CN111939482B - Optical device of flexible implanted nerve photoelectric electrode and design and preparation method thereof - Google Patents
Optical device of flexible implanted nerve photoelectric electrode and design and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an optical device of a flexible implanted nerve photoelectric electrode, which is arranged on a flexible polymer substrate and comprises: the single-cell optical stimulation device comprises an input grating, a waveguide and an output grating, wherein the input grating is a parallel grating and is used for coupling incident light, the input end of the waveguide is coupled and connected with the input grating, the output end of the waveguide is coupled and connected with the output grating, and the output grating is a focusing grating and is used for coupling and focusing light to irradiate above a recording electrode so as to provide optical stimulation with single-cell resolution. The invention also discloses a design and preparation method of the optical device. The optical device of the flexible implanted nerve photoelectric electrode provided by the invention provides light stimulation and in-situ recording of single-cell resolution by designing the waveguide and the grating; the small size of the device can reduce implantation damage, and has low loss, high coupling and strong focusing; the high integration level is beneficial to realizing multi-channel and high-density nerve stimulation and recording; the flexible polymer substrate can reduce the formation of nerve scars and realize long-term in-vivo stable work.
Description
Technical Field
The invention relates to the field of neuroscience, in particular to an optical device of a flexible implantable nerve photoelectric electrode and a design and preparation method thereof.
Background
The photoelectrode is an important component of the application of the optogenetic tool, and has the functions of guiding light into the brain to regulate the activity of neurons and recording the change condition of electrical signals of the neurons under the condition of light regulation. With the application of the optogenetic technology in neuroscience research and the exploration of the optogenetic technology in disease treatment, photoelectrode matched with the optogenetic technology shows a full-fledged development situation from the aspects of material selection, device structure, light supply mode, integration process and the like.
Among them, there are two main ways of supplying Light to the implanted nerve Light electrode, one is to provide Light stimulation by disposing a Light Emitting Diode (LED) or a Laser Diode (LD) as a Light source near the recording electrode device, and the other is to provide Light stimulation by guiding Light in an optical fiber to the vicinity of the recording electrode through an optical waveguide and Emitting the Light. On one hand, the LED or LD is easy to generate heat to cause nerve damage when working, heat generation evaluation and control need to be additionally considered, and the waterproof performance of the device needs to be considered when in preparation, so that the biocompatibility and the reliability of the device are inferior to those of a waveguide; on the other hand, the waveguide has smaller size, the damage is reduced in the implantation process, the integration level of the device can be improved, the number and density of recording channels are improved, in addition, the grating is used at the front end of the waveguide for coupling and outputting light, and the profile of the output light can be conveniently controlled through the design of the grating.
The material selection of the waveguide of the implanted nerve photoelectric electrode is also mainly two, one is the optical waveguide realized based on SU-8 and other polymer materials, but the length and width of the waveguide section generally reach 10-20 μm, which results in larger size of the implanted body, increased implantation damage, low device integration level and is not beneficial to realizing high-density and multi-channel nerve cell stimulation and signal recording; the substrate of the optical waveguide is made of hard materials such as a silicon substrate, the Young modulus of the hard substrate is not matched with that of brain tissue after the device is implanted, so that relative movement of an implant and the brain tissue in the body process of the device can cause large stress such as shearing force and the like, a large number of nerve scars are formed around the implant, and long-term stable operation in the body is difficult to realize.
Optical waveguides fabricated based on micro electro-Mechanical systems (MEMS) processes exhibit the advantages of integrated devices: the waveguide size of dozens of microns greatly reduces the cross section damage caused by photoelectrode implantation, and simultaneously, the flexibility of the MEMS process enables the photoelectrode to be more easily integrated with an electrode device, and a photoelectrode device containing a plurality of photoelectric channels, multiple colors and multiple sites can be manufactured. The size of the electrical and optical devices is defined by photoetching, and the accurate control of the relative position between the stimulation site and the recording electrode can be realized.
Therefore, compared with the advantages and disadvantages of the light supply mode, material selection and processing technology, a new optical device structure comprising a waveguide and a grating needs to be designed and used in a flexible implanted nerve photoelectric electrode, so that the size of the electrode is smaller, the integration degree is higher, and the light supply is more accurate and efficient.
Disclosure of Invention
The invention aims to solve the technical problems of reducing the size of an optical device in an implanted nerve photoelectrode, improving the integration level of the optical device and providing accurate and efficient light stimulation.
In order to solve the technical problems, the invention discloses an optical device of a flexible implantable nerve photoelectric electrode and a design and preparation method thereof. The specific technical scheme is as follows:
in a first aspect, the present invention discloses an optical device of a flexible implantable nerve-light electrode, wherein the optical device is disposed on a flexible polymer substrate of the flexible implantable nerve-light electrode, and the optical device includes:
an input grating, a waveguide and an output grating,
the input grating is a parallel grating structure and is used for coupling incident light with preset wavelength and incident angle,
the input end of the waveguide is coupled with the input grating, the output end of the waveguide is coupled with the output grating,
the output grating is a focusing grating structure and is used for coupling and focusing light to irradiate the upper part of a recording electrode of the flexible implanted nerve photoelectric electrode so as to provide light stimulation with single cell resolution.
