A method for preparing hollow glass microneedles by laser-guided anisotropic etching
By employing a laser-guided anisotropic etching method and a two-step laser modification and wet etching process, the problem of integrating sharp shapes and hollow channels in the fabrication of hollow glass microneedles has been solved, achieving high-precision and integrated microneedle fabrication suitable for biomedical applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GUANGDONG UNIV OF TECH
- Filing Date
- 2026-06-25
- Publication Date
- 2026-07-31
AI Technical Summary
Existing technologies struggle to maintain a sharp shape while achieving integrated hollow channel formation during the fabrication of glass hollow microneedles, and also suffer from issues such as short mold life and demanding equipment requirements in high-temperature molding.
By employing a laser-guided anisotropic etching method, and through a two-step laser modification and a two-step wet etching process, the outer contour shaping of the microneedle and the substrate thinning are completed simultaneously in the same wet etching process, forming an integrated glass hollow microneedle with a sharp tip and a smooth conical surface.
It achieves high-precision shape control and retention of sharp needle tips, eliminates the risk of interface leakage and assembly errors, and has the potential for large-area, high-consistency and mass production.
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Figure CN122479293A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of medical device technology, and in particular to a method for preparing hollow glass microneedles by laser-guided anisotropic etching. Background Technology
[0002] Microneedles, as a minimally invasive percutaneous drug delivery and body fluid extraction tool, have attracted widespread attention in the biomedical field because they can penetrate the stratum corneum of the skin without touching pain nerves. Glass materials, with their high hardness, excellent chemical stability, and biocompatibility, have become ideal candidates for high-performance microneedles. In particular, hollow glass microneedles allow drug solutions to be injected directly into the body through internal channels, offering advantages such as high drug delivery efficiency and strong controllability.
[0003] Currently, the main methods for manufacturing glass microneedles include precision hot stretching, grinding, and mold forming, such as the microneedle mold making, microneedle manufacturing method, microneedle mold, and microneedle disclosed in CN121225885A. Hot stretching makes it difficult to precisely control the geometric dimensions and arrangement of the microneedles; mechanical grinding causes severe tool wear and low yield; while high-temperature molding faces challenges such as short mold life and high equipment requirements. In recent years, femtosecond laser-assisted wet etching technology has shown great potential in three-dimensional glass micromachining due to its advantages of being non-contact and free from thermal stress damage.
[0004] Despite their respective advantages, the aforementioned methods still have significant shortcomings in the fabrication of hollow glass microneedles. On one hand, glass itself exhibits isotropic properties during conventional wet etching, causing the already formed sharp structure to easily become rounded during subsequent etching processes, making it difficult to maintain the high-sharpness tip required for the microneedle. On the other hand, achieving a hollow structure requires the formation of a through-channel within the microneedle; however, in existing technologies, processes such as through-hole fabrication, outer contour shaping, and substrate thinning often interfere with each other, making it difficult to achieve a highly consistent integrated structure within the same process flow. Furthermore, existing laser-assisted etching methods are mostly focused on the fabrication of solid microneedles or simple microstructures, such as the glass microgroove fabrication method disclosed in CN117430339A. An effective and stable process path is still lacking for integrating a hollow channel through the tip within the microneedle while maintaining a sharp shape. This significantly limits the application of glass microneedles in high-end biomedical devices.
[0005] Therefore, developing a method for preparing glass hollow microneedles that can simultaneously achieve high-precision shape control, sharp tip retention, and integrated hollow channel forming is an urgent problem to be solved in this field. Summary of the Invention
[0006] The purpose of this invention is to provide a method for preparing hollow glass microneedles using laser-guided anisotropic etching, achieving integrated molding of the microneedle's sharp tip and smooth conical surface. The hollow glass microneedles prepared by this method achieve both high-precision shape control and sharp tip retention control.
[0007] To achieve this objective, the present invention adopts the following technical solution:
[0008] A method for preparing hollow glass microneedles by laser-guided anisotropic etching, characterized by comprising the following steps:
[0009] A: Clean and dry the glass substrate;
[0010] B: The first Bessel laser beam is focused onto the first surface of the glass substrate to form a vertical modification line that runs through the thickness direction inside the glass substrate;
[0011] C: A vertical through-hole is formed along the vertical modification line by first wet etching;
[0012] D: Clean and dry the glass substrate with vertical through holes;
[0013] E: The second Bessel laser beam is focused on the first or second surface of the glass substrate to form a closed-loop modification line array with a preset depth outside the vertical through hole, and then scans the outer area of the closed-loop modification line to form a thinning modification area with a preset depth.
