CN111134654B - Photoelectric nerve probe integrated with internal metal shielding layer and preparation method thereof - Google Patents
Photoelectric nerve probe integrated with internal metal shielding layer and preparation method thereof Download PDFInfo
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Abstract
The invention provides a photoelectric nerve probe integrated with an internal metal shielding layer and a preparation method thereof, wherein the preparation method comprises the following steps: the electrophysiological signal recording channel is used for conducting the neural electric signal from the electrode point to a channel of the acquisition system; the laser diode power supply channel is used for conducting a pulse type current or voltage signal to a path used for driving the laser diode to work at a welding pad at the base part of the nerve probe; and the metal shielding layer is integrated between the electrophysiological signal recording channel and the laser diode power supply channel. The invention not only has the functions of recording the neural signals and photostimulating, but also separates an electrophysiological signal recording channel from a power supply channel of a laser diode by layers by the middle metal shielding layer integrated at the base part of the probe, so that stimulation following artifacts generated by electromagnetic interference recorded by the electrophysiological channel are greatly attenuated, and the pollution to the neural action potential caused by the stimulation following artifacts in the optogenetic experiment carried out in an animal body is reduced. The invention adopts MEMS process, and has high reproducibility.
Description
Technical Field
The invention relates to a neural signal recording and stimulating microelectrode in the field of biomedical engineering, in particular to a photoelectric neural probe integrated with an internal metal shielding layer and a preparation method thereof.
Background
In the past decades, the electrical stimulation of the brain has made it possible to learn about the function of the brain. To further advance the development of neuroscience and study the mechanism of action between a large number of neurons in a complex neural network, it is necessary to selectively activate or inhibit a particular type of individual neuron. Currently, methods using electrical stimulation are still ineffective at activating or inhibiting specific neurons. More recently, optogenetics has revolutionized the development of neural circuit research by introducing light-sensitive proteins into specific cells to enable them to respond to light stimuli with action potentials. Activation or inhibition of specific neurons with controllable temporal resolution can be achieved using appropriate wavelengths to excite specific opsins. For example, light sensitive channel protein (ChR2) and halorhodopsin can be expressed simultaneously in the same cell, allowing the activation or inhibition of target neurons with blue light (473 nm) or yellow light (590 nm). This allows us to precisely modulate neural circuits to further understand neural coding and the link between neural activity and behavioral response.
In the field of neuroscience, a widely used tool in optogenetic experiments is the integration of optical fibers (about 200 μm in diameter) directly with neuro-recording probes. Although some fiber-based nerve probes are now commercially available, the larger size of the fiber during implantation presses against the brain tissue, causing tissue damage during implantation, while the external bulky fiber light source also limits the mobility of the animal. In order to overcome the limitation of the integrated optical fiber nerve probe, the photoelectric nerve probe which utilizes a micromachining process to realize an on-chip integrated light source becomes a new solution of the optogenetic technology. In 2015, Fan Wu and Euisik Yoon et al proposed that a gallium nitride (GaN) layer was grown on the wafer and a micro LED was directly formed at the tip of the probe to form a photoelectric nerve probe for defibrination, but since the micro LED was operated too close to the tissue, the tissue was overheated due to temperature rise caused by light irradiation, which affects normal neuroelectrophysiological activities. The other photoelectric nerve probe without fiber is bonded with a laser diode at the rear end of a silicon probe, light emitted by the laser diode is coupled to an optical waveguide on an integrated chip, and light rays are emitted from the front end of the waveguide to perform optical stimulation. The disadvantage of this approach is the close distance between the laser diode's power supply line and the recording channel, which can create stimulus-locked artifacts caused by electromagnetic interference (EMI) coupling, contaminating the recording of normal neural action potentials. In view of the above, there is a strong need in optogenetic technology for a low-noise optical nerve probe tool without optical fibers to make the technology highly distinctive in the neuroscience field.
Disclosure of Invention
In view of the shortcomings in the prior art, it is an object of the present invention to provide an optoelectronic nerve probe integrated with an internal metal shield.
