CN104826676B - Micro-fluidic chip, system and application thereof - Google Patents
Micro-fluidic chip, system and application thereof Download PDFInfo
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- CN104826676B CN104826676B CN201510221090.1A CN201510221090A CN104826676B CN 104826676 B CN104826676 B CN 104826676B CN 201510221090 A CN201510221090 A CN 201510221090A CN 104826676 B CN104826676 B CN 104826676B
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Abstract
The present invention relates to micro-fluidic chip, system and application thereof, include inside this micro-fluidic chip: some chambers；Some biological supports, constitute some organoids in being correspondingly arranged in described some chambers；And some microfluidic channel, it being correspondingly arranged between corresponding organoid composition class blood circulation, at least one microfluidic channel arranges pump interface.This micro-fluidic chip system includes: above-mentioned micro-fluidic chip；Fluid pump, connects with described pump interface；And control device, electrically connect with described fluid pump, to regulate and control the running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs.This application includes: be full of cytotrophy liquid, injection of medicine in corresponding chamber in described class blood circulation；Start fluid pump, promote described liquid at class blood circulation internal circulation flow；And the organoid that monitoring is relevant.It can substitute human body or animal body carries out the screening of medicine, has the advantages such as low cost, safety, cycle be short.
Description
Technical field
The present invention relates to the fields such as micro-fluidic chip, Computer-aided Tissue Engineering, biological 3D printing, more specifically, relate to
And one micro-fluidic chip, system and application thereof.
Background technology
Composition analyzed is the important step of drug research and drug development, medicine is used for zoopery and clinical trial needs to put into
Plenty of time and fund cost, and the data provided also are limited, this all limits the research and development of medicine.
Summary of the invention
It is an object of the invention to provide a kind of micro-fluidic chip, system and application thereof, enter with solution zoopery and clinical trial
The above-mentioned technological deficiency that row Composition analyzed exists.
The concrete technical scheme of the present invention is:
A kind of micro-fluidic chip, includes inside it:
Some chambers, each chamber has independent inlet；
Some biological supports, are correspondingly arranged in described some chambers, constitute the some organoids corresponding with some organs of human body；
And
Some microfluidic channel, are correspondingly arranged between corresponding organoid, constitute identical with blood circulation between human organ
Class blood circulation, at least one microfluidic channel is disconnected and channel end upon opening arranges pump interface.
In above-mentioned micro-fluidic chip, it is preferable that described micro-fluidic chip is from up to down by cover plate, intermediate plate and base plate stacking
Sealing and constitute, described some chambers take shape in described base plate, and described some microfluidic channel take shape in described intermediate plate.
In above-mentioned micro-fluidic chip, it is preferable that the microfluidic channel taking shape in described intermediate plate is narrow slit.
In above-mentioned micro-fluidic chip, it is preferable that described some organoids include brain, lung, heart, liver, spleen, stomach, little
Intestinal, large intestine and kidney, described pump interface is arranged at the microfluidic channel connecting heart.
In above-mentioned micro-fluidic chip, it is preferable that described some organoids also include skeletal muscle and/or skin.
In above-mentioned micro-fluidic chip, it is preferable that described biological support is with the crisscross three-dimensional knot of biomaterial structure
Structure.
A kind of micro-fluidic chip system, comprising:
Micro-fluidic chip described in above-mentioned any one；
Fluid pump, connects with the pump interface of described micro-fluidic chip；And
Control device, electrically connect with described fluid pump, to regulate and control the running status of fluid in micro-fluidic chip, simulate blood in human body in
Fluid circulation runs.
A kind of application of micro-fluidic chip system, described micro-fluidic chip system includes:
Micro-fluidic chip described in above-mentioned any one；
Fluid pump, connects with the pump interface of described micro-fluidic chip；And
Control device, electrically connect with described fluid pump, to regulate and control the running status of fluid in micro-fluidic chip, simulate blood in human body in
Fluid circulation runs；
Described application includes:
Cytotrophy liquid, injection of medicine in corresponding chamber it is full of in the class blood circulation of described micro-fluidic chip；
Start fluid pump, promote described liquid at class blood circulation internal circulation flow；And
The organoid that monitoring is relevant, carries out drug efficacy study.
Application at above-mentioned micro-fluidic chip system, it is preferable that described in corresponding chamber the step of injection of medicine include:
Open the inlet of this chamber；From this inlet injection of medicine；Close this inlet.The organoid that described monitoring is relevant, is carried out
The step of drug efficacy study includes: close fluid pump, and the sample extracting organoid from the inlet of this organoid place chamber is examined
Survey.
