CN112034029B - Microfluid dielectrophoresis separation device and manufacturing method thereof - Google Patents
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Abstract
The invention relates to a microfluid dielectrophoresis separation device and a manufacturing method thereof, wherein the microfluid dielectrophoresis separation device comprises: a microfluidic channel; the electrode, with the microfluid passageway corresponds the setting, the electrode includes first electrode region and the second electrode region that sets gradually along the flow direction of fluid, first electrode region is close to microfluid passageway's entry is located the first telluric electricity field orientation of the regional both sides of first electrode one side in the microfluid passageway is arc electrode array, is located the second central electrode at the regional middle part of second electrode is lemon shape electrode array. By designing the structures of the electrode and the microfluidic channel, the efficient separation of particles can be realized through the mutual assistance of the electrode and the microfluidic channel without pre-aggregation operation; meanwhile, the integration performance of the device can be obviously improved, the difficulty of mutual integration or matching with external equipment is reduced, and the applicability of the device is improved.
Description
Technical Field
The invention relates to the technical field of particle separation, in particular to a microfluid dielectrophoresis separation device and a manufacturing method thereof.
Background
Dielectrophoresis (DEP) separation techniques have been widely used in the fields of particle sorting, biological cell sorting, and the like. Separation technologies based on microfluidic platforms allow for a reduction in the size of the separated sample while minimizing sample consumption and provide the possibility of active real-time control of the separation process. Therefore, the separation technology based on microfluidics has been rapidly developed in recent years, and is widely applied to the fields of biology and medical treatment. In order to achieve a good separation effect, the separation technology based on a microfluidic platform and the dielectrophoresis separation technology are combined in the prior art. The realization mode of the dielectrophoresis separation technology based on the microfluidic chip is as follows: in a microfluidic system, particles or cells to be separated are generally dispersed in a fluid, the fluid is introduced from an inlet of a chip, and after separation in the microfluidic chip is completed, the fluid respectively flows out through a plurality of outlets, and the purity of the particles flowing out from different outlets after separation is changed. The dielectrophoretic separation technique requires the implementation of an electric field applied to the microfluidic chip. The external electric field usually requires that conductive materials such as Indium Tin Oxide (ITO), gold or carbon electrodes are placed in the channels of the microfluidic chip as electrodes to provide the electric field. The micro-nano particles dispersed in the fluid are acted by dielectrophoresis force under the action of the electric field and move along the direction of high field intensity (positive dielectrophoresis force) or the direction of low field intensity (negative dielectrophoresis force). Because different particles have different parameters such as particle size, conductivity, dielectric constant, particle shape and the like, and are subjected to different dielectrophoresis forces and different fluid resistances, different particles are dragged to different positions in the channel to complete separation. In the prior art, before particle separation, a pre-aggregation operation is usually required, and the particles to be separated are extruded into narrow particle lines just after being introduced into a channel by the pre-aggregation, so that the particles to be separated can be separated from the particle lines after being slightly stressed and reach other positions of the channel to realize separation. Common pre-assembly techniques include sheath flow pre-assembly, dielectrophoresis pre-assembly, electroosmotic flow pre-assembly, and the like. These techniques may increase the complexity of chip integration or have limitations on the types of particles to be separated, and good separation cannot be achieved.
In the dielectrophoresis separation technology based on the microfluidic chip, the design of the electrode is the key of the design of the microfluidic chip. The existing electrode is generally a planar interdigital electrode, and the electrode design is usually applied to a discontinuous separation microfluidic chip. The electrode collects particles subject to positive dielectrophoresis forces at the electrode tip and particles subject to negative dielectrophoresis forces at the electrode recess. Because the electric field intensity near the surface of the electrode tip is high and the gradient value of the electric field intensity is large, particles gathered at the electrode tip can overcome the dragging force of the fluid and cannot be taken away by the fluid. Because the electric field intensity at the electrode groove is low, the field intensity change rate is low, and the negative dielectrophoresis force borne by nearby particles is weak. Thus, particles that are subjected to negative dielectrophoretic forces or are not subjected to forces will be carried away by the fluid drag forces. When the ideal number of particles are gathered at the tip of the interdigital electrode, pure fluid is introduced, and the power supply is cut off, the particles near the tip of the electrode can be taken away and dispersed in the introduced pure fluid, so that the separation purpose is achieved. However, the electrode design cannot complete continuous sorting, two fluids need to be sequentially introduced into the microfluidic system in sequence, and the operation is complex.
