CN108018207A - The biomechanical system with stretching culture is sheared for cell flow - Google Patents
The biomechanical system with stretching culture is sheared for cell flow Download PDFInfo
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- CN108018207A CN108018207A CN201610968521.5A CN201610968521A CN108018207A CN 108018207 A CN108018207 A CN 108018207A CN 201610968521 A CN201610968521 A CN 201610968521A CN 108018207 A CN108018207 A CN 108018207A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/16—Microfluidic devices; Capillary tubes
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/34—Internal compartments or partitions
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
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Abstract
The present invention provides a kind of biomechanical system sheared for cell flow with stretching culture, has a work top.The biomechanical system includes a stretching device and an at least micro-fluidic chip, and the micro-fluidic chip is connected by an at least clamping device with the stretching device.
Description
Technical field
It is specifically a kind of to be used to cell flow shearing and stretch train the present invention relates to biomechanical environment bionics techniques
Foster biomechanical system.
Background technology
In cell micro-environment, mechanical environment is one of important composition of one of which, it can be with regulating cell skeleton egg
White structure, the apoptosis of cell, break up, stick, polarity, contractility, migration, the transfection of gene, the expression of protein, secretion
The ability such as matter and metabolism.It is the research hand generally used in biomedicine to study influence of the mechanical stimulation to biosystem
Section, cell how to be carried out in this mechanics microenvironment reaction be nowadays cell biomechanics field researchers it is of concern
Problem.
For this reason, Chinese patent CN 104342370A " are used for the biomethanics system of cell three-dimensional perfusion Compression and Expansion culture
A kind of device that can apply two kinds of power of stretching and shearing to cell at the same time is devised in system ".
However, in existing device, can not implementation rule stretching and fluid shearing effect be combined, and will stretching and
The device that fluid shearing effect combines can not then accomplish in the same size, the direction unification that exerts a force.
, can will it would therefore be desirable to a kind of new cell flow that is used for shears biomechanical system with stretching culture
Rule, uniform stretching and fluid shearing both mechanical environments combine, to overcome the shortcomings of existing apparatus.
The content of the invention
To solve the deficiencies in the prior art, the present invention proposes a kind of Biological Strength sheared for cell flow with stretching culture
System, the combination come the stretching of implementation rule and shear force is combined using microflow control technique with mechanical linear module.
In order to achieve the above object, the present invention provides a kind of biomethanics system sheared for cell flow with stretching culture
System, has a work top.The biomechanical system includes a stretching device and an at least micro-fluidic chip, described micro-fluidic
Chip is connected by an at least clamping device with the stretching device, wherein, the stretching device includes:One first screw rod bracket
With one second screw rod bracket, first screw rod bracket and second screw rod bracket are relatively fixed and are arranged at the work top
On;One forward lead screw, the forward lead screw are supported by first screw rod bracket and second screw rod bracket;At least one is reciprocal
Slider waveguide rod, the reciprocating block slider guide rod are arranged in parallel with the forward lead screw, and the reciprocating block slider guide rod is by described
One screw rod bracket and second screw rod bracket support;One first reciprocating block slider and one second reciprocating block slider, described first is reciprocal
Sliding block and second reciprocating block slider are respectively arranged in the forward lead screw, and the reciprocating block slider guide rod is past through described first
Multiple sliding block and the second reciprocating block slider, the rotation of the forward lead screw drive first reciprocating block slider and second reciprocating block slider
Relatively moved along the reciprocating block slider guide rod;And a motor, the motor are fixedly installed on the work top, institute
The rotation for stating motor drives the forward lead screw rotation;There is a cavity, the cavity has one inside the micro-fluidic chip
Entrance and an outlet, the connecting conduit are fluidly connected with the entrance of the micro-fluidic chip and outlet respectively;Also, institute
Clamping device is stated to be fixedly installed on first reciprocating block slider and/or second reciprocating block slider.
In an embodiment of the present invention, the micro-fluidic chip is made of elastic material.
In an embodiment of the present invention, the micro-fluidic chip includes a substrate and a cover plate, in a table of the cover plate
There is a groove so that the substrate forms the micro-fluidic core with the cavity after fitting with the cover plate on face
Piece;The connecting conduit is connected by the entrance and outlet with the recessed fluid.
