CN117815566A

CN117815566A - Stainless steel composite phototherapy microneedle with different light output modes and preparation method thereof

Info

Publication number: CN117815566A
Application number: CN202311780289.9A
Authority: CN
Inventors: 吴道澄; 赵晨宇; 张帅; 王榕; 雒思远
Original assignee: Xian Jiaotong University
Current assignee: Xian Jiaotong University
Priority date: 2023-12-22
Filing date: 2023-12-22
Publication date: 2024-04-05

Abstract

The stainless steel composite phototherapy micro needle with different light output modes and the preparation method thereof are provided, the micro needle structure comprises a tubular hollow needle body and a needle point bevel opening integrated with the tubular hollow needle body, and the outer surface of the hollow needle body is provided with a wall hole; the optical fiber which passes through the cavity of the needle body and extends to the bevel opening of the needle point from the end surface is subjected to cladding optical power stripping treatment; filling and curing an optical transparent high polymer material between the optical fiber and the needle cavity; the invention can transmit light from the end surface, can uniformly leak from the fiber core to the periphery of the cladding, and combines the number, shape and position of the upper wall holes of the hollow needle body to determine the design mode and the light output position of the optical waveguide, thereby realizing uniform light energy output and adjustable output mode and meeting the complex requirements in practical situations; the needle body of the invention can not generate electric stimulation when being contacted with a human body, the light output characteristic is not interfered by external electromagnetic environment, and the light can be continuously emitted; the material is firm, has good durability and can be repeatedly used; simple structure, simple process and convenient mass production.

Description

Stainless steel composite phototherapy microneedle with different light output modes and preparation method thereof

Technical Field

The invention belongs to the technical field of medical instruments, and particularly relates to a stainless steel composite phototherapy microneedle with different light output modes and a preparation method thereof.

Background

The tumor seriously threatens the life safety of human beings due to high morbidity and mortality, and the traditional treatment modes comprise limitations and indissolvable defects such as surgical excision, chemotherapy, radiotherapy and the like, including incomplete treatment, large toxic and side effects, lack of specificity and the like, and can not obviously improve the life quality of patients. Tumor phototherapy is a method for inducing and treating diseases by using light radiation energy, and has gradually come into the field of vision of people since the application of the laser technology in the 60 th century to clinical tumor ablation. Because of the characteristics of simple method, good curative effect, small side effect and the like, the tumor phototherapy becomes a novel tumor treatment means with potential, and the treatment means not only has high specificity and repeated treatment, but also has noninvasive property and good space selectivity, so that the phototherapy has good development prospect for treating tumors.

The key to phototherapy technology is phototherapy agents and phototherapy devices. With the development of materials and nanotechnology, various nanomaterials having photoreactivity have been used for phototherapy of tumors as photothermal agents and photosensitizers. The phototherapy device also has made obvious progress, and current phototherapy device mainly comprises laser source and optic fibre collimating lens, and the laser of specific wavelength is sent from the light source, gets into optic fibre by interior lens array space coupling, and then exports through the tail fiber, is connected to the flange joint of laser outside fixed, connects optic fibre collimating lens to the flange, can export laser through collimating lens, reaches the purpose of shining the affected part. There are many reports of phototherapy apparatuses based on this structure, for example, patent application CN202211691679.4 designs a dual-wavelength alternative pulse laser collaborative acupuncture simulation system, in which light source lasers are coupled into optical fibers through a coupling lens group and an optical fiber coupler, and then split by a beam splitter and output from a laser acupuncture head. The patent application CN201810005185.3 designs a diagnosis and treatment integrated tumor laser hyperthermia and multi-parameter real-time monitoring probe, and the laser emergent optical fiber and the plurality of near infrared sensing optical fibers are inserted into the rigid shell, so that multi-parameter indexes in tumor tissues can be monitored in real time during laser hyperthermia, but the probe cannot be inserted into the tumor. Patent application CN202210535559.9 devised a new phototherapy device, which irradiates the scalp, auditory canal, nasal cavity, acupoints, etc. of a patient with light via optical fiber output. Still other improvements are made to basic phototherapy devices, for example, patent application CN202221855967.4 designs a phototherapy device, and a laser module and a temperature control overload protector are placed on a base to form a surface irradiation device, so that an object placed on the irradiation device is irradiated and is powered off when the temperature exceeds a set temperature, and the optimal therapeutic effect is achieved. Patent application CN202222629992.7 designs a portable fixable phototherapy apparatus mainly composed of an integrated circuit back cover, a lens and a patch with a hole structure, which makes light irradiate only the treated area as much as possible, thereby improving the treatment efficiency. Patent application CN202110307983.3 discloses a phototherapy device composed of blue-green light chips, which comprises a substrate, a reflective DBR layer, a first n-type GaN layer, a first quantum well layer, a first p-type GaN layer, an emergent DBR layer, and a tunnel-combined GaN-based LED epitaxial wafer, wherein the light-emitting device has a multi-layer light-emitting structure, a large light-emitting angle, and is beneficial to reducing light loss.

