CN109929761A - Cell dynamic cultivation chip and cell dynamic cultivation device - Google Patents
Cell dynamic cultivation chip and cell dynamic cultivation device Download PDFInfo
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- CN109929761A CN109929761A CN201910366162.XA CN201910366162A CN109929761A CN 109929761 A CN109929761 A CN 109929761A CN 201910366162 A CN201910366162 A CN 201910366162A CN 109929761 A CN109929761 A CN 109929761A
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Abstract
The present invention relates to cell dynamic cultivation chip and cell dynamic cultivation devices, wherein the former includes chip substrate and at least two cell culture chambers that are set on chip substrate;It is sequentially communicated to form closed circuit by circulatory flow between at least two cell culture chambers;And elastic-sealing-valve is provided on the position between flanking cell culturing room of circulatory flow;Circulatory flow includes the stretch section made of elastic film material, and stretch section includes at least one section of bending part;The latter includes the former and the first function pedestal, and the first function pedestal includes the first base body, the rotating disk that is installed on by rotating mechanism on the first base body, end face idler wheel is provided on the end face of rotating disk, end face idler wheel is contacted with stretch section.The present invention can carry out dynamic cultivation to multiple types cell simultaneously, have the beneficial effects such as easy to operate, conventional efficient is high.
Description
Technical field
The present invention relates to biological cell culture technique fields, in particular to a kind of cell dynamic cultivation chip and carefully
Born of the same parents' dynamic cultivation device.
Background technique
With the continuous development of cell culture technology, in order to solve plane static culture to cell growth microenvironment simulation journey
Low, the problem of cell growing environment and organism itself differ greatly is spent, people begin to use the mode of dynamic cultivation in biology
External to carry out cell culture, common cell dynamic cultivation mode includes perfusion culture, microgravity culture, organizational project three-dimensional branch
Frame culture, the diversified forms such as mechanical force stimulation culture.Cell dynamic cultivation is due to can more preferably simulation organism inner cell grow
Microenvironment, and introduce shearing force, mechanical force, the external force such as microgravity stimulation, to the Proliferation, Differentiation etc. for promoting target culture cell
There is preferable effect.With research development and deeply, for often needing to use the researcher of cell dynamic cultivation technology
For engineers and technicians, it usually can all face and need the problem of cultivating multiple cell types.
Since different types of cell needs to be cultivated using different dynamic cultivation methods, corresponding thereto,
Need the cell cultivation equipment and consumptive material using different function;Cultivate different types of cell may mean that need replacing with
Its laboratory apparatus and consumptive material for matching, this will undoubtedly bring the problem that laboratory apparatus is idle and experiment progress is slow.
In addition, can be used for the cell culture apparatus of various kinds of cell joint dynamic cultivation due to there is no in currently available technology,
Thus, for there are many for the engineers and technicians of cell joint dynamic cultivation demand, then self assemble difference can only be passed through
The culture apparatus or even designed, designed of manufacturer's production make new culture apparatus to complete experiment purpose, and there are when Preparatory work of experiment
Between long and experimentation it is cumbersome difficult the problems such as.
Summary of the invention
Present invention has been made in view of the above problems, and its purpose is to provide a kind of cell dynamic cultivation chip and cells
Dynamic cultivation device can be connected to multiple cell culture chambers by circulatory flow, and by applying to the stretch section of circulatory flow
Add external force to make the culture solution in circulatory flow be in flow regime to meet cell dynamic cultivation condition;Meanwhile it needing
When to variety classes cell culture, can by elastic-sealing-valve to being carried out between each cell culture chamber for sexual isolation culture,
And then the cell of a variety of types is cultivated simultaneously, there are the beneficial effects such as easy to operate, conventional efficient is high.
The following technical scheme is adopted to achieve the purpose of the present invention:
In a first aspect, the embodiment of the present invention provides a kind of cell dynamic cultivation chip, which includes
Chip substrate and at least two cell culture chambers being set on chip substrate;
It is sequentially communicated to form closed circuit by circulatory flow between at least two cell culture chambers;And in circulatory flow
Elastic-sealing-valve is provided on position between two neighboring cell culture chamber, elastic-sealing-valve is configured to control loop stream
The on-off in road;Circulatory flow includes the stretch section made of elastic film material, and stretch section includes at least one section of bending part.
With reference to first aspect, the embodiment of the invention provides the first possible embodiments of first aspect, in chip
It is provided with multiple culture tanks on substrate, and is spaced apart from each other between every two culture tank;The corresponding installation at least two culture tanks
There is cell culture unit, constitutes cell culture chamber between cell culture unit and corresponding culture tank.
With reference to first aspect and its first possible embodiment, the embodiment of the invention provides the second of first aspect
The possible embodiment of kind, cell culture unit includes semi-transparent Membrance cuiture unit;
Semi-transparent Membrance cuiture unit includes the semi-permeable membrane cell culture container for being sequentially communicated setting from the bottom to top, semi-transparent theca cell
Culturing room's sealing cover and top cover are equipped with gas-tpe fitting on semi-permeable membrane cell culture chamber sealing cover, are equipped on top cover
Medium circulation pipeline;Semi-permeable membrane cell culture container is installed on a culture tank and constitutes between corresponding culture tank semi-transparent
Theca cell culturing room.
With reference to first aspect and its first possible embodiment, the embodiment of the invention provides the thirds of first aspect
The possible embodiment of kind, cell culture unit includes histocyte culture unit;
Histocyte culture unit includes tissue block cell culture container, the capping of tissue block cell culture chamber and heparin
Cap;The capping of tissue block cell culture chamber has downward opening accommodating chamber, and calparine cap is installed on the capping of tissue block cell culture chamber
Top and be connected to the inside of accommodating chamber;Tissue block cell culture container is installed on the inside of accommodating chamber;The training of tissue block cell
Room capping is supported to be installed on a culture tank and constitute histocyte culturing room between corresponding culture tank.
One of with reference to first aspect and its first to the third possible embodiment, and the embodiment of the invention provides first
4th kind of possible embodiment of aspect, the cell dynamic cultivation chip further include ventilative unit, and ventilative unit includes de-bubble
Structure, vent seal lid and air filter, and from bottom to top successively except bubble structure, vent seal lid and air filter
Setting;The inside of air filter and vent seal lid is interconnected;Vent seal lid is installed on a culture tank simultaneously
It will be closed in the inside of corresponding culture tank except bubble structure, is constituted between vent seal lid and corresponding culture tank and remove bubble chamber;
Circulatory flow is flowed through except bubble chamber, forms closed circuit between bubble chamber and each cell culture chamber to make to remove;And
Being located on the position removed between bubble chamber and flanking cell culturing room for circulatory flow is respectively arranged with elastic-sealing-valve.
Second aspect, the embodiment of the present invention also provide a kind of cell dynamic cultivation device, the cell dynamic cultivation device packet
The cell dynamic cultivation chip of one of tissue cultures component and above-mentioned first aspect and its each possible embodiment offer is provided;
The tissue cultures component includes the first function pedestal, and the first function pedestal includes the first base body, passes through rotation
Mechanism is installed on the rotating disk on the first base body, and end face idler wheel, end face idler wheel and bullet are provided on the end face of rotating disk
Property section contact;
Rotating mechanism includes rotation axis, and rotating disk is installed in rotation axis, and rotating disk can be rotated around rotation axis.
In conjunction with second aspect, the embodiment of the invention provides the first possible embodiment of second aspect, stretch sections
It is set to the lower surface of chip substrate;First base body is set to the lower surface of chip substrate;
Rotating mechanism further includes floating spring and bearing block;
Rotation axis is vertically arranged on the first base body, and floating spring and bearing block are from bottom to top successively sheathed on rotation
On axis, and bearing block can slide up and down to discharge along rotation axis or compression floating spring, rotating disk are installed on bearing block
Top, end face idler wheel are set on the top surface of rotating disk, are configured to squeeze stretch section;Under the action of rotating mechanism, rotating disk
It can float along the vertical direction.
In conjunction with second aspect, the embodiment of the invention provides second of possible embodiment of second aspect, the first function
Energy pedestal further includes lifting body;
Lifting body includes jacking valve lever and jacking valve reseting spring;It is provided on the first base body along vertical
The through-hole that direction extends, jacking valve lever are installed on the inside of through-hole, and jacking valve reseting spring sleeve is set to jacking valve lever
Upper end, and jacking valve lever can be in the rising of the inside of through-hole to compress jacking valve reseting spring, in jacking valve reset bullet
Spring is under the operating condition of compressive state, is jacked and is pierced by through-hole at the top of valve lever;Free shape is in jacking valve reseting spring
Under state, the top for jacking valve lever is located at the inside of through-hole.