The other type of electrodes are rectangular array electrodes, the rectangular array being at an acute angle to the direction of the fluid. The microfluidic system comprises two inlets for introducing a sample to be separated and a buffer solution respectively. When the buffer solution (sheath flow) and the sample liquid are simultaneously introduced, all kinds of particles dispersed in the sample liquid are gathered in a narrow range, so that the particles are limited in a narrow and long area to continue moving along the flow field, and the pre-gathering operation is completed. Further, the particles pass through the area where the electrodes are located and slide along the edges of the electrodes under the action of dielectrophoretic force. Because the electrodes form a certain angle with the flow field direction, the particles which are acted by positive dielectrophoresis force can be deviated in the direction vertical to the flow field, thereby being separated from the particles which are not acted by or only acted by weak dielectrophoresis force. Although the electrode can realize effective separation of particles, the electrode needs to be subjected to pre-aggregation operation, and has the disadvantages of complex operation and high cost.
Disclosure of Invention
In view of the above problems in the prior art, an object of the present invention is to provide a microfluid dielectrophoresis separation device and a method for manufacturing the same, which can achieve high-efficiency separation without a pre-aggregation operation during particle separation.
In order to achieve the above object, an embodiment of the present invention provides a microfluidic dielectrophoresis separation device, including:
a microfluidic channel for flowing a fluid containing particles therethrough;
the electrode, with the microfluid passageway corresponds the setting, the electrode includes first electrode region and the second electrode region that sets gradually along the flow direction of fluid, first electrode region is close to microfluid passageway's entry is located the first telluric electricity field orientation of the regional both sides of first electrode one side in the microfluid passageway is arc electrode array, is located the second central electrode at the regional middle part of second electrode is lemon shape electrode array.
In some embodiments, the ratio of the length of the first electrode region to the second electrode region is 0.1-1.
In some embodiments, the first central electrode located in the middle of the first electrode region is a planar electrode, and the contour of the first central electrode is a smooth straight line; the second grounding electrodes positioned on two sides of the second electrode area are planar electrodes, and the outline of each second grounding electrode is a smooth straight line.
In some embodiments, the microfluidic channel is curvilinear in shape, the microfluidic channel comprises a bend and no bend, the width of the no bend is 8h-15h, wherein h represents the height of the microfluidic channel, and the height of the microfluidic channel is 10 μm-80 μm.
In some embodiments, the arc electrode array of the first ground electrode includes a plurality of arc portions, the plurality of arc portions are arranged at intervals in an array along the length direction of the microfluidic channel, the arc portions are in an arc structure, the radius of each arc portion is 0.3h-h, the distance between adjacent arc portions is 0.6h-2h, the distance between the first ground electrode and the first central electrode is 0.6h-1.2h, and the included angle between the first ground electrode and the horizontal direction is 0.5 ° to 5 °.
In some embodiments, the lemon-shaped electrode array comprises a plurality of lemon-shaped electrode units, adjacent lemon-shaped electrode units are connected and conducted with each other, and each lemon-shaped electrode unit is provided with an oval hole.
In some embodiments, the size of the long axis of the lemon-shaped electrode unit is 8h-15h, and the size of the short axis of the lemon-shaped electrode unit is 4h-8h; the distance between the center of the second central electrode and the second grounding electrode is 0.8h-1.2h; in the lemon-shaped electrode array, the distance between the vertexes of two adjacent lemon-shaped electrode units is 4-8 h; in the lemon-shaped electrode unit, an included angle between the long axis of the elliptical hole and the horizontal direction is 10-40 degrees, the long axis of the elliptical hole is 5-7 h, the short axis of the elliptical hole is 2.5-3.5 h, and h represents the height of the microfluidic channel.
In some embodiments, the lemon-shaped electrode array comprises a first array segment and a second array segment disposed along a direction of flow of the fluid, the plurality of elliptical apertures of the first array segment being inclined upwardly and the plurality of elliptical apertures of the second array segment being inclined downwardly.
The embodiment of the invention also provides a manufacturing method of the microfluid dielectrophoresis separation device, which comprises the following steps:
photoetching a negative photoresist pattern on a substrate, and processing a micro-fluid channel by pouring;
photoetching an electrode pattern on a glass substrate by using positive photoresist, and forming an electrode by using an etching process;
and aligning and bonding the microfluidic channel and the glass substrate etched with the electrode.
Furthermore, the microfluidic channel is made of polydimethylsiloxane, and the electrode is made of ITO conductive material.