However, the above phototherapy apparatus still does not solve the following problems: firstly, the penetration depth of light is limited, and the penetration depth of light into tissues is critical in phototherapy because it determines whether photothermal agents and photosensitizers can exert maximum efficacy. However, the penetration of light into human tissue is very limited, and even the near infrared light with the strongest penetration can only reach a penetration depth of about 1 cm, so that the treatment of large-volume and deep tumors can not be realized. Despite some reports of improvement such as concentration of light irradiation area, shortening of irradiation distance, etc., light transmission is blocked by the skin. Most of the light energy is absorbed by the skin and tissues and cannot be efficiently delivered to the affected part. Secondly, the output light energy is unevenly distributed, most light energy is concentrated on the surface of the skin, so that the temperature of the skin is increased without obvious change of the temperature in the tumor, and even the skin is burnt to further obstruct light transmission and temperature diffusion, thereby causing normal tissue injury and reducing the treatment efficiency. Thirdly, the output mode of the light energy is single, most of the light energy of the phototherapy equipment is single-point output, the size and the shape of the actual tumor are different, and single-point irradiation cannot be fully covered. Thus, current phototherapy apparatuses do not fully exert the performance of phototherapy.

Up to now, phototherapy microneedles capable of being used for deep tumor treatment and adjustable in light output mode have not been reported.

Disclosure of Invention

In order to solve the problems of poor penetrating power of optical tissues, concentration of energy on the surface of skin, uneven heat distribution and single output mode in the existing tumor phototherapy process, the invention aims to provide the stainless steel compound phototherapy microneedle with different light output modes, namely, wall holes are drilled at different positions of a hollow needle, an optical fiber passes through a cavity of the needle body, the end face of the optical fiber extends to a bevel of the needle tip, and a solidified optical transparent high polymer material is filled between the optical fiber and the cavity of the hollow needle body to form the phototherapy microneedle with compact and closed structure; the microneedle has simple process, high firmness and durability, and can protect the optical fiber from penetrating into tumor tissues to develop phototherapy; the invention can be used for tumor phototherapy, and can also be used for auxiliary thermotherapy of other diseases by switching laser wavelength and power and utilizing the thermal effect of laser.

In order to achieve the above purpose, the technical scheme of the invention is as follows:

the stainless steel composite phototherapy micro-needle with different light output modes comprises a tubular hollow needle body 1 and a needle point bevel 2 integrated with the tubular hollow needle body; the outer surface of the hollow needle body 1 is provided with at least one wall hole 3, and the wall hole 3 is communicated with the cavity of the hollow needle body 1; the optical fiber 4 passes through the hollow needle body 1 cavity, the end face of the optical fiber 4 extends to the needle tip bevel 2, and the top end of the bevel 2, the optical fiber 4 and the hollow needle body 1 cavity are filled with solidified optical transparent high polymer material 5 to form the phototherapy microneedle with a closed structure.

The hollow needle body 1 is made of stainless steel, has an inner diameter of 0.5-1.2mm, an outer diameter of 0.7-1.5mm and a length of 50-130mm.

The bevel angle of the needle point bevel 2 is set to 9-17 degrees.

The wall holes 3 are round holes or square holes, the directions are all directions, three directions, two directions and one direction, the aperture of the round holes is 0.2-0.8mm, the hole spacing is 0.6-2mm, the number of punching lines is 1-20, and the number of holes in each line is 1-4; the square hole has a width of 0.2-0.8mm and a length of 6-20mm.

The optically transparent high polymer material 5 is Polydimethylsiloxane (PDMS) or polymethyl methacrylate (PMMA), and the filling length is 20-30mm.

Based on the preparation method of the stainless steel composite phototherapy micro needle with different light output modes, the preparation method is realized through the following steps:

(1) The optical fiber 4 with the surface treated is penetrated through the hollow needle body 1, the end face of the optical fiber extends to the inclined opening 2 of the needle point, the epoxy adhesive is used for pointing at the joint of the optical fiber and the flat opening end of the needle body, and the ultraviolet lamp is used for irradiation curing at normal temperature;

(2) And filling the optically transparent high polymer material 5 into a cavity between the optical fiber and the needle body from the bevel opening of the needle point, filling the cavity with a wall hole of 20-30mm, then placing the cavity in a constant temperature drying oven, and reacting and solidifying to form a compact closed structure.

The wall hole 3 is prepared by a laser drilling technology, and the construction is realized by the following steps:

(1) And manufacturing an aluminum plate groove matched with the outer diameter of the tubular hollow needle body according to the size parameters of the tubular hollow needle body, and placing the needle body into the groove.

