CN114534809B - Microfluidic particle control device with adjustable cross section shape and particle control method - Google Patents
Microfluidic particle control device with adjustable cross section shape and particle control method Download PDFInfo
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- CN114534809B CN114534809B CN202210178718.4A CN202210178718A CN114534809B CN 114534809 B CN114534809 B CN 114534809B CN 202210178718 A CN202210178718 A CN 202210178718A CN 114534809 B CN114534809 B CN 114534809B
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
Abstract
The invention discloses a microfluidic particle control device with an adjustable cross-sectional shape and a particle control method. The chip bonds the inertia runner layer to the PDMS film, air pressure is introduced below the film, and the film is pressed to deform upwards, so that the cross section shape of the runner is changed. The deformation degree of the film can be accurately regulated and controlled by regulating the flow, changing the input air pressure and the like, so that the microfluidic chip with the adjustable cross section shape is obtained. The micro-nano biological particle manipulation by utilizing the micro-fluidic device can obtain higher manipulation precision and expand the application range of the micro-nano biological particle manipulation.
Description
Technical Field
The invention relates to a microfluidic particle control device with an adjustable cross-sectional shape and a particle control method, belongs to the field of microfluidics, and can be used for precise control application of micro-nano biological particles, such as precise capture, focusing, separation and the like of micro-nano biological cells.
Background
Capturing and analyzing micro-nano-biological particles is extremely important for life science research, for example, capturing and detecting rare cells in blood such as Circulating Tumor Cells (CTCs) is beneficial for early diagnosis of malignant tumors; the separation of red blood cells, white blood cells and platelets in blood and the analysis of the isolated high purity cells is beneficial to the detection of parameters of some diseases (such as diabetes, liver cirrhosis, coronary heart disease, etc.), so that the research on the manipulation technology of micro-nano biological particles is necessary.
By constructing a micro-scale runner network, the micro-fluidic technology has been developed into a research hot spot and mainstream technology for micro-nano biological particle manipulation. In view of this, scholars at home and abroad develop on-chip microparticle manipulation technologies with different working principles by introducing external field effects (active technology) such as electric field, sound field and magnetic field, or by utilizing special microstructures and micro-fluid effects induced by the special microstructures (passive technology). The real-time controllability of the active control is good, but the sample treatment flux is low and the operation process is complex, and the treatment flux of the passive control is high, the operation is convenient and fast, and an external physical field is not needed, so that the active control has better integration advantage in a miniaturized device. The inertial microfluidic technology is used as a passive particle manipulation technology, based on the size dependence of transverse inertial migration of particles in Newtonian fluid, the inertial lift force and the secondary flow drag force in a straight flow channel or a bent flow channel are utilized to jointly act to enable particles with different sizes to be focused at different positions of the flow channel to achieve accurate manipulation, and the device has the advantages of being simple in flow channel structure, convenient to operate, high in manipulation accuracy and the like. The cross section of the flow channel of the traditional inertial microfluidic chip is mainly rectangular and trapezoidal, and once the cross section is set, the size of the flow channel cannot be changed any more, so that the flow channel can only be used for controlling particles with specific sizes. However, inertial microfluidic chips, when used in biomedical applications, cannot be precisely manipulated with many different cells using conventional chips due to the extremely complex size polydispersity of biological cells.
Therefore, the traditional inertia micro-fluidic technology is broken through, so that the inertia micro-fluidic chip is used for precisely controlling particles with different sizes, the control performance of micro-nano biological particles is improved, the application range of the micro-nano biological particles in the biomedical field is expanded, and technical support is provided for finally realizing industrial transformation of the micro-nano biological particles.
