CN106311107B - A kind of method of centrifugal type microfludic chip and continuous synthesis Janus particles - Google Patents

Abstract

A centrifugal microfluidic chip and a method for continuously synthesizing Janus particles; the chip is composed of an upper substrate, an intermediate substrate and a lower substrate; the upper substrate is provided with an upper central hole, a circular liquid pool, and several upper layers The dispersed circular channel is connected with several first-level straight channels; the middle layer substrate is provided with a central circular hole in the middle layer; the lower layer substrate is provided with a central liquid pool, a lower dispersed circular channel, several second-level straight channels and several third-level Straight channel; method: 1) fix the centrifugal microfluidic chip on the suction cup of the homogenizer; 2) inject different test solutions into the central liquid pool and the ring-shaped liquid pool; turn on the homogenizer to rotate and centrifuge, and form a two-phase at the outlet of the channel liquid droplets; 3) the two-phase liquid droplets are thrown into the external annular liquid pool to form Janus particles; the method of the present invention ensures the continuous introduction of the test solution and realizes the continuous synthesis of two-phase particles; arrayed synthesis channels, high-speed rotation-driven liquids and continuous Synthesis, increase the synthesis rate of Janus particles.

Description

A centrifugal microfluidic chip and a method for continuously synthesizing Janus particles

technical field

The invention belongs to the field of microfluidic technology, in particular to a centrifugal microfluidic chip and a method for continuously synthesizing Janus particles.

Background technique

Janus is a god with two faces in ancient Roman mythology. In 1991, De Gennes used Janus to visualize asymmetric particles for the first time in his Nobel acceptance speech. Because different properties can be exhibited on the same particle, this Janus particle with asymmetric double-sided structure shows better performance than particles with a single property in some application fields, such as emulsion stability, optics, biosensing , drug delivery, and electronics have potential applications.

The synthesis method based on microfluidic technology has high mass and heat transfer efficiency, easy and accurate control of reaction conditions, fast mixing speed, and low reagent consumption. The use of microfluidic technology in the synthesis of Janus particles is beneficial to control the size and shape of the particles. The synthesized particles are highly uniform and the preparation process is simple [Xiao-Ting Sun, Mei Liu, Zhang-Run Xu. Talanta. 2014 , 121, 163-177.]. There are two common methods for preparing Janus particles based on microfluidic technology: one is to prepare particles using liquid droplets as a template, and the other is to directly solidify particles through a mask. For the former method, generally, microfluidic technology is used to form Janus droplets first, and then the droplets are solidified into Janus particles. Janus droplets can be formed on a chip by constructing a flow focusing structure [Zhi-Hong Nie, Li Wei, Min-Seok Seo, Sheng-Qing Xu, and Eugenia Kumacheva. J. Am. Chem. Sco. 2006, 128, 9408 -9412.], can also use porous capillary to form asymmetric droplets [Shin-Hyun Kim, Seog-Jin Jeon, WoongChan Jeong, Hyo Sung Park, and Seung-Man Yang. Adv. Mater. 2008, 20, 4129-4134 .], and asymmetric droplets can also be formed using a centrifugal microfluidic chip [Mei Liu, Xiao-Ting Sun, Chun-Guang Yang, and Zhang-Run Xu. J. Colloid Interface Sci. 2016, 466, 20-27. ]. Synthesis of particles with complex morphologies, such as heterogeneous asymmetric particles, using such methods requires channels with three-dimensional geometries and precise control of multiphase fluid flow [Andreas Walther, Axel H. E. Müller. Chem. Rev. 2013, 113, 5194-5261.]. For the latter method, lithographic printing technology and microfluidic multiphase laminar flow technology are often combined to form two-phase or more-phase laminar flow in the microchannel of the chip, and cover the mask with a set shape. On the channel, solidified into particles within the channel by photolithography, the shape of the particle depends on the shape of the mask [Ki-Wan Bong, Ki-Tae Bong, Daniel C. Pregibon, and Patrick S. Doyle. Angew. Chem. Int. Ed. 2010, 49, 87-90.].