Preferably, the optical device further comprises:
the input end of the tapered waveguide is coupled with the input grating, and the output end of the tapered waveguide is optically connected with the waveguide so as to realize the coupling connection of the input end of the waveguide and the input grating;
the width of the input end of the tapered waveguide is larger than that of the output end of the tapered waveguide, and the tapered waveguide is used for converting a transmission mode of light;
the waveguide is a rectangular waveguide, and the transmission mode of light in the waveguide is single-mode transmission.
Preferably, the grating period of the input grating is set to be the maximum grating period capable of coupling incident light with a preset incident wavelength and a preset incident angle, and the setting of the etching depth and the duty ratio of the input grating satisfies the coupling efficiency condition of light at the preset incident wavelength.
Preferably, the output grating is of an elliptical focusing grating structure, the grating period of the output grating is variable, the setting of the variable grating period meets the requirement that the light intensity distribution focus of the emergent light is matched with a preset light stimulation point and an electrode recording point, and the setting of the etching depth and the duty ratio of the output grating meets the requirement of the coupling efficiency condition and the focusing intensity condition of light at the preset wavelength.
Preferably, the input grating, the tapered waveguide, the waveguide and the output grating are made of silicon nitride, and the flexible polymer substrate is made of SU-8 photoresist.
In a second aspect, the invention discloses a design method of an optical device of a flexible implantable nerve-light electrode, wherein the optical device is arranged on a flexible polymer substrate of the flexible implantable nerve-light electrode, and the method comprises the following steps:
respectively arranging a mode light source and a field monitor at two sides of a waveguide, simulating based on a time domain finite difference method, determining the size parameter of the waveguide, and finishing the design of the waveguide;
arranging a mode light source on one side of an input grating, arranging a field monitor on one side of the waveguide, simulating based on a time domain finite difference method, and optimizing the structural parameters of the input grating to complete the design of the input grating;
and arranging a mode light source on one side of the waveguide, arranging field monitors on three planes where the light stimulation points are located, simulating based on a time domain finite difference method, optimizing the structural parameters of the output grating, and finishing the design of the output grating.
Preferably, the design of the waveguide comprises:
performing initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises a flexible polymer substrate refractive index, a waveguide size, waveguide surface roughness and/or a light source wavelength;
arranging a mode light source at the input end of the waveguide to analyze the waveguide effective refractive index under different light transmission modes; setting a field monitor at the output end of the waveguide to analyze the transmission loss of the waveguides with different sizes;
simulating based on a finite difference time domain method, and obtaining a first simulation analysis result;
and determining the size parameters of the waveguide meeting the effective refraction condition and the transmission loss condition according to the first simulation analysis result, and finishing the design of the waveguide.
Preferably, the design of the input grating comprises:
carrying out initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises a flexible polymer substrate refractive index, a waveguide size, waveguide surface roughness, an incident light wavelength and/or an incident angle;
disposing a mode light source obliquely above the input grating, disposing a field monitor at an output end of the waveguide to analyze a coupling efficiency of the input grating;
obtaining the grating period of the input grating through a first phase matching condition, and performing primary simulation based on a finite difference time domain method to obtain a second simulation analysis result;
optimizing the grating period of the input grating according to the second simulation analysis result to meet the coupling requirement of the incident light wavelength and the incident angle, optimizing the etching depth and the duty ratio of the input grating according to the second simulation analysis result to meet the coupling efficiency condition at the incident light wavelength, and completing the design of the input grating.
Preferably, the design of the output grating comprises:
carrying out initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises a flexible polymer substrate refractive index, a waveguide size, waveguide surface roughness, incident light wavelength and/or light stimulation point coordinates;
setting a mode light source at the input end of the waveguide, and respectively setting field monitors on three planes where the optical stimulation point coordinates are located so as to analyze the distribution of output light intensity;
obtaining a grating groove line equation of the output grating through a second phase matching condition, and performing primary simulation based on a time domain finite difference method to obtain a third simulation analysis result;
determining the focus and the coordinate of the output light intensity distribution according to the third simulation analysis result;
and optimizing the grating period of the output grating according to the focus and the coordinates thereof, so that the coordinates of the focus are matched with the coordinates of the optical stimulation point under the incident light wavelength, optimizing the etching depth and the duty ratio of the output grating according to the third simulation analysis result, meeting the coupling efficiency condition and the focusing intensity condition at the incident light wavelength, and finishing the design of the output grating.