Compared with the prior art, the microfluid dielectrophoresis separation device provided by the embodiment of the invention can realize the high-efficiency separation of particles by designing the structures of the electrode and the microfluid channel, without pre-aggregation operation and through the mutual assistance of the electrode and the microfluid channel; meanwhile, the integration performance of the device can be obviously improved, the difficulty of mutual integration or matching with external equipment is reduced, and the applicability of the device is improved.
Drawings
In the drawings, which are not necessarily drawn to scale, like reference numerals may describe similar components in different views. Like reference numerals having letter suffixes or different letter suffixes may represent different instances of similar components. The drawings illustrate various embodiments generally, by way of example and not by way of limitation, and together with the description and claims serve to explain the embodiments of the invention. The same reference numbers will be used throughout the drawings to refer to the same or like parts, where appropriate. Such embodiments are illustrative, and are not intended to be exhaustive or exclusive embodiments of the present apparatus or method.
FIG. 1 is a schematic structural diagram of a microfluidic dielectrophoresis separation device according to an embodiment of the present invention;
FIG. 2 is a partial top view of a microfluidic dielectrophoretic separation device according to an embodiment of the invention;
FIG. 3 is an enlarged schematic view of a portion of block A in FIG. 2;
FIG. 4 is an enlarged schematic view of the second electrode region of FIG. 2;
FIG. 5 is a schematic diagram of the separation of yeast cells from PS particles using a microfluidic dielectrophoresis separation device according to an embodiment of the invention;
FIG. 6 (a) is a schematic diagram of the separation of the red blood cells and the tumor cells of the microfluidic dielectrophoresis separation device according to the embodiment of the invention;
fig. 6 (b) is another schematic diagram of the separation of the red blood cells and the tumor cells of the microfluidic dielectrophoresis separation device according to the embodiment of the invention.
Reference numerals are as follows:
1-microfluidic channel, 11-arc structure, 101-inlet, 102-outlet, 1021-first outlet, 1022-second outlet, 1023-third outlet;
2-an electrode; 21-first electrode region, 211-first ground electrode, 2111-arc, 2112-straight, 212-first center electrode; 22-second electrode area, 221-second ground electrode, 222-second center electrode, 2221-lemon-shaped electrode unit, 2222-elliptical hole;
3-glass substrate.
Detailed Description
The following detailed description of specific embodiments of the present invention is provided in connection with the accompanying drawings, which are not intended to limit the invention.
It will be understood that various modifications may be made to the embodiments disclosed herein. Accordingly, the foregoing description should not be construed as limiting, but merely as exemplifications of embodiments. Other modifications will occur to those skilled in the art which are within the scope and spirit of the invention.
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with a general description of the invention given above, and the detailed description of the embodiments given below, serve to explain the principles of the invention.
These and other features of the invention will become apparent from the following description of preferred forms of embodiment, given as non-limiting examples, with reference to the accompanying drawings.
It should also be understood that, although the invention has been described with reference to some specific examples, a person of skill in the art shall certainly be able to achieve many other equivalent forms of the invention, having the characteristics as set forth in the claims and hence all coming within the field of protection defined thereby.
The above and other aspects, features and advantages of the present invention will become more apparent in view of the following detailed description when taken in conjunction with the accompanying drawings.
Specific embodiments of the present invention are described hereinafter with reference to the accompanying drawings; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which can be embodied in various forms. Well-known and/or repeated functions and constructions are not described in detail to avoid obscuring the invention in unnecessary or unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed structure.
Fig. 1 to 4 are schematic structural views of a microfluidic dielectrophoresis separation device according to an embodiment of the present invention. As shown in fig. 1 to 4, an embodiment of the present invention provides a microfluidic dielectrophoresis separation device, including:
a microfluidic channel 1 for flowing a fluid containing particles therethrough;
the electrode 2 is arranged in the microfluidic channel 1, the electrode 2 comprises a first electrode area 21 and a second electrode area 22 which are sequentially arranged along the flow direction of the fluid, the first electrode area 21 is close to the inlet 101 of the microfluidic channel 1, one side of the first grounding electrode 211, which is positioned at two sides of the first electrode area 21 and faces the microfluidic channel 2, is an arc-shaped electrode array, and the second central electrode 222, which is positioned at the middle part of the second electrode area 22, is a lemon-shaped electrode array.
The microfluidic channel 1 is used for providing a flow field to enable a fluid containing particles to flow through, the electrode 2 is used for generating a dielectrophoresis force (providing an electric field) to drive the particles in the fluid in the microfluidic channel 1 to move, the fluid containing the particles enters the microfluidic channel 1 from an inlet, the particles can be guided to a preset position under the synergistic action of the flow field and the electric field, particle separation is achieved, and the separated particles flow out from the outlet 102.