[0014] F: The thinning modification area is thinned by the second wet etching process, and the area surrounded by the closed-loop modification line forms a conical protrusion structure to obtain an integrally formed glass hollow microneedle.
[0015] Furthermore, the etching solution used in the first wet etching step C is an alkaline solution;
[0016] The etching solution used in the second wet etching process in step F is an acidic etching solution.
[0017] Furthermore, the alkaline solution is a strong alkaline solution with a concentration of 25~40wt%, and etching is performed at 75~85℃ to penetrate the vertical modification line and form a vertical through hole;
[0018] The concentration of the acidic etching solution is 4~16wt%, and etching is performed at 0~70℃ to form the outer contour of the microneedle.
[0019] Furthermore, in step E, the laser pulse energy for scanning the closed-loop modified region and the thinning modified region is 2.0~4.0μJ.
[0020] Furthermore, in step E, the depth of the closed-loop modification line and the thinning modification region is at least 80% of the target microneedle height.
[0021] Furthermore, in step E, the outer region of the closed-loop modification line is scanned using parallel lines, with a spacing of 2~5μm between two adjacent scan lines.
[0022] Furthermore, in step F, the vertical cross-section of the conical protrusion structure is V-shaped, and the relationship between the included angle θ at the top of the V-shaped cross-section and the ratio δ of the etching rate of the modified region to the etching rate of the unmodified glass is: θ = 2 × arcsin(1 / δ).
[0023] The included angle θ at the top of the V-shaped cross section ranges from 30° to 77°.
[0024] Furthermore, in step F, etching is terminated at or before the closed-loop modification line is completely consumed.
[0025] The depth h and diameter d of the closed-loop modification line satisfy geometric constraints: .
[0026] Furthermore, when the second wet etching time is reduced or increased, the included angle θ remains unchanged, and the width and height of the V-shaped section are increased or decreased proportionally.
[0027] When the etching temperature or etching solution concentration of the second wet etching increases, the included angle θ increases.
[0028] A hollow glass microneedle is prepared by the above-mentioned method of laser-guided anisotropic etching.
[0029] The technical solution provided by this invention may include the following beneficial effects:
[0030] This solution achieves integrated molding of the sharp tip and smooth conical surface of the microneedle through two-step laser modification (through-hole modification and contour / thinning modification) and two-step wet etching. It fabricates an integrated hollow glass microneedle on a glass substrate, possessing a precise shape and a sharp tip. This solution offers the following advantages:
[0031] 1. The principle of "laser-guided anisotropic etching" is applied to the integrated fabrication of hollow glass microneedles. The outer contour shaping of the microneedle and the thinning of the substrate are completed simultaneously in the same wet etching process, resulting in a simple and efficient process path.
[0032] 2. By performing pre-modification of vias and structural contour modification on the same glass substrate, and then wet etching, via channels that penetrate microneedles and a conical outer contour can be formed. No subsequent assembly is required, which fundamentally eliminates the risk of interface leakage and assembly errors.
[0033] 3. Based on the mechanism of laser-guided anisotropic etching, the geometric parameters of the microneedle, such as the cone angle and height, can be flexibly adjusted within a wide range, with a large process window and strong adaptability.
[0034] 4. This method inherits the advantage of programmable laser processing paths, making it easy to fabricate large-area, highly consistent microneedle arrays, and has the potential for large-scale production. Attached Figure Description
[0035] Figure 1 This is a process flow diagram of a method for preparing hollow glass microneedles by laser-guided anisotropic etching according to an embodiment of the present invention.
[0036] Figure 2 This is a schematic diagram of the scanning path arrangement for focusing the second Bessel laser beam onto the surface of the glass substrate in step E;
[0037] Figure 3 yes Figure 2 A schematic diagram illustrating the evolution of the AA section during the second wet etching process in step F;
[0038] Figure 4 This is a schematic diagram of the V-shaped cross-section of the conical protrusion structure of a glass hollow microneedle with an included angle θ at the top.
[0039] Figure 5 This is a schematic diagram of a conical glass hollow microneedle array prepared according to the method of the present invention. Detailed Implementation
[0040] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the present invention.
