Optogenetic neural probe device with multiple inputs and outputs, and method of manufacturing the same

Abstract

To provide an optogenetic neural probe device with multiple inputs and outputs by focusing optogenetic neural probe manufacturing technology utilizing an optical semiconductor device process, and a method of manufacturing the same.SOLUTION: An optogenetic neural probe device 10 includes: an optical device alignment substrate 100; an optical device group 200 disposed on the optical device alignment substrate 100 and including multiple optical devices 210; an optical neural probe substrate 310; and an optical signal input / output port 323 positioned in proximity to a nerve cell on the optical neural probe substrate 310. An optical signal emitted from the optical device group 200 is transmitted to the optical signal input / output port 323 through an optical waveguide 322 present on the optical neural probe substrate 310.SELECTED DRAWING: Figure 1a

Description

[Technical field]

[0001] The present invention relates to a configuration of a neural probe device that utilizes optogenetic technology to stimulate or inhibit nerve cells and extract neural signals, and a method for manufacturing the same. [Background technology]

[0002] In general, signal transmission in nerve cells occurs through electrochemical action. Therefore, in the past, a method of applying an appropriate amount of current or voltage by placing an electrode next to a nerve cell was used to artificially activate nerves. Furthermore, by implanting a protein that acts as a light-responsive ion channel, such as channelrhodopsin-2 (ChR2), into a nerve cell and irradiating this protein with light of a specific wavelength, it is possible to activate the nerve not by electrical stimulation but by light stimulation. In this way, optogenetics technology, which uses light to stimulate or inhibit only specific types of nerves, was announced in 2005. With the existing electrical stimulation method, it was not possible to know the role of each nerve in an organism, but since the announcement of optogenetics technology, it has become possible to explore the role of nerves at the cell level using optogenetics technology, opening up new horizons in nerve research.

[0003] In early optogenetics experiments, light was applied to neurons by placing the light-emitting surface of a light source close to the target neuron or by connecting an external light source to an optical fiber and placing the end of the optical fiber close to the neuron through the optical fiber. However, because external light sources are generally very large, complex optical system combinations are required to reduce the area irradiated with light. This makes the overall volume of the optical system even larger, making it difficult to apply it in a form that can be inserted into a living organism. In addition, optical fibers have limitations in their processing methods, and it is structurally difficult to irradiate light to areas other than the end of the optical fiber, which acts as a constraint in the study of three-dimensional neural tissues in which many cells exist in bundles.

[0004] As part of efforts to overcome this, research has been conducted on a method in which tiny light emitters such as micro-LEDs are integrated into a probe-type electrode, inserted into neural tissue, and placed adjacent to the target neural cells. However, this method requires a light source for each area to be irradiated, and since the light sources are located in the immediate vicinity of the neural cells, there is a problem that the risk of thermal damage is increased. Summary of the Invention [Problem to be solved by the invention]

[0005] In order to overcome the above-mentioned problems, the present invention aims to provide an optogenetic neural probe device with multiple inputs and outputs and a manufacturing method thereof, focusing on optogenetic neural probe manufacturing technology utilizing optical semiconductor element processes.

[0006] Specifically, the present invention aims to provide an optogenetic neural probe device with multiple inputs and outputs, which has an independent optical element array chip as its base to allow for physical separation between the light source and the living body, and which employs a probe array based on optical waveguide technology that has structural expandability in design and production to realize optical signal input and output that can be used for research on neural tissue with a three-dimensional volume, and a method for manufacturing the same.

[0007] The objects of the present invention are not limited to those mentioned above, and other objects not mentioned will be clearly understood by those skilled in the art from the following description. [Means for solving the problem]

[0008] An optogenetic neural probe device according to one embodiment of the present invention transmits optical signals to neural cells and receives fluorescent signals from neural cells.

[0009] The optogenetic neural probe device includes an optical element alignment substrate; an optical element group arranged on the optical element alignment substrate and consisting of one or more optical elements; and one or more optogenetic neural probes including an optical probe substrate, an optical waveguide arranged on the optical probe substrate, and an optical signal input / output port.

[0010] The optogenetic neural probe transmits the optical signal emitted from the optical element group to the optical signal input / output port through the optical waveguide.

[0011] In one embodiment of the present invention, the optical element group may include a first optical element and a second optical element.

[0012] In an embodiment of the present invention, the first optical element and the second optical element may have different central wavelength characteristics.

[0013] In one embodiment of the present invention, the first optical element may be a light emitting element, and the second optical element may be a light receiving element.

[0014] In one embodiment of the present invention, the optical signal input / output port can transmit the fluorescent signal of the neuron to the optical waveguide, and the optical waveguide can transmit the fluorescent signal of the neuron to the optical element group.

[0015] In one embodiment of the present invention, the optical neural probe substrate may be packaged on one side of the optical element array substrate in a direction perpendicular to the optical element array substrate.

[0016] In one embodiment of the present invention, the optogenetic neural probe includes a plurality of probe portions, including a protrusion of the optical neural probe substrate, the optical waveguide, and the optical signal input / output port.

[0017] In one embodiment of the present invention, the plurality of probe portions may be spaced apart from each other by a predetermined distance.

[0018] In one embodiment of the present invention, a portion of the optical neural probe substrate that is packaged on the optical element alignment substrate may be in direct contact with the optical element group, and a recess structure having a step equal to the height of the optical element group may be formed in the portion.

[0019] In one embodiment of the present invention, a fixing resin may be applied onto the optical element alignment substrate in order to fix the optical neural probe substrate in a direction perpendicular to the optical element alignment substrate.

[0020] In an embodiment of the present invention, the fixing resin may be one of a thermosetting resin and a photosetting resin.

[0021] In one embodiment of the present invention, the optical signal input / output port may be disposed at an end of the optical waveguide.

[0022] In an embodiment of the present invention, two or more of the optical signal input / output ports may be disposed on an optical waveguide included in at least one of the plurality of probe parts.

