A microfluidic chip structure for preparing liposomes and a design method thereof

Abstract

The application discloses a kind of microfluidic chip structure for preparing liposome and its design method, belong to microfluidic chip technical field.It includes chip ontology, first injection channel, second injection channel, mixing cavity and flow channel are arranged on chip ontology, one end of mixing cavity is communicated first injection channel and second injection channel, other end is communicated with flow channel, and mixing cavity includes mixing channel, and mixing channel includes circular arc channel, and the shape of cross section of circular arc channel is rectangle.Through being set as the circular arc channel of rectangular section of mixing channel, on the one hand, the circular arc channel of rectangular section can generate vortex flow, and this flow field characteristic can promote convection mass transfer, to improve the mixing efficiency between emulsion and liquid phase;Under the condition of same microfluidic chip structure size, improve the mixing efficiency between emulsion and liquid phase.In addition, the circular arc channel of rectangular section is convenient for the processing and manufacture of chip.

Description

Technical Field

[0001] This invention relates to the field of microfluidic chip technology, and in particular to a microfluidic chip structure for preparing liposomes and its design method. Background Technology

[0002] Liposomes are artificial carriers with biomembrane-like structures, mostly made of phospholipid molecules. Phospholipid molecules are amphiphilic, forming spherical vesicles with a bilayer membrane in water, with the hydrophilic end facing outward and the hydrophobic end facing inward. The diameter of these vesicles ranges from tens of nanometers to tens of micrometers. Liposomes can be used as drug carriers to load chemical drugs, gene drugs, and proteins, achieving purposes such as sustained release, targeted delivery, or improved drug stability.

[0003] In existing technologies, microfluidic chip technology is used for the preparation of liposomes via a double emulsion method. This method involves dissolving phospholipids in an organic solvent, adding the solution of the drug to be encapsulated, emulsifying to obtain an emulsion, then adding the emulsion to a liquid phase of 10 times its volume and mixing to obtain an emulsion solution. Finally, the organic solvent is removed at a certain temperature to obtain liposomes. Microfluidic chips include mixing channels where the emulsion and liquid phase are mixed. However, due to the limited size of microfluidic chips, the length of the mixing channels for mixing the emulsion and liquid phase is limited, resulting in insufficient mixing and poor mixing uniformity, which fails to meet user requirements.

[0004] Therefore, there is an urgent need for a microfluidic chip structure for preparing liposomes to solve the above problems. Summary of the Invention

[0005] The purpose of this invention is to provide a microfluidic chip structure for preparing liposomes, which solves the problem of low mixing efficiency between emulsions and liquid phases.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] A microfluidic chip structure for preparing liposomes includes: a chip body, wherein the chip body is provided with a first injection channel, a second injection channel, a mixing chamber and an outflow channel, one end of the mixing chamber is connected to the first injection channel and the second injection channel, and the other end is connected to the outflow channel, the mixing chamber includes a mixing channel, the mixing channel includes an arc channel, and the cross-sectional shape of the arc channel is rectangular.

[0008] Preferably, multiple arc channels are provided, and the multiple arc channels are connected end to end in sequence.

[0009] Preferably, the central angle corresponding to the arc length of the arc channel is greater than 180 degrees, so that the connection between two adjacent arc channels forms a detour.

[0010] Preferably, multiple arc channels are provided, and the mixed channel also includes a straight channel, which connects two adjacent arc channels.

[0011] Preferably, the central angle corresponding to the arc length of the arc channel is 180 degrees.

[0012] Preferably, the outlet of the second injection channel is located within the first injection channel, so that the second injection channel communicates with the mixing chamber through the first injection channel.

[0013] Preferably, the first injection channel is an L-shaped channel, which includes a first channel portion communicating with the mixing chamber and a second channel portion communicating with the outside, with the second injection channel passing through the first channel portion.