In a third aspect, the invention discloses a preparation method of an optical device of a flexible implanted nerve photoelectrode, which comprises the following steps:
s1: patterning the photoresist on a clean substrate by photoetching to obtain an alignment mark structure;
s2: depositing metal on the patterned photoresist to obtain a metal alignment mark structure;
s3: preparing a flexible polymer substrate on the metal alignment mark structure prepared in the step S2 through photoetching;
s4: depositing a silicon nitride film on the flexible polymer substrate prepared in the step S3;
s5: and taking the metal alignment mark structure obtained in the step S2 as a photoetching alignment mark, and carrying out twice patterning on the silicon nitride film through photoetching to respectively obtain a waveguide and a grating structure, wherein the grating structure comprises an input grating and an output grating, and the input grating, the waveguide and the output grating form an optical device of the flexible implanted nerve photoelectric electrode and are arranged on a flexible polymer substrate of the flexible implanted nerve photoelectric electrode.
Preferably, the substrate is a single polished silicon wafer with the thickness of 300-500 μm.
Preferably, the step S2 specifically includes:
depositing a chromium/gold alloy layer with the thickness of 5nm/50nm-10nm/100nm on the patterned photoresist through thermal evaporation, and obtaining a metal alignment mark structure through a stripping process.
Preferably, the step S3 specifically includes:
and spin-coating SU-8 photoresist on the metal alignment mark structure at the rotating speed of 500-.
Preferably, the step S4 specifically includes:
and depositing a silicon nitride film with the thickness of 100-300nm on the flexible polymer substrate taking SU-8 as the material by a low-temperature chemical vapor deposition process to serve as a preparation material of the optical device.
By adopting the technical scheme, the optical device of the flexible implantable nerve photoelectric electrode and the design and preparation method thereof have the following beneficial effects:
1) the optical device of the flexible implanted nerve photoelectrode has the advantages that through the optimized design of the waveguide and the grating, the transmission loss is low, the coupling efficiency is high, the focusing characteristic is strong, the optical stimulation with single cell resolution can be realized, and the realization of accurate stimulation, in-situ recording and cross-brain area synchronous recording through the interconnection of photoelectric signals is facilitated;
2) the optical device of the flexible implanted nerve photoelectrode provided by the invention adopts a flexible polymer material as a substrate, so that the injury of the device during implantation and the nerve scar caused in the body can be reduced, and the long-term stable in-vivo work can be realized;
3) the optical device of the flexible implanted nerve photoelectric electrode provided by the invention is based on an MEMS (micro-electromechanical systems) processing technology, has small size and high integration level, further reduces implantation damage, and is favorable for realizing high-density and multi-channel nerve cell stimulation and signal recording.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
Fig. 1 is a structural exploded view of a flexible implantable nerve photoelectrode provided by an embodiment of the invention;
fig. 2 is a schematic structural diagram of an optical device of a flexible implantable nerve photoelectrode according to an embodiment of the present invention;
FIG. 3 is a diagram of a simulated design structure of a waveguide according to a second embodiment of the present invention;
fig. 4 is a diagram illustrating a first simulation analysis result of effective refractive indexes of different transmission modes under different waveguide widths according to a second embodiment of the present invention;
FIG. 5 is a diagram of a simulated design structure of an input grating according to a second embodiment of the present invention;
fig. 6 is a diagram illustrating a second simulation analysis result of the variation of the coupling efficiency of the input grating structure with the wavelength of the incident light according to the second embodiment of the present invention;
fig. 7 is a simulation design structure diagram of an output grating according to a second embodiment of the present invention;
FIG. 8 is a diagram illustrating a light intensity distribution of emergent light focused by an output grating according to a second embodiment of the present invention;
FIG. 9 is a diagram illustrating a light intensity distribution of an exit light focus according to a second embodiment of the present invention;
FIG. 10 is a schematic diagram of the light intensity distribution of the exit light focus along the major axis of the ellipse according to the second embodiment of the present invention;
FIG. 11 is a schematic diagram of the light intensity distribution of the exit light focus along the minor axis of the ellipse according to the second embodiment of the present invention;
fig. 12 is a schematic flow chart of a method for manufacturing an optical device of a flexible implantable nerve photoelectrode according to a third embodiment of the invention;
in the figure, 1-optics, 2-input grating, 3-tapered waveguide, 4-waveguide, 5-output grating, 6-flexible polymer substrate, 7-mode light source, 8-field monitor, 9-incident light, 10-photostimulation point/focus.
Detailed Description
In order to make the technical solutions of the present invention better understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic may be included in at least one implementation of the invention. In describing the present invention, it is to be understood that the terms "first," "second," "third," and "fourth," etc. in the description and claims of the present invention and the above-described drawings are used for distinguishing between different objects and not for describing a particular order. Furthermore, the terms "include" and "have," as well as any variations thereof, are intended to cover non-exclusive inclusions. For example, a process, method, system, article, or apparatus that comprises a list of steps or elements is not limited to only those steps or elements listed, but may alternatively include other steps or elements not listed, or inherent to such process, method, article, or apparatus.
Example one
The embodiment of the invention provides an optical device of a flexible implanted nerve photoelectric electrode, wherein the optical device 1 is arranged on a flexible polymer substrate 6 of the flexible implanted nerve photoelectric electrode. The split structure of the flexible implantable nerve photoelectrode is shown in figure 1. The bottom layer of the flexible implantable nerve photoelectric electrode is an optical device 1, the optical device 1 is arranged on a flexible polymer substrate 6, and the flexible polymer substrate 6 is made of flexible polymer materials.