[0023] In an embodiment of the present invention, at least one of the plurality of probe parts may include two or more optical waveguides.

[0024] In one embodiment of the present invention, the optical signal input / output port may be a diffraction grating.

[0025] In one embodiment of the present invention, the optical signal input / output port may be a 45 degree mirror surface.

[0026] In an embodiment of the present invention, the number of the optical element groups may be multiple.

[0027] In one embodiment of the present invention, the optogenetic neural probe device may further include an optical mode-magnitude converter disposed between the optical element group and the optical waveguide.

[0028] An optogenetic neural probe device according to an embodiment of the present invention transmits an optical signal to a neuron or receives a fluorescent signal from a neuron, the optogenetic neural probe device including an optical element array substrate, one or more optical element groups arranged on the optical element array substrate, an optical mode-magnitude converter coupled to each of the one or more optical element groups, and an optogenetic neural probe including the optical neural probe substrate, one or more probe portions, and one or more optical switches.

[0029] In one embodiment of the present invention, the probe part may include a protrusion of the optical neural probe substrate, an optical waveguide, and one or more optical signal input / output ports.

[0030] In one embodiment of the present invention, the optical switch may be disposed between the optical mode-magnitude converter and the optical waveguide.

[0031] In one embodiment of the present invention, the optical switch is optically connected to the optical mode magnitude converter and the optical waveguide, and can transmit an optical signal emitted from the optical element group and having its optical mode magnitude adjusted by the optical mode magnitude converter to an optical waveguide connected to a target optical signal input / output port in response to an external control signal.

[0032] In an embodiment of the present invention, the optical switch may be implemented using any one of a phased-array type, an arrayed waveguide grating (AWG) type, a Mach-Zehnder interferometer (MZI) type, a ring resonator type, and a directional coupler type.

[0033] A manufacturing method for an optogenetic neural probe device according to one embodiment of the present invention includes the steps of aligning a plurality of optogenetic neural probes using fixed spacers; positioning the plurality of optogenetic neural probes on an optical element alignment substrate on which a plurality of optical element groups are arranged; applying a liquid fixing resin to a surface where the optical element alignment substrate and the optogenetic neural probes contact; and hardening the fixing resin.

[0034] In one embodiment of the present invention, the optogenetic neural probe includes an optical neural probe substrate, an optical waveguide disposed on the optical neural probe substrate, and an optical signal input / output port.

[0035] In one embodiment of the present invention, the end of the optical neural probe substrate may have a recess structure, in which case the step of positioning the optical neural probe substrate on the optical element alignment substrate may include disposing the recess structure in contact with the optical element group and the optical element alignment substrate. Effect of the Invention

[0036] The optogenetic neural probe device of one embodiment of the present invention is based on an independent optical element array chip, and thus has the effect of preventing biological damage caused by heat by realizing physical separation between the optical element that generates heat, such as a light source, and the living body.

[0037] In addition, the optogenetic neural probe device according to one embodiment of the present invention has the advantage that it can be applied to study neural tissue having a three-dimensional volume through an optical signal input / output method that employs a probe array based on optical waveguide technology, which has structural scalability in design and manufacturing.

[0038] In addition, the optogenetic neural probe device according to one embodiment of the present invention can be equipped with various optical mode magnitude converters, which has the effect of reducing the enormous optical loss that occurs during the process of combining the optical element array chip and the optical neural probe chip.

[0039] In addition, the optogenetic neural probe device according to one embodiment of the present invention provides multiple switch regions within the optical neural probe, thereby reducing the number of optical elements relative to the number of input / output terminals.

[0040] Meanwhile, in a manufacturing method for an optogenetic neural probe device according to one embodiment of the present invention, by applying a recess area structure for coupling a three-dimensional probe array, it is possible to ensure optical coupling with an optical element array chip and ease of alignment.

[0041] The effects that can be obtained by the present invention are not limited to those mentioned above, and other effects not mentioned will be clearly understood by those having ordinary skill in the art to which the present invention pertains from the following description. [Brief description of the drawings]

[0042] [Figure 1a] FIG. 2 is a front view showing one embodiment of an optogenetic neural probe device and an optogenetic neural probe having multiple inputs and outputs according to the present invention. [Figure 1b] FIG. 2 is a front view showing one embodiment of an optogenetic neural probe device and an optogenetic neural probe having multiple inputs and outputs according to the present invention. [Figure 2a] FIG. 2 is a side view showing one embodiment of an optogenetic neural probe device and an optogenetic neural probe having multiple inputs and outputs according to the present invention. [Figure 2b] FIG. 2 is a side view showing one embodiment of an optogenetic neural probe device and an optogenetic neural probe having multiple inputs and outputs according to the present invention. [Diagram 3] 1 is a flowchart illustrating a method for manufacturing an optogenetic neural probe device with multiple inputs and outputs according to one embodiment of the present invention. [Figure 4a] 1 is a reference diagram for explaining a manufacturing method of an optogenetic neural probe device having multiple inputs and outputs according to the present invention. FIG. [Figure 4b]1 is a reference diagram for explaining a manufacturing method of an optogenetic neural probe device having multiple inputs and outputs according to the present invention. FIG. [Figure 4c] 1 is a reference diagram for explaining a manufacturing method of an optogenetic neural probe device having multiple inputs and outputs according to the present invention. FIG. [Figure 5a] 1A-1C are diagrams illustrating various configurations of an optical mode magnitude converter. [Figure 5b] 1A-1C are diagrams illustrating various configurations of an optical mode magnitude converter. [Figure 5c] 1A-1C are diagrams illustrating various configurations of an optical mode magnitude converter. [Figure 5d] 1A-1C are diagrams illustrating various configurations of an optical mode magnitude converter. [Figure 6] FIG. 2 is an exemplary diagram showing an embodiment of an optogenetic neural probe having multiple inputs and outputs according to the present invention, including an optical switch. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0043] The present invention relates to an optogenetic neural probe device that utilizes optogenetic technology to stimulate or inhibit nerve cells and extract neural signals, and a method for manufacturing the same.

