NL2038129B1 - An Interventional Optical Neural Stimulation Device - Google Patents

Abstract

An Interventional Optical Neural Stimulation Device The present invention belongs to the interdisciplinary research field of biophotonics and involves an interventional optical neural stimulation device. The device comprises a light source generation module, a transmission guidance module, and an optical stimulation terminal module; the light source generation module is used to generate a light source with specific wavelength, power, pulse period, and pulse width according to actual requirements, coupled into the transmission guidance module; the transmission guidance module serves as a medium connecting the light source generation module and the optical stimulation terminal module, accepting the laser beam generated by the light source generation module and guiding it to the designated brain area of the target biological organism; the optical stimulation terminal module is used to fix the laser beam transmitted by the transmission guidance module in a pre-specified target brain area of the biological organism.

Description

An Interventional Optical Neural Stimulation Device

Technical Field

The present invention belongs to the interdisciplinary research field of biophotonics in biology, involving an interventional optical neural stimulation device.

Background Art

Photonics biology is a discipline that studies the interaction between light and biological organisms, utilizing light (photons) to image, detect, and manipulate biological materials. In this field, various forms of neural modulation such as light, electricity, magnetism, and sound have been extensively researched by the academic community and applied clinically to treat brain functional disorders such as mental illnesses, drug-resistant epilepsy, and neurodegenerative diseases. In the realm of optogenetics and mid-infrared modulation techniques, significant progress has been made in recent years.

Optogenetics involves introducing exogenous light-sensitive proteins into specific living cells using viruses and stimulating these proteins with light of specific wavelength, power, pulse period, and pulse width to modulate neuronal activity, control cell behavior, and even animal behavior. This technology offers excellent characteristics such as high sensitivity, low toxicity, millisecond-level temporal accuracy, subcellular spatial precision, enabling researchers to explore the interconnections of various neurons and brain region functions, opening up new frontiers in brain science and neurobiology research.

Mid-infrared modulation is a promising modulation method applicable in clinical settings, exerting regulatory effects on neuronal signals and behaviors, possessing non-thermal, long- distance, and reversible qualities. This technology has been shown to inhibit cancer cell migration and glycolysis regulation, with research results in live experiments showing accelerated associative learning in mice and modulation of zebrafish larval neuronal activity, demonstrating significant research potential.

Current implementations of light excitation or mid-infrared modulation in optogenetics require special procedures such as opening the animal's brain, removing the skull, or thinning the skull, causing significant damage to experimental animals, hindering live experiments and obtaining stable and reliable experimental data, and failing to provide long-term, stable, and sustainable experimental conditions.

Summary of the Invention

The present invention provides an interventional optical neural stimulation device to address the difficulty in achieving experimental conditions for optical neural stimulation in existing technologies, providing an experimental platform for optical neural stimulation and other biophotonics research.

To achieve the above objectives, the present invention adopts the following technical solution:

An interventional optical neural stimulation device comprising a light source generation module, a transmission guidance module, and an optical stimulation terminal module;

The light source generation module is used to generate a light source of specific wavelength, power, pulse period, and pulse width according to actual requirements, coupled into the transmission guidance module;

The transmission guidance module serves as a medium to connect the light source generation module and the optical stimulation terminal module, receiving the laser beam generated by the light source generation module and guiding it to the designated brain area of the target organism;

The optical stimulation terminal module is used to fix the laser beam transmitted by the transmission guidance module in the pre-specified target brain area of the target organism.

In a further improved embodiment of this technical solution, the light source generation module comprises a light source, an attenuating section, and a coupling part; wherein, the light source, attenuating section, and coupling part are connected via a collimated light path: the light source emits a laser beam of a specified wavelength, pulse period, and pulse width, obtains a laser beam of specified power after passing through the attenuating section, and couples into the transmission guidance module at the coupling part.

In a further improved embodiment of this technical solution, the light source and the attenuating section are detachably connected.

In a further improved embodiment of this technical solution, the coupling part is a mechanical device fixed to the first end of the transmission guidance module, with an internal groove structure and a surface protrusion that fits the first end of the transmission guidance module, horizontally fixed with a nut.

In a further improved embodiment of this technical solution, the transmission guidance module comprises a fiber layer, a support layer, and a protective layer; wherein, the support layer and the protective layer tightly wrap around the fiber layer from the inner layer to the outer layer, and the resulting transmission guidance module is implanted along a pre-designed path in the blood vessels of the target organism's brain, with its end combined with the optical stimulation terminal module.

