Microfluidic chip for inhalation sprayer
By introducing cutting buffer lines and spray guide lines into the microfluidic chip, the problem of chip fragility during the cutting process was solved, the yield rate was improved, the spraying effect was maintained, and the production cost was reduced.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- QILU PHARMA CO LTD
- Filing Date
- 2025-12-12
- Publication Date
- 2026-07-02
AI Technical Summary
Existing microfluidic chips are fragile during the cutting process, resulting in low yield of sprayers, increased production costs, and reduced spraying performance.
By introducing a cutting buffer line and a spray guide line into the microfluidic chip, the fluid is ensured to be sprayed out from the cutting buffer line and collide with the outside, protecting the integrity of the outlet end and improving the yield.
It improved the yield rate of microfluidic chips from 70% to 95%, and the spraying effect is basically the same as that of existing technologies, while reducing production costs.
Smart Images
Figure CN2025142063_02072026_PF_FP_ABST
Abstract
Description
A microfluidic chip for inhalation sprayers Technical Field
[0001] This invention relates to a microfluidic chip, and more particularly to a microfluidic chip for use in an inhaler for drug delivery, belonging to the field of medical device technology. Background Technology
[0002] Microfluidics integrates the basic operational units of biological, chemical, and medical analysis processes—sample preparation, reaction, separation, and detection—onto a single micrometer-scale chip, automating the entire analytical process. Microfluidic chips are the primary platform for realizing microfluidic technology. Their key characteristic is that the effective structure for containing fluids (channels, reaction chambers, and other functional components) is at least micrometer-scale in one dimension. Due to this micrometer-scale structure, fluids exhibit and produce unique properties different from those at the macroscopic scale. Because of its enormous potential in biology, chemistry, and medicine, it has developed into a new interdisciplinary research field encompassing biology, chemistry, medicine, fluid dynamics, electronics, materials science, and mechanics.
[0003] Handheld inhaler sprayers manufactured by Boehringer Ingelheim, Germany, can A nebulizer is a device used by patients long-term without supervision. In some cases, such as asthma patients, the width and angle of the spray, as well as the angle between the nebulizer and the throat, are crucial indicators for evaluating the final drug deposition in the lungs. CN1809424A discloses a microstructured high-pressure nozzle with built-in filtration and a method for manufacturing the same. This high-pressure nozzle is obtained through a process of photolithography and etching of a silicon wafer followed by anodic bonding to a glass sheet, and then individual cutting (hereinafter referred to as "microfluidic chip"). As a component of the nebulizer, the width and angle of the spray are largely determined by the microfluidic chip; therefore, the quality of the microfluidic chip directly determines the quality of the nebulizer to a certain extent.
[0004] Specifically, it has a cutting start line (refer to U0 in Figure 3-6) and cuts at that point, but lacks a cutting buffer line (refer to U1 in Figure 3-6) and spray guide lines (refer to T and T' in Figure 3-6). Therefore, if it breaks at the cutting start line during the microfluidic chip cutting process, the spray outlet of the chip will be incomplete, thus affecting the spray effect. Typically, such broken microfluidic chips are rejected during product sampling and testing before leaving the factory, meaning it has a relatively high product defect rate. In summary, its disadvantages are: firstly, a low product yield leads to a higher total production cost; secondly, a higher defect rate increases the frequency and quantity of sampling and inspection during product delivery, further increasing the production cost. Summary of the Invention
[0005] The purpose of this invention is to overcome the above-mentioned shortcomings of the prior art, improve the overall quality and yield of microfluidic chips, reduce production costs, and ensure that the microfluidic chip assembled into an inhalation atomizer can form the expected spray angle, spray area and particle size.
[0006] Preferably, the microfluidic chip of the present invention is mainly implemented through the following structure.
[0007] A microfluidic chip comprises a silicon wafer and a glass wafer bonded together by anodizing to form a semi-enclosed internal cavity. The chip includes an inlet and an outlet, with a left outlet and a right outlet. The left and right outlets are axially symmetrical with respect to the central axis X of the microfluidic chip. The centerlines Y of the left outlet and Y' of the right outlet intersect the central axis X at point A. The outlet includes a cutting start line U0, with a vertical distance L from point A to the cutting start line U0. The outlet also includes a cutting buffer line U1, from which fluid within the microfluidic chip is ejected. The vertical distance from the cutting buffer line U1 to the cutting start line U0 is the cutting buffer distance L', where L' ≤ L.