[0044] Specifically, the present invention targets a nerve bundle having a three-dimensional volume and realizes connection with nerves at a specific position. The present invention relates to an optogenetic nerve probe device having a configuration in which a number of optical element array chips and a number of optical nerve probe arrays are optically connected to each other, the array chips transmitting optical signals generated by the array chips to a specific nerve region, or receiving fluorescent signals generated in the brain and then transmitting the fluorescent signals to the optical element array chip, and a method for manufacturing the same.

[0045] The advantages and features of the present invention, as well as the methods for achieving the same, will become apparent from the following detailed description of the embodiments in conjunction with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below, but may be embodied in various different forms, and the embodiments are provided to fully disclose the present invention and fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims. Meanwhile, the terms used in the present specification are for the purpose of describing the embodiments, and are not intended to limit the present invention. In the present specification, the singular form includes the plural form unless otherwise specified in the text. When used in the specification, "comprises" and / or "comprising" means that the referenced components, steps, operations and / or elements do not exclude the presence or addition of one or more other components, steps, operations and / or elements.

[0046] Terms such as "first," "second," etc. may be used to describe various components, but the components should not be limited by the terms. The terms may be used to distinguish one component from another. For example, a first component may be named a second component, and similarly, a second component may be named a first component, without departing from the scope of the present invention.

[0047] When an element is referred to as being "coupled" or "connected" to another element, it should be understood that it may be directly coupled or connected to the other element, but that there may be other elements in between. Conversely, when an element is referred to as being "directly coupled" or "directly connected" to another element, it should be understood that there are no other elements in between. Other expressions describing the relationship between elements, such as "between" and "immediately between" or "adjacent to" and "directly adjacent to," should be interpreted similarly.

[0048] In describing the present invention, if it is determined that a detailed description of related known techniques may unnecessarily obscure the gist of the present invention, the detailed description will be omitted.

[0049] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. In describing the present invention, the same reference numerals will be used to refer to the same means regardless of the drawing numbers in order to facilitate overall understanding.

[0050] 1a and 1b are front views of one embodiment of an optogenetic neural probe device and an optogenetic neural probe with multiple inputs and outputs according to the present invention.

[0051] 1a and 1b, configurations and embodiments of an optogenetic neural probe device and an optogenetic neural probe according to the present invention will be described.

[0052] The optogenetic neural probe device 10 according to the present invention is capable of conducting research on neural tissue having a three-dimensional volume by adopting a probe array structure based on optical waveguide technology. The optogenetic neural probe device 10 according to an embodiment of the present invention includes an optical element alignment substrate 100, one or more optical elements 210 or optical element groups 200, and an optogenetic neural probe (300, hereinafter abbreviated as "probe"), and may further include an optical mode-magnitude converter 400.

[0053] The probe 300 includes an optical neural probe substrate 310, one or more optical waveguides 322, and one or more optical signal input / output ports 323. An optical mode magnitude converter 400 may further be included in the probe 300 (see FIG. 1b). The optical mode magnitude converter 400 may be disposed between one or more optical elements (e.g., light emitters) 210 and the waveguide 322. The cross-sectional area of ​​the optical mode magnitude converter 400 may decrease along a path from the optical elements 210 to the optical signal input / output port 323. The optical signal input / output port 323 may output an optical signal to a subject (e.g., a neuron) and receive a response signal (e.g., a fluorescent signal) generated from the subject by stimulating the subject with the optical signal.

[0054] In this specification, the configuration including the protruding portion 321 of the optical neural probe substrate 310 and the optical waveguide 322 and optical signal input / output port 323 arranged on the protruding portion 321 is referred to as a probe portion 320. Thus, the probe 300 includes one or more probe portions 320. The number and positions of the optical waveguides 322 and optical signal input / output ports 323 included in each probe portion 320 may differ depending on the probe portion 320. The portion of the optical neural probe substrate 310 excluding the protruding portion 321 is referred to as a "substrate portion."

[0055] On the other hand, although not shown in FIGS. 1a and 1b, the probe 300 may further include an optical switch 330.

[0056] Meanwhile, although not shown in Fig. 1a and Fig. 1b, an electrode capable of receiving an electrophysiological signal generated in a nerve may be integrated in the probe unit 320. The number of electrodes may be one or more, similar to the optical signal input / output port 323, and each electrode transmits the collected nerve signal to a circuit, terminal, or system capable of finally analyzing the signal through an electrical or wireless communication method.

[0057] Meanwhile, the end of the protrusion 321 close to the nerve cell may have a pointed probe-shaped structure for easy insertion, and this structure is referred to as a probe peak 321a in this specification.

[0058] Various types of optical elements 210 or optical element groups 200 may be aligned and disposed on an optical element alignment substrate 100. As shown in Fig. 1a, optical element groups 200 including optical elements 210-1 and 210-2 may be disposed adjacent to each other or spaced apart by a certain distance on an optical element alignment substrate 100. In this specification, when an optical element group 200 includes a plurality of optical elements 210, the corresponding optical elements are distinguished and referred to by reference characters such as 210-1, 210-2, ..., 210-n.

[0059] The optical element 210 arranged on the optical element alignment substrate 100 may be a light emitting element or a light receiving element. For example, the optical element 210 may be any one of a light emitting element of an LED, a micro-LED, a mini-LED, an OLED, an LD, and a VCSEL, or any one of a light receiving element of a Si PD, a Ge PD, and an APD.

[0060] In the optogenetic neural probe device 10 according to an embodiment of the present invention, as shown in FIG. 1a, two or more adjacent optical elements 210-1, 210-2, ... constitute an optical element group 200, and the optical element groups 200 are arranged on the optical element alignment substrate 100 with a predetermined interval (for example, the same interval) between them. As another example, the optical element groups 200 may be arranged on the optical element alignment substrate 100 with non-uniform intervals. Also, unlike the above-mentioned embodiment, each single optical element 210 may be arranged on the optical element alignment substrate 100 with a uniform interval or different intervals. Also, the arrangement method of the optical elements 210-1, 210-2, ... 210-n included in the optical element group 200 may vary depending on the optical element group 200.