Although the Janus particle synthesis method based on microfluidic technology can prepare particles with uniform size and controllable morphology, the preparation rate is generally very low, which cannot meet the needs of mass production. Centrifugal microfluidic technology uses simple equipment and can drive parallel array channels on a circular chip at the same time, which is very conducive to improving the preparation rate of particles. Maeda et al. fixed side-by-side capillaries in a centrifuge tube. A solution was passed into each capillary, and a crosslinking agent was added at the bottom of the centrifuge tube. The solution in the capillary was thrown out under the action of centrifugal force, and the crosslinking agent occurred rapidly Synthesis of Asymmetric Particles by Crosslinking and Curing [Kazuki Maeda, Hiroaki Onoe, Masahiro Takinoue, and Shoji Takeuchi. Adv.Mater. 2012, 24, 1340-1346.]. However, this method needs to inject the solution into the capillary in advance, and it is difficult to realize the continuous introduction of reagents and continuous synthesis. Liu et al. designed a centrifugal microfluidic chip and synthesized calcium alginate asymmetric particles using parallel channels on the chip [Mei Liu, Xiao-Ting Sun, Chun-Guang Yang, and Zhang-Run Xu. J. Colloid Interface Sci. 2016, 466, 20-27.], but still failed to achieve continuous injection and synthesis.

Despite the obvious potential of centrifugal microfluidics in the preparation of Janus particles, its advantages in this regard have not been effectively realized due to the difficulty of introducing different reaction solutions into the high-speed rotating chip. It is of great significance for the preparation of Janus particles to solve the bottleneck problem of centrifugal microfluidic technology in the introduction of various solutions, improve the yield of Janus particles synthesized by microfluidic chips, and maintain the high quality of Janus particles.

Contents of the invention

Aiming at the problems in the production rate of Janus particles synthesized by existing microfluidic methods, the present invention provides a centrifugal microfluidic chip and a method for continuously synthesizing Janus particles.

The centrifugal microfluidic chip of the present invention is composed of an upper substrate, a middle substrate and a lower substrate; the upper substrate, the middle substrate and the lower substrate are concentric circles with equal sizes;

For the upper substrate, an upper central circular hole is arranged at the center of the upper substrate; an annular liquid pool is arranged on the upper substrate, the annular liquid pool is concentric with the upper substrate, and the annular liquid pool penetrates On the upper substrate, several upper dispersed circular channels are arranged on the outside of the annular liquid pool, and several upper dispersed circular channels are evenly distributed on the upper substrate along the circumferential direction, and the upper dispersed circular channels and the annular liquid pool pass through The first-level straight channels are connected, and the extension line of the first-level straight channels passes through the center of the upper substrate;

In the intermediate layer substrate, an intermediate layer central circular hole is provided at the center of the intermediate layer substrate, and the intermediate layer substrate is provided with several intermediate layer dispersed circular holes, the number, position and size of the intermediate layer dispersed circular holes, The same as the upper scattered circular channel;

For the lower substrate, a central liquid pool is provided at the center of the lower substrate, and the lower substrate is provided with a number of lower dispersed circular channels, and the number, position and size of the lower dispersed circular channels are the same as those of the upper dispersed circular channels. The same; the circular channel at the center of the lower layer is connected to the edge through several secondary straight channels, and the connection point at the edge is the channel outlet. The number of secondary straight channels = the number of scattered circular channels in the lower layer; the lower layer is scattered The circular channel communicates with the adjacent secondary straight channel on the same side through a tertiary straight channel, and the tertiary channel is located outside the circle formed by the scattered circular channels in the lower layer.

The outer edge of the annular liquid pool of the upper substrate is provided with an annular baffle; The sheet is concentric with the central hole, and its diameter is smaller than the diameter of the annular liquid pool of the upper substrate.

The annular liquid pool of the upper substrate is an annular microchannel for liquid introduction; the upper primary straight channel is distributed in a divergent manner.

The diameter of the annular liquid pool is set as S, and the diameter of the upper substrate is set as D, then S: D=(1~100): (4~400); and the inner diameter and outer diameter difference of the upper layer annular liquid pool 1~2mm;

The upper layer substrate is provided with 1~200 upper layer dispersed circular channels, the diameter of the upper layer dispersed circular channel is X, then X: D=(0.5~10):(4~400); the upper layer The distance between the centers of the dispersed circular channels and the upper substrate is set as H, then, H: D=(1~200):(4~400);

The width of the first-level straight channel=the width of the second-level straight channel=the width of the third-level straight channel, all set as L, then L:D=(0.05～2):(4～400);

The distance between the connecting point of the secondary straight channel and the tertiary straight channel of the lower substrate is set as Y from the edge of the lower substrate, then Y: D=(0.5~20):(4~400);

The lower central liquid pool is circular, and the diameter of the upper central circular hole=the diameter of the middle central circular hole=the diameter of the lower central liquid pool;

The diameter of the upper substrate is 4 ~ 400 mm, the thickness of the upper substrate = the thickness of the lower substrate = 1 ~ 50 mm, the thickness of the middle substrate is 30 ~ 500 μm; the diameter of the upper central hole is 0.5 ~ 100 mm; the diameter of the upper circular liquid pool is 1-100 mm; the diameter of the upper dispersed circular channel is 0.5-10 mm, and the width of the upper-level straight channel=the width of the second-level straight channel=third-level The width of the straight channel = 0.05~2 mm; the length of the upper straight channel is 1~100 mm; the length of the lower secondary straight channel is 2~200 mm, the length of the lower third straight channel is 1~100 mm, The distance between the connecting point of the straight channel and the straight channel of the third level is 0.5-20 mm from the edge of the lower substrate.

