Biological probe and preparation method thereof

Abstract

The present invention discloses a biological probe and a preparation method thereof. The biological probe comprises a substrate; a bonding metal layer, which is covered on the substrate and used for bonding the substrate and a first metal reflective layer; the first metal reflective layer, which is covered on the bonding metal layer and used for serving as a bottom reflector so that light is emitted from the front; an epitaxial layer, which is arranged on the first metal reflective layer and used for forming a light-emitting area; a second metal reflective layer, which covers the first metal reflective layer and the edge of the epitaxial layer and is used for defining an effective area and a first electrode area of ​​the probe, and restricting a side wall of the epitaxial layer so that light is emitted from the front of the epitaxial layer; an electrode layer, which is formed in the effective area, covers the edge of the epitaxial layer and contacts the epitaxial layer; an optical regulation layer, which defines a second electrode area of ​​the electrode layer by covering the electrode layer, and forms a photonic crystal by covering the epitaxial layer; wherein the optical regulation layer and the second metal reflective layer comprise a layered structure formed by periodically arranging materials with different dielectric constants.

Description

Technical Field

[0001] The present invention relates to the field of optogenetics, and in particular to a biological probe with adjustable light output angle and a preparation method thereof. Background Art

[0002] Due to the development of medicine and biological neurology, researchers have found that changes in the function of neurons and neural circuits are the basis of a variety of neurological diseases. Traditionally, the regulation of neurons mainly includes two methods: electrical stimulation and drug stimulation. Among them, electrical stimulation has low temporal and spatial precision, poor specificity in stimulating nerve cells, and cannot inhibit neuronal activity; while drug stimulation takes a long time to take effect and has large side effects. In order to solve these problems, optogenetics was proposed by researchers. Compared with electrical stimulation and drug stimulation, optogenetics has high temporal and spatial precision and strong specificity, and currently has great research prospects in the field of neurology. It also has great advantages in the treatment of brain diseases such as depression, epilepsy, Alzheimer's disease, and anxiety. Summary of the invention

[0003] In view of the above technical problems, the present invention provides a biological probe with adjustable light output angle and a preparation method thereof, which can effectively improve the light output efficiency at a lower cost and process difficulty, and solve the problem of the influence of uncontrollable light output angle on neuronal activity during optical regulation.

[0004] According to one aspect of the present invention, there is provided a biological probe, comprising:

[0005] substrate;

[0006] A bonding metal layer, covering the substrate and used for bonding the substrate and the first metal reflective layer;

[0007] The first metal reflective layer is covered on the bonding metal layer and is used as a bottom reflector to emit light from the front side;

[0008] An epitaxial layer, disposed on the first metal reflective layer, for forming a light-emitting area;

[0009] A second metal reflective layer, covering the first metal reflective layer and the edge of the epitaxial layer, and used to define the effective area of ​​the probe and the first electrode area, and to limit the side wall of the epitaxial layer so that light is emitted from the front side of the epitaxial layer;

[0010] An electrode layer, formed in the effective area, covering the edge of the epitaxial layer and contacting the epitaxial layer;

[0011] An optical regulation layer, which defines a second electrode region of the electrode layer by covering the electrode layer, and forms a photonic crystal by covering the epitaxial layer;

[0012] Wherein, the optical regulation layer and the second metal reflective layer include a layered structure formed by periodically arranging materials with different dielectric constants.

[0013] According to an embodiment of the present invention, the epitaxial layer comprises:

[0014] p-GaN layer, used to provide holes to recombine with electrons in the active region to generate photons;

[0015] An electron blocking layer, covering the p-GaN layer, and used to form a potential barrier to block the electrons from flowing into the p-GaN layer;

[0016] A multi-quantum well active layer, covering the electron blocking layer, used to form the active region where the electrons and holes recombine to generate the photons;

[0017] The n-GaN layer covers the multi-quantum well active layer and is used to provide the electrons for recombination with the holes.

[0018] According to an embodiment of the present invention, the multi-quantum well active layer is Al X Ga 1-X N / GaN or In Y Ga 1-Y N / GaN quantum well light emitting layer, 0 <X<1,0<Y<1。

[0019] According to an embodiment of the present invention, the substrate is made of one or more of silicon, SiC, diamond, polyethylene terephthalate layer, polyimide layer, polyparaxylene layer, polyurethane layer, and polydimethylsiloxane layer.