(2) Debugging laser drilling instrument parameters, positioning laser to a designated position and drilling, and continuously adjusting the laser positioning points to form round holes or square holes, wherein the aperture of the round holes is 0.2-0.8mm, the hole spacing is 0.6-2mm, the number of drilling lines is 1-20, and the number of holes in each line is 1-4; the square hole has a width of 0.2-0.8mm and a length of 6-20mm;

(3) And (3) repeating the step (2) to realize wall holes with different numbers and different positions on the needle body.

The optical fiber 4 is prepared from a single-joint single-mode optical fiber or a multimode optical fiber jumper by a cladding optical power stripping technology, and the construction is realized by the following steps:

(1) Pretreatment of optical fibers: stripping the outer sleeve of the non-joint end of the optical fiber jumper by using an optical fiber stripper to expose bare optical fibers with the length of 60-80mm, stripping the coating layer of the bare optical fibers, stripping the length of 10-15mm, cleaning the bare optical fibers by using absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

(2) Cladding light stripping: fully soaking the pretreated optical fiber in a stripping liquid at normal temperature for 2.5-4 hours, and corroding the cladding to 60-250 mu m in diameter;

the stripping liquid is a hydrofluoric acid aqueous solution with the mass fraction of 20%;

(3) And (3) post-treatment of the optical fiber: and (3) washing the treated optical fiber with water, and then soaking the optical fiber with absolute ethyl alcohol until the surface of the optical fiber is clean.

Compared with the existing phototherapy equipment, the phototherapy microneedle provided by the invention has the following advantages:

1. the wall holes are punched at different positions of the hollow needle, an optical fiber passes through the needle cavity, the end face of the optical fiber extends to the bevel mouth of the needle point, a solidified optical transparent high polymer material is filled between the optical fiber and the hollow needle cavity, the phototherapy micro needle with a compact and closed structure is formed, the optical fiber is processed by a cladding optical power stripping technology, the transmission light can be emitted from the end face of the needle point and can also be emitted from the fiber core to the periphery of the cladding through the wall holes, the design mode and the light output position of the optical waveguide are determined by combining the number, the shape and the position of the wall holes on the hollow needle body, the light output of different modes is realized, and the requirements of phototherapy of tumors with different sizes and shapes can be met. Because the outer layer of the phototherapy microneedle is made of stainless steel, the phototherapy microneedle can be inserted into a tumor to realize phototherapy, the external energy output of the original phototherapy is changed into the internal energy output, the light does not need to pass through skin and tissues any more, the light energy utilization efficiency is high, the output is even, the treatment effect is better, and the side effect on normal tissues is small. In addition, the optical fiber has good insulativity and electromagnetic interference resistance, the needle body of the invention can not generate electric stimulation when being contacted with a human body, the light output characteristic is not interfered by external electromagnetic environment, and the light energy can be continuously and uniformly output.

2. The optical fiber can be used as the optical waveguide to directly guide the light energy into the tumor by inserting the phototherapy microneedle into the tumor, thereby avoiding the absorption and dissipation of the tissue to the light, improving the energy utilization rate and solving the problems of poor light penetration capability, energy concentration on the skin surface and uneven heat distribution in the phototherapy process of the tumor. The optical fiber is processed by cladding optical power stripping technology, and the transmission light can be emitted from the end face, and can also be emitted from the fiber core to the periphery through cladding wall holes, and the design mode and the optical energy output position of the optical waveguide are determined by combining the number, the shape and the position of the upper wall holes of the hollow needle body, so that the optical outputs in different modes are realized.

3. Because the optical fiber has good insulativity and electromagnetic interference resistance, the needle body of the invention can not generate electric stimulation when being contacted with a human body, the light output characteristic is not interfered by external electromagnetic environment, and the light energy can be continuously and uniformly emitted; the cladding material is firm, has good durability and can be repeatedly used; the optical microneedle has simple structure and simple process, and is convenient for mass production.

Drawings

Fig. 1A is an omnidirectional square hole array type phototherapy microneedle, and fig. 1B is an omnidirectional round hole array type phototherapy microneedle.

Fig. 2A is an overall view of an omnidirectional square hole array type phototherapy microneedle, fig. 2B is a partial view of the wall hole position of the omnidirectional square hole array type phototherapy microneedle, fig. 2C is an overall view of the omnidirectional round hole array type phototherapy microneedle, and fig. 2D is a partial view of the wall hole position of the omnidirectional round hole array type phototherapy microneedle.

Fig. 3A is a graph showing a temperature change of 1mg/mL of a photo-thermal agent Polydopamine (PDA) and an iron-Polydopamine (Fe-PDA) aqueous solution with respect to time at 500mW of light power, and fig. 3B is a graph showing a temperature change of 1mg/mL of a Polydopamine aqueous solution with respect to time at different light powers for the omnidirectional square-hole array type photo-therapeutic microneedle.

FIG. 4 is a graph showing the temperature change over time of the omnidirectional square-hole array type phototherapy microneedle according to the present invention at different optical powers in 1mg/mL Polydopamine (PDA) gel.