Disclosure of Invention
The invention aims to: in order to overcome the defects in the prior art, the invention provides the microfluidic particle control device with the adjustable cross-sectional shape and the particle control method thereof, and the device has small volume, high control precision and flux, can realize the accurate control of various micro-nano biological particles with different sizes, and expands the application range thereof.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a microfluidic particle control device with an adjustable cross-sectional shape comprises a top plate, an inertial microfluidic chip, a bottom plate and a glass sheet from top to bottom. The inertial microfluidic chip is embedded into the bottom plate, the top plate is movably connected to the bottom plate, and the glass sheet is positioned at the bottom of the bottom plate.
In the above microfluidic device, the inertial microfluidic chip includes an inertial flow channel layer and a PDMS film; the inertia runner layer and the PDMS film are mutually bonded.
In the inertial microfluidic chip, the inertial flow channel layer is provided with a liquid inlet hole, an inlet liquid storage tank, an inertial flow channel, an outlet liquid storage tank and a liquid outlet hole, the structure of the inertial flow channel is an Archimedes spiral structure, the number of the liquid inlet hole and the number of the inlet liquid storage tank are one or two, the number of the liquid outlet hole and the number of the outlet liquid storage tank are two, and the liquid inlet hole and the liquid outlet hole are communicated with the outside and are used for guiding in and guiding out micro-nano particle solution.
In the inertial microfluidic chip, the PDMS film can be divided into a full-area compression film and a direct current channel area compression film according to different compression areas; the thickness of the PDMS film is 50-500 mu m.
When the PDMS film is a direct current channel region compression film, a layer of silica gel film is needed to be bonded below the PDMS film in order to achieve the purpose that only an outlet direct current channel region is compressed, and the thickness of the silica gel film is larger than 1mm, so that the silica gel film is prevented from being deformed due to compression; the silica gel membrane is provided with a micro groove, and the position of the micro groove is right below the outlet direct current channel area.
In the microfluidic device, the top plate is provided with a groove, and an inlet observation groove and an outlet observation groove are also formed in the groove and are used for observing the distribution state of micro-nano particles at the inlet and the outlet of the flow channel; a square groove I is arranged above the bottom plate, a square groove II is arranged below the bottom plate, and an air inlet hole is arranged on the side edge of the bottom plate; and the space formed by overlapping the groove with the square groove is the same as the size of the inertial microfluidic chip, and is used for placing and fixing the inertial microfluidic chip.
In the microfluidic device, the square groove II is used for placing a glass sheet; the air inlet is located between the glass plate and the inertial microfluidic chip, and an air needle is inserted into the air inlet and connected to the compressor for providing the pressure required for deformation of the membrane.
A particle manipulation method using a microfluidic particle manipulation device with an adjustable cross-sectional shape is provided, which is based on the principle that:
the sectional shape of the flow channel which is originally rectangular is changed by utilizing the characteristic that the PDMS film is easy to deform under pressure, and the degree of deformation of the film is controlled by adjusting the flow, changing the size of the input air pressure and the like, so that the inertial microfluidic chip with the adjustable sectional shape is obtained.
The beneficial effects of the invention are as follows:
according to the micro-fluidic device, the inertia flow channel layer is bonded on the PDMS film, and the air pressure is added to the bottom of the film, so that the flow channel section can be dynamically changed, and the limitation of the fixed flow channel section of the traditional inertia micro-fluidic chip is overcome. Compared with the traditional microfluidic device, the design can control the deformation degree of the film by means of adjusting the flow, changing the input air pressure and the like, so that the inertial microfluidic chip with the adjustable cross section shape is obtained, the microfluidic device is used for controlling the micro-nano biological particles, the capability of controlling the micro-nano biological particles of the chip can be improved, and the application range of particle control is expanded. Meanwhile, the microfluidic device provided by the invention has the advantages of small volume, high control precision, high flux, simplicity and convenience in manufacturing and the like.