[0020] According to an embodiment of the present invention, the first metal reflective layer is a layered structure formed by Ni / Ag / Pt / Au film-based metals.

[0021] According to an embodiment of the present invention, the electrode layer is a Cr / Al / Ti / Au, Ti / Al / Ti / Au or Ni / Au film system.

[0022] According to an embodiment of the present invention, the biological probe is wrapped with a biological encapsulation layer, and the biological encapsulation layer includes a layer for reducing biological tissue damage and maintaining the device working stably in the body;

[0023] The material of the biological encapsulation layer is one or more of polydimethylsiloxane, polyethylene terephthalate, polyparaxylene, negative epoxy photoresist, epoxy resin, polyisobutylene, silica gel, and hydrogel.

[0024] According to another aspect of the present invention, there is provided a method for preparing the above-mentioned biological probe, comprising:

[0025] preparing a bonding metal layer on the substrate;

[0026] preparing the epitaxial layer to obtain an epitaxial structure covering the epitaxial layer;

[0027] Preparing the first metal reflective layer and bonding metal layer on the epitaxial structure;

[0028] Through the bonding metal layer, the substrate and the first metal reflective layer are bonded and adhered by wafer bonding;

[0029] By stripping and etching the epitaxial structure, the light-emitting region formed by the epitaxial layer is obtained;

[0030] Forming the second metal reflective layer to cover the first metal reflective layer and the edge of the epitaxial layer, so as to define the effective area of ​​the probe, the first electrode area, and the side wall of the epitaxial layer;

[0031] Preparing the electrode layer on the second metal reflective layer;

[0032] An optical regulation layer is formed, and a periodic array is formed by evaporation and etching to form a photonic crystal, thereby obtaining the above-mentioned probe.

[0033] According to an embodiment of the present invention, the step of preparing the epitaxial layer to obtain an epitaxial structure covering the epitaxial layer comprises:

[0034] An AlN buffer layer, a u-GaN layer, an n-GaN layer, a multi-quantum well active layer and an electron blocking layer are sequentially grown on a sapphire substrate to obtain the epitaxial structure covering the epitaxial layer.

[0035] According to an embodiment of the present invention, the light-emitting region formed by the epitaxial layer obtained by stripping and etching the epitaxial structure comprises:

[0036] peeling off the AlN buffer layer and the u-GaN layer grown on the sapphire substrate;

[0037] The second metal reflective layer is exposed by etching the epitaxial layer to form the light emitting area.

[0038] It can be seen from the above technical solutions that the biological probe and the preparation method thereof provided by the present invention have the following beneficial effects:

[0039] The stimulating light source currently used in optogenetics has a large light output angle, which can easily stimulate neighboring neurons stained with photosensitive proteins during neural regulation, thus adversely affecting the study of biological neuron regulation. The present invention provides a biological probe with a controllable light output angle and a preparation method thereof, and the light output angle can be controlled according to the photonic crystal structure (such as the number of periods, thickness, duty cycle, etc.). On the one hand, since photonic crystals can enhance spontaneous radiation and change the light output angle, they are of great help in improving the light output efficiency of the stimulating light source and controlling the angle. On the other hand, biological probes with controllable light output angles are more accurate in stimulating neurons, and are less likely to cause light crosstalk during multi-channel stimulation, providing a method for studying neuronal activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 is a cross-sectional view of a biological probe according to an embodiment of the present invention;

[0041] Figure 2 A schematic diagram of the structure of a biological probe according to an embodiment of the present invention;

[0042] Figure 3 is a flow chart of the preparation of a biological probe according to an embodiment of the present invention;

[0043] Figure 4 This is a diagram of the preparation process of the epitaxial layer of the biological probe according to an embodiment of the present invention.

[0044] In the figure:

[0045] 01-substrate;

[0046] 02-bonding metal layer;

[0047] 03-first metal reflective layer;

[0048] 04-Epitaxial layer;

[0049] 05- second metal reflective layer;

[0050] 06-electrode layer;

[0051] 07-Optical regulation layer;

[0052] 08-Bioencapsulation layer;

[0053] 09-p-GaN layer;

[0054] 10- electron blocking layer;

[0055] 11-Multiple quantum well active layer;

[0056] 12-n-GaN layer;

[0057] 13-u-GaN layer;

[0058] 14-AlN buffer layer;

[0059] 15-Sapphire substrate. DETAILED DESCRIPTION

[0060] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings.

