CN109055204B - Organ chip for drug screening - Google Patents
Organ chip for drug screening Download PDFInfo
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- CN109055204B CN109055204B CN201811223566.5A CN201811223566A CN109055204B CN 109055204 B CN109055204 B CN 109055204B CN 201811223566 A CN201811223566 A CN 201811223566A CN 109055204 B CN109055204 B CN 109055204B
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- 210000000056 organ Anatomy 0.000 title claims abstract description 70
- 238000007877 drug screening Methods 0.000 title claims abstract description 30
- 238000012546 transfer Methods 0.000 claims abstract description 99
- 239000001963 growth medium Substances 0.000 claims abstract description 67
- 238000010146 3D printing Methods 0.000 claims abstract description 48
- 238000012360 testing method Methods 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 16
- 229940079593 drug Drugs 0.000 claims abstract description 14
- 238000012216 screening Methods 0.000 claims abstract description 10
- 239000007788 liquid Substances 0.000 claims description 58
- 239000012528 membrane Substances 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 7
- 239000012466 permeate Substances 0.000 claims description 3
- 238000007639 printing Methods 0.000 abstract description 14
- 230000004083 survival effect Effects 0.000 abstract description 4
- 239000007789 gas Substances 0.000 description 17
- 238000010586 diagram Methods 0.000 description 14
- 239000002609 medium Substances 0.000 description 10
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 6
- 229960002897 heparin Drugs 0.000 description 6
- 229920000669 heparin Polymers 0.000 description 6
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- 239000004205 dimethyl polysiloxane Substances 0.000 description 3
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- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 3
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- 229910052760 oxygen Inorganic materials 0.000 description 2
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- 238000011160 research Methods 0.000 description 2
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Classifications
-
- 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 invention provides an organ chip for drug screening, which relates to the technical field of tissue engineering and comprises a transfer unit and an organ chip main body, wherein the transfer unit is detachably embedded into the organ chip main body, so that a culture medium in the organ chip main body can conveniently enter the transfer unit, and the test tissue screening of drugs to be screened is realized; the organ chip main body is used for placing a culture medium containing medicines to be screened; the transfer unit is used for placing test tissues, and the test tissues are biological 3D printing tissues containing cells. The invention can solve the problem of cell shedding through the transfer unit, avoid the blockage of the micro-channel and improve the survival rate of cells; meanwhile, the standardization and modularization of the transfer unit can improve the printing stability and the high consistency.
Description
Technical Field
The invention relates to the technical field of tissue engineering, in particular to an organ chip for drug screening.
Background
The organ chip provides a novel culture platform for cell or tissue culture, pathology research, drug screening and other works, and has the main characteristic of being capable of more effectively simulating interaction of organs in a human body. The organ chip is composed of a three-dimensional culture system containing a multichannel fluid chip and an imaging device for on-line real-time observation of the growth state of cells or tissues.
However, the current research on organ chips is still immature, and the organ tissues of the current organ chips are grown on the tissue culture modules of the chips in an attached mode, and the design can increase the death rate of cells or block the micro-channels due to the massive proliferation and shedding of cells.
Disclosure of Invention
In view of the above, the present invention aims to provide an organ-chip for drug screening, which avoids the technical difficulty of printing directly in the organ-chip, solves the problem of cell shedding, avoids the blockage of a micro-channel, and improves the survival rate of cells.
In a first aspect, an embodiment of the present invention provides an organ-chip for drug screening, including: the transfer unit is detachably embedded in the organ chip main body, so that a culture medium in the organ chip main body can enter the transfer unit conveniently, and the screening of the medicines to be screened by test tissues is realized;
the organ chip main body is used for placing a culture medium containing medicines to be screened;
the transfer unit is used for placing test tissues, and the test tissues are biological 3D printing tissues containing cells.
With reference to the first aspect, the embodiment of the present invention provides a first possible implementation manner of the first aspect, wherein the transferring unit includes a transferring unit main body and a transferring unit chassis; the transfer unit main body and the transfer unit chassis are integrated, or the transfer unit main body and the transfer unit chassis are buckled.
With reference to the first aspect, the embodiment of the present invention provides a second possible implementation manner of the first aspect, where the lateral surface of the transferring unit body includes an aperture, or the transferring unit chassis includes an aperture.
With reference to the first aspect, the embodiment of the present invention provides a third possible implementation manner of the first aspect, wherein the transport unit chassis includes a semipermeable membrane, so that the culture medium permeates into the transport unit through the semipermeable membrane.
With reference to the first aspect, an embodiment of the present invention provides a fourth possible implementation manner of the first aspect, wherein a top portion of the transferring unit includes an eave and a positioning opening on the eave.
With reference to the first aspect, an embodiment of the present invention provides a fifth possible implementation manner of the first aspect, wherein the organ chip further includes: and the transparent top cover is covered on the organ chip main body or the transparent plug is covered on the culture chamber of the organ chip main body.
The transparent plug is provided with a heparin cap at the top, and the syringe with a needle can be used for adding liquid into the culture chamber or extracting liquid from the culture chamber through the heparin cap by the needle.
With reference to the first aspect, an embodiment of the present invention provides a sixth possible implementation manner of the first aspect, wherein the organ-chip main body is further configured to be connected to a driving system, and the driving system is configured to drive the culture medium to flow in the organ-chip main body.
With reference to the first aspect, an embodiment of the present invention provides a seventh possible implementation manner of the first aspect, where the organ-chip main body further includes a liquid inlet and a liquid outlet, so that the culture medium enters the organ-chip main body from the liquid inlet, and the culture medium is output from the liquid outlet to the outside of the organ-chip main body.