In an embodiment of the present invention, the elastic material selection dimethyl siloxane.
In an embodiment of the present invention, the biomechanical system further includes a fluid pushing meanss, the fluid forces
Device is fluidly connected by connecting conduit and the micro-fluidic chip.
In an embodiment of the present invention, the one kind of the fluid forces device in peristaltic pump or syringe pump.
In an embodiment of the present invention, the groove is divided into inlet region, cell culture area and outlet area, the inlet region with
The entrance of the micro-fluidic chip fluidly connects, and the outlet fluid of the outlet area and the micro-fluidic chip connects
Connect;Also, the width of the groove gradually increases from the inlet region and the outlet area to the cell culture area.
In an embodiment of the present invention, a protein modification is formed on the inner surface of the cavity of the micro-fluidic chip
Layer.
In an embodiment of the present invention, above-mentioned protein is selected from matrigel, fibronectin or gelation
solution。
In the present invention, the motor drives the forward lead screw to rotate, and then makes first reciprocating block slider and second
Reciprocating block slider relatively moves, and forms the drawing process of the micro-fluidic chip.In the drawing process, the rotating speed of the motor with
And rotation angle is adjustable, it is possible to achieve the tension test under different stretch frequency and length.The control system of the motor be by
What driver, regulated power supply, arduino microcontrollers and control program formed, be this area routine techniques, therefore herein no longer
Repeat.
It should be noted that unless otherwise specified, heretofore described reagent is commercially available product.
In biomechanical system of the present invention, using the micro-fluidic chip with regular shape cavity come instead of existing
Having has the timbering material of irregular holes in technology so that the flow field that fluid passes through is more uniform and stable, so that cell
The size direction of suffered hydrodynamic shear is consistent;At the same time under stretching action, the deformation of the chip direction on microcosmic is consistent, makes
The drawing force size and Orientation obtained suffered by cell is also consistent.In addition, biomechanical system of the present invention is compared with the prior art,
Structure is more succinct, using the design of positive anti-leading screw then under the driving of same motor, it can be achieved that two sliding blocks move toward one another,
Observed easy to install microscope additional.
Brief description of the drawings
Fig. 1 is the main view for being used for the biomechanical system that cell flow is sheared with stretching culture of one embodiment of the invention
Figure;
Fig. 2 is the structure bottom view of the micro-fluidic chip in one embodiment of the invention.
Embodiment
The present invention is described in detail with reference to embodiments, embodiment is intended to explain and non-limiting technology of the invention
Scheme.
A kind of biomechanical system sheared for cell flow with stretching culture is provided in the present embodiment, and structure is as schemed
Shown in 1.
As shown in Figure 1, described sheared for cell flow has a job with the biomechanical system 100 for stretching culture
Table top 10.It is described to include for cell flow shearing and the biomechanical system 100 of stretching culture:Stretching device 20 and at least one
Micro-fluidic chip 30, the micro-fluidic chip 30 are connected by an at least clamping device 40 with the stretching device 20.In this reality
Apply in example, it is described for cell flow shear with stretch culture biomechanical system 100 include a micro-fluidic chip 30 and
One clamping device 40.Certainly, in other embodiments, multiple micro-fluidic chips can be fixed using a clamping device 40
30, or fix multiple micro-fluidic chips 30 using multiple clamping devices 40.
The structure of the stretching device 20 is specifically described below in conjunction with Fig. 1.
The stretching device 20 includes:One first screw rod bracket 210, one second screw rod bracket 212, a forward lead screw 220,
Two reciprocating block slider guide rods (being overlapped in figure with the forward lead screw 220), one first reciprocating block slider 230, one second reciprocating block sliders
232 and a motor 240.
First screw rod bracket 210 and second screw rod bracket 220, which are relatively fixed, is arranged at the work top 10
On;The forward lead screw 220 is supported by first screw rod bracket 210 and second screw rod bracket 212.It is and described reciprocal sliding
Block guide rod is arranged in parallel and by first screw rod bracket 210 and second screw rod bracket 212 with the forward lead screw 220
Support.Also, the reciprocating block slider guide rod is divided into the both sides of the forward lead screw 220, thus, in Fig. 1, the reciprocating block slider
Guide rod is overlapped with the forward lead screw 220.