The centrifugal microfluidic chip of the present invention is used in conjunction with a homogenizer. When in use, the centrifugal microfluidic chip is placed on a suction cup of the homogenizer, and the diameter of the suction cup is smaller than that of the centrifugal microfluidic chip.

The material of the centrifugal microfluidic chip of the present invention is polydimethylsiloxane.

For the centrifugal microfluidic chip of the present invention, when the material is polydimethylsiloxane, the preparation process of the upper chip and the lower chip is all in accordance with the standard manufacturing process of the SU-8 photoresist male mold, and a solid with SU-8 photoresist male mold with channel configuration; the preparation process of the middle layer chip is in accordance with the standard process of AZ photoresist male mold to complete the production of the microfluidic chip male mold.

The centrifugal microfluidic chip of the present invention, when the material is polydimethylsiloxane, the preparation process of the upper chip is as follows:

Pouring polydimethylsiloxane prepolymer on the SU-8 photoresist male mold with the upper channel configuration, after heating and polymerization, curing and molding, it is removed from the male mold; according to the circle on the chip Cut out an annular liquid pool that runs through it, and this liquid pool is used as the sample inlet of the first test solution, so that the disc-shaped upper substrate (without the upper central circular hole) is made like this;

The preparation process of the middle layer chip is as follows: pour polydimethylsiloxane prepolymer on the AZ positive mold, heat polymerization and solidify to shape, remove it from the positive mold, and use a puncher to pour polydimethylsiloxane prepolymer On the alkane layer, punch holes corresponding to the circle of the upper substrate;

The preparation process of the lower chip is as follows: pouring polydimethylsiloxane prepolymer on the SU-8 photoresist male mold with the lower channel configuration, after heating and polymerization, curing and molding, and taking it out from the male mold Next, make the lower substrate;

After modifying the surfaces of the upper substrate and the intermediate substrate to be sealed with a plasma cleaner, align and seal the side of the upper substrate with channels with the modified intermediate substrate to form a closed A microchannel network; punch a through hole in the center of the sealed two-layer substrate, the through hole is the center hole of the middle layer, as the entrance of another test solution; , and the middle layer of the closed microchannel network is aligned and sealed, and the small circular holes in the middle layer correspond to the scattered circular channels in the lower layer of the lower substrate, and are sealed together after surface modification with a plasma cleaner ; In this way, the required microfluidic chip is prepared.

When using a centrifugal microfluidic chip, according to the size of the central liquid pool and the annular liquid pool, a plastic tube with a relatively small diameter is bonded to the periphery of the sample port of the central liquid pool of the chip with silicone rubber, as the central liquid pool liquid guide groove, the diameter The relatively large plastic tube is glued on the periphery of the circular injection port with silicone rubber, and together with the plastic tube with a relatively small diameter, it forms a circular liquid pool guide groove; The test solution is introduced into two sets of channels respectively.

The method for continuously synthesizing Janus particles using a centrifugal microfluidic chip comprises the following steps:

step 1:

(1) Place the external annular liquid pool outside the suction cup of the homogenizer, and inject the test solution into the external annular liquid pool; fix the centrifugal microfluidic chip on the suction cup of the homogenizer;

(2) Adjust the centrifugal microfluidic chip so that the channel outlet leads to the liquid storage tank of the external annular liquid pool;

Step 2:

(1) Continuously inject the polymer test solution into the central liquid pool, and continuously inject another polymer test solution with different properties into the annular liquid pool; the first-level straight channel of the upper substrate and the second-level straight channel of the lower substrate and the three-level straight channel are filled with test solution;

(2) Turn on the homogenizer to rotate and centrifuge, and the test solution that continuously enters the channel of the chip will form two-phase droplets at the outlet of the channel under the action of centrifugal force;

(3) Adjust the speed at which the test solution enters the central liquid pool and the test liquid enters the circular liquid pool, so that both speeds are equal to the speed at which the test liquid is thrown out from the chip;

Step 3:

The two-phase liquid droplets are continuously thrown into the external annular liquid pool, and react with the test solution in the external annular liquid pool, and the two-phase liquid droplets are deposited to form Janus particles.

in:

In the step 1, the external annular liquid pool is placed concentrically with the centrifugal microfluidic chip.

