CN108855267B - Micro-channel platform for micro-control of biological micro-nano particles - Google Patents
Micro-channel platform for micro-control of biological micro-nano particles Download PDFInfo
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- CN108855267B CN108855267B CN201810820387.3A CN201810820387A CN108855267B CN 108855267 B CN108855267 B CN 108855267B CN 201810820387 A CN201810820387 A CN 201810820387A CN 108855267 B CN108855267 B CN 108855267B
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- 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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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Abstract
The invention discloses a micro-channel platform for micro-control of biological micro-nano particles, which can realize position and flow velocity constraint on the biological micro-nano particles; the platform includes: the device comprises a single-channel injection pump, a conical pipeline, a pipeline frame, a cover glass, a micro-channel and a base; wherein the single-channel injection pump is communicated with the conical pipeline; the conical pipeline is fixed on the pipeline frame, the cone angle of the conical pipeline is 6-12 degrees, and the cone opening of the conical pipeline is aligned with the runner opening of the micro-channel; the pipeline rack and the cover glass are fixed on the base, and the base is of an insert type structure; the micro-channel is fixed on the cover glass and is a symmetrical double-arc structure with two wide sides and a narrow middle part, the curvature radius of the symmetrical double-arc structure is 10-20mm, and the distance between the closest points of the two arcs is 50-200 mu m. The invention has the characteristics of convenient operation and control, high degree of freedom, low cost and mass production.
Description
Technical Field
The invention relates to a device for structural design of a micro-channel, in particular to a micro-channel platform for micro-control of biological micro-nano particles.
Background
In the past decade, micromanipulation (micromanipulation) of biological objects on the micro-nano scale has become an important issue in the field of bio-nanotechnology. Depending on the complexity and scale of the application process, micromanipulation includes a series of increasingly refined manipulations such as trapping, translation/rotation, collection or separation in three-dimensional space, live cell surgery/microinjection, and the like. On a scale, there has been more manipulation of entry into subcellular processes from the cellular level. In several competing 3D micromanipulation techniques (including electrophoresis, magnetic, mechanical, etc.), microscopic optical tweezers technology is used as a nearly non-invasive (non-invasive) method, with the outstanding advantage that tunable 10 can be applied over a large fraction of the scale of cellular and subcellular components-14-10-8And the control force of N is used for realizing a micro-control process. Manipulation of biological objects using optical tweezers is currently divided into direct and indirect manipulation (i.e. whether the laser is directly acting on the biological object or not). In future bioengineering, cell trapping using direct laser beam should be avoided as much as possibleOr micromanipulation to eliminate the adverse effects of the laser on the biological subject. Thus, indirect micromanipulation (indirect micromanipulation) of cellular and subcellular objects is becoming a very important tool and research topic in biotechnology.
Under the condition of not being influenced by direct illumination of laser, the indirect micro-control finishes the process control of positioning, transporting, sorting and the like of a biological object, and can research, diagnose, treat and transmit medicaments through the processes in medical research, so that researchers in different disciplines can carry out basic and application research on living cells and subcellular scales, thereby carrying out highly accurate cell and medicament interaction judgment, developing new medicaments and new diagnosis methods, detecting the onset of fatal diseases at an early stage, being basic research work with great innovative significance and having huge biomedical application value and market potential.
In terms of indirect micromanipulation, a large amount of resources have been internationally invested in recent years to investigate this problem. To achieve indirect manipulation of the biological object, the optical tweezers are instead used to capture dielectric microspheres (e.g., latex, polystyrene, silica, etc.) and are connected to two ends or boundary surfaces of the biological object by the microspheres to drive various spatial motions of the biological object. Different from magnetic force or electrophoresis control technology, the optical tweezers can realize multiple controls without mutual interference by simultaneously using a plurality of laser beams, and the characteristic provides good conditions for indirect micro control. With the development of indirect control, the design requirements of indirectly controlled micro-channels are increasing, and the micro-moving rotation of biological micro-nano particles is considered under the condition of meeting the control, so that the control and classification of rare cells are realized.
Disclosure of Invention
The invention aims to provide a device for a micro-channel platform for micro-manipulation of biological micro-nano particles aiming at the defects of the prior art.