[0041] Reference Figure 1 A method for preparing hollow glass microneedles by laser-guided anisotropic etching according to an embodiment of the present invention includes the following steps:
[0042] A: Clean and dry the glass substrate;
[0043] B: The first Bessel laser beam is focused onto the first surface of the glass substrate to form a vertical modification line that runs through the thickness direction inside the glass substrate;
[0044] C: A vertical through-hole is formed along the vertical modification line by first wet etching;
[0045] D: Clean and dry the glass substrate with vertical through holes;
[0046] E: The second Bessel laser beam is focused on the first or second surface of the glass substrate to form a closed-loop modification line array with a preset depth outside the vertical through hole, and then scans the outer area of the closed-loop modification line to form a thinning modification area with a preset depth.
[0047] F: The thinning modification area is thinned by the second wet etching process, and the area surrounded by the closed-loop modification line forms a conical protrusion structure to obtain an integrally formed glass hollow microneedle.
[0048] This method achieves the integrated molding of sharp tips and smooth conical surfaces of microneedles through two-step laser modification (through-hole modification + contour / thinning modification) + two-step wet etching, efficiently fabricating integrated hollow glass microneedles on a glass substrate. Specifically, it breaks the conventional wisdom that "glass wet etching can only create concave structures and cannot create sharp protrusions." Utilizing the directional etching effect of laser-guided anisotropic etching (LGAE), sharp microneedle protrusion structures are obtained through wet etching. This invention abandons the multi-step process of "fabricating solid needles first and then drilling holes" or "separate bonding," completing all structural fabrication on the same substrate. This results in integrated hollow glass microneedles without any bonding interfaces, reducing drug leakage to zero, and eliminating assembly errors.
[0049] It should be noted that the closed-loop modification trajectory can be a circular or polygonal closed-loop scanning path to prepare microneedle arrays of various shapes, such as conical or pyramidal. By controlling the diameter of the closed-loop scanning trajectory, the diameter of the microneedle root can be adjusted.
[0050] Specifically, glass, as an amorphous material, exhibits a uniform rate of chemical reaction with the etching solution in all spatial directions when untreated; this characteristic is known as "isotropic etching." As a result, etching proceeds uniformly along the normal direction of the glass surface, rapidly rounding any sharp edges. This invention utilizes a femtosecond Bessel beam to pre-modify the glass, forming a high aspect ratio linear modified region within the glass. This results in a densification of the microstructure of this region, specifically a significant increase in the proportion of ternary and quaternary rings in the glass network structure. This structural change leads to a substantial increase in the chemical activity of the modified region in hydrofluoric acid, resulting in an etching rate significantly higher than the surrounding unmodified original glass. The modified line guides directional anisotropic etching along the modified trajectory, facilitating the formation of a V-shape with an angle varying with the etching ratio. The two etching modes described above—namely, directional guided etching along the modification trajectory at the bottom and isotropic expansion along the normal of the sidewalls—occur synchronously in time and continuously in space, constraining the final groove cross-section into a stable V-shaped profile, i.e., a microneedle structure. This etching process, guided by the laser-modified region and exhibiting macroscopic anisotropy, is known as "laser-guided anisotropic etching."
[0051] This scheme uses a closed-loop Bessel beam modification trajectory as a "guide tool". In step E, the modification trajectory extends from the glass surface inward to a predetermined depth rather than penetrating through it. During the etching process, rapid directional etching along the closed-loop trajectory drives the formation of the tapered outer contour of the microneedle. The outer modification area simultaneously guides the substrate thinning, and the two are directly adjacent.
[0052] As an example, the glass substrate of this invention is borosilicate glass with a thickness ranging from 100 μm to 2 mm. Bessel laser parameters: center wavelength 400–1064 nm, pulse width 100 fs–10 ps, objective lens NA 0.3–0.6, depth of focus 50–500 μm, and spot diameter 2–5 μm. The closed-loop modification line shape includes regular polygons such as circles, equilateral triangles, squares, hexagons, and octagons, corresponding to the fabrication of conical, triangular, square, hexagonal, and octagonal microneedles. The scanning lines for thinning the modification region can be parallel line scanning, serpentine scanning, or raster scanning, with parallel line scanning being the optimal method.
[0053] In one embodiment of the present invention, the etching solution for the first wet etching in step C is an alkaline solution; and the etching solution for the second wet etching in step F is an acidic etching solution.
[0054] Alkaline solutions selectively etch through-line modification without damaging subsequent contours or thinning of the modified area; acidic solutions, on the other hand, precisely shape non-through-line modification areas. This division of labor prevents excessive erosion of the contour modification area by the alkaline solution. Furthermore, alkaline solutions etch through-holes at a faster rate (5-10 times faster than acidic solutions), while acidic solutions offer higher contour etching accuracy, balancing production efficiency and product dimensional accuracy.