Beneficial effects of the present invention is as follows:
This micro-fluidic chip simulates human organ and blood circulation, is combined with fluid pump and control device, it is possible to promote also
Liquid in regulation chip circulates between organoid, the blood of simulation human body shuttling movement between organ, therefore can
Enough replacement human body or animal bodies carry out the screening of medicine.With the method phase being carried out Composition analyzed by zoopery and clinical trial
Ratio, the present invention has low cost, safety and the advantage such as the cycle is short.
It can aids drug the most once circulate, secondary cycle or repeatedly circulate, grind for drug effect reaction and cell tolerance etc.
Study carefully and provide convenience.
Accompanying drawing explanation
Fig. 1 is some structural representations within embodiment micro-fluidic chip；
Fig. 2 is some embodiment micro-fluidic chip decomposing state figures；
Fig. 3 is the structural representation of biological support in some embodiments；
Fig. 4 is the structural representation of some embodiment micro-fluidic chip systems.
Detailed description of the invention
The present invention is further described with embodiment below in conjunction with the accompanying drawings.These more detailed descriptions are intended to help and understand the present invention,
And should not be taken to be limiting the present invention.According to present disclosure, it will be understood by those skilled in the art that and can need not
Or all these specific detail can implement the present invention.And in other cases, in order to avoid innovation and creation are desalinated, the most in detail
The well-known content of thin description.
Fig. 1 schematically illustrates the internal structure of some embodiment micro-fluidic chips.With reference to Fig. 1, the miniflow of some embodiments
The inside of control chip includes: some chambers 101 (with reference to Fig. 2), some biological supports 3, some microfluidic channel 2.Each
Chamber 101 has independent inlet 4, for injection of medicine and extract histioid sample in chamber 101 in chamber 101
Product.Some biological supports 3 are correspondingly arranged in described some chambers 101 (in conjunction with Fig. 2), constitute the some organs with human body
Corresponding some organoids.Some microfluidic channel 2 are correspondingly arranged between corresponding organoid, constitute and blood between human organ
The class blood circulation that fluid circulation is identical, wherein, two microfluidic channel 2 are disconnected and channel end upon opening
Pump interface 1,1 ' is set.The liquid outlet of 5 and 5 ' expression corresponding chambers in Fig. 1 and inlet opening.
With reference to Fig. 2, the micro-fluidic chip of some embodiments is from up to down by cover plate 100, intermediate plate 200 and base plate 300 stacking
Sealing and constitute, described some chambers 101 take shape in described base plate 300, and described some microfluidic channel 2 take shape in described centre
Plate 200.The via of inlet 4 it is provided with on top board 100.Wherein, the microfluidic channel 2 of described intermediate plate 200 is taken shape in
It it is narrow slit.It can be seen that this micro-fluidic chip uses the structure of three substrate superpositions, this structure makes the one-tenth of microfluidic channel 2
Type is convenient.It is to be appreciated that micro-fluidic chip can also use the structure of two substrate superpositions, specifically, can save
Intermediate plate 200, and microfluidic channel 2 is taken shape in base plate 300 upper end or cover plate 100 lower end.
In the micro-fluidic chip of some embodiments, the organoid of structure include brain, lung, heart, liver, spleen, stomach, small intestinal,
Large intestine and kidney, also include skeletal muscle and skin.Specifically, in FIG, from right to left, the organoid of structure corresponds to
Brain, lung, heart, liver, spleen, stomach, small intestinal, large intestine, kidney, skeletal muscle, skin.Described pump interface 1 and 1 ' is arranged at
Connect the microfluidic channel of heart, specifically, in the microfluidic channel connecting the left heart and brain, a pair pump interface is set, to connect one
Individual fluid pump；The microfluidic channel connecting the right heart and brain arrange another to pump interface, to connect another fluid pump.Can manage
Xie Di, in some embodiments, can be increased or decreased chamber and biological support to construct more or less of organoid, such as:
Do not construct skin and/or do not construct skeletal muscle etc., or constructing other organoid further.