[0008] The microfluidic chip of the present invention controls L'≤L, thereby ensuring that the fluid inside the microfluidic chip is ejected from the left and right outlets and then collides and sprays outside the microfluidic chip. Furthermore, the cutting buffer distance can protect the integrity of the outlet end when the microfluidic chip is cut, thereby improving the overall quality of the microfluidic chip.
[0009] In some preferred embodiments of the microfluidic chip of the present invention, L' is approximately 0.1 micrometers to 5 micrometers. In other preferred embodiments, L' is approximately 0.5 micrometers to 1.5 micrometers. In still some preferred embodiments, L' is approximately 1.5 micrometers.
[0010] In some preferred embodiments of the microfluidic chip of the present invention, the angle between Y and Y' ranges from 80° to 120°. In other preferred embodiments, the angle between Y and Y' ranges from 85° to 95°.
[0011] In some preferred embodiments, when the angle between Y and Y' is 90°, L is approximately 25 micrometers.
[0012] In some preferred embodiments, the microfluidic chip of the present invention further includes spray guide lines on both sides at the outlet end, wherein the left spray guide line T and the right spray guide line T' are axially symmetrical with respect to the central axis X.
[0013] In some preferred embodiments of the microfluidic chip of the present invention, the angle α between the spray guide line T / T' and the axis Y / Y' ranges from 0° to 135°. In other preferred embodiments, the angle α between the spray guide line T / T' and the axis Y / Y' ranges from 0° to 90°. In still some preferred embodiments, the angle α between the spray guide line T / T' and the axis Y / Y' ranges from 45° to 90°.
[0014] The present invention also provides an inhalation aerosol comprising a microfluidic chip as described in any of the preceding claims, wherein the spray outlet of the inhalation aerosol is the outlet end of the microfluidic chip.
[0015] Technical effect: This invention adds a cutting buffer line (U1) and a spray guide line (T, T') to the existing microfluidic chip. During the product manufacturing process, the cutting buffer line is cut directly. As a result, it was found that the spraying effect was unexpectedly not affected while improving the product yield.
[0016] Specifically:
[0017] 1. The spray yield of microfluidic chips has increased from 70% to 95%.
[0018] 2. The spray effect data of using this microfluidic chip is basically consistent with the spray effect data of existing microfluidic chips. Attached Figure Description
[0019] Figure 1-1 and Figure 1-3 are schematic diagrams of the overall structure of the microfluidic chip. Figure 1-2 is a partial enlarged view of part A in Figure 1-1, and Figure 1-4 is a partial enlarged view of part B in Figure 1-3.
[0020] Figure 2 is a schematic diagram of the arrangement of multiple microfluidic chips (wafer layout);
[0021] Figure 3 is a schematic diagram of the outlet end structure when the angle between the spray guide line of the microfluidic chip and the center line of the outlet channel is 0°.
[0022] Figure 4 is a schematic diagram of the outlet end structure when the angle between the spray guide line of the microfluidic chip and the center line of the outlet channel is 45°.
[0023] Figure 5 is a schematic diagram of the outlet end structure when the angle between the spray guide line of the microfluidic chip and the center line of the outlet channel is 90°.
[0024] Figure 6 is a schematic diagram of the outlet end structure when the angle between the spray guide line of the microfluidic chip and the center line of the outlet channel is 135°.
[0025] Figure 7 is The side view of the spray angle formed when the inhalation atomizer uses the microfluidic chip with the structure shown in Figure 4 to spray shows that the overall spray angle can reach 21.5°.
[0026] Figure 8 is The diagram shows a cross-section of the inhalation atomizer at a distance of 3 cm from the nozzle when using the microfluidic chip with the structure shown in Figure 4. As can be seen from the figure, the spray cross-section reaches 199.6 mm at 3 cm. 2 ;
[0027] Figure 9 is The diagram shows a cross-section at 6 cm from the nozzle of the inhalation nebulizer using the microfluidic chip structure shown in Figure 4. As can be seen from the figure, the spray cross-section reaches 409.2 mm at 6 cm. 2 ;
[0028] Figure 10 is The side view of the spray angle formed when the inhalation atomizer uses the microfluidic chip with the structure shown in Figure 5 to spray shows that the overall spray angle can reach 21.15°.
