CN109055204A - Drug screening organ chip - Google Patents
Drug screening organ chip Download PDFInfo
- Publication number
- CN109055204A CN109055204A CN201811223566.5A CN201811223566A CN109055204A CN 109055204 A CN109055204 A CN 109055204A CN 201811223566 A CN201811223566 A CN 201811223566A CN 109055204 A CN109055204 A CN 109055204A
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- organ chip
- transhipment unit
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- 210000000056 organ Anatomy 0.000 title claims abstract description 130
- 238000007877 drug screening Methods 0.000 title claims abstract description 39
- 239000001963 growth medium Substances 0.000 claims abstract description 69
- 239000012530 fluid Substances 0.000 claims abstract description 53
- 238000010146 3D printing Methods 0.000 claims abstract description 44
- 238000012360 testing method Methods 0.000 claims abstract description 22
- 230000008520 organization Effects 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 15
- 238000012258 culturing Methods 0.000 claims description 62
- 239000007788 liquid Substances 0.000 claims description 46
- 238000001514 detection method Methods 0.000 claims description 9
- 239000012528 membrane Substances 0.000 claims description 9
- 230000008859 change Effects 0.000 claims description 3
- 238000005192 partition Methods 0.000 claims description 3
- 230000037237 body shape Effects 0.000 claims 1
- 238000007639 printing Methods 0.000 abstract description 13
- 230000000903 blocking effect Effects 0.000 abstract description 5
- 230000004083 survival effect Effects 0.000 abstract description 3
- 239000007789 gas Substances 0.000 description 14
- 230000032258 transport Effects 0.000 description 7
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- 206010036590 Premature baby Diseases 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
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- 229910052760 oxygen Inorganic materials 0.000 description 2
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- 230000017260 vegetative to reproductive phase transition of meristem Effects 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
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- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
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- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Toxicology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The present invention provides a kind of drug screening organ chips, it is related to the technical field of organizational project, including transporting unit, organ chip body, transhipment unit is removably embedded in the inside of organ chip body, facilitate the culture medium in organ chip body to enter transhipment unit, realizes that drug to be screened screens in test organization；Organ chip body is for placing the culture medium comprising drug to be screened；Transhipment unit is celliferous biological 3D printing class loading for placing test organization, test organization.The present invention can solve the problems, such as cell detachment by transporting unit, avoid the blocking of fluid channel, and improve the survival rate of cell；Meanwhile the stability and high consistency of printing can be improved in the standardization of transportation organization, modularization.
Description
Technical field
The present invention relates to tissue engineering technique fields, more particularly, to a kind of drug screening organ chip.
Background technique
Organ chip for the work such as cell or tissue culture, pathological research and drug screening provide one it is novel
Cultivation platform, main characteristics are the reciprocations that can more effectively simulate people's intracorporeal organ.Organ chip is mostly wrapped by one
The three dimensional culture system of the chip containing multi-channel fluid, and the image device group of the online cell or tissue growth conditions of observation in real time
At.
However, current organ chip research still prematurity, the organ-tissue adherent growth of existing organ chip is in chip
Tissue cultures module, this design can be because being largely proliferated of cell, falling off causes the death rate of cell to increase or make miniflow
Road blocking.
Summary of the invention
In view of this, avoiding directly the purpose of the present invention is to provide drug screening organ chip in organ chip
The technical difficulty of interior printing, meanwhile, it solves the problems, such as cell detachment, avoids the blocking of fluid channel, and improve cell
Survival rate.
In a first aspect, the embodiment of the invention provides a kind of drug screening organ chips, comprising: transhipment unit, organ
Chip body, the transhipment unit are removably embedded in the inside of the organ chip body, facilitate in organ chip body
Culture medium enter transhipment unit, realize that drug to be screened screens in test organization；
The organ chip body is for placing the culture medium comprising drug to be screened；
The transhipment unit is celliferous biological 3D printing class loading for placing test organization, test organization.
With reference to first aspect, the embodiment of the invention provides the first possible embodiments of first aspect, wherein institute
Stating transhipment unit includes transhipment unit main body and transhipment unit chassis；The transhipment unit main body is with the transhipment unit chassis
One entirety or the transhipment unit main body are interlocked with the transhipment unit chassis.
With reference to first aspect, the embodiment of the invention provides second of possible embodiments of first aspect, wherein institute
The side for stating transhipment unit main body includes aperture or the transhipment unit chassis includes aperture.
With reference to first aspect, the embodiment of the invention provides the third possible embodiments of first aspect, wherein institute
Stating transhipment unit chassis includes semi-permeable membrane, so that the culture medium is entered in the transhipment unit by the semipermeable membrane
Portion.
With reference to first aspect, the embodiment of the invention provides the 4th kind of possible embodiments of first aspect, wherein institute
Stating at the top of transhipment unit includes eaves and the positioning port on eaves.
With reference to first aspect, the embodiment of the invention provides the 5th kind of possible embodiments of first aspect, wherein institute
State organ chip further include: transparent cap, the transparent cap is covered in the organ chip body or transparent plug,
The transparent plug is covered in the culturing room of the organ chip body.
