A viscoelastic microfluidic particle sorting mechanism modeling method, chip and application

Abstract

The present invention provides a viscoelastic microfluidic particle sorting mechanism modeling method, chip and application, belonging to the field of viscoelastic microfluidic particle sorting technology. By analyzing the variation law of the inertial lift and elastic force exerted on the particles in the straight channel section along the channel width direction and the movement trajectory of the particles after completely penetrating the sample-sheath liquid interface and entering the sheath liquid, the lateral displacement of the particles when reaching the end position of the straight channel section is obtained, and then the distribution of the sheath liquid and the sample in the amplification section is calculated, and the movement trajectory of the particles in the amplification section is obtained in combination with the lateral equilibrium position of the particles at the end of the straight channel section. Since the inertial lift and elastic force that play a leading role in the movement of the particles are related to the size of the particles, small-diameter and large-diameter particles will flow out from outlet one and outlet two respectively after passing through the straight channel section and the amplification section, thereby realizing particle sorting. The present invention can provide a theoretical basis for the optimization design of viscoelastic microfluidics, and realize flexible expansion and rapid iteration.

Description

Technical Field

[0001] The invention relates to the technical field of viscoelastic microfluidic particle sorting, and in particular to a viscoelastic microfluidic particle sorting mechanism modeling method, a chip and an application thereof. Background Art

[0002] Particle sorting is widely used in research in many disciplines such as biology, chemistry, and medicine. Among them, circulating tumor cell (CTC) sorting in the biomedical field is one of the typical applications. CTC refers to tumor cells that fall off from primary or metastatic tumor lesions and undergo epithelial-mesenchymal transformation to enter the peripheral blood circulation. In the early stages of tumor metastasis, the patient's tumor burden is low, and it is difficult to locate metastases and extract tumor tissue for analysis using traditional imaging methods. Studies have shown that CTCs already exist in the peripheral blood of cancer patients in the early stages of tumor metastasis. Therefore, CTC liquid biopsy technology has shown unique advantages in early cancer diagnosis and treatment guidance.

[0003] CTC sorting is the upstream technology of CTC liquid biopsy. The existing sorting methods can be divided into two categories: active manipulation and passive manipulation. Active manipulation refers to the sorting of cells by forming an external driving force through magnetic fields, electric fields, acoustic fields, light fields, and centrifugal motion. Due to its reliance on external forces, active methods often require the use of large and expensive instruments and the introduction of additional manual operations, and usually face problems such as high instrument costs, large system volume, and complex operations. Passive sorting technology does not require the use of forces formed by external physical fields to drive cells, but instead relies on the coupling between microstructures, microfluidics, and cells in microfluidic chips to achieve cell sorting. Passive technology can avoid the disadvantages of active methods, but it requires lysing red blood cells and diluting the blood nearly 100 times before sorting, which severely limits the sample processing throughput.

[0004] Viscoelastic microfluidic cell sorting technology uses viscoelastic fluid media to drive cells. Compared with the most widely used inertial microfluidic technology, viscoelastic microfluidic technology strengthens the control of cells by introducing additional elastic forces, and has the ability to directly sort CTCs from whole blood. However, the current research on viscoelastic microfluidic cell sorting technology at the level of sorting mechanism is not in-depth, and usually relies on a large number of experimental attempts to achieve the final sorting purpose, and cannot achieve the rapid design of viscoelastic microfluidic chips through theoretical guidance. Therefore, by constructing a theoretical model to reveal the viscoelastic microfluidic sorting mechanism, it can provide a theoretical basis for the optimization of viscoelastic microfluidics, and can be quickly iterated according to the sorting requirements of different applications, so that it can be flexibly expanded and widely used in other research fields. Summary of the invention

[0005] The purpose of the present invention is to provide a viscoelastic microfluidic particle sorting mechanism modeling method, chip and application, which can provide a theoretical basis for viscoelastic microfluidic optimization design and achieve flexible expansion and rapid iteration.