The structure of the optical device 1 of the flexible implantable nerve photoelectrode is shown in fig. 2. The optical device 1 comprises:
an input grating 2, a waveguide 4 and an output grating 5,
the input grating 2 is a parallel grating structure and is used for coupling incident light 9 with preset wavelength and incident angle,
the input end of the waveguide 4 is coupled with the input grating 2, the output end of the waveguide 4 is coupled with the output grating 5,
the output grating 5 is a focusing grating structure and is used for coupling and focusing light to irradiate the upper part of a recording electrode of the flexible implanted nerve photoelectric electrode so as to provide light stimulation with single cell resolution.
Further, the optical device 1 further includes: the input end of the tapered waveguide 3 is coupled with the input grating 2, and the output end of the tapered waveguide 3 is optically connected with the waveguide 4, so that the input end of the waveguide 4 is coupled with the input grating 2; the width of the input end of the tapered waveguide 3 is larger than that of the output end, and the tapered waveguide is used for converting a transmission mode of light; the waveguide 4 is a rectangular waveguide, and the transmission mode of light in the waveguide 4 is single-mode transmission.
In the first embodiment of the present invention, the input grating 2, the tapered waveguide 3, the waveguide 4, and the output grating 5 are made of silicon nitride to reduce transmission loss, and the flexible polymer substrate 6 is made of SU-8 photoresist, so that device implantation damage and nerve scar caused during in vivo period can be reduced, and long-term stable in vivo operation can be achieved.
In the first embodiment of the present invention, based on the convenience of the processing technology, the grating period of the input grating 2 is set to be the maximum grating period capable of coupling the incident light 9 with the preset incident wavelength and the preset incident angle, and the etching depth and the duty ratio of the input grating 2 are set to satisfy the condition of the coupling efficiency of the light at the preset incident wavelength, for example, the coupling efficiency is the highest at or near the wavelength. The output grating 5 is of an oval focusing grating structure, the grating period of the output grating 5 is variable, the setting of the variable grating period meets the requirement that the light intensity distribution focus of emergent light is matched with a preset light stimulation point and an electrode recording point, the setting of the etching depth and the duty ratio of the output grating 5 meets the requirement that the coupling efficiency condition and the focusing intensity condition of light at the preset wavelength, for example, the focus size is smaller than the size of nerve cells.
Example two
The second embodiment of the present invention provides a design method for an optical device of a flexible implantable nerve photoelectric electrode, where the optical device 1 is disposed on a flexible polymer substrate 6 of the flexible implantable nerve photoelectric electrode, and the method includes:
s100: and respectively arranging a mode light source 7 and a field monitor 8 at two sides of the waveguide 4, simulating based on a time domain finite difference method, determining the size parameter of the waveguide 4, and finishing the design of the waveguide 4.
Specifically, as shown in fig. 3 and 4, step S100 provided in the second embodiment of the present invention may include the following steps:
s110: and carrying out initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises the refractive index of the flexible polymer substrate, the refractive index of the waveguide, the size of the waveguide, the roughness of the surface of the waveguide and/or the wavelength of the light source.
Specifically, the waveguide material is silicon nitride, the refractive index is 1.9, and the root-mean-square roughness of the waveguide surface is 0.5 nm; a flexible polymer substrate is arranged below the waveguide, SU-8 photoresist is used as the material of the flexible polymer substrate, and the refractive index of the flexible polymer substrate is 1.57 so as to ensure that an optical field cannot leak through the substrate; the waveguide height was set at 220nm and the light source wavelength was 532 nm.
In some other possible embodiments, to meet the small size requirements of the device, simulation analysis can be performed on waveguide widths in the range of 100nm-1000nm and waveguide heights in the range of 100nm-500 nm.
S120: arranging a mode light source 7 at the input end of the waveguide 4 to analyze the waveguide effective refractive index under different light transmission modes; a field monitor 8 is provided at the output of the waveguide 4 to analyze the transmission losses of different sized waveguides.
S130: and carrying out simulation based on a time domain finite difference method, and obtaining a first simulation analysis result.
S140: and determining the size parameters of the waveguide 4 meeting the effective refraction condition and the transmission loss condition according to the first simulation analysis result, and finishing the design of the waveguide 4.
Specifically, the effective refractive index n of different transmission modes at different waveguide widths shown in FIG. 4effIt can be known that, under the current preset condition, when the waveguide width is less than 630nm, the effective refractive index of the TE1 mode is lower than 1.57, that is, the effective refractive index of the substrate material, so that when the waveguide width is less than 600nm, only the fundamental mode can be propagated in the waveguide, and a single-mode waveguide is realized; furthermore, considering that the effective refractive index cannot be too small, and that too close to the refractive index of the substrate material results in too long attenuation length of the optical field in the substrate material, resulting in large waveguide propagation loss, it is preferable that the transmission loss of the waveguide be controlled to 1dB/cm or less,
according to the simulation result, in order to ensure that the single-mode propagation waveguide width should not be too close to 600nm, and considering the reduction of the device size as much as possible, a value in the range of 400-500nm may be selected as a suitable waveguide width.