In conjunction with second aspect the first possible embodiment and second aspect second of possible embodiment it
One, the embodiment of the invention provides the third possible embodiments of second aspect, set in the side portion of the first base body
It is equipped with buckle, buckle is configured to for chip substrate to be fixed on the top of the first base body.
In conjunction with second aspect, the embodiment of the invention provides the 4th kind of possible embodiment of second aspect, cell trainings
Feeding unit includes semi-transparent Membrance cuiture unit;Semi-transparent Membrance cuiture unit includes semi-permeable membrane cell culture container, semi-permeable membrane cell culture
Room sealing cover and top cover, and semi-permeable membrane cell culture container, semi-permeable membrane cell culture chamber sealing cover and top cover are from bottom to top successively
Connection;Gas-tpe fitting is installed on semi-permeable membrane cell culture chamber sealing cover, medium circulation pipeline is installed on top cover;It is semi-transparent
Theca cell culture vessel is installed on a culture tank and constitutes semi-permeable membrane cell culture chamber between corresponding culture tank;
Cell dynamic cultivation device further includes outer plunger pump assembly, and outer plunger pump assembly includes the second function pedestal,
Second function pedestal includes that the second base body and the accurate sample injector being set on the second base body and accurate sample injector push away
Into mechanism;
Accurate sample injector includes the injection piston of injection-tube with the inside for being installed on injection-tube;The liquid outlet of injection-tube is logical
The first connecting line is crossed to be connected to gas-tpe fitting;Accurate sample injector propulsive mechanism is configured to control injection piston and is injecting
The inside of pipe is moved back and forth to control accurate sample injector and carry out suction action.
In conjunction with second aspect and its 4th kind of possible embodiment, the embodiment of the invention provides the 5th of second aspect the
Kind possible embodiment, accurate sample injector propulsive mechanism include lead screw and the feed screw nut that is sheathed on lead screw, feed screw nut
It is fixedly connected with injection piston, lead screw can be rotated to drive feed screw nut to move back and forth to drive along the length direction of lead screw
Dynamic injection piston is moved back and forth in the inside of injection-tube.
In conjunction with second aspect and its 4th kind of possible embodiment, the embodiment of the invention provides the 6th of second aspect the
The possible embodiment of kind, cell dynamic cultivation device further includes external peristaltic pump component, and external peristaltic pump component includes third
Function pedestal;
Third function pedestal includes third base body, peristaltic pump and peristaltic pump driving mechanism, and peristaltic pump and peristaltic pump drive
Motivation structure is mounted on third base body;The inlet of peristaltic pump is by the second connecting line and is loaded with drug to be checked
Medicine storing pot connection;The liquid outlet of peristaltic pump is connect by third connecting line with medium circulation pipeline;Peristaltic pump driving mechanism is matched
Being set to can drive peristaltic pump rotation to which drug to be checked is pumped into medium circulation pipe road.
In conjunction with second aspect and its 6th kind of possible embodiment, the embodiment of the invention provides the 7th of second aspect the
The possible embodiment of kind, cell dynamic cultivation device further includes Multi-channel switching valve component;
Medicine storing pot has multiple, and the second connecting line includes main line and multiple bye-passes for connecting respectively with main line,
Separate main line one end of each bye-pass is connected to multiple medicine storing pots one-to-one correspondence;
Multi-channel switching valve component Configuration is in fluid connection at that can control only one between bye-pass and main line
State.
In conjunction with second aspect and its 7th kind of possible embodiment, the embodiment of the invention provides the 8th of second aspect the
The possible embodiment of kind, Multi-channel switching valve component include the 4th function pedestal;
4th function pedestal includes the 4th base body, rotary spool and multiple communicating pipes;In the 4th base body
Inside installation rotary spool, installs multiple communicating pipes on the 4th base body;Multiple communicating pipes include middle part communicating pipe and enclose
Around multiple edge communicating pipes of middle part communicating pipe annular array;
Rotary spool includes valve plate, the valve core shaft for being installed on valve plate lower end and the valve core tube being installed on valve plate, valve
One end of core pipe is connected to middle part communicating pipe, and the other end of valve core tube is formed as open end;Valve plate can be rotated around valve core shaft
So that the open end of valve core tube is connected to an edge communicating pipe;
One end of the separate valve core tube of middle part communicating pipe is connected to main line, the separate valve core tube of each edge communicating pipe
One end corresponds with one end of the separate medicine storing pot of each bye-pass and is connected to.
In conjunction with second aspect and its 8th kind of possible embodiment, the embodiment of the invention provides the 9th of second aspect the
The possible embodiment of kind, Multi-channel switching valve component further includes rotation angle measurement sensing arrangement;
Rotation angle measurement sensing arrangement includes grating disc and photoelectric sensor;
Grating disc is installed on valve core shaft in a manner of it can rotate synchronously with valve plate, equal in the edge of grating disc
It is even that grid is distributed with;Photoelectric sensor is set to the edge of grating disc, is configured to the rotation angle of detection valve plate.
In conjunction with second aspect, the embodiment of the invention provides the tenth kind of possible embodiment of second aspect, cell is dynamic
State culture chip further includes ventilative unit, and unit of breathing freely includes except bubble structure, vent seal lid and air filter, and de-bubble
Structure, vent seal lid and air filter are from bottom to top set gradually;Vent seal lid is installed on a culture tank
And the inside for corresponding culture tank being closed in except bubble structure, bubble chamber is removed to constitute between corresponding culture tank;Recycle stream
Road is flowed through except bubble chamber, forms closed circuit between bubble chamber and each cell culture chamber to make to remove;And being located in circulatory flow
Except elastic-sealing-valve is respectively arranged on the position between bubble chamber and flanking cell culturing room, elastic-sealing-valve is configured to control and follows
The on-off in circulation road;
Cell dynamic cultivation device further includes gas tank, and gas tank is connected to by the 4th connecting line with air filter.
In conjunction with second aspect and its 8th kind of possible embodiment, the embodiment of the invention provides the tenth of second aspect the
A kind of possible embodiment, cell dynamic cultivation device further include master control driver and motion actuators;
Motion actuators have multiple, and the first function pedestal, the second function pedestal, third function pedestal, the 4th function
Pedestal and motion actuators are respectively provided with respective rotary clutch, standardized handover interfaces and sensor interface;Movement
Actuator further includes the rotary drive mechanism connecting with respective rotary clutch;
Multiple motion actuators pass through respectively respective rotary clutch, standardized handover interfaces and sensor interface with
Rotary clutch, the standardization switching of first function pedestal, the second function pedestal, third function pedestal and the 4th function pedestal
Interface and sensor interface connect one to one;
Master control driver passes through connecting cable respectively and connect with each motion actuators, and master control driver can be controlled respectively
Make the operating condition of the rotary drive mechanism of each motion actuators with control respectively the first function pedestal, the second function pedestal,
The respective working condition of third function pedestal and the 4th function pedestal.
In conjunction with second aspect and its second of possible embodiment, the embodiment of the invention provides the tenth of second aspect the
Two kinds of possible embodiments, cell dynamic cultivation device further include master control driver and motion actuators;
Motion actuators include the first motion actuators, and the first motion actuators and the first function pedestal respectively include respectively
Rotary clutch, standardized handover interfaces and sensor interface;The rotary clutch and rotation axis of first function pedestal connect
It connects;The rotary clutch of the rotary clutch of first motion actuators and the first function pedestal is cooperatively connected;First Motor execution
The standardized handover interfaces of device are connect with the standardized handover interfaces of the first function pedestal;The sensor of first motion actuators connects
Mouth is connect with the sensor interface of the first function pedestal;
First motion actuators further include rotary drive mechanism and lift drive mechanism, and rotary drive mechanism and first move
The rotary clutch of actuator connects;Lift drive mechanism alignment jacking valve lever is configured to make to jack valve lever in through-hole
Inside lifting;
Master control driver is connect by connecting cable with the first motion actuators, and master control driver can control rotation respectively
Turn the working condition of driving mechanism and lift drive mechanism, to control the rotary state of rotation axis and the lifting shape of jacking valve lever
State.
In conjunction with second aspect and its 12nd kind of possible embodiment, the embodiment of the invention provides the of second aspect
13 kinds of possible embodiments, the first motion actuators further include display screen and button, display screen and button respectively with rotation
Driving mechanism and lift drive mechanism electrical connection;Display screen is used to show the movement shape of rotary drive mechanism and lift drive mechanism
State information;Button for controlling rotary drive mechanism and the respective start and stop of lift drive mechanism respectively.