[0006] To achieve the above object, the present invention provides a viscoelastic microfluidic particle sorting mechanism modeling method, comprising the following steps:

[0007] S1. Use the total flow rate Q in the straight channel section to construct the velocity distribution function u in the mid-plane in the height direction x (y), through the sheath fluid flow Q c The distance between the sheath fluid-sample interface and the centerline of the straight channel segment is calculated by using the total flow rate Q in the straight channel segment. w1 is the transverse coordinate value of the sheath fluid-sample interface in the straight channel section;

[0008] S2, using the cubic polynomial in the transition interval 0.5 (w1-a p )≤y≤0.5(w1+a p ) to construct a virtual PEO transition concentration, and then obtain the distribution function c(y) of the PEO concentration in the channel width direction;

[0009] S3, based on the particle transverse coordinate y p , particle diameter a p , particle velocity u in the main flow direction px , the particle velocity u in the direction from the center of the channel to the wall py , channel height h, channel width w, sheath fluid flow rate Q c , total flow rate Q in the straight channel section, fluid density ρ f 、PEO molecular weight M W , PEO concentration of sheath fluid c c , PEO concentration of the sample c s , solvent viscosity η of PEO solution s , shear rate Avogadro's constant N A , Boltzmann constant k B and temperature T, construct the inertial lift force F on the particle i , elastic force F e , viscous drag F d and virtual mass force F v Expression of

[0010] S4, get F by calculation i and F eThe distribution along the width of the channel is used to construct the sample-sheath interface penetration criterion to determine whether the particles can completely penetrate the sample-sheath interface. The particle dynamics model is further constructed to calculate the movement trajectory of the particles after they completely enter the sheath liquid.

[0011] S5. Use ANSYS Fluent to calculate the distribution of sheath fluid and sample in the amplification section;

[0012] S6. Based on the lateral equilibrium position of the particle at the end of the straight channel section and the distribution of the sheath fluid and the sample in the amplification section, the movement trajectory of the particle in the amplification section is obtained.

[0013] Preferably, in step S1, the flow velocity distribution function u x (y) is a parabolic function, through the condition u x (0) = u xmax =2u xavg =2Q / wh,u x (w / 2)=0, as shown in formula (1):

[0014]

[0015] Among them, u x (0) is the flow velocity at the center of the straight channel section; u xmax is the maximum flow velocity in the straight channel section; u xavg is the average flow velocity in the straight channel section; y is the transverse coordinate value in the straight channel section;

[0016] Sheath fluid-sample interface position and sheath fluid flow rate Q c The relationship between the total flow rate Q in the straight channel section is characterized by formula (2), and then w1 is solved by formula (3), as follows:

[0017]

[0018]

[0019] Among them, Q c (w1) represents Q c is a function of w1.

[0020] Preferably, in step S2, the transition interval is 0.5(w1-a p )≤y≤0.5(w1+a p ), the distribution function c(y) of PEO concentration in the channel width direction is expressed by formula (4):

[0021]

[0022] Where c(y) is the PEO concentration function; C1, C2, C3, and C4 are coefficients.

[0023] Preferably, in step S3, the inertial lift force F exerted on the particle is i , elastic force F e , viscous drag F d and virtual mass force F v The expression is as follows:

[0024]

[0025] Among them, e j is the unit vector from the center of the channel to the wall; e i is the unit vector for the main flow direction; is the gradient operator.

[0026] Preferably, in step S4, the sample-sheath fluid interface penetration criterion is: when F i With F e When the resultant force has a negative slope zero point in the transition interval, the particle cannot completely penetrate the sample-sheath liquid interface; otherwise, the particle will completely penetrate the sample-sheath liquid interface and enter the sheath liquid.

[0027] The particle dynamics model is characterized by equation (6) and further organized into a differential equation form as shown in equation (7):

[0028]

[0029]

[0030] Among them, x p is the coordinate value of the particle in the main flow direction; u p is the velocity vector of the particle; t is the time; k1, k2, k3, k4, k5, k6, k7, k8 are all coefficients.

[0031] Preferably, in step S5, the method for analyzing the movement trajectory of the particle in the amplification section is as follows: when the particle is located at the sample-sheath fluid interface when it reaches the end of the straight channel section, the particle will flow into outlet one along the sample-sheath fluid interface in the amplification section after entering the amplification section; when the particle is completely located in the sheath fluid when it reaches the end of the straight channel section, the particle will flow into outlet two along the equilibrium trajectory in the straight channel section after entering the amplification section.