S200: and arranging a mode light source 7 at one side of the input grating 2, arranging a field monitor 8 at one side of the waveguide 4, simulating based on a time domain finite difference method, and optimizing the structural parameters of the input grating 2 to complete the design of the input grating 2.
Specifically, as shown in fig. 5 and fig. 6, step S200 provided in the second embodiment of the present invention may include the following steps:
s210: and carrying out initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises the refractive index of the flexible polymer substrate, the refractive index of the waveguide, the size of the waveguide, the roughness of the surface of the waveguide, the wavelength of incident light and/or the incident angle.
Specifically, SU-8 photoresist is used as a material of a flexible polymer substrate, and the refractive index of the material is 1.57 so as to ensure that an optical field cannot leak through the substrate; the method comprises the following steps that three structures of an input grating, a tapered waveguide and a waveguide are placed on a substrate, the input grating is used for coupling incident light into the waveguide, the tapered waveguide grating is used for converting a light mode from a multimode mode into a single mode to enter the waveguide for single mode transmission, materials of the tapered waveguide grating are silicon nitride, the refractive index of the silicon nitride is 1.9, and the root-mean-square roughness of the surface of the waveguide is 0.5 nm; the height of the waveguide is set to be 220nm, the wavelength of the light source is set to be 600-660nm, the angle between incident light and the vertical direction is 10 degrees, and the design requirement is that the coupling efficiency is highest near 637nm wavelength.
S220: a mode light source 7 is arranged obliquely above the input grating 2 and a field monitor 8 is arranged at the output of the waveguide 4 to analyze the coupling efficiency of the input grating 2.
Specifically, incident light is emitted from a mode light source and is incident on an input grating in parallel at an angle.
S230: and obtaining the grating period of the input grating 2 through a first phase matching condition, and performing preliminary simulation based on a time domain finite difference method to obtain a second simulation analysis result.
Specifically, the initial setting of the grating period is based on the phase matching condition,
where β is the wavevector of the propagating mode in the grating region, k is the wavevector of the incident light in vacuum, nmIs the refractive index of the medium in the spatial propagation region, θ is the incident angle of the incident light, Λ is the period of the grating, and m is 0,1,2.
In some possible embodiments, the grating period of the input grating is constant, and is used to couple collimated light incident at a specific angle into the waveguide, different grating periods can be solved for different values of m, and these different grating periods can all satisfy the design requirements, and the maximum grating period satisfying the conditions is generally selected as the grating period of the input grating based on the consideration of processing convenience.
S240: optimizing the grating period of the input grating 2 according to the second simulation analysis result to meet the coupling requirement of the incident light wavelength and the incident angle, optimizing the etching depth and the duty ratio of the input grating 2 according to the second simulation analysis result to meet the coupling efficiency condition at the incident light wavelength, and completing the design of the input grating 2.
Specifically, the grating period mainly affects the wavelength and angle of incident light, and the etching depth and duty cycle affect the coupling efficiency. The grating period is optimized to achieve the required incident wavelength and angle, and then the etching depth and the duty ratio are adjusted to achieve the maximum coupling efficiency. From the analysis graph of the change of the coupling efficiency of the grating structure with the wavelength of the incident light shown in fig. 6, under the current preset condition, the optimized grating period is 442nm, the etching depth is 110nm, the duty ratio is 50%, the coupling efficiency at or near 637nm wavelength is the highest, the wavelengths corresponding to half-peak are 0.6303 μm and 0.6415 μm respectively, and the full width at half-peak FWMH is 11.2nm, which meets the design requirement.
S300: and arranging a mode light source 7 at one side of the waveguide 4, arranging field monitors 8 on three planes where the light stimulation points 10 are positioned, simulating based on a finite difference time domain method, and optimizing the structural parameters of the output grating 5 to complete the design of the output grating 5.
Specifically, as shown in fig. 7 to 11, step S300 provided in the second embodiment of the present invention may include the following steps:
s310: and carrying out initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises the refractive index of the flexible polymer substrate, the refractive index of the waveguide, the size of the waveguide, the roughness of the surface of the waveguide, the wavelength of incident light and/or the coordinates of a light stimulation point.
Specifically, SU-8 photoresist is used as a material of a flexible polymer substrate, and the refractive index of the material is 1.57 so as to ensure that an optical field cannot leak through the substrate; the single cell stimulation device comprises a substrate, an output grating and a waveguide, wherein the substrate is provided with two parts of structures, the output grating selects a focusing grating structure and is used for converging light on a focus of a single cell scale to realize accurate stimulation of the single cell, the materials of the output grating are all silicon nitride, the refractive index of the silicon nitride is 1.9, the root-mean-square roughness of the surface of the waveguide is 0.5nm, the height of the waveguide is 220nm, and the wavelength of a light source is 637 nm.