Compared with prior art, the embodiment of the present invention has the following beneficial effects:
The first aspect of the embodiment of the present invention provides a kind of cell dynamic cultivation chip, the cell dynamic cultivation chip packet
At least two cell culture chambers for including chip substrate and being set on chip substrate;By following between at least two cell culture chambers
Circulation road is sequentially communicated to form closed circuit;And it is provided on the position between flanking cell culturing room of circulatory flow
Elastic-sealing-valve, elastic-sealing-valve are configured to the on-off of control loop runner;Circulatory flow includes made of elastic film material
Stretch section, and stretch section includes at least one section of bending part.
In said structure, due between at least two cell culture chambers by circulatory flow be connected to, thus, can pass through to
The stretch section of circulatory flow applies external force and then so that the culture solution in circulatory flow is in flow regime to meet cell dynamic and train
The condition of supporting;Simultaneously as it is provided with elastic-sealing-valve on the position between flanking cell culturing room of circulatory flow, from
It, can be by elastic-sealing-valve to carrying out specific aim between each cell culture chamber and when needing to variety classes cell culture
Isolation culture, and then the cell of a variety of types is cultivated simultaneously;With the beneficial effects such as easy to operate, conventional efficient is high.
In addition, the second aspect of the embodiment of the present invention additionally provides a kind of cell dynamic cultivation device, cell dynamic is trained
Feeding device includes the cell dynamic training that one of tissue cultures component and above-mentioned first aspect and its each possible embodiment provide
Support chip;The tissue cultures component includes the first function pedestal, and the first function pedestal includes the first base body, passes through rotating machine
Structure is installed on the rotating disk on the first base body, and end face idler wheel, end face idler wheel and elasticity are provided on the end face of rotating disk
Section contact;Wherein, rotating mechanism includes rotation axis, and rotating disk is installed in rotation axis, and rotating disk can be rotated around rotation axis.
In use, rotating disk can be made to rotate by driving rotation axis rotation, to roll by the end face in rotating disk
Wheel carries out External force interference to stretch section, makes liquid in circulatory flow forward or reverse flow, to reach cell dynamic cultivation
Function.
To sum up, cell cultivation chip and cell culture apparatus provided in an embodiment of the present invention can be simultaneously to variety classes cells
Dynamic cultivation is carried out, there are the beneficial effects such as easy to operate, conventional efficient is high.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be to needed in the embodiment attached
Figure is briefly described, it should be understood that the following drawings illustrates only certain embodiments of the present invention, therefore is not construed as pair
The restriction of range for those of ordinary skill in the art without creative efforts, can also be according to this
A little attached drawings obtain other relevant attached drawings.
Fig. 1 is the configuration schematic diagram of cell dynamic cultivation chip provided in an embodiment of the present invention;
Fig. 2 is that the detonation configuration of the semi-transparent Membrance cuiture unit in cell dynamic cultivation chip provided in an embodiment of the present invention shows
It is intended to;
Fig. 3 is the detonation configuration of the histocyte culture unit in cell dynamic cultivation chip provided in an embodiment of the present invention
Schematic diagram;
Fig. 4 is the configuration schematic diagram of the ventilative unit in cell dynamic cultivation chip provided in an embodiment of the present invention;
Fig. 5 is the connection figure of the circulatory flow in cell dynamic cultivation chip provided in an embodiment of the present invention;
Fig. 6 is the overall structure signal of the tissue cultures component of cell dynamic cultivation device provided in an embodiment of the present invention
Figure;
Fig. 7 is the overall structure signal of the outer plunger pump assembly of cell dynamic cultivation device provided in an embodiment of the present invention
Figure;
Fig. 8 is the overall structure signal of the external peristaltic pump component of cell dynamic cultivation device provided in an embodiment of the present invention
Figure;
Fig. 9 is that the overall structure of the Multi-channel switching valve component of cell dynamic cultivation device provided in an embodiment of the present invention is shown
It is intended to;
Figure 10 is the overall structure diagram of the master control driver of cell dynamic cultivation device provided in an embodiment of the present invention;
Figure 11 is the overall structure diagram of the motion actuators of cell dynamic cultivation device provided in an embodiment of the present invention;
Figure 12 is the connecting cable wiring diagram of cell dynamic cultivation device provided in an embodiment of the present invention;
Figure 13 is the overall structure diagram of cell dynamic cultivation device provided in an embodiment of the present invention.
Appended drawing reference: the first motion actuators of A1-;The sensor interface of the first motion actuators of A1-1-;A1-2- rotation
Driving mechanism;A1-3- lift drive mechanism;A1-4- display screen;A1-5- button;A1-6- control circuit;A1-7- first is moved
The standardized handover interfaces of actuator;The rotary clutch of the first motion actuators of A1-8-;The first base body of B1-;B1-1-
End face idler wheel;B1-2- rotating disk;B1-3- floating spring;The sensor interface of B1-4- the first function pedestal;The first function of B1-5-
The rotary clutch of energy pedestal;B1-6- jacks valve lever;The standardized handover interfaces of B1-7- the first function pedestal;The top B1-8-
Rise valve reseting spring;B1-9- buckle;B1-10- rotation axis;B1-11- bearing block;B1-12- through-hole;B2- the second pedestal sheet
Body;B2-1- lead screw;B2-2- feed screw nut;The rotary clutch of B2-3- the second function pedestal;B2-4- the second function pedestal
Standardized handover interfaces;The sensor interface of B2-5- the second function pedestal;B2-6- precision sample injector;B2-61- injection-tube;B2-
62- injection piston;B3- third base body;The standardized handover interfaces of B3-1- third function pedestal;B3-2- third function
The sensor interface of pedestal;The rotary clutch of B3-3- third function pedestal;B3-4- peristaltic pump;The 4th base body of B4-;
The standardized handover interfaces of the 4th function pedestal of B4-1-;The sensor interface of the 4th function pedestal of B4-2-;The 4th function of B4-3-
The rotary clutch of pedestal;B4-4- photoelectric sensor;B4-5- grating disc;B4-6- rotary spool;B4-61- valve plate;B4-62-
Valve core shaft;B4-63- valve core tube;B4-7- communicating pipe;Communicating pipe in the middle part of B4-71-;B4-72- edge communicating pipe;C1-1- is semi-transparent
Theca cell culturing room sealing cover;C1-2- air hole;The capping of C1-3- tissue block cell culture chamber;C1-4- calparine cap;C1-5- bullet
Property sealing valve;C1-6- vent seal lid;C1-7- stretch section;C1-8- chip substrate;C1-9- removes bubble structure;C1-10- air
Filter;C1-11- tissue block cell culture container;C1-12- semi-permeable membrane cell culture container;C1-13- gas-tpe fitting;C1-
14- top cover;C1-15- medium circulation pipeline;C1-16- culture tank;C1-17- circulatory flow;D-1- air pump;D-2- built-in power
Module;D-3- mainboard;G- connecting cable;The first connecting line of E1-;E21- main line;E22- bye-pass;The second connecting tube of E2-
Road;E3- third connecting line;The 4th connecting line of E4-;F1- drug to be checked;F3- sampling injector;F4- gas tank.
Specific embodiment
In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with the embodiment of the present invention
In attached drawing, technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described embodiment is
A part of the embodiment of the present invention, instead of all the embodiments.The present invention being usually described and illustrated herein in the accompanying drawings is implemented
The component of example can be arranged and be designed with a variety of different configurations.
Therefore, the detailed description of the embodiment of the present invention provided in the accompanying drawings is not intended to limit below claimed
The scope of the present invention, but be merely representative of selected embodiment of the invention.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without creative efforts belongs to the model that the present invention protects
It encloses.
It should also be noted that similar label and letter indicate similar terms in following attached drawing, therefore, once a certain Xiang Yi
It is defined in a attached drawing, does not then need that it is further defined and explained in subsequent attached drawing.
In the description of the present invention, it should be noted that term " center ", "upper", "lower", "left", "right", "vertical",
The orientation or positional relationship of the instructions such as "horizontal", "inner", "outside" is to be based on the orientation or positional relationship shown in the drawings, or be somebody's turn to do
Invention product using when the orientation or positional relationship usually put, be merely for convenience of description of the present invention and simplification of the description, without
It is that the device of indication or suggestion meaning or element must have a particular orientation, be constructed and operated in a specific orientation, therefore not
It can be interpreted as limitation of the present invention.In addition, term " first ", " second ", " third " etc. are only used for distinguishing description, and cannot manage
Solution is indication or suggestion relative importance.