The first electrode region 21 includes three electrodes, which are two first ground electrodes 211 disposed at both sides of the first electrode region 21 and a first center electrode 212 disposed at a middle position of the first electrode region 21, and the two first ground electrodes 211 and the first center electrode 212 function; the second electrode region 22 also includes three electrodes, i.e., two second ground electrodes 221 disposed on both sides of the second electrode region 22 and a second center electrode 222 disposed at a central position of the second electrode region 22, and the two second ground electrodes 221 and the second center electrode 222 function. The three electrodes of the second electrode region 22 are respectively connected to the three electrodes of the first electrode region 21 to form an electric field.
The two side and middle positions are relative positions between the center electrode and the ground electrode in the electrode region, and are not limited to specific installation positions. For example, in the present embodiment, as shown in fig. 2 and 3, a first center electrode 212 is provided between the two first ground electrodes 211, and the first center electrode 212 is provided corresponding to the first ground electrode 211 near the edge of the first electrode region 21.
According to the microfluid dielectrophoresis separation device provided by the embodiment of the invention, the electrode 2 is divided into the first electrode area 21 and the second electrode area 22 along the flowing direction of the fluid containing particles, the first electrode area 21 is a guide area, one side of the first grounding electrode 211 positioned at two sides of the first electrode area 21, which faces the inside of the microfluid channel 2, is an arc-shaped electrode array, so that the particles in the fluid can be guided, and part of the particles are prevented from leaning against the edge of the channel; the second electrode region 22 is a separation region, and the second central electrode 222 located in the middle of the second electrode region 22 is a lemon-shaped electrode array, which can provide a continuous electric field gradient distribution (along the flow direction of the fluid) for the particles, so as to generate a lateral dielectrophoresis separation effect (LDEP), so that the particles move along the direction perpendicular to the flow direction of the fluid, and realize efficient separation. By designing the electrodes 2, the effect of dielectrophoresis can be improved, enhancing the efficiency of particle separation in the microfluidic channel 1.
Specifically, as shown in fig. 2 and 3, after particles enter the first electrode region 21 from the inlet 101, the particles, most of which are subjected to a negative dielectrophoretic force (nDEP), are directed to a region away from the channel sidewall, thereby significantly reducing the number of particles near the channel sidewall. In addition, since the flow velocity near the channel wall surface is low, the particles are discharged near the wall surface, so that the particles can be positioned at a high flow velocity position (the middle portion of the microfluidic channel 1) and smoothly flow toward the second electrode region 22, and the high-efficiency separation can be accomplished.
As shown in fig. 3, the first center electrode 212 located in the middle of the first electrode region 21 is a planar electrode, the contour of the first center electrode 212 is a smooth straight line, and the field intensity near the arc-shaped structure of the first ground electrode 211 is higher than the field intensity near the first center electrode 212. Thus, particles subjected to a negative dielectrophoretic force will move from the first ground electrode 211 on both sides towards the first central electrode 212 to direct the particles to the central region of the microfluidic channel 1.
The ratio of the lengths of the first electrode region 21 and the second electrode region 22 is 0.1-1, i.e. the length of the separation region is greater than the length of the guiding region, so that the particles can be quickly guided to the second electrode region 22 and sufficiently separated at the second electrode region 22. The lemon-shaped electrode array can provide a continuous long-scale electric field gradient profile for the particles.
In this embodiment, the length of the microfluidic channel 1 (the sum of the length of the first electrode region 21 and the length of the second electrode region 22) is preferably 0.5cm to 30cm.
In some embodiments, the microfluidic channel 1 has a curved shape, and as shown in fig. 2, the microfluidic channel 1 may have a complex curved shape composed of a plurality of straight lines and a plurality of bends, including a bend and a bend-free portion, and a width w of the bend-free portion 1 From 8h to 15h, where h denotes the height of the microfluidic channel 1 and the height h is from about 10 μm to about 80 μm.
The side of the microfluidic channel 1 is provided with an arc structure 11 to make the microfluidic channel 1 in a curve shape, and the arc structure 11 is preferably an arc structure to provide an ideal flow field for the movement of particles, so that the particles in a weak field strong regionThe particles pass through a strong field intensity area under the action of a flow field, and the bending part are transited through a smooth fillet, so that the particles can be prevented from being accumulated on the arc-shaped structure by the optimized fillet design. As shown in FIG. 4, in the present embodiment, the distance w from the arc top of the arc-shaped structure 11 to the outermost side wall of the microfluidic channel 1 2 The distance d between the arc tops of the adjacent arc structures 11 is 4h-9h 1 Is 50-100 h. In a specific embodiment, the microfluidic channel 1 may be entirely curved.