In the described step 2 (1), by injecting the polymer test solution into the liquid guide tank of the central liquid pool, the central liquid pool is filled with the test solution; , so that the circular liquid pool is filled with the test solution;

In the step 2, the specific method for continuously injecting the test solution into the central liquid pool and the annular liquid pool is: respectively inject the test solution into the liquid pool through the syringe needle or catheter; the syringe needle or catheter is located above the liquid pool , the needle of the syringe is connected with the syringe through the catheter, and the syringe is fixed on the micro peristaltic pump or the syringe pump; the catheter is connected with the syringe, and the syringe is fixed on the micro peristaltic pump or the syringe pump.

In the step 2 (3), the three speeds are equal, so that the test solution keeps flowing continuously in the channel.

In the described step 2(2), the centrifugal speed is 500~2000 r/min.

In the step 2(3), the rate at which the test solution is thrown out from the chip is 3-6400 μL/min.

In the method of using the centrifugal microfluidic chip, the centrifugal force generated by the rotation drives the flow of the test solution on the chip, and the centrifugal speed is controlled at 500-2000 r/min to ensure that the test solution entering the liquid pool from above the liquid pool can flow into the In the microchannel, and thrown out from the channel; correspondingly, the test solution injection speed is controlled at 3~6400μL/min to ensure that the channel is filled with continuous flow of liquid.

In the using method of the centrifugal microfluidic chip, the polymer test solution injected into the central liquid pool is a test solution for nano-deposition reaction or cross-linking reaction; the polymer test solution with different properties injected into the annular liquid pool The liquid is a test solution of the same type as that injected into the central liquid pool, and the test liquid injected into the external annular liquid pool is a test liquid that triggers a polymer deposition reaction or a cross-linking reaction.

In the method of the present invention, the two test solutions are introduced from different liquid pools and different layers of the chip, and the two test solutions converge at the outlet end of the channel in the lower layer. One of the test solutions enters from the annular liquid pool through the channel on the upper substrate, flows through the small hole on the middle layer, and flows into the short channel on the lower substrate. Another test solution directly enters the divergent straight channel on the lower substrate from the central solution pool. The two test solutions meet at the outlet of the channel on the lower substrate.

In the method of the invention, the Janus droplets formed on the chip are solidified in an external annular liquid pool through a cross-linking reaction or a nano-deposition method to form Janus particles. Since the continuous introduction of the test solution is guaranteed, the continuous synthesis of Janus particles is realized. Arrayed synthesis channels, high-speed rotation-driven liquid and continuous synthesis improve the synthesis yield of Janus particles.

Description of drawings

Fig. 1 is a schematic diagram of a microfluidic chip according to an embodiment of the present invention;

Among them: a is the upper substrate, b is the middle substrate, c is the lower substrate, 1: circular liquid pool; 2: a straight channel on the upper substrate; 3: scattered circular holes in the middle layer; 4: Center liquid pool; 5: secondary straight channel on the lower substrate; 6: tertiary straight channel on the lower substrate.

The device schematic diagram of the continuous synthesis Janus particle of Fig. 2 embodiment of the present invention;

Among them: 7: syringe; 8: connecting tube; 9: two liquid guiding grooves on the chip; 10: external annular liquid pool; 11: microfluidic chip.

Fig. 3 Fluorescent microscopic image of Janus particles prepared in Example 1 of the present invention; wherein: the small dots in the box A are the parts of the synthetic particles emitting green fluorescence; the small dots in the box B are the synthetic particles emitting red fluorescence part.

Fig. 4 Fluorescent microscopic images of Janus particles prepared in Example 2 of the present invention; wherein: the small dots in box A are the part where the synthetic particles emit green fluorescence; the small dots in box B are the synthetic particles that emit red fluorescence part.