According to a first aspect of the present invention, there is provided an optoelectronic neural probe integrated with an internal metal shielding layer, comprising:
the electrophysiological signal recording channel is used for conducting the neural electric signal from the electrode point to a channel of the acquisition system;
the laser diode power supply channel is used for conducting a pulse type current or voltage signal to a path used for driving the laser diode to work at a welding pad at the base part of the nerve probe;
the metal shielding layer is integrated between the electrophysiological signal recording channel and the laser diode power supply channel and used for isolating the electrophysiological signal recording channel and the laser diode power supply channel, and the metal shielding layer is grounded, so that the attenuation of the stimulation following artifact generated by electromagnetic interference is realized, and the pollution of the stimulation following artifact to the nerve action potential in the optogenetic experiment process can be reduced.
Preferably, the electrophysiological signal recording channel is made of a biocompatible material;
the biocompatible material comprises any one of gold, titanium, platinum or platinum iridium alloy.
Preferably, the material of the laser diode power supply channel is selected from biocompatible materials;
the biocompatible material comprises any one of gold, titanium, platinum or platinum iridium alloy.
Preferably, the method further comprises the following steps:
the first insulating layer is positioned at the bottommost layer, and the electrophysiological signal recording channel is arranged above the first insulating layer;
the second insulating layer is arranged above the electrophysiological signal recording channel, and the metal layer is arranged above the second insulating layer;
and the third insulating layer is arranged above the metal shielding layer, and the laser diode power supply channel is arranged above the third insulating layer.
Preferably, the method further comprises the following steps:
the waveguide lower cladding is arranged above the laser diode power supply channel;
an optical waveguide layer disposed above the waveguide lower cladding layer;
a waveguide upper cladding layer disposed above the optical waveguide layer.
According to a second aspect of the present invention, a package structure of a photoelectric nerve probe and a laser diode is provided, where the photoelectric nerve probe is the above photoelectric nerve probe integrated with an internal metal shielding layer, an anode pad of the photoelectric nerve probe is in communication with an anode of the laser diode through anisotropic conductive adhesive bonding, and a cathode pad of the photoelectric nerve probe is in communication with a cathode of the laser diode through gold wire ball bonding, so as to implement packaging of the laser diode.
According to a third aspect of the present invention, there is provided a method for preparing an optoelectronic nerve probe integrated with an internal metal shielding layer, comprising: preparing an electrophysiological signal recording channel, preparing a metal shielding layer above the electrophysiological signal recording lead layer, and then preparing a laser diode power supply channel above the metal shielding layer.
Preferably, the method further comprises the following steps: before the step of preparing the electrophysiological signal recording channel, preparing a first insulating layer and then preparing the electrophysiological signal recording channel above the first insulating layer; then after the step of preparing the electrophysiological signal recording channel, preparing a second insulating layer above the electrophysiological signal recording channel, then preparing the metal shielding layer above the second insulating layer, after the step of preparing the metal shielding layer, preparing a third insulating layer above the metal shielding layer, and finally preparing the laser diode power supply channel above the third insulating layer.