[0061] In the optogenetic neural probe device 10 according to an embodiment of the present invention, assuming that each optical element group 200 is composed of two optical elements 210-1 and 210-2, the first optical element 210-1 and the second optical element 210-2 may have different functions or characteristics. For example, the first optical element 210-1 and the second optical element 210-2 may have different central wavelength characteristics even though they are both micro-LED light emitting elements. As another example, the first optical element 210-1 may be a light emitting element that is a VCSEL, and the second optical element 210-2 may be a light receiving element that is a Si PD. It goes without saying that even if an optical element group is composed of three or more optical elements, each optical element included in the optical element group may have different functions or characteristics.

[0062] The optical neural probe substrate 310 is packaged in the optical element array substrate 100 in a direction perpendicular to the optical element array substrate 100. The optical neural probe substrate 310 may be packaged in the optical element array substrate 100 through a fixing resin 500. Since the optical neural probe substrate 310 is included in the optogenetic neural probe 300, it can be said that the optogenetic neural probe 300 is packaged in the optical element array substrate 100.

[0063] The optical neural probe substrate 310 may be made of a silicon (Si)-based material having high physical strength. However, the material of the optical neural probe substrate 310 according to the present invention is not limited to the above-mentioned example (silicon-based). The optical neural probe substrate 310 supports the optical waveguide 322 arranged on the optical neural probe substrate 310 so that the optical waveguide 322 can transmit the light emitted by the optical element 210 to the target neuron. Specifically, an optical waveguide (322, which may be abbreviated as "waveguide" hereinafter) is present on the optical neural probe substrate 310, and the optical signal emitted by the optical element 210 passes through the inside of the waveguide 322 and reaches the target neuron through the optical signal input / output port 323. In Figures 1a, 1b, 2a, and 2b, a single optical signal input / output port 323 is illustrated at the end of the waveguide 322 for each waveguide 322, but this should be understood as one example. That is, in the present invention, there is no limitation on the position or number of optical signal input / output ports 323 arranged on waveguide 322. In the present invention, optical signal input / output port 323 may be arranged at any position on waveguide 322, and not only one but also multiple optical signal input / output ports 323 may be arranged on waveguide 322. For example, optical signal input / output port 323 may be arranged at an end of waveguide 322, but may also be arranged at a portion other than the end of waveguide 322.

[0064] The optical waveguide 322 includes a core portion 322a and a cladding layer 322b (see FIG. 2a and FIG. 2b). Unless otherwise specified in this specification, the term "optical waveguide 322" or "waveguide 322" refers to the core portion 322a.

[0065] In an embodiment of the present invention, the core portion 322a may include a high refractive index material capable of transmitting visible light. For example, the high refractive index material included in the core portion 322a may have a refractive index of 1.45 or more. For example, the high refractive index material that may be included in the core portion 322a may include SiN, SiO2, SiON, polymer, SU-8, parylene, etc. However, the material included in the core portion 322a is not limited to the above examples.

[0066] Although the core 322a may be entirely or partially exposed to air, it is preferable to surround the core 322a with the cladding layer 322b in order to reduce optical propagation loss. The cladding layer 322b in FIG. 2a and FIG. 2b surrounds the core 322a. As shown in FIG. 2a and FIG. 2b, the cladding layer 322b is located between the core 322a and the optical mode magnitude converter 400, and between the optical neural probe substrate 310 and the core 322a. For example, SiN, SiO2, SiON, polymer, PDMA, SU-8, parylene, etc. may be used as the material of the cladding layer 322b. However, it is preferable that the refractive index of the material of the cladding layer 322b is lower than that of the material of the core 322a. In the present invention, the material of the cladding layer 322b is not limited to the above-mentioned examples.

[0067] 2a, an optical mode magnitude converter 400 is disposed on top of the optical element 210. The optical mode magnitude converter 400 is located near the area where the optical neural probe substrate 310 and the optical element alignment substrate 100 are connected. The optical mode magnitude converter 400 resolves the difference in optical mode magnitude between the waveguide 322 and the optical element group 200.

[0068] Incidentally, when light is transmitted to a target point through a medium such as an optical waveguide or optical fiber, the spatial shape (magnitude and pattern) of the light confined within the medium changes depending on the refractive index and design characteristics of the material that constitutes each medium. Here, the spatial shape (magnitude and pattern) of light is called the "optical mode." In an active optical element (light emitting device) such as a laser, the optical mode magnitude of the emitted light changes depending on the structure and direction that amplifies the light. The optical mode magnitude converter 400 plays a role in overcoming the difference in optical mode magnitude between the optical element 210 and the waveguide 322.

[0069] The optical mode magnitude converter 400 adjusts the modal magnitude of the optical signal transmitted between the optical element 210 and the waveguide 322 .

[0070] When the optical element group 200 is disposed on the optical element alignment substrate 100 , the optical mode magnitude converter 400 adjusts the mode magnitude of an optical signal transmitted between the optical element group 200 and the waveguide 322 .

[0071] When the optical element group 200 emits an optical signal, the optical mode magnitude converter 400 adjusts the mode magnitude of the optical signal emitted by the optical element group 200 so that the mode magnitude of the optical signal becomes closer to the optical mode magnitude of the waveguide 322. Incidentally, when the optical element group 200 emits an optical signal, the optical element group 200 includes the light emitting element 210.

[0072] In addition, when the optical element group 200 receives an optical signal, the optical mode magnitude converter 400 adjusts the mode magnitude of the optical signal transmitted to the optical element group 200 through the waveguide 322 so that the mode magnitude of the optical signal becomes closer to the optical mode magnitude of the optical element group 200. Incidentally, when the optical element group 200 receives an optical signal, the optical element group 200 includes a light receiving element 210.