[0014] Preferably, the mixing chamber further includes:

[0015] A first contraction channel, the first contraction channel connecting the first injection channel and the mixing chamber, wherein the diameter of the first contraction channel at the end facing the first injection channel is larger than the diameter at the end facing the mixing chamber; and / or

[0016] A second contraction channel connects the outflow channel and the mixing chamber, wherein the diameter of the second contraction channel at the end facing the outflow channel is smaller than the diameter at the end facing the mixing chamber.

[0017] A method for designing a microfluidic chip structure for fabricating liposomes, wherein the design steps of the arcuate channel include:

[0018] S100. The mathematical model of the objective function established according to the response surface methodology is as follows:

[0019] f = k0 + k1A + k2B + k3C + k4A 2 +k5B 2 +k6C 2 +k7AB+k8AC+k9BC, Equation (1)

[0020] Where f represents the mixing index of various substances in the objective function;

[0021] k0, k1, k2, k3, k4, k5, k6, k7, k8, and k9 are all undetermined constants;

[0022] A∈(0,+∞); B∈(0,+∞); C=θ, C is between 0 degrees and 360 degrees; where w is the length of the rectangular cross section of the arc channel, h is the width of the rectangular cross section of the arc channel, C is the central angle of the arc channel corresponding to the arc length, and r is the radius of the arc channel on the side closer to the center.

[0023] S200. Through least squares fitting and simulation experiments, it was determined that:

[0024] k0, k1, k2, k3, k4, k5, k6, k7, k8, k9, thus obtaining the objective function;

[0025] S300、Substitute k0, k1, k2, k3, k4, k5, k6, k7, k8, k9 into equation (1) to simplify and obtain the objective function. Determine the maximum and minimum points of variables A, B, and C in the objective function. When variables A, B, and C take values, select the maximum points of the objective function and avoid the minimum points.

[0026] S400. Determine the values ​​of w, h, and C based on the values ​​of variables A, B, and C, so as to determine the structure of the arc channel.

[0027] Preferably, after step S400, the following is also included:

[0028] S500, the number of cycles of the arc channel (2022) is m, the flow velocity of the liquid at the inlet of the arc channel (2022) is v, f represents the mixing index of various substances in the objective function, and the mixing index f has a functional relationship with the number of cycles m and the liquid flow velocity v, denoted as g. According to experimental calculation, f = g(m,v);

[0029] When v > v1, m < m1, and f > f1, take m = m3;

[0030] When v < v1, m > m2, f > f1, take m = m4, where m3 < m1 < m2 < m4;

[0031] Where v1 and v2 are two preset flow velocity values ​​of the liquid flow velocity at the inlet of the arc channel (2022), m1, m2, m3, and m4 are four preset number of cycles of the arc channel (2022), and f1 is a preset mixing index.

[0032] The beneficial effects of this invention are:

[0033] The microfluidic chip structure for liposome preparation provided by this invention uses a circular arc channel with a rectangular cross-section as the mixing channel. On one hand, the circular arc channel has a rectangular cross-section, and a corner is formed between two adjacent sides. This causes the emulsion and liquid phase to pass through the corner when passing through the bend, increasing the instability of the emulsion and liquid phase flow at the bend. When the emulsion and liquid phase flow through the corner of the channel, a portion of the emulsion and liquid phase is affected, increasing its velocity and generating vortices. This vortex generated by the circular arc channel with a rectangular cross-section can promote convective mass transfer between the emulsion and liquid phase, thereby improving the mixing efficiency between the emulsion and liquid phase. On the other hand, the arc-shaped channel design allows the emulsion and liquid phase to follow a curved path during flow, extending the path they travel when mixing. When passing through the curved section, the emulsion and liquid phase flowing within the mixing channel need to turn. During this turning process, the emulsion and liquid phase interact with the sidewalls of the mixing channel, generating mutual action and reaction forces. This results in convection between the emulsion and liquid phases, improving their mixing efficiency. Under the same microfluidic chip structure size, this improves the mixing efficiency between the emulsion and liquid phase. Furthermore, the rectangular cross-section of the arc-shaped channel facilitates chip fabrication.