[0055] As an example, the alkaline solution is selected from one or more aqueous solutions of potassium hydroxide (KOH), sodium hydroxide (NaOH), and lithium hydroxide (LiOH), preferably an aqueous solution of KOH. The acidic solution is selected from hydrofluoric acid (HF), ammonium bifluoride (NH4HF2), HF / HCl mixture, and HF / HNO3 mixture, with low concentration HF being the optimal choice for precision molding.
[0056] Preferably, the alkaline solution is a strong alkaline solution with a concentration of 25~40wt%, and etching is performed at 75~85℃ to penetrate the vertical modification line and form a vertical through hole;
[0057] The concentration of the acidic etching solution is 4~16wt%, and etching is performed at 0~70℃ to form the outer contour of the microneedle.
[0058] By limiting the concentration and temperature range of two separate wet etching processes, taking a 0.5mm thick glass substrate as an example, the etching rate of through-holes should be above 25μm / h, and the contour etching rate should be stable at 2~10μm / min. This avoids surface roughness and over-corrosion caused by high-concentration, high-temperature etching, and also avoids excessively low efficiency caused by low-concentration, low-temperature etching. The temperature and concentration of the acidic solution are the core parameters for adjusting the etching rate ratio δ, and the above range covers all δ values required for a cone angle of 20°~80°.
[0059] As an example, with only the concentration of the acidic etching solution and the second etching temperature as variables, the values of δ and θ change as follows:
[0060] At 10wt%HF and 0℃: δ=2.8, θ≈42;
[0061] At 10wt%HF and 30℃: δ=2.3, θ≈52;
[0062] At 10wt%HF and 40℃: δ=1.99, θ≈60;
[0063] At 10wt%HF and 55℃: δ=1.75, θ≈70;
[0064] At 16wt%HF and 70℃: δ=1.6, θ≈77;
[0065] At 4wt%HF and 0℃: δ=3.86, θ≈30.
[0066] Furthermore, in step F, the vertical cross-section of the conical protrusion structure is V-shaped, and the relationship between the included angle θ at the top of the V-shaped cross-section and the ratio δ of the etching rate of the modified region to the etching rate of the unmodified glass is: θ = 2 × arcsin(1 / δ).
[0067] The included angle θ at the top of the V-shaped cross section ranges from 30° to 77°.
[0068] This approach applies the basic geometric relationships of LGAE to the design of microneedle cone angles, allowing the calculation of the required δ value based on the target cone angle without repeated trials.
[0069] Preferably, when the time for the second wet etching is reduced or increased, the included angle θ remains constant, and the width and height of the V-shaped cross section are increased or decreased proportionally.
[0070] When the etching temperature or etching solution concentration of the second wet etching increases, the included angle θ increases.
[0071] Therefore, by changing the etching temperature and etching solution concentration of the second wet etching process, the included angle θ can be precisely adjusted from 30 to 77°, thereby enabling precise control of parameters such as the cone angle, height, and diameter of the microneedle.
[0072] In one embodiment of the present invention, in step F, etching is terminated at or before the closed-loop modification line is completely consumed. At this time, the root diameter of the resulting microneedle is substantially the same as the diameter of the closed-loop modification line. By precisely controlling the etching time, etching is terminated at or before the closed-loop modification trajectory is completely consumed, thereby obtaining an integrated hollow glass microneedle with a sharp tip and a smooth conical surface. The depth h and diameter d of the closed-loop modification line satisfy geometric constraints: .
[0073] In actual process design, the required etching selectivity δ (θ = 2×arcsin(1 / δ)) is first determined based on the target microneedle cone angle θ, and then the required modification depth h (h = d × √(δ²-1) / 2) is calculated based on the target root diameter d. The geometric constraints of h and d are necessary conditions to ensure that a sharp cone is formed precisely when the etching terminates.
[0074] Preferably, in step E, the laser pulse energy for scanning the closed-loop modification region and the thinning modification region is 2.0~4.0 μJ. The laser pulse energy for scanning the closed-loop modification region is the same as that for scanning the thinning modification region. The closed-loop energy independently controls the cone angle, and the scanning energy for the thinning modification region independently controls the thinning rate.
[0075] In one embodiment of the present invention, in step E, the depth of the closed-loop modification line and the thinning modification region is at least 80% of the target height of the microneedle. Preferably, it is not less than 100% to ensure the continuous guiding effect of anisotropic etching throughout the structure formation process. If the modification depth is insufficient, the modification line will be exhausted in the later stage of etching, and the isotropic etching of the unmodified glass will quickly round the tip. Moreover, the modification depth is positively correlated with the microneedle height, and the microneedle height can be precisely controlled by controlling the modification depth.