In a further improved embodiment of this technical solution, the support layer is made of titanium alloy material with a collapsible mesh structure, with a diameter less than 0.8mm when collapsed; the protective layer is a microtube with a diameter of 1mm; the fiber layer is an IRF-Se series selenium-based infrared fiber with a diameter of 100um and a numerical aperture of 0.27.

In a further improved embodiment of this technical solution, the optical stimulation terminal module comprises a fiber end and a supporting stent, with the fiber end fixed inside the supporting stent; wherein, the fiber end is the fiber tail of the fiber layer, and the supporting stent is a titanium alloy mesh structure with extensibility and collapsibility.

In a further improved embodiment of this technical solution, the supporting stent has a collapsing diameter smaller than the inner diameter of the protective layer.

In a further improved embodiment of this technical solution, the final emitted power Poyr at the end of the optical neural stimulation device satisfies:

Pout = Ro + (py, Bm, A) +10 10°

Where P‚ut and P, represent the output power and the power of the input fiber layer, respectively; the term 102 describes the attenuation of the beam in the fiber layer, a indicating the fiber's loss coefficient; (ny: 61, A) describes the attenuation from the light source to the coupling into the fiber layer, for the case of Gaussian beam incidence, it can be expressed as: erf Ce (ny, ben A) = Tero] * 1)

Where w‚y represents the near-field width of the laser beam, A is the wavelength of the beam, 6. is the numerical aperture of the fiber, erf is the error function, and 1 represents the reflection loss at the fiber end;

The loss coefficient a comes from transmission losses due to the optical material and manufacturing, as well as bending during use, considering macro-bending losses since the transmission guidance module needs to enter the blood vessels of the target organism's brain, macro-bending loss is considered: ak? TT Gn)

GXP [2 B* n;koa 7 R] [R/B2 — n5k3a2k3(n? — n3)

Where a is the core radius, n; and n, are the refractive indices of the core and cladding, k and kg are the wave vectors of light in the fiber and in vacuum, B is the propagation constant, R is the curvature radius of the fiber bend.

In contrast to existing technologies, the above technical solution has the following beneficial effects: the present invention provides an interventional optical neural stimulation device that achieves optical stimulation of designated brain areas in organisms in a minimally invasive manner.

The interventional approach reduces the damage caused to organisms in existing technologies to achieve optical neural stimulation, with the stimulation location inside the biological brain area, ensuring the effectiveness of stimulation and the accuracy of subsequent data collection; by following a designated path along the blood vessels of the biological brain area, precise stimulation of the designated area by the beam is achieved; the light source and attenuator can be replaced according to actual requirements, outputting a laser beam of specific wavelength, power, pulse period, and pulse width, suitable for optical stimulation experiments under different conditions; the transmission guidance module has a certain extensibility, and its specifications can be adjusted within a certain range with the optical stimulation terminal module, making it suitable for biological experiments on different brain structures, with strong universality; additionally, the support is made of titanium alloy material, which has good biocompatibility, reducing the exclusion of biological tissues.

Description of the Drawings

Figure 1 is a schematic diagram of the structure of the interventional optical neural stimulation device;

Figure 2 is a schematic diagram of the light source generation module;

Figure 3 is a schematic diagram of the transmission guidance module;

Figure 4 is a sectional schematic diagram of the transmission guidance module;

Figure 5 is a schematic diagram of the optical stimulation terminal module;

Figure 6 is a top view schematic diagram of interventional optical neural stimulation through sheep brain blood vessels.

Reference signs:

Light source generation module 1; Light source 11; Attenuating section 12; Coupling part 13; Transmission guidance module 2; Fiber layer 21; Support layer 22; Protective layer 23; Optical stimulation terminal module 3; Fiber end 31; Supporting stent 32.

Detailed Description of Embodiments

To explain the technical content, structural features, achieved objectives, and effects of the technical solution in detail, specific embodiments are described below with detailed explanations and accompanying drawings.