With reference to the first aspect, an embodiment of the present invention provides an eighth possible implementation manner of the first aspect, wherein the organ-chip main body includes: the micro-channel layer is arranged between the hard top layer and the transparent bottom layer, and the sensing chip is arranged between the micro-channel layer and the transparent bottom layer;
the hard top layer comprises at least one culture chamber, a gas channel, a top surface groove, a bottom surface groove and a detection area; the bottom surface groove is used for placing the micro-channel layer;
the micro-channel layer comprises at least one culture chamber, a micro-channel, a one-way valve, a driving groove, a liquid storage groove, a dividing groove, a fence-shaped valve, a soft film, a liquid inlet and a liquid outlet; the micro-flow channel connects the at least one culture chamber, the driving groove, the liquid storage groove and the dividing groove; the fence-shaped valve separates and breaks the dividing grooves; the driving groove is separated from the liquid storage groove and the dividing groove by the soft film;
wherein the transfer unit is matched with at least one culture chamber in the hard top layer and at least one culture chamber in the micro-channel layer.
With reference to the first aspect, the embodiment of the present invention provides a ninth possible implementation manner of the first aspect, wherein the organ-chip main body may be rectangular parallelepiped or hexahedral in shape.
The embodiment of the invention has the following beneficial effects: can add the transfer unit in organ chip main part, transfer the detachable embedding of unit in the inside of organ chip main part, when transferring the unit embedding in the inside of organ chip main part, the culture medium in the organ chip main part enters into the transfer unit, realizes that experimental tissue screening waits to select the medicine, accomplishes the medicine screening, through can bear biological 3D printing class tissue owing to transfer the unit, has provided the means of transporting between biological 3D printer and organ chip, has avoided directly printing at the organ chip technical difficulty, simultaneously, adopts biological 3D to print class tissue and bears experimental tissue, has solved the problem that the cell drops, has avoided the jam of microchannel to the survival rate of cell has been improved.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and drawings.
In order to make the above objects, features and advantages of the present invention more comprehensible, preferred embodiments accompanied with figures are described in detail below.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1a is a block diagram of an organ-chip for drug screening according to one embodiment of the present invention;
FIG. 1b is a block diagram of an organ-chip for drug screening according to another embodiment of the present invention;
fig. 2a is a block diagram of a first transfer unit according to an embodiment of the present invention;
fig. 2b is a block diagram of a second transfer unit according to an embodiment of the present invention;
fig. 2c is a block diagram of a third transfer unit according to an embodiment of the present invention;
fig. 2d is a block diagram of a fourth transfer unit according to an embodiment of the present invention;
FIG. 3a is a schematic view of a transparent top cover according to an embodiment of the present invention;
FIG. 3b is a schematic view of a transparent plug according to an embodiment of the present invention;
fig. 4a is a schematic diagram of the front surface of the first micro flow channel layer according to the embodiment of the present invention;
FIG. 4b is a schematic diagram of the reverse side of the micro flow channel layer according to the embodiment of the present invention;
fig. 5 is a schematic structural diagram illustrating the operation of the check valve in the micro flow channel layer according to the embodiment of the present invention;
FIG. 6a is a schematic diagram showing the control principle of the culture medium in the organ-on-chip for drug screening according to one embodiment of the present invention;
FIG. 6b is a schematic diagram showing the control principle of the culture medium in the organ-on-chip for drug screening according to another embodiment of the present invention;
FIG. 7 is a schematic diagram of the principle of medium renewal in an organ-chip for drug screening according to an embodiment of the present invention;
fig. 8 is a schematic diagram of the front surface of a second micro flow channel layer according to an embodiment of the present invention;
fig. 9 is a schematic diagram of the front surface of a third micro flow channel layer according to an embodiment of the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The organ chip for drug screening provided by the embodiment of the invention can be added with a transfer unit on an organ chip main body, wherein the transfer unit is detachably embedded in the organ chip main body, and when the transfer unit is embedded in the organ chip main body, a culture medium in the organ chip main body enters the transfer unit, so that the test tissue screening of drugs to be screened is realized, drug screening is completed, a transfer means is provided between a biological 3D printer and the organ chip by virtue of the transfer unit capable of bearing biological 3D printing tissues, the technical difficulty of printing directly in the organ chip is avoided, meanwhile, the biological 3D printing tissue bearing test tissue is adopted, the problem of cell shedding is solved, the blockage of the micro flow channel is avoided, and the survival rate of cells is improved.
For the convenience of understanding the present embodiment, first, a detailed description will be given of an organ-chip for drug screening disclosed in the embodiment of the present invention.
Referring to fig. 1a, an embodiment of the present invention provides an organ chip for drug screening, the shape of the organ chip for drug screening is rectangular, the chip includes: transfer unit 1000, organ-chip main body 2000, transfer unit 1000 is detachably embedded inside organ-chip main body 2000. As an example of a practical application, when a user starts an experiment, the user takes out one of the transfer units 1000, places the biological 3D printing-like tissue on the transfer unit 1000, and then mounts the transfer unit 1000 with the biological 3D printing-like tissue to the organ-chip main body 2000 in an embedded manner.
Wherein, the organ-chip main body 2000 is used for placing a culture medium containing medicines to be screened; the transfer unit 1000 is used for placing test tissues, the transfer unit 1000 is embedded in the organ chip main body 2000, a culture medium in the organ chip main body 2000 is convenient to enter the transfer unit 1000, the test tissues are used for screening medicines to be screened, and the test tissues comprise: biological 3D printing of tissue.