[0076] In one embodiment of the present invention, in step E, parallel lines are used to scan the outer region of the closed-loop modification line, with the spacing between two adjacent scan lines being 2~5μm. The smaller the line spacing, the more uniform the distribution of the modified area, and the better the consistency of the substrate thinning thickness, ensuring a smooth substrate surface after etching. As an example, the relationship between line spacing and surface roughness is: 2μm line spacing: Ra < 10nm; 3μm line spacing: Ra < 15nm; 5μm line spacing: Ra < 30nm. The optimal line spacing is 3μm when the line spacing is ≤ 80% of the laser spot diameter; for example, when the spot diameter is 3.8μm.
[0077] Understandably, etching should be terminated immediately when the closed-loop modification line is completely consumed, at which point the microneedle tip is just formed and has not yet been rounded by subsequent isotropic etching. As an example, pre-experimental calibration, in-situ optical monitoring, or spectral monitoring methods can be used to determine the etching termination time. For instance, experimental calibration has shown that the optimal etching time for 10wt% HF at 40°C with a 100μm modification depth is 25–35 minutes.
[0078] After etching is complete, immediately remove the glass substrate, rinse it with deionized water 3-5 times, then ultrasonically clean it in deionized water for 5-10 minutes, and finally dry it with nitrogen.
[0079] Accordingly, this invention also provides a hollow glass microneedle, prepared using the method described above. This hollow glass microneedle possesses a sharp tip, no bonding interface, high mechanical strength, and precise dimensions, making it suitable for various biomedical applications such as transdermal drug delivery, micro-blood collection, body fluid detection, and cell injection. For example, this hollow glass microneedle can be used directly for transdermal drug delivery of insulin, vaccines, growth hormones, and other drugs, and can also be used for real-time monitoring of physiological parameters such as blood glucose and electrolytes.
[0080] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed according to conventional methods and conditions or according to the product instructions. Unless otherwise specified, the reagents are commercially available; and the performance of products from different sources does not have a significant impact.
[0081] Example 1
[0082] This embodiment uses 0.5mm thick borosilicate glass (BF33) as the substrate and a femtosecond laser with a center wavelength of 520nm and a pulse width of 300fs as the light source. The laser beam is first phase-modulated by an axial prism through a spatial light modulator, transforming it into a Bessel beam, and then focused into the interior of the glass by a 4f system and an objective lens (NA0.45). The focused spot diameter of the Bessel beam is approximately 3.8μm, and the depth of focus is approximately 288μm, enabling the generation of a high aspect ratio linear modification region within the glass using a single pulse.
[0083] The preparation of the hollow glass microneedles in this embodiment includes the following steps:
[0084] A: Clean and dry the glass substrate, then ultrasonically clean it for 10 minutes each with acetone, anhydrous ethanol and deionized water, and then dry it with nitrogen.
[0085] B: A first Bessel laser beam is focused onto the first surface of the glass substrate, so that the central spot of the Bessel beam is located within a predetermined depth range inside the glass. Through single-pulse irradiation, a vertical modification line penetrating the thickness direction is formed inside the glass substrate; the laser pulse energy is 4.5 μJ.
[0086] C: The first wet etching was performed at 80°C using a 30wt% KOH aqueous solution for 20 hours, forming vertical through-holes with a diameter of approximately 10μm.
[0087] D: Clean and dry the glass substrate with vertical through holes;
[0088] E: A second Bessel laser beam with a pulse energy of 3.0 μJ is focused on the first surface of the glass substrate, forming a closed-loop modification line array with a predetermined depth outside the vertical via via along an 80 μm circular path. The scanning speed is 10 mm / s, the pulse repetition frequency is 10 kHz, and the corresponding pulse separation distance is approximately 1 μm. Then, the outer region of the closed-loop modification lines is scanned to form a thinning modification region with a predetermined depth. The depth of the closed-loop modification lines and the thinning modification region is at least 100% of the target microneedle height. Parallel lines are used to scan the outer region of the closed-loop modification lines, with a spacing of 3 μm between adjacent scan lines.