[0034] The present invention provides a design method for a microfluidic chip structure for preparing liposomes. By setting three variables A, B and C, a mathematical model is established based on the three variables to design the cross-sectional ratio of the arc channel. After determining the objective function, the three variables are set to the optimal values, thereby further optimizing the arc channel and achieving precise design of the cross-sectional ratio of the arc channel, thereby further improving the mixing efficiency of the solution in the arc channel. Attached Figure Description

[0035] Figure 1 This is an isometric view of the microfluidic chip structure for preparing liposomes provided in Embodiment 1 of the present invention;

[0036] Figure 2 This is a schematic diagram of the arc channel provided in Embodiment 1 of the present invention;

[0037] Figure 3 This is a cross-sectional view of the microfluidic chip structure for preparing liposomes provided in Embodiment 1 of the present invention;

[0038] Figure 4 This is a flowchart of the design method for a microfluidic chip structure for preparing liposomes provided in Embodiment 1 of the present invention;

[0039] Figure 5 This is a graph showing the functional relationship between variable A and the mixing index f in the design method of the microfluidic chip structure for preparing liposomes provided in Embodiment 1 of the present invention.

[0040] Figure 6 This is a graph showing the functional relationship between variable B and the mixing index f in the design method of the microfluidic chip structure for preparing liposomes provided in Embodiment 1 of the present invention.

[0041] Figure 7 This is a graph showing the functional relationship between variable C and mixing index f in the design method of microfluidic chip structure for preparing liposomes provided in Embodiment 1 of the present invention.

[0042] Figure 8 This is a graph showing the functional relationship between flow rate v, circular channel circulation number m, and mixing index f in the microfluidic chip structure design method for preparing liposomes provided in Embodiment 1 of the present invention.

[0043] Figure 9 This is a cross-sectional view of the microfluidic chip structure for preparing liposomes provided in Embodiment 2 of the present invention.

[0044] In the picture:

[0045] 1. Chip body;

[0046] 101. First injection channel; 1011. First channel section; 1012. Second channel section; 102. Second injection channel;

[0047] 2. Mixing chamber; 201. First contraction channel; 202. Mixing channel; 2021. First connecting channel; 2022. Arc channel; 2023. Second connecting channel; 2024. Straight channel; 2025. Detour section; 203. Second contraction channel;

[0048] 3. Outflow channel. Detailed Implementation

[0049] Embodiments of the present invention are described in detail below. Examples of these embodiments are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0050] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance. The terms "first position" and "second position" refer to two different positions.

[0051] Unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing" should be interpreted broadly. For example, they can refer to fixed connections or detachable connections; mechanical connections or electrical connections; direct connections or indirect connections through an intermediate medium; and connections within two components or interactions between two components. Those skilled in the art can understand the specific meaning of these terms in this invention based on the specific circumstances.

[0052] Unless otherwise expressly specified and limited, "above" or "below" a second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of a second feature includes the first feature directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" of a second feature includes the first feature directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0053] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0054] Example 1

[0055] like Figures 1 to 4 As shown, this application provides a microfluidic chip structure and its design method for preparing liposomes, which improves the mixing efficiency of emulsion and aqueous phase during liposome preparation.

[0056] See Figures 1 to 3A microfluidic chip structure for preparing liposomes includes a chip body 1. The chip body 1 has a first injection channel 101, a second injection channel 102, a mixing chamber 2, and an outflow channel 3. One end of both the first injection channel 101 and the second injection channel 102 is connected to the outside. The first injection channel 101 is used to introduce a first substance, and the second injection channel 102 is used to allow a second substance to flow through. The other end of both the first injection channel 101 and the second injection channel 102 is connected to one end of the mixing chamber 2. The first substance and the second substance are mixed inside the mixing chamber 2 to form a mixture. One end of the outflow channel 3 is connected to the outside, and the other end is connected to the other end of the mixing chamber 2. The mixture in the mixing chamber 2 flows out of the chip body 1 through the outflow channel 3.