Fig. 3 shows the structure of biological support 3.As it is shown on figure 3, biological support 3 be with biomaterial structure crisscross
Stereochemical structure.Biomaterial comprises nutrient substance and relevant cell, nutrient substance prioritizing selection gelatin and sodium alginate.Specifically
Ground, can print the biological support 3 containing cell and nutrient substance with biological 3D printer.In Fig. 3,6 represent biology
One component of support 3.
Fig. 4 schematically illustrates the structure of some embodiment micro-fluidic chip systems.With reference to Fig. 4, this micro-fluidic chip system
Including: above-mentioned micro-fluidic chip, two fluid pumps 400, control device 500.Two fluid pumps 400 are micro-fluidic with described
The pump interface 1,1 ' of chip connects, concrete, fluid pump (pump 1) with in the microfluidic channel being connected the left heart and brain
A pair pump interface connects, another fluid pump (pump 2) with another in the microfluidic channel being connected the right heart and brain to pump interface phase
Connect.Control device 500 to electrically connect with described fluid pump 400, to regulate and control the running status of fluid in micro-fluidic chip, simulate people
Internal blood circulation is run.Here two fluid pumps 400 and control device 500 combine, and simulate left and right heart respectively
Actuating unit, control device 500 regulate and control the rotating speed of fluid pump 400 liquid circulation velocity in regulating and controlling chip, according to reality
Demand is optional uses single pump or double pump.Arrow in figure represents the flow direction of liquid in chip.
Above-mentioned micro-fluidic chip system may be used for drug screening.During more specifically, be applied to drug screening, including:
In the class blood circulation of described micro-fluidic chip, it is full of cytotrophy liquid, in corresponding chamber 101, injects medicine
Thing；
Start fluid pump 400, promote described liquid at class blood circulation internal circulation flow；And
The organoid that monitoring is relevant, carries out drug efficacy study.
The described step of injection of medicine in corresponding chamber 101 includes: open the inlet 4 of this chamber；From this inlet
4 injection of medicines；It is then shut off this inlet 4.
The organoid that described monitoring is relevant, the step carrying out drug efficacy study includes: close fluid pump 400, from this organoid institute
Inlet 4 at chamber extracts the sample of organoid and detects.
From above-mentioned, the micro-fluidic chip system of some embodiments constructs organoid and class blood vessel (microfluidic channel 2),
Construct a complete simulation circulating system (class blood circulation), simulate human organ and blood circulation.Logical
Cross fluid pump 400 and control device 500 and simulate Cardiac Power mechanism to regulate and control the running status of fluid in chip apparatus, will carry
Medicine deliver to each organoid, and simulate blood in human body in fluid circulation and run, the organoid relevant by monitoring in real time is carried out
Drug efficacy study, thus reach the purposes such as drug screening.
The micro-fluidic chip system of some embodiments is capable of the drug effect Circulation of an organoid, and multiple organoid generation
Thank to influencing each other of medicine.Concrete, by one or more for infusion of medicine organoids, under the effect of fluid pump 400, medicine
After organoid metabolism, enter class blood circulation, act in multiple organoids, be again introduced into class blood circulation,
It is thus possible to realize medicine one-level metabolism, secondary metabolism or multistage metabolism such that it is able to grind for drug effect reaction and cell tolerance etc.
Study carefully offer convenient.
The present invention is drug research, screens and develop new thinking and the method for providing, and the fund that simultaneously significantly reduces became with the time
This.
Claims (7)
1. a micro-fluidic chip, it is characterised in that the inside of described micro-fluidic chip includes:
Some chambers (101), each chamber has independent inlet (4)；
Some biological supports (3), are correspondingly arranged in described some chambers, if constituting the Ganlei corresponding with some organs of human body
Organ, described some organoids include that brain, lung, heart, liver, spleen, stomach, small intestinal, large intestine and kidney, described biological support are
Crisscross stereochemical structure with biomaterial structure；And
Some microfluidic channel (2), are correspondingly arranged between corresponding organoid, constitute and blood circulation between human organ
Identical class blood circulation, arranges a pair pump interface (1,1 ') to connect one in the microfluidic channel connecting the left heart and brain
Individual fluid pump, arranges another to pump interface to connect another fluid pump in the microfluidic channel connecting the right heart and brain.
Micro-fluidic chip the most according to claim 1, it is characterised in that described micro-fluidic chip is from up to down by cover plate
(100), intermediate plate (200) and base plate (300) stacking seal and constitute, described some chambers (101) take shape in the described end
Plate, described some microfluidic channel take shape in described intermediate plate.