[0073] The optogenetic neural probe device 10 according to one embodiment of the present invention utilizes an optical mode-magnitude converter 400 to reduce optical coupling loss.

[0074] When the optical neural probe substrate 310 is viewed as being located at the bottom end, the optical mode magnitude converter 400 is located above the core portion 322a or the cladding layer 322b. In other words, when the optical neural probe substrate 310 is viewed as being located at the bottom end, the optical mode magnitude converter 400 is located at the top.

[0075] The material of the optical mode magnitude converter 400 may be SiN, SiO2, SiON, polymer, PDMA, SU-8, parylene, etc. However, the material of the optical mode magnitude converter 400 must have a refractive index different from that of the core 322a or the cladding layer 322b. The material of the optical mode magnitude converter 400 in the present invention is not limited to the above examples.

[0076] The optical mode magnitude converter 400 may be configured in a tapered (trapezoidal) shape, but may also be configured in various shapes other than a tapered shape, as will be described later.

[0077] On the waveguide 322, there is an optical signal input / output port 323 that performs input / output of an optical signal to / from the outside of the waveguide 322. The optical signal input / output port 323 may be made of a diffraction grating. Also, the optical signal input / output port 323 may be a mirror surface. For example, the optical signal input / output port 323 may be a 45-degree mirror surface, in which case the optical signal is switched in a direction perpendicular to the traveling direction. Although the optical signal input / output port 323 is illustrated as being present at the end of the waveguide 322 in FIG. 1a and FIG. 1b, the position of the optical signal input / output port 323 is not limited thereto. For example, the optical signal input / output port 323 may be formed at a position other than the end of the waveguide 322. The optical signal input / output port 323 is made of a diffraction grating and switches the traveling direction of light transmitted through the waveguide 322. For example, the optical signal input / output port 323 can switch the traveling direction of the light to a direction perpendicular to the waveguide 322. The optical signal input / output port 323 outputs the light whose direction has been switched to the outside of the waveguide 322. In addition, the optical signal input / output port 323 inputs external light (e.g., a neural response fluorescent signal or light emitted from an optical element or optical fiber) into the inside of the waveguide 322. In the embodiment of FIG. 1a and FIG. 1b, the optical signal input / output port 323 is integrated at the end of each core portion 322a. As shown in FIG. 1a and FIG. 1b, a certain portion of the protruding portion 321 of the optical neural probe substrate 310 is narrowed so that it can be inserted into biological tissue, and a portion close to a nerve cell has a pointed probe-shaped structure, i.e., a probe peak portion 321a. The probe peak portion 321a makes it easy for the probe portion 320 to be inserted into neural tissue. The portion of the protruding portion 321 of the optical neural probe substrate 310 that is inserted into biological tissue may have a thinner thickness than other portions of the optical neural probe substrate 310 by removing a part of the substrate. It is preferable that the recess structure 315 of the optical neural probe substrate 310 is formed at the same height as the contact portion between the optical element 210 and the optical waveguide 322 (or the contact portion between the optical element 210 and the optical mode magnitude converter 400). When the probe 300 includes a plurality of probe portions 320, the probe portions 320 may be aligned at a constant interval. As another example, the probe portions 320 included in the probe 300 may be spaced apart at different intervals depending on the structure of the neural tissue. Each probe portion 320 has one or more optical signal input / output ports 323.

[0078] 2a and 2b are side views of one embodiment of an optogenetic neural probe device and an optogenetic neural probe with multiple inputs and outputs according to the present invention.

[0079] 2a, the optogenetic neural probe device 10 according to an embodiment of the present invention may be expanded in a form in which a plurality of optical neural probe substrates 310 are aligned and arranged in a direction perpendicular to the optical neural probe substrate 310. That is, the optogenetic neural probe device 10 may be configured in a form in which a plurality of optical neural probe substrates 310 parallel to each other are coupled to one optical element alignment substrate 100.

[0080] In other words, the optogenetic neural probe device 10 may be configured in a form in which a plurality of probes 300 are mounted on the optical element alignment substrate 100. In this case, the plurality of probes 300 may have the same structure, some of them may have different structures, or all of them may have different structures. For example, the number of probe portions 320 included in each probe 300, the interval between the probe portions 320, and the presence or absence and structure of the optical switch 330 may be different from each other. In addition, the plurality of probe portions 320 included in the optogenetic neural probe device 10 may have the same or different structures from each other. For example, the number and positions of the waveguides 322 and the optical signal input / output ports 323 of each probe portion 320 may be different from each other. Meanwhile, the number and positions of the optical mode magnitude converters 400 arranged in the optogenetic neural probe device 10 may also be different for each probe 300 and each probe portion 320.

[0081] 2a, a fixing resin 500 may be applied to fix the optical neural probe substrate 310 vertically on the optical element alignment substrate 100. For example, the fixing resin 500 may be a thermosetting resin such as SOG or BCB, or a photocurable resin such as UV-epoxy, PDMA, SU-8, or a photocurable polymer. The type of the fixing resin 500 in the present invention is not limited to the above examples.

[0082] 2a, the end of the optical neural probe substrate 310 closest to the optical element alignment substrate 100 can be in direct contact with the optical element 210. Also, since the optical element 210 is integrated and present in a structure having a certain height on the optical element alignment substrate 100, the application of a recess structure 315 having a step at the end of the optical neural probe substrate 310 by the height of the optical element 210 can make it easier to bond the two substrates 110 and 130.

[0083] 3 is a flow chart for explaining a method for manufacturing an optogenetic neural probe having multiple inputs and outputs according to one embodiment of the present invention. The method for manufacturing an optogenetic neural probe having multiple inputs and outputs according to one embodiment of the present invention includes steps S210 to S240. The method for manufacturing an optogenetic neural probe having multiple inputs and outputs illustrated in FIG. 3 is according to one embodiment, and the steps of the method for manufacturing an optogenetic neural probe having multiple inputs and outputs according to the present invention are not limited to the embodiment illustrated in FIG. 3, and may be added, changed or deleted as necessary.