[0057] For example, in this application, the first substance is a liquid phase and the second substance is an emulsion.

[0058] Optionally, the first injection channel 101 and the second injection channel 102 are provided with threaded holes at the ends facing the outside, so as to facilitate connection with an external liquid supply device.

[0059] See Figures 1 to 3 The mixing chamber 2 includes a mixing channel 202, which includes an arc-shaped channel 2022 with a rectangular cross-sectional shape. When the first and second substances flow within the mixing channel 202, they pass through the arc-shaped channel 2022. The arc-shaped channel 2022 causes the first and second substances to follow a curved path during flow. During this curvature, both substances collide with the sidewalls of the arc-shaped channel 2022, generating action and reaction forces. These forces act within the first and second substances, causing convection between them and improving mixing efficiency. The arc-shaped channel 2022 extends the path through which the first and second substances mix, ensuring thorough mixing. The rectangular cross-section generates eddies, promoting convective mass transfer between the first and second substances and further enhancing mixing efficiency. Furthermore, the rectangular cross-section of the arc-shaped channel 2022 facilitates its forming and processing.

[0060] Optionally, the microfluidic chip structure used to prepare liposomes is produced by a photopolymerization 3D printer to form an integrated structure. While ensuring accuracy, this reduces processing and time costs, and has good economic efficiency and practicality.

[0061] Further, see Figure 3Multiple arc channels 2022 are configured, and these multiple arc channels 2022 are connected end to end in sequence. The configuration of multiple arc channels 2022 allows the substances to be mixed to form multiple curved loops during the flow process. On the one hand, this can lengthen the flow path, and on the other hand, multiple curved loops can apply different forces to the substances to be mixed from different directions and angles, thereby improving the mixing efficiency between the first substance and the second substance.

[0062] Further, see Figure 3 The central angle of the corresponding arc length of the circular arc channel 2022 is greater than 180 degrees, so that the connection between two adjacent circular arc channels 2022 forms a detour section 2025. The formation of the detour section 2025 causes a certain circumferential backflow to occur when the substances to be mixed flow, which can enhance the convection effect of the force inside the substances to be mixed, thereby improving the mixing efficiency between the first substance and the second substance.

[0063] Further, see Figure 3 The outlet of the second injection channel 102 is located within the first injection channel 101, so that the second injection channel 102 is connected to the mixing chamber 2 through the first injection channel 101. With this configuration, the substance in the second injection channel 102 first enters the first injection channel 101 before flowing out and then enters the mixing chamber 2. The second substance in the second injection channel 102 mixes with the first substance inside the first injection channel 101 before flowing into it. In other words, the first and second substances mix before entering the mixing chamber, which effectively extends the length of the mixing chamber, resulting in more thorough mixing and improved mixing effect.

[0064] Optionally, a portion of the second injection channel 102 is located inside the first channel. The first injection channel 101 does not limit the structure in which it encloses the second injection channel 102. This application provides one implementation; other implementations can be selected by those skilled in the art based on actual circumstances. Optionally, see [link to relevant documentation]. Figure 3 The first injection channel 101 is an L-shaped channel, comprising a first channel portion 1011 and a second channel portion 1012. The first channel portion 1011 communicates with the mixing chamber 2, and the second channel portion 1012 communicates with the outside. The second injection channel 102 passes through the first channel portion 1011. The L-shaped design of the first injection channel 101 facilitates the entry of the second injection channel 102 into the first injection channel 101 at the bend, reducing the impact of the injection of the second substance in the second injection channel on the injection of the first substance in the first injection channel.

[0065] Further, see Figure 3The mixing chamber 2 also includes a first contraction channel 201, which connects the first injection channel 101 and the mixing chamber 2. The diameter of the first contraction channel 201 facing the first injection channel 101 is larger than the diameter facing the mixing chamber 2. The first contraction channel 201 adopts a constricted design, which can generate a circumferential contraction force on the different substances to be mixed, thereby strengthening the convection inside the different substances to be mixed and improving the mixing efficiency between the different substances.