[0061] Optogenetics refers to transfecting proteins that are sensitive to light of a specific wavelength into the neurons being studied, and then using light stimulation to regulate them, so as to study their effects on neurons. The earliest light stimulation device used in optogenetics was in the form of fiber-coupled lasers, but it was very restrictive to the animals and had low efficiency. Therefore, there is a fully implantable device, which usually uses LEDs with long life, large scattering angle, luminous wavelength covering the entire visible light range, capable of ms-level pulse switching, and suitable for rapid neural responses as light sources to achieve optical regulation. However, the LED light output angle integrated on the biological probe in optogenetics is basically 360°, and the use of opaque substrates (such as Si) can achieve 180° light output. At the same time, when transfecting light-sensitive proteins into target neurons, it is usually contaminated on neighboring neurons. At this time, if the light output angle of the optical regulation is large, it will interfere with the experimental results.

[0062] Figure 1 4 is a cross-sectional view of a biological probe according to an embodiment of the present invention.

[0063] Figure 2 Schematic diagram of the structure of the biological probe according to an embodiment of the present invention.

[0064] According to one aspect of the present invention, the general inventive concept is as follows: Figure 1-2 As shown, a biological probe is provided, including a substrate 01, a bonding metal layer 02, a first metal reflective layer 03, an epitaxial layer 04, a second metal reflective layer 05, an electrode layer 06 and an optical regulation layer 07;

[0065] The bonding metal layer 02 covers the substrate 01 and is used for bonding the substrate 01 and the first metal reflective layer 03 .

[0066] The first metal reflective layer 03, which covers the bonding metal layer 02, is used as a bottom reflector to emit light from the front side.

[0067] The epitaxial layer 04 is disposed on the first metal reflective layer 03 and is used to form a light-emitting area.

[0068] The second metal reflective layer 05 covers the first metal reflective layer 03 and the edge of the epitaxial layer 04 , and is used to define the effective area of ​​the probe and the first electrode area, and to limit the side wall of the epitaxial layer 04 so that light is emitted from the front side of the epitaxial layer 04 .

[0069] The electrode layer 06 is formed in the effective area, covers the edge of the epitaxial layer 04 and contacts the epitaxial layer 04 .

[0070] The optical regulation layer 07 defines the second electrode region of the electrode layer 06 by covering the electrode layer 06 , and forms a photonic crystal by covering the epitaxial layer 04 .

[0071] The optical regulation layer 07 and the second metal reflective layer 05 include a layered structure formed by periodically arranging materials with different dielectric constants.

[0072] The present invention adopts a double-layer reflector + photonic crystal to realize controllable light output angle. The light output angle is regulated by the periodically arranged layered structure of the second metal reflective layer 05 and the optical regulation layer 07, which is more accurate for stimulating neurons and is not prone to light crosstalk during multi-channel stimulation.

[0073] The present invention provides a biological probe with controllable light output angle and a preparation method thereof. The light output angle can be controlled according to the photonic crystal structure (such as the number of periods, thickness, duty cycle, etc.). On the one hand, since photonic crystals can enhance spontaneous radiation and change the light output angle, they are of great help in improving the light output efficiency of the stimulation light source and controlling the angle. On the other hand, the biological probe with controllable light output angle is more accurate in stimulating neurons, and is not prone to light crosstalk during multi-channel stimulation, providing a method for studying neuronal activity.

[0074] According to an embodiment of the present invention, the biological probe is in the shape of a pointed tip and a long handle.

[0075] Since the biological probe with integrated multi-color RCLED is used to stimulate neurons in the animal brain, it needs to be implanted into biological tissues, and the shape of the probe needs to be a long handle. The shape of the front end of the probe is usually a pointed tip, mainly because when the pointed probe is implanted into biological tissues, the force point is relatively small, so the damage to the biological tissues is less. At the same time, the angle of the pointed tip also has a certain influence on the damage to the biological tissues. The smaller the angle, the smaller the damage to the tissues. For flat-headed probes, the force range is relatively large during implantation. On the one hand, it is not convenient to implant, and on the other hand, it causes greater damage to the tissues. From this perspective, this patent proposes the use of a biological probe with a pointed tip and a long handle.