S320: a mode light source 7 is arranged at the input end of the waveguide 4, and field monitors 8 are respectively arranged on three planes where the coordinates of the optical stimulation points 10 are located so as to analyze the distribution of output light intensity.
Specifically, three field monitors are placed in the xy plane, the xz plane, and the yz plane, respectively, which contain the light stimulation points. The incident light is emitted from the mode light source to the waveguide, passes through the output grating and is focused and irradiated.
S330: and obtaining a grating groove line equation of the output grating 5 through a second phase matching condition, and performing preliminary simulation based on a time domain finite difference method to obtain a third simulation analysis result.
In particular, the initial setting of the grating geometry is based on the phase matching equation,
wherein n iseffIs the effective refractive index in the grating region, f (x), f (y), f (z) are the coordinates of the predetermined light stimulation points, nmThe grating groove is formed by solving a plurality of elliptic lines corresponding to different m values, wherein the elliptic lines are the grating grooves, and m is 0,1,2. Due to the setting of the coordinate axes, y in the grating groove line equation is 0.
S340: and determining the focus and the coordinates of the output light intensity distribution according to the third simulation analysis result.
Specifically, the output light intensity distribution obtained by the field monitor above the output grating is shown in fig. 8, and the x and y axes of the light intensity distribution map correspond to the x and y axes in fig. 7. It can be seen that by focusing the output grating an elliptical focus is obtained, the intensity distribution of which is shown in fig. 9, with the coordinates of the focus being (20,19.7, 0).
S350: optimizing the grating period of the output grating 5 according to the focus and the coordinates thereof, so that the coordinates of the focus are matched with the coordinates of the optical stimulation point 10 under the incident light wavelength, optimizing the etching depth and the duty ratio of the output grating 5 according to the third simulation analysis result, meeting the coupling efficiency condition and the focusing intensity condition at the incident light wavelength, and completing the design of the output grating 5.
Specifically, the position of the groove line of the output grating is adjusted, for example, the major axis and the minor axis of the elliptical groove line are adjusted to realize the required focal coordinates, namely the coordinates of the photostimulation point, under the required wavelength, so that the focal point of the light focusing is positioned above the recording electrode, the same cell for photostimulation and electrophysiological recording is ensured, and the in-situ recording is realized. The grating period of the output grating is variable, that is, the interval width between different groove lines is different. The etch depth and duty cycle are readjusted to achieve maximum coupling efficiency at a given wavelength. Under the current preset condition, the etching depth is 110nm, and the duty ratio is 50%.
As shown in fig. 10 and 11, the light intensity distribution near the focal point along the major axis α and the minor axis β of the ellipse shows that the full width at half maximum (FWMH) of the light intensity distribution along the α axis is 7.594 μm, and the full width at half maximum (FWMH) of the light intensity distribution along the β axis is 0.669 μm, so that the focal point with small size and high focusing intensity can completely realize accurate light focusing irradiation on a single cell and realize accurate light stimulation on a single cell scale, compared with a general nerve cell with a size of several tens of micrometers.
EXAMPLE III
The third embodiment of the present invention provides a method for manufacturing an optical device of a flexible implantable nerve photoelectric electrode, as shown in fig. 12, the method includes:
s1: and patterning the photoresist on a clean substrate by photoetching to obtain an alignment mark structure.
Preferably, the substrate is a single polishing silicon wafer with a thickness of 300-500 μm (for example, 400 μm), and the single polishing silicon wafer is cleaned for use.
S2: and depositing metal on the patterned photoresist to obtain a metal alignment mark structure.
Specifically, on the patterned photoresist, a chromium/gold alloy layer with a thickness of 5nm/50nm-10nm/100nm (e.g. 5nm/100nm) is deposited by thermal evaporation, and a metal alignment mark structure is obtained by a lift-off process.
S3: a flexible polymer substrate 6 is prepared on the metal alignment mark structure prepared in step S2 by photolithography.
Specifically, an SU-8 photoresist is spin-coated on the metal alignment mark structure at a rotation speed of 500-1500r/min (e.g., 1000r/min) for 20-40s (e.g., 30s), an SU-8 thin film with a thickness of 1500-2500nm (e.g., 2000nm) is prepared, and the SU-8 thin film is patterned by photolithography, so as to obtain the flexible polymer substrate 6 using SU-8 as a material.
S4: and depositing a silicon nitride film on the flexible polymer substrate prepared in the step S3.
Specifically, a silicon nitride film with the thickness of 100-300nm (for example, 200nm) is deposited on the flexible polymer substrate 6 taking SU-8 as a material through a low-temperature chemical vapor deposition process to serve as a preparation material of an optical device.
S5: and taking the metal alignment mark structure obtained in the step S2 as a lithography alignment mark, and performing two-time patterning on the silicon nitride film through lithography to obtain a waveguide 4 and a grating structure, respectively, where the grating structure includes an input grating 2 and an output grating 5, and the input grating 2, the waveguide 4, and the output grating 5 constitute an optical device of the flexible implanted nerve light electrode and are disposed on a flexible polymer substrate 6 of the flexible implanted nerve light electrode.