[0066] Similarly, further see Figure 3 The mixing chamber 2 also includes a second contraction channel 203, which connects the outflow channel 3 and the mixing chamber 2. The diameter of the second contraction channel 203 facing the mixing chamber 2 is larger than the diameter of the outflow channel 3. The first contraction channel 201 adopts a constricted design, which can generate a circumferential contraction force on the different substances to be mixed, further improving the mixing efficiency between different substances.

[0067] Optionally, see Figure 3 A first connecting channel 2021 is provided between the first contraction channel 201 and the arc channel 2022, and a second connecting channel 2023 is provided between the arc channel 2022 and the second contraction channel 203. Both the first connecting channel 2021 and the second connecting channel 2023 are arc-shaped and correspond to the arc channel 2022. This arrangement enables a smooth transition between the first injection channel 101 and the arc channel 2022, and between the arc channel 2022 and the outflow channel 3, smoothly connecting the straight first contraction channel 201 and the curved arc channel 2022, which facilitates the smooth entry of different substances into the arc channel 2022 for thorough mixing.

[0068] This embodiment also provides a design method for a microfluidic chip structure for preparing liposomes as described above. The design steps for the arc channel 2022 include:

[0069] S100. The mathematical model of the objective function established according to the response surface methodology is as follows:

[0070] f = k0 + k1A + k2B + k3C + k4A 2 +k5B 2 +k6C 2 +k7AB+k8AC+k9BC, Equation (1)

[0071] Where f represents the mixing index of various substances in the objective function;

[0072] k0, k1, k2, k3, k4, k5, k6, k7, k8, and k9 are all undetermined constants;

[0073] A∈(0,+∞); B∈(0,+∞); C=θ, C is between 0 degrees and 360 degrees; where w is the length of the rectangular cross section of the arc channel (2022), h is the width of the rectangular cross section of the arc channel (2022), C is the central angle of the arc corresponding to the arc length of the arc channel (2022), and r is the radius of the arc channel (2022) on the side closer to the center;

[0074] S200. Through least squares fitting and simulation experiments, it was determined that:

[0075] k0, k1, k2, k3, k4, k5, k6, k7, k8, k9;

[0076] S300, simplified formula (1), obtain the objective function, determine the maximum and minimum points of variables A, B and C in the objective function, select the maximum point of the objective function when variables A, B and C take values, and avoid the minimum point;

[0077] S400. Determine the values ​​of w, h, and C based on the values ​​of variables A, B, and C, so as to determine the structure of the arc channel (2022).

[0078] Optionally, in step S200, the objective function is fitted using the least squares method;

[0079] First, the system provides several groups (f) i A i B i C i ), where i = 1, 2, 3, 4..., and (f i A i B i C i Substituting these values ​​into equation (1), we fit and determine k0, k1, k2, k3, k4, k5, k6, k7, k8, and k9, obtaining the following results.

[0080] f′=k 10 +k 11 A+k 12 B+k 13 C+k 14 A 2 +k 15 B 2 +k 16 C 2 +k 17 AB+k 18 AC+k 19 BC, Equation (2)

[0081] Where, k 10 k 11 k12 k 13 k 14 k 15 k 16 k 17 k 18 k 19 It is a constant;

[0082] Then, through simulation experiments, several sets of (f) are obtained from equation (2). 1i A 1i B 1i C 1i ), where i = 1, 2, 3, 4..., and (f i A i B i C i Substituting into equation (1), we fit k0, k1, k2, k3, k4, k5, k6, k7, k8, and k9 to obtain the following results:

[0083] f″=k 20 +k 21 A+k 22 B+k 23 C+k 24 A 2 +k 25 B 2 +k 26 C 2 +k 27 AB+k 28 AC+k 29 BC, Equation (3)

[0084] Where, k 20 k 21 k 22 k 23 k 24 k 25 k 26 k 27 k 28 k 29 It is a constant;

[0085] By repeatedly fitting the data several times, we can obtain...