Detailed ways

Example 1

The centrifugal microfluidic chip of the present invention, as shown in Figure 1, consists of an upper substrate a, an intermediate substrate b and a lower substrate c; the upper substrate, the intermediate substrate and the lower substrate are concentric round and equal in size;

For the upper substrate, an upper central circular hole is arranged at the center of the upper substrate; an annular liquid pool 1 is arranged on the upper substrate, and the annular liquid pool 1 is concentric with the upper substrate a, and the annular liquid pool 1 is concentric with the upper substrate a. The pool 1 penetrates the upper substrate a, and the outer side of the annular liquid pool 1 is provided with several upper dispersed circular channels, and several upper dispersed circular channels are evenly distributed on the upper substrate along the circumferential direction. The annular liquid pools are connected through a first-level straight channel 2, and the extension line of the first-level straight channel 2 passes through the center of the upper substrate;

Described intermediate layer substrate b, the middle layer substrate b circle center is provided with 1 intermediate layer central circular hole, intermediate layer substrate is provided with several intermediate layer dispersed circular holes 3, the number of central layer dispersed circular holes 3, The position and size are the same as the upper scattered circular channel;

For the lower substrate c, a lower circular liquid pool 4 (central liquid pool) is arranged at the center of the lower substrate, and the lower substrate is provided with several lower dispersed circular channels, the number and position of the lower dispersed circular channels and size, the same as the upper scattered circular channel; the circular liquid pool 4 at the center of the lower floor communicates with the edge through several secondary straight channels 5, and the connection point at the edge is the channel outlet, and the secondary straight channel Quantity = the number of scattered circular channels in the lower layer; the dispersed circular channel in the lower layer communicates with the adjacent secondary straight channel 5 on the same side through the tertiary straight channel 6, and the tertiary channel 6 is formed by the dispersed circular channel in the lower layer outside of the circle.

The outer edge of the annular liquid pool 1 of the upper substrate is provided with an annular baffle; The baffle is concentric with the central hole, and its diameter is smaller than the diameter of the annular liquid pool of the upper substrate.

The annular liquid pool of the upper substrate is an annular microchannel for liquid introduction; the upper primary straight channel is distributed in a divergent manner.

The diameter of the annular liquid pool is 14 mm, and the diameter of the upper substrate is 70 mm, then S:D=14:70; and the difference between the inner diameter and outer diameter of the upper annular liquid pool is 1 mm;

The upper substrate is provided with 36 upper dispersed circular holes, the diameter of the upper dispersed circular hole is 0.9 mm; the center distance between the upper dispersed circular channel and the upper substrate is 28.45 mm;

The width of the first-level straight channel=the width of the second-level straight channel=the width of the third-level straight channel, both of which are 100 μm;

The distance between the connecting point of the secondary straight channel and the tertiary straight channel of the lower substrate is 1 mm from the edge of the lower substrate, then Y: D=1:70;

The diameter of the upper center hole = the diameter of the middle hole = the diameter of the lower circular channel;

The diameter of the upper substrate is 70mm, the thickness of the upper substrate=the thickness of the lower substrate=1mm, the thickness of the middle substrate is 100 μm; the diameter of the upper central hole is 2mm; the diameter of the upper annular liquid pool is 14mm ; The diameter of the upper scattered circular channel is 0.9mm, the width of the first-level straight channel in the upper strata=the width of the second-level straight channel=the width of the third-level straight channel=100 μm; the length of the upper-level straight channel is 27mm; The length of the lower secondary straight channel is 34 mm, the length of the lower tertiary straight channel is 7 mm, and the distance between the connecting point of the secondary straight channel and the tertiary straight channel is 1 mm from the edge of the lower substrate.

The material of the centrifugal microfluidic chip in this embodiment is polydimethylsiloxane.

In the centrifugal microfluidic chip of the present invention, the preparation process of the upper layer chip is all in accordance with the standard manufacturing process of the SU-8 photoresist male mold to obtain a firm SU-8 photoresist male mold with a channel configuration. The manufacturing process It is: according to the standard manufacturing process of the SU-8 photoresist positive mold, a microchannel network positive mold is formed on the silicon wafer, the height of the positive mold is about 100 μm, and then polydimethylsiloxane prepolymerized After heating and polymerizing, solidified and formed, it was removed from the male mold, and in the center of the substrate, a drill with a diameter of 13 mm and a diameter of 14 mm was used to make a penetrating polydimethylsiloxane The annular liquid pool of layer, this liquid pool is used as the sample inlet of a kind of test solution, thus just makes the disc-shaped upper layer substrate;

The preparation process of the middle layer chip is to complete the production of the microfluidic chip positive mold according to the standard process of the AZ photoresist positive mold. The ends of the channels on the chip correspond one by one; pour a layer of polydimethylsiloxane prepolymer on the glass male mold, control its thickness to 100 μm, heat and cure it, and remove it from the male mold; use a puncher Holes were punched at the circles on the polydimethylsiloxane layer with a diameter of 0.9 mm. Align and seal the side of the upper substrate with the microchannels to the manufactured intermediate substrate to form a closed microchannel network. Drill a through hole with a diameter of 2 mm in the center of the sealed two-layer substrate as the entrance of another test solution;