Preferably, the tapered waveguide 3 can also be obtained by patterning the silicon nitride film twice by photolithography.
The preparation method provided by the third embodiment of the invention is mainly based on the MEMS processing technology, further reduces the size, improves the integration level, can reduce implantation damage, and is favorable for realizing high-density and multi-channel nerve cell stimulation and signal recording.
On the basis of the flexible polymer substrate and the optical device obtained by the preparation method provided by the third embodiment of the invention, the flexible implantable nerve photoelectrode can be further prepared to research neuroscience.
The optical device of the flexible implantable nerve photoelectric electrode and the design and preparation method thereof provided by the embodiment of the invention have the following beneficial effects:
1) the optical device of the flexible implanted nerve photoelectrode provided by the embodiment of the invention has the advantages that through the optimized design of the waveguide and the grating, the transmission loss is low, the coupling efficiency is high, the focusing characteristic is strong, the optical stimulation with single cell resolution can be realized, and the realization of accurate stimulation, in-situ recording and cross-brain area synchronous recording through the interconnection of photoelectric signals is facilitated;
2) the optical device of the flexible implanted nerve photoelectrode provided by the embodiment of the invention adopts a flexible polymer material as a substrate, so that the injury of the device during implantation and the nerve scar caused in the body can be reduced, and the long-term stable in-vivo work can be realized;
3) the optical device of the flexible implanted nerve photoelectric electrode provided by the embodiment of the invention is based on an MEMS (micro-electromechanical systems) processing technology, has small size and high integration level, further reduces implantation damage, and is favorable for realizing high-density and multi-channel nerve cell stimulation and signal recording.
It should be noted that: the precedence order of the above embodiments of the present invention is only for description, and does not represent the merits of the embodiments. And specific embodiments thereof have been described above. Other embodiments are within the scope of the following claims. In some cases, the actions or steps recited in the claims may be performed in a different order than in the embodiments and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (14)
1. The optical device of the flexible implanted nerve photoelectric electrode is characterized in that the optical device (1) is arranged on a flexible polymer substrate (6) of the flexible implanted nerve photoelectric electrode, and the optical device (1) comprises:
an input grating (2), a waveguide (4) and an output grating (5),
the input grating (2) is of a parallel grating structure and is used for coupling incident light (9) with preset wavelength and incident angle,
the input end of the waveguide (4) is coupled with the input grating (2), the output end of the waveguide (4) is coupled with the output grating (5),
the output grating (5) is a focusing grating structure and is used for coupling and focusing light to irradiate the upper part of a recording electrode of the flexible implanted nerve photoelectrode and providing light stimulation with single cell resolution.
2. The optical device of the flexible implantable neuro-photoelectrode according to claim 1, wherein the optical device (1) further comprises:
a tapered waveguide (3), wherein the input end of the tapered waveguide (3) is coupled with the input grating (2), and the output end of the tapered waveguide (3) is optically connected with the waveguide (4) so as to realize the coupling connection of the input end of the waveguide (4) and the input grating (2);
the width of the input end of the tapered waveguide (3) is larger than that of the output end, and the tapered waveguide is used for converting a transmission mode of light;
the waveguide (4) is a rectangular waveguide, and the transmission mode of light in the waveguide (4) is single-mode transmission.
3. The optical device of the flexible implantable neuro-photoelectrode according to claim 1, wherein the grating period of the input grating (2) is set to be the maximum grating period capable of coupling incident light (9) with a preset incident wavelength and a preset incident angle, and the etching depth and the duty cycle of the input grating (2) are set to satisfy the condition of coupling efficiency of light at the preset incident wavelength.
4. The optical device of the flexible implantable nerve photoelectric electrode according to claim 1, wherein the output grating (5) is of an elliptical focusing grating structure, the grating period of the output grating (5) is variable, the setting of the variable grating period meets the requirements that the light intensity distribution focus of the emergent light is matched with a preset light stimulation point and an electrode recording point, and the setting of the etching depth and the duty ratio of the output grating (5) meets the requirements of the coupling efficiency and the focusing intensity of light at a preset wavelength.
5. The optical device of the flexible implantable neuro-photoelectrode as claimed in claim 2, wherein the material of the input grating (2), the tapered waveguide (3), the waveguide (4) and the output grating (5) is silicon nitride, and the material of the flexible polymer substrate (6) is SU-8 photoresist.
6. The design method of the optical device of the flexible implanted nerve photoelectric electrode is characterized in that the optical device (1) is arranged on a flexible polymer substrate (6) of the flexible implanted nerve photoelectric electrode, and the method comprises the following steps:
respectively arranging a mode light source (7) and a field monitor (8) on two sides of a waveguide (4), simulating based on a time domain finite difference method, determining the size parameters of the waveguide (4), and finishing the design of the waveguide (4);
arranging a mode light source (7) on one side of an input grating (2), arranging a field monitor (8) on one side of the waveguide (4), simulating based on a finite difference time domain method, optimizing the structural parameters of the input grating (2), and finishing the design of the input grating (2);
and arranging a mode light source (7) on one side of the waveguide (4), arranging field monitors (8) on three planes where the light stimulation points (10) are located, simulating based on a time domain finite difference method, optimizing the structural parameters of the output grating (5), and finishing the design of the output grating (5).