As shown in fig. 3, the arc electrode array of the first ground electrode 211 includes a plurality of arc portions 2111, the plurality of arc portions 2111 are arranged at a certain distance along the length direction of the microfluidic channel 1, the arc portions 2111 are arc structures, the radius of the arc portions 2111 is 0.3h-h, and the distance d between adjacent arc portions 2111 is 2 0.6h-2h, the spacing g between the first ground electrode 211 and the first center electrode 212 1 The included angle between the first grounding electrode 211 and the horizontal direction is 0.5-5 degrees. The angle between the first ground electrode 211 and the horizontal direction is the angle between the straight line 2112 aligned with the arc electrode array and the horizontal direction.
In some embodiments, as shown in fig. 2 and 4, the second ground electrodes 222 located on both sides of the second electrode region 22 are planar electrodes whose contours are smooth straight lines. The lemon-shaped electrode array comprises a plurality of lemon-shaped electrode units 2221, adjacent lemon-shaped electrode units 2221 are connected and conducted with each other, and each lemon-shaped electrode unit 2221 is provided with an oval hole 2222. An elliptical hole 2222 is provided inside each of the lemon-shaped electrode units 2221, and an electric field gradient can be generated in the weak field intensity region, so that particles acted by positive dielectrophoresis force (pDEP) move to the strong field intensity region, and meanwhile, particles acted by negative dielectrophoresis force (nDEP) are more efficiently gathered inside the electrode, and the separation effect is improved.
The major axis dimension w of the lemon-shaped electrode unit 2221 3 The short axis is 8-15 h, and the short axis is 4-8 h; the distance between the center of the second center electrode 222 and the second ground electrode 221 is about 0.8h to 1.2h, and the distance w between the two second ground electrodes 221 located at both sides of the second center electrode 222 4 About 0.6h to about 1.2h. Lemon-shaped electrode arrayThe distance d between the apexes of two adjacent lemon-shaped electrode units 2221 in a row 3 Is within 4-8 h. In the lemon-shaped electrode unit 2221, the included angle between the long axis of the elliptical hole 2222 and the horizontal direction is 10-40 degrees, the long axis of the elliptical hole 2222 is 5-7 hours, the short axis is 2.5-3.5 hours, and the center of the elliptical hole 2222 and the center of the lemon-shaped electrode unit 2221 are offset in the y-axis direction by 0.5-1.5 hours.
Further, in some embodiments, the lemon-shaped electrode array comprises a first array segment and a second array segment disposed along the flow direction of the fluid, each array segment comprising a plurality of lemon-shaped electrode units 2221, the plurality of elliptical apertures 2222 of the first array segment are inclined upward, and the plurality of elliptical apertures 2222 of the second array segment are inclined downward. That is, the second electrode region 22 may be divided into a first half separation region and a second half separation region, the oval holes 2222 located in the first half separation region are inclined upward, and the oval holes 2222 located in the second half separation region are inclined downward, so that the movement of particles may be guided, and the separation effect may be improved.
According to the microfluid dielectrophoresis separation device provided by the embodiment of the invention, the structures of the electrodes and the microfluid channels are designed, pre-aggregation operation is not needed, and efficient separation of particles can be realized through mutual assistance of the electrodes and the microfluid channels; meanwhile, the integration performance of the device can be obviously improved, and the difficulty of mutual integration or matching with external equipment (such as a flow rate control instrument) is reduced.
In particular, no pre-aggregation operation is required, and the complex steps brought by the pre-aggregation operation are greatly reduced in use, such as: rinsing the sheath flow channel, controlling the stable sheath flow and the flow rate of the sample, and directly introducing the fluid into the microfluidic channel 1; the use quantity of external accurate flow velocity control instruments can be reduced without pre-gathering operation, the experiment cost can be saved, and the device is wider in application range.
The invention also provides a manufacturing method of the microfluid dielectrophoresis separation device, which comprises the following steps:
step S1, photoetching a negative photoresist pattern on a substrate, and processing a micro-fluid channel 1 by pouring;
step S2, photoetching an electrode pattern on the glass substrate 3 by using positive photoresist, and forming an electrode 2 by using an etching process;
and step S3: the microfluidic channel 1 is bonded in alignment with a glass substrate 3 etched with electrodes 2.
Specifically, the microfluid dielectrophoresis separation device is a microfluidic chip and can be processed and manufactured by adopting a photoetching technology.