[0029] Figure 11 is The diagram shows a cross-section of the inhalation atomizer at a distance of 3 cm from the nozzle when using the microfluidic chip with the structure shown in Figure 5. As can be seen from the figure, the spray cross-section reaches 196.3 mm at 3 cm. 2 ;
[0030] Figure 12 is The diagram shows a cross-section at 6 cm from the nozzle of the inhalation atomizer using the microfluidic chip with the structure shown in Figure 5. As can be seen from the figure, the spray cross-section reaches 400.0 mm at 6 cm. 2 .
[0031] Figure Label Explanation: 1. Silicon Wafer; 2. Glass Sheet; 3. Inlet End; 4. Outlet End; 5. Anode Bonding Line; 41. Left Outlet; 42. Right Outlet; X. Chip Center Line; Y, Y' Outlet Channel Center Line; A. Spray Collision Point; U0. Cutting Start Line; U1. Cutting Buffer Line; L. Vertical Distance from Spray Collision Point A to Cutting Start Line; L'. Cutting Buffer Distance; T, T'. Spray Guide Line; α. Spray Guide Angle Detailed Implementation
[0032] To make the objectives, technical solutions, and advantages of this invention clearer, the specific embodiments of the microfluidic chip for sprayers of this invention are further described below with reference to the accompanying drawings. It should be understood that the embodiments of this invention are merely illustrative and not intended to limit the invention. Simple improvements to this invention based on its technical solutions fall within the scope of protection of this invention. Furthermore, descriptions of well-known structures and technologies are omitted in the following description to avoid unnecessarily obscuring the concept of this invention.
[0033] The accompanying drawings illustrate structural schematic diagrams of some specific embodiments of the present invention. These drawings are not to scale, and some details may be enlarged or omitted for clarity. The various regions, shapes, and their relative sizes and positional relationships shown in the drawings are merely exemplary and not intended to limit the specific parameters or positional relationships of the present invention.
[0034] Referring to Figures 1-1, 1-2, 1-3, and 1-4, a microfluidic chip comprises a silicon wafer 1 and a glass sheet 2 bonded together by anodizing to form a semi-enclosed internal cavity, including an inlet end 3 and an outlet end 4. The outlet end includes a left outlet 41 and a right outlet 42. Referring to Figure 3-6, the left outlet 41 and the right outlet 42 are axially symmetrical with respect to the central axis X of the microfluidic chip. The axis Y of the left outlet 41 and the axis Y' of the right outlet 42 intersect the central axis X at point A. This ensures that when the microfluidic chip is assembled into an inhalation nebulizer, fluid enters the internal cavity channel of the chip from the inlet end, generating two liquid jets at the outlet that converge and collide at a set angle to produce an aerosol. The outlet includes a cutting start line U0, and the vertical distance from point A to the cutting start line U0 is L. The outlet also includes a cutting buffer line U1. The fluid in the microfluidic chip is ejected from the cutting buffer line U1. The vertical distance from the cutting buffer line U1 to the cutting start line U0 is the cutting buffer distance L', where L'≤L.
[0035] Referring to Figures 3-6, L' is approximately 0.1 μm to 5 μm. Preferably, L' is approximately 0.5 μm to 1.5 μm. More preferably, L' is approximately 1.5 μm.
[0036] Referring to Figures 3-6, the angle between Y and Y' ranges from 80° to 120°. Preferably, the angle between Y and Y' ranges from 85° to 95°. Based on this angle, the shape of the aerosol spray, including its angle and width, can be defined. When the angle between Y and Y' is 90°, L is approximately 25 micrometers.
[0037] As shown in Figure 3-6, the outlet end also includes spray guide lines on both sides, with the left spray guide line T and the right spray guide line T' being axially symmetrical with respect to the central axis X.
[0038] The angle α between the spray guide line T (or T') and the axis Y (or Y') ranges from 0° to 135°.
[0039] Figure 3 shows that the spray guidance angle α of the microfluidic chip is 0°.
[0040] Figure 4 shows that the spray guidance angle α of the microfluidic chip is 45°.
[0041] Figure 5 shows that the spray guidance angle α of the microfluidic chip is 90°.
[0042] Figure 6 shows that the spray guidance angle α of the microfluidic chip is 135°.
