CN104826676A - Microfluidic chip, microfluidic chip system and applications of microfluidic chip system - Google Patents
Microfluidic chip, microfluidic chip system and applications of microfluidic chip system Download PDFInfo
- Publication number
- CN104826676A CN104826676A CN201510221090.1A CN201510221090A CN104826676A CN 104826676 A CN104826676 A CN 104826676A CN 201510221090 A CN201510221090 A CN 201510221090A CN 104826676 A CN104826676 A CN 104826676A
- Authority
- CN
- China
- Prior art keywords
- micro
- fluidic chip
- microfluidic chip
- fluid
- organoid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Infusion, Injection, And Reservoir Apparatuses (AREA)
Abstract
The present invention relates to a microfluidic chip, a microfluidic chip system and applications of the microfluidic chip system. The internal of the microfluidic chip comprises: a plurality of chambers; a plurality of biological scaffolds, wherein the biological scaffolds are correspondingly arranged in the plurality of the chambers so as to form a plurality of organoids; and a plurality of microfluidic channels, wherein the microfluidic channels are correspondingly arranged among the corresponding organoids so as to form a blood circulation-like system, and at least a microfluidic channel is provided with a pump interface. The microfluidic chip system comprises: the microfluidic chip; a fluid pump connected with the pump interface; and a control device electrically connected with the fluid pump so as to regulate the operation state of the fluid in the microfluidic chip and simulate the operation of the blood circulation system in the human body. The applications comprise: filling a cell nutrition liquid in the blood circulation system, injecting a drug into the corresponding chamber, starting the fluid pump to push the liquid to perform circulating flowing in the blood circulation-like system, and monitoring the related organoids. With the microfluidic chip and the microfluidic chip system, the product can replace the human or animal body to carry out drug screening, and advantages of low cost, safety, short period, and the like are provided.
Description
Technical field
The present invention relates to the fields such as micro-fluidic chip, Computer-aided Tissue Engineering, biological 3D printing, more particularly, relate to a kind of 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 testing needs devote considerable time and fund cost, and the data provided also are limited, and this all limits the research and development of medicine.
Summary of the invention
The object of this invention is to provide a kind of micro-fluidic chip, system and application thereof, to solve the above-mentioned technological deficiency of carrying out Composition analyzed existence with zoopery and clinical testing.
Concrete technical scheme of the present invention is:
A kind of micro-fluidic chip, its inside comprises:
Some chambers, each chamber has independently inlet;
Some biological supports, correspondence is arranged in described some chambers, forms the some organoids corresponding with some organs of human body; And
Some microfluidic channel, correspondence is arranged between corresponding organoid, forms the class blood circulation system identical with blood circulation system between human organ, and at least one microfluidic channel is disconnected and channel end upon opening arranges pump interface.
In above-mentioned micro-fluidic chip, preferably, described micro-fluidic chip is from up to down made up of the stacked sealing of cover plate, intermediate plate and base plate, and 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, preferably, the microfluidic channel taking shape in described intermediate plate is narrow slit.
In above-mentioned micro-fluidic chip, preferably, described some organoids comprise brain, lung, heart, liver, spleen, stomach, small intestine, large intestine and kidney, and described pump interface is arranged at the microfluidic channel connecting heart.
In above-mentioned micro-fluidic chip, preferably, described some organoids also comprise skeletal muscle and/or skin.
In above-mentioned micro-fluidic chip, preferably, described biological support is the crisscross stereochemical structure with biomaterial structure.
A kind of micro-fluidic chip system, it comprises:
Micro-fluidic chip described in above-mentioned any one;
Fluid pump, connects with the pump interface of described micro-fluidic chip; And
Control device, is electrically connected with described fluid pump, and to regulate and control the running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs.