The preparation process of the lower chip is all in accordance with the standard manufacturing process of the SU-8 photoresist male mold, and a solid SU-8 photoresist male mold with a channel configuration is obtained. The manufacturing process is: Forming microchannels on the silicon wafer The male mold of the network, the height of the male mold is about 100 μm, and then polydimethylsiloxane prepolymer is poured on it, and after heating and polymerization, it is cured and formed, and it is removed from the male mold to obtain the lower layer Substrate;

Align and seal the side of the lower substrate with channels and the middle side of the substrate where the upper layer and the middle layer are sealed together, and the small round holes correspond to the starting ends of the short channels on the lower substrate; use a plasma cleaner After surface modification, they are sealed together, so that the desired microfluidic chip is produced.

Take a plastic tube with a diameter of 8 mm and a height of 15 mm, and glue it to the center of the chip with silicone rubber as the central liquid pool; take a plastic tube with a diameter of 16 mm and a height of 15 mm, and glue it to the center of the chip with silicone rubber. Adhere to the periphery of the central liquid pool to form an annular liquid pool; in this way, the liquid guide groove of the annular liquid pool is made.

The external annular liquid tank used to store poor solvents is assembled from three layers of glass with different thicknesses. Use a compass glass knife to cut two circular glasses with a diameter of 73 mm from two pieces of glass with a thickness of 1 mm. , cut out a circular glass with a diameter of 93 mm on a piece of glass with a thickness of 5 mm, stack three pieces of glass with a round hole, the thick glass is sandwiched between two thin glasses, aligned concentrically, The three layers of glass are bonded together with light-curing glass glue to form a glass liquid pool with one side open and three sides closed.

Using a centrifugal microfluidic chip to continuously synthesize Janus particles, the device for continuously synthesizing Janus particles containing a centrifugal microfluidic chip is shown in Figure 2, specifically as follows:

step 1:

(1) Place the external annular liquid pool outside the suction cup of the homogenizer, place the external annular liquid pool concentrically with the centrifugal microfluidic chip, and inject the poor solvent of PLGA into the external annular liquid pool; place the centrifugal microfluidic chip Fixed on the suction cup of the homogenizer;

(2) Adjust the centrifugal microfluidic chip so that the channel outlet leads to the liquid storage tank of the external annular liquid pool;

Step 2:

(1) Continuously inject rhodamine B-labeled 10 mg/mL PLGA acetonitrile solution into the central liquid pool through syringe 7 and connecting tube 8, and continuously inject fluorescent yellow-labeled 10 mg/mL PLGA acetonitrile solution into the annular liquid pool; The first-level straight channel of the upper substrate, the second-level straight channel and the third-level straight channel of the lower substrate are filled with test solution;

(2) Turn on the homogenizer to rotate and centrifuge, and the test solution that continuously enters the channel of the chip will form two-phase droplets at the outlet of the channel under the action of centrifugal force; wherein, the centrifugal rotation speed of the homogenizer is 1000 r/min;

(3) Adjust the rate at which the test solution enters the central liquid pool and the test liquid enters the annular liquid pool, so that both speeds are equal to the rate at which the test solution is thrown out from the chip; The rate is 400μL/min,

Step 3:

The two-phase liquid droplets are continuously thrown into the external annular liquid pool, and react with the aqueous solution in the external annular liquid pool, and the two-phase liquid droplets are deposited to form Janus particles.

The fluorescence microscopic image of the Janus particles prepared in this example is shown in FIG. 3 . Under different excitation wavelengths, it can be observed that each particle has two different parts, red and green.

Example 2

The structure and material of the centrifugal microfluidic chip used in this example are the same as in Example 1, but the size is different:

In this implementation, the diameter of the annular liquid pool is 14mm, and the diameter of the upper substrate is 70mm, then S:D=14:70; and the difference between the inner diameter and outer diameter of the upper annular liquid pool is 1mm;

In this implementation, the upper substrate is provided with 36 upper dispersed circular holes, and the diameter of the upper dispersed circular hole is 0.9 mm; the center distance between the upper dispersed circular channel and the upper substrate is 28.45 mm;

In this implementation, the width of the first-level straight channel=the width of the second-level straight channel=the width of the third-level straight channel, both of which are 200 μm;

In this implementation, the distance between the connecting point of the secondary straight channel and the tertiary straight channel of the lower substrate is 1 mm from the edge of the lower substrate, then Y: D=1:70;