[0043] As shown in Figures 3-6, the cutting buffer distance L' restricts the cutting position to outside the cutting start line U0, without hindering the drug solution from being sprayed out from the left and right outlets of the microfluidic chip and colliding at the spray collision point A outside the chip.
[0044] In some embodiments, the microfluidic chip of the present invention can be installed in a suitable inhalation nebulizer, and the spray outlet of the inhalation nebulizer is the outlet end 4 of the microfluidic chip.
[0045] Spray effect test
[0046] In the following spray effect tests, the inhalation sprayers used in this invention were all manufactured by Boehringer Ingelheim, Germany. Inhalers, existing microfluidic chips refer to The inhaler uses the original microfluidic chip. See Figures 7-12 for spray effect diagrams.
[0047] Specific operation method:
[0048] The testing instruments used for test items 1 to 3 are from the following sources:
[0049] Perform the calibration of the weight sensor of the pressing device and the operation calibration of the pressing device in sequence according to the instrument's standard operating procedures. After the calibration is passed, conduct the test.
[0050] Select Tiotropium Br Spr Method 3 under Method to perform a spray pattern test; select Tiotropium Br Spr Method 6 under Method to perform a 3cm spray pattern test; select Tiotropium Br Spr Method 5 under Method to perform a 6cm spray pattern test.
[0051] The testing instruments used for test item number 4 were sourced from the following sources:
[0052] Insert the device with the microfluidic chip into the instrument, balance the relative humidity and flow rate of the instrument system, and then read the particle size data after the measurement is completed.
[0053] The experimental results are shown in Table 1.
[0054] Table 1 Results of the spray effect test
[0055] According to the results of Examples 1 and 2 in Table 1, when the α angle in the microfluidic chip of the present invention is approximately 45° (Example 1) or approximately 90° (Example 2), the spraying effect of the sprayer using the microfluidic chip is comparable to that using a conventional microfluidic chip (Comparative Example 1, manufactured by Boehringer Ingelheim AG, Germany). The spray effect of the inhaler and its original microfluidic chip is basically the same. That is to say, a good spray effect can be achieved when the α angle is 45°-90°. Based on this, it can be inferred that a good spray effect can also be achieved when the α angle is 0-135°.
[0056] Spraying yield test
[0057] Referring to the layout shown in Figure 2, there are approximately 2,000 microfluidic chips on the entire wafer after all manufacturing processes are completed. 200 chips were randomly sampled from the wafer and subjected to the spray test described above. The results showed that the yield rate reached 95%.
Claims
1. A microfluidic chip, comprising a semi-closed internal cavity formed by anodizing a silicon wafer (1) and a glass sheet (2), including an inlet end (3) and an outlet end (4), wherein the outlet end includes a left outlet (41) and a right outlet (42), the left outlet (41) and the right outlet (42) being axially symmetrical with respect to the central axis X of the microfluidic chip, the axis Y of the left outlet and the axis Y' of the right outlet intersecting the central axis X at point A, the outlet end including a cutting start line U0, the vertical distance from point A to the cutting start line U0 being L, characterized in that, The outlet end also includes a cutting buffer line U1, from which fluid in the microfluidic chip is ejected. The vertical distance from the cutting buffer line U1 to the cutting start line U0 is the cutting buffer distance L', where L' ≤ L.
2. The microfluidic chip of claim 1, wherein, L' ranges from 0.1 μm to 5 μm.
3. The microfluidic chip of claim 1, wherein, L' ranges from 0.5 μm to 1.5 μm.
4. The microfluidic chip of claim 1, wherein, L' is 1.5 μm.
5. The microfluidic chip of claim 1, wherein, The angle between Y and Y' ranges from 80° to 120°.
6. The microfluidic chip of claim 1, wherein, The angle between Y and Y' ranges from 85° to 95°.
7. The microfluidic chip of claim 1, wherein, The outlet end also includes spray guide lines on both sides, and the left spray guide line T and the right spray guide line T' are axially symmetrical with respect to the central axis X.
8. The microfluidic chip of claim 7, wherein, The angle α between the spray guide line and the axis line ranges from 0° to 135°.
9. The microfluidic chip according to claim 7, characterized in that, The angle α between the spray guide line and the axis line ranges from 0° to 90°.
10. The microfluidic chip according to claim 7, characterized in that, The angle α between the spray guide line and the axis line is in the range of 45° to 90°.