve chip integrating photoelectrode and microelectrode and preparation method thereof |
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CN201810332745.6A CN108389931B (en) | 2018-04-13 | 2018-04-13 | Biological nerve chip integrating photoelectrode and microelectrode and preparation method thereof |
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CN108389931A CN108389931A (en) | 2018-08-10 |
CN108389931B true CN108389931B (en) | 2024-07-02 |
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