Specifically, in the test, biological 3D printing tissue is placed in the transfer unit 1000, the transfer unit 1000 carrying biological 3D printing tissue is embedded in the organ-chip body 2000, and a culture medium is provided in the organ-chip body 2000, wherein the culture medium may include a drug to be screened, and the biological 3D printing tissue is soaked in the culture medium, that is, the biological 3D printing tissue is soaked in the drug to be screened, so that after a period of time, the effect of the drug on the biological 3D printing tissue can be evaluated by observing the condition of cells in the biological 3D printing tissue, thereby screening the drug.
The present invention further defines the structure of the transfer unit, and in particular, the transfer unit may be a unitary structure, while the transfer unit includes an aperture 1300 through which the culture medium in the organ-chip main body 2000 can enter the transfer unit 1000. Alternatively, the transferring unit 1000 may be a separate structure, and specifically includes a transferring unit main body 1100 and a transferring unit chassis 1200; the transfer unit body 1100 is fastened to the transfer unit chassis 1200. In this case, the apertures 1300 may be located on the sides of the transfer unit body or on the transfer unit chassis. Further, a semipermeable membrane 1400 is included in the transport unit tray 1200, and the culture medium in the organ-chip main body 2000 can permeate into the transport unit 1000 through the semipermeable membrane. The shape of the transferring unit can be cuboid, square, round through type, polyhedron and the like.
As a structural feature of the above-defined transfer unit, there may be the following several forms of transfer unit 1000.
As shown in fig. 2 a-2 d, four types of transfer units 1000 are disclosed, the transfer unit a being of the type shown in fig. 2a, the sides of the transfer unit 1000 comprising apertures 1300. In this way, the culture medium in the organ-chip main body can enter the transport unit 1000 through the small hole 1300.
As shown in fig. 2b to 2d, the transfer unit 1000 is disclosed as a split structure, and in particular, the transfer unit 1000 includes a transfer unit body 1100 and a transfer unit chassis 1200; the transfer unit body 1100 is fastened to the transfer unit chassis 1200.
However, the 3 structures are different in that, in connection with fig. 2b, the transferring unit b type, the side surface of the transferring unit body includes a small hole 1300, wherein, the transferring unit chassis 1200 may have a chassis locking strip, and when the transferring unit body 1100 is installed on the transferring unit chassis 1200, the transferring unit body is deformed by pressing and then is buckled with the transferring unit chassis. The small holes on the side surfaces can be utilized to correspond to the positions of the chassis clamping strips, and the area of the chassis clamping strips is smaller than that of the small holes on the side surfaces, so that the chassis clamping strips cannot be embedded into the small holes on the side surfaces to form a small hole for liquid to flow.
Referring to fig. 2c, the side of the main body of the transferring unit includes a small hole 1300, where the chassis of the transferring unit includes a chassis clamping strip 1200 and a semipermeable membrane 1400, after the main body 1100 of the transferring unit is deformed by extrusion, the main body of the transferring unit is buckled with the chassis 1200 of the transferring unit, and the small hole on the side corresponds to the position of the chassis clamping strip, and the chassis clamping strip is completely attached to the small hole on the side to seal the side of the transferring unit, so that the culture medium is permeated into the transferring unit 1000 only through the semipermeable membrane.
Referring to fig. 2d, the transfer unit d-type is shown, in which the transfer unit body 1100 is not modified, and the transfer unit tray 1200 includes the small holes 1300, so that the culture medium can flow into the interior of the transfer unit 1000 through the small holes in the transfer unit tray 1200.
As shown in connection with fig. 2 a-2 d, embodiments of the present invention define that the top of the transfer unit 1000 includes a ledge 1500 and a locating opening 1600 in the ledge.
As an example, when the organ-chip body includes a hard top layer and a micro-channel layer, the hard top layer includes positioning points, the positioning opening 1600 of the transferring unit may be matched with the positioning points of the culture chambers in the hard top layer, the bottom of the positioning opening 1600 of the transferring unit is provided with a plurality of small holes, and when the organ-chip body is matched with the positioning points of the hard top layer, the positions of the small holes or the semi-permeable membrane of the transferring unit should correspond to the positions where the culture chambers of the micro-channel layer are connected with the micro-channel layer. When the transfer unit is provided with a positioning opening and an eave, the transfer unit can be more stably and fixedly arranged on the organ chip main body and matched with devices in the organ chip main body.
Optionally, the organ-chip further comprises: and the transparent top cover is covered on the organ chip main body or the transparent plug is covered on the organ chip main body culture chamber.
As shown in connection with fig. 3a, the transparent top cover 3000 includes a ventilation port 3100, a chamfer 3200.
As shown in connection with fig. 3b, the transparent plug 3010 includes a heparin cap 3011, a positioning port 3012.
Wherein, transparent top cap can be the rectangle transparent hard plastic lid through chamfer processing, and the shape of one of them location chamfer is different with other three to provide the location, transparent top cap's size, appearance coincide with the stereoplasm top layer, can include location chamfer 2160 and transparent top cap draw-in groove 2150 in the stereoplasm top layer, when having made things convenient for transparent top cap 3000 to cover the opening of all culture chambers in the stereoplasm top layer 2100 through these two points of usefulness of location, can install transparent top cap on transparent top cap draw-in groove 2150. In addition, the transparent top cover can also be provided with an air vent 3100 for exchanging air with the outside; or a transparent plug can be used for replacing the function of sealing the culture room from the transparent top cover, and the hard top layer is provided with a positioning point and a positioning eave which can be matched with the positioning opening 3012 on the transparent plug.
Referring again to fig. 1a, the organ-chip main body 2000 includes: the micro-fluidic channel layer 2200 is arranged between the hard top layer 2100 and the transparent bottom layer 2300, and the sensing chip is arranged between the micro-fluidic channel layer 2200 and the transparent bottom layer 2300.