The purpose of the invention is realized by the following technical scheme: a micro-channel platform for micro-manipulation of biological micro-nano particles can realize position and flow velocity constraint on the biological micro-nano particles, and further realize manipulation and classification of rare cells; the platform includes: the device comprises a single-channel injection pump, a conical pipeline, a pipeline frame, a cover glass, a micro-channel and a base; wherein the single-channel injection pump is communicated with the conical pipeline; the conical pipeline is fixed on the pipeline frame, the cone angle of the conical pipeline is 6-12 degrees, and the cone opening of the conical pipeline is aligned with the runner opening of the micro-channel; the pipeline rack and the cover glass are fixed on the base, and the base is of an insert type structure; the micro-channel is fixed on the cover glass and is a symmetrical double-arc structure with two wide sides and a narrow middle part, the curvature radius of the symmetrical double-arc structure is 10-20mm, and the distance between the closest points of the two arcs is 50-200 mu m.
Further, the injection speed of the single-channel injection pump is 0.1-1 ml/h.
Further, the single-channel injection pump is communicated with the conical pipeline through a hose, the hose is fixed on the X-shaped metal frame, the flow velocity of liquid in the hose is reduced through screwing screws at the tail end of the X-shaped metal frame, and micro-adjustment of the flow velocity is achieved.
Furthermore, the material of the conical pipeline is glass, and the conical angle is manufactured through an electric coil heating method.
Further, the slope angle of the conduit rack is consistent with the cone angle of the tapered conduit to facilitate forward flow of liquid into the microchannel.
Further, the pipeline frame and the base are integrally formed and are realized by adopting a 3D printing technology.
Further, the 3D printing technology material is ABS or PBS.
Further, the gluing among the cover glass, the micro flow channel and the base and the gluing among the conical pipeline and the pipeline frame are specifically as follows: and the uv glue is adopted for gluing, so that the connection and the fixation of each component are realized.
The invention has the beneficial effects that:
1. the invention has the characteristic of low cost, the insertion piece type structure provides possibility for batch production, and the invention has the characteristic of one-time replacement.
2. The invention has the potential of commercialization and miniaturization, and can be combined with a microfluidic chip to realize Lab-on-a-chip integration.
3. The symmetrical double-arc structure of the micro-channel is convenient for observing liquid flow, the influence of the surface tension of the liquid is reduced by the selection of the flow speed and the cone angle, and the position and flow velocity constraint accuracy of the biological micro-nano particles is improved.
4. The invention has the development potential of indirectly controlling the micro-movement and rotation of the micro-nano particles, controlling, detecting and separating rare cells and other functions, and is a core component for micro-control of nano particles.
Drawings
FIG. 1 is a schematic diagram of the overall structure of a micro-flow channel platform for micro-manipulation of biological micro-nano particles according to the invention;
FIG. 2 is a schematic view of a tapered channel of the microchannel platform;
FIG. 3 is a schematic diagram of a micro-manipulation system for constraining the position and flow velocity of biological micro-nano particles by using the micro-channel platform of the invention;
FIG. 4 is an assembly drawing of the microchannel platform;
FIG. 5 is an exploded view of the microchannel platform;
in the figure, a single-channel injection pump 1, a hose 2, a conical pipeline 3, a pipeline frame 4, a cover glass 5, a micro-channel 6, a base 7, an optical fiber operation frame 8, a micro-channel platform 9, a micro-objective 10 and an optical fiber 11.
Detailed Description
The invention is described in further detail below with reference to the figures and specific examples.
The working principle of the invention is as follows:
analyzing the influence of the cross section shape of the flow channel on the fluid according to a continuity equation, a Navier-stokes motion equation, an energy conservation equation and a rheological constitutive equation in the microfluid flow dynamics:
according to Navier-stokes equation of motion
Therefore, the following steps are carried out: when the fluid is in a stable laminar flow state in the flow channel, the pressure loss of the fluid is as follows:
wherein λ is the coefficient of on-way resistance; v isA hydrodynamic viscosity; ρ is the fluid density; d is the diameter of the flow channel; l is the length of the flow channel; re is Reynolds number.