There is calparine cap at the top of the transparent plug, can be by the syringe with syringe needle, syringe needle passes through calparine cap, with injection
Device adding liquid or extracting liq from culturing room into culturing room.
With reference to first aspect, the embodiment of the invention provides the 6th kind of possible embodiments of first aspect, wherein institute
It states organ chip body to be also used to be connected with drive system, the drive system is for driving the culture medium in the organ core
Flowing in piece main body.
With reference to first aspect, the embodiment of the invention provides the 7th kind of possible embodiments of first aspect, wherein institute
Stating further includes having inlet and liquid outlet in organ chip body, so that the culture medium enters the device from the inlet
In official's chip body, so that the culture medium exports outside the organ chip body from the liquid outlet.
With reference to first aspect, the embodiment of the invention provides the 8th kind of possible embodiments of first aspect, wherein institute
Stating organ chip body includes: hard top layer, miniflow channel layer, transparent underlayer, sensing chip, and the miniflow channel layer is arranged described
Between hard top layer and the transparent underlayer, the sensing chip is arranged between the miniflow channel layer and the transparent underlayer；
The hard top layer includes at least one culturing room, gas passage, top surface groove, bottom recesses, detection zone；Institute
Bottom recesses are stated for placing the miniflow channel layer；
The miniflow channel layer includes at least one culturing room, fluid channel, check valve, drives groove, liquid storage groove, segmentation recessed
Slot, paliform valve, flexible film, inlet, liquid outlet；The fluid channel will at least one described culturing room, driving groove,
Liquid storage groove, dividing grooves connect；The paliform valve opens dividing grooves partition；The flexible film will drive
Dynamic groove is separated with liquid storage groove, dividing grooves；
Wherein, the transhipment unit and at least one culturing room in the hard top layer, in the miniflow channel layer extremely
Few culturing room matching.
With reference to first aspect, the embodiment of the invention provides the 9th kind of possible embodiment of first aspect, wherein device
The shape of official's chip body can be cuboid or hexahedron.
The embodiment of the present invention brings following the utility model has the advantages that can add transhipment unit, transhipment in organ chip body
Unit is removably embedded in the inside of organ chip body, when transhipment unit is embedded in the inside of organ chip body,
Culture medium in the organ chip body enters transhipment unit, realizes that drug to be screened screens in test organization, completes drug
Screening is mentioned between biological 3D printer and organ chip by that can carry biological 3D printing class loading due to transhipment unit
The means for having supplied transhipment, avoid the technical difficulty directly printed in organ chip, meanwhile, using biological 3D printing class loading
Bearing test tissue, solves the problems, such as cell detachment, avoids the blocking of fluid channel, and improves the survival rate of cell.
Other features and advantages of the present invention will illustrate in the following description, also, partly become from specification
It obtains it is clear that understand through the implementation of the invention.The objectives and other advantages of the invention are in specification, claims
And specifically noted structure is achieved and obtained in attached drawing.
To enable the above objects, features and advantages of the present invention to be clearer and more comprehensible, preferred embodiment is cited below particularly, and cooperate
Appended attached drawing, is described in detail below.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art be briefly described, it should be apparent that, it is described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, is also possible to obtain other drawings based on these drawings.
Fig. 1 a is the structure chart of drug screening organ chip provided by one embodiment of the present invention；
Fig. 1 b is the structure chart for the drug screening organ chip that another embodiment of the present invention provides；
Fig. 2 a is the structure chart of the first transhipment unit provided in an embodiment of the present invention；
Fig. 2 b is the structure chart of second provided in an embodiment of the present invention transhipment unit；
Fig. 2 c is the structure chart of the third transhipment unit provided in an embodiment of the present invention；
Fig. 2 d is the structure chart of 4th kind provided in an embodiment of the present invention transhipment unit；
Fig. 3 a is the structural schematic diagram of transparent cap provided in an embodiment of the present invention；
Fig. 3 b is the structural schematic diagram of transparent plug provided in an embodiment of the present invention；
Fig. 4 a is the positive structure chart of the first miniflow channel layer provided in an embodiment of the present invention；
Fig. 4 b is the structure chart of the reverse side of miniflow channel layer provided in an embodiment of the present invention；
Fig. 5 is the structural schematic diagram of the work of the check valve in miniflow channel layer provided in an embodiment of the present invention；
Fig. 6 a carries out control principle with the culture medium in organ chip for drug screening provided by one embodiment of the present invention
Schematic diagram；
Fig. 6 b is that the drug screening that another embodiment of the present invention provides carries out control original with the culture medium in organ chip
The schematic diagram of reason；
Fig. 7 is the schematic diagram of the culture medium more new principle in drug screening organ chip provided in an embodiment of the present invention；
Fig. 8 is the positive structure chart of second of miniflow channel layer provided in an embodiment of the present invention；
Fig. 9 is the positive structure chart of the third miniflow channel layer provided in an embodiment of the present invention.
Specific embodiment
In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with attached drawing to the present invention
Technical solution be clearly and completely described, it is clear that described embodiments are some of the embodiments of the present invention, rather than
Whole embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not making creative work premise
Under every other embodiment obtained, shall fall within the protection scope of the present invention.