[0084] 4a to 4c are reference diagrams for explaining a method for manufacturing an optogenetic neural probe having multiple inputs and outputs according to the present invention. In the order of FIG. 4a to FIG. 4c, a method for packaging a probe 300 on an optical element array substrate 100 on which optical elements 210 are arranged is illustrated.

[0085] Hereinafter, with reference to FIG. 3 and FIG. 4a to FIG. 4c, a method for manufacturing an optogenetic neural probe having multiple inputs and outputs according to one embodiment of the present invention will be described.

[0086] Step S210 is a step of aligning the optical neural probe substrate 310 using the fixed spacer 51.

[0087] 4a, a waveguide 322, an optical signal input / output port 323, and an optical mode magnitude converter 400 may be disposed on an optical neural probe substrate 310. Therefore, step S210 may be regarded as a step of aligning a plurality of probes 300 using fixed spacers 51.

[0088] First, the optical neural probe substrate 310 that needs to be packaged is fixed to the fixed spacer 51. The fixed spacer 51 is used to align the optical neural probe substrates 310 at the same intervals as the optical elements 210 are aligned on the optical element alignment substrate 100. The fixed spacer 51 allows the optical neural probe substrates 310 to be aligned and fixed at a certain distance from each other. At this time, the recess structure 315 at the end of the optical neural probe substrate 310 has the effect of making it easier to combine the two substrates 100 and 310 (see FIG. 4a).

[0089] Meanwhile, before step S210, a step of arranging a plurality of optical element groups 200, each including two or more optical elements, on the optical element alignment substrate 100 at a predetermined interval may be added.

[0090] Step S220 is a step of disposing the optical neural probe substrate 310 on the optical element alignment substrate 100. After the optical neural probe substrates 310 are aligned through the fixed spacers 51, the optical neural probe substrates 310 are disposed on the optical element alignment substrate 100 (see FIG. 4b). Step S220 can also be said to be a step of positioning the probes 300 on the optical element alignment substrate 100. As described with reference to FIG. 2a, the optical neural probe substrate 310 may have a recess structure 315 at its end. In step S220, the recess structure 315 of the optical neural probe substrate 310 is disposed to be in contact with the optical element group 200 and the optical element alignment substrate 100, which can further facilitate the bonding of the optical neural probe substrate 310 and the optical element alignment substrate 100.

[0091] Step S230 is a step of applying a fixing resin. When all the optical neuroprobe substrates 310 are physically arranged in the correct positions, a liquid fixing resin 500 is applied to the surfaces where the optical element alignment substrate 100 and the optical neuroprobe substrate 310 contact each other. The fixing resin 500 in FIG. 4b shows the curable resin before curing.

[0092] Step S240 is a step of hardening the fixing resin. The fixing resin 500 firmly fixes the optical element alignment substrate 100 and the optical neural probe substrate 310 through a hardening process. That is, step S240 is a step of bonding the optical element alignment substrate 100 and the optical neural probe substrate 310 by hardening the fixing resin 500. In other words, step S240 can be said to be a step of bonding the optical element alignment substrate 100 and the optogenetic neural probe 300 by hardening the fixing resin 500. The fixing resin 500 in FIG. 4c shows the hardened curable resin (see FIG. 4c).

[0093] The method for manufacturing an optogenetic neural probe having multiple inputs and outputs described above has been described with reference to the flowcharts presented in the drawings. For ease of explanation, the method has been illustrated and described as a series of blocks, but the invention is not limited to the order of the blocks, and some blocks may occur in a different order or simultaneously with other blocks than those illustrated and described herein, and various other branches, flow paths, and orders of blocks that achieve the same or similar results may be implemented. In addition, not all of the blocks illustrated may be required to implement the method described herein.

[0094] Meanwhile, in the description with reference to Figs. 3 to 4c, each step may be further divided into additional steps or combined into fewer steps according to the embodiment of the present invention. Also, some steps may be omitted, and the order of steps may be changed, as necessary. Also, the contents of Figs. 1a, 1b, 2a, 2b, 5a to 5d, and 6 may be applied to the contents of Figs. 3 to 4c, even if other contents are omitted. Also, the contents of Figs. 3 to 4c may be applied to the contents of Figs. 1a, 1b, 2a, 2b, 5a to 5d, and 6.

[0095] 5a to 5d are exemplary diagrams showing various types of optical mode magnitude converters. FIG. 5a to 5d show various types of optical mode magnitude converters 400 that may be included in the optogenetic neural probe device 10 according to the present invention. In order to minimize optical coupling loss under given conditions, various types of optical mode magnitude converters 400 may be applied to the optogenetic neural probe device 10. Specifically, different types of optical mode magnitude converters 400 may be applied to the optogenetic neural probe device 10 depending on the number of optical elements 210 included in the optical element group 200, the optical mode magnitude emitted by the optical elements 210, and the manufacturing process and manufacturing technology level of the optical mode magnitude converter 400.

[0096] 5a illustrates a basic tapered optical mode magnitude converter 400-1. The tapered optical mode magnitude converter 400-1 is one of the most basic forms of optical mode magnitude converter 400. The tapered optical mode magnitude converter 400-1 is the most commonly used form due to its easy fabrication process and simple design and working principle.

[0097] 5b illustrates a round-shaped optical mode magnitude converter having a single lens shape (400-2, hereinafter referred to as a "single lens type optical mode magnitude converter"). The single lens type optical mode magnitude converter 400-2 reduces optical loss by focusing light when the light emitted from the optical element 210 has a large radiation angle in the horizontal direction. However, the lens type optical mode magnitude converter 400-2 requires highly complex optical calculations during design and a bent pattern must be created during its manufacture, making it difficult to apply when there is no manufacturing process or technology capable of implementing fine patterns.