[0076] According to an embodiment of the present invention, the epitaxial layer 04 includes:

[0077] p-GaN layer 09, used to provide holes to recombine with electrons in the active region to generate photons;

[0078] The electron blocking layer 10 covers the p-GaN layer 09 and is used to form a potential barrier to block electrons from flowing into the p-GaN layer 09;

[0079] The multi-quantum well active layer 11 covers the electron blocking layer 10 and is used to form an active region for generating photons by recombination of electrons and holes;

[0080] The n-GaN layer 12 covers the multi-quantum well active layer 11 and is used to provide electrons for recombination with holes.

[0081] Since GaN itself is weakly n-type, the hole concentration is low and the mobility is smaller than that of electrons. The electron blocking layer 10 prevents the electrons in the n-GaN layer 12 from flowing to the p-GaN layer 09, so that a large number of electron-hole recombination cannot occur in the active area. Therefore, the electron blocking layer 10 is required as a potential barrier to limit the recombination of electrons and holes to the multi-quantum well active layer 11.

[0082] According to an embodiment of the present invention, the p-GaN layer 09 may be, for example, Mg-doped GaN, with a Mg doping concentration of approximately 3.6×10 19 cm -3 .

[0083] According to an embodiment of the present invention, the electron blocking layer 10 may be Mg-doped AlGaN or p-Al 0.1 Ga 0.9 N.

[0084] According to an embodiment of the present invention, the multi-quantum well active layer 11 may be In 0.17 Ga 0.83 N / GaN.

[0085] According to an embodiment of the present invention, the n-GaN layer 12 may be GaN doped with Si, and the Si doping concentration is about 2×10 19 cm -3 .

[0086] According to an embodiment of the present invention, the multi-quantum well active layer 11 is Al X Ga 1-X N / GaN or In Y Ga 1-Y N / GaN quantum well light emitting layer, 0 <X<1,0<Y<1。

[0087] According to an embodiment of the present invention, the substrate 01 serves as the overall support of the device and may be made of one or more of silicon, SiC, diamond, polyethylene terephthalate layer, polyimide layer, polyparaxylene layer, polyurethane layer, and polydimethylsiloxane layer.

[0088] According to an embodiment of the present invention, the first metal reflective layer 03 uses a metal reflector as a bottom reflective layer to allow light to be emitted from the front side. At the same time, it can also serve as an electrode for the p-GaN layer 09. The first metal reflective layer 03 is a layered structure formed by Ni / Ag / Pt / Au film-based metals.

[0089] According to an embodiment of the present invention, the first metal reflective layer 03 may be made of a metal with high reflectivity such as Au, Ag, Cu, Pt, Cr, Ni, Al, or Ti.

[0090] According to an embodiment of the present invention, the second metal reflective layer 05 serves as a top reflective layer on the one hand, and can serve as an electrical isolation layer for the n and p electrodes and a sidewall protection for the light-emitting area on the other hand. It can be a SiO2 / TiO2 distributed Bragg reflector alternately grown or evaporated with materials of different refractive indices.

[0091] According to an embodiment of the present invention, the bonding metal layer 02 is used as an intermediate material for wafer bonding to bond the carrier wafer to the transferred wafer, and generally uses metal systems such as Au / In, Au / Au, Au / Sn, for example, one or more of Au, Sn, and In.

[0092] According to an embodiment of the present invention, the optical regulation layer 07 can regulate the light emission angle of the light emitting area on the one hand, and can serve as an insulating protection layer for the electrode layer 0606 on the other hand. It can be a distributed Bragg reflector, such as a dielectric distributed Bragg reflector alternately grown or evaporated with materials of different refractive indices. For example, 15 pairs of TiO2 / SiO2 distributed Bragg reflectors can be grown.