[0032] The present invention also provides a viscoelastic microfluidic chip constructed by the viscoelastic microfluidic particle sorting mechanism modeling method as described above, comprising an inlet 1, an inlet 2, a circular bifurcation branch, a straight channel section, an amplification section, an outlet 1 and an outlet 2;

[0033] The initial end of the circular forked branch is connected to the end of the inlet 1, the end of the circular forked branch is connected to the straight channel section, the inlet 2 is arranged inside the circular forked branch, the initial end of the enlarged section is connected to the end of the straight channel section, the end of the enlarged section is connected to the outlet 1 and the outlet 2, the outlet 1 is provided with two, and is symmetrical with respect to the outlet 2;

[0034] The channel height in the viscoelastic microfluidic chip is 50 μm, the width and length of the straight channel section are 120 μm and 38 mm respectively, the total width of the amplified section is 1080 μm, the widths of the outlet 1 channel and the outlet 2 channel are 356 μm and 280 μm respectively, and the particle solution in the inlet 1 is introduced into the straight channel section together with the sheath solution in the inlet 2 through a circular bifurcation branch with a width of 120 μm;

[0035] The sheath liquid in the second inlet is prepared by dissolving a powder of a high molecular weight polymer polyethylene oxide in deionized water to obtain a PEO stock solution with a concentration of 1% to 2% w / v, and then further diluted to a PEO working solution with a concentration of 0.03% to 0.15% w / v;

[0036] The flow rates of the inlet 1 and the inlet 2 are 1-3 mL / h and 9-20 mL / h respectively.

[0037] The present invention also provides an application of the viscoelastic microfluidic chip as described above in sorting particles with a diameter of 5 μm and particles with a diameter of 10 μm, comprising the following steps:

[0038] Step a1, dissolving 600 kDa PEO powder in deionized water, shaking for 28 to 36 hours, to prepare a PEO stock solution with a concentration of 1% to 2% w / v;

[0039] Step b1, diluting a PEO stock solution with a concentration of 1% to 2% w / v into a working solution with a PEO concentration of 0.03% w / v as a sheath liquid;

[0040] Step c1, using two syringe pumps to inject the particle solution and 0.03% w / v working solution into the viscoelastic microfluidic chip from inlet 1 and inlet 2, respectively, with flow rates at inlet 1 and inlet 2 being 2 mL / h and 20 mL / h, respectively;

[0041] Step d1, collecting particles with a diameter of 5 μm and particles with a diameter of 10 μm from outlet 1 and outlet 2 respectively.

[0042] The present invention also provides an application of the viscoelastic microfluidic chip as described above in sorting particles with a diameter of 10 μm and particles with a diameter of 15 μm, comprising the following steps:

[0043] Step a2, dissolving 600 kDa PEO powder in deionized water, shaking for 28 to 36 hours, and preparing a PEO stock solution with a concentration of 1% to 2% w / v;

[0044] Step b2, diluting a PEO stock solution with a concentration of 1% to 2% w / v into a working solution with a PEO concentration of 0.05% w / v as a sheath liquid;

[0045] Step c2, using two syringe pumps to inject the particle solution and 0.05% w / v working solution into the viscoelastic microfluidic chip from inlet 1 and inlet 2, respectively, with flow rates of 1.5 mL / h and 9 mL / h at inlet 1 and inlet 2, respectively;

[0046] Step d2, collecting particles with a diameter of 10 μm and particles with a diameter of 15 μm from outlet 1 and outlet 2 respectively.

[0047] The present invention also provides an application of the viscoelastic microfluidic chip as described above in sorting particles with a diameter of 15 μm and particles with a diameter of 20 μm, comprising the following steps:

[0048] Step a3, dissolving 600 kDa PEO powder in deionized water, shaking for 28 to 36 hours, and preparing a PEO stock solution with a concentration of 1% to 2% w / v;

[0049] Step b3, diluting a PEO stock solution with a concentration of 1% to 2% w / v into a working solution with a PEO concentration of 0.15% w / v as a sheath liquid;

[0050] Step c3, adding a PEO stock solution with a concentration of 1% to 2% w / v to the particle solution to make the PEO concentration in the particle solution 0.05% w / v;

[0051] Step d3, using two syringe pumps to inject the particle solution and 0.15% w / v working solution into the viscoelastic microfluidic chip from inlet 1 and inlet 2, respectively, with flow rates of 2.5 mL / h and 16 mL / h at inlet 1 and inlet 2, respectively;

[0052] Step e3, collecting particles with a diameter of 15 μm and particles with a diameter of 20 μm from outlet 1 and outlet 2 respectively.