An application for micro-fluidic chip system, described micro-fluidic chip system comprises:
Micro-fluidic chip described in above-mentioned any one;
Fluid pump, connects with the pump interface of described micro-fluidic chip; And
Control device, is electrically connected with described fluid pump, and to regulate and control the running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs;
Described application comprises:
Cytotrophy liquid is full of, injection of medicine in corresponding chamber in the class blood circulation system of described micro-fluidic chip;
Start fluid pump, promote described liquid at class blood circulation system internal circulation flow; And
The organoid that monitoring is relevant, carries out drug efficacy study.
In the application of above-mentioned micro-fluidic chip system, preferably, describedly to comprise to the step of injection of medicine in corresponding chamber: the inlet opening this chamber; From this inlet injection of medicine; Close this inlet.The organoid that described monitoring is relevant, the step of carrying out drug efficacy study comprises: close fluid pump, and the sample extracting organoid from the inlet of this organoid place chamber detects.
Beneficial effect of the present invention is as follows:
This micro-fluidic chip simulates human organ and blood circulation system, be combined with fluid pump and control device, can promote and regulate the liquid in chip to circulate between organoid, the shuttling movement of blood between organ of simulation human body, therefore, it is possible to alternative human body or animal body carry out the screening of medicine.As compared to the method for carrying out Composition analyzed by zoopery and clinical testing, the present invention has that cost is low, safety and the advantage such as the cycle is short.
It can aids drug once circulate in vivo, secondary cycle or repeatedly circulate, study for drug effect reaction and cell tolerance etc. and provide convenience.
Accompanying drawing explanation
Fig. 1 is the structural representation of some embodiment micro-fluidic chip inside;
Fig. 2 is some embodiment micro-fluidic chip decomposing states figure;
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
Below in conjunction with drawings and Examples, the present invention is further described.These more detailed descriptions are intended to help and understand the present invention, and should not be used to limit the present invention.According to content disclosed by the invention, it will be understood by those skilled in the art that and some or all these specific detail can not be needed to implement the present invention.And in other cases, in order to avoid innovation and creation being desalinated, do not describe well-known content in detail.
Fig. 1 schematically illustrates the internal structure of some embodiment micro-fluidic chips.With reference to Fig. 1, the inside of the micro-fluidic chip of some embodiments comprises: some chambers 101 (with reference to Fig. 2), some biological supports 3, some microfluidic channel 2.Each chamber 101 has independently inlet 4, for extracting histioid sample to injection of medicine in chamber 101 with in chamber 101.Some biological support 3 correspondences are arranged in described some chambers 101 (composition graphs 2), form the some organoids corresponding with some organs of human body.Some microfluidic channel 2 correspondences are arranged between corresponding organoid, form the class blood circulation system identical with blood circulation system between human organ, and wherein, two microfluidic channel 2 are disconnected and channel end upon opening arranges pump interface 1,1 '.In Fig. 15 and 5 ' represents fluid hole and the inlet opening of corresponding chambers.
With reference to Fig. 2, the micro-fluidic chip of some embodiments is from up to down made up of cover plate 100, intermediate plate 200 and the stacked sealing of base plate 300, and described some chambers 101 take shape in described base plate 300, and described some microfluidic channel 2 take shape in described intermediate plate 200.Top board 100 is provided with the via hole of inlet 4.Wherein, the microfluidic channel 2 taking shape in described intermediate plate 200 is narrow slits.Can find out, this micro-fluidic chip adopts the structure of three substrate superpositions, and this structure makes the shaping convenient of microfluidic channel 2.Understandably, micro-fluidic chip also can adopt the structure of two substrate superpositions, particularly, can save intermediate plate 200, and microfluidic channel 2 be 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 comprises brain, lung, heart, liver, spleen, stomach, small intestine, large intestine and kidney, also comprises skeletal muscle and skin.Particularly, in FIG, from right to left, the organoid of structure corresponds to brain, lung, heart, liver, spleen, stomach, small intestine, large intestine, kidney, skeletal muscle, skin.Described pump interface 1 is arranged at 1 ' microfluidic channel being connected heart, particularly, arranges a pair pump interface, to connect a fluid pump in the microfluidic channel connecting the left heart and brain; Another is set to pump interface, to connect another fluid pump in