Fig. 5A is an infrared thermal imaging diagram of an omnidirectional square hole array type phototherapy microneedle, and fig. 5B is an infrared thermal imaging diagram of an omnidirectional round hole array type phototherapy microneedle.

Detailed Description

The present invention will be described in detail with reference to the accompanying drawings.

Referring to fig. 1A and 1B, a stainless steel packaging optical fiber composite phototherapy micro-needle with an adjustable light output mode comprises a tubular hollow needle body 1 and a needle tip bevel 2 integrated with the tubular hollow needle body; at least one wall hole 3 is drilled on the outer surface of the hollow needle body 1, and the wall hole 3 is communicated with the cavity of the hollow needle body 1; an optical fiber 4 passes through the needle cavity, the end face of the optical fiber extends to the needle tip bevel 2, and an optically transparent high polymer material 5 is filled between the optical fiber 4 and the needle cavity to form the phototherapy microneedle with compact and closed structure. The optical fiber 4 is processed by cladding optical power stripping technology, the transmission light can be emitted from the end face, and can uniformly leak from the fiber core to the periphery of the cladding, and the design mode and the light output position of the optical waveguide are determined by combining the number, the shape and the position of the upper wall holes of the hollow needle body 1, so that uniform light energy output and adjustable output mode are realized.

The bevel angle of the needle point bevel 2 is set to 9-17 degrees.

The wall holes 3 are round holes or square holes, and the directions are all-direction, three-direction, two-direction and one-direction, so that the wall holes are divided into all-direction square hole array type phototherapy micro-needles, three-direction square hole array type phototherapy micro-needles, two-direction square hole array type phototherapy micro-needles, one-direction square hole type phototherapy micro-needles, all-direction round hole array type phototherapy micro-needles, three-direction round hole array type phototherapy micro-needles and one-direction round hole array type phototherapy micro-needles. The aperture of the round holes is 0.2-0.8mm, the hole spacing is 0.6-2mm, the number of the punching lines is 1-20, and the number of the holes in each line is 1-4; the square hole has a width of 0.2-0.8mm and a length of 6-20mm.

The working principle of the invention is as follows:

as shown in FIG. 1A, the omnidirectional square hole array phototherapy microneedle uses a laser drilling technology to manufacture square wall holes in four directions on the outer wall of a hollow needle body 1, and an optical fiber 4 subjected to cladding power stripping treatment passes through a needle body cavity, the end face of the optical fiber extends to a needle tip bevel 2, an optically transparent high polymer material 5 is filled between the optical fiber 4 and the needle body cavity, and optical fiber output light can be emitted uniformly from the needle tip and the surrounding wall holes. The three-direction square hole array type phototherapy micro needle, the two-direction square hole array type phototherapy micro needle and the one-direction square hole phototherapy micro needle are similar to the all-direction square hole array type phototherapy micro needle in structure, and are obtained through respectively manufacturing square wall holes in three directions, two directions and one direction on a hollow needle body and through the same subsequent preparation process. By adjusting the width, length, direction and number of the square wall holes, the light output mode can be adjusted, and the specific wall hole positions can be designed according to actual needs.

As shown in FIG. 1B, the omnidirectional round hole array type phototherapy microneedle uses a laser drilling technology to manufacture round wall holes with 20 circles in four directions on the outer wall of a hollow needle body 1, and an optical fiber 4 subjected to cladding power stripping treatment passes through a needle body cavity, the end face of the optical fiber extends to a needle point bevel 2, an optically transparent high polymer material 5 is filled between the optical fiber 4 and the needle body cavity, and optical fiber output light can be emitted uniformly from the needle point and the wall holes around. The three-direction round hole array type phototherapy micro-needle, the two-direction round hole array type phototherapy micro-needle and the unidirectional round hole array type phototherapy micro-needle are similar to the all-direction round hole array type phototherapy micro-needle in structure, are obtained through respectively manufacturing round wall holes with different rows in three directions, two directions and one direction on a hollow needle body and through the same subsequent preparation process. By adjusting the aperture, direction and number of the circular wall holes, the light output mode can be adjusted, and the specific wall hole positions can be designed according to actual needs.

Fig. 2A is a full view of an omnidirectional square hole array type phototherapy microneedle, fig. 2B is a partial enlarged view of a wall hole position of the omnidirectional square hole array type phototherapy microneedle, fig. 2C is a full view of an omnidirectional round hole array type phototherapy microneedle, and fig. 2D is a partial enlarged view of a wall hole position of the omnidirectional round hole array type phototherapy microneedle. The optical fiber subjected to cladding power stripping treatment passes through the cavity of the needle body, the end face of the optical fiber extends to the bevel mouth of the needle tip, and when the other end of the optical fiber is connected with a light source, light is uniformly output from the positions of the needle tip and the wall hole.