[0053] Therefore, the present invention adopts the above-mentioned viscoelastic microfluidic particle sorting mechanism modeling method, chip and application, which can provide a theoretical basis for the optimization of viscoelastic microfluidics, and can perform rapid iterative design according to the sorting requirements of different application scenarios, greatly reducing the large amount of unnecessary investment caused by traditional empirical design, thereby achieving flexible expansion and wide application in other research fields. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1is a flow chart of a viscoelastic microfluidic particle sorting mechanism modeling method in an embodiment of the present invention;

[0055] Figure 2 The viscoelastic microfluidic chip design structure diagram in the embodiment of the present invention;

[0056] Figure 3 Schematic diagram of the movement of particles in a viscoelastic microfluidic chip channel in an embodiment of the present invention;

[0057] Figure 4 This is a schematic diagram of the motion analysis of particles in a straight channel section of a viscoelastic microfluidic chip in an embodiment of the present invention;

[0058] Figure 5 is a sample-sheath fluid interface penetration criterion analysis result diagram in an embodiment of the present invention; wherein, Figure 5 (a) shows the distribution of the force on particles with a diameter of 5 μm and 10 μm in the y direction under the flow conditions of a sample liquid flow rate of 2 mL / h, a PEO concentration of 0% in the sample liquid, a sheath liquid flow rate of 20 mL / h, and a PEO concentration of 0.03% in the sheath liquid; Figure 5 (b) shows the distribution of the force on the 10 μm diameter particle and the 15 μm diameter particle in the y direction under the flow conditions of the sample liquid flow rate of 1.5 mL / h, the PEO concentration in the sample liquid of 0%, the sheath liquid flow rate of 9 mL / h, and the PEO concentration in the sheath liquid of 0.05%; Figure 5 (c) shows the distribution of the force on the 15 μm diameter particle and the 20 μm diameter particle in the y direction under the flow conditions of the sample liquid flow rate of 2.5 mL / h, the PEO concentration in the sample liquid of 0.05%, the sheath liquid flow rate of 16 mL / h, and the PEO concentration in the sheath liquid of 0.15%;

[0059] Figure 6 It is a graph showing the analysis results of the particle dynamics model in an embodiment of the present invention;

[0060] Figure 7 This is a schematic diagram of the motion analysis principle of particles in the amplification section of a viscoelastic microfluidic chip in an embodiment of the present invention;

[0061] Figure 8 is a distribution diagram of the sheath fluid and the sample in the amplified section in an embodiment of the present invention; Figure 8 (a) shows the distribution of sheath liquid and sample liquid in the amplification section under the flow conditions of sample liquid flow rate of 2 mL / h, PEO concentration in the sample liquid of 0%, sheath liquid flow rate of 20 mL / h, and PEO concentration in the sheath liquid of 0.03%; Figure 8(b) shows the distribution of sheath liquid and sample liquid in the amplification section under the flow conditions of sample liquid flow rate of 1.5 mL / h, PEO concentration in the sample liquid of 0%, sheath liquid flow rate of 9 mL / h, and PEO concentration in the sheath liquid of 0.05%; Figure 8 (c) shows the distribution of sheath liquid and sample liquid in the amplification section under the flow conditions of sample liquid flow rate of 2.5 mL / h, PEO concentration in the sample liquid of 0.05%, sheath liquid flow rate of 16 mL / h, and PEO concentration in the sheath liquid of 0.15%;

[0062] Fig. 9 The figure is a diagram of theoretical and experimental results of the distance between the particle and the center line of the enlarged section of the viscoelastic microfluidic chip in the embodiment of the present invention; Fig. 9 (a) shows the distance between the 5 μm diameter particle and the 10 μm diameter particle and the center line of the channel in the amplified section under the flow conditions of sample liquid flow rate of 2 mL / h, PEO concentration in the sample liquid of 0%, sheath liquid flow rate of 20 mL / h, and PEO concentration in the sheath liquid of 0.03%; Fig. 9 (b) shows the distance between the 10 μm diameter particle and the 15 μm diameter particle and the center line of the channel in the amplified section under the flow conditions of sample liquid flow rate of 1.5 mL / h, PEO concentration in the sample liquid of 0%, sheath liquid flow rate of 9 mL / h, and PEO concentration in the sheath liquid of 0.05%; Fig. 9 (c) shows the distance between the 15 μm diameter particle and the 20 μm diameter particle and the center line of the channel in the amplified section under the flow conditions of sample liquid flow rate of 2.5 mL / h, PEO concentration in the sample liquid of 0.05%, sheath liquid flow rate of 16 mL / h, and PEO concentration in the sheath liquid of 0.15%;