In step S1, a material for fabricating the microfluidic channel 1 may be Polydimethylsiloxane (PDMS), a negative photoresist pattern is patterned on the substrate, a channel pattern is formed by pouring a PDMS conversion model, and then heating and curing are performed to form the microfluidic channel 1. The microfluidic channel 1 is a flexible PDMS channel, and the inlet 101 and outlet 102 portions can be made by punching with a punch.
In one embodiment, a plurality of inlets 101 and outlets 102 may be formed. When a plurality of inlets 101 are provided, the plurality of inlets may simultaneously introduce the fluid, or the corresponding inlets 101 may be opened to introduce the fluid according to actual needs, and the other inlets may be closed. Different outlets 102, such as a first outlet 1021, a second outlet 1022, and a third outlet 1023, are provided to effectively separate different particles.
The substrate may comprise any suitable material, for example a semiconductor material such as silicon, other inorganic materials such as glass, quartz, or organic materials such as plexiglass, polycarbonate, or the like. In this embodiment, the substrate is preferably a silicon wafer.
In step S2, the electrode 2 may be made of an ITO conductive material, specifically, an electrode pattern is photo-etched on an ITO glass substrate using a positive photoresist, and then an ITO electrode pattern is obtained by using an etching process to form the electrode 2.
Step S3, aligning the PDMS material with the channel structure and the ITO glass substrate etched with the electrode 2, treating the surface with a Plasma cleaner, and bonding the two together to form the microfluidic dielectrophoresis separation device, wherein a schematic structural diagram of the bonded microfluidic dielectrophoresis separation device is shown in fig. 1.
When the microfluid dielectrophoresis separation device is used, fluid containing particles is introduced from the inlet 101, and the ITO electrodes are connected with an external alternating current signal generating instrument so as to connect a circuit.
When the microfluid dielectrophoresis separation device is manufactured by the manufacturing method, the microfluid channel parameters and the electrode parameters of the microfluid dielectrophoresis separation device are set as follows:
width w of the microfluidic channel 1 (PDMS channel) without bends 1 The height h is 30 mu m, the arc structure 11 is arranged on the side edge in the microfluidic channel 1, the arc structure 11 adopts an arc design to provide an ideal flow field, so that particles in a weak field strength area pass through a strong field strength area under the action of the flow field, and a non-bending part and a bending part are transited through a smooth fillet to avoid accumulation of the particles at the arc structure 11. The distance w from the arc top of the arc-shaped structure 11 to the outermost side wall of the fluid channel 1 2 A pitch d of 210 μm between the arc tops of the adjacent arc structures 11 1 Is 2mm.
The length of the first electrode region 21 is about 1/10 of the length of the microfluidic channel 1, the radius of the arc-shaped portion 2111 of the first ground electrode 211 is 20 μm, and the interval d between the adjacent arc-shaped portions 2111 2 A gap g between the first ground electrode 211 and the first center electrode 212 of 60 μm 1 And 30 d, the first ground electrode 211 included an angle of 1.15 deg. with the horizontal direction.
The length of the second electrode region 22 is about 9/10 of the length of the microfluidic channel 1, the lemon-shaped electrode units 2221 in the lemon-shaped electrode array are connected and conducted with each other, and the size w of the long axis of the lemon-shaped electrode units 2221 3 310 μm with a minor axis size of 180 μm; the spacing between the center of the second center electrode 222 and the second ground electrode 221 is about 34 μm. Distance d at vertexes of two adjacent lemon-shaped electrode units 2221 3 And 180 μm. In the lemon-shaped electrode unit 2221, the included angle between the long axis of the oval holes 2222 and the horizontal direction is 25 °, wherein the oval holes 2222 in the first half separation area are inclined upward, and the oval holes 2222 in the second half separation area are inclined downward; the elliptical holes 2222 have a major axis of 160 μm and a minor axis of 80 μm, and the centers of the elliptical holes 2222 and the center of the lemon-shaped electrode unit 2221 are offset by 20 μm in the y-axis direction.
The parameters of the microfluid channel and the parameters of the electrodes are the optimal parameters of the microfluid dielectrophoresis separation device, and the microfluid dielectrophoresis separation device manufactured based on the parameters can achieve better separation effect when in use.
The manufacturing method is convenient to manufacture, the whole manufacturing difficulty and manufacturing cost of the microfluid dielectrophoresis separation device can be reduced, and the application range of the device is widened.
In the embodiment of the present invention, the separation effect of the microfluidic dielectrophoresis separation device is further described according to the microfluidic dielectrophoresis separation device manufactured in the steps S1 to S3.