[0098] FIG. 5c illustrates an optical mode magnitude converter 400-3 having a plurality of lens shapes. The optical mode magnitude converter 400-3 of FIG. 5c has a form in which one lens is assigned to each optical element 210. That is, the optical mode magnitude converter 400-3 of FIG. 5c is an optical mode magnitude converter having one lens for each optical element. The optical mode magnitude converter 400-3 having one lens for each optical element is an improved form of the single lens type optical mode magnitude converter 400-2, and has an advantage that when a plurality of optical elements 210 are present on the optical element alignment substrate 100, the total optical coupling efficiency can be increased by optimizing the bending of the lens according to the characteristics of each optical element 210. However, when a lens is manufactured for each optical element 210, the radius of the lens becomes smaller than that of the single lens type optical mode magnitude converter 400, and therefore a manufacturing process or technology capable of manufacturing a finer pattern is required.

[0099] FIG. 5d illustrates an optical mode magnitude converter (400-4, hereinafter referred to as an "inverse tapered optical mode magnitude converter") including an inverse tapered waveguide. Specifically, the inverse tapered optical mode magnitude converter 400-4 has one inverse tapered waveguide for each optical element 210 corresponding to the optical element 210. The inverse tapered optical mode magnitude converter 400-4 has a tapered mode magnitude converter on the top of the inverse tapered waveguide along a direction perpendicular to the optical neural probe substrate 310. The inverse tapered optical mode magnitude converter 400-4 has a high effect of improving optical coupling loss when the mode magnitude of the light emitted from the optical element 210 is large in the vertical direction. That is, when the optical mode is large in the vertical direction, mode matching is performed by the inverse tapered waveguide, and the optical mode can be coupled to the waveguide 322 while reducing loss. However, since the width of the waveguide of inverse tapered optical mode magnitude converter 400-4 must be narrowed on the side closer to optical element 210, the pattern width required for fabrication is smaller than that of tapered optical mode magnitude converter 400-1. It is preferable to set the width of the narrow waveguide in the inverse tapered portion of inverse tapered optical mode magnitude converter 400-4 to the smallest width possible in the manufacturing process.

[0100] The optical mode magnitude converter 400 may be embodied in various ways other than the shapes of FIGS. 5a to 5d.

[0101] FIG. 6 is an illustrative diagram showing an embodiment of an optogenetic neural probe having multiple inputs and outputs including an optical switch according to the present invention.

[0102] The probe 300 of the optogenetic neural probe device 10′ according to one embodiment shown in FIG 6 includes an optical switch 330. The optogenetic neural probe device 10′ of FIG 6 further includes an optical switch 330 in the above-described probe 300. As shown in FIG 6, the optical switch 330 may be disposed between the optical mode-magnitude converter 400 and the plurality of waveguides 322.

[0103] 6 illustrates an embodiment in which the optical signal input / output port 323 is disposed at the end of the waveguide 322, but as described above, it goes without saying that the optical signal input / output port 323 may be disposed at any position on the waveguide 322. In other words, the optical signal input / output port 323 may be disposed at the end of the waveguide 322, but may also be disposed at a portion other than the end of the waveguide 322.

[0104] Meanwhile, not only one but also a plurality of optical signal input / output ports 323 may be arranged on one waveguide 322. Also, a plurality of waveguides 322 may be formed on one probe portion 320, or only one waveguide 322 may be formed thereon.

[0105] In the embodiment of FIG. 6, the optical switch 330 included in a particular probe 300 is an N*(M*j) switch ("*" means a multiplication symbol). In the embodiment of FIG. 6, it is assumed that each probe portion 320 has the same number (j) of optical signal input / output ports 323. However, it goes without saying that the optogenetic neural probe device 10' according to the present invention may have a different number of optical signal input / output ports 323 for each probe portion 320. N means the number of optical element groups 200, M means the number of probe portions 320, and j means the number of optical signal input / output ports 323 arranged in each probe portion 320. Incidentally, since the number of optical element groups 200 is N, the number of optical mode magnitude converters 400 is also N.

[0106] As described above, when there are N optical element groups 200, M probe units 320, and j optical signal input / output ports 323 for each probe unit 320, an optical switch 330 is required to control connections between the N optical element groups 200 and the M*j optical signal input / output ports 323 included in the probe 300. In Fig. 6, the M*j optical signal input / output ports 323 are respectively identified by symbols O11, ..., O1j, ..., OM1, ..., OMj.

[0107] For example, when the optogenetic neural probe device 10' transmits optical signals generated by the optical element group 200 to the optical signal input / output port 323, the wavelengths of the optical signals of the first input I1 and the second input I2 may be different from each other, and each wavelength may have a different effect on the neuron. The optogenetic neural probe device 10' transmits each optical signal to the optical signal input / output port 323, which is the destination of each optical signal, through the optical switch 330. That is, the optical switch 330 is an element that realizes switching of an optical signal. For this purpose, the probe 300 needs to be manufactured in a form in which N*(M*j) optical switches 330 are integrated. For example, the optical switch 330 may be realized using various functional elements such as a phased-array type, an arrayed waveguide grating (AWG) type, a Mach-Zehnder interferometer (MZI) type, a ring resonator type, a directional coupler type, or the like.

[0108] When the optical element 210 arranged on the optical element alignment substrate 100 is a light source that generates an optical signal, the optical signal output from the optical element 210 passes through the optical switch 330 and is transmitted to the optical signal input / output port 323 as a destination.

[0109] On the other hand, when the optical element 210 is a light receiving element (light receiving element) that converts an optical signal into an electrical signal, the fluorescent signal generated in the neuron is received inside the waveguide 322 through a specific optical signal input / output port 323, and the fluorescent signal is transmitted to the optical element 210 through the optical switch 330.

[0110] Meanwhile, although not shown in Fig. 6, the optogenetic neural probe device 10' according to an embodiment of the present invention may include an optical switch driving circuit or an optical element driving circuit. The optical switch driving circuit is electrically connected to the optical switch and controls the operation of the optical switch. The optical element driving circuit is electrically connected to the optical element and controls the operation of the optical element 120. The optical switch driving circuit or the optical element driving circuit may be mounted on a substrate included in the optogenetic neural probe device 10' or may be manufactured on a separate substrate and additionally mounted thereon.