[0063] Fig.10 This is a graph showing the results of a particle sorting experiment in an enlarged section of a viscoelastic microfluidic chip according to an embodiment of the present invention; Fig.10 (a) shows the distribution of 5 μm diameter particles and 10 μm diameter particles in the amplified section under the flow conditions of sample liquid flow rate of 2 mL / h, PEO concentration in the sample liquid of 0%, sheath liquid flow rate of 20 mL / h, and PEO concentration in the sheath liquid of 0.03%; Fig.10 (b) shows the distribution of 10 μm diameter particles and 15 μm diameter particles in the enlarged section under the flow conditions of sample liquid flow rate of 1.5 mL / h, PEO concentration in the sample liquid of 0%, sheath liquid flow rate of 9 mL / h, and PEO concentration in the sheath liquid of 0.05%; Fig.10 (c) shows the distribution of 15 μm diameter particles and 20 μm diameter particles in the amplified section under the flow conditions of sample liquid flow rate of 2.5 mL / h, PEO concentration in the sample liquid of 0.05%, sheath liquid flow rate of 16 mL / h, and PEO concentration in the sheath liquid of 0.15%.

[0064] Reference numerals

[0065] 1. Entrance 1; 2. Entrance 2; 3. Circular branch; 4. Straight section; 5. Enlarged section; 6. Exit 1; 7. Exit 2. DETAILED DESCRIPTION

[0066] The technical solution of the present invention is further described below through the accompanying drawings and embodiments.

[0067] Unless otherwise defined, technical or scientific terms used in the present invention shall have the common meanings understood by one having ordinary skills in the field to which the present invention belongs.

[0068] Embodiment 1

[0069] like Figure 1 As shown, the present invention proposes a viscoelastic microfluidic particle sorting mechanism modeling method, which includes two parts: a straight channel segment particle trajectory prediction model and an amplified segment particle trajectory analysis method.

[0070] Among them, the straight channel section particle trajectory prediction model consists of two parts: the sample-sheath liquid interface penetration criterion and the particle dynamics model. By analyzing the variation law of the inertial lift and elastic force on the particles in the straight channel section 4 along the channel width direction and the movement trajectory of the particles after completely penetrating the sample-sheath liquid interface and entering the sheath liquid, the lateral displacement of the particles when they reach the end of the straight channel section 4 can be obtained. Furthermore, the distribution of the sheath liquid and the sample in the amplification section 5 is calculated by ANSYS Fluent, and the movement trajectory of the particles in the amplification section 5 can be obtained in combination with the lateral equilibrium position of the particles at the end of the straight channel section 4. Since the inertial lift and elastic force that play a dominant role in particle movement are related to the size of the particles, small-diameter and large-diameter particles will flow out from outlet 1 6 and outlet 2 7 respectively after passing through the straight channel section 4 and the amplification section 5, realizing particle sorting.

[0071] Sample refers to a particle solution, i.e., a particle suspension, such as blood cells suspended in plasma, polystyrene microspheres suspended in ultrapure water. Particles refer to objects such as polystyrene microspheres, cells, or chemical particles. For example, 5μm particles in the following text generally refer to all spheres with a diameter of approximately 5μm, which can be cells of corresponding size, polystyrene microspheres, drug capsules, or chemical particles.

[0072] like Figure 2 As shown, a viscoelastic microfluidic chip is designed based on the analysis results of the viscoelastic microfluidic particle sorting mechanism modeling method. The viscoelastic microfluidic chip consists of an inlet 1, an inlet 2, a circular bifurcation branch 3, a straight channel section 4, an amplification section 5, an outlet 1 6 and an outlet 2 7. Figure 2 In, a p is the particle diameter.

[0073] Among them, the initial end of the circular forked branch 3 is connected to the end of the inlet 1, the end of the circular forked branch 3 is connected to the straight channel section 4, the inlet 2 2 is arranged inside the circular forked branch 3, the initial end of the enlarged section 5 is connected to the end of the straight channel section 4, the end of the enlarged section 5 is connected to the outlet 1 6 and the outlet 2 7, and the outlet 1 6 is provided with two, and is symmetrical about the outlet 2 7;

[0074] The channel height in the viscoelastic microfluidic chip is 50 μm, the width and length of the straight channel section 4 are 120 μm and 38 mm respectively, the total width of the enlarged section 5 is 1080 μm, the widths of the outlet 1 channel 6 and the outlet 2 channel 7 are 356 μm and 280 μm respectively, and the particle solution in the inlet 1 is introduced into the straight channel section 4 together with the sheath solution in the inlet 2 through the circular bifurcation branch 3 with a width of 120 μm;

[0075] The sheath liquid in the inlet 2 is prepared by dissolving a powder of a high molecular weight polymer polyethylene oxide in deionized water to obtain a PEO solution having a concentration of 0.03% to 0.15% w / v;

[0076] The flow rates of inlet 1 and inlet 2 are 1-3 mL / h and 9-20 mL / h respectively.