Wherein the hard top layer 2100 is made of a transparent, non-toxic material to cells, which may include, but is not limited to, polystyrene Plastic (PS), polycarbonate (PC), cyclic olefin copolymer plastic (COC plastic), polyethylene (PE), polypropylene (PP).
The hard top layer 2100 comprises at least one culture room, positioning points, positioning eaves, gas channels, top surface grooves, bottom surface grooves, detection areas 2130, transparent top cover clamping grooves 2150 and culture room numbers; the bottom surface groove is used for placing the micro-channel layer.
At least one culture chamber contained in the rigid top layer 2100 can hold test tissue for testing, such as cells, tissue or biological 3D printing tissue, and can also hold a transport unit containing cells, tissue or biological 3D printing tissue; and the positioning point and the positioning eave are arranged on the culture room and can be matched with the positioning opening of the transferring unit.
The grooves on the top surface can distinguish different micro-channel layers and are matched with the serial numbers of the culture chambers for use. Detection area 2130 may be provided with 96-well plate enzyme-labeled strips for analysis of the removed medium or directly in the detection area.
In addition, the culture room number is mainly used for distinguishing, and the organ chip main body can comprise a plurality of culture rooms and can culture different types of test tissues at the same time, so that the culture room number can enable a user to do distinguishing work in the test. The function of the positioning chamfer is to be matched with the transparent top cover for installation, and the correct installation direction of the transparent top cover can be conveniently and rapidly found when the transparent top cover is used.
The micro-channel layer 2200 comprises at least one culture chamber, a micro-channel, a one-way valve, a driving groove, a liquid storage groove, a dividing groove, a fence-shaped valve, a soft film, a liquid inlet and a liquid outlet; the micro-flow channel connects the at least one culture chamber, the driving groove, the liquid storage groove and the dividing groove; the fence-shaped valve separates and breaks the dividing grooves; the soft film separates the driving groove from the liquid storage groove and the dividing groove.
The micro flow channel layer is composed of Polydimethylsiloxane (PDMS) or a soft material which contains polydimethylsiloxane and is harmless to cell growth, and two sides of the micro flow channel layer are bonded with the hard top layer and the transparent bottom layer in an irreversible bonding mode through oxygen plasma treatment.
As shown in fig. 4a and 4b, the micro flow path 2220 is connected to the culture chamber 2210 in the micro flow path layer, the flow path width gradient, the dividing groove 2240, the liquid storage groove 2230, the driving groove 2260, and is partitioned by the barrier-like valve 2250 in the dividing groove 2240, or as shown in fig. 5, the flow direction control and the back flow prevention can be achieved by adding the check valve 2270 in the micro flow path 2220. Specifically, the micro flow channel 2220 on the organ chip main body 2000 is in a vertical structure, and the culture medium enters the culture chamber 2210 of the micro flow channel layer after passing through the one-way valve 2270 from the micro flow channel 2220, and then leaves the culture chamber 2210 of the micro flow channel layer through the other one-way valve 2270 to enter the other section of micro flow channel 2220 in the vertical direction; after the medium is added to the culture chamber 2210, the entire micro flow path 2220 is filled. The diameter of the micro flow channel is less than or equal to 1mm, a circulating flowing liquid culture medium is provided for a culture chamber of the micro flow channel layer, nutrition is provided for the growth of cells, tissues or biological 3D printing tissues, and metabolic wastes are discharged;
alternatively, the micro flow channel 2220 has a micro flow channel with gradually changed width, which may be referred to as a flow channel width gradient, where the width of the flow channel width gradient near one end of the culture chamber is greater than the width near one end of the micro flow channel, or the flow channel width gradient is a micro flow channel with gradually changed diameter when the micro flow channel and the culture chamber are connected through a vertical flow channel.
As shown in connection with fig. 6a, the organ-chip main body 2000 is further adapted to be connected to a driving system 5000 via a conduit 3500, the driving system 5000 being adapted to drive the flow of the culture medium within the organ-chip main body.
Since the driving system 5000 uses the difference of air pressure to control the flow of the culture medium in the organ-chip main body 2000 and the culture medium is mainly in the hard top layer 2100 and the micro flow channel layer 2200, the air path of the hard top layer 2100 will be described first. In the invention, the hard top layer 2100 comprises a gas channel, the gas channel comprises a gas pipe interface and a gas output port, the gas pipe interface and the gas output port can be communicated together through a conduit to form a gas channel, and the gas output port can be connected with a driving groove 2260 of the micro-channel layer; the air tube interface 2140 may be connected to the drive system 5000 by tubing 3500, with the air output port on the rigid top layer corresponding in position and shape to the drive recess 2260 in the micro-fluidic channel layer. In the micro flow channel layer 2200, the driving groove 2260 may be separated from the dividing groove 2240 or the liquid storage groove 2230 by a flexible film; the driving groove 2260 corresponds to the position and shape of the gas outlet on the hard top layer, and the driving system 5000 outputs gas to the organ-chip main body through the pipeline 3500, in the organ-chip main body, the gas pipe interface 2140 is connected with the pipeline 3500, and when the gas is conveyed to the organ-chip main body through the gas pipe interface 2140, the soft film can be deformed by changing the gas pressure in the gas channel, so that the volumes of the dividing groove 2240 and the liquid storage groove 2230 are changed, the opening and closing of the fence-shaped valve 2250 and the control of the liquid volume in the liquid storage groove 2230 are realized, and the flow of the culture medium in the organ-chip main body is realized.