As shown in Figure 1, a schematic diagram of the structure of the interventional optical neural stimulation device. The interventional optical neural stimulation device provided by the present invention includes sequentially connected light source generation module 1, transmission guidance module 2, and optical stimulation terminal module 3. The light source generation module 1 is used to generate a light source of specific wavelength, power, pulse period, and pulse width according to actual requirements, coupled into the transmission guidance module 2. The transmission guidance module 2 serves as a medium to connect the light source generation 5 module and the optical stimulation terminal module, receiving the laser beam generated by the light source generation module and guiding it to the designated brain area of the target organism. The optical stimulation terminal module 3 is used to fix the laser beam transmitted by the transmission guidance module in the pre-specified target brain area of the target organism.

The light source generation module 1 includes a light source 11, an attenuating section 12, and a coupling part 13.

The transmission guidance module 2 includes a fiber layer 21, a support layer 22, and a protective layer 23.

The optical stimulation terminal module 3 includes a fiber end 31 and a supporting stent 32.

As shown in Figure 2, a schematic diagram of the light source generation module. The light source generation module 1 includes a light source 11, an attenuating section 12, and a coupling part 13. The light source 11 is a tunable laser that supports different wavelengths, pulse periods, and pulse widths output according to actual wavelength requirements; the attenuating section 12 is a device that can attenuate the laser beam selected according to actual power requirements, such as an attenuator or a power adjustment device built into the laser; the coupling part 13 is a mechanical device fixed to the first end of the transmission guidance module 2, with an internal groove structure, a surface protrusion that fits the first end of the transmission guidance module 2, and is horizontally fixed with a nut.

The light source 11, attenuating section 12, and coupling part 13 are connected via a collimated light path: the light source 11 emits a laser beam of a specified wavelength, obtains a laser beam of specified power after passing through the attenuating section 12, and couples into the fiber layer 21 of the transmission guidance module 2 at the coupling part 13. The light source 11 and the attenuating section 12 are detachable and can be replaced according to actual requirements. In this embodiment, the light source 11 uses a quantum cascade mid-infrared laser with a wide wavelength range and easy integration to generate mid-infrared beam, the attenuating section 12 uses an attenuator to output laser beam power at the mW level at the fiber end, and the coupling part 13 is a mechanical device fixed to the first end of the transmission guidance module 2, with an internal groove structure, a surface protrusion that fits the first end of the transmission guidance module 2, and is horizontally fixed with a nut. The light source 11 and the attenuating section 12 are detachable and can be replaced according to actual requirements. The actual requirements refer to the optical parameters that the light source should have when using this device for optical neural stimulation.

As shown in Figure 3, a schematic diagram of the transmission guidance module. The specifications of the support layer 22, protective layer 23, and fiber layer 21 of the transmission guidance module 2 can be customized according to actual requirements; in this embodiment, the support layer 22 is made of titanium alloy material with a collapsible mesh structure, with a diameter less than 0.8mm when collapsed, the protective layer 23 is a microtube with a diameter of 1mm, and the fiber layer 21 is an IRF-Se series selenium-based infrared fiber with a diameter of 100um and a numerical aperture of 0.27. Referring to the sectional schematic diagram of the transmission guidance module shown in Figure 4, the support layer 22 and the protective layer 23 tightly wrap around the fiber layer 21 from the inner layer to the outer layer, and the resulting transmission guidance module 2 has a certain extensibility, allowing it to be implanted along a pre- designed path in the blood vessels of the target organism's brain, with its end combined with the optical stimulation terminal module 3, ensuring that the fiber end 31 is close to the designated biological brain area.

The transmission guidance module 2 includes a fiber layer 21, a support layer 22, and a protective layer 23. The fiber layer 21 is a fiber with a specified working window and supporting a specific mode selected according to actual requirements; the support layer 22 is made of titanium alloy material, connected to the supporting stent 32 at the tail end; the protective layer 23 is a microtube with a diameter larger than the collapsed diameter of the supporting stent 32. The transmission guidance module 2 has a certain extensibility and can navigate through the nonlinear biological brain blood vessel structure.

As shown in Figure 5, a schematic diagram of the optical stimulation terminal module. The supporting stent 32, with its mesh metal structure fitting the blood vessel wall of the biological brain area, has a groove on the inner side to fix the fiber end 31; the fiber end 31 emits the laser beam propagated from the fiber layer 21 ata set angle to stimulate the designated brain area. The optical stimulation terminal module 3 includes a fiber end 31 and a supporting stent 32. The fiber end 31 is the fiber tail of the fiber layer 21, and the supporting stent 32 is a titanium alloy mesh structure with extensibility and collapsibility.