Example one
Fig. 5 shows a schematic diagram of the separation of yeast cells and PS particles by using a microfluidic dielectrophoresis separation device according to an embodiment of the present invention, in which red polystyrene microspheres (PS particles) with a particle size of 7 μm are mixed with yeast cells, and the separation effect of the microfluidic dielectrophoresis separation device is tested.
First, a particle mixture is introduced into the microfluidic channel 1 from the inlet 101. Therefore, the mixed particles do not need to be subjected to a pre-aggregation operation. The conductivity of the mixed liquid of particles is preferably in the range of 10-100ms/cm, and when separating yeast from PS particles, an electric field is generated by using a sinusoidal signal of 20Vpp and 500kHz. As shown in fig. 5, yeast cells are subjected to a positive dielectrophoretic force (pDEP) moving towards a region of high field strength at the tip of the electrode. The curved configuration of the electrode 2 (arcuate portion 2111) and the arcuate configuration 11 of the microfluidic channel 1 help to transport particles to regions of high field strength, thereby significantly increasing separation efficiency.
As shown in FIGS. 1 and 5, the experiment was conducted by applying a pulse voltage, which is turned on for 0.6s and turned off for 0.2s during the pulse application period, so that the particles subjected to dielectrophoresis force can be continuously separated. Finally, most of the PS particles flow out from the second outlet 1022 located in the middle of the microfluidic channel 1, and the yeast cells flow out from the first outlet 1021 and the third outlet 1023 located at both sides of the microfluidic channel 1.
Example two
Fig. 6 (a) and 6 (b) show schematic diagrams of the separation of the red blood cells and the tumor cells by using the microfluidic dielectrophoresis separation device according to the embodiment of the invention, the left diagram of fig. 6 (a) shows a schematic diagram of a state where the red blood cells and the tumor cells just enter the microfluidic channel 1, and the right diagram of fig. 6 (a) shows a schematic diagram of a state where the red blood cells and the tumor cells are separated at the second electrode region 22. Example two the feasibility of microfluidic dielectrophoresis separation devices for separation of biological cells was verified using the same parameters of microfluidic dielectrophoresis separation devices as in example one.
The tumor cells may be breast cancer cells (MDA-MB-231), and the electric field is generated by separating red blood cells (erythrocytes) from breast cancer cells using a 17Vpp,75kHz sinusoidal signal. The mixed liquid of the red blood cells and the breast cancer cells is introduced into the microfluidic channel 1 from the inlet 101, and after the electric current is applied, the separation effect as shown in fig. 6 (a) and 6 (b) can be realized. In this embodiment, the concentration of red blood cells is preferably 4.9X 10 6 cells/ml, the concentration of breast cancer cells is preferably 1.1X 10 6 cells/ml. As shown in fig. 6 (a), the mixed liquid of the red blood cells and the tumor cells can achieve a better separation effect at a flow rate of 0.6 μ L/min, the red blood cells and the tumor cells are randomly distributed in the channel before separation, and the separated red blood cells are gathered in the middle of the microfluidic channel 1 and flow out from the second outlet 1022 located in the middle of the microfluidic channel 1; the tumor cells move to the two sides of the microfluidic channel 1 and gather and flow out of the first outlet 1021 and the third outlet 1023 which are positioned at the two sides of the microfluidic channel 1. As shown in fig. 6 (b), the separation effect is more remarkable when the mixed solution is in quasi-static flow.
The experiments show that the microfluid dielectrophoresis separation device provided by the embodiment of the invention can realize a good cell separation effect, and the device has good practicability.
The above embodiments are only exemplary embodiments of the present invention, and are not intended to limit the present invention, and the scope of the present invention is defined by the claims. Various modifications and equivalents may be made by those skilled in the art within the spirit and scope of the present invention, and such modifications and equivalents should also be considered as falling within the scope of the present invention.
Claims (10)
1. A microfluidic dielectrophoretic separation device, comprising:
a microfluidic channel for flowing a fluid containing particles therethrough;
the electrode, with the microfluid passageway corresponds the setting, the electrode includes first electrode region and the second electrode region that sets gradually along the flow direction of fluid, first electrode region is close to microfluid passageway's entry is located the first telluric electricity field orientation of the regional both sides of first electrode one side in the microfluid passageway is arc electrode array, is located the second central electrode at the regional middle part of second electrode is lemon shape electrode array.
2. The microfluidic dielectrophoretic separation device of claim 1, wherein the ratio of the length of the first electrode region to the second electrode region is from 0.1 to 1.
