Phosphate glass micro-reaction chip and preparation method and application thereof

Abstract

The application provides a phosphate glass micro-reaction chip and a preparation method and application thereof. Compared with existing quartz glass and polymer biomaterials, the phosphate glass has more excellent biological activity, degradability and biocompatibility, and is more widely applied; and the phosphate glass avoids problems such as high manufacturing difficulty and high cost of the quartz glass micro-reaction chip and insufficient mechanical property and poor stability of the polymer biomaterial. Main preparation steps of the chip include the following steps. S1, according to input of a drawing of a micro-channel structure of the chip, focusing an ultrafast laser on the inside of phosphate glass, modifying the inside of the phosphate glass by direct writing, and forming a micro-channel modification region in the inside of the phosphate glass, wherein the micro-channel includes an inlet and an outlet, and the inlet and the outlet are located on end faces in a thickness direction of the phosphate glass; S2, etching from the inlet and the outlet by using a first etching liquid and a second etching liquid in sequence, and then cleaning and drying; and S3, annealing the phosphate glass with the micro-channel etched in the inside.

Description

Technical Field

[0001] This invention relates to the field of phosphate glass technology, and more particularly to a corrosive solution for phosphate glass microreactor chips and its preparation method. Background Technology

[0002] Biomicroreaction chips are a cutting-edge interdisciplinary product integrating microfluidics, materials science, and bioengineering. They integrate micrometer-scale channels and chambers on a chip to precisely control fluid movement, mass exchange, and cell localization, enabling high-throughput, low-consumption biological reactions. By constructing biomimetic systems at the micrometer scale, they simulate the microenvironment and function of human organs, providing revolutionary tools for drug development, disease modeling, and personalized medicine.

[0003] Currently, chip materials utilize fused silica and polymer biomaterials. Polymer biomaterials are generally produced using micro / nano 3D printing technology. However, biomaterials suffer from several performance challenges: insufficient mechanical properties, exhibiting strength and durability deficiencies; most 3D-printed polymer biomaterials (such as PLA and PEGDA) have low mechanical strength, making them prone to brittle fracture, especially under load or in dynamic environments; high porosity: during printing, polymer flowability issues easily lead to micropore formation, reducing material density and impacting mechanical stability. Furthermore, functional modification of polymer biomaterials is challenging, particularly in introducing reinforcing agents: while adding fibers (carbon fiber, glass fiber) or particles (hydroxyapatite) can improve performance, fibers are easily damaged by compression and friction during printing, and their uneven distribution (up to 20%) significantly weakens the reinforcing effect; poor thermal stability: biodegradable materials (such as PLLA) have low heat resistance and weak melt strength, making them prone to deformation or degradation during high-temperature printing, limiting their application in complex structures. There are also process defects in 3D printing technology, such as limitations in accuracy and resolution: Although SLA technology has high resolution, the photosensitive resin is prone to shrinkage and deformation during curing, leading to dimensional deviations (typical error ±0.1mm), affecting the molding accuracy of delicate structures such as microvessels or tissue scaffolds; uncontrolled fiber orientation: In the printing of continuous fiber reinforced composite materials, fibers are prone to breakage in the turning areas, and it is difficult to precisely control the orientation (requiring an electromagnetic auxiliary system), resulting in anisotropic mechanical properties. There are also issues with poor process compatibility, such as the slow curing of thermosetting materials: Most thermosetting polymers (such as epoxy resin) require long-term high-temperature curing, which cannot match the rapid layer-by-layer prototyping rhythm of 3D printing, limiting their application in high-throughput biomanufacturing. Finally, there are difficulties in multi-material printing: Different polymers have large differences in melting temperature and viscosity, making it difficult to achieve multi-material collaborative printing in the same system (such as the integration of rigid bone and soft tissue).

[0004] One method for fused silica chips involves femtosecond laser surface writing modification etching followed by bonding. Another recent report suggests that East China Normal University uses ultrafast laser processing to fabricate microstructures inside quartz glass. Numerous etching auxiliary holes are created on both the top and bottom surfaces of the microstructure. KOH alkaline solution is then used for etching to etch through both the microstructure and the auxiliary holes. Finally, a carbon dioxide laser is used to ablate and melt the etched holes, sealing them off.