Preferably, the method comprises the following steps:
s1: selecting on-chip insulating silicon as a substrate, wherein the substrate comprises top silicon, an oxygen burying layer and bottom silicon, depositing a layer of silicon oxide on the substrate as a first insulating layer, and the first insulating layer is positioned above the top silicon;
s2: preparing a metal adhesion layer on the first insulating layer, preparing a metal conductive layer on the metal adhesion layer, preparing a metal layer on the metal conductive layer as an etching barrier layer, and patterning to obtain an electrophysiological signal recording channel with bent wiring;
s3: depositing a layer of silicon oxide on the electrophysiological signal recording wire layer to serve as an intermediate insulating layer to obtain a second insulating layer, preparing a metal adhesion layer on the second insulating layer, then preparing a metal conducting layer on the metal adhesion layer, then preparing a layer of metal on the metal conducting layer to serve as an etching barrier layer, and patterning to obtain the metal shielding layer;
s4: depositing a layer of silicon oxide on the metal shielding layer to serve as a top insulating layer to obtain a third insulating layer, preparing a metal adhesion layer on the third insulating layer, then preparing a metal conducting layer on the metal adhesion layer, then preparing a layer of metal on the metal conducting layer to serve as an etching barrier layer, and patterning to obtain the power supply channel of the laser diode;
s5: depositing a layer of silicon oxide on the power supply channel of the laser diode, preparing a layer of metal on the silicon oxide as an etching barrier layer, depositing a layer of silicon oxide on the etching barrier layer, and depositing a layer of silicon oxynitride on the silicon oxide;
s6: forming an optical waveguide layer and a waveguide lower cladding layer by a dry etching process, and then removing the barrier layer in S5 by wet etching;
s7: depositing a layer of silicon oxide on the optical waveguide as an upper waveguide cladding, etching the upper waveguide cladding, the third insulating layer and the second insulating layer by a dry etching process, exposing a power supply pad of the laser diode, the outside of the metal shielding layer, a recording electrode point and a pad region, and then removing the barrier layers S2-S4 by wet etching.
S8: etching the first insulating layer by a dry etching process, and etching the top silicon of the on-chip insulating silicon by deep reactive ions to be used as a contour line of release of the nerve probe;
s9: spin-coating positive glue with a certain thickness on the upper surface of the on-chip insulating silicon to serve as a protective layer;
s10: and etching the bottom silicon of the on-chip insulating silicon by deep reactive ion etching, and etching the buried oxide layer in the middle of the on-chip insulating silicon wafer by a reactive ion etching process to release the nerve probe.
Preferably, a layer of metal prepared in S2, S3, S4, S5 serves as the etch stop layer to enable etching of silicon oxide at different depths.
Preferably, the thickness of the first insulating layer is 1 to 2 μm.
The thickness of the second insulating layer is: 500-2000 nm.
The thickness of the third insulating layer is: 500-2000 nm.
Preferably, the metal used as the etch stop layer is a chromium metal layer of 100-200 nm.
Preferably, the metal as the metal adhesion layer is 30nm of chromium and the metal as the metal conductive layer is 300nm of gold.
Compared with the prior art, the invention has at least one of the following beneficial effects:
compared with the common nerve probe, the nerve signal recording and optical stimulation probe has the functions of recording nerve signals and performing optical stimulation, and the middle metal shielding layer integrated on the base of the probe is integrated between the electrophysiological signal recording channel and the power supply channel of the laser diode, so that the electrophysiological signal recording channel and the power supply channel of the laser diode are separated in a layered mode, stimulation generated by electromagnetic interference recorded by the electrophysiological channel is greatly attenuated along with an artifact, the pollution of stimulation along with the artifact to nerve action potential in the process of performing an optogenetic experiment in an animal body is reduced, and the quality of signals recorded by the photoelectric nerve probe in the optogenetic experiment is improved; the low-noise electrophysiological signal recording can be realized while the laser diode coupled optical waveguide is used for performing optical stimulation, and the amplitude of the artifact followed by stimulation is greatly reduced due to the grounding design of the internal metal shielding layer.
Furthermore, in the structure, the anode is bonded by using anisotropic conductive Adhesive (ACF), and the cathode is bonded by using gold wire ball bonding to realize the packaging of the laser diode, so that the cost for packaging the laser diode is reduced; the packaging mode is simple and reliable, expensive flip chip equipment is not needed, the packaging threshold is reduced, and the packaging cost is reduced.
Furthermore, in the structure of the invention, the laser diode is coupled with the silicon oxynitride optical waveguide to guide light to the vicinity of the electrode point for optical stimulation, the electrophysiological acquisition channel synchronously records nerve signals, and the middle grounding metal layer is integrated to inhibit electromagnetic noise interference.
In the method, the photoelectric nerve probe is processed and manufactured by an MEMS (micro-electromechanical systems) process, and the probe can realize low-noise nerve action potential recording in a optogenetic experiment and has great application value in the field of neuroscience.