Fig. 3A and 3B are diagrams showing the temperature change of the omnidirectional square hole array type phototherapy microneedle working in an aqueous solution for 5min with time, wherein the wall holes are four-directional shaped wall holes, the width is 0.4mm, and the length is 10mm. The solution container is in a truncated cone shape, the radius of the top surface is 5mm, the radius of the bottom surface is 2mm, the height is 40mm, and the total volume is about 0.8mL. The omnidirectional square hole array type phototherapy microneedle can enable a photo-thermal agent Polydopamine (PDA) aqueous solution and an iron-polydopamine (Fe-PDA) aqueous solution to achieve higher photo-thermal temperature with lower optical power, enable 1mg/mL of PDA solution to reach 41.4 ℃ photo-thermal temperature under 500mW light source output power, and enable 1mg/mL of Fe-PDA solution to reach 51.5 ℃ photo-thermal temperature.

FIG. 4 is a graph showing the temperature change over time of an omnidirectional square-hole array phototherapy microneedle of the present invention operating in 1mg/mL Polydopamine (PDA) gel for 5min, wherein the photothermal temperature of 1mg/mL PDA gel can reach 58.9 ℃ at 500mW light source output power, 64.6 ℃ at 700mW light power, and 74.9 ℃ at 1000mW light power.

Fig. 5A is an infrared thermal imaging diagram of an omnidirectional square hole array phototherapy microneedle, the wall holes are square wall holes in four directions, the width is 0.4mm, the length is 10mm, it can be clearly seen that the temperature of the needle tip and the wall hole area is obviously higher than that of other parts of the needle body, and effective output of light from the needle tip and the wall holes is realized. Fig. 5B is an infrared thermal imaging diagram of the all-directional circular hole array type phototherapy micro needle, the wall holes are circular wall holes of 20 rows in four directions of each row, the diameter is 0.4mm, it can be clearly seen that the temperature of the needle tip and the wall hole area is higher than that of other parts of the needle body, the temperature distribution is obviously different from that of the all-directional square hole array type phototherapy micro needle, and the light output mode is adjustable.

The wall hole fabrication process, the fiber fabrication process, and the stainless steel encapsulated fiber composite fabrication process of the present invention are further described below in connection with various embodiments.

Example 1

The structural schematic diagram of the omnidirectional square hole array type phototherapy microneedle is shown in fig. 1A.

The wall holes 3 of the omnidirectional square hole array type phototherapy microneedle are realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 100mm, the inner diameter of 1.2mm, the outer diameter of 1.5mm and the tip bevel angle of 13 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 1.5mm and the length of 100 mm;

(2) The parameters of the laser drilling instrument are adjusted, the parameter treatment effect is better, and the side effect is low. The method comprises the steps of positioning laser to a designated position by laser pulse energy density, pulse width, pulse waveform and defocus, and forming square holes in four directions by continuously adjusting laser positioning points, wherein the width of each hole is 0.8mm, and the length of each hole is 20mm;

the optical fiber 4 is prepared by cladding optical power stripping technology, and the construction is realized by the following steps:

(1) Pretreatment of optical fibers: selecting a single-end SMA joint multimode optical fiber jumper with the core diameter of 400 mu m, stripping an external sleeve at the non-joint end of the optical fiber jumper by using an optical fiber wire stripper to expose a bare optical fiber with the length of 80mm, stripping a coating layer of the bare optical fiber, stripping the length of 15mm, cleaning the bare optical fiber with absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

(2) Cladding light stripping: fully soaking the pretreated optical fiber in a stripping liquid for 4 hours at normal temperature, and corroding the diameter of the cladding to 150 mu m;

the stripping liquid is a hydrofluoric acid aqueous solution with the mass fraction of 20%.

(3) And (3) post-treatment of the optical fiber: and (3) washing the treated optical fiber with water, and then soaking the optical fiber in absolute ethyl alcohol for 5min to clean the surface of the optical fiber.

The construction of the stainless steel packaging optical fiber composite structure is realized by the following steps:

(1) The treated optical fiber 4 passes through the hollow needle body 1, the end face of the optical fiber extends to the needle tip bevel 2, 0.1mL of epoxy adhesive is used for pointing at the joint of the optical fiber and the flat end of the needle body, and the optical fiber is irradiated and solidified for 10 minutes by an ultraviolet lamp at normal temperature; using 0.1mL of epoxy adhesive to spot at the joint of the optical fiber and the flat end of the needle body, and using an ultraviolet lamp to irradiate and cure for 10 minutes at normal temperature; the components of the epoxy adhesive include prepolymer epoxy acrylate and initiator benzophenone.

(2) And filling the optically transparent high polymer material PDMS into a cavity between the optical fiber and the needle body from the bevel opening of the needle tip, filling a wall hole with a filling length of 30mm, then placing the cavity in a constant temperature drying oven, and reacting and curing for 2 hours at the temperature of 100 ℃ to form a compact closed structure.