Current organ chip research still prematurity, the organ-tissue adherent growth of existing organ chip is in the tissue of chip
Cultivate module, this design can because being largely proliferated of cell, falling off causes the death rate of cell to increase or block fluid channel,
Based on this, a kind of drug screening organ chip provided in an embodiment of the present invention can add transhipment in organ chip body
Unit, transhipment unit are removably embedded in the inside of organ chip body, when being embedded in organ chip body in transhipment unit
The inside when, the culture medium in the organ chip body enters transhipment unit, realize that drug to be screened screens in test organization,
Drug screening is completed, by the way that biological 3D printing class loading can be carried due to transhipment unit, in biological 3D printer and organ core
The means of transhipment are provided between piece, avoid the technical difficulty directly printed in organ chip, meanwhile, it is beaten using biological 3D
Class loading bearing test tissue is printed, cell detachment is solved the problems, such as, avoids the blocking of fluid channel, and improve depositing for cell
Motility rate.
For convenient for understanding the present embodiment, first to a kind of drug screening organ disclosed in the embodiment of the present invention
Chip describes in detail,
In conjunction with shown in Fig. 1 a, the embodiment of the invention provides a kind of drug screening organ chip, drug screening organs
The shape of chip is rectangle, and chip includes: transhipment unit 1000, organ chip body 2000, and transhipment unit 1000 is detachable
The inside for being embedded in organ chip body 2000.As the example of a practical application, when user starts to test, user
A transhipment unit 1000 is taken out, then biological 3D printing class loading, which is placed on transhipment unit 1000, will be equipped with biological 3D
It prints histioid transhipment unit 1000 and is installed to organ chip body 2000 in a manner of insertion.
Wherein, organ chip body 2000 is for placing the culture medium comprising drug to be screened；Transhipment unit 1000 is used for
Test organization is placed, the inside of organ chip body 2000 is embedded in transhipment unit 1000, facilitates organ chip body 2000
In culture medium enter transhipment unit 1000, realize that drug to be screened screens in test organization, the test organization includes: biology
3D printing class loading.
Specifically, in test, biological 3D printing class loading is placed in transhipment unit 1000, biological 3D is carried
Print the inside that histioid transhipment unit 1000 is embedded in organ chip body 2000, the culture in organ chip body 2000
Base, wherein it may include drug to be screened in culture medium, biological 3D printing class loading impregnated in the medium, i.e., it is biological
3D printing class loading is immersed in drug to be screened, in this way, after a period of time, can be by observing biological 3D printing class
In tissue the case where cell, to assess drug to the histioid effect of biological 3D printing, to screen drug.
The present invention further defines the structure of transhipment unit, and specifically, transhipment unit can be an overall structure,
Meanwhile transporting unit includes aperture 1300, and the culture medium in organ chip body 2000 can be made to enter by aperture and turned
In transportation unit 1000.Another way is that transhipment unit 1000 can also be seperated structure, specifically includes transhipment unit main body
1100 and transhipment unit chassis 1200；Transhipment unit main body 1100 is interlocked with transhipment unit chassis 1200.At this point, aperture 1300
It can be located on the side or transhipment unit chassis of transhipment unit main body.Further, include in transhipment unit chassis 1200
There is semi-permeable membrane 1400, the culture medium in organ chip body 2000 can be entered to transport in unit 1000 by semipermeable membrane
Portion.Wherein, the shape for transporting unit can be cuboid, square, circle flow-through, polyhedron etc..
As the structure feature of transhipment unit defined above, there may be the transhipment units 1000 of following several forms.
In conjunction with shown in Fig. 2 a~Fig. 2 d, the transhipment unit 1000 of four seed types is disclosed, transporting unit a type is, in conjunction with
Shown in Fig. 2 a, the side of transhipment unit 1000 includes aperture 1300.In this way, the culture medium in organ chip body can pass through
Aperture 1300 enters in transhipment unit 1000.
In conjunction with shown in Fig. 2 b~Fig. 2 d, disclosing transhipment unit 1000 is split type structure, specifically, transhipment unit
1000 include transhipment unit main body 1100 and transhipment unit chassis 1200；Transport unit main body 1100 and transhipment unit chassis 1200
It is interlocked.
However, 3 kinds of structures transport unit b type, the side of the transhipment unit main body the difference lies in that in conjunction with shown in Fig. 2 b
Face includes aperture 1300, wherein transhipment unit chassis 1200 can have chassis strip, when transhipment unit main body 1100 and transhipment
When unit chassis 1200 is installed, after being allowed to deformation by extruding transhipment unit main body, fastened with transhipment unit chassis.It can use
The aperture of side is corresponding with the position of chassis strip, and the area of chassis strip is less than side aperture area, so that chassis strip is not
Side aperture portion can be embedded in and form an aperture for liquid flowing.
In conjunction with shown in Fig. 2 c, unit c type is transported, the side of the transhipment unit main body includes aperture 1300, wherein institute
Stating transhipment unit chassis includes chassis strip 1200 and semi-permeable membrane 1400, can be allowed to by squeezing transhipment unit main body 1100
It after deformation, is fastened with transhipment unit chassis 1200, and the aperture of side is corresponding with chassis strip position, and chassis strip is completely and side
Aperture fitting in face makes to transport the sealing of unit side, is only infiltrated through culture medium inside transhipment unit 1000 by semi-permeable membrane.