Micro-fluidic chip the most according to claim 2, it is characterised in that take shape in the microfluidic channel of described intermediate plate
(2) it is narrow slit.
Micro-fluidic chip the most according to claim 1, it is characterised in that described some organoids also include skeletal muscle,
And/or skin.
5. a micro-fluidic chip system, it is characterised in that described micro-fluidic chip system includes:
Micro-fluidic chip described in any one in Claims 1-4；
Two fluid pumps (400), corresponding with the two of the described micro-fluidic chip pairs of pump interfaces (1,1 ') connect；And
Control device (500), electrically connect with said two fluid pump, simulate the actuating unit of left and right heart respectively, with regulation and control
The running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs.
6. an application for micro-fluidic chip system, described micro-fluidic chip system includes:
Micro-fluidic chip described in any one in Claims 1-4；
Two fluid pumps (400), corresponding with the two of the described micro-fluidic chip pairs of pump interfaces (1,1 ') connect；And
Control device (500), electrically connect with said two fluid pump, simulate the actuating unit of left and right heart respectively, with regulation and control
The running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs；
Described application includes:
In the class blood circulation of described micro-fluidic chip, it is full of cytotrophy liquid, notes in corresponding chamber (101)
Enter medicine；
Start fluid pump (400), promote described liquid at class blood circulation internal circulation flow；And
The organoid that monitoring is relevant, carries out drug efficacy study.
The application of micro-fluidic chip system the most according to claim 6, it is characterised in that
Described in corresponding chamber the step of injection of medicine include: open the inlet (4) of this chamber；Inject from this inlet
Medicine；Close this inlet；
The organoid that described monitoring is relevant, the step carrying out drug efficacy study includes: close fluid pump, from this organoid place chamber
Inlet extract organoid sample detect.
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| CN201510221090.1A CN104826676B (en) | 2015-05-04 | 2015-05-04 | Micro-fluidic chip, system and application thereof |
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| CN201510221090.1A CN104826676B (en) | 2015-05-04 | 2015-05-04 | Micro-fluidic chip, system and application thereof |
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| CN104826676A CN104826676A (en) | 2015-08-12 |
| CN104826676B true CN104826676B (en) | 2016-08-24 |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105170205B (en) * | 2015-09-19 | 2017-01-25 | 大连理工大学 | Bionic chip constructed based on micro-fluidic chip technology |
| FR3050664B1 (en) * | 2016-04-27 | 2018-05-25 | Microfactory | SYSTEM FOR IN VITRO EVALUATION OF THE EFFICIENCY OF A DEODORANT. |
| CN107955788A (en) * | 2016-10-14 | 2018-04-24 | 中国科学院大连化学物理研究所 | A kind of micro fluid dynamcis method on organ chip |
| CN107955781B (en) * | 2016-10-14 | 2021-03-09 | 中国科学院大连化学物理研究所 | Liver-kidney system for simulating in-vivo metabolic process of medicine based on micro-fluidic chip |
| CN110042077B (en) * | 2019-04-22 | 2021-10-19 | 清华-伯克利深圳学院筹备办公室 | High-flux culture method of organoid spheres |
| CN114414531B (en) * | 2022-01-30 | 2023-07-28 | 福州大学 | In-situ on-line detection method and device for organoid metabolic molecules |
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| US8343740B2 (en) * | 2007-03-29 | 2013-01-01 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Micro-organ device |
| US8748180B2 (en) * | 2009-07-29 | 2014-06-10 | Cornell University | Microfluidic device for pharmacokinetic-pharmacodynamic study of drugs and uses thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101063084A (en) * | 2007-05-24 | 2007-10-31 | 泰州伯克利生物技术有限公司 | Method for making minitype integrated outer liver tissue culture chip |
| CN102728422A (en) * | 2012-06-11 | 2012-10-17 | 清华大学 | Microfluidic chip apparatus and application thereof |
| EP2712918A1 (en) * | 2012-09-28 | 2014-04-02 | Technische Universität Berlin | Multi-organ-chip with improved life time and homoeostasis |
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Address after: 518055 Guangdong city of Shenzhen province Nanshan District Xili of Tsinghua Patentee after: Shenzhen International Graduate School of Tsinghua University Address before: 518055 Guangdong city of Shenzhen province Nanshan District Xili of Tsinghua Patentee before: GRADUATE SCHOOL AT SHENZHEN, TSINGHUA University |
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Granted publication date: 20160824 |