[0086] f (n) =k n0 +k n1 A+k n2 B+k n3 C+k n4 A 2 +k n5 B 2 +k n6 C 2 +kn7 AB+k n8 AC+k n9 BC, Equation (4)

[0087] Where, k n0 k n1 k n2 k n3 k n4 k n5 k n6 k n7 k n8 k n9 It is a constant.

[0088] For example, the objective function, after multiple fittings, yields the following function:

[0089] f=0.31-22.11A+149.79B+0.04C+39.76A 2 -180.21B 2 +0.00021C 2 -50.22AB-0.12AC+0.10BC,

[0090] The coefficient of the squared term of variable C is 0.00021, which is relatively small, so the squared term of variable C can be ignored. The objective function can then be further simplified to...

[0091] f=0.31-22.11A+149.79B+0.04C+39.76A 2 -180.21B 2 -50.22AB-0.12AC+0.10BC

[0092] Optionally, in step S300:

[0093] For variable A, simplifying equation (4) yields f (n) =a0+a1A+a2A 2 Equation (5)

[0094] Where a0 = k n0 +k n2 B+k n3 C+k n5 B 2 +k n6 C 2 +k n9 BC, a1 = k n1 +k n7 B+k n8 C,a2=k n4 ;

[0095] If a2 > 0, find the maximum point A = a3; if a2 < 0, find the minimum point A = a4.

[0096] Variable A takes the maximum value point and avoids the minimum value point; among them, the mixing efficiency between different substances is better at the maximum value point of variable A, and the mixing efficiency between different substances is lower at the minimum value point.

[0097] For example, the objective function simplifies to f (n) = a0 + a1A + 39.76A 2 Where a2 = 39.76 > 0, variable A has a local minimum with respect to the objective function f. The graph of variable A with respect to the objective function f is approximately as follows: Figure 5 As shown, the minimum point is located near A = 0.8. Therefore, the value of variable A should avoid the area near A = 0.8.

[0098] For variable B, simplifying equation (4) yields f (n) =b0+b1B+b2B 2 Equation (6) where b0 = k n0 +k n1 A+k n3 C+k n4 A 2 ++k n6 C 2 +k n8 AC, b1 = k n2 +k n7 A+k n9 C,b2=k n5 ;

[0099] If b2 > 0, the maximum point B = b3 is found; if b2 < 0, the minimum point B = b4 is found.

[0100] Variable B takes the maximum value point and avoids the minimum value point; among them, the mixing efficiency between different substances is better at the maximum value point of variable B, and the mixing efficiency between different substances is lower at the minimum value point.

[0101] For example, the objective function simplifies to f (n) =b0+b1B-180.21B 2 Where b2 = -180.21 < 0, variable B has a local maximum with respect to the objective function f, and the graph of variable B with respect to the objective function f is approximately as follows. Figure 6 As shown, the maximum value is located near B = 0.4. Therefore, the value of variable B should be around B = 0.4.

[0102] For variable C, simplifying equation (4) yields f (n) =c0+c1C+c2C 2Equation (7)

[0103] Where c0 = k n0 +k n1 A+k n2 B++k n4 A 2 +k n5 B 2 +k n7 AB, c1 = k n3 +k n8 A+k n9 B,c2=k n6 ;

[0104] If c2 > 0, the maximum point C = c3 is found; if b2 < 0, the minimum point C = c4 is found.

[0105] The variable C takes the maximum value point and avoids the minimum value point; the mixing efficiency between different substances is better at the maximum value point of variable C, and lower at the minimum value point.

[0106] For example, the objective function simplifies to f (n) = c0 + 0.06C + 0.0012C 2 Where c2 = 0.0012, the quadratic term of variable C can be ignored, and we can directly look at the linear term of variable C, c1 = 0.06. That is, the objective function f corresponding to variable C is a monotonically increasing linear function, and its graph is approximately as follows. Figure 7 As shown, the larger the value of variable C is within the operable range, the better.