Phototherapy performance test: the prepared omnidirectional square hole array type phototherapy microneedle is connected with a light source, 500-1000mW of light power is output, the test results in a photothermal agent Polydopamine (PDA) water solution and an iron-polydopamine (Fe-PDA) water solution are shown in a graph 3, the abscissa is time, the ordinate is temperature, the total volume of the solution is 0.8mL, when the light source power is 500mW, the temperature of 1mg/mL PDA solution can reach 41.4 ℃ within 5min, the temperature of the same concentration Fe-PDA solution reaches 51.5 ℃, when the light source power is increased to 700mW, the temperature of the same concentration PDA solution can reach 56.0 ℃, and the temperature of the same concentration PDA solution can reach 67.7 ℃ when the temperature is increased to 1000 mW. FIG. 4 is a graph showing the temperature change of the omnidirectional square hole array type phototherapy micro needle in the gel during 5min operation over time, wherein the photothermal temperature of 1mg/mL PDA gel can reach 58.9 ℃ under the output power of a 500mW light source, the photothermal temperature of 64.6 ℃ under the light power of 700mW, and the photothermal temperature of 74.9 ℃ under the light power of 1000 mW. Fig. 5A is an infrared thermal imaging diagram of the omnidirectional square hole array phototherapy microneedle when the output optical power of the PDA gel is 500mW, and in the PDA gel added with 1mg/mL, it can be clearly seen that the temperature of the needle tip and the position of the fiber stripped area corresponding to the wall hole is obviously higher than the other parts of the needle body, the temperature can reach 64.6 ℃, and the effective output of light from the needle tip and the wall hole is realized.

Example two

The wall holes 3 of the three-direction square hole array type phototherapy microneedle are realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 110mm, the inner diameter of 0.9mm, the outer diameter of 1.2mm and the tip bevel angle of 9 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 1.2mm and the length of 110 mm;

(2) Debugging parameters of a laser drilling instrument, positioning laser to a designated position, and continuously adjusting the laser positioning points to form square holes in four directions, wherein the width of each hole is 0.6mm, and the length of each hole is 12mm;

(1) Pretreatment of optical fibers: selecting a single-end SMA joint multimode optical fiber jumper with the core diameter of 250 mu m, stripping an external sleeve at the non-joint end of the optical fiber jumper by using an optical fiber wire stripper to expose a bare optical fiber with the length of 70mm, stripping a coating layer of the bare optical fiber, stripping the length of 10mm, cleaning the bare optical fiber with absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

(2) Cladding light stripping: fully soaking the pretreated optical fiber in a stripping liquid at normal temperature for 3 hours, and corroding the diameter of the cladding to 150 mu m;

(1) The treated optical fiber 4 passes through the hollow needle body 1, the end face of the optical fiber extends to the needle tip bevel 2, 0.1mL of epoxy adhesive is used for pointing at the joint of the optical fiber and the flat end of the needle body, and the optical fiber is irradiated and solidified for 10 minutes by an ultraviolet lamp at normal temperature;

(2) And filling the optically transparent high polymer material PDMS into a cavity between the optical fiber and the needle body from the bevel opening of the needle tip, filling the cavity with a wall hole of 25mm, and then placing the cavity in a constant-temperature drying oven for reaction and curing for 2 hours at the temperature of 100 ℃ to form a compact closed structure.

Phototherapy performance test: the working effect was substantially similar to that of example one.

Example III

The wall holes 3 of the two-direction square hole array type phototherapy microneedle are realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 80mm, the inner diameter of 0.5mm, the outer diameter of 0.7mm and the bevel angle of the needle tip of 15 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 0.7mm and the length of 80 mm;

(2) Debugging parameters of a laser drilling instrument, positioning laser to a designated position, and continuously adjusting the laser positioning points to form square holes in four directions, wherein the width of each hole is 0.2mm, and the length of each hole is 10mm;

(1) Pretreatment of optical fibers: selecting a single-ended FC/APC connector single-mode optical fiber jumper with the core diameter of 125 mu m, stripping an external sleeve at the non-connector end of the optical fiber jumper by using an optical fiber stripper to expose a bare optical fiber with the length of 50mm, stripping a coating layer of the bare optical fiber, stripping the length of 11mm, cleaning the bare optical fiber with absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

(2) Cladding light stripping: fully soaking the pretreated optical fiber in a stripping liquid at normal temperature for 3.5 hours, and corroding the diameter of the cladding to 90 mu m;

(2) And (3) filling an optically transparent high polymer material PMMA into a cavity between the optical fiber and the needle body from the bevel opening of the needle point, filling a wall hole with a filling length of 20mm, and then placing the cavity in a constant-temperature drying oven for reaction and curing for 2 hours at the temperature of 100 ℃ to form a compact closed structure.