The supporting stent 32, when not expanded, is wrapped inside the protective layer 23.

Before optical neural stimulation, by pulling the protective layer 23 outward, the supporting stent 32 naturally expands, fitting the blood vessel wall of the biological brain area with its mesh metal structure, with a groove on the inner side to fix the fiber end 31; the fiber end 31 emits the laser beam propagated from the fiber layer 21 at a set angle to stimulate the designated brain area.

The specifications of the transmission guidance module 2 and the optical stimulation terminal module 3 can be customized within a certain range; in the application scenarios of the present invention, different organisms have individual differences, with varying brain vessel structures, distributions, and diameters, and different designated brain area positions during specific experiments, suitable specifications can be selected according to actual requirements. The actual requirements refer to the specification parameters required to reach the target brain area for neural stimulation and meet the requirements of the vascular structure and application during specific experiments.

In practical applications, the optical neural stimulation effect is highly related to the wavelength and optical power; after determining the wavelength of the light source, the selection of the light source generation module, attenuating section, and fiber layer should prioritize the final emitted power.

Regarding the power attenuation issue of the fiber optic output, the interventional optical neural stimulation device ensures that the final emitted power Py at the fiber end 31 meets: ~axLy

Pout = Pin * f{wpy, 8,m, A) * 10710

Where Pu and Pi, are the output power and the power into the fiber layer 21 respectively; the term 1052 describes the attenuation of the beam in the fiber layer 21, a indicating the fiber's loss coefficient; (ny; ben, A) describes the attenuation from the light source 11 to coupling into the fiber layer 21, for the case of Gaussian beam incidence, it can be expressed as: erf CN (ny, bn, A) = Tele] #1)

Where w,, represents the laser beam's near-field width, A is the beam's wavelength, 6; is the aperture angle of the fiber, erf is the error function, and 1 is the reflection loss of the fiber end face.

The loss coefficient a comes from transmission losses generated by optical materials and manufacturing, as well as bending during use. Since the transmission guidance module 2 needs to enter the target biological brain vessels, macro-bending losses need to be considered, especially for multimode fibers: ak? - 2 (92 — ng)?

A= nn exp [2 |B? - n;kga —=——p7—R]

JR/B? — njkja?kj(nî — nd)

Where a is the core radius, n: and n2 are the refractive indices of the core and cladding, k and ko are the wave vectors in the fiber and vacuum, B is the propagation constant, R is the radius of curvature of the fiber bend, similar results apply for single-mode fibers.

In this embodiment, the selected biological target for optical neural stimulation is a sheep.

The light beam output by the light source generation module 1 based on the required optical parameters is coupled into the transmission guidance module 2, which is pre-implanted along a specified path within the sheep's brain vessels to reach the designated brain area. The optical stimulation terminal module 3 expands the titanium support frame and attaches it to the vessel wall, fixing the beam end near the designated brain area's vessel, allowing the beam to act on the target brain area at a specified angle.

As shown in Figure 6, a top view schematic of interventional optical neural stimulation through sheep brain vessels. After selecting the sheep brain area for optical neural stimulation, based on techniques like angiography, the structure of the sheep's brain vessels in the target area is obtained to determine the path of the transmission guidance module 2 to reach the vessels near the sheep's brain area; an incision is made at the specified vessel position, and the transmission guidance module 2 is pushed into the vessel from the incision, adhering to the vessel wall along the specified path to reach the target position.

As shown in Figure 6, after removing the microcatheter, the supporting stent 32 of the optical stimulation terminal module 3 naturally expands, closely adhering to the vessel wall, and the fiber end 31 emits the beam at a specified angle, acting on the specific brain area of the sheep.

It should be noted that in this document, terms such as "first" and "second" are used merely to distinguish one entity or operation from another, without necessarily implying any actual relationship or order between these entities or operations. Additionally, terms like "comprising," "including," or any variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, item, or terminal device comprising a series of elements includes not only those elements explicitly listed but also other elements not explicitly listed but inherent to the process, method, item, or terminal device. Without further limitations, elements limited by the phrases "comprising..." or "including..." do not exclude additional elements in the process, method, item, or terminal device that includes these elements. Furthermore, in this document, terms like "greater than," "less than," "exceeding" are understood to exclude the number itself; terms like "above," "below," "within" are understood to include the number.