In the case of internal circulation of the culture medium in the organ-chip main body 2000, the micro flow path layer 2200 may have the following structure, and as shown in fig. 4a, the micro flow path 2220 may be a closed loop flow path, and the culture medium in the micro flow path is self-circulated by the driving system 5000 and updated by periodically replacing the culture medium manually. The manual periodic replacement may be performed by pouring out the original medium and then placing a new medium into the organ-chip main body 2000 using a tool that can hold a liquid.
Or the micro-fluidic channel 2220 may be made to flow in one or more height dimensions, i.e., the medium may flow in the same plane as the channel, or may continue to circulate through a vertical channel into a channel of another height dimension.
When the drive system 5000 is used to update the culture medium in the organ-chip main body 2000, as shown in fig. 7, the drive system 5000 may be connected to the liquid storage tank 6100 and the liquid waste tank 6200 through a pipeline, meanwhile, the surface of the hard top layer may be added with a liquid inlet 2110 and a liquid outlet 2120 as required, the drive system 5000 is connected to the liquid inlet 2110 and the liquid outlet 2120 in the organ-chip main body 2000, and new culture medium enters the liquid inlet 2110 through the pipeline under the drive of the drive system, and leaves the organ-chip main body 2000 through the pipeline from the liquid outlet 2120 after the circulation in the organ-chip main body 2000 is completed.
In the case of completing the update of the culture medium in the organ-chip main body 2000, the micro flow channel layer may also have a structure, as shown in fig. 8, in which the micro flow channel 2220 may be an open loop flow channel, a liquid inlet 2221 and a liquid outlet 2222 are provided in the micro flow channel and correspond to the positions of the liquid inlet 2110 and the liquid outlet 2120 of the hard top layer, the driving system 5000 drives the fresh culture medium in the liquid reservoir to the liquid inlet 2110 of the hard top layer through a pipe, and enters the micro flow channel 2220, after the culture medium completes the circulation in the micro flow channel 2220, the culture medium leaves the micro flow channel through the liquid outlet 2222 in the micro flow channel and is discharged into the liquid waste reservoir through a pipe connected to the liquid outlet 2120 of the hard top layer, and the culture medium is extracted and analyzed or discarded after entering the liquid waste reservoir 6200.
Wherein the transfer unit is matched with at least one culture chamber in the hard top layer and at least one culture chamber in the micro-channel layer.
Wherein, the hard top layer 2100, the micro flow channel layer 2200, and the transparent bottom layer 2300 are bonded by an irreversible bonding manner through an oxygen plasma treatment, and the culture chamber of the hard top layer 2100 is correspondingly matched with the culture chamber of the micro flow channel layer 2200 during the bonding process, and the micro flow channel layer 2200 and the transparent bottom layer 2300 fix the sensing chip between the micro flow channel layer 2200 and the transparent bottom layer 2300 during the bonding process, and can be in contact with the culture medium in the micro flow channel 2220 of the micro flow channel layer 2200, and the organ chip main body 2000 is used as a whole.
The transparent bottom layer 2300 may be composed of a transparent hard glass or other transparent hard material, is irreversibly bonded to the micro flow channel layer, provides a substrate for the micro flow channel layer 2200, and includes a sensor chip.
The sensing chip is a biochip with a surface functionalized with a biomarker, is arranged at the top end or the bottom end of a culture chamber in a micro-channel, a hard top layer or a micro-channel layer and is contacted with a culture medium; according to the selected sensing principle and the sensing conditions required by the sensing chip, a channel for leading the sensing conditions to enter and exit the organ chip main body is arranged on the organ chip main body and is communicated with the sensing chip; the sensed conditions include, but are not limited to, light, current, voltage, magnetic field, and various aspects of the characteristics are detected and recorded in real time as they enter and exit the organ-chip body.
As described in connection with FIG. 1b, another embodiment of the present invention provides an organ chip for drug screening, which may be made as a hexahedron, wherein the culture chamber 2110 in the rigid top layer 2100 is sealed with a transparent stopper 3010, the transparent stopper 3010 is provided with a heparin cap, and liquid can be added to or extracted from the culture chamber by a syringe with a needle passing through the heparin cap 3011.
As shown in fig. 6a, the present invention further includes a printing head 4000, and the printing head 4000 can directly print biological 3D printing tissue and put it into the transfer unit 1000.
As described in connection with fig. 6b, the organ chip of the invention may be integrated with the driving system 5000, and the driving system 5000 is connected to the display control means 5100, and the control operation is performed by the display control means 5100.
In the case of the operation of the organ-chip described with reference to fig. 6b, the micro flow path layer 2220 may have a structure in which, as shown in fig. 9, the micro flow path layer 2200 includes one micro flow path 2220 connected to the micro flow paths communicating all of the culture chambers in the hard top layer 2100, and the micro flow path layer 2200 is sealed to the hard top layer 2100 by irreversible bonding. When in use, the culture chamber is sealed by the transparent plug 3010, and the organ-chip main body 2000 is connected with the driving system 5000, so that the driving system 5000 periodically extrudes the micro flow channels 2220 of the micro flow channel layer 2200 to drive the culture medium to complete circulation in the organ chip; in the drug screening process, a culture medium containing the screened drug is added or a test sample containing a metabolite is extracted from the heparin cap 3011 of the transparent plug 3010 through a syringe with a needle.
Several examples of practical applications of the organ-a-chip for drug screening provided by the present invention are described below.
Example 1, biological 3D printing tissue 4000 is printed by a transfer unit a-type receiving printing spray head, the transfer unit a-type containing the biological 3D printing tissue is placed in a culture medium, and the biological 3D printing tissue is cultured; after a certain time of culture, the transfer unit a-type is positioned and placed into the organ chip main body 2000 through the positioning opening 1600, the whole micro-flow channel 2220 is filled with the culture medium after the culture medium is added into the culture chamber, the transparent top cover 3000 is placed on the transparent top cover clamping groove 2150, and then the driving system 5000 and the air pipe interface 2140 are connected through the pipeline 3500, so that the biological 3D printing tissue is subjected to drug screening.