[0093] The optical regulation layer 07 mainly uses periodic structures to artificially control optical properties. Its important feature is that since the size of the periodic structure is comparable to the wavelength, there is a photon bandgap, that is, the electron wave whose energy falls in the bandgap cannot propagate. Due to the advantage of the structure of the photonic crystal itself - the existence of a photon bandgap, the passage of light can be blocked, so that the light can be confined to a certain area, and the final manifestation is that the light is emitted at a specific angle. Usually, a series of periodic arrays are formed mainly by etching and the like. The surface of the light-emitting surface can be etched, or a periodic material with a large difference in reflectivity such as SiO2 / TiO2 can be used as a photonic crystal material, and then an etching method such as RIE is used to form a periodic array. This patent adopts the second method, using evaporation and other methods to deposit a multilayer SiO2 / TiO2 periodic structure, which can be but not limited to 15 pairs, and can be determined according to actual conditions. For example, the specific parameters of the photonic crystal can be set to: lattice period of 300nm, duty cycle of 60%, etching depth of 200nm, and finally a light output angle of about 90° can be obtained, and the light output efficiency has also been improved to a certain extent. By adjusting the lattice period and duty cycle, the photonic band gap can be changed, thereby affecting the light restriction effect, and ultimately showing the regulation of the light output angle. The specific requirements for light output angle and efficiency can be regulated by changing the photonic crystal lattice period, duty cycle, etching depth and material system.

[0094] According to an embodiment of the present invention, the electrode layer 06 is a Cr / Al / Ti / Au, Ti / Al / Ti / Au or Ni / Au film system.

[0095] According to an embodiment of the present invention, the electrode layer 06 may be made of one of Au, Ag, Cu, Pt, Cr, Ni, Al, Ti or any combination thereof.

[0096] According to an embodiment of the present invention, the biological probe is wrapped with a biological encapsulation layer 08, and the biological encapsulation layer 08 includes a layer for reducing biological tissue damage and maintaining the device working stably in the body;

[0097] The material of the biological encapsulation layer 08 is one or more of polydimethylsiloxane, polyethylene terephthalate, polyparaxylene, negative epoxy photoresist, epoxy resin, polyisobutylene, silica gel, and hydrogel.

[0098] Since the biological probe needs to be implanted in the body, it needs to be covered on the surface with a material that has good biocompatibility and waterproof properties, so as to reduce damage to biological tissues while allowing the device to work stably in the body.

[0099] Figure 3 Flow chart of the preparation of the biological probe according to an embodiment of the present invention.

[0100] According to another aspect of the invention, Figure 3 As shown, a method for preparing a biological probe is provided, comprising:

[0101] S101: preparing a bonding metal layer 02 on a substrate 01;

[0102] S102: preparing an epitaxial layer 04 to obtain an epitaxial structure covering the epitaxial layer 04;

[0103] S103: preparing a first metal reflective layer 03 and a bonding metal layer 02 on the epitaxial structure;

[0104] S104: bonding the adhesive substrate 01 and the first metal reflective layer 03 by bonding the metal layer 02 in a wafer bonding manner;

[0105] S105: obtaining a light-emitting area formed by the epitaxial layer 04 by stripping and etching the epitaxial structure;

[0106] S106: forming a second metal reflective layer 05 to cover the first metal reflective layer 03 and the edge of the epitaxial layer 04, so as to define the effective area of ​​the probe, the first electrode area, and the side wall of the epitaxial layer 04;

[0107] S107: preparing an electrode layer 06 on the second metal reflective layer 05;

[0108] S108: forming an optical regulation layer 07, forming a periodic array through evaporation and etching to form a photonic crystal, and obtaining a probe.

[0109] The present invention adopts a double-layer reflector + photonic crystal to realize controllable light output angle. The light output angle is regulated by the periodically arranged layered structure of the second metal reflective layer 05 and the optical regulation layer 07, which is more accurate for stimulating neurons and is not prone to light crosstalk during multi-channel stimulation.

[0110] The present invention provides a biological probe with controllable light output angle and a preparation method thereof. The light output angle can be controlled according to the photonic crystal structure (such as the number of periods, thickness, duty cycle, etc.). On the one hand, since photonic crystals can enhance spontaneous radiation and change the light output angle, they are of great help in improving the light output efficiency of the stimulation light source and controlling the angle. On the other hand, the biological probe with controllable light output angle is more accurate in stimulating neurons, and is not prone to light crosstalk during multi-channel stimulation, providing a method for studying neuronal activity.