Drawings
Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:
FIG. 1 is a schematic diagram of an optoelectronic nerve probe incorporating an internal metal shield in accordance with a preferred embodiment of the present invention;
FIG. 2 is an exploded view of the base of an optoelectronic nerve probe in accordance with a preferred embodiment of the present invention;
FIG. 3 is an enlarged view of a portion of FIG. 1 at A in accordance with a preferred embodiment of the present invention;
FIG. 4 is a flow chart of a process for fabricating an optoelectronic neural probe in accordance with a preferred embodiment of the present invention;
FIG. 5 is a graph showing the result of the EMI suppression effect test of a general nerve probe (without a shielding layer) according to a preferred embodiment of the present invention;
fig. 6 is a diagram illustrating the results of the electromagnetic interference suppression effect test of the photoelectric nerve probe integrated with the internal metal shielding layer according to a preferred embodiment of the present invention.
The scores in the figure are indicated as: the device comprises a silicon substrate layer 1, a bottom insulating layer 2, an intermediate insulating layer 3, an electrophysiological signal recording channel 4, a metal shielding layer 5, a top insulating layer 6 and a laser diode power supply channel layer 7.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
Referring to fig. 1-3, there are shown schematic structural diagrams of an optoelectronic nerve probe integrated with an internal metal shielding layer according to a preferred embodiment of the present invention, which includes an electrophysiological signal Recording channel, a laser diode power supply channel and a metal shielding layer, wherein the electrophysiological signal Recording channel is used for conducting an electrical neural signal from an electrode point to a path of a back-end acquisition system (RHD200 Recording system). The laser diode power supply channel is used for conducting a pulse type current or voltage signal to a path used for driving the laser diode to work at a bonding pad at the base part of the nerve probe. The metal shielding layer is integrated between the electrophysiological signal recording channel and the power supply channel of the laser diode, the electrophysiological signal recording channel and the power supply channel of the laser diode are isolated in a layered mode, and the metal shielding layer is grounded, so that the stimulation following artifact generated by electromagnetic interference is attenuated, and the pollution of the stimulation following artifact to the nerve action potential in the optogenetic experiment process can be reduced.
In some other preferred embodiments, the electrophysiological signal recording channel is made of a biocompatible material;
the biocompatible material comprises any of gold, titanium, platinum or platinum iridium alloy.
In some other preferred embodiments, the material of the power supply channel of the laser diode is selected from biocompatible materials;
the biocompatible material comprises any of gold, titanium, platinum or platinum iridium alloy.
In some other preferred embodiments, the optoelectronic nerve probe further comprises: the electrophysiological signal recording device comprises a first insulating layer, a second insulating layer and a third insulating layer, wherein the first insulating layer is positioned at the bottommost layer, and an electrophysiological signal recording channel is arranged above the first insulating layer. The second insulating layer is arranged above the electrophysiological signal recording channel, and the metal layer is arranged above the second insulating layer. The third insulating layer is arranged above the metal shielding layer, and the laser diode power supply channel is arranged above the third insulating layer.
The materials of the first insulating layer, the second insulating layer and the third insulating layer can be silicon oxide.
The thickness of the first insulating layer may be: 1-2 μm.
The thickness of the second insulating layer may be: 500-2000nm
The thickness of the third insulating layer may be: 500-2000nm
In some other preferred embodiments, the optoelectronic nerve probe further comprises: the laser diode power supply device comprises a waveguide lower cladding layer, a waveguide layer and a waveguide upper cladding layer, wherein the waveguide lower cladding layer is arranged above a laser diode power supply channel; the optical waveguide layer is arranged above the waveguide lower cladding layer; the waveguide upper cladding layer is disposed above the optical waveguide layer. The photoelectric nerve probe guides light to the vicinity of the electrode point through the silicon oxynitride optical waveguide for optical stimulation, the electrophysiological signal recording channel synchronously records nerve signals, and the middle grounding metal layer is integrated to inhibit electromagnetic noise interference.