In addition, the terms such as term "horizontal", "vertical", " pendency " are not offered as requiring component abswolute level or pendency, and
It is that can be slightly tilted.It is not to indicate the structure if "horizontal" only refers to that its direction is more horizontal with respect to for "vertical"
It has to fully horizontally, but can be slightly tilted.
In the description of the present invention, it is also necessary to which explanation is unless specifically defined or limited otherwise, term " setting ",
" installation ", " connected ", " connection " shall be understood in a broad sense, for example, it may be fixedly connected, may be a detachable connection or one
Connect to body;It can be mechanical connection, be also possible to be electrically connected;It can be directly connected, it can also be indirect by intermediary
It is connected, can be the connection inside two elements.For the ordinary skill in the art, on being understood with concrete condition
State the concrete meaning of term in the present invention.
With reference to the accompanying drawing, it elaborates to some embodiments of the present invention.In the absence of conflict, following
Feature in embodiment and embodiment can be combined with each other.
First embodiment
Fig. 1 is please referred to, in conjunction with Fig. 5, the present embodiment provides a kind of cell dynamic cultivation chip, the cell dynamic cultivation chips
Including chip substrate C1-8 and at least two cell culture chambers being set on chip substrate C1-8.
It is sequentially communicated to form closed circuit by circulatory flow C1-17 between at least two above-mentioned cell culture chambers;And
Elastic-sealing-valve C1-5, elastic packing are provided on the position between flanking cell culturing room of circulatory flow C1-17
Valve C1-5 is configured to the on-off of control loop runner C1-17;Circulatory flow C1-17 includes the stretch section made of elastic film material
C1-7, and stretch section C1-7 includes at least one section of bending part.Wherein, bending part may include but be not limited to include one or more snippets half
Annular bending pipeline section is bent in an arc shape pipeline section etc. including one or more snippets.
In said structure, due to being connected between at least two cell culture chambers by circulatory flow C1-17, thus, it can
The culture solution in circulatory flow C1-17 is set to be in flowing and then applying external force to the stretch section C1-7 of circulatory flow C1-17
State is to meet cell dynamic cultivation condition;Simultaneously as in circulatory flow C1-17 between flanking cell culturing room
Elastic-sealing-valve C1-5 is provided on position, thus, when needing to variety classes cell culture, can by squeeze or other outside
The mode that power deforms it ends runner, so that the mass exchange between interconnected cell culture chamber is disconnected, to each thin
It is carried out between born of the same parents culturing room for sexual isolation culture, and then cultivates the cell of a variety of types simultaneously;With easy to operate, experiment effect
The high beneficial effect of rate.
The set-up mode of above-mentioned cell culture chamber have it is a variety of, for example, by directly on chip substrate C1-8 be arranged training
Container is supported, the inner space of culture vessel itself constitutes above-mentioned cell culture chamber etc., it is preferable that is arranged on chip substrate C1-8
There are multiple culture tank C1-16, and is spaced apart from each other between every two culture tank C1-16;It is corresponding at least two culture tank C1-16
Cell culture unit is installed, constitutes above-mentioned cell culture chamber between cell culture unit and corresponding culture tank C1-16.
Optionally, for can the semi-transparent theca cell such as dynamic cultivation intestinal epithelial cell, referring to Fig. 2, in conjunction with Fig. 5, above-mentioned
On the basis of the structure of preferred cell culture chamber, above-mentioned cell culture unit includes semi-transparent Membrance cuiture unit.Semi-permeable membrane training
Feeding unit includes semi-permeable membrane cell culture container C1-12, semi-permeable membrane cell culture chamber sealing cover C1-1 and top cover C1-14, and half
Permeable membrane cell culture container C1-12, semi-permeable membrane cell culture chamber sealing cover C1-1 and top cover C1-14 are from bottom to top sequentially communicated;
Gas-tpe fitting C1-13 is installed on semi-permeable membrane cell culture chamber sealing cover C1-1, is formed at the nozzle of gas-tpe fitting C1-13
Stomata C1-2;Medium circulation pipeline C1-15 is installed on top cover C1-14;Semi-permeable membrane cell culture container C1-12 is installed on one
Semi-permeable membrane cell culture chamber is constituted on a culture tank C1-16 and between corresponding culture tank C1-16.Thus can be by semi-permeable membrane
Cell is placed in semi-permeable membrane cell culture chamber and carries out dynamic cultivation to it.Wherein, the envelope to ensure semi-permeable membrane cell culture chamber
Closing property can make semi-permeable membrane cell culture chamber sealing cover C1-1 by screw thread or be pressed into semi-permeable membrane cell culture container C1-12, and
The semi-permeable membrane cell culture consumptive material of standard, the semi-transparent Membrance cuiture after insertion are inserted into semi-permeable membrane cell culture chamber sealing cover C1-1
The lateral wall of consumptive material and the inner sidewall of semi-permeable membrane cell culture container C1-12 fit closely to form sealing.
Optionally, for can the histocytes such as dynamic cultivation liver organization, renal tissue, spleen tissue, cardiac muscular tissue, ginseng
According to Fig. 3, in conjunction with Fig. 5, on the basis of the structure of above-mentioned preferred cell culture chamber, above-mentioned cell culture unit includes that tissue is thin
Born of the same parents cultivate unit.The histocyte culture unit includes tissue block cell culture container C1-11, the capping of tissue block cell culture chamber
C1-3 and calparine cap C1-4;Tissue block cell culture chamber, which covers C1-3, has downward opening accommodating chamber, calparine cap C1-4 peace
Top loaded on tissue block cell culture chamber capping C1-3 is simultaneously connected to the inside of accommodating chamber;Tissue block cell culture container C1-
11 are installed on the inside of accommodating chamber;Tissue block cell culture chamber capping C1-3 be installed on a culture tank C1-16 and with it is corresponding
Culture tank C1-16 between constitute histocyte culturing room.To tissue block cell is placed in histocyte culturing room
Dynamic cultivation is carried out to it.Wherein, it is the closure for ensuring histocyte culturing room, tissue block cell culture chamber can be made to cover
C1-3 passes through in screw thread or indentation culture tank C1-16.In addition, can by calparine cap C1-4 as syringe from histocyte culture
The channel of reagent is extracted or injected in room.
Optionally, referring to Fig. 4, in conjunction with Fig. 5, above-mentioned cell dynamic cultivation chip further includes ventilative unit, above-mentioned preferred
Cell culture chamber structure on the basis of, ventilative unit includes de-bubble structure C 1-9, vent seal lid C1-6 and air mistake
Filter C1-10, and de-bubble structure C 1-9, vent seal lid C1-6 and air filter C1-10 are from bottom to top set gradually;It is empty
The inside of air filter C1-10 and vent seal lid C1-6 is interconnected;Vent seal lid C1-6 is installed on a culture
Be closed in the inside of corresponding culture tank C1-16 on slot C1-16 and by de-bubble structure C 1-9, vent seal lid C1-6 with it is corresponding
Culture tank C1-16 between constitute remove bubble chamber;Circulatory flow C1-17 is flowed through except bubble chamber, to make to train except bubble chamber and each cell
It supports and forms closed circuit between room;And being located at except the position between bubble chamber and flanking cell culturing room in circulatory flow C1-17
On be respectively arranged with elastic-sealing-valve C1-5, elastic-sealing-valve C1-5 is configured to the on-off of control loop runner C1-17.To,
It can stop the bubble or impurity that swim in cell dynamic cultivation chip interior circulatory mediator surface by de-bubble structure C 1-9, pass through
Air filter C1-10 is filtered the gas diffused into cell culture room;To improve cell survival rate.Similarly,
Vent seal lid C1-6 can be by screw thread or indentation culture tank C1-16.
The above semi-transparent Membrance cuiture unit, histocyte culture unit and ventilative unit can need to carry out according to actual tests
Selectivity configuration, for example, configuration cell culture unit includes semi-transparent Membrance cuiture unit, histocyte culture unit and ventilative list
One or both of member, or configuration cell culture unit include semi-transparent Membrance cuiture unit, histocyte culture unit and thoroughly
Gas unit.
Second embodiment
Fig. 6 is please referred to, the present embodiment provides a kind of cell dynamic cultivation devices, which includes tissue
Culture assembly and above-mentioned cell dynamic cultivation chip.