7. The design method of the optical device of the flexible implantable nerve-light electrode according to claim 6, characterized in that the design of the waveguide (4) comprises:
performing initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises a flexible polymer substrate refractive index, a waveguide size, waveguide surface roughness and/or a light source wavelength;
arranging a mode light source (7) at the input end of the waveguide (4) to analyze the waveguide effective refractive index in different light transmission modes; -providing a field monitor (8) at the output of the waveguide (4) to analyze the transmission losses of waveguides of different sizes;
simulating based on a finite difference time domain method, and obtaining a first simulation analysis result;
and determining the size parameters of the waveguide (4) meeting the effective refraction condition and the transmission loss condition according to the first simulation analysis result, and finishing the design of the waveguide (4).
8. The design method of the optical device of the flexible implantable nerve light electrode according to claim 7, characterized in that the design of the input grating (2) comprises:
carrying out initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises a flexible polymer substrate refractive index, a waveguide size, waveguide surface roughness, an incident light wavelength and/or an incident angle;
-arranging a mode light source (7) obliquely above the input grating (2), and arranging a field monitor (8) at the output of the waveguide (4) to analyze the coupling efficiency of the input grating (2);
obtaining the grating period of the input grating (2) through a first phase matching condition, and carrying out primary simulation based on a time domain finite difference method to obtain a second simulation analysis result;
optimizing the grating period of the input grating (2) according to the second simulation analysis result to meet the coupling requirement of the incident light wavelength and the incident angle, optimizing the etching depth and the duty ratio of the input grating (2) according to the second simulation analysis result to meet the coupling efficiency condition at the incident light wavelength, and completing the design of the input grating (2).
9. The design method of the optical device of the flexible implantable nerve light electrode according to claim 7, characterized in that the design of the output grating (5) comprises:
carrying out initial structure setting and parameter setting according to selected materials and process parameters, wherein the parameter setting comprises a flexible polymer substrate refractive index, a waveguide size, waveguide surface roughness, incident light wavelength and/or light stimulation point coordinates;
a mode light source is arranged at the input end of the waveguide (4), and field monitors are respectively arranged on three planes where the optical stimulation point coordinates are located so as to analyze the distribution of output light intensity;
obtaining a grating groove line equation of the output grating (5) through a second phase matching condition, and performing primary simulation based on a time domain finite difference method to obtain a third simulation analysis result;
determining the focus and the coordinate of the output light intensity distribution according to the third simulation analysis result;
optimizing the grating period of the output grating (5) according to the focus and the coordinates thereof, so that the coordinates of the focus are matched with the coordinates of the light stimulation point (10) under the incident light wavelength, optimizing the etching depth and the duty ratio of the output grating (5) according to the third simulation analysis result, meeting the coupling efficiency condition and the focusing intensity condition at the incident light wavelength, and finishing the design of the output grating (5).
10. The preparation method of the optical device of the flexible implanted nerve photoelectrode is characterized by comprising the following steps:
s1: patterning the photoresist on a clean substrate by photoetching to obtain an alignment mark structure;
s2: depositing metal on the patterned photoresist to obtain a metal alignment mark structure;
s3: preparing a flexible polymer substrate on the metal alignment mark structure prepared in the step S2 through photoetching;
s4: depositing a silicon nitride film on the flexible polymer substrate prepared in the step S3;
s5: and taking the metal alignment mark structure obtained in the step S2 as a photoetching alignment mark, and patterning the silicon nitride film twice through photoetching to respectively obtain a waveguide (4) and a grating structure, wherein the grating structure comprises an input grating (2) and an output grating (5), and the input grating (2), the waveguide (4) and the output grating (5) form an optical device of the flexible implanted nerve light electrode and are arranged on a flexible polymer substrate (6) of the flexible implanted nerve light electrode.
11. The method for preparing an optical device of a flexible implantable nerve photoelectrode as claimed in claim 10, wherein the substrate is a single polished silicon wafer with a thickness of 300-500 μm.
12. The method for preparing an optical device of a flexible implantable nerve photoelectric electrode according to claim 10, wherein the step S2 specifically comprises:
depositing a chromium/gold alloy layer with the thickness of 5nm/50nm-10nm/100nm on the patterned photoresist through thermal evaporation, and obtaining a metal alignment mark structure through a stripping process.
13. The method for preparing an optical device of a flexible implantable nerve photoelectric electrode according to claim 10, wherein the step S3 specifically comprises:
and spin-coating SU-8 photoresist on the metal alignment mark structure at the rotating speed of 500-.
14. The method for preparing an optical device for a flexible implantable nerve-light electrode according to claim 13, wherein the step S4 specifically comprises:
and depositing a silicon nitride film with the thickness of 100-300nm on the flexible polymer substrate taking SU-8 as the material by a low-temperature chemical vapor deposition process to serve as a preparation material of the optical device.
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