[0077] like Figure 3 – Figure 7 As shown, the microsphere solution will reach the beginning of the straight channel section 4 through the circular bifurcation branch 3. Since the sheath liquid is introduced from the inlet 2, the particles will be subject to inertial lift when moving in the straight channel section 4. Elastic force and the viscous drag F d ~a p The combined effect of F i and F e Small diameter particles play a leading role in F e The large diameter particles cannot completely penetrate the sample-sheath interface due to the repulsive effect, and eventually reach equilibrium near the interface. i F e repulsion, into the intermediate sheath fluid, while F e The direction of the small diameter particles and the large diameter particles will change from the original direction pointing to the channel wall to the middle of the channel, pushing the large diameter particles to migrate further to the center of the channel to reach the equilibrium position. Therefore, the small diameter particles and the large diameter particles will have a lateral position difference in the straight channel section 4, and the difference will be further increased when the particles enter the enlargement section 5, so that the small diameter particles will flow out from the outlet 1 6, and the large diameter particles will flow out from the outlet 2 7.

[0078] Figure 5 (a) shows the F curves of 5 μm diameter particles and 10 μm diameter particles. i 、Fe The distribution of the combined force along the width of the channel under the working condition is shown in Figure 1. According to the sample-sheath interface penetration criterion, the 5 μm diameter particle will be balanced near the sample-sheath interface in the straight channel section 4, and the 10 μm diameter particle will be balanced at the lateral position of y = 30.59, as shown in Figure 1. Figure 6 shown. Figure 5 (b) shows the F curves of particles with diameters of 10 μm and 15 μm. i 、F e The distribution of the combined force along the width of the channel under working condition 2. According to the sample-sheath interface penetration criterion, the 10 μm diameter particle will be balanced near the sample-sheath interface in the straight channel section 4, and the 15 μm diameter particle will be balanced at the lateral position of y = 29.83, as shown in Figure 6 shown. Figure 5 (c) shows the F curves of particles with diameters of 15 μm and 20 μm. i 、F e The distribution of the combined force along the width of the channel under working condition 3. According to the sample-sheath interface penetration criterion, the 15 μm diameter particle will be balanced near the sample-sheath interface in the straight channel section 4, and the 20 μm diameter particle will be balanced at the lateral position of y = 20.60, as shown in Figure 6 shown.

[0079] like Figure 7 As shown in Figure 5, the small diameter particle is still near the sample-sheath interface when it reaches the end of the straight channel section 4. However, the distance between the small diameter particle and the channel wall suddenly increases after entering the amplification section 5, making F i Rapidly decays and cannot balance the F generated by the sheath fluid side e , allowing small diameter particles to move closer to the channel wall. Increasing the distance between small diameter particles and the channel wall cannot completely eliminate F i Therefore, small diameter particles will only be affected by F e The small diameter particles cannot completely enter the sample liquid if they are pushed for a very short distance. Considering that the size of the small diameter particles is very small relative to the channel, the movement trajectory of the small diameter particles in the amplification section 5 can be approximated as the interface between the sample and the sheath liquid. ANSYS Fluent can be used to calculate the distribution of the sheath liquid and the sample liquid in the amplification section 5 under working conditions 1, 2, and 3. The results are shown in the figure. Figure 8 As shown in Figure 2, the large-diameter particles in the mixed solution have completely entered the sheath liquid in the straight channel section 4, and their lateral equilibrium position is determined by the F pointing to the channel wall. i With F pointing to the center of the channel e Decision. i ~w -7 and F e ~w -6There are different sensitivities to the channel width. After entering the amplification section 5, F i The larger diameter particles are still completely in the sheath fluid when entering the amplification section 5. e During the migration of large-diameter particles, it will always point to the center of the channel, inhibiting the lateral expansion movement of large-diameter particles to both sides of the channel, so that the large-diameter particles flow out from the outlet 2 7 along the equilibrium position in the straight channel section 4.

[0080] like Fig. 9 As shown in the figure, based on the straight channel section particle trajectory prediction model and the amplified section particle trajectory analysis method, the distances between the small-diameter particles and the large-diameter particles and the centerline of the amplified section can be calculated. The results show that the theoretical calculation results are basically consistent with the experimental calculation results.