Wherein, tissue cultures component includes the first function pedestal, and the first function pedestal includes the first base body B1, passes through
Rotating mechanism is installed on the rotating disk B1-2 on the first base body B1, and end face idler wheel is provided on the end face of rotating disk B1-2
B1-1, end face idler wheel B1-1 are contacted with stretch section C1-7;Rotating mechanism includes rotation axis B1-10, and rotating disk B1-2, which is installed on, to be turned
On moving axis B1-10, and rotating disk B1-2 can be rotated around rotation axis B1-10.
In use, rotating disk B1-2 can be made to rotate by driving rotation axis B1-10 rotation, to pass through rotating disk
End face idler wheel B1-1 on B1-2 carries out External force interference to stretch section C1-7, make liquid in circulatory flow C1-17 forward or
Reverse flow, to reach cell dynamic cultivation function.
Optionally, the lower surface of chip substrate C1-8 is set to continued reference to Fig. 6, stretch section C1-7;First base body
B1 is set to the lower surface of chip substrate C1-8;Rotating mechanism further includes floating spring B1-3 and bearing block B1-11;Rotation axis
B1-10 is vertically arranged on the first base body B1, and floating spring B1-3 and bearing block B1-11 are from bottom to top successively sheathed on and turn
On moving axis B1-10, and bearing block B1-11 can slide up and down to discharge or compress floating spring B1-3 along rotation axis B1-10,
Rotating disk B1-2 is installed on the top of bearing block B1-11, and end face idler wheel B1-1 is set on the top surface of rotating disk B1-2, is configured to
Squeeze stretch section C1-7;Under the action of rotating mechanism, rotating disk B1-2 can float along the vertical direction.
To rotating disk B1-2 be made to float along the vertical direction using floating spring B1-3 so that end face is rolled in assembly
Wheel B1-1 and stretch section C1-7 comes into full contact with, and is further ensured that under the action of rotating mechanism, the first pedestal can drive recycle stream
Liquid flowing in road C1-17.Certainly, above-mentioned stretch section C1-7 may not be the lower surface for being set to chip substrate C1-8,
But it hangs and is inverted the first base body B1 and the liquid in circulatory flow C1-17 is driven etc..
Optionally, with continued reference to Fig. 6, the first function pedestal further includes lifting body;Lifting body includes jacking valve lever
B1-6 and jacking valve reseting spring B1-8;The through-hole B1-12 extended along the vertical direction is provided on the first base body B1,
Jacking valve lever B1-6 is installed on the inside of through-hole B1-12, and jacking valve reseting spring B1-8 is sheathed on jacking valve lever B1-6
Upper end, and jack valve lever B1-6 can the inside of through-hole B1-12 rise with compress jacking valve reseting spring B1-8,
Jacking valve reseting spring B1-8 is under the operating condition of compressive state, is jacked and is pierced by through-hole B1-12 at the top of valve lever B1-6;?
Jacking valve reseting spring B1-8 is under free state, and the top of jacking valve lever B1-6 is located at the inside of through-hole B1-12.By
This, can make to jack valve lever B1-6 alignment elastic-sealing-valve C1-5, thus by being pierced by or contracting at the top of jacking valve lever B1-6
Through-hole B1-12 is returned to close or open to elastic-sealing-valve C1-5, realizes the dynamic cultivation of multiple types cell.
Optionally, with continued reference to Fig. 6, the side portion of the first base body B1 is provided with buckle B1-9, buckle B1-9 matches
It is set to the top that chip substrate C1-8 is fixed on to the first base body B1.Thus can be by buckle B1-9 to chip substrate C1-
8 are fixed, and improve the stability of chip substrate C1-8 in experimentation.
Optionally, Fig. 7 is please referred to, in conjunction with Fig. 2 and Figure 13, above-mentioned cell culture unit includes semi-transparent Membrance cuiture unit;Phase
Ying Di, which further includes outer plunger pump assembly.Outer plunger pump assembly includes the second function pedestal, the
Two function pedestals include the second base body B2 and the accurate sample injector B2-6 that is set on the second base body B2 and it is accurate into
Sample device propulsive mechanism;Accurate sample injector B2-6 includes that injection-tube B2-61 and the injection for the inside for being installed on injection-tube B2-61 are living
Fill in B2-62;The liquid outlet of injection-tube B2-61 is connected to by the first connecting line E1 with gas-tpe fitting C1-13;Accurate sample injector pushes away
Control injection piston B2-62 is configured into mechanism to move back and forth in the inside of injection-tube B2-61 to control accurate sample introduction
Device B2-6 carries out suction action.
To be pressed when carrying out dynamic cultivation to the semi-transparent theca cell such as intestinal epithelial cell by outer plunger pump assembly
Setpoint frequency cyclic suction provides pressure positively or negatively for semi-transparent Membrance cuiture unit, and semi-permeable membrane is driven to shrink by corresponding frequencies
Wriggling is provided with diastole and then for the cell cultivated on semi-permeable membrane.
Optionally, with continued reference to Fig. 7, above-mentioned precision sample injector propulsive mechanism includes lead screw B2-1 and is sheathed on lead screw B2-1
On feed screw nut B2-2, feed screw nut B2-2 is fixedly connected with injection piston B2-62, and lead screw B2-1 can be rotated to drive
Feed screw nut B2-2 moves back and forth to drive injection piston B2-62 in injection-tube B2-61 along the length direction of lead screw B2-1
Inside move back and forth.Certainly, above-mentioned accurate sample injector propulsive mechanism may be the directly transmitting straight line fortune such as cylinder assembly
Dynamic composed structure etc., still, to guarantee to promote accuracy the combination, it is preferable to use above-mentioned lead screw B2-1 and feed screw nut B2-2
Structure.
Optionally, Fig. 8 is please referred to, in conjunction with Fig. 2 and Figure 13, which further includes external peristaltic pump group
Part.External peristaltic pump component includes third function pedestal;Third function pedestal include third base body B3, peristaltic pump B3-4 and
Peristaltic pump driving mechanism, peristaltic pump B3-4 and peristaltic pump driving mechanism are mounted on third base body B3;Peristaltic pump B3-4
Inlet connect with the medicine storing pot for being loaded with drug F1 to be checked by the second connecting line E2;The liquid outlet of peristaltic pump B3-4 is logical
Third connecting line E3 is crossed to connect with medium circulation pipeline C1-15;Peristaltic pump actuator configuration is at can drive peristaltic pump B3-
4 rotations are to be pumped into medium circulation pipeline C1-15 for drug F1 to be checked.To can be by external wriggling component to each cell
Culture unit is pumped into drug F1 to be checked, wherein drug F1 to be checked can be single drug or a variety of drugs, and drug F1 to be checked is flowed through
It is absorbed into the circulatory flow C1-17 below cell chip when semi-transparent theca cell by semi-transparent theca cell, is absorbed by semi-transparent theca cell
Drug flow through each cell culture unit through circulatory flow C1-17.
Optionally, Fig. 9 is please referred to, in conjunction with Fig. 2 and Figure 13, which further includes Multi-channel switching valve group
Part.Medicine storing pot has multiple, and the second connecting line E2 includes main line E21 and multiple branch pipes for connecting respectively with main line E21
One end separate main line E21 of road E22, each bye-pass E22 are connected to multiple medicine storing pots one-to-one correspondence;Multi-channel switching valve group
Part is configured to control only between a bye-pass E22 and main line E21 in fluid connection state.
To unused medicament categories be selected to cultivate the cells by Multi-channel switching valve component.
Optionally, with continued reference to Fig. 9, which includes the 4th function pedestal;4th function pedestal packet
Include the 4th base body B4, rotary spool B4-6 and multiple communicating pipe B4-7;Rotation is installed in the inside of the 4th base body B4
Rotary plate B4-6 installs multiple communicating pipe B4-7 on the 4th base body B4;Multiple communicating pipe B4-7 include middle part communicating pipe
B4-71 and multiple edge communicating pipes B4-72 around middle part communicating pipe B4-71 annular array;Rotary spool B4-6 includes valve plate
B4-61, the valve core shaft B4-62 for being installed on the lower end valve plate B4-61 and the valve core tube B4-63 being installed on valve plate B4-61, valve
One end of core pipe B4-63 is connected to middle part communicating pipe B4-71, and the other end of valve core tube B4-63 is formed as open end;Valve plate B4-
61 can rotate around valve core shaft B4-62 so that the open end of valve core tube B4-63 is connected to edge communicating pipe B4-72;In
One end of the separate valve core tube B4-63 of portion's communicating pipe B4-71 is connected to main line E21, each edge communicating pipe B4-72 it is separate
One end of valve core tube B4-63 corresponds with one end of the separate medicine storing pot of each bye-pass E22 and is connected to.