Or a transfer unit a-type receiving printing nozzle 4000 is used for printing biological 3D printing tissues, the transfer unit a-type containing the biological 3D printing tissues is placed in a culture medium, and the biological 3D printing tissues are cultured; after culturing for a certain time, placing the type a transfer unit with biological 3D printing tissue into a culture chamber 2110 on the organ chip main body 2000; after the culture medium is added into the culture chamber and fills the whole micro flow channel 2220, the culture chamber is sealed by a transparent plug, and then the driving system 5000 and the air pipe interface 2140 are connected by a pipeline 3500, so that the biological 3D printing tissue is subjected to drug screening.
Example 2, biological 3D printing tissue printed by a transfer unit type a receiving printing nozzle 4000 is put into a culture medium together, and the biological 3D printing tissue is cultured; after a certain period of time, placing the a-type transfer unit with biological 3D printing tissue into a culture chamber on the organ chip main body 2000, adding a culture medium into the culture chamber, filling the whole micro-channel 2220, sealing all culture chambers by a transparent plug, then connecting the organ chip main body 2000, a driving system 5000, a liquid storage tank 6100, a liquid waste tank 6200 and a liquid inlet 2110 of the liquid storage tank 6100 with a hard top layer 2100 by pipelines, connecting the liquid outlet 2120 of the hard top layer with the liquid waste tank 6200 by pipelines, when the biological 3D printing tissue screening device is used, the driving system 5000 drives the culture medium in the liquid storage tank 6100 by the pipelines to the liquid inlet 2110, then the culture medium enters the micro-channel 2220 by the liquid inlet 2221 of the micro-channel layer, leaves the micro-channel 2220 by the liquid outlet 2222 of the micro-channel layer after circulation, and then enters the pipelines by the liquid outlet 2120, and is then introduced into the liquid waste tank 6200, thereby screening the biological 3D printing tissue.
Example 3, a biological 3D printing tissue printed by the printing nozzle 4000 is received by the transfer unit chassis of the transfer unit b type, and then the transfer unit body 1100 of the transfer unit b type is pressed by a finger to deform and align with the transfer unit chassis 1200 of the transfer unit b type, the chassis clip and the small holes 1300 on the side are matched, and the finger is released to restore the transfer unit body 1100 of the transfer unit b type and fix it with the transfer unit chassis 1200 of the transfer unit b type; b, placing the fixed transfer unit b type with the biological 3D printing tissue into a culture medium for culture; after culturing for a certain time, placing the b-type transfer unit with the biological 3D printing tissue into a culture room on the organ chip main body 2000; after the culture medium is added into the culture room and fills the whole micro-channel 2220, the transparent top cover 3000 is placed in the transparent top cover clamping groove 2150, and then the driving system 5000 and the air pipe interface 2140 are connected by using a pipeline 3500, so that the biological 3D printing tissue is subjected to drug screening.
Or the biological 3D printing tissue printed by the printing spray head 4000 is received by the transport unit chassis of the transport unit c type, then the transport unit main body 1100 of the transport unit c type is pressed by fingers to deform and align with the transport unit chassis 1200 of the transport unit c type, the chassis clamping strips are matched with the small holes 1300 on the side surface, and the fingers are released to restore the transport unit main body 1100 of the transport unit c type and fix the transport unit main body 1100 of the transport unit c type with the transport unit chassis 1200 of the transport unit c type; c-type transferring unit c-type with biological 3D printing tissue is placed into a culture medium for culture; after culturing for a certain time, placing the c-type transfer unit with the biological 3D printing tissue into a culture chamber on the organ chip main body 2000, adding a culture medium into the culture chamber and filling the whole micro-flow channel 2220, placing the transparent top cover 3000 into the transparent top cover clamping groove 2150, and then connecting the driving system 5000 and the air pipe interface 2140 by using a pipeline 3500, thereby carrying out drug screening on the biological 3D printing tissue.
Or the biological 3D printing tissue printed by the printing spray head 4000 is received by the transport unit chassis of the transport unit D type, and then the transport unit main body 1100 of the transport unit D type is pressed by fingers to deform and align with the transport unit chassis 1200 of the transport unit D type, and the transport unit main body 1100 of the transport unit D type is restored to the original shape by loosening fingers and is fixed with the transport unit chassis 1200 of the transport unit D type; d-type transferring units with biological 3D printing tissues after fixation are placed into a culture medium for culture; d-type transferring unit with biological 3D printing tissue is placed into a culture room on the organ chip main body 2000 after culturing for a certain time; after the culture medium is added into the culture room and fills the whole micro-channel 2220, the transparent top cover 3000 is placed in the transparent top cover clamping groove 2150, and then the driving system 5000 and the air pipe interface 2140 are connected by using a pipeline 3500, so that the biological 3D printing tissue is subjected to drug screening.
Example 4, biological 3D printing tissue printed by a printing nozzle is received by a transfer unit, and the biological 3D printing tissue are put into a culture medium together to culture the biological 3D printing tissue; after culturing for a certain time, placing the transfer unit 1000 with the biological 3D printing tissue into a culture room on the organ chip main body 2000; the micro flow channel 2220 on the organ chip main body 2000 adopts a vertical structure, and the culture medium enters the culture chamber after passing through the one-way valve from the micro flow channel 2220, and then leaves the culture chamber through the other one-way valve to enter the other section of micro flow channel 2220; after the culture medium is added into the culture room and fills the whole micro-channel 2220, the transparent top cover 3000 is placed in the transparent top cover clamping groove 2150, and then the driving system 5000 and the air pipe interface 2140 are connected by using a pipeline 3500, so that the biological 3D printing tissue is subjected to drug screening.