Although the above embodiments have been described, once those skilled in the art are aware of the basic creative concept, they may make additional changes and modifications to these embodiments. Therefore, the above description is only an embodiment of the present invention and does not limit the scope of the patent protection of the present invention. Any equivalent structural or procedural changes made using the specification and drawings of the present invention, or directly or indirectly applied in other related technical fields, are also included within the scope of the patent protection of the present invention.

Claims (9)

Conclusions 1. An interventional optical neural stimulation device comprising a light source generating module, a transmission conducting module, and an optical stimulation terminal module; the light source generating module being operable to generate a light source having a specific wavelength, power, pulse period and pulse width according to present requirements, which is coupled to the transmission conducting module; the transmission conducting module serving as a medium to connect the light source generating module to the optical stimulation terminal module, receiving the laser beam generated by the light source generating module and conducting it to a designated brain region of a target organism; the optical stimulation terminal module being operable to fix the laser beam transmitted by the transmission conducting module in a pre-specified target region of the brain. 2. The interventional optical neural stimulation device according to claim 1, wherein the light source generating module includes a light source, an attenuator section and a coupling member; the light source, the attenuator section and the coupling member are connected by a collimating light path: the light source is arranged to emit a laser beam having a specific wavelength, pulse period and pulse width, which, after passing through the attenuator section, will be a laser beam having a specific power and is coupled to the transmission conducting module at the coupling member. 3. The interventional optical neural stimulation device of claim 2, wherein the light source and the attenuation section are detachably connected. 4. The interventional optical neural stimulation device according to claim 2, wherein the coupling member is a mechanical device fixedly connected to a first end of the transmission conductive module, having an internal groove structure and a surface protrusion that fits onto the first end of the transmission conductive module, horizontally anchored with a nut. 5. The interventional optical neural stimulation device of claim 1, wherein the transmission conductive module comprises a fiber layer, a supporting layer and a protective layer, the supporting layer and the protective layer being tightly wrapped around the fiber layer from inner to outer layers and the resulting transmission conductive module being implanted along a pre-drawn path in the blood vessels of the brain of the target organism, with its end connected to the optical stimulation end module. 6. The interventional optical neural stimulation device according to claim 5, wherein the supporting layer is made of a titanium alloy and can form a constricting mesh structure, having a diameter of less than 0.8 mm in the constricted state; the protective layer is a microtube having a diameter of 1 mm; the fiber layer is a selenium-based IRF-Se series infrared fiber having a diameter of 100 µm and a numerical aperture of 0.27. 7. The interventional optical neural stimulation device of claim 5, wherein the optical stimulation end module includes a fiber end and a support stent, with the fiber end secured within the support stent, the fiber end being the tail of the fiber of the fiber layer, and the support stent being a titanium alloy mesh structure that is stretchable and constrictable. 8. The interventional optical neural stimulation device of claim 7, wherein the narrowing diameter of the support stent is narrower than the inner diameter of the protective layer. 9. Interventional optical neural stimulation device according to claim 7, wherein the emitted final power Po at the end of the light line corresponds to: Pour = Pin * F005, 01, A) + 1052 where Pow and Pm represent the output power and the power at the input of the fiber layer; the term 105 describes the attenuation of the beam in the fiber layer, a indicates the loss coefficient of the fiber; (ny, 81,4) describes the attenuation shape of the light source (11) to the coupling in the fiber layer, which for the case of a Gaussian incidence beam can be expressed as: erf [Frontal] (Oy, Oem A) = adie] 0 where wn represents the near-field width of the laser, A is the wavelength of the beam, δ; is the opening angle of the fiber, erf is the Gaussian error function, and n represents the reflection loss at the end of the fiber; the loss coefficient a is from the transmission loss generated by the optical material and its manufacturing, as well as the bending during use, taking into account macro-diffraction losses since the transmission conducting module must necessarily enter the blood vessels of the brain of the target organism; ak? | 2 (B* — n3 K2)3 HS: tidi)”iirrsiir’insadii Xp [EJB nikia 2 ok] Ry B2 — nèkla?k?(n?2 — n2) where a is the radius of the core, n: and n2 are the refractive indices of the core and cladding, k and ko are the wave vectors in the fiber and in vacuum, B is the propagation constant, R is the radius of curvature of the bent fiber.