In conjunction with shown in Fig. 2 d, unit d type is transported, is not made any changes in transhipment unit main body 1100, transports unit chassis
Include aperture 1300 on 1200, culture medium can be flowed by transhipment unit 1000 by the aperture in transhipment unit chassis 1200
It is internal.
In conjunction with shown in Fig. 2 a~Fig. 2 d, the embodiment of the present invention defines that the top of transhipment unit 1000 includes 1500 He of eaves
Positioning port 1600 on eaves.
As an example, when organ chip body includes hard top layer and miniflow channel layer, include in hard top layer
There is anchor point, the positioning port 1600 for transporting unit can coincide with the anchor point of the culturing room in hard top layer, and bottom has several small
Hole, and it is described transhipment unit positioning port 1600 and hard top layer anchor point coincide, organ chip body collocation in use,
The position of the aperture or semi-permeable membrane of transporting unit should be corresponding with the position that the culturing room of miniflow channel layer and fluid channel are connected.When
Transport unit have positioning port and when eaves, be better able to make to transport unit it is more stable and fixed be placed on organ chip master
Device matching inside body, with organ chip body uses.
Optionally, the organ chip further include: transparent cap, the transparent cap are covered on the organ chip body
On or transparent plug, the transparent plug be covered in organ chip body culturing room.
In conjunction with shown in Fig. 3 a, transparent cap 3000 includes ventilation mouth 3100, chamfering 3200.
In conjunction with shown in Fig. 3 b, transparent plug 3010 includes calparine cap 3011, positioning port 3012.
Wherein, transparent cap can be the rectangle clear hard plastic lid by chamfered, and one of positioning is fallen
The shape at angle and other three differences, to provide positioning, size, the shape of transparent cap match with hard top layer, hardtop
It may include positioning chamfering 2160 and transparent cap card slot 2150 to facilitate transparent top by the point of the two positioning in layer
When lid 3000 covers the opening of culturing room all in hard top layer 2100, transparent cap can be installed to transparent cap card slot
On 2150.In addition, transparent cap can also have ventilation mouth 3100 and extraneous progress gas exchanges；Or transparent plug can be used
Instead of arriving the effect of sealing culturing room on transparent cap, hard top layer has anchor point and positioning eaves, can determine on transparent plug
Position mouth 3012 matches.
In conjunction with shown in Fig. 1 a, the organ chip body 2000 includes: hard top layer 2100, miniflow channel layer 2200, thoroughly
Bright bottom 2300, sensing chip, miniflow channel layer 2200 are arranged between hard top layer 2100 and transparent underlayer 2300, sensing chip
It is arranged between miniflow channel layer 2200 and transparent underlayer 2300.
Wherein, hard top layer 2100 by it is transparent, the material of cytotoxic is made, material can include but is not limited to gather
Polyglass (PS), polycarbonate (PC), cyclenes hydrocarbon type copolymer plastics (COC plastics), polyethylene (PE), polypropylene
(PP)。
Hard top layer 2100 is recessed including at least one culturing room, anchor point, positioning eaves, gas passage, top surface groove, bottom surface
Slot, detection zone 2130, transparent cap card slot 2150, culturing room's number；Bottom recesses are for placing miniflow channel layer.
At least one culturing room contained in hard top layer 2100 can place cell, tissue or biological 3D printing class loading etc.
Deng the test organization for test, can also place containing cell, tissue or the histioid transhipment unit of biological 3D printing；And
Anchor point and positioning eaves are arranged in culturing room, can coincide with the positioning port of transhipment unit.
Top surface groove can distinguish different miniflow channel layer, and cooperate culturing room number carry out using.Detection zone
2130,96 orifice plate enzyme mark strips can be placed, analysis detection are carried out to the culture medium of taking-up, or directly detected in detection zone.
In addition, culturing room's number uses primarily to distinguishing, since organ chip body may include multiple culturing room,
Different types of test organization can be cultivated simultaneously, so, culturing room's number enables to user to carry out differentiation work in test
Make.The effect of positioning chamfering be in order to transparent cap Matching installation, and convenient to be quickly found out transparent cap when in use correct
Installation direction.
Miniflow channel layer 2200 includes at least one culturing room, fluid channel, check valve, drives groove, liquid storage groove, segmentation recessed
Slot, paliform valve, flexible film, inlet, liquid outlet；The fluid channel will at least one described culturing room, driving groove,
Liquid storage groove, dividing grooves connect；The paliform valve opens dividing grooves partition；The flexible film will drive
Dynamic groove is separated with liquid storage groove, dividing grooves.
Soft by dimethyl silicone polymer (PDMS) or comprising dimethyl silicone polymer of miniflow channel layer and cell is grown
Harmless material is constituted, and its two sides passes through oxygen plasma treatment, irreversible bonding pattern and hard top layer and clear bottom
Layer is mutually bonded.