Example 5 after drug screening was started according to the above example, the medium in the culture chamber was taken out with a pipette and added to the detection area 2130, or the medium taken out of the culture chamber was added to the ELISA strip after the ELISA strip was placed in the detection area 2130; fluorescent markers were added to the medium, transparent top 3000 was placed in transparent top card slot 2150, and organ-chip main body 2000 was then placed in an enzyme-labeled instrument for analysis of the medium components.
The relative steps, numerical expressions and numerical values of the components and steps set forth in these embodiments do not limit the scope of the present invention unless it is specifically stated otherwise.
Any particular values in all examples shown and described herein are to be construed as merely illustrative and not a limitation, and thus other examples of exemplary embodiments may have different values.
It should be noted that: like reference numerals and letters denote like items in the following figures, and thus once an item is defined in one figure, no further definition or explanation thereof is necessary in the following figures.
In addition, in the description of embodiments of the present invention, unless explicitly stated and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.
In the description of the present invention, it should be noted that the directions or positional relationships indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings, are merely for convenience of describing the present invention and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be configured and operated in a specific orientation, and thus should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
Finally, it should be noted that: the above examples are only specific embodiments of the present invention, and are not intended to limit the scope of the present invention, but it should be understood by those skilled in the art that the present invention is not limited thereto, and that the present invention is described in detail with reference to the foregoing examples: any person skilled in the art may modify or easily conceive of the technical solution described in the foregoing embodiments, or perform equivalent substitution of some of the technical features, while remaining within the technical scope of the present disclosure; such modifications, changes or substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention, and are intended to be included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (3)
1. An organ-chip for drug screening, comprising a transfer unit and an organ-chip body; the organ chip main body is used for placing a culture medium containing medicines to be screened; the transfer unit is used for placing test tissues, and the test tissues are biological 3D printing tissues containing cells; the transferring unit is detachably embedded in the organ chip main body; when the transfer unit is embedded into the organ chip main body, a culture medium in the organ chip main body can enter the transfer unit to realize screening of the drug to be screened by the test tissue; the organ chip main body is connected with a driving system, and the driving system drives the culture medium to flow in the organ chip main body through air pressure; wherein,
the transfer unit comprises a transfer unit main body and a transfer unit chassis, and the transfer unit main body is buckled with the transfer unit chassis; the transferring unit comprises a small hole, and the small hole is positioned on the side surface of the transferring unit main body or on the chassis of the transferring unit; the top of the transferring unit comprises an eave and a positioning opening on the eave;
the transport unit chassis comprises a semipermeable membrane through which the culture medium permeates into the interior of the transport unit;
the organ chip main body comprises a hard top layer, a micro-channel layer, a transparent bottom layer and a sensing chip, wherein the micro-channel layer is arranged between the hard top layer and the transparent bottom layer, and the sensing chip is arranged between the micro-channel layer and the transparent bottom layer;
the hard top layer comprises at least one culture room, positioning points, positioning eaves, a gas channel, a top surface groove, a bottom surface groove, a detection area, a transparent top cover clamping groove and a culture room number, wherein the bottom surface groove is used for placing a micro-channel layer; the micro-channel layer comprises at least one culture chamber, a micro-channel, a one-way valve, a driving groove, a liquid storage groove, a dividing groove, a fence-shaped valve, a soft film, a liquid inlet and a liquid outlet, wherein a culture medium enters the organ chip main body from the liquid inlet, and the culture medium is output out of the organ chip main body from the liquid outlet; the micro-flow channel is connected with the at least one culture chamber, the driving groove, the liquid storage groove and the dividing groove, and is provided with a section of micro-flow channel with gradually changed width; the fence-shaped valve separates and breaks the dividing grooves; the driving groove is separated from the liquid storage groove and the dividing groove by the soft film; the positioning points in the hard top layer are matched with the positioning openings in the transferring unit, the transferring unit is matched with at least one culture chamber in the hard top layer and at least one culture chamber in the micro-channel layer, and the connection position of the culture chamber in the micro-channel layer and the micro-channel corresponds to the position of the small hole or the semi-permeable membrane in the transferring unit; the gas channel in the hard top layer comprises a gas pipe interface and a gas output port, the gas pipe interface is communicated with the gas output port through a guide pipe and jointly forms a gas channel, the gas output port is connected with the driving groove of the micro-channel layer, and the gas output port corresponds to the driving groove in the micro-channel layer in position and shape; the air pipe interface is connected with the driving system through a pipeline and is used for outputting air to the organ chip main body, the air pipe interface is used for conveying the air to the organ chip main body, the air pressure in the air channel can be changed, the soft film is deformed, the volumes of the dividing grooves and the liquid storage grooves are changed, so that the opening and closing of the fence-shaped valve and the control of the liquid volume in the liquid storage grooves are realized, and the culture medium is driven to flow in the organ chip main body.
2. The organ-on-chip for drug screening according to claim 1, further comprising a transparent cap covering the organ-on-chip body; or further comprises a transparent plug which covers the culture chamber of the organ-chip main body.
3. The organ-chip for drug screening according to claim 2, wherein the organ-chip main body is in the shape of a rectangular parallelepiped or a hexahedral shape.