Its working principle is that: when needing to replace drug, rotational valve core shaft B4-62, then valve plate B4-61 turns
It is dynamic, valve core tube B4-63 rotation is driven, stops turning when the open end of valve core tube B4-63 is connected to edge communicating pipe B4-72
It is dynamic, then corresponding edge communicating pipe B4-72 can be connected to middle part communicating pipe B4-71, i.e., by a bye-pass E22 and main line
E21 connection, then for medicine.
Optionally, with continued reference to Fig. 9, which further includes rotation angle measurement sensing arrangement.Rotation
Angle measurement sensing arrangement includes grating disc B4-5 and photoelectric sensor B4-4;Grating disc B4-5 is with can be same with valve plate B4-61
The mode of step rotation is installed on valve core shaft B4-62, is evenly distributed with grid in the edge of grating disc B4-5;Photoelectric transfer
Sensor B4-4 is set to the edge of grating disc B4-5, is configured to the rotation angle of detection valve plate B4-61.To pass through
Above structure detects the rotational angle of valve plate B4-61, to cooperate external control unit outside to carry out accurate control to rotational angle
System avoids drug from leaking while improving conventional efficient.
Optionally, referring to Fig.1 3, in conjunction with Fig. 4, Fig. 5, which further includes ventilative unit, correspondingly,
The cell dynamic cultivation device further includes gas tank F4, and gas tank F4 is connected to by the 4th connecting line E4 with air filter C1-10.
As a result, clean gas can be provided to each cell culture unit by gas tank F4.
In the above structure, damaged caused by tissue block cell for clear various kinds of drug, it can be when one section of drug effect
Between after stop external peristaltic pump component operation.Jacking valve lever B1-6 lifting on first base body B1 is close with sealed elastic
Seal valve C1-5.Each histocyte culture unit is in the state of individual segmentation at this time.It will be in each histocyte culture unit
Histocyte independently cultivate and punctured on each histocyte culture unit respectively using sampling injector F3 after a period of time
Calparine cap C1-4, is added the detection tissue block cell such as trypan blue dead reagent living, and sampling injector is used in reaction again after a certain period of time
F3 punctures calparine cap C1-4 abstraction reaction liquid, detects tissue damaged's situation.
Further optionally, 0, Figure 11 and Figure 12, the cell dynamic cultivation device further include master control driver D referring to Fig.1
With motion actuators A.
Motion actuators A has multiple, and the first function pedestal, the second function pedestal, third function pedestal, the 4th function
Pedestal and motion actuators A are respectively provided with respective rotary clutch, standardized handover interfaces and sensor interface;Movement
Actuator A further includes the rotary drive mechanism connecting with respective rotary clutch;Multiple motion actuators A pass through respectively respectively
Rotary clutch, standardized handover interfaces and sensor interface and the first function pedestal, the second function pedestal, third function
The respective rotary clutch of pedestal and the 4th function pedestal, standardized handover interfaces and sensor interface, which correspond, to be connected
It connects.Master control driver D passes through connecting cable G respectively and connect with each motion actuators A, and master control driver D can be controlled respectively
Make the operating condition of the rotary drive mechanism of each motion actuators A with control respectively the first function pedestal, the second function pedestal,
The respective working condition of third function pedestal and the 4th function pedestal.
Specifically, as shown in fig. 6, in cell culture assembly, the first function pedestal, which has, is set to the first base body
The sensor interface B1-4 of the first function pedestal on B1, the rotary clutch B1-5 of the first function pedestal, the first function pedestal
Standardized handover interfaces B1-7;
As shown in fig. 7, the second function pedestal, which has, to be set on the second base body B2 in external assembly of the plunger pump
The standard of the sensor interface B2-5 of second function pedestal, the rotary clutch B2-3 of the second function pedestal, the second function pedestal
Change switching interface B2-4;
As shown in figure 8, third function pedestal, which has, to be set on third base body B3 in external peristaltic pump component
The standard of the sensor interface B3-2 of third function pedestal, the rotary clutch B3-3 of third function pedestal, third function pedestal
Change switching interface B3-1;
As shown in figure 9, the 4th function pedestal, which has, to be set on the 4th base body B4 in Multi-channel switching valve component
The sensor interface B4-2 of the 4th function pedestal, the rotary clutch B4-3 of the 4th function pedestal, the 4th function pedestal mark
Standardization switching interface B4-1.
On the basis of the first function pedestal had not only included rotating mechanism but also had included lifting body, with the first function pedestal pair
For the motion actuators A that should be connected is the first motion actuators A1, the structure of motion actuators A is illustrated, and specific
Illustrate the connection relationship between motion actuators A and function pedestal:
The rotary clutch B1-5 of first function pedestal is connect with rotation axis B1-10;The rotation of first motion actuators from
The rotary clutch B1-5 of clutch A1-8 and the first function pedestal is cooperatively connected;The standardized handover interfaces of first motion actuators
A1-7 is connect with the standardized handover interfaces B1-7 of the first function pedestal;The sensor interface A1-1 of first motion actuators and
The sensor interface B1-4 connection of one function pedestal;
First motion actuators A1 further includes rotary drive mechanism A1-2 and lift drive mechanism A1-3, rotary drive mechanism
A1-2 is connect with the rotary clutch A1-8 of the first motion actuators;Lift drive mechanism A1-3 alignment jacking valve lever B1-6,
Being configured to makes to jack valve lever B1-6 goes up and down in the inside of through-hole B1-12.
Wherein, servo rotation motor or air motor etc. can be used in above-mentioned rotary drive mechanism A1-2, by stepping electricity
Machine or other kinds of rotating electric machine provide rotary power;Can be connected with each other by way of insertion between rotary clutch or
It is connected with each other using the modes such as frictional disk or magnetic pole attraction to realize transmitting rotary motion;Lift drive mechanism A1-3 can be used
Linear stepping motor or straight line steering engine or cylinder etc. are used as linear movement actuator;Can by way of jacking-spring return function or
Person realizes transmitting linear movement using the modes such as rack-and-pinion or magnet attraction;Insertion-rotation can then be passed through between standard interface
The mode or relatively fixed using the forms progress such as magnet actuation or bonding turned;Electric signal transmitting between sensor can pass through electricity
The mode of magnetic induction or optic communication is realized.Furthermore it is also possible to which as shown in figure 11, making the first motion actuators A1 further includes display screen
A1-4 and button A1-5, display screen A1-4 and button A1-5 are electric with rotary drive mechanism A1-2 and lift drive mechanism A1-3 respectively
Connection;Display screen A1-4 is used to show the movement state information of rotary drive mechanism A1-2 and lift drive mechanism A1-3;Button
A1-5 for controlling rotary drive mechanism A1-2 and the respective start and stop of lift drive mechanism A1-3 respectively.
Master control driver D is connect by connecting cable G with the first motion actuators A1, and master control driver D can distinguish
The working condition of rotary drive mechanism A1-2 and lift drive mechanism A1-3 are controlled, to control the rotary state of rotation axis B1-10
With the jacking condition of jacking valve lever B1-6.Skilled person will appreciate that ground, as shown in Figure 10, master control driver D include master
Plate D-3 and built-in power module D-2, thus, it can be mainboard D-3 power supply by built-in power module D-2;In addition, must be first
Motion actuators A1 configures control circuit A1-6, for make mainboard D-3 on the first motion actuators A1 and master control driver D it
Between carry out the operating status of each component inside the first motion actuators A1 of two-way data communication and control, wherein concrete application
When, mainboard D-3 can be made to connect with the PC for being equipped with upper computer software, wherein control circuit A1-6 and upper computer software can lead to
It crosses and the simple parameter transformation of prior art progress, components is replaced and are obtained, details are not described herein.In addition, having in application pneumatic
In the case where the pneumatic actuations component such as motor, air pump D-1 can be set on master control driver D, for providing the defeated of positive/negative pressure
Out.
Similarly, other motion actuators A can carry out concrete configuration according to the specific structure of each function pedestal, can also be configured
For unified one kind, to be attached between standardized handover interfaces and each function pedestal.
Certainly, it should be understood that above-mentioned master control driver D and motion actuators A can also be not provided with, but pass through
Other modes control each function pedestal and work, for example, rotating electric machine etc. is separately configured for each function pedestal.