In conjunction with shown in Fig. 4 a and Fig. 4 b, fluid channel 2220 connect miniflow channel layer in culturing room 2210, width of flow path gradient,
Dividing grooves 2240, liquid storage groove 2230, driving groove 2260, and in dividing grooves 2240 by paliform valve 2250 every
It is disconnected, or, the control of flow direction can be realized by addition check valve 2270 as shown in connection with fig. 5, in fluid channel 2220 and is contained back
Stream.Specific zipper, the fluid channel 2220 in organ chip body 2000 use vertical structure, and culture medium passes through from fluid channel 2220
The culturing room 2210 of the laggard flow channel layer in a subtle way of check valve 2270, then pass through the culture that another check valve 2270 leaves miniflow channel layer
Room 2210 enters another section of fluid channel 2220 in vertical direction；After culture medium is added in culturing room 2210 and full of entire micro-
Runner 2220.Diameter≤1mm of fluid channel provides the fluid nutrient medium circulated for the culturing room of miniflow channel layer, be cell,
Tissue or the biological histioid growth of 3D printing provide nutrition, and metabolic waste is discharged；
Optionally, width of flow path gradient, runner are properly termed as with the fluid channel of one section of width gradual change in fluid channel 2220
Width gradient is greater than logical close to the width of fluid channel one end or the fluid channel and culturing room in the width close to culturing room one end
When crossing vertical run connection, then the width of flow path gradient is the fluid channel of one section of Diameter Gradual Change.
In conjunction with shown in Fig. 6 a, the organ chip body 2000 is also used to through pipeline 3500 and 5000 phase of drive system
Even, the drive system 5000 is for driving the culture medium to flow in the organ chip body.
Since drive system 5000 controls what culture medium flowed in organ chip body 2000 using the difference of air pressure,
Meanwhile culture medium is mainly in hard top layer 2100, miniflow channel layer 2200, then first introducing the gas circuit of hard top layer 2100.This
Hard top layer 2100 includes gas passage in invention, and gas passage includes air pipe interface and gas delivery port, air pipe interface and gas
Body delivery outlet can be collectively constituted by conduit connection as a gas passage, and gas delivery port can be with the driving of miniflow channel layer
Groove 2260 is connected；Air pipe interface 2140 can be connected by pipeline 3500 with drive system 5000, on hard top layer
Gas delivery port is corresponding with the position of the driving groove 2260 in miniflow channel layer, shape.It, can be soft in miniflow channel layer 2200
Matter film will drive groove 2260 to separate with dividing grooves 2240 or liquid storage groove 2230；Drive groove 2260 and hard top layer
On gas delivery port position, shape it is corresponding, and drive system 5000 by pipeline 3500 to organ chip body export gas
Body, in organ chip body, air pipe interface 2140 is connected with pipeline 3500, is being transported to organ chip by air pipe interface 2140
Main body, can making flexible film by changing the air pressure in gas passage, deformation occurs, leads to dividing grooves 2240 and liquid storage groove
2230 volume changes, and realizes the control of liquid volume in the opening and closing and liquid storage groove 2230 of paliform valve 2250, from
And it realizes culture medium and is flowed in the organ chip body.
Inside the culture medium in organ chip body 2000 recycle in the case where, miniflow channel layer 2200 can also have with
Flowering structure, in conjunction with shown in Fig. 4 a, fluid channel 2220 can be closed loop runner, and the culture medium in fluid channel passes through drive system 5000
Self-loopa is carried out, and realizes the update of culture medium by manually regularly replacing culture medium.The mode manually regularly replaced can be with
First to outwell former culture medium, the tool of liquid can be held by, which reusing, is put into new culture medium in organ chip body 2000.
Or the fluid channel 2220 can be fabricated in one or more elevation dimensions, i.e., culture medium both can be in runner
It is flowed in approximately the same plane, can also be entered by a vertical channel in the runner of another elevation dimension and be continued cycling through.
When carrying out the update of the culture medium in organ chip body 2000 using drive system 5000, as shown in connection with fig. 7,
Drive system 5000 can be connected by pipeline with liquid storage tank 6100, waste liquid pool 6200, meanwhile, hard topsheet surface can basis
Need to increase inlet 2110 and liquid outlet 2120, drive system 5000 and the inlet 2110 in organ chip body 2000
It is connected with liquid outlet 2120, new culture medium enters inlet 2110 in the case where drive system drives, through pipeline, in organ chip
It completes to leave organ chip body 2000 from liquid outlet 2120 by pipeline after recycling in main body 2000.
In the case where completing the update of the culture medium in organ chip body 2000, miniflow channel layer can also have following
Structure, as shown in connection with fig. 8, fluid channel 2220 can be open loop runner, and inlet 2221 and liquid outlet 2222 are equipped in fluid channel,
And it is corresponding with the inlet of hard top layer 2110 and 2120 position of liquid outlet, drive system 5000 is by the fresh cultured in liquid storage tank
Base is driven by pipeline to hard top layer inlet 2110, and into fluid channel 2220, culture medium is completed to follow in fluid channel 2220
After ring, fluid channel, and the pipeline by connecting with hard top layer liquid outlet 2120 are left by the liquid outlet 2222 in fluid channel
It is discharged into waste liquid pool, culture medium is extracted analysis after entering waste liquid pool 6200 or throws aside.