Drawings
Fig. 1 is an exploded view of a 3D structure of a microfluidic device;
FIG. 2 is a schematic 3D structure of a full area thin film pressed inertial microfluidic chip;
FIG. 3 is a schematic view of a 3D structure of a thin film compression inertial microfluidic chip in the DC channel region;
FIG. 4 is a top view of a thin film compression inertial microfluidic chip in the direct channel region;
FIG. 5 is a 3D schematic of an inertial flow layer;
FIG. 6 is a schematic view of a top plate 3D structure;
FIG. 7 is a schematic view of a 3D structure of a base plate;
FIG. 8 is a schematic view of a single-inlet, double-outlet spiral flow channel;
FIG. 9 is a schematic diagram of a dual inlet dual outlet spiral flow channel;
FIG. 10 is a schematic diagram of a micro-nano biological particle separation experiment platform;
FIG. 11 is a simulation model of an asymmetric secondary flow field in a concave-section flow channel caused by film deformation;
FIG. 12 is a focusing experiment result of 10 μm particles in a conventional rectangular section microfluidic chip;
FIG. 13 is a result of a focusing experiment of 10 μm particles in a cross-section-adjustable microfluidic chip;
wherein, 1 is a top plate, 2 is an inertial micro-fluidic chip, 3 is a bottom plate, 4 is a glass sheet, 11 is an inertial flow channel layer, 12 is a PDMS film, 13 is a silica gel film, 21 is a micro groove formed by the silica gel film, 31 is a liquid inlet, 32 is an inlet liquid storage pool, 33 is an inertial flow channel, 34 is an outlet liquid storage pool, 35 is a liquid outlet, 41 is a groove, 42 is an inlet observation groove, 43 is an outlet observation groove, 51 is a square groove I, 52 is a square groove II, and 53 is an air inlet hole.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are some, but not all embodiments of the invention. It should be noted here that example 1 is a specific detailed description; examples 2 to 4 are for simplicity of explanation, and only the differences from example 1 are pointed out. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, are intended to fall within the scope of the present invention.
Example 1: microfluidic particle control device with adjustable cross section shape
As shown in fig. 1 and 2, the microfluidic particulate control device with an adjustable cross-sectional shape comprises a top plate 1, an inertial microfluidic chip 2, a bottom plate 3 and a glass sheet 4 from top to bottom. The inertial microfluidic chip 2 is embedded in the bottom plate 3, the top plate 1 is movably connected to the bottom plate 3, and the glass sheet 4 is positioned at the bottom of the bottom plate 3. The inertial microfluidic chip 2 comprises an inertial flow channel layer 11 and a PDMS membrane 12. The inertial flow channel layer 11 and the PDMS film 12 are bonded to each other.
As shown in fig. 5, the inertia runner layer 11 is provided with a liquid inlet hole 31, an inlet liquid reservoir 32, an inertia runner 33, an outlet liquid reservoir 34 and a liquid outlet hole 35 which are sequentially communicated, and the liquid inlet hole 31 and the liquid outlet hole 35 are communicated with the outside for leading in and leading out the micro-nano particle solution.
The PDMS membrane 12 is a full area pressed membrane (fig. 2) with a thickness of 300 μm.
As shown in fig. 8, the inertial flow path 33 has an archimedes spiral structure and a rectangular cross section. The number of the liquid inlet holes 31 and the liquid inlet reservoirs 32 is one, and the number of the liquid outlet holes 35 and the liquid outlet reservoirs 34 is two. The flow channel has a height of 160 μm and a width of 500. Mu.m. The diameters of the circular arcs at the inlet and the outlet of the flow channel are 8.9mm and 21.8mm respectively, the adjacent circular arcs are spaced by 1mm, and the total length of the flow channel is 120mm.
The material of the inertia runner layer 11 is PDMS, and the materials of the top plate 1 and the bottom plate 3 are plastics.