3. The microfluidic dielectrophoresis separation device according to claim 1, wherein the first central electrode located in the middle of the first electrode region is a planar electrode, the first central electrode having a smooth rectilinear profile; the second grounding electrodes positioned at two sides of the second electrode area are planar electrodes, and the outline of the second grounding electrode is a smooth straight line.
4. The microfluidic dielectrophoretic separation device of claim 3, wherein the microfluidic channel is curvilinear in shape, comprises bends and no bends, the width of the no bends being 8h-15h, wherein h represents the height of the microfluidic channel, the height of the microfluidic channel being 10 μm-80 μm.
5. The microfluidic dielectrophoresis separation device according to claim 4, wherein the array of arcuate electrodes of the first ground electrode comprises a plurality of arcuate portions arranged at intervals along the length of the microfluidic channel, the arcuate portions being in an arcuate configuration, the arcuate portions having a radius of 0.3h-h, the spacing between adjacent arcuate portions being 0.6h-2h, the spacing between the first ground electrode and the first central electrode being 0.6h-1.2h, the first ground electrode being at an angle of 0.5 ° to 5 ° to the horizontal.
6. The microfluidic dielectrophoresis separation device according to claim 3, wherein the lemon-shaped electrode array comprises a plurality of lemon-shaped electrode units, adjacent lemon-shaped electrode units are connected and conducted with each other, and each lemon-shaped electrode unit is provided with an oval hole.
7. The microfluidic dielectrophoresis separation device according to claim 6, wherein the lemon-shaped electrode units have a major axis size of 8h to 15h and a minor axis size of 4h to 8h; the distance between the center of the second central electrode and the second grounding electrode is 0.8h-1.2h; in the lemon-shaped electrode array, the distance between the vertexes of two adjacent lemon-shaped electrode units is 4-8 h; in the lemon-shaped electrode unit, an included angle between the long axis of the oval hole and the horizontal direction is 10-40 degrees, the long axis of the oval hole is 5-7 h, the short axis of the oval hole is 2.5-3.5 h, and h represents the height of the microfluidic channel.
8. The microfluidic dielectrophoretic separation device of claim 6, wherein the array of lemon-shaped electrodes comprises a first array segment and a second array segment disposed in a direction of flow of the fluid, the plurality of elliptical apertures of the first array segment being inclined upwardly and the plurality of elliptical apertures of the second array segment being inclined downwardly.
9. A method of making a microfluidic dielectrophoretic separation device, for use in making a microfluidic dielectrophoretic separation device according to any of claims 1 to 8; the manufacturing method comprises the following steps:
photoetching a negative photoresist pattern on a substrate, and processing the microfluidic channel by pouring;
photoetching an electrode pattern on a glass substrate by using positive photoresist, and forming an electrode by using an etching process;
and aligning and bonding the microfluidic channel and the glass substrate etched with the electrode.
10. The method of claim 9, wherein the microfluidic channel is fabricated using polydimethylsiloxane and the electrodes are fabricated using ITO conductive material.
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| US8968542B2 (en) * | 2009-03-09 | 2015-03-03 | Virginia Tech Intellectual Properties, Inc. | Devices and methods for contactless dielectrophoresis for cell or particle manipulation |
| KR20160048929A (en) * | 2013-08-29 | 2016-05-04 | 아포셀, 인코퍼레이티드 | Method and apparatus for isolation, capture and molecular analysis of target particles |
| US10274492B2 (en) * | 2015-04-10 | 2019-04-30 | The Curators Of The University Of Missouri | High sensitivity impedance sensor |
| CN106824318B (en) * | 2017-03-29 | 2019-03-08 | 哈尔滨工业大学 | A kind of minute yardstick particle separating chips and the preparation method and application thereof based on induced charge electric osmose and dielectrophoresis |
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| CN109456879B (en) * | 2018-12-18 | 2021-08-13 | 北京化工大学 | Dielectrophoresis micro-fluidic chip for cell sorting and focusing and alignment-free micro-processing method thereof |
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| CN1990093A (en) * | 2005-12-30 | 2007-07-04 | 财团法人工业技术研究院 | Multiple-sample microfluid dielectric electrophoretic separation apparatus |
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| CN108977343A (en) * | 2018-09-04 | 2018-12-11 | 哈尔滨工业大学 | The micro-fluidic chip separated for cell with capture based on dielectrophoresis principle |
| CN211255889U (en) * | 2019-11-26 | 2020-08-14 | 海南大学 | Triangular electrode red blood cell and platelet micro-separation device |
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