[0111] In one embodiment of the optogenetic neural probe device 10' in Figure 6, the optical switch 330 enables routing of optical signals emitted by the optical element 210, which was not possible in the optogenetic neural probe device 10 in the embodiment of Figure 1a, thereby having the effect of reducing the number of optical elements 210.

[0112] Although the present invention has been described above with reference to preferred embodiments, it will be understood by those skilled in the art that various modifications and variations of the present invention may be made without departing from the spirit and scope of the present invention as set forth in the following claims. [Explanation of symbols]

[0113] 10, 10': Optogenetic neural probe device 51: Fixed spacer 100: Optical element alignment substrate 200: Optical element group 210: Optical element 210-1: First optical element 210-2: Second optical element 300: Optogenetic neural probes 310: Optical neural probe substrate 315: Recess structure 320: Probe section 321:Protrusion 321a: Tip peak part 322: Optical waveguide 322a: Core 322b: Cladding layer 323: Optical signal input / output port 330: Optical switch 400: Optical mode magnitude converter 400-1: Tapered optical mode magnitude converter 400-2: Single lens type optical mode magnitude converter 400-3: Optical mode magnitude converter with one lens per optical element 400-4: Inverse tapered optical mode magnitude converter 500: Fixing resin

Claims

1. An optogenetic neural probe device for transmitting an optical signal to a neuron or receiving a fluorescent signal from the neuron, Optical element alignment substrate; an optical element group arranged on the optical element alignment substrate and including one or more optical elements; and one or more optogenetic neural probes including an optical neural probe substrate, an optical waveguide disposed on the optical neural probe substrate, and an optical signal input / output port; The optogenetic neural probe comprises: An optogenetic neural probe device that transmits optical signals emitted from the optical element group to the optical signal input / output port through the optical waveguide.

2. the optical element group includes a first optical element and a second optical element, The optogenetic neural probe device of claim 1 , wherein the first optical element and the second optical element have different central wavelength characteristics.

3. the optical element group includes a first optical element and a second optical element, The optogenetic neural probe device of claim 1 , wherein the first optical element is a light emitting element and the second optical element is a light receiving element.

4. The optical signal input / output port includes: Transmitting a fluorescent signal from a neuron to the optical waveguide; The optical waveguide is The optogenetic neural probe device of claim 1 , which transmits the fluorescent signal of the neuronal cell to the group of optical elements.

5. The optical neural probe substrate comprises: The optogenetic neural probe device of claim 1 , which is packaged on one side of the optical element alignment substrate.

6. The optogenetic neural probe comprises: a plurality of probe portions including a protruding portion of the optical neural probe substrate, the optical waveguide, and the optical signal input / output port; The plurality of probe portions include The optogenetic neural probe device of claim 1 , wherein the probes are spaced apart from each other by a predetermined distance.

7. The optical neural probe substrate comprises: a part of the packaged portion of the optical element alignment substrate directly contacts the optical element group; The optogenetic neural probe device according to claim 5 , wherein a recess structure having a step equal to the height of the optical element group is formed in the portion.

8. The optogenetic neural probe device of claim 5 , wherein a fixing resin is applied onto the optical element alignment substrate to fix the optical neural probe substrate to the optical element alignment substrate.

9. The fixing resin is The optogenetic neural probe device of claim 8 , which is one of a thermosetting resin and a photocurable resin.

10. The optical signal input / output port includes: The optogenetic neural probe device of claim 1 , characterized in that it is disposed at the end of the optical waveguide.

11. At least one of the plurality of probe parts is The optogenetic neural probe device according to claim 6 , wherein two or more optical signal input / output ports are arranged on an optical waveguide included in at least one of the probe portions.

12. At least one of the plurality of probe parts is The optogenetic neural probe device of claim 6 , comprising two or more optical waveguides.

13. The optical signal input / output port includes: The optogenetic neural probe device of claim 1 , characterized in that it comprises a diffraction grating.

14. The optical signal input / output port includes: The optogenetic neural probe device of claim 1 , characterized in that it has a 45 degree mirror surface.

15. The optical element group includes: The optogenetic neural probe device of claim 1 , characterized in that it is multiple in number.

16. Aligning a plurality of optogenetic neural probes using fixed spacers; Positioning the plurality of optogenetic neural probes on an optical element alignment substrate having a plurality of optical element groups disposed thereon; Applying a liquid fixing resin to the surface where the optical element alignment substrate and the optogenetic neural probe contact each other; and A method for manufacturing an optogenetic neural probe device, comprising: a step of hardening the fixing resin.

17. The optogenetic neural probe comprises: an optical probe substrate; an optical waveguide and an optical signal input / output port disposed on the optical probe substrate; The end of the optical neural probe substrate has a recess structure; The step of placing the optical element on the optical element alignment substrate includes: The method for manufacturing an optogenetic neural probe device of claim 16, comprising positioning the recess structure in contact with the optical element group and the optical element alignment substrate.

18. at least one light emitter configured to emit a light signal; an optical waveguide providing an optical path for the optical signal; an optical signal input / output port for outputting an optical signal to an object; and an optical mode-magnitude converter disposed between the at least one light emitter and the optical waveguide; Including, The optical mode magnitude converter comprises: An optogenetic neural probe, wherein the cross-sectional area of ​​the optical mode magnitude converter decreases along a path from the at least one light emitter to the optical signal input / output port.

19. the optical signal input / output port is configured to receive a response signal from the subject; The optogenetic neural probe of claim 18 , wherein the optical waveguide is configured to provide an optical path for a response signal from the optical signal input / output port to at least one optical receiver.

20. the subject is a neuron, The optogenetic neural probe of claim 19, wherein the response signal is a fluorescent signal generated by the neuron when stimulated by the optical signal.

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