The optical waveguide layer can be made of silicon oxynitride, polymer SU8 or silicon nitride, and the processing modes of optical waveguides made of different materials are slightly different, but the optical waveguides have coupling transmission effect on blue light, and the internal metal shielding layer has the same effect on inhibiting the laser diode. The materials of the waveguide lower cladding and the waveguide upper cladding can be silicon oxide.
In one embodiment, referring to fig. 2, the optoelectronic nerve probe comprises a silicon substrate layer (silicon on chip) 1, a bottom insulating layer (first insulating layer) 2, an intermediate insulating layer (second insulating layer) 3, an electrophysiological signal recording channel 4, a metal shield layer 5, a top insulating layer (third insulating layer) 6, and a laser diode power supply channel layer 7. The following describes a method for fabricating the above-described photoelectric nerve probe integrated with an internal metal shield layer using micromachining technology.
Preparing a silicon oxynitride optical waveguide-based photoelectric nerve probe:
an SOI (i.e. silicon on an insulating substrate, which is a technique in which a buried oxide layer is introduced between top silicon and bottom silicon) silicon wafer is used as the substrate material of the sensor, and the thicknesses of the top silicon, the buried oxide layer and the bottom silicon are 30 μm, 2 μm and 475 μm, respectively. And respectively putting the SOI into acetone, ethanol and deionized water, ultrasonically cleaning for 5 minutes, blow-drying by using nitrogen, and then putting into an oven at 180 ℃ for baking for 3 hours.
S1: referring to fig. 4 (a), 1 μm silicon oxide is deposited on the SOI silicon wafer substrate material as a bottom insulating layer (first insulating layer) on the top silicon of the SOI silicon wafer.
S2: referring to fig. 4 (b), sputtering (or evaporating) a Cr metal adhesion layer (30nm), an Au conductive layer (300nm) and a Cr layer as an etching barrier layer (100nm) on the bottom insulating layer, spin-coating a 3 μm positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking, and performing ion beam etching to obtain the electrophysiological signal recording channel of the meandering trace.
S3: referring to fig. 4 (c), 500nm silicon oxide is deposited on the electrophysiological signal recording channel as an intermediate insulating layer (second insulating layer), a Cr metal adhesion layer (30nm), an Au conductive layer (300nm) and a Cr layer as an etching stop layer (100nm) are sputtered (or evaporated) on the intermediate insulating layer, a positive photoresist is spin-coated as a mask, and a rectangular intermediate metal shielding layer is obtained by pre-baking, exposure, development and post-baking and ion beam etching;
s4: referring to fig. 4 (d), depositing 500nm silicon oxide on the middle metal shielding layer as a top insulating layer (third insulating layer), sputtering (or evaporating) a Cr metal adhesion layer (30nm), an Au conductive layer (300nm) and a Cr layer as an etching barrier layer (100nm) on the top insulating layer, spin-coating a positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking by using ion beam etching to obtain a top laser diode power supply channel;
s5: referring to fig. 4 (e), depositing a layer of 500nm silicon oxide on the power supply channel of the laser diode, then sputtering (or evaporating) a layer of Cr on the silicon oxide as an etching barrier layer (100nm), depositing 3 μm silicon oxide on the etching barrier layer as a waveguide lower cladding, and depositing an 8 μm silicon oxynitride waveguide layer;
s6: referring to fig. 4 (f), after the positive photoresist is patterned into a mask, a silicon oxynitride optical waveguide and a silicon oxide waveguide lower cladding are formed by a reactive ion etching process, and then a 100nm metal barrier layer is removed by wet etching;
s7: referring to fig. 4 (g), 3 μm silicon oxide is deposited on the silicon oxynitride optical waveguide as a waveguide upper cladding layer, after positive photoresist is patterned as a mask, the 3 μm waveguide upper cladding layer and the 500nm upper insulating layer and the 500nm intermediate insulating layer are etched by a reactive ion etching process, the laser diode power supply pad, the shield layer outer portion and the recording electrode point and the pad region are exposed, and then the 100nm metal barrier layer in S2-S4 is removed by wet etching.