It is as shown in Figure 1, first reciprocating block slider 230 and second reciprocating block slider 232 be respectively arranged at it is described just
On anti-screw 220, that is to say, that the forward lead screw 220 runs through first reciprocating block slider 230 and second reciprocating block slider
232.Also, the reciprocating block slider guide rod also extends through first reciprocating block slider 230 and second reciprocating block slider 232.
As shown in Figure 1, the motor 240 is fixedly installed on the work top 10, the rotation band of the motor 240
The forward lead screw 220 is moved to rotate.
Based on above-mentioned structure, when the motor 240 rotates, the rotation of the motor 240 drives the forward lead screw
Rotation, and then drive first reciprocating block slider 230 opposite along the reciprocating block slider guide rod with second reciprocating block slider 232
It is mobile.
It is bonded and is formed by cover plate 312 and substrate 314 continuing with referring to Fig. 1, the micro-fluidic chip 30.The micro-fluidic core
The inside of piece 30 has a cavity (not showing in figure, described in detail below).The cavity has an entrance and an outlet, can be with leading
Pipe 320 fluidly connects respectively to be fluidly connected with the entrance of the micro-fluidic chip 30 and outlet;Also, the clamping device
40 are fixedly installed on first reciprocating block slider 230 and/or second reciprocating block slider 232.
The structure of the micro-fluidic chip 30 is specifically described below in conjunction with Fig. 2.
Shown in Fig. 2 is the bottom view of the cover plate 312, as shown in Figure 2, have on a surface of the cover plate 312
There is a groove 316 so that the substrate 312 forms described micro-fluidic with the cavity after fitting with the cover plate 314
Chip 30.As shown in Figure 2, the groove 316 divides for inlet region 3162, cell culture area 3164 and outlet area 3166, described
Inlet region 3162 and the entrance of the micro-fluidic chip 30 fluidly connect, the outlet area 3166 and the micro-fluidic chip
30 outlet fluidly connects;Also, the width of the groove 316 from the inlet region 3162 and the outlet area 3166 to
The cell culture area 3164 gradually increases.
As depicted in figs. 1 and 2, in use, the micro-fluidic chip 30 after being loaded onto cell first is put into incubator
It is middle culture 12 it is small when so that cell is covered on the micro-fluidic chip 30.Due to being formed on the surface of the cover plate 314
Groove 316 is stated, and the groove 316 has the cell culture area 3164, and therefore, the cell after culture is covered in described thin
In born of the same parents cultivation region 3164.Then, the first reciprocating block slider 230 and described second are placed into the both ends of the micro-fluidic chip 30 respectively
On reciprocating block slider 232.It is past that the both ends of the micro-fluidic chip 30 are separately fixed at described first by the clamping device 40
On multiple sliding block 230 and second reciprocating block slider 232.After starting the motor 240, the motor 240 drives the positive and negative silk
Bar 220 rotates, and then drives first reciprocating block slider 230 to be led with second reciprocating block slider 232 along the reciprocating block slider
Bar relatively moves.Since the micro-fluidic chip 30 is made of elastic material, with first reciprocating block slider 230
With the relative movement of second reciprocating block slider 232, it is possible to achieve the periodic reverse of the micro-fluidic chip 30 is stretched, from
And the mechanical stimulation that the cell being covered in the cell culture area 3164 is stretched at the same time.
In addition, by the conduit 320, fluid forces device (not shown) and the micro-fluidic chip 30 can be connected
Connect, the fluid forces device can be peristaltic pump or syringe pump.In this way, circulating liquid can be carried out to cell by peristaltic pump
Shearing, or acyclic liquid shear effect is carried out to cell by syringe pump.
Due to the structure design of biological Force system of the present invention so that can be separately through the adjusting motor 240
Rotary speed and angle, are realized to the different frequency of cell in the micro-fluidic chip 30 and the stretching of length, meanwhile, also may be used
To carry out liquid shear to the cell in the micro-fluidic chip 30 by the fluid forces device.It is micro- outside by system
Mirror can observe the difference of cell morphologically in the micro-fluidic chip 30.Outlet liquid is collected, carries out ALP detections, can
Draw the cellular change under different mechanical stimulations.