[0111] According to an embodiment of the present invention, steps S101, S103 and S107 can adopt thermal evaporation, electron beam evaporation or sputtering methods to prepare a bonding metal layer 02 on the substrate 01, prepare a first metal reflective layer 03 on the p-GaN layer 09, prepare a bonding metal layer 02 on the first metal reflective layer 03, and prepare an electrode layer 06 on the epitaxial layer 04.

[0112] According to an embodiment of the present invention, the second metal reflective layer 05 and the optical regulation layer 07 may be alternately grown or evaporated using materials with different refractive indices.

[0113] Figure 4 This is a diagram of the preparation process of the epitaxial layer of the biological probe according to an embodiment of the present invention.

[0114] According to an embodiment of the present invention, Figure 4 As shown, in S102, preparing the epitaxial layer 04, and obtaining the epitaxial structure covering the epitaxial layer 04 includes:

[0115] An AlN buffer layer 14 , a u-GaN layer 13 , an n-GaN layer 12 , a multi-quantum well active layer 11 and an electron blocking layer 10 are sequentially grown on a sapphire substrate 15 to obtain an epitaxial structure covering the epitaxial layer 04 .

[0116] According to an embodiment of the present invention, in S102 , a sapphire-based GaN epitaxial wafer with a complete structure may be used to perform wafer bonding, laser lift-off, and CMP steps to obtain the epitaxial layer 04 .

[0117] According to the embodiment of the present invention, in S102, due to the large lattice mismatch between the sapphire substrate 15 and the GaN layer, defects are easily generated during the material growth process, thereby affecting the crystal quality. Therefore, inserting the u-GaN layer 13 can merge some defects, thereby improving the quality of the upper n-GaN layer 12.

[0118] According to an embodiment of the present invention, in S102, the AlN buffer layer 14 causes the GaN layer to merge, changing from 3D growth to 2D growth.

[0119] According to an embodiment of the present invention, in S105, the light-emitting region formed by the epitaxial layer 04 is obtained by stripping and etching the epitaxial structure, including:

[0120] The AlN buffer layer 14 and the u-GaN layer 13 grown on the sapphire substrate 15 are peeled off;

[0121] The second metal reflective layer 05 is exposed by etching the epitaxial layer 04 to form a light emitting area.

[0122] According to an embodiment of the present invention, S105 specifically includes: using laser lift-off to lift off the substrate 01 , for example, including a 248nm KrF excimer laser and a 355nm tripled frequency Nd:YVO4 laser.

[0123] Alternatively, a 248 nm KrF excimer laser is used to realize substrate 01 stripping. Since laser stripping will sacrifice other layers to a certain extent, the u-GaN layer 13 is exposed at this time.

[0124] According to the embodiment of the present invention, in S105 , the surface of the n-GaN layer 12 may be polished by CMP.

[0125] According to the embodiment of the present invention, specifically, the excess u-GaN layer 13 is polished away by chemical mechanical polishing, and the surface of the n-GaN layer 12 is made smoother, so as to obtain the epitaxial layer 04 .

[0126] According to an embodiment of the present invention, in S105 , the epitaxial layer 04 may be etched by ICP to expose the first metal reflective layer 03 .

[0127] According to the embodiment of the present invention, specifically, a light emitting area is first defined by using a photoresist, and the photoresist is used as an etching mask to perform ICP etching until the first metal reflective layer 03 is etched.

[0128] According to an embodiment of the present invention, S107 specifically comprises: etching the second metal reflective layer 05 by RIE to expose the epitaxial layer 04 and the first metal reflective layer 03. For example, the light emitting area and the first metal reflective layer 03 are first defined by photoresist, and ICP etching is performed using the photoresist as an etching mask until etching reaches the desired position.

[0129] According to an embodiment of the present invention, S108 specifically includes etching the optical regulation layer 07 on the n-GaN layer 12 by RIE to form a photonic crystal.

[0130] According to an embodiment of the present invention, for example, EBL is used for photolithography, and photoresist is used to define an etched periodic structure of the optical regulation layer 07 on the light-emitting area, and RIE is used as an etching mask until etching reaches the surface of the epitaxial layer 04.

[0131] According to an embodiment of the present invention, the method further includes S109: using a laser to define the shape of the probe and sharpen the tip of the probe.