S8: referring to (h) in fig. 4, after the positive photoresist is patterned into a mask, etching the 1 μm bottom insulating layer by a reactive ion etching process, and deeply reacting 30 μm top silicon of the silicon on the wafer as a contour line of release of the nerve probe;
s9: referring to (i) in fig. 4, 5 μm of positive photoresist is spin-coated on the upper surface of the on-chip silicon-on-insulator to serve as a protective layer;
s10: referring to (j) in fig. 4, after a positive photoresist with the bottom of the on-chip insulating silicon being 5 μm is patterned into a mask, the back oxide layer is etched by a reactive ion etching process, the 475 μm bottom silicon of the on-chip insulating silicon wafer is etched by deep reactive ion etching, and the 2 μm buried oxide layer in the middle of the on-chip insulating silicon wafer is etched by the reactive ion etching process, so that the release of the nerve probe is realized.
And a layer of metal prepared in S2, S3, S4 and S5 is used as the etching barrier layer to realize etching of silicon oxide with different depths.
In another embodiment, a package structure of an optoelectronic nerve probe and a laser diode is provided, wherein the optoelectronic nerve probe is the optoelectronic nerve probe integrated with an internal metal shielding layer. Referring to fig. 1 and 3, the anode of the laser diode 9 is electrically connected to the anode pad by a hot-pressed Anisotropic Conductive Film (ACF)10, and the cathode is electrically connected to the cathode pad by a gold wire ball bonding process, so as to package the laser diode 9. With the aid of the micro-stick, the laser diode 9 achieves a precise coupling with the optical waveguide 8. The low-noise photoelectric nerve probe realizes the collection and transmission of electrophysiological signals through an electrophysiological recording channel layer, realizes optical stimulation through a laser diode 9 coupled optical waveguide, and realizes the suppression of electromagnetic interference through grounding a metal shielding layer 5 to realize low-noise collection.
The packaging structure of the photoelectric nerve probe and the laser diode can be prepared by the following method:
fixing the photoelectrode on a glass slide by using double-sided adhesive tape, attaching anisotropic conductive adhesive ACF10 on a pad of the photoelectrode, aligning a pressure head of a hot press with the ACF (anisotropic conductive adhesive film) on the pad, and pre-pressing, wherein the pre-pressing pressure is 0.14MPa, the temperature is 140 ℃, and the hot-pressing time is 3-5 s. And after the pre-pressing is finished, the ACF diaphragm is taken off.
Transferring the photoelectric nerve probe to a heating table for fixing, then raising the temperature to more than 200 ℃ to melt the ACF, transferring the laser diode 9 to the ACF by using a micro-operation rod, finely adjusting the laser diode to be aligned and coupled with the optical waveguide 8, applying certain pressure to enable the anode of the laser diode to be fully contacted with conductive particles in the ACF, then transferring the photoelectric nerve probe to another platform, cooling to room temperature to solidify the ACF, and realizing the packaging of the anode of the laser diode.
The cathode (upper surface) pad of the laser diode 9 and the cathode pad on the photoelectric nerve probe are connected together using a wire bonding machine, and the encapsulation of the cathode is realized.
In order to further illustrate the capability of the photoelectric nerve probe integrated with the internal metal shielding layer to inhibit the electromagnetic interference from a power supply channel of a laser diode, the in-vitro test of the low-noise photoelectric nerve probe is realized through an MEMS processing technology.
Referring to fig. 5 and 6, stimulation following artifact signals recorded in phosphate buffer when a common nerve probe and the photoelectric nerve probe in the embodiment are lighted in a pulse mode by a laser diode are respectively shown.
In FIG. 5, (a) shows a drive pulse current of a blue laser diode (wavelength 420nm) having an amplitude of 100mA, a frequency of 10Hz, and a duty ratio of 10%. As can be seen from (b) and (c) of fig. 5, the dc bias of a conventional neural probe is as high as 5.8 mv, and thus a neural action potential having an amplitude of several hundred microvolts is submerged. As can be seen from (d) and (e) in fig. 6, the dc bias is only 26 microvolts during the laser diode lighting time, and the pollution to the nerve action potential is greatly reduced.