[0107] Optionally, in step S400:

[0108] The values ​​of w, h, and C are determined based on the values ​​of variables A, B, and C in step S300, thereby determining the structure of the arc channel;

[0109] The value of r is determined based on the size of the chip body 1. It can be selected based on experience or experimentation. Then, the values ​​of w, h, and C are determined according to the corresponding values ​​of A, B, and C, thereby determining the cross-sectional dimensions of the arc channel 2022.

[0110] In one implementation, after step S400, the method further includes:

[0111] S500, the number of cycles of the arc channel (2022) is m, the flow velocity of the liquid at the inlet of the arc channel (2022) is v, f represents the mixing index of various substances in the objective function, the mixing index f has a functional relationship with the number of cycles m and the liquid flow velocity v, denoted as g, according to experimental calculation, f=g(m,v);

[0112] When v > v1 and m < m1, f > f1; that is, when the flow velocity v is greater than v1, even if the number of cycles in the arc channel 2022 is less than m1, the mixing index f will be greater than f1.

[0113] When v < v1 and m > m2, f > f1; that is, when the flow velocity v is less than v1, the number of cycles in the arc channel 2022 needs to be greater than m2 for the mixing index f to be greater than f1.

[0114] Where m1 < m2.

[0115] Therefore, when v > v1, take m = m3;

[0116] When v < v1, take m = m4; where m3 < m1, m4 > m2.

[0117] Where v1 and v2 are two preset flow velocity values ​​of the liquid flow velocity at the inlet of the arc channel (2022), m1, m2, m3, and m4 are four preset number of cycles of the arc channel (2022), and f1 is a preset mixing index.

[0118] For example, the functional relationship between the mixing index f and the flow velocity v and the number of circular channels m, calculated experimentally, is as follows: Figure 8 As shown.

[0119] Combination Figure 8 When the flow rate v is 200 μL / min (greater than 150 μL / min), the mixing index will be greater than 50 when the number of circular channel cycles m is 2 (less than 3); when the flow rate v is 100 μL / min (less than 150 μL / min), the mixing index will be greater than 50 when the number of circular channel cycles m is 7 (greater than 4). When those skilled in the art select the number of circular channel cycles m, they should combine the flow rate v and the desired mixing index f.

[0120] Example 2

[0121] This embodiment provides a microfluidic chip structure for preparing liposomes, which is basically the same as the structure of Embodiment 1. The similarities will not be repeated here. The differences are as follows: [See...] Figure 9 Multiple arc channels 2022 are provided, and the mixing channel 202 also includes a straight channel 2024, which connects two adjacent arc channels 2022. The straight channel 2024 can further lengthen the flow path of different substances to be mixed in the mixing channel 202, thereby improving the mixing efficiency between different substances.

[0122] In one embodiment, two adjacent arcuate channels 2022 are connected by a straight channel 2024. In another embodiment, some adjacent arcuate channels 2022 are connected by a straight channel 2024, while other adjacent arcuate channels 2022 are connected by channels of other shapes, or adjacent arcuate channels 2022 are directly connected. The configuration is set according to actual needs and is not limited.

[0123] Optionally, see Figure 9 The central angle corresponding to the arc length of the arc channel 2022 is set to 180 degrees. This setting allows the straight channels 2024 to be parallel to each other, effectively utilizing the structural space of the chip body 1. It also lengthens the foldback path of different substances to be mixed inside the mixing channel 202, thereby improving the mixing efficiency between different substances.