In addition, cell dynamic cultivation chip and cell dynamic cultivation device of the invention can be by the various knots of above-described embodiment
Structure is composed, and can equally play above-mentioned effect.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations;To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement;And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (19)
1. a kind of cell dynamic cultivation chip, which is characterized in that the cell dynamic cultivation chip includes chip substrate (C1-8)
With at least two cell culture chambers being set on the chip substrate (C1-8);
It is sequentially communicated to form closed circuit by circulatory flow (C1-17) between at least two cell culture chamber;And institute
It states and is provided with elastic-sealing-valve (C1-5) on the position between the adjacent cell culture chamber of circulatory flow (C1-17),
The elastic-sealing-valve (C1-5) is configured to control the on-off of the circulatory flow (C1-17);Circulatory flow (C1-17) packet
It includes the stretch section made of elastic film material (C1-7), and the stretch section (C1-7) includes at least one section of bending part.
2. cell dynamic cultivation chip according to claim 1, which is characterized in that set on the chip substrate (C1-8)
It is equipped with multiple culture tanks (C1-16), and is spaced apart from each other between culture tank described in every two (C1-16);In at least two trainings
Support it is corresponding on slot (C1-16) cell culture unit is installed, the cell culture unit and the corresponding culture tank (C1-16)
Between constitute the cell culture chamber.
3. cell dynamic cultivation chip according to claim 2, which is characterized in that the cell culture unit includes semi-transparent
Membrance cuiture unit;
The semi-transparent Membrance cuiture unit includes semi-permeable membrane cell culture container (C1-12), semi-permeable membrane cell culture chamber sealing cover
(C1-1) and top cover (C1-14), and the semi-permeable membrane cell culture container (C1-12), the semi-permeable membrane cell culture chamber seal
Lid (C1-1) and the top cover (C1-14) are from bottom to top sequentially communicated;In the semi-permeable membrane cell culture chamber sealing cover (C1-1)
On gas-tpe fitting (C1-13) is installed, medium circulation pipeline (C1-15) is installed on the top cover (C1-14);It is described semi-transparent
Theca cell culture vessel (C1-12) be installed on the culture tank (C1-16) and with the corresponding culture tank (C1-16)
Between constitute semi-permeable membrane cell culture chamber.
4. cell dynamic cultivation chip according to claim 2, which is characterized in that the cell culture unit includes tissue
Cell culture unit;
The histocyte culture unit includes tissue block cell culture container (C1-11), the capping of tissue block cell culture chamber
(C1-3) and calparine cap (C1-4);The tissue block cell culture chamber capping (C1-3) has downward opening accommodating chamber, institute
It states calparine cap (C1-4) and is installed on the top of the tissue block cell culture chamber capping (C1-3) and the inside with the accommodating chamber
Connection;The tissue block cell culture container (C1-11) is installed on the inside of the accommodating chamber;The tissue block cell culture chamber
Capping (C1-3) is installed on the culture tank (C1-16) and the composition group between the corresponding culture tank (C1-16)
Knit cell culture chamber.
5. cell dynamic cultivation chip according to any one of claim 2 to 4, which is characterized in that the cell dynamic
Culture chip further includes ventilative unit, and the ventilative unit includes except bubble structure (C1-9), vent seal lid (C1-6) and sky
Air filter (C1-10), and it is described except bubble structure (C1-9), the vent seal lid (C1-6) and the air filter
(C1-10) it from bottom to top sets gradually;The inside phase of the air filter (C1-10) and the vent seal lid (C1-6)
It is intercommunicated;The vent seal lid (C1-6) is installed on the culture tank (C1-16) and will be described except bubble structure
(C1-9) be closed in the inside of the corresponding culture tank (C1-16), the vent seal lid (C1-6) with it is corresponding described
It is constituted between culture tank (C1-16) and removes bubble chamber;
The circulatory flow (C1-17) flow through it is described except bubble chamber, thus make it is described except bubble chamber and each cell culture chamber it
Between form closed circuit;And the circulatory flow (C1-17) be located at it is described except bubble chamber and the adjacent cell culture chamber it
Between position on be respectively arranged with elastic-sealing-valve (C1-5).
6. a kind of cell dynamic cultivation device, which is characterized in that the cell dynamic cultivation device include tissue cultures component and
Cell dynamic cultivation chip described in any one of claims 1 to 5;
The tissue cultures component includes the first function pedestal, and the first function pedestal includes the first base body (B1), leads to
The rotating disk (B1-2) that rotating mechanism is installed on first base body (B1) is crossed, in the end face of the rotating disk (B1-2)
On be provided with end face idler wheel (B1-1), the end face idler wheel (B1-1) contacts with the stretch section (C1-7);
The rotating mechanism includes rotation axis (B1-10), and the rotating disk (B1-2) is installed on the rotation axis (B1-10),
And the rotating disk (B1-2) can rotate around the rotation axis (B1-10).
7. cell dynamic cultivation device according to claim 6, which is characterized in that the stretch section (C1-7) is set to institute
State the lower surface of chip substrate (C1-8);First base body (B1) is set to the following table of the chip substrate (C1-8)
Face;
The rotating mechanism further includes floating spring (B1-3) and bearing block (B1-11);
The rotation axis (B1-10) is vertically arranged on first base body (B1), the floating spring (B1-3) and institute
It states bearing block (B1-11) to be from bottom to top successively sheathed on the rotation axis (B1-10), and the bearing block (B1-11) can
It slides up and down to discharge or compress the floating spring (B1-3), the rotating disk (B1-2) along the rotation axis (B1-10)
It is installed on the top of the bearing block (B1-11), the end face idler wheel B1-1 is set on the top surface of the rotating disk (B1-2),
It is configured to squeeze the stretch section (C1-7);Under the action of the rotating mechanism, the rotating disk (B1-2) can be vertically
It floats in direction.
8. cell dynamic cultivation device according to claim 6, which is characterized in that the first function pedestal further includes top
Rise mechanism;
The lifting body includes jacking valve lever (B1-6) and jacking valve reseting spring (B1-8);In the first pedestal sheet
The through-hole (B1-12) extended along the vertical direction is provided on body (B1), the jacking valve lever (B1-6) is installed on the through-hole
(B1-12) inside, jacking valve reseting spring (B1-8) are sheathed on the upper end of jacking valve lever (B1-6), and institute
Stating jacking valve lever (B1-6) can rise in the inside of the through-hole (B1-12) to compress the jacking valve reseting spring
(B1-8), in the case where jacking valve reseting spring (B1-8) is in the operating condition of compressive state, the jacking valve lever (B1-6)
Top be pierced by the through-hole (B1-12);In the case where the jacking valve reseting spring (B1-8) is in free state, the jacking
The top of valve lever (B1-6) is located at the inside of the through-hole (B1-12).
9. cell dynamic cultivation device according to claim 7 or 8, which is characterized in that in first base body
(B1) side portion is provided with buckle (B1-9), and the buckle (B1-9) is configured to the chip substrate (C1-8) being fixed on institute
State the top of the first base body (B1).
10. cell dynamic cultivation device according to claim 6, which is characterized in that the cell culture unit includes half
Permeable membrane culture unit;The semi-transparent Membrance cuiture unit includes semi-permeable membrane cell culture container (C1-12), semi-permeable membrane cell culture chamber
Sealing cover (C1-1) and top cover (C1-14), and the semi-permeable membrane cell culture container (C1-12), the semi-permeable membrane cell culture
Room sealing cover (C1-1) and the top cover (C1-14) are from bottom to top sequentially communicated;In the semi-permeable membrane cell culture chamber sealing cover
(C1-1) gas-tpe fitting (C1-13) is installed on, medium circulation pipeline (C1-15) is installed on the top cover (C1-14);Institute
State semi-permeable membrane cell culture container (C1-12) be installed on the culture tank (C1-16) and with the corresponding culture tank
(C1-16) semi-permeable membrane cell culture chamber is constituted between;
The cell dynamic cultivation device further includes outer plunger pump assembly, and the outer plunger pump assembly includes the second function base
Seat, the second function pedestal include the second base body (B2) and be set on second base body (B2) precision into
Sample device (B2-6) and accurate sample injector propulsive mechanism;
The precision sample injector (B2-6) includes the note of injection-tube (B2-61) and the inside for being installed on the injection-tube (B2-61)
It penetrates with piston (B2-62);The liquid outlet of the injection-tube (B2-61) passes through the first connecting line (E1) and the gas-tpe fitting
(C1-13) it is connected to;The precision sample injector propulsive mechanism is configured to control the injection piston (B2-62) in the note
The inside for penetrating pipe (B2-61) is moved back and forth to control the accurate sample injector (B2-6) and carry out suction action.