In biomechanical system of the present invention, using the micro-fluidic chip with regular shape cavity come instead of existing
Having has the timbering material of irregular holes in technology so that the flow field that fluid passes through is more uniform and stable, so that cell
The size direction of suffered hydrodynamic shear is consistent;At the same time under stretching action, the deformation of the chip direction on microcosmic is consistent, makes
The drawing force size and Orientation obtained suffered by cell is also consistent.In addition, biomechanical system of the present invention is compared with the prior art,
Structure is more succinct, using the design of positive anti-leading screw then under the driving of same motor, it can be achieved that two sliding blocks move toward one another,
Observed easy to install microscope additional.
The present invention is described by above-mentioned related embodiment, but above-described embodiment is only the example for implementing the present invention.
It must be noted that, it has been disclosed that embodiment be not limiting as the scope of the present invention.On the contrary, it is contained in the spirit of claims
And the modification of scope and impartial setting are included in the scope of the present invention.
Claims (9)
1. a kind of biomechanical system sheared for cell flow with stretching culture, has a work top, it is characterised in that
The biomechanical system includes a stretching device and an at least micro-fluidic chip, and the micro-fluidic chip is clamped by least one
Device is connected with the stretching device, wherein,
The stretching device includes:
One first screw rod bracket and one second screw rod bracket, first screw rod bracket and second screw rod bracket are relatively fixed
It is arranged on the work top;
One forward lead screw, the forward lead screw are supported by first screw rod bracket and second screw rod bracket;
An at least reciprocating block slider guide rod, the reciprocating block slider guide rod are arranged in parallel with the forward lead screw, and described reciprocal sliding
Block guide rod is supported by first screw rod bracket and second screw rod bracket;
One first reciprocating block slider and one second reciprocating block slider, first reciprocating block slider and second reciprocating block slider are set respectively
In in the forward lead screw, the reciprocating block slider guide rod passes through first reciprocating block slider and the second reciprocating block slider, described positive and negative
The rotation of screw drives first reciprocating block slider to be relatively moved with second reciprocating block slider along the reciprocating block slider guide rod;
And
One motor, the motor are fixedly installed on the work top, and the rotation of the motor drives the forward lead screw rotation
Turn;
There is a cavity, the cavity has an entrance and an outlet, the connecting conduit difference inside the micro-fluidic chip
Fluidly connected with the entrance of the micro-fluidic chip and outlet;
Also, the clamping device is fixedly installed on first reciprocating block slider and/or one second reciprocating block slider.
2. biomechanical system as claimed in claim 1, it is characterised in that the micro-fluidic chip is made of elastic material.
3. biomechanical system as claimed in claim 2, it is characterised in that the micro-fluidic chip includes a substrate and a lid
Piece, has a groove on a surface of the cover plate so that the substrate is formed with described after fitting with the cover plate
The micro-fluidic chip of cavity;The connecting conduit is connected by the entrance and outlet with the recessed fluid.
4. biomechanical system as claimed in claim 2, it is characterised in that the elastic material selects dimethyl siloxane.
5. biomechanical system as claimed in claim 2, it is characterised in that the biomechanical system further includes a fluid and pushes away
Dynamic device, the fluid forces device are fluidly connected by connecting conduit and the micro-fluidic chip.
6. biomechanical system as claimed in claim 5, it is characterised in that the fluid forces device is selected from peristaltic pump or note
Penetrate one kind in pump.
7. biomechanical system as claimed in claim 3, it is characterised in that the groove is divided into inlet region, cell culture area
And outlet area, the entrance of the inlet region and the micro-fluidic chip fluidly connect, the outlet area with it is described micro-fluidic
The outlet of chip fluidly connects;Also, the width of the groove is from the inlet region and the outlet area to the cell
Cultivation region gradually increases.
8. biomechanical system as claimed in claim 3, it is characterised in that the interior table of the cavity of the micro-fluidic chip
A protein modification layer is formed on face.
9. biomechanical system as claimed in claim 8, it is characterised in that the protein is selected from matrigel, fine even egg
White and gelation solution.
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Cited By (1)
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CN110438004A (en) * | 2019-09-04 | 2019-11-12 | 北京航空航天大学 | Flat flow chamber that is a kind of while applying static stretch power and Osima jacoti, Osima excavata |
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