[0005] The process is shown in the attached diagram in the instruction manual. Figure 1 As shown, Figure 1 The process flow for the quartz glass microfluidic chip from East China Normal University (the open extra-access hole is the etching auxiliary hole) is detailed in the paper "Efficient synthesis of vitamin D3 in a 3D ultraviolet photochemical microreactor fabricated using an ultrafast laser" published in Light: Advanced Manufacturing, Volume 5, 2024.

[0006] However, the reaction contact area between the ultrafast laser-modified region and the KOH alkaline solution is relatively small, resulting in a slow reaction rate and low efficiency. This limits the chip size, reduces liquid holding capacity, and prevents high-throughput processing, thus failing to meet production demands and restricting its application to laboratory settings. Furthermore, the high stress after carbon dioxide ablation and fusion sealing of the auxiliary holes reduces the chip's pressure resistance, and numerous etched auxiliary holes equate to numerous damage points, posing a risk for long-term use and making it unsuitable for continuous industrial production. Moreover, the manufacturing cost of fused silica chips is high.

[0007] Compared to quartz glass and polymer biomaterials, phosphate bioglasses exhibit superior bioactivity, biodegradability, and biocompatibility, thus attracting wider attention in the biomedical field. Therefore, we propose a phosphate glass microreaction chip, its preparation method, and its applications to address the aforementioned problems associated with quartz glass and polymer biomaterials. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to overcome the defects of the existing technology. The present invention proposes a phosphate glass microreactor chip, its preparation method and application, which has better corrosion selectivity, does not require opening holes for auxiliary corrosion, and is more efficient.

[0009] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is: a method for preparing a phosphate glass microreaction chip, comprising the following steps:

[0010] S1. Based on the chip microchannel structure drawing input, an ultrafast laser is focused on the inside of the phosphate glass to perform direct writing modification on the inside of the phosphate glass, forming a microchannel modification region inside the phosphate glass. The microchannel includes an inlet and an outlet, and the inlet and outlet are both located on the end face of the phosphate glass in the thickness direction.

[0011] S2. The first and second corrosive solutions are used to corrode the inlet and outlet sections in sequence, followed by cleaning and drying.

[0012] S3. Anneal the phosphate glass with microchannels etched inside.

[0013] Furthermore, in step S1, the parameters for direct writing modification using ultrafast laser are: pulse width 100-2000 fs, frequency 100-800 kHz, and power 0.00001-0.1 W.

[0014] Further, in step S2, the first etching solution consists of 10-30% pure water, 30-70% isopropanol, and 10-30% benzenesulfonic acid, and the second etching solution consists of 20-50% pure water, 10-20% ethanol, 10-40% ammonia, and 10-40% hydrogen peroxide.

[0015] Furthermore, the corrosion time for both the first and second corrosive solutions is 1-10 hours.

[0016] Furthermore, in step S3, the annealing process specifically involves:

[0017] The temperature is increased from room temperature to 430℃-460℃ at a rate of 1℃ / min, and then held at 430℃-460℃ for 60min.

[0018] Heat to 480℃-530℃ at a rate of 10℃ / min, and hold at 480℃-530℃ for 10min.

[0019] Then the temperature is lowered to 430℃-460℃ at a rate of 10℃ / min, and held at 430℃-460℃ for 60min, before being lowered to 380℃ at a rate of 0.1℃ / min.

[0020] Finally, the temperature was reduced from 380℃ to room temperature at a rate of 1℃ / min.

[0021] A phosphate glass microreactive chip is fabricated according to the above-described method for preparing a phosphate glass microreactive chip.

[0022] Such as the applications of phosphate glass microreaction chips in biomedicine and pharmacy.