As shown in fig. 6 and 7, a groove 41 is arranged below the top plate 1, a square groove 51 is arranged above the bottom plate 3, and the space formed by overlapping the groove 41 and the square groove 51 is the same as the inertial microfluidic chip 2 in size and is used for placing and fixing the inertial microfluidic chip 2. In addition, an inlet observation groove 43 and an outlet observation groove 44 are arranged in the groove 41 above the top plate 1 and are used for observing the distribution state of micro-nano particles at the inlet and the outlet of the runner. A square groove II 52 is arranged below the bottom plate 3, and an air inlet 53 is arranged on the side edge. The square groove two 52 is used for placing the glass sheet 4, and the air inlet 53 on the side is used for inserting an air needle and is connected to a compressor to provide pressure for deformation of the PDMS film 12.
As shown in fig. 10, the microfluidic device in this embodiment can be used for precise focusing applications of micro-nano particles. The specific operation is as follows: particle solution containing 10 mu m polystyrene particles is injected into a microfluidic chip (an experimental platform in fig. 10) at a flow rate of 1.2ml/min by a precision injection pump, and the micro-nano particle solution enters an inertial flow channel 33 from an inlet liquid storage tank 32 through a liquid inlet hole 31. The micro-nano particles in the solution are randomly distributed in the flow channel at the inlet under the influence of the turbulence of the micro-fluid in the inlet reservoir 32. The compressor is turned on to adjust the input pressure to 25kPa, and the pressure is delivered to the cavity between the glass plate 4 and the inertial microfluidic chip 2 through the air inlet 53 and acts on the bottom of the PDMS film 12 to deform it upwards, so that the flow channel cross section is gradually changed from the original rectangular shape to the concave shape. This change in cross-section disrupts the symmetrical secondary flow within the rectangular cross-section perpendicular to the primary flow direction such that the secondary flow is asymmetrically distributed in the transverse direction of the flow path cross-section (simulation results of fig. 11). In the concave section, the secondary flow distribution is in a situation of weak middle and strong two sides, so particles in the flow channel can migrate to the wall surface of the flow channel under the action of the secondary flow and the inertia lift force. As shown in fig. 13, the 10 μm polystyrene particles are focused on the inner wall surface of the flow channel under the above experimental conditions, and compared with the experimental results (fig. 12) of the traditional microfluidic chip with rectangular cross section, it can be obviously seen that in the microfluidic device provided by the invention, the focusing band width of the 10 μm polystyrene particles is narrower, and the focusing effect is better.
Example 2: microfluidic particle control device with adjustable cross section shape
As shown in fig. 1 and 2, the microfluidic particulate control device with an adjustable cross-sectional shape comprises a top plate 1, an inertial microfluidic chip 2, a bottom plate 3 and a glass sheet 4 from top to bottom. The inertial microfluidic chip 2 is embedded in the bottom plate 3, the top plate 1 is movably connected to the bottom plate 3, and the glass sheet 4 is positioned at the bottom of the bottom plate 3. The inertial microfluidic chip 2 comprises an inertial flow channel layer 11 and a PDMS membrane 12. The inertial flow channel layer 11 and the PDMS film 12 are bonded to each other.
As shown in fig. 5, the inertia runner layer 11 is provided with a liquid inlet hole 31, an inlet liquid reservoir 32, an inertia runner 33, an outlet liquid reservoir 34 and a liquid outlet hole 35 which are sequentially communicated, and the liquid inlet hole 31 and the liquid outlet hole 35 are communicated with the outside for leading in and leading out the micro-nano particle solution.
The PDMS membrane 12 is a full area pressed membrane (fig. 2) with a thickness of 100 μm.
As shown in fig. 9, the inertial flow path 33 has an archimedes spiral structure and a rectangular cross section. The number of the liquid inlet holes 31 and the liquid inlet reservoirs 32 is two, and the number of the liquid outlet holes 35 and the liquid outlet reservoirs 34 is two. The flow channel has a height of 160 μm and a width of 500. Mu.m. The diameters of the circular arcs at the inlet and the outlet of the flow channel are 8.9mm and 21.8mm respectively, the adjacent circular arcs are spaced by 1mm, and the total length of the flow channel is 120mm.