In the process of microfluidic flow, due to the effect of a microscale effect, the surface force effect is enhanced, the viscous force far exceeds the inertial force, the Reynolds number of the microfluidic is reduced due to the reduction of the diameter of the flow channel, the on-way resistance coefficient is increased, and the long-jing ratio of the microfluidic is increased. As can be seen from the pressure loss equation: the smaller the diameter of the micro-channel is, the larger the pressure loss of the micro-fluid in the flowing process is, and the poorer the fluidity of the fluid is;
therefore, the flow length of the microfluid in the micro flow channel is inversely proportional to the specific surface area of the cross section of the flow channel (the ratio of the perimeter of the cross section to the area of the cross section), and when the specific surface area of the micro flow channel is small, the influence of the temperature of the fluid and the injection pressure on the flow length is large.
Specifically, the micro flow channel platform for micro-manipulation of biological micro-nano particles provided by the invention can realize position and flow velocity constraint on the biological micro-nano particles as shown in fig. 1 and 2, and further realize manipulation classification of rare cells; the platform includes: the device comprises a single-channel injection pump 1, a conical pipeline 3, a pipeline frame 4, a cover glass 5, a micro-channel 6 and a base 7; wherein the single-channel injection pump 1 is communicated with the conical pipeline 3; the conical pipeline 3 is fixed on the pipeline frame 4, the cone angle of the conical pipeline 3 is 6-12 degrees, and the cone opening of the conical pipeline 3 is aligned with the runner opening of the micro-runner 6; the pipeline frame 4 and the cover glass 5 are fixed on a base 7, and the base 7 is of a plug-in sheet type structure; the micro-channel 6 is fixed on the cover glass 5, the micro-channel 6 is a symmetrical double-arc structure with two wide sides and a narrow middle part, which is convenient for observing the liquid flow and controlling, the curvature radius of the symmetrical double-arc structure is 10-20mm, and the distance between the closest points of the two arcs is 50-200 μm.
Further, the injection speed of the single-channel injection pump 1 is 0.1-1 ml/h.
Further, single channel syringe pump 1 and conical duct 3 pass through hose 2 intercommunication, hose 2 is fixed on X type metal frame, reduces the liquid velocity of flow in hose 2 through precession X type metal frame tail end screw, realizes the micro-adjustment to the velocity of flow.
Furthermore, the material of the tapered pipe 3 is glass, and the taper angle is manufactured by an electric coil heating method.
Further, the slope angle of the pipe rack 4 is kept consistent with the taper angle of the tapered pipe 3 to facilitate the forward flow of liquid into the microchannel 6.
Further, the pipeline frame 4 and the base 7 are integrally formed and are realized by adopting a 3D printing technology.
Further, the 3D printing technology material is ABS or PBS.
Further, the gluing among the cover glass 5, the micro flow channel 6 and the base 7 and the gluing among the conical pipeline 3 and the pipeline rack 4 are specifically as follows: and the uv glue is adopted for gluing, so that the connection and the fixation of each component are realized.
As shown in fig. 3, in the micro-manipulation system for constraining the position and the flow velocity of the biological micro-nano particles by using the micro-channel platform of the invention, the optical fiber 11 is manipulated by the optical fiber manipulation frame 8 to focus the light spot on the micro-channel plane, and the flow position and the flow velocity of the biological micro-nano particles are constrained by the micro-channel platform 9, so that the light spot is aligned with the biological micro-nano particles to realize manipulation and capture. The experimental phenomenon is observed and recorded through the microscope objective 10. In which the micro flow channel insert-type structure is directly inserted into the groove in fig. 4 and 5.
The above-described embodiments are intended to illustrate rather than to limit the invention, and any modifications and variations of the present invention are within the spirit of the invention and the scope of the appended claims.