Example IV

The wall hole 3 of the unidirectional hole type phototherapy microneedle is realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 50mm, the inner diameter of 0.7mm, the outer diameter of 0.9mm and the needle tip bevel angle of 9 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 0.9mm and the length of 50 mm;

(2) Debugging parameters of a laser drilling instrument, positioning laser to a designated position, and continuously adjusting the laser positioning points to form square holes in four directions, wherein the width of each hole is 0.3mm, and the length of each hole is 6mm;

(1) Pretreatment of optical fibers: selecting a single-end SMA joint multimode optical fiber jumper with the core diameter of 400 mu m, stripping an external sleeve at the non-joint end of the optical fiber jumper by using an optical fiber wire stripper to expose a bare optical fiber with the length of 60mm, stripping a coating layer of the bare optical fiber, stripping the length of 13mm, cleaning the bare optical fiber with absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

(2) Cladding light stripping: fully soaking the pretreated optical fiber in a stripping liquid for 2.5 hours at normal temperature, and corroding the diameter of the cladding to 250 mu m;

(2) And (3) filling an optically transparent high polymer material PMMA into a cavity between the optical fiber and the needle body from the bevel opening of the needle point, filling a wall hole with a filling length of 30mm, and then placing the cavity in a constant-temperature drying oven for reaction and curing for 2 hours at the temperature of 100 ℃ to form a compact closed structure.

Example five

The structural schematic diagram of the omnidirectional round hole array type phototherapy microneedle is shown in fig. 1B.

The wall holes 3 of the omnidirectional round hole array type phototherapy micro needle are realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 120mm, the inner diameter of 1.0mm, the outer diameter of 1.3mm and the tip bevel angle of 13 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 1.2mm and the length of 120 mm;

(2) Debugging parameters of a laser drilling instrument, positioning laser to a designated position, and forming round holes in four directions by continuously adjusting the laser positioning points, wherein the aperture is 0.4mm, the hole spacing is 0.6mm and the Kong Hangshu is 20;

Phototherapy performance test: the results were substantially similar to those of example one, but the infrared thermography is shown in FIG. 5B, in a 1mg/mL PDA gel, the temperature at the point and fiber stripped area corresponding to the wall hole was significantly higher than in the other areas, with a maximum temperature of 61.2 ℃.

Example six

The wall holes 3 of the three-way round hole array type phototherapy microneedle are realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 100mm, the inner diameter of 1.1mm, the outer diameter of 1.4mm and the needle tip bevel angle of 17 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 1.5mm and the length of 100 mm;

(2) Debugging parameters of a laser drilling instrument, positioning laser to a designated position, and forming round holes in four directions by continuously adjusting the laser positioning points, wherein the aperture is 0.8mm, the hole spacing is 2.0mm and the Kong Hangshu is 16;

(1) Pretreatment of optical fibers: selecting a single-end SMA joint multimode optical fiber jumper with the core diameter of 400 mu m, stripping an external sleeve at the non-joint end of the optical fiber jumper by using an optical fiber wire stripper to expose a bare optical fiber with the length of 70mm, stripping a coating layer of the bare optical fiber, stripping the length of 13mm, cleaning the bare optical fiber with absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

Phototherapy performance test: the working effect was substantially similar to that of example five.

Example seven

The wall holes 3 of the two-direction round hole array type phototherapy micro needle are realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 90mm, the inner diameter of 0.6mm, the outer diameter of 0.9mm and the tip bevel angle of 13 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 0.9mm and the length of 90 mm;

(2) Debugging parameters of a laser drilling instrument, positioning laser to a designated position, and forming round holes in four directions by continuously adjusting the laser positioning points, wherein the aperture is 0.2mm, the hole spacing is 0.8mm and the number of hole rows is 6;

(1) Pretreatment of optical fibers: selecting a single-ended FC/APC connector single-mode optical fiber jumper with the core diameter of 125 mu m, stripping an external sleeve at the non-connector end of the optical fiber jumper by using an optical fiber stripper to expose a bare optical fiber with the length of 40mm, stripping a coating layer of the bare optical fiber, stripping the length of 11mm, cleaning the bare optical fiber with absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

(2) Cladding light stripping: fully soaking the pretreated optical fiber in a stripping liquid for 4 hours at normal temperature, and corroding the diameter of the cladding to 60 mu m;

Example eight

The wall holes 3 of the unidirectional round hole array type phototherapy micro needle are realized through the following steps:

(1) Selecting a hollow stainless steel needle with the length of 80mm, the inner diameter of 0.8mm, the outer diameter of 1.1mm and the tip bevel angle of 11 degrees, and fixing the hollow stainless steel needle in an aluminum plate groove with the diameter of 1.2mm and the length of 120 mm;

(2) Debugging parameters of a laser drilling instrument, positioning laser to a designated position, and forming round holes in four directions by continuously adjusting the laser positioning points, wherein the aperture is 0.5mm and Kong Hangshu is 1;