Wherein, the transhipment unit and at least one culturing room in the hard top layer, in the miniflow channel layer extremely
Few culturing room matching.
Wherein, hard top layer 2100, miniflow channel layer 2200, transparent underlayer 2300 is by oxygen plasma treatment, with irreversible
Bonding pattern is bonded, and in bonding process hard top layer 2100 culturing room, be with the culture of miniflow channel layer 2200
Room Corresponding matching, and sensing chip is fixed on miniflow channel layer in bonding process by miniflow channel layer 2200 and transparent underlayer 2300
Between 2200 and transparent underlayer 2300, and it can be in contact with the culture medium in the fluid channel 2220 of miniflow channel layer 2200, organ core
Piece main body 2000 carry out as a whole using.
Transparent underlayer 2300 can be made of the material of the glass of clear hard or other clear hards, be passed through with miniflow channel layer
It is irreversibly bonded, provides substrate for miniflow channel layer 2200, and include sensing chip.
Sensing chip is the surface-functionalized biochip for having biomarker, is placed in fluid channel, hard top layer or micro-
It the top or bottom end of culturing room and is contacted with culture medium in flow channel layer；According to sensing needed for selected sensing principle and sensing chip
Condition, organ chip body is equipped with the channel that organ chip body is passed in and out for sensed condition, and it is made to be connected with sensing chip
It is logical；The sensed condition includes but is not limited to light, electric current, voltage, magnetic field, and various aspects when passing in and out organ chip body are special
Sign is detected and is recorded in real time.
In conjunction with described in Fig. 1 b, another embodiment of the present invention provides a kind of drug screening organ chip, can be made as
Hexahedron, the culturing room 2110 in hard top layer 2100 are sealed with transparent plug 3010, have liver at the top of transparent plug 3010
Plain cap, can be by the syringe with syringe needle, and syringe needle passes through calparine cap 3011, with syringe into culturing room adding liquid or from
Extracting liq in culturing room.
In conjunction with shown in Fig. 6 a, the invention also includes printing head 4000, printing head 4000 can directly print biological 3D
Class loading is printed, is put into transhipment unit 1000.
In conjunction with described in Fig. 6 b, organ chip of the present invention can be combined into an entirety, drive system with 5000 groups of drive system
5000 connect with display control unit 5100, carry out control operation by display control unit 5100.
In the case where the operation of organ chip in conjunction with described in Fig. 6 b, fluid channel 2220 be can have with flowering structure, in conjunction with
Shown in Fig. 9, miniflow channel layer 2200 contains a fluid channel 2220, with the fluid channel for being connected to all culturing room in hard top layer 2100
It is connected, miniflow channel layer 2200 is sealed by irreversible bonding with hard top layer 2100.In use, being trained with 3010 Duis of transparent plug
Feeding room is sealed, and organ chip body 2000 is connected with drive system 5000, squeezes drive system 5000 periodically
The fluid channel 2220 of miniflow channel layer 2200 is pressed, driving culture medium completes circulation in organ chip；In drug screening process, pass through
Syringe with syringe needle adds the culture medium containing screened drug from the calparine cap 3011 of transparent plug 3010 or extracts containing generation
Thank to the detection sample of product.
It is introduced below several to utilize the drug screening provided by the invention example of the practical application of organ chip.
Example 1 receives the biological 3D printing class loading of printing head printing 4000 with transhipment unit a type, is contained with biology
The histioid transhipment unit a type of 3D printing is put into culture medium, is cultivated biological 3D printing class loading；Cultivate certain time
Afterwards, the unit a type positioning of transhipment is put into organ chip body 2000 by positioning port 1600, culturing room is added in culture medium
In after and be full of entire fluid channel 2220, transparent cap 3000 is placed on transparent cap card slot 2150, then by drive system
5000 connect with the pipeline 3500 of air pipe interface 2140, and then carry out drug screening to biological 3D printing class loading.
Or the biological 3D printing class loading that printing head 4000 prints is received with transhipment unit a type, it is contained with biological 3D and beats
It prints histioid transhipment unit a type to be put into culture medium, biological 3D printing class loading is cultivated；It cultivates after a certain period of time,
It will be put into organ chip body 2000 in culturing room 2110 with the biological histioid transhipment unit a type of 3D printing；It will culture
After base is added in culturing room and it is full of entire fluid channel 2220, is sealed culturing room with transparent plug, then by drive system
5000 connect with the pipeline 3500 of air pipe interface 2140, and then carry out drug screening to biological 3D printing class loading.