In this implementation, the diameter of the central circular hole in the upper layer=the diameter of the central circular hole in the middle layer=the diameter of the circular channel in the lower layer;

In this implementation, the diameter of the upper substrate is 70 mm, the thickness of the upper substrate = the thickness of the lower substrate = 2 mm, the thickness of the middle substrate is 200 μm; the diameter of the upper central hole is 2 mm; the upper circular liquid pool The diameter is 14 mm; the diameter of the upper scattered circular channel is 0.9 mm, the width of the upper straight channel = the width of the second straight channel = the width of the third straight channel = 200 μm; the upper straight channel The length is 27 mm; the length of the lower secondary straight channel is 34 mm, the length of the lower third straight channel is 7 mm, and the distance between the connecting point of the second straight channel and the third straight channel is 1 mm from the edge of the lower substrate.

Using a centrifugal microfluidic chip to continuously synthesize Janus particles, the device for continuously synthesizing Janus particles containing a centrifugal microfluidic chip is shown in Figure 2, specifically as follows:

step 1:

(1) Place the external annular liquid pool outside the suction cup of the homogenizer, place the external annular liquid pool concentrically with the centrifugal microfluidic chip, and inject the poor solvent of PLGA into the external annular liquid pool; place the centrifugal microfluidic chip Fixed on the suction cup of the homogenizer;

(2) Adjust the centrifugal microfluidic chip so that the channel outlet leads to the liquid storage tank of the external annular liquid pool;

Step 2:

(1) Continuously inject rhodamine B-labeled 10 mg/mL PLGA acetonitrile solution into the central liquid pool through syringe 7 and connecting tube 8, and continuously inject fluorescent yellow-labeled 10 mg/mL PLGA acetonitrile solution into the circular annular liquid pool; The first-level straight channel of the upper substrate, the second-level straight channel and the third-level straight channel of the lower substrate are filled with test solution;

(2) Turn on the homogenizer to rotate and centrifuge, and the test solution that continuously enters the channel of the chip will form two-phase droplets at the outlet of the channel under the action of centrifugal force; wherein, the centrifugal rotation speed of the homogenizer is 1000 r/min;

(3) Adjust the rate at which the test solution enters the central liquid pool and the test liquid enters the annular liquid pool, so that both speeds are equal to the rate at which the test solution is thrown out from the chip; The rate is 800μL/min,

Step 3:

The two-phase liquid droplets are continuously thrown into the external annular liquid pool, and react with the aqueous solution in the external annular liquid pool, and the two-phase liquid droplets are deposited to form Janus particles.

The fluorescence microscopic image of the Janus particles prepared in this example is shown in FIG. 4 . The prepared particles were observed to have two different parts, red and green, under different excitation wavelengths.

Claims (9)

1. a kind of centrifugal type microfludic chip, which is characterized in that the chip is by upper substrate, middle layer substrate and underlying basal Composition；Upper substrate, middle layer substrate and the underlying basal is concentric circles, and equal in magnitude；

The upper substrate, upper substrate circle centre position are provided with 1 upper layer center hole；Circular ring shape is provided on upper substrate Liquid pool, circular ring shape liquid pool and upper substrate are concentric, and circular ring shape liquid pool penetrates upper substrate, is provided on the outside of circular ring shape liquid pool several A upper layer disperses circular channel, and several upper layers dispersion circular channel is evenly distributed and is arranged on upper substrate, upper layer point It dissipates and is connected by level-one straight channel between circular channel and circular ring shape liquid pool, the extended line of level-one straight channel passes through upper substrate The center of circle；

The middle layer substrate, middle layer substrate circle centre position are provided with 1 middle tier central circular hole, and middle layer substrate is provided with Several middle layers disperse circular hole, and middle layer disperses quantity, position and the size of circular hole, identical as upper layer dispersion circular channel；

The underlying basal, underlying basal circle centre position are provided with 1 center liquid pool, and underlying basal is provided with several lower layer's dispersions Circular channel, lower layer disperse quantity, position and the size of circular channel, identical as upper layer dispersion circular channel；Lower layer's circle centre position Center liquid pool and edge between be connected by several two level straight channels, the connectivity points of edge are channel outlet, two The quantity of the quantity of grade straight channel=lower layer's dispersion circular channel；Lower layer disperses the circular channel two level straight channel adjacent with homonymy Between be connected by three-level straight channel, and three-level channel be located at lower layer dispersion circular channel be formed by round outside.