[0089] F: A second wet etching process was performed at 40°C using a 10wt% HF aqueous solution to thin the modified region. The etching was terminated when the closed-loop modification line was completely consumed. A conical protrusion structure was formed in the region surrounded by the closed-loop modification line, resulting in an integrally formed hollow glass microneedle. The root diameter d of the microneedle was 80μm (the root diameter is equal to the diameter of the closed-loop scan), and the height of the microneedle was 55μm (h=55μm). The δ value was approximately 1.7, and the included angle θ=2×arcsin(1 / δ)≈72°.
[0090] Example 2
[0091] The glass substrate and femtosecond laser used in this embodiment are the same as those in Embodiment 1. The preparation of the hollow glass microneedles in this embodiment includes the following steps:
[0092] A: Clean and dry the glass substrate, then ultrasonically clean it for 10 minutes each with acetone, anhydrous ethanol and deionized water, and then dry it with nitrogen.
[0093] B: A first Bessel laser beam is focused onto the first surface of the glass substrate, so that the central spot of the Bessel beam is located within a predetermined depth range inside the glass. Through single-pulse irradiation, a vertical modification line penetrating the thickness direction is formed inside the glass substrate; the laser pulse energy is 4.5 μJ.
[0094] C: A first wet etching process was performed at 80°C for about 20 hours using a 30wt% KOH aqueous solution to form a vertical through-hole with a diameter of about 10μm.
[0095] D: Clean and dry the glass substrate with vertical through holes;
[0096] E: A second Bessel laser beam with a pulse energy of 2.0 μJ is focused on the first surface of the glass substrate, forming a closed-loop modification line array with a predetermined depth outside the vertical via via along an 80 μm circular path. The scanning speed is 10 mm / s, the pulse repetition frequency is 10 kHz, and the corresponding pulse separation distance is approximately 1 μm. Then, the outer region of the closed-loop modification lines is scanned to form a thinning modification region with a predetermined depth. The depth of the closed-loop modification lines and the thinning modification region is at least 100% of the target microneedle height. Parallel lines are used to scan the outer region of the closed-loop modification lines, with a spacing of 5 μm between adjacent scan lines.
[0097] F: A second wet etching process was performed at 70°C using a 16wt% HF aqueous solution to thin the modified region. The etching was terminated when the closed-loop modification line was completely consumed. The region surrounded by the closed-loop modification line formed a conical protrusion structure, resulting in a one-piece hollow glass microneedle with a δ value of approximately 1.6, an included angle θ = 2 × arcsin(1 / δ) ≈ 77°, a microneedle root diameter d of 40 μm (the root diameter is equal to the diameter of the closed-loop scan), and a microneedle height h of 25 μm.
[0098] Example 3
[0099] The glass substrate and femtosecond laser used in this embodiment are the same as those in Embodiment 1. The preparation of the hollow glass microneedles in this embodiment includes the following steps:
[0100] A: Clean and dry the glass substrate, then ultrasonically clean it for 10 minutes each with acetone, anhydrous ethanol and deionized water, and then dry it with nitrogen.
[0101] B: A first Bessel laser beam is focused onto the first surface of the glass substrate, so that the central spot of the Bessel beam is located within a predetermined depth range inside the glass. Through single-pulse irradiation, a vertical modification line penetrating the thickness direction is formed inside the glass substrate; the laser pulse energy is 4.5 μJ.
[0102] C: A first wet etching process was performed at 80°C for about 20 hours using a 30wt% KOH aqueous solution to form a vertical through-hole with a diameter of about 10μm.
[0103] D: Clean and dry the glass substrate with vertical through holes;
[0104] E: A second Bessel laser beam with a pulse energy of 2.0 μJ is focused on the first surface of the glass substrate, forming a closed-loop modification line array with a preset depth outside the vertical via via along an 80 μm circular path. The scanning speed is 10 mm / s, the pulse repetition frequency is 10 kHz, and the corresponding pulse separation distance is approximately 1 μm. Then, the outer region of the closed-loop modification lines is scanned to form a thinning modification region with a preset depth. The depth of the closed-loop modification lines and the thinning modification region is 100% of the target microneedle height. Parallel lines are used to scan the outer region of the closed-loop modification lines, with a spacing of 2 μm between adjacent scan lines.
[0105] F: A second wet etching process was performed at 0°C using a 4wt% HF aqueous solution to thin the modified region. The etching was terminated when the closed-loop modification line was completely consumed. The region surrounded by the closed-loop modification line formed a conical protrusion structure, resulting in a one-piece hollow glass microneedle with a δ value of approximately 3.86, an included angle θ = 2 × arcsin(1 / δ) ≈ 30°, a microneedle root diameter d of 60 μm (the root diameter is equal to the diameter of the closed-loop scan), and a microneedle height h of 112 μm.