Claims (7)
1. A micro-channel platform for micro-manipulation of biological micro-nano particles is characterized in that the platform can realize position and flow velocity constraint on the biological micro-nano particles, and further realize manipulation and classification of rare cells; the platform includes: the device comprises a single-channel injection pump (1), a conical pipeline (3), a pipeline rack (4), a cover glass (5), a micro-channel (6) and a base (7); wherein the single-channel injection pump (1) is communicated with the conical pipeline (3); the conical pipeline (3) is fixed on the pipeline frame (4), the cone angle of the conical pipeline (3) is 6-12 degrees, and the cone opening of the conical pipeline (3) is aligned with the runner opening of the micro-channel (6); the pipeline rack (4) and the cover glass (5) are fixed on a base (7), and the base (7) is of a plug-in sheet type structure; the micro-channel (6) is fixed on the cover glass (5), the micro-channel (6) is a symmetrical double-arc structure with two wide sides and a narrow middle part, the curvature radius of the symmetrical double-arc structure is 10-20mm, and the distance between the closest points of the two arcs is 50-200 mu m; single channel syringe pump (1) and conical duct (3) pass through hose (2) intercommunication, hose (2) are fixed on X type metal frame, reduce the liquid velocity of flow in hose (2) through precession X type metal frame tail end screw, realize the fine-tuning to the velocity of flow.
2. The micro flow channel platform for micro manipulation of biological micro-nano particles according to claim 1, wherein the injection speed of the single-channel injection pump (1) is 0.1-1 ml/h.
3. The micro flow channel platform for micro-manipulation of biological micro-nano particles according to claim 1, wherein the conical channel (3) is made of glass, and a cone angle is manufactured by an electric coil heating method.
4. The micro flow channel platform for micro manipulation of biological micro-nano particles according to claim 1, wherein the slope inclination angle of the pipeline frame (4) is consistent with the cone angle of the conical pipeline (3) so as to facilitate forward flow of liquid into the micro flow channel (6).
5. The micro flow channel platform for micro manipulation of biological micro-nano particles according to claim 1, wherein the channel frame (4) and the base (7) are integrally formed and realized by a 3D printing technology.
6. The micro flow channel platform for micro manipulation of biological micro-nano particles according to claim 5, wherein the 3D printing technical material is ABS or PBS.
7. The micro flow channel platform for micro-manipulation of biological micro-nano particles according to claim 1, wherein the gluing among the cover glass (5), the micro flow channel (6) and the base (7) and the gluing among the conical pipeline (3) and the pipeline rack (4) are specifically as follows: and the uv glue is adopted for gluing, so that the connection and the fixation of each component are realized.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN202465675U (en) * | 2012-03-16 | 2012-10-03 | 大连理工大学 | Microfluidics shearing device of flow method controlling two dynamic biochemical signals to fast switch stimulus |
| CN106238111A (en) * | 2016-07-28 | 2016-12-21 | 南京理工大学 | A kind of microcapsule preparation method based on micro-fluidic chip shear flow |
| CN106732839A (en) * | 2016-12-30 | 2017-05-31 | 天津禄浩科技股份有限公司 | A kind of cellular fat particle detections chip and its detection reagent |
| CN106902906A (en) * | 2017-04-28 | 2017-06-30 | 清华大学 | A kind of method that micro-fluid chip and its focusing are focused on without sheath fluid formula particle three-dimensional |
| CN107099456A (en) * | 2017-06-08 | 2017-08-29 | 北京工业大学 | A kind of digital pcr droplet preparation method |
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| US7250139B2 (en) * | 2003-03-19 | 2007-07-31 | Northwestern University | Nanotipped device and method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN202465675U (en) * | 2012-03-16 | 2012-10-03 | 大连理工大学 | Microfluidics shearing device of flow method controlling two dynamic biochemical signals to fast switch stimulus |
| CN106238111A (en) * | 2016-07-28 | 2016-12-21 | 南京理工大学 | A kind of microcapsule preparation method based on micro-fluidic chip shear flow |
| CN106732839A (en) * | 2016-12-30 | 2017-05-31 | 天津禄浩科技股份有限公司 | A kind of cellular fat particle detections chip and its detection reagent |
| CN106902906A (en) * | 2017-04-28 | 2017-06-30 | 清华大学 | A kind of method that micro-fluid chip and its focusing are focused on without sheath fluid formula particle three-dimensional |
| CN107099456A (en) * | 2017-06-08 | 2017-08-29 | 北京工业大学 | A kind of digital pcr droplet preparation method |
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