(1) Pretreatment of optical fibers: selecting a single-end SMA joint multimode optical fiber jumper with the core diameter of 250 mu m, stripping an external sleeve at the non-joint end of the optical fiber jumper by using an optical fiber wire stripper to expose a bare optical fiber with the length of 60mm, stripping a coating layer of the bare optical fiber, stripping the length of 12mm, cleaning the bare optical fiber with absolute ethyl alcohol to remove surface stains, and cutting the end face flat by using an optical fiber cutting knife;

In summary, as shown in fig. 5A and 5B, in the gel added with the photo-thermal agent, the temperature of the corresponding wall holes of the tip and the fiber stripping region is significantly higher than that of the other regions, which indicates that the light is uniformly emitted from the tip and the surrounding wall holes. The optical fiber is processed by cladding optical power stripping technology, the transmission light can be emitted from the end face, can be uniformly leaked from the fiber core to the periphery of the cladding, and the design mode and the light output position of the optical waveguide are determined by combining the number, the shape and the position of the upper wall holes of the hollow needle body, so that uniform light energy output and adjustable output mode are realized. In addition, because the optical fiber has good insulativity and electromagnetic interference resistance, the needle body of the invention can not generate electric stimulation when being contacted with a human body, the light output characteristic is not interfered by external electromagnetic environment, and the light can be continuously emitted; the material is firm, has good durability and can be repeatedly used; simple structure, simple process and convenient mass production.

The above-described embodiments are only for illustrating the present invention and should not be construed as limiting the present invention, and any modifications and changes made to the present invention within the scope of the appended claims are within the scope of the present invention.

Claims

1. The stainless steel composite phototherapy micro-needle with different light output modes is characterized by comprising a tubular hollow needle body (1) and a needle point bevel (2) integrated with the tubular hollow needle body; the outer surface of the hollow needle body (1) is at least provided with one wall hole (3), and the wall hole (3) is communicated with the cavity of the hollow needle body (1); the optical fiber (4) passes through the cavity of the needle body, the end face of the optical fiber (4) extends to the bevel mouth (2) of the needle tip, and a solidified optical transparent high polymer material (5) is filled among the top end of the bevel mouth (2), the optical fiber (4) and the cavity of the hollow needle body (1) to form the phototherapy micro needle with a closed structure.

2. The stainless steel composite phototherapy micro-needle with different light output modes according to claim 1, wherein the hollow needle body (1) is made of stainless steel, the inner diameter is 0.5-1.2mm, the outer diameter is 0.7-1.5mm, and the length is 50-130mm.

3. The stainless steel composite phototherapy micro-needle with different light output modes according to claim 1, wherein the bevel angle of the needle tip bevel (2) is set to 9-17 °.

4. The stainless steel composite phototherapy microneedle with different light output modes according to claim 1, wherein the wall holes (3) are square or round, the directions are all directions, three directions, two directions and one direction, the aperture of the round holes is 0.2-0.8mm, the hole spacing is 0.6-2mm, the number of punching lines is 1-20 lines, and the number of holes in each line is 1-4; the square hole has a width of 0.2-0.8mm and a length of 6-20mm.

5. The stainless steel composite phototherapy microneedle with different light output modes according to claim 1, wherein the optically transparent high molecular polymer material (5) is polydimethylsiloxane or polymethyl methacrylate, and the filling length is 20-30mm.

6. The preparation method of the stainless steel composite phototherapy microneedle with different light output modes is characterized by comprising the following steps:

(1) The optical fiber (4) with the surface treated is penetrated through the hollow needle body (1), the end face of the optical fiber extends to the inclined opening (2) of the needle point, the epoxy adhesive is used for pointing at the joint of the optical fiber and the flat opening end of the needle body, and the optical fiber is irradiated and solidified by an ultraviolet lamp at normal temperature;

(2) And filling an optical transparent high polymer material (5) into a cavity between the optical fiber and the needle body from the bevel opening of the needle tip, filling a wall hole with the filling length of 20-30mm, and then placing the optical transparent high polymer material into a constant temperature drying oven for reaction and solidification to form a compact closed structure.

7. The method for preparing the stainless steel composite phototherapy micro-needle with different light output modes according to claim 6, wherein,

the wall hole (3) is prepared by using a laser drilling technology, and the construction is realized by the following steps:

(1) And manufacturing a groove matched with the outer diameter of the tubular hollow needle body according to the size parameters of the tubular hollow needle body, and placing the needle body into the groove.

8. The method for preparing the stainless steel-encapsulated fiber composite phototherapy microneedle with different light output modes according to claim 6, which is characterized in that,

the optical fiber (4) is prepared from a single-joint single-mode optical fiber or a multimode optical fiber jumper wire by a cladding optical power stripping technology, and the construction is realized by the following steps:

(3) And (3) post-treatment of the optical fiber: and (3) washing the treated optical fiber with water, and then soaking the optical fiber with absolute ethyl alcohol until the surface of the optical fiber is cleaned.