2. centrifugal type microfludic chip according to claim 1, which is characterized in that the circular ring shape liquid of the upper substrate It is provided with circular ring shape catch on the outside of the edge in pond；It is provided with circular ring shape catch on the outside of the center hole of the upper substrate, in The circular ring shape catch and center hole of heart circular hole are concentric, and its diameter is less than the diameter of the circular ring shape liquid pool of upper substrate.

3. centrifugal type microfludic chip according to claim 1, which is characterized in that the centrifugal type microfludic chip Material is dimethyl silicone polymer.

4. the production method of the centrifugal type microfludic chip described in claim 3, which is characterized in that the centrifugal type microfludic The preparation process of chip, upper substrate and underlying basal is to obtain heavily fortified point according to the standard manufacture craft of SU-8 photoresist formpistons Solid the SU-8 photoresist formpistons with channel configurations；The preparation process of middle layer substrate is the standard according to AZ photoresist formpistons Technique is completed micro-fluidic chip formpiston and is made；

It will be after the upper substrate of sealing-in and the surface of middle layer substrate be modified, by upper substrate with plasma cleaner One side with channel is aligned with modified middle layer substrate to seal, and forms closed microchannel network；It is sealing A through-hole is made a call in the center of the two layers of substrate connected, which is middle tier central circular hole, and alternatively test solution enters Mouthful；The one side that underlying basal is had to straight channel, the laminated alignment in centre with closed microchannel network, middle layer disperse circular hole It is corresponded with lower layer's dispersion circular channel of underlying basal, seals, obtain required through plasma cleaner is modified Micro-fluidic chip.

5. the production method of centrifugal type microfludic chip according to claim 4, which is characterized in that the upper substrate Preparation process be：In the SU-8 photoresist formpiston upper polydimethylsiloxane prepolymer objects with upper channel configuration, warp Heating polymerization process is crossed, curing molding removes it from formpiston；One, which is cut out, according to the circular channel on substrate runs through it In circular ring shape liquid pool, injection port of this liquid pool as the first test solution, in this way be made discoidal upper substrate；

The preparation process of the middle layer substrate is：In AZ formpiston upper polydimethylsiloxane prepolymer objects, by heating Polymerizing curable is molded, it is removed from formpiston, with card punch on dimethyl silicone polymer layer, the circle of corresponding upper substrate Place's punching；

The preparation process of the underlying basal is：In the poly- diformazan of SU-8 photoresist formpiston uppers with lower channel configuration Radical siloxane prepolymer, by heating polymerization process, curing molding removes it from formpiston, and underlying basal is made.

6. the method for continuously synthesizing Janus particles using centrifugal type microfludic chip described in claim 1, which is characterized in that Include the following steps：

Step 1：

(1) external ring-shaped liquid pool is placed on outside sol evenning machine sucker, and test solution is injected into external ring-shaped pool；Centrifugation is declined Fluidic chip is fixed on sol evenning machine sucker；

(2) centrifugal type microfludic chip is adjusted, its channel outlet is made to lead to the reservoir of external ring-shaped liquid pool；

Step 2：

(1) continue, to center liquid pool injection of polymer test solution, to continue to inject into circular ring shape liquid pool another of different nature poly- Close object test solution；In the level-one straight channel of upper substrate, in the two level straight channel and three-level straight channel of underlying basal, it is each filled with examination Liquid；

(2) sol evenning machine rotating centrifugal is opened successively under the action of the centrifugal force into the test solution in chip channel to go out in channel Two-phase drop is formed at mouthful；

(3) adjustment test solution enters center liquid pool and test solution enters the rate of circular ring shape liquid pool, the rate both made with test solution from The rate thrown away on chip is equal；

Step 3：

Two-phase drop is continuously dumped into external ring-shaped liquid pool, and is reacted with the test solution in external ring-shaped liquid pool, two-phase Droplet deposition out forms Janus particles.

7. the method for continuous synthesis Janus particles according to claim 6, which is characterized in that in the step 2, continue Into center liquid pool and circular ring shape liquid pool, the specific method of injection test solution is respectively：Respectively by syringe needle or conduit to liquid Test solution is injected in pond；The syringe needle or conduit is located above liquid pool, and syringe needle is connected by conduit and syringe It connects, syringe is fixed on micro peristaltic pump or syringe pump；Or the conduit is connect with syringe, syringe is fixed on micro On peristaltic pump or syringe pump.

8. the method for continuous synthesis Janus particles according to claim 6, which is characterized in that in the step 2 (2), Centrifugal speed is 500~2000r/min.

9. the method for continuous synthesis Janus particles according to claim 6, which is characterized in that in the step 2 (3), The rate that test solution is thrown away from chip is 3~6400 μ L/min.