In conclusion, the photoelectric nerve probe integrated with the internal metal layer provided by the invention isolates the electrophysiological signal recording channel and the power supply channel of the laser diode in a layered manner, so that the stimulation following artifact generated by electromagnetic interference recorded by the electrophysiological channel is greatly attenuated, and the pollution to nerve action potential caused by the stimulation following artifact in the process of carrying out optogenetic experiment in an animal body is reduced. Meanwhile, the anode is bonded by using anisotropic conductive Adhesive (ACF), and the cathode is bonded by using gold wire ball bonding to realize the packaging of the laser diode, so that the cost for packaging the laser diode is reduced. The invention has great promotion effect on the wide application of the optogenetic technology.
The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention.
Claims (9)
1. The utility model provides an integrated inside metal shielding layer's photoelectric nerve probe which characterized in that: the method comprises the following steps:
a silicon substrate layer;
the electrophysiological signal recording channel is arranged on the silicon substrate layer and is used for conducting the neural electric signal from the electrode point to a channel of an acquisition system;
the laser diode power supply channel is arranged on the silicon substrate layer and is used for conducting a pulse type current or voltage signal to a path used for driving the laser diode to work at a pad at the base part of the nerve probe;
a metal shielding layer disposed on the silicon substrate layer; the metal shielding layer is integrated between the electrophysiological signal recording channel and the laser diode power supply channel and used for isolating the electrophysiological signal recording channel and the laser diode power supply channel, and the metal shielding layer is grounded, so that the attenuation of a stimulation following artifact generated by electromagnetic interference is realized, and the pollution of the stimulation following artifact to a nerve action potential in the optogenetic experiment process can be reduced;
a laser diode; the anode of the laser diode is connected with the anode bonding pad of the photoelectric nerve probe through anisotropic conductive adhesive bonding, the cathode of the laser diode is connected with the cathode bonding pad of the photoelectric nerve probe through gold wire ball bonding, and the laser diode is packaged, namely the laser diode is integrated to the rear end base of the photoelectric nerve probe.
2. The optoelectronic neural probe integrated with an internal metal shielding layer as claimed in claim 1, wherein: the electrophysiological signal recording channel is made of biocompatible materials;
the biocompatible material comprises any one of gold, titanium, platinum or platinum iridium alloy.
3. The optoelectronic neural probe integrated with an internal metal shielding layer as claimed in claim 1, wherein: the laser diode power supply channel is made of a biocompatible material;
the biocompatible material comprises any one of gold, titanium, platinum or platinum iridium alloy.
4. The optoelectronic neural probe integrated with an internal metal shielding layer as claimed in claim 1, wherein: further comprising:
a first insulating layer; the first insulating layer is arranged on the silicon substrate layer, and the electrophysiological signal recording channel is arranged above the first insulating layer;
the second insulating layer is arranged above the electrophysiological signal recording channel, and the metal shielding layer is arranged above the second insulating layer;
and the third insulating layer is arranged above the metal shielding layer, and the laser diode power supply channel is arranged above the third insulating layer.
5. The integrated inner metal shielding layer photoelectric nerve probe according to claim 4, wherein: further comprising:
the waveguide lower cladding is arranged above the laser diode power supply channel;
an optical waveguide layer disposed above the waveguide lower cladding layer;
a waveguide upper cladding layer disposed above the optical waveguide layer.
6. The method for preparing the photoelectric nerve probe integrated with the internal metal shielding layer according to claim 1, which comprises the following steps: preparing an electrophysiological signal recording channel, preparing a metal shielding layer above the electrophysiological signal recording lead layer, and then preparing a laser diode power supply channel above the metal shielding layer.