[0081] like Fig.10 As shown in (a), particles with a diameter of 5 μm and particles with a diameter of 10 μm can be sorted in the enlargement section 5 under the working condition. Fig.10 As shown in (b), particles with a diameter of 10 μm and particles with a diameter of 15 μm can be sorted in the enlargement section 5 under the second working condition. Fig.10 As shown in (c), particles with a diameter of 15 μm and particles with a diameter of 20 μm can be sorted in the amplification section 5 under working condition three.

[0082] Therefore, the present invention adopts the above-mentioned viscoelastic microfluidic particle sorting mechanism modeling method, chip and application, which can provide a theoretical basis for the viscoelastic microfluidic optimization design and achieve flexible expansion and rapid iteration.

[0083] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A viscoelastic microfluidic particle sorting mechanism modeling method, characterized in that: The following steps are involved: S1. Utilize the total flow in the straight channel section Construct the velocity distribution function in the mid-plane in the height direction , through the sheath fluid flow and the total flow in the straight channel section Calculate the distance between the sheath fluid-sample interface and the centerline of the straight channel segment ; is the transverse coordinate value of the sheath fluid-sample interface in the straight channel section; S2, using cubic polynomial in transition interval The virtual PEO transition concentration is constructed inside, and then the distribution function of PEO concentration in the channel width direction is obtained. ; S3, based on particle transverse coordinates , particle diameter , particle velocity in the main flow direction , the velocity of the particle in the direction from the center of the channel to the wall , channel height , Channel Width , Sheath fluid flow , total flow in the straight channel section , fluid density 、PEO molecular weight , PEO concentration of sheath fluid , PEO concentration of the sample , Solvent viscosity of PEO solution , shear rate , Avogadro's constant , Boltzmann constant and temperature , construct the inertial lift force on the particle , elastic force , viscous drag and virtual mass force Expression of S4, obtained by calculation and The distribution along the width of the channel is used to construct the sample-sheath interface penetration criterion to determine whether the particles can completely penetrate the sample-sheath interface. The particle dynamics model is further constructed to calculate the movement trajectory of the particles after they completely enter the sheath liquid. S5. Use ANSYS Fluent to calculate the distribution of sheath fluid and sample in the amplification section; S6. Based on the lateral equilibrium position of the particle at the end of the straight channel section and the distribution of the sheath fluid and the sample in the amplification section, the movement trajectory of the particle in the amplification section is obtained.

2. A viscoelastic microfluidic particle sorting mechanism modeling method according to claim 1, characterized in that: In step S1, the velocity distribution function is a parabolic function, through the condition , The specific formula is as shown in formula (1): （1） in, is the flow velocity at the center of the straight channel section; is the maximum flow velocity in the straight channel section; is the average flow velocity in the straight channel section; is the lateral coordinate value in the straight channel section; Sheath fluid-sample interface position and sheath fluid flow rate and the total flow in the straight channel section The relationship between is represented by formula (2), and then solved by formula (3) , as follows: （2） （3） in, express yes function.

3. A viscoelastic microfluidic particle sorting mechanism modeling method according to claim 2, characterized in that: In step S2, the transition interval is , the distribution function of PEO concentration in the channel width direction It can be expressed by formula (4): （4） in, is the PEO concentration function; , , , is the coefficient.

4. A viscoelastic microfluidic particle sorting mechanism modeling method according to claim 3, characterized in that: In step S3, the inertial lift force on the particle , elastic force , viscous drag and virtual mass force The expression is as follows: （5） in, is the unit vector from the center of the channel to the wall; is the unit vector for the main flow direction; is the gradient operator.

5. A viscoelastic microfluidic particle sorting mechanism modeling method according to claim 4, characterized in that: In step S4, the sample-sheath interface penetration criterion is: and When the resultant force has a negative slope zero point in the transition interval, the particle cannot completely penetrate the sample-sheath liquid interface; otherwise, the particle will completely penetrate the sample-sheath liquid interface and enter the sheath liquid. The particle dynamics model is characterized by equation (6) and further organized into a differential equation form as shown in equation (7): （6） （7） in, is the coordinate value of the particle in the main flow direction; is the velocity vector of the particle; For time; , , , , , , , All are coefficients.

6. A viscoelastic microfluidic particle sorting mechanism modeling method according to claim 5, characterized in that: In step S5, the motion trajectory analysis method of the particle in the amplification section is as follows: when the particle is located at the sample-sheath fluid interface when reaching the end of the straight channel section, the particle will flow into outlet one along the sample-sheath fluid interface in the amplification section after entering the amplification section; when the particle is completely located in the sheath fluid when reaching the end of the straight channel section, the particle will flow into outlet two along the equilibrium trajectory in the straight channel section after entering the amplification section.