[0106] Example 4
[0107] The glass substrate and femtosecond laser used in this embodiment are the same as those in Embodiment 1. The preparation of the hollow glass microneedles in this embodiment includes the following steps:
[0108] A: Clean and dry the glass substrate, then ultrasonically clean it for 10 minutes each with acetone, anhydrous ethanol and deionized water, and then dry it with nitrogen.
[0109] B: A first Bessel laser beam is focused onto the first surface of the glass substrate, so that the central spot of the Bessel beam is located within a predetermined depth range inside the glass. Through single-pulse irradiation, a vertical modification line penetrating the thickness direction is formed inside the glass substrate; the laser pulse energy is 4.5 μJ.
[0110] C: A first wet etching process was performed at 85°C for about 18 hours using a 40wt% KOH aqueous solution to form a vertical through-hole with a diameter of about 12μm.
[0111] D: Clean and dry the glass substrate with vertical through holes;
[0112] E: A second Bessel laser beam with a pulse energy of 4.0 μJ is focused on the first surface of the glass substrate, forming a closed-loop modification line array with a preset depth outside the vertical via via along an 80 μm circular path. The scanning speed is 10 mm / s, the pulse repetition frequency is 10 kHz, and the corresponding pulse separation distance is approximately 1 μm. Then, the outer region of the closed-loop modification lines is scanned to form a thinning modification region with a preset depth. The depth of the closed-loop modification lines and the thinning modification region is 100% of the target microneedle height. Parallel lines are used to scan the outer region of the closed-loop modification lines, with a spacing of 3 μm between adjacent scan lines.
[0113] F: A second wet etching process was performed at 40°C using a 10wt% HF aqueous solution to thin the modified region. The etching was terminated when the closed-loop modification line was completely consumed. The region surrounded by the closed-loop modification line formed a conical protrusion structure, resulting in an integrally formed glass hollow microneedle with a δ value of approximately 1.99, an included angle θ = 2 × arcsin(1 / δ) ≈ 60.3, a microneedle root diameter d of 47 μm (the root diameter is equal to the diameter of the closed-loop scan), and a microneedle height h of 40.4 μm.
[0114] Example 5
[0115] The glass substrate and femtosecond laser used in this embodiment are the same as those in Embodiment 1. The preparation of the hollow glass microneedles in this embodiment includes the following steps:
[0116] A: Clean and dry the glass substrate, then ultrasonically clean it for 10 minutes each with acetone, anhydrous ethanol and deionized water, and then dry it with nitrogen.
[0117] B: A first Bessel laser beam is focused onto the first surface of the glass substrate, so that the central spot of the Bessel beam is located within a predetermined depth range inside the glass. Through single-pulse irradiation, a vertical modification line penetrating the thickness direction is formed inside the glass substrate; the laser pulse energy is 4.5 μJ.
[0118] C: A first wet etching process was performed at 75°C for about 20 hours using a 25wt% KOH aqueous solution to form a vertical through-hole with a diameter of about 9μm.
[0119] D: Clean and dry the glass substrate with vertical through holes;
[0120] E: A second Bessel laser beam with a pulse energy of 3.0 μJ is focused on the first surface of the glass substrate, forming a closed-loop modification line array with a preset depth outside the vertical via via along an 80 μm circular path. The scanning speed is 10 mm / s, the pulse repetition frequency is 10 kHz, and the corresponding pulse separation distance is approximately 1 μm. Then, the outer region of the closed-loop modification lines is scanned to form a thinning modification region with a preset depth. The depth of the closed-loop modification lines and the thinning modification region is 80% of the target microneedle height. Parallel lines are used to scan the outer region of the closed-loop modification lines, with a spacing of 3 μm between adjacent scan lines.
[0121] F: A second wet etching process was performed at 40°C using a 10wt% HF aqueous solution to thin the modified region. The etching was terminated when the closed-loop modification line was completely consumed. The region surrounded by the closed-loop modification line formed a conical protrusion structure, resulting in a one-piece hollow glass microneedle with a δ value of approximately 1.99, an included angle θ = 2 × arcsin(1 / δ) ≈ 60.3°, a microneedle root diameter d of 47 μm (the root diameter is equal to the diameter of the closed-loop scan), and a microneedle height h of 40.4 μm.