7. The method for preparing an optoelectronic neural probe integrated with an internal metal shielding layer as claimed in claim 6, further comprising: before the step of preparing the electrophysiological signal recording channel, preparing a first insulating layer and then preparing the electrophysiological signal recording channel above the first insulating layer; then after the step of preparing the electrophysiological signal recording channel, preparing a second insulating layer above the electrophysiological signal recording channel, then preparing the metal shielding layer above the second insulating layer, after the step of preparing the metal shielding layer, preparing a third insulating layer above the metal shielding layer, and finally preparing the laser diode power supply channel above the third insulating layer.
8. The method for preparing the photoelectric nerve probe integrated with the internal metal shielding layer as claimed in claim 6, wherein the method comprises the following steps:
s1: selecting on-chip insulating silicon as a substrate, wherein the substrate comprises top silicon, an oxygen burying layer and bottom silicon, depositing a layer of silicon oxide on the substrate as a first insulating layer, and the first insulating layer is positioned above the top silicon;
s2: preparing a metal adhesion layer on the first insulating layer, preparing a metal conductive layer on the metal adhesion layer, preparing a metal layer on the metal conductive layer as an etching barrier layer, and patterning to obtain an electrophysiological signal recording channel with bent wiring;
s3: depositing a layer of silicon oxide on the electrophysiological signal recording wire layer to serve as an intermediate insulating layer to obtain a second insulating layer, preparing a metal adhesion layer on the second insulating layer, then preparing a metal conducting layer on the metal adhesion layer, then preparing a layer of metal on the metal conducting layer to serve as an etching barrier layer, and patterning to obtain the metal shielding layer;
s4: depositing a layer of silicon oxide on the metal shielding layer to serve as a top insulating layer to obtain a third insulating layer, preparing a metal adhesion layer on the third insulating layer, then preparing a metal conducting layer on the metal adhesion layer, then preparing a layer of metal on the metal conducting layer to serve as an etching barrier layer, and patterning to obtain the power supply channel of the laser diode;
s5: depositing a layer of silicon oxide on the power supply channel of the laser diode, preparing a layer of metal on the silicon oxide as an etching barrier layer, depositing a layer of silicon oxide on the etching barrier layer, and depositing a layer of silicon oxynitride on the silicon oxide;
s6: forming an optical waveguide layer and a waveguide lower cladding layer by a dry etching process, and then removing the barrier layer in S5 by wet etching;
s7: depositing a layer of silicon oxide on the optical waveguide as an upper waveguide cladding, etching the upper waveguide cladding, the third insulating layer and the second insulating layer by a dry etching process, exposing a power supply pad of the laser diode, the outer part of the metal shielding layer, a recording electrode point and a pad region, and then removing the barrier layer from S2 to S4 by wet etching;
s8: etching the first insulating layer by a dry etching process, and etching the top silicon of the on-chip insulating silicon by deep reactive ions to be used as a contour line of release of the nerve probe;
s9: spin-coating positive glue with a certain thickness on the upper surface of the on-chip insulating silicon to serve as a protective layer;
s10: and etching the bottom silicon of the on-chip insulating silicon by deep reactive ion etching, and etching the buried oxide layer in the middle of the on-chip insulating silicon wafer by a reactive ion etching process to release the nerve probe.
9. The method for preparing an integrated inner metal shielding layer photoelectric nerve probe of claim 8, wherein a layer of metal prepared in S2, S3, S4 and S5 is used as the etching barrier layer to realize etching of silicon oxide with different depths.
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| CN111863777B (en) * | 2020-07-30 | 2022-05-31 | 中山大学 | Low-noise single-sided integrated injectable biological photoelectric electrode microprobe and preparation method thereof |
| CN111863776B (en) * | 2020-07-30 | 2022-09-20 | 中山大学 | Low-noise double-sided integrated injectable biological photoelectric electrode microprobe and preparation method thereof |
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| CN113476050B (en) * | 2021-07-01 | 2022-09-27 | 中国科学院空天信息创新研究院 | Nerve microprobe and preparation method thereof |
| CN115285930A (en) * | 2022-07-25 | 2022-11-04 | 武汉衷华脑机融合科技发展有限公司 | Micro-needle and flat cable inverse welding connecting structure and preparation process thereof |
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