11. cell dynamic cultivation device according to claim 10, which is characterized in that the precision sample injector propulsive mechanism
Including lead screw (B2-1) and the feed screw nut (B2-2) being sheathed on the lead screw (B2-1), the feed screw nut (B2-2) and institute
It states injection piston (B2-62) to be fixedly connected, the lead screw (B2-1) can rotate to drive the edge the feed screw nut (B2-2)
The length direction of the lead screw (B2-1) moves back and forth to drive the injection piston (B2-62) in the injection-tube (B2-
61) inside moves back and forth.
12. cell dynamic cultivation device according to claim 10, which is characterized in that the cell dynamic cultivation device is also
Including external peristaltic pump component, the external peristaltic pump component includes third function pedestal;
The third function pedestal includes third base body (B3), peristaltic pump (B3-4) and peristaltic pump driving mechanism, described compacted
Dynamic pump (B3-4) and the peristaltic pump driving mechanism are mounted on the third base body (B3);The peristaltic pump (B3-4)
Inlet connect with the medicine storing pot for being loaded with drug to be checked (F1) by the second connecting line (E2);The peristaltic pump (B3-4)
Liquid outlet connect with the medium circulation pipeline (C1-15) by third connecting line (E3);The peristaltic pump driving mechanism
It is configured to drive the peristaltic pump (B3-4) rotation to which the drug (F1) to be checked is pumped into the medium circulation pipeline
(C1-15)。
13. cell dynamic cultivation device according to claim 12, which is characterized in that the cell dynamic cultivation device is also
Including Multi-channel switching valve component;
The medicine storing pot have it is multiple, second connecting line (E2) include main line (E21) and respectively with the main line
(E21) connect multiple bye-passes (E22), each bye-pass (E22) far from main line one end (E21) with it is multiple
The medicine storing pot corresponds connection;
The Multi-channel switching valve component Configuration is at can control only bye-pass (E22) and the main line
(E21) fluid connection state is between.
14. cell dynamic cultivation device according to claim 13, which is characterized in that the Multi-channel switching valve component packet
Include the 4th function pedestal;
The 4th function pedestal includes the 4th base body (B4), rotary spool (B4-6) and multiple communicating pipes (B4-7);
The rotary spool (B4-6) is installed in the inside of the 4th base body (B4), is pacified on the 4th base body (B4)
Fill multiple communicating pipes (B4-7);Multiple communicating pipes (B4-7) include middle part communicating pipe (B4-71) and surround in described
Multiple edge communicating pipes (B4-72) of portion's communicating pipe (B4-71) annular array;
The rotary spool (B4-6) includes valve plate (B4-61), the valve core shaft (B4- for being installed on the lower end the valve plate (B4-61)
62) and the valve core tube (B4-63) that is installed on the valve plate (B4-61), one end of the valve core tube (B4-63) and it is described in
Portion's communicating pipe (B4-71) connection, the other end of the valve core tube (B4-63) are formed as open end;The valve plate (B4-61) can
Open end and an edge communicating pipe so that the valve core tube (B4-63) are rotated around the valve core shaft (B4-62)
(B4-72) it is connected to;
One end far from the valve core tube (B4-63) of the middle part communicating pipe (B4-71) is connected to the main line (E21),
The one end of separate valve core tube (B4-63) of each edge communicating pipe (B4-72) and each bye-pass (E22)
One end far from the medicine storing pot corresponds connection.
15. cell dynamic cultivation device according to claim 14, which is characterized in that the Multi-channel switching valve component is also
Including rotation angle measurement sensing arrangement;
The rotation angle measurement sensing arrangement includes grating disc (B4-5) and photoelectric sensor (B4-4);
The grating disc (B4-5) is installed on the valve core shaft in a manner of it can rotate synchronously with the valve plate (B4-61)
(B4-62) on, grid is evenly distributed in the edge of the grating disc (B4-5);Photoelectric sensor (B4-4) setting
In the edge of the grating disc (B4-5), it is configured to detect the rotation angle of the valve plate (B4-61).
16. cell dynamic cultivation device according to claim 6, which is characterized in that the cell dynamic cultivation chip is also
Including unit of breathing freely, the ventilative unit includes except bubble structure (C1-9), vent seal lid (C1-6) and air filter
(C1-10), and it is described except bubble structure (C1-9), the vent seal lid (C1-6) and the air filter (C1-10) by
It is set gradually on down;The vent seal lid (C1-6) is installed on the culture tank (C1-16) and removes by described in
Bubble structure (C1-9) is closed in the inside of the corresponding culture tank (C1-16), thus with the corresponding culture tank (C1-16)
Between constitute remove bubble chamber;The circulatory flow (C1-17) removes bubble chamber described in flowing through, to make described except bubble chamber and each described thin
Closed circuit is formed between born of the same parents culturing room;And it is described except bubble chamber and adjacent described thin in being located at for the circulatory flow (C1-17)
It is respectively arranged on position between born of the same parents culturing room elastic-sealing-valve (C1-5), the elastic-sealing-valve (C1-5) is configured to control
The on-off of the circulatory flow (C1-17);
The cell dynamic cultivation device further includes gas tank (F4), the gas tank (F4) by the 4th connecting line (E4) with it is described
Air filter (C1-10) connection.
17. cell dynamic cultivation device according to claim 14, which is characterized in that the cell dynamic cultivation device is also
Including master control driver (D) and motion actuators (A);
The motion actuators (A) have multiple, and the first function pedestal, the second function pedestal, the third function
Energy pedestal, the 4th function pedestal and the motion actuators (A) are respectively provided with respective rotary clutch, standardization is cut
Alias and sensor interface;The motion actuators (A) further include the rotation connecting with the respective rotary clutch
Driving mechanism;
Multiple motion actuators (A) are connect by respective rotary clutch, standardized handover interfaces and sensor respectively
Mouth and the first function pedestal, the second function pedestal, the third function pedestal and the 4th function pedestal
Rotary clutch, standardized handover interfaces and sensor interface connect one to one;
The master control driver (D) is connect by connecting cable (G) with each motion actuators (A) respectively, and the master
Control driver (D) can control the operating condition of the rotary drive mechanism of each motion actuators (A) respectively to control respectively
Make each of the first function pedestal, the second function pedestal, the third function pedestal and the 4th function pedestal
From working condition.
18. cell dynamic cultivation device according to claim 8, which is characterized in that the cell dynamic cultivation device is also
Including master control driver (D) and motion actuators (A);
The motion actuators (A) include the first motion actuators (A1), first motion actuators (A1) and described first
Function pedestal respectively includes respective rotary clutch, standardized handover interfaces and sensor interface;First function pedestal
Rotary clutch (B1-5) is connect with the rotation axis (B1-10);The rotary clutch (A1-8) of first motion actuators and institute
The rotary clutch (B1-5) for stating the first function pedestal is cooperatively connected;The standardized handover interfaces (A1-7) of first motion actuators
It is connect with the standardized handover interfaces (B1-7) of the first function pedestal;The sensor interface (A1-1) of first motion actuators and the
The sensor interface (B1-4) of one function pedestal connects;
First motion actuators (A1) further include rotary drive mechanism (A1-2) and lift drive mechanism (A1-3), the rotation
Turn driving mechanism (A1-2) to connect with the rotary clutch (A1-8) of the first motion actuators;The lift drive mechanism (A1-3)
It is directed at the jacking valve lever (B1-6), is configured to make the jacking valve lever (B1-6) in the inside of the through-hole (B1-12)
Lifting;
The master control driver (D) is connect by connecting cable (G) with first motion actuators (A1), and the master control is driven
Dynamic device (D) can control the working condition of the rotary drive mechanism (A1-2) and the lift drive mechanism (A1-3) respectively,
To control the rotary state of the rotation axis (B1-10) and the jacking condition of jacking valve lever (B1-6).
19. cell dynamic cultivation device according to claim 18, which is characterized in that first motion actuators (A1)
Further include display screen (A1-4) and button (A1-5), the display screen (A1-4) and the button (A1-5) respectively with the rotation
Driving mechanism (A1-2) and the lift drive mechanism (A1-3) electrical connection;The display screen (A1-4) is for showing the rotation
The movement state information of driving mechanism (A1-2) and the lift drive mechanism (A1-3);The button (A1-5) for controlling respectively
Make the rotary drive mechanism (A1-2) and the lift drive mechanism (A1-3) respective start and stop.
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