[0122] Example 6
[0123] The glass substrate and femtosecond laser used in this embodiment are the same as in Embodiment 1. The fabrication of the hollow glass microneedle is basically the same as in Embodiment 1, except that in step E, a closed-loop modification line is formed using a regular hexagonal scanning path with a side length of 50 μm. After etching in step F, a hollow hexagonal pyramidal microneedle is generated. This embodiment demonstrates the universality of the closed-loop scanning path shape; various pyramidal microneedles can be obtained by designing different closed-loop paths.
[0124] Example 7
[0125] The glass substrate and femtosecond laser used in this embodiment are the same as in Example 1. The preparation of the hollow glass microneedles is basically the same as in Example 1, except that in step F, a second wet etching is performed at 0°C using a 10wt% HF aqueous solution. δ is approximately 2.8, the obtained hollow glass microneedles have an θ angle of approximately 42°, a root diameter d of 55 μm (the root diameter is equal to the diameter of the closed-loop scan), and a height h of 72 μm.
[0126] Example 8
[0127] The glass substrate and femtosecond laser used in this embodiment are the same as in Example 1. The preparation of the hollow glass microneedles is basically the same as in Example 1, except that in step F, a second wet etching is performed at 30°C using a 10wt% HF aqueous solution. δ is approximately 2.3, the obtained hollow glass microneedles have an θ angle of approximately 52°, a root diameter d of 55 μm (the root diameter is equal to the diameter of the closed-loop scan), and a height h of 57 μm.
[0128] Other configurations and operations of the laser-guided anisotropic etching method for fabricating hollow glass microneedles according to embodiments of the present invention are known to those skilled in the art and will not be described in detail here. When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. The described performance can be achieved within the proportions specified in the present invention. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by those skilled in the art to which this invention pertains.
[0129] Although embodiments of the invention have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
Claims
1. A method for preparing hollow glass microneedles by laser-guided anisotropic etching, characterized in that, Includes the following steps: A: Clean and dry the glass substrate; B: The first Bessel laser beam is focused onto the first surface of the glass substrate to form a vertical modification line that runs through the thickness direction inside the glass substrate; C: A vertical through-hole is formed along the vertical modification line by first wet etching; D: Clean and dry the glass substrate with vertical through holes; E: The second Bessel laser beam is focused on the first or second surface of the glass substrate to form a closed-loop modification line array with a preset depth outside the vertical through hole, and then the peripheral area of the closed-loop modification line is scanned to form a thinning modification area with a preset depth. F: The thinning modification area is thinned by the second wet etching process, and the area surrounded by the closed-loop modification line forms a conical protrusion structure to obtain an integrally formed glass hollow microneedle.
2. The method according to claim 1, characterized in that, The etching solution used in the first wet etching step C is an alkaline solution; The etching solution used in the second wet etching process in step F is an acidic etching solution.
3. The method according to claim 2, characterized in that, The alkaline solution is a strong alkaline solution with a concentration of 25~40wt%. It is etched through the vertical modification line at 75~85℃ to form a vertical through hole. The concentration of the acidic etching solution is 4~16wt%, and etching is performed at 0~70℃ to form the outer contour of the microneedle.
4. The method according to claim 1, characterized in that, In step E, the laser pulse energy for scanning the closed-loop modified region and the thinning modified region is 2.0~4.0μJ.
5. The method according to claim 1, characterized in that, In step E, the depth of the closed-loop modification line and the thinning modification region is at least 80% of the target microneedle height.
6. The method according to claim 1, characterized in that, In step E, the outer region of the closed-loop modification line is scanned using parallel lines, with a spacing of 2~5μm between two adjacent scan lines.
7. The method according to claim 1, characterized in that, In step F, the vertical cross-section of the conical protrusion structure is V-shaped. The relationship between the included angle θ at the top of the V-shaped cross-section and the ratio δ of the etching rate of the modified region to the etching rate of the unmodified glass is: θ = 2 × arcsin(1 / δ). The included angle θ at the top of the V-shaped cross section ranges from 30° to 77°.
8. The method according to claim 7, characterized in that, In step F, etching is terminated at or before the closed-loop modification line is completely consumed. The depth h and diameter d of the closed-loop modification line satisfy geometric constraints: .
9. The method according to claim 7, characterized in that, When the time for the second wet etching process is reduced or increased, the included angle θ remains constant, and the width and height of the V-shaped section are increased or decreased proportionally. When the etching temperature or etching solution concentration of the second wet etching increases, the included angle θ increases.
10. A hollow glass microneedle, characterized in that, The hollow glass microneedles were prepared using the laser-guided anisotropic etching method described in any one of claims 1 to 9.