7. A viscoelastic microfluidic chip constructed according to the viscoelastic microfluidic particle sorting mechanism modeling method according to any one of claims 1 to 6, characterized in that: It includes entrance one, entrance two, circular bifurcated branch, straight channel section, enlarged section, exit one and exit two; The initial end of the circular forked branch is connected to the end of the inlet 1, the end of the circular forked branch is connected to the straight channel section, the inlet 2 is arranged inside the circular forked branch, the initial end of the enlarged section is connected to the end of the straight channel section, the end of the enlarged section is connected to the outlet 1 and the outlet 2, the outlet 1 is provided with two, and is symmetrical with respect to the outlet 2; The channel height in the viscoelastic microfluidic chip is 50 μm, the width and length of the straight channel section are 120 μm and 38 mm respectively, the total width of the amplified section is 1080 μm, the widths of the outlet 1 channel and the outlet 2 channel are 356 μm and 280 μm respectively, and the particle solution in the inlet 1 is introduced into the straight channel section together with the sheath solution in the inlet 2 through a circular bifurcation branch with a width of 120 μm; The sheath liquid in the second inlet is prepared by dissolving a powder of a high molecular weight polymer polyethylene oxide in deionized water to obtain a PEO stock solution with a concentration of 1% to 2% w / v, and then further diluted to a PEO working solution with a concentration of 0.03% to 0.15% w / v; The flow rates of the inlet 1 and the inlet 2 are 1-3 mL / h and 9-20 mL / h respectively.

8. A method for sorting particles with a diameter of 5 μm and particles with a diameter of 10 μm using a viscoelastic microfluidic chip as claimed in claim 7, characterized in that: The steps include: Step a1, dissolving 600 kDa PEO powder in deionized water, shaking for 28 to 36 hours, and preparing a PEO stock solution with a concentration of 1% to 2% w / v; Step b1, diluting a PEO stock solution with a concentration of 1% to 2% w / v into a working solution with a PEO concentration of 0.03% w / v as a sheath liquid; Step c1, using two syringe pumps to inject the particle solution and 0.03% w / v working solution into the viscoelastic microfluidic chip from inlet 1 and inlet 2, respectively, with flow rates of 2 mL / h and 20 mL / h at inlet 1 and inlet 2, respectively; Step d1, collecting 5 μm diameter particles and 10 μm diameter particles from outlet 1 and outlet 2 respectively.

9. A method for sorting particles with a diameter of 10 μm and particles with a diameter of 15 μm using a viscoelastic microfluidic chip as claimed in claim 7, characterized in that: The steps include: Step a2, dissolving 600 kDa PEO powder in deionized water, shaking for 28 to 36 hours, and preparing a PEO stock solution with a concentration of 1% to 2% w / v; Step b2, diluting a PEO stock solution with a concentration of 1% to 2% w / v into a working solution with a PEO concentration of 0.05% w / v as a sheath liquid; Step c2, using two syringe pumps to inject the particle solution and 0.05% w / v working solution into the viscoelastic microfluidic chip from inlet 1 and inlet 2, respectively, with flow rates of 1.5 mL / h and 9 mL / h at inlet 1 and inlet 2, respectively; Step d2, collecting particles with a diameter of 10 μm and particles with a diameter of 15 μm from outlet 1 and outlet 2 respectively.

10. A method for sorting particles with a diameter of 15 μm and particles with a diameter of 20 μm using a viscoelastic microfluidic chip as claimed in claim 7, characterized in that: The steps include: Step a3, dissolving 600 kDa PEO powder in deionized water, shaking for 28 to 36 hours, and preparing a PEO stock solution with a concentration of 1% to 2% w / v; Step b3, diluting a PEO stock solution with a concentration of 1% to 2% w / v into a working solution with a PEO concentration of 0.15% w / v as a sheath liquid; Step c3, adding a PEO stock solution with a concentration of 1% to 2% w / v to the particle solution to make the PEO concentration in the particle solution 0.05% w / v; Step d3, using two syringe pumps to inject the particle solution and 0.15% w / v working solution into the viscoelastic microfluidic chip from inlet 1 and inlet 2, respectively, with flow rates of 2.5 mL / h and 16 mL / h at inlet 1 and inlet 2, respectively; Step e3, collecting particles with a diameter of 15 μm and particles with a diameter of 20 μm from outlet 1 and outlet 2 respectively.

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