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| CN109929761B (en) * | 2019-04-30 | 2024-02-02 | 杭州捷诺飞生物科技股份有限公司 | Cell dynamic culture chip and cell dynamic culture device |
| CN113186162B (en) * | 2021-04-19 | 2023-08-15 | 西安交通大学 | Three-dimensional active brain tissue biochip with bionic structure |
Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2528020Y (en) * | 2002-03-29 | 2002-12-25 | 成都夸常科技有限公司 | Dismounting biological chip |
| CN102023205A (en) * | 2009-09-09 | 2011-04-20 | 上海裕隆生物科技有限公司 | Detachable film chip |
| CN102382758A (en) * | 2011-10-14 | 2012-03-21 | 杭州电子科技大学 | Three-dimensional cell chip based on cell printing and multi-parameter sensing array integrated technology |
| WO2013086329A1 (en) * | 2011-12-08 | 2013-06-13 | Research Triangle Institute | Human emulated response with microfluidic enhanced systems |
| CN203238271U (en) * | 2013-04-24 | 2013-10-16 | 宁波美晶医疗技术有限公司 | Easy-to-pull detachable biochip |
| CN103981085A (en) * | 2014-05-27 | 2014-08-13 | 东南大学 | Self-set concentration gradient drug screening organ chip and preparation method thereof |
| CN103981096A (en) * | 2014-05-27 | 2014-08-13 | 东南大学 | Two-layer cell culture system organ chip and preparation method thereof |
| CN105754856A (en) * | 2016-04-12 | 2016-07-13 | 中国航天员科研训练中心 | Drawer type three-dimensional quasi-vascularization tissue culture organ chip and establishment method thereof |
| CN106811409A (en) * | 2015-12-01 | 2017-06-09 | 中国科学院大连化学物理研究所 | Multiple organ tumor-targeting drug test platform and its application based on micro-fluidic chip |
| WO2017175236A1 (en) * | 2016-04-06 | 2017-10-12 | Dandekar Jain Prajakta | Microfluidic platform for developing in-vitro co-cultures of mammalian tissues. |
| CN107254406A (en) * | 2017-05-23 | 2017-10-17 | 北京大学 | Biological cell chip high flux, high intension, parallel imaging arrangement and screening system |
| WO2017177839A1 (en) * | 2016-04-14 | 2017-10-19 | 清华大学 | Super-hydrophobic micro-pit array chip, preparation method therefor and applications thereof |
| CN108641931A (en) * | 2018-04-04 | 2018-10-12 | 浙江大学 | A kind of digitlization microarray organ chip and its application |
| CN209352912U (en) * | 2018-10-19 | 2019-09-06 | 杭州捷诺飞生物科技股份有限公司 | Drug screening organ chip |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013086502A1 (en) * | 2011-12-09 | 2013-06-13 | President And Fellows Of Harvard College | Organ chips and uses thereof |
| JP6423082B2 (en) * | 2015-04-03 | 2018-11-14 | 国立研究開発法人産業技術総合研究所 | Cell culture device and cell culture method |
-
2018
- 2018-10-19 CN CN201811223566.5A patent/CN109055204B/en active Active
Patent Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2528020Y (en) * | 2002-03-29 | 2002-12-25 | 成都夸常科技有限公司 | Dismounting biological chip |
| CN102023205A (en) * | 2009-09-09 | 2011-04-20 | 上海裕隆生物科技有限公司 | Detachable film chip |
| CN102382758A (en) * | 2011-10-14 | 2012-03-21 | 杭州电子科技大学 | Three-dimensional cell chip based on cell printing and multi-parameter sensing array integrated technology |
| WO2013086329A1 (en) * | 2011-12-08 | 2013-06-13 | Research Triangle Institute | Human emulated response with microfluidic enhanced systems |
| CN203238271U (en) * | 2013-04-24 | 2013-10-16 | 宁波美晶医疗技术有限公司 | Easy-to-pull detachable biochip |
| CN103981096A (en) * | 2014-05-27 | 2014-08-13 | 东南大学 | Two-layer cell culture system organ chip and preparation method thereof |
| CN103981085A (en) * | 2014-05-27 | 2014-08-13 | 东南大学 | Self-set concentration gradient drug screening organ chip and preparation method thereof |
| CN106811409A (en) * | 2015-12-01 | 2017-06-09 | 中国科学院大连化学物理研究所 | Multiple organ tumor-targeting drug test platform and its application based on micro-fluidic chip |
| WO2017175236A1 (en) * | 2016-04-06 | 2017-10-12 | Dandekar Jain Prajakta | Microfluidic platform for developing in-vitro co-cultures of mammalian tissues. |
| CN105754856A (en) * | 2016-04-12 | 2016-07-13 | 中国航天员科研训练中心 | Drawer type three-dimensional quasi-vascularization tissue culture organ chip and establishment method thereof |
| WO2017177839A1 (en) * | 2016-04-14 | 2017-10-19 | 清华大学 | Super-hydrophobic micro-pit array chip, preparation method therefor and applications thereof |
| CN107254406A (en) * | 2017-05-23 | 2017-10-17 | 北京大学 | Biological cell chip high flux, high intension, parallel imaging arrangement and screening system |
| CN108641931A (en) * | 2018-04-04 | 2018-10-12 | 浙江大学 | A kind of digitlization microarray organ chip and its application |
| CN209352912U (en) * | 2018-10-19 | 2019-09-06 | 杭州捷诺飞生物科技股份有限公司 | Drug screening organ chip |
Non-Patent Citations (2)
| Title |
|---|
| The recent development and applications of fluidic channels by 3D printing;Yufeng Zhou;《J Biomed Sci》;第24卷(第1期);全文 * |
| 生物3D打印——打印生命的希望;徐铭恩;《杭州科技》(第05期);全文 * |
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|---|---|
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