Example 2 receives the biological 3D printing class loading that printing head 4000 prints with transhipment unit a type, and the two is put together
Enter in culture medium, biological 3D printing class loading is cultivated；Culture after a certain period of time, will be histioid with biological 3D printing
Transhipment unit a type is put into organ chip body 2000 in culturing room, after culture medium is added in culturing room and full of entire micro-
All culturing room are sealed by runner 2220 with transparent plug, then by organ chip body 2000, drive system 5000,
Liquid storage tank 6100, waste liquid pool 6200, is connected by pipeline, and the inlet of liquid storage tank 6100 and hard top layer 2100
2110 are connected with pipeline, and hard top layer liquid outlet 2120 is connected with waste liquid pool 6200 by pipeline, in use, drive system 5000
Culture medium in liquid storage tank 6100 is driven by pipeline into inlet 2110, subsequent culture medium passes through the inlet of miniflow channel layer
2221 enter fluid channel 2220, complete to leave fluid channel 2220 by the liquid outlet 2222 of miniflow channel layer after recycling, then by going out
Liquid mouth 2120 enters pipeline, is then passed into waste liquid pool 6200, and then carry out drug screening to biological 3D printing class loading.
Example 3 receives the biological 3D printing class group that printing head 4000 prints with the transhipment unit chassis of transhipment unit b type
It knits, the transhipment unit main body 1100 of transhipment unit b type is then squeezed with finger, makes its deformation, by turn of itself and transhipment unit b type
Transportation unit chassis 1200 is aligned, and chassis strip and the aperture of side 1300 is made to coincide, and unclamping finger makes the transhipment for transporting unit b type
Unit main body 1100 resiles and keeps it fixed with the transhipment unit chassis 1200 of transhipment unit b type；By having after fixation
The biological histioid transhipment unit b type of 3D printing, which is put into culture medium, to be cultivated；Culture after a certain period of time, will be with biological 3D printing
Histioid transhipment unit b type is put into organ chip body 2000 in culturing room；After culture medium is added in culturing room and fill
Full entire fluid channel 2220, is placed in transparent cap card slot 2150 for transparent cap 3000, then by drive system 5000 and tracheae
Interface 2140 is connected with pipeline 3500, and then carries out drug screening to biological 3D printing class loading.
Or the biological 3D printing class loading that printing head 4000 prints is received with the transhipment unit chassis of transhipment unit c type,
Then the transhipment unit main body 1100 that transhipment unit c type is squeezed with finger, makes its deformation, by the transhipment of itself and transhipment unit c type
Unit chassis 1200 is aligned, and chassis strip and the aperture of side 1300 is made to coincide, and unclamping finger makes the transshipment note for transporting unit c type
First main body 1100 resiles and keeps it fixed with the transhipment unit chassis 1200 of transhipment unit c type；Life will be had after fixation
The histioid transhipment unit c type of object 3D printing, which is put into culture medium, to be cultivated；Culture after a certain period of time, will be with biological 3D printing class
The transhipment unit c type of tissue is put into organ chip body 2000 in culturing room, after culture medium is added in culturing room and is full of
Entire fluid channel 2220, is placed in transparent cap card slot 2150 for transparent cap 3000, then connects drive system 5000 with tracheae
Mouth 2140 is connected with pipeline 3500, and then carries out drug screening to biological 3D printing class loading.
Or the biological 3D printing class loading that printing head 4000 prints is received with the transhipment unit chassis of transhipment unit d type,
Then the transhipment unit main body 1100 that transhipment unit d type is squeezed with finger, makes its deformation, by the transhipment of itself and transhipment unit d type
Unit chassis 1200 is aligned, and unclamping finger makes the transhipment unit main body 1100 for transporting unit d type resile and make itself and transhipment
The transhipment unit chassis 1200 of unit d type is fixed；By being put into the biological histioid transhipment unit d type of 3D printing after fixation
It is cultivated in culture medium；Culture after a certain period of time, will be put into organ chip master with the biological histioid transhipment unit d type of 3D printing
On body 2000 in culturing room；After culture medium is added in culturing room and it is full of entire fluid channel 2220, transparent cap 3000 is set
In transparent cap card slot 2150, then drive system 5000 and the pipeline 3500 of air pipe interface 2140 are connected, and then right
Biological 3D printing class loading carries out drug screening.
Example 4, the biological 3D printing class loading of printing head printing is received with transhipment unit, and the two is put into togerther culture medium
In, biological 3D printing class loading is cultivated；Culture after a certain period of time, will be with the histioid transhipment unit of biological 3D printing
1000 are put into organ chip body 2000 in culturing room；Fluid channel 2220 in the organ chip body 2000 uses vertical junction
Structure, culture medium leave culturing room's entrance from fluid channel 2220 by entering culturing room after check valve, then by another check valve
Another section of fluid channel 2220；After culture medium is added in culturing room and it is full of entire fluid channel 2220, transparent cap 3000 is set
In transparent cap card slot 2150, then drive system 5000 and the pipeline 3500 of air pipe interface 2140 are connected, and then right
Biological 3D printing class loading carries out drug screening.
Example 5 after starting drug screening according to above-mentioned example, will cultivate indoor culture medium and be taken out with liquid-transfering gun, be added
In detection zone 2130, or in detection zone 2130 place enzyme mark strip after by the culture medium taken out in culturing room be added enzyme mark
Item；Fluorescent marker is added into culture medium, transparent cap 3000 is placed in transparent cap card slot 2150, then by organ chip
Main body 2000 is put into the analysis that medium component is carried out in microplate reader.
Unless specifically stated otherwise, the opposite step of the component and step that otherwise illustrate in these embodiments, digital table
It is not limit the scope of the invention up to formula and numerical value.