[0023] Compared with existing technologies, the beneficial effects of this invention include: This invention uses a femtosecond laser to focus and directly modify the interior of phosphate glass, followed by treatment with a specific etching solution to remove the modified areas within the phosphate glass, thus forming microchannels inside. Compared to bonding and the sealing process used by East China Normal University, this method offers better overall integrity, and the combined annealing process further enhances its strength. Furthermore, compared to the open-hole assisted etching process used by East China Normal University, this invention offers better etching selectivity, eliminates the need for open-hole assisted etching, and is more efficient. Attached Figure Description

[0024] The disclosure of this invention is illustrated with reference to the accompanying drawings. It should be understood that the drawings are for illustrative purposes only and are not intended to limit the scope of protection of this invention. In the drawings, the same reference numerals are used to refer to the same parts. Wherein:

[0025] Figure 1 The schematic illustration shows the process flow of a quartz glass microfluidic chip according to the background art of the present invention. Detailed Implementation

[0026] It is readily understood that, based on the technical solution of this invention, those skilled in the art can propose various interchangeable structural methods and implementations without altering the essential spirit of the invention. Therefore, the following detailed embodiments and accompanying drawings are merely illustrative examples of the technical solution of this invention and should not be considered as the entirety of the invention or as limitations or restrictions on the technical solution of this invention.

[0027] Phosphate-based bioactive glass (P-BG) is an important class of bioactive materials. Its main component is based on a phosphate (P₂O₅) network and contains oxides such as calcium (CaO) and sodium (Na₂O). Sometimes, other elements (such as magnesium, zinc, and silver) are added to impart specific functions. It has attracted widespread attention in the biomedical field due to its excellent bioactivity, biodegradability, and biocompatibility.

[0028] This invention leverages the biocompatibility of phosphate glass to apply phosphate glass microreaction chips in biomedicine and pharmaceutical fields. Specifically, the fabrication steps of this chip are as follows:

[0029] Based on the chip microchannel structure drawing, an ultrafast laser is focused inside the phosphate glass to perform direct writing modification on the phosphate glass, forming a microchannel modification region inside the phosphate glass. The microchannel has inlet and outlet sections, which are located on the end face of the phosphate glass in the thickness direction.

[0030] The subsequent etching process and annealing treatment will be further explained below with reference to several embodiments of the phosphate glass microreactor chip prepared by the present invention.

[0031] Example 1

[0032] S1. The parameters for direct writing modification using ultrafast laser are: pulse width 1000 fs, frequency 400 kHz, and power 0.05 W.

[0033] S2. The modified phosphate glass is etched starting from the inlet and outlet sections, then cleaned and dried. The first etching solution contains the following components by mass percentage: 30wt% pure water, 50wt% isopropanol, 20wt% benzenesulfonic acid, and the etching time is 5h. The second etching solution contains the following components by mass percentage: 20wt% pure water, 15wt% ethanol, 40wt% ammonia, 25wt% hydrogen peroxide, and the etching time is 6h.

[0034] S3. Anneal the phosphate glass with microchannels etched inside. The specific annealing steps are as follows:

[0035] The temperature is increased from room temperature to 430℃-460℃ at a rate of 1℃ / min, and then held at 430℃-460℃ for 60min.

[0036] Heat to 480℃-530℃ at a rate of 10℃ / min, and hold at 480℃-530℃ for 10min.

[0037] Then the temperature is lowered to 430℃-460℃ at a rate of 10℃ / min, and held at 430℃-460℃ for 60min, before being lowered to 380℃ at a rate of 0.1℃ / min.

[0038] Finally, the temperature was reduced from 380℃ to room temperature at a rate of 1℃ / min.

[0039] The parameters for preparing the phosphate glass chip in this embodiment are as follows:

[0040] Temperature withstand -80℃ Flow rate 20 nanoliters / second withstand pressure 0.1MPa

[0041] Example 2

[0042] The difference from Example 1 is that the corresponding first etching solution comprises the following components by mass percentage: 20wt% pure water, 50wt% isopropanol, 30% benzenesulfonic acid, and etching time of 8h; the second etching solution comprises the following components by mass percentage: 35wt% pure water, 20wt% ethanol, 35wt% ammonia, 20wt% hydrogen peroxide, and etching time of 8h.