[0132] According to an embodiment of the present invention, the process further includes S109: preparing a biological encapsulation layer 08 .

[0133] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A biological probe comprising: substrate; A bonding metal layer, covering the substrate and used for bonding the substrate and the first metal reflective layer; The first metal reflective layer covers the bonding metal layer and is used as a bottom reflector to emit light from the front side; An epitaxial layer, disposed on the first metal reflective layer, for forming a light-emitting area; A second metal reflective layer, covering the first metal reflective layer and the edge of the epitaxial layer, and used to define the effective area of ​​the probe and the first electrode area, and to limit the side wall of the epitaxial layer so that light is emitted from the front side of the epitaxial layer; an electrode layer, formed in the active area, covering an edge of the epitaxial layer and contacting the epitaxial layer; An optical regulation layer, which defines a second electrode region of the electrode layer by covering the electrode layer, and forms a photonic crystal by covering the epitaxial layer; Wherein, the optical regulation layer and the second metal reflective layer include a layered structure formed by periodically arranging materials with different dielectric constants.

2. The biological probe according to claim 1, wherein The epitaxial layer comprises: p-GaN layer, used to provide holes to recombine with electrons in the active region to generate photons; An electron blocking layer, covering the p-GaN layer, and used to form a potential barrier to block the electrons from flowing into the p-GaN layer; A multi-quantum well active layer, covering the electron blocking layer, and used to form the active region where the electrons and holes recombine to generate the photons; The n-GaN layer covers the multi-quantum well active layer and is used for providing the electrons for recombining with the holes.

3. The biological probe according to claim 2, wherein: The multi-quantum well active layer is Al X Ga 1-X N / GaN or In Y Ga 1-Y N / GaN quantum well light emitting layer, 0 <X<1, 0<Y<1。 4. The biological probe according to claim 1, wherein The substrate is made of silicon, SiC, diamond, polyethylene terephthalate layer, polyimide layer, polyparaxylene layer, polyurethane layer, One or more layers.

5. The biological probe according to claim 1, wherein The first metal reflective layer is a layered structure formed by Ni / Ag / Pt / Au film-based metals.

6. The biological probe according to claim 1, wherein The electrode layer is a Cr / Al / Ti / Au, Ti / Al / Ti / Au or Ni / Au film system.

7. The biological probe according to claim 1, wherein The biological probe is wrapped with a biological packaging layer, and the biological packaging layer is used to reduce biological tissue damage and keep the device working stably in the body; The material of the biological encapsulation layer is one or more of polydimethylsiloxane, polyethylene terephthalate, polyparaxylene, negative epoxy photoresist, epoxy resin, polyisobutylene, silica gel, and hydrogel.

8. A method for preparing the biological probe according to any one of claims 1 to 7, comprising: preparing a bonding metal layer on the substrate; preparing the epitaxial layer to obtain an epitaxial structure covering the epitaxial layer; Preparing the first metal reflective layer and the bonding metal layer on the epitaxial structure; The substrate and the first metal reflective layer are bonded and adhered by using the bonding metal layer in a wafer bonding manner; The light-emitting region formed by the epitaxial layer is obtained by stripping and etching the epitaxial structure; forming the second metal reflective layer, covering the first metal reflective layer and the edge of the epitaxial layer, and used to define the effective area of ​​the probe, the first electrode area, and the side wall of the epitaxial layer; preparing the electrode layer on the second metal reflective layer; An optical regulation layer is formed, and a periodic array is formed by evaporation and etching to form a photonic crystal, thereby obtaining the probe.

9. The method according to claim 8, wherein: The step of preparing the epitaxial layer to obtain an epitaxial structure covering the epitaxial layer comprises: An AlN buffer layer, a u-GaN layer, an n-GaN layer, a multi-quantum well active layer and an electron blocking layer are sequentially grown on a sapphire substrate to obtain the epitaxial structure covering the epitaxial layer.

10. The method according to claim 9, wherein: The step of obtaining the light-emitting region formed by the epitaxial layer by stripping and etching the epitaxial structure comprises: peeling off the AlN buffer layer and the u-GaN layer grown on the sapphire substrate; The second metal reflective layer is exposed by etching the epitaxial layer to form the light emitting area.

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