In all examples being illustrated and described herein, any occurrence should be construed as merely illustratively, without
It is as limitation, therefore, other examples of exemplary embodiment can have different values.
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 addition, in the description of the embodiment of the present invention unless specifically defined or limited otherwise, term " installation ", " phase
Even ", " connection " shall be understood in a broad sense, for example, it may be being fixedly connected, may be a detachable connection, or be integrally connected；It can
To be mechanical connection, it is also possible to be electrically connected；It can be directly connected, can also can be indirectly connected through an intermediary
Connection inside two elements.For the ordinary skill in the art, above-mentioned term can be understood at this with concrete condition
Concrete meaning in invention.
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" be based on the orientation or positional relationship shown in the drawings, merely to
Convenient for description the present invention and simplify description, rather than the device or element of indication or suggestion meaning must have a particular orientation,
It is constructed and operated in a specific orientation, therefore is not considered as limiting the invention.In addition, term " first ", " second ",
" third " is used for descriptive purposes only and cannot be understood as indicating or suggesting relative importance.
Finally, it should be noted that embodiment described above, only a specific embodiment of the invention, to illustrate the present invention
Technical solution, rather than its limitations, scope of protection of the present invention is not limited thereto, although with reference to the foregoing embodiments to this hair
It is bright to be described in detail, those skilled in the art should understand that: anyone skilled in the art
In the technical scope disclosed by the present invention, it can still modify to technical solution documented by previous embodiment or can be light
It is readily conceivable that variation or equivalent replacement of some of the technical features；And these modifications, variation or replacement, do not make
The essence of corresponding technical solution is detached from the spirit and scope of technical solution of the embodiment of the present invention, should all cover in protection of the invention
Within the scope of.Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. a kind of drug screening organ chip characterized by comprising transhipment unit, organ chip body, the transshipment note
Member is removably embedded in the inside of the organ chip body, and the culture medium in organ chip body is facilitated to enter transshipment note
Member realizes that drug to be screened screens in test organization；
The organ chip body is for placing the culture medium comprising drug to be screened；
The transhipment unit is celliferous biological 3D printing class loading for placing test organization, test organization.
2. drug screening according to claim 1 organ chip, which is characterized in that the transhipment unit includes aperture.
3. drug screening according to claim 2 organ chip, which is characterized in that the transhipment unit includes transshipment note
First main body and transhipment unit chassis；The transhipment unit main body is interlocked with the transhipment unit chassis, wherein the small hole location
In on the side of transhipment unit main body or the transhipment unit chassis.
4. drug screening according to claim 3 organ chip, which is characterized in that the transhipment unit chassis includes
Semi-permeable membrane, so that the culture medium is entered inside the transhipment unit by the semipermeable membrane.
5. drug screening according to claim 1 organ chip, which is characterized in that the top of the transhipment unit includes
There are eaves and the positioning port on eaves.
6. drug screening according to claim 1 organ chip, which is characterized in that the organ chip further include: thoroughly
Bright top cover, the transparent cap is covered in the organ chip body or transparent plug, the transparent plug are covered on institute
In the culturing room for stating organ chip body.
7. drug screening according to claim 1 organ chip, which is characterized in that the organ chip body is also used to
It is connected with drive system, the drive system is for driving the culture medium to flow in the organ chip body.
8. drug screening according to claim 7 organ chip, which is characterized in that also wrapped in the organ chip body
Inlet and liquid outlet are included, so that the culture medium enters in the organ chip body from the inlet, so that institute
Culture medium is stated to export outside the organ chip body from the liquid outlet.
9. drug screening according to claim 1-8 organ chip, which is characterized in that the organ chip master
Body includes: hard top layer, miniflow channel layer, transparent underlayer, sensing chip, and the miniflow channel layer is arranged in the hard top layer and institute
It states between transparent underlayer, the sensing chip is arranged between the miniflow channel layer and the transparent underlayer；
The hard top layer include at least one culturing room, anchor point, positioning eaves, gas passage, top surface groove, bottom recesses,
Detection zone, transparent cap card slot, culturing room's number；The bottom recesses are for placing the miniflow channel layer；
The miniflow channel layer include at least one culturing room, fluid channel, check valve, driving groove, liquid storage groove, dividing grooves,
Paliform valve, flexible film, inlet, liquid outlet；The fluid channel will at least one described culturing room, driving groove, storage
Liquid groove, dividing grooves connect, with the fluid channel of one section of width gradual change in the fluid channel；The paliform valve will
The dividing grooves partition is opened；The flexible film will drive groove to separate with liquid storage groove, dividing grooves；Wherein, described
Transhipment unit is matched at least one culturing room in the hard top layer, at least one culturing room in the miniflow channel layer.
10. drug screening according to claim 9 organ chip, which is characterized in that the shape of the organ chip body
Shape is cuboid or hexahedron.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811223566.5A CN109055204B (en) | 2018-10-19 | 2018-10-19 | Organ chip for drug screening |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811223566.5A CN109055204B (en) | 2018-10-19 | 2018-10-19 | Organ chip for drug screening |
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| CN109055204B CN109055204B (en) | 2024-03-26 |
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