The material of the inertia runner layer 11 is PDMS, and the materials of the top plate 1 and the bottom plate 3 are plastics.
Example 3: microfluidic particle control device with adjustable cross section shape
As shown in fig. 1 and 2, the microfluidic particulate control device with an adjustable cross-sectional shape comprises a top plate 1, an inertial microfluidic chip 2, a bottom plate 3 and a glass sheet 4 from top to bottom. The inertial microfluidic chip 2 is embedded in the bottom plate 3, the top plate 1 is movably connected to the bottom plate 3, and the glass sheet 4 is positioned at the bottom of the bottom plate 3. The inertial microfluidic chip 2 comprises an inertial flow channel layer 11 and a PDMS membrane 12. The inertial flow channel layer 11 and the PDMS film 12 are bonded to each other.
As shown in fig. 5, the inertia runner layer 11 is provided with a liquid inlet hole 31, an inlet liquid reservoir 32, an inertia runner 33, an outlet liquid reservoir 34 and a liquid outlet hole 35 which are sequentially communicated, and the liquid inlet hole 31 and the liquid outlet hole 35 are communicated with the outside for leading in and leading out the micro-nano particle solution.
The PDMS membrane 12 is a direct channel area pressed membrane (fig. 3, 4) with a thickness of 200 μm.
As shown in fig. 8, the inertial flow path 33 has an archimedes spiral structure and a rectangular cross section. The number of the liquid inlet holes 31 and the liquid inlet reservoirs 32 is one, and the number of the liquid outlet holes 35 and the liquid outlet reservoirs 34 is two. The flow channel has a height of 160 μm and a width of 500. Mu.m. The diameters of the circular arcs at the inlet and the outlet of the flow channel are 8.9mm and 21.8mm respectively, the adjacent circular arcs are spaced by 1mm, and the total length of the flow channel is 120mm.
The material of the inertia runner layer 11 is PDMS, and the materials of the top plate 1 and the bottom plate 3 are plastics.
Example 4: microfluidic particle control device with adjustable cross section shape
As shown in fig. 1 and 2, the microfluidic particulate control device with an adjustable cross-sectional shape comprises a top plate 1, an inertial microfluidic chip 2, a bottom plate 3 and a glass sheet 4 from top to bottom. The inertial microfluidic chip 2 is embedded in the bottom plate 3, the top plate 1 is movably connected to the bottom plate 3, and the glass sheet 4 is positioned at the bottom of the bottom plate 3. The inertial microfluidic chip 2 comprises an inertial flow channel layer 11 and a PDMS membrane 12. The inertial flow channel layer 11 and the PDMS film 12 are bonded to each other.
As shown in fig. 5, the inertia runner layer 11 is provided with a liquid inlet hole 31, an inlet liquid reservoir 32, an inertia runner 33, an outlet liquid reservoir 34 and a liquid outlet hole 35 which are sequentially communicated, and the liquid inlet hole 31 and the liquid outlet hole 35 are communicated with the outside for leading in and leading out the micro-nano particle solution.
The PDMS membrane 12 is a direct channel area pressed membrane (fig. 3, 4) with a thickness of 400 μm.
As shown in fig. 9, the inertial flow path 33 has an archimedes spiral structure and a rectangular cross section. The number of the liquid inlet holes 31 and the liquid inlet reservoirs 32 is two, and the number of the liquid outlet holes 35 and the liquid outlet reservoirs 34 is two. The flow channel has a height of 160 μm and a width of 500. Mu.m. The diameters of the circular arcs at the inlet and the outlet of the flow channel are 8.9mm and 21.8mm respectively, the adjacent circular arcs are spaced by 1mm, and the total length of the flow channel is 120mm.
The material of the inertia runner layer 11 is PDMS, and the materials of the top plate 1 and the bottom plate 3 are plastics.