[0043] The parameters for preparing the phosphate glass chip in this embodiment are as follows:

[0044] Temperature withstand 100℃ Flow rate 0.5 ml / s withstand pressure 5MPa

[0045] Example 3

[0046] The difference from Example 1 is that the corresponding first etching solution comprises the following components by mass percentage: 15wt% pure water, 60wt% isopropanol, 25% benzenesulfonic acid, and etching time of 7.5h; the second etching solution comprises the following components by mass percentage: 20wt% pure water, 20wt% ethanol, 30wt% ammonia, 30wt% hydrogen peroxide, and etching time of 10h.

[0047] The parameters for preparing the phosphate glass chip in this embodiment are as follows:

[0048] Temperature withstand 300℃ Flow rate 300 ml / min withstand pressure 10MPa

[0049] In summary, this invention utilizes femtosecond laser focusing to directly modify the interior of phosphate glass, followed by treatment with a specific etching solution to remove the modified areas within the phosphate glass, thereby forming microchannels inside. This achieves the following effects:

[0050] Temperature withstand -80～300℃ Flow rate 20 nanoliters / second to 300 milliliters / minute withstand pressure 0.1~10MPa

[0051] As can be seen, this invention uses a femtosecond laser to focus on the internal structure of phosphate glass for direct writing modification, followed by treatment with a specific etching solution to remove the modified areas within the phosphate glass, thus forming microchannels inside. Compared to bonding and the sealing process used by East China Normal University, this method offers better overall integrity, and the strength is further enhanced when combined with annealing. Furthermore, compared to the open-hole assisted etching process used by East China Normal University, this invention offers better etching selectivity, eliminates the need for open-hole assisted etching, and is more efficient.

[0052] The technical scope of this invention is not limited to the content described above. Those skilled in the art can make various modifications and variations to the above embodiments without departing from the technical concept of this invention, and all such modifications and variations should fall within the protection scope of this invention.

Claims

1. A method for preparing a phosphate glass microreaction chip, characterized in that, Includes the following steps: S1. Based on the chip microchannel structure drawing input, an ultrafast laser is focused on the inside of the phosphate glass to perform direct writing modification on the inside of the phosphate glass, forming a microchannel modification region inside the phosphate glass. The microchannel includes an inlet and an outlet, and the inlet and outlet are both located on the end face of the phosphate glass in the thickness direction. S2. The first and second corrosive solutions are used to corrode the inlet and outlet parts in sequence, followed by cleaning and drying. The first corrosive solution consists of 10-30% pure water, 30-70% isopropanol, and 10-30% benzenesulfonic acid. The second corrosive solution consists of 20-50% pure water, 10-20% ethanol, 10-40% ammonia, and 10-40% hydrogen peroxide. S3. Anneal the phosphate glass with microchannels etched inside.

2. The method for preparing a phosphate glass microreaction chip according to claim 1, characterized in that, In step S1, the parameters for direct writing modification using ultrafast laser are: pulse width 100-2000 fs, frequency 100-800 kHz, and power 0.00001-0.1 W.

3. The method for preparing a phosphate glass microreaction chip according to claim 1, characterized in that, The corrosion time for both the first and second corrosive solutions is 1-10 hours.

4. The method for preparing a phosphate glass microreaction chip according to claim 1, characterized in that, In step S3, the annealing process specifically includes: The temperature is increased from room temperature to 430℃-460℃ at a rate of 1℃ / min, and then held at 430℃-460℃ for 60min. Heat to 480℃-530℃ at a rate of 10℃ / min, and hold at 480℃-530℃ for 10min. Then the temperature is lowered to 430℃-460℃ at a rate of 10℃ / min, and held at 430℃-460℃ for 60min, before being lowered to 380℃ at a rate of 0.1℃ / min. Finally, the temperature was reduced from 380℃ to room temperature at a rate of 1℃ / min.

5. A phosphate glass microreaction chip, characterized in that, It is prepared according to the method for preparing a phosphate glass microreaction chip according to any one of claims 1-4.

6. The application of the phosphate glass microreaction chip as described in claim 5 in biomedicine and pharmaceutical fields.

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