[0124] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for designing a microfluidic chip structure for preparing liposomes, characterized in that, The microfluidic chip structure for preparing liposomes has a chip body (1), on which a first injection channel (101), a second injection channel (102), a mixing chamber (2), and an outflow channel (3) are provided. One end of the mixing chamber (2) is connected to the first injection channel (101) and the second injection channel (102), and the other end is connected to the outflow channel (3). The mixing chamber (2) includes a mixing channel (202), which includes an arc channel (2022), and the cross-sectional shape of the arc channel (2022) is rectangular. The design steps for the arc channel (2022) include: S100. The mathematical model of the objective function established according to the response surface methodology is as follows: Equation (1) in, The mixing index of various substances representing the objective function; All are undetermined constants; , ; , ; C is between 0 degrees and 360 degrees; where w is the length of the rectangular cross section of the arc channel (2022), h is the width of the rectangular cross section of the arc channel (2022), C is the central angle of the arc corresponding to the arc length of the arc channel (2022), and r is the radius of the arc channel (2022) on the side closer to the center. S200. Through least squares fitting and simulation experiments, it was determined that: Thus, the objective function is obtained; S300, will Substitute into equation (1) and simplify to obtain the objective function. Determine the maximum and minimum points of variables A, B, and C in the objective function. When variables A, B, and C take values, select the maximum points of the objective function and avoid the minimum points. S400. Determine the values ​​of w, h, and C based on the values ​​of variables A, B, and C, so as to determine the structure of the arc channel (2022).

2. The design method for a microfluidic chip structure for preparing liposomes according to claim 1, characterized in that, Multiple arc channels (2022) are provided, and the multiple arc channels (2022) are connected end to end in sequence.

3. The design method for a microfluidic chip structure for preparing liposomes according to claim 2, characterized in that, The central angle corresponding to the arc length of the arc channel (2022) is greater than 180 degrees, so that the connection between two adjacent arc channels (2022) forms a detour (2025).

4. The design method for a microfluidic chip structure for preparing liposomes according to claim 1, characterized in that, Multiple circular arc channels (2022) are provided, and the mixed channel (202) also includes a straight channel (2024), which is connected between two adjacent circular arc channels (2022).

5. The design method for a microfluidic chip structure for preparing liposomes according to claim 4, characterized in that, The arc length of the circular arc channel (2022) corresponds to a central angle of 180 degrees.

6. The method for designing a microfluidic chip structure for preparing liposomes according to any one of claims 1-5, characterized in that, The outlet of the second injection channel (102) is located within the first injection channel (101) so that the second injection channel (102) communicates with the mixing chamber (2) through the first injection channel (101).

7. The method for designing a microfluidic chip structure for preparing liposomes according to claim 6, characterized in that, The first injection channel (101) is an L-shaped channel. The first injection channel (101) includes a first channel portion (1011) that communicates with the mixing chamber (2) and a second channel portion (1012) that communicates with the outside. The second injection channel (102) passes through the first channel portion (1011).

8. The method for designing a microfluidic chip structure for preparing liposomes according to any one of claims 1-5, characterized in that, The mixing chamber (2) further includes: A first contraction channel (201) connects the first injection channel (101) and the mixing chamber (2), wherein the diameter of the first contraction channel (201) facing the first injection channel (101) is larger than the diameter facing the mixing chamber (2); and / or The second contraction channel (203) connects the outflow channel (3) and the mixing chamber (2). The diameter of the second contraction channel (203) facing the outflow channel (3) is smaller than the diameter facing the mixing chamber (2).

9. The design method for a microfluidic chip structure for preparing liposomes according to claim 1, characterized in that, Following step S400, the following is also included: S500, the number of cycles in the arc channel (2022) is m, and the flow velocity of the liquid at the inlet of the arc channel (2022) is v. The mixing index represents the mixture index of various substances in the objective function. The function relationship between the number of cycles m and the liquid flow velocity v is denoted as g. Based on experimental calculations, we obtain: ; when , , At that time, take ; when , , At that time, take ,in ; Where v1 is a preset flow rate value of the liquid flow rate at the inlet of the arc channel (2022), m1, m2, m3, and m4 are four preset number of cycles of the arc channel (2022), and f1 is a preset mixing index.

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