The above examples are given for clarity of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.
Claims (8)
1. The micro-fluidic particle control device with the adjustable cross-sectional shape is characterized by comprising a top plate (1), an inertial micro-fluidic chip (2), a bottom plate (3) and a glass sheet (4) from top to bottom; the inertial microfluidic chip (2) is embedded in the bottom plate (3), the top plate (1) is movably connected to the bottom plate (3), and the glass sheet (4) is positioned at the bottom of the bottom plate (3); the inertial microfluidic chip (2) comprises an inertial flow channel layer (11) and a PDMS film (12); the inertial flow channel layer (11) is provided with a liquid inlet (31), an inlet liquid storage pool (32), an inertial flow channel (33), an outlet liquid storage pool (34) and a liquid outlet (35); the inertial flow channel (33) is a flexible structure flow channel, namely the cross section shape and the size of the flow channel can be adjusted in real time by applying pressure deformation to the PDMS film (12);
the sectional shape of the flow channel which is originally rectangular is changed by utilizing the characteristic that the PDMS film (12) is easy to deform under pressure, and the degree of deformation of the film is controlled by adjusting the flow rate, changing the size of the input air pressure and the like, so that the inertial microfluidic chip (2) with the adjustable sectional shape is obtained.
2. A microfluidic particulate manipulation device according to claim 1, wherein the inertial flow channel layer (11) and the PDMS membrane (12) are bonded to each other.
3. The microfluidic particulate manipulation device with an adjustable cross-sectional shape according to claim 2, wherein the inertial flow channel (33) has an archimedes spiral structure, the number of the liquid inlet holes (31) and the liquid inlet reservoirs (32) is one or two, the number of the liquid outlet holes (35) and the liquid outlet reservoirs (34) is two, and the liquid inlet holes (31) and the liquid outlet holes (35) are communicated with the outside for guiding in and guiding out the micro-nano particle solution.
4. The microfluidic particulate manipulation device with adjustable cross-sectional shape according to claim 2, wherein the PDMS film (12) is divided into a full-area compression film and a direct channel area compression film according to the compression area; the thickness of the PDMS film (12) is 50 mu m-500 mu m.
5. The microfluidic particulate manipulation device with an adjustable cross-sectional shape according to claim 4, wherein when the PDMS film (12) is a direct flow channel region pressurized film, a silica gel film (13) can be bonded under the PDMS film for achieving the purpose of pressurizing only the outlet direct flow channel region.
6. The microfluidic particulate manipulation device with adjustable cross-sectional shape according to claim 5, wherein the thickness of the silica gel film (13) is greater than 1mm in order to avoid deformation of the silica gel film (13) under pressure; the silica gel membrane (13) is provided with a micro groove (21), and the micro groove (21) is positioned right below the outlet direct current channel area.
7. The microfluidic particulate manipulation device with the adjustable cross-sectional shape according to claim 1, wherein a groove (41) is formed in the top plate (1), and an inlet observation groove (42) and an outlet observation groove (43) are further formed in the groove (41) and are used for observing the distribution state of micro-nano particles at the inlet and the outlet of the flow channel; a square groove I (51) is arranged above the bottom plate, a square groove II (52) is arranged below the bottom plate, and an air inlet hole (53) is formed in the side edge of the bottom plate; the space formed by overlapping the groove (41) and the square groove I (51) is the same as the size of the inertia micro-fluidic chip (2) and is used for placing and fixing the inertia micro-fluidic chip (2).
8. A microfluidic particulate manipulation device with an adjustable cross-sectional shape according to claim 7, wherein the square groove two (52) is used for placing a glass sheet (4); the air inlet hole (53) is positioned between the glass sheet (4) and the inertial microfluidic chip (2), and an air needle is inserted into the air inlet hole (53) and connected to the compressor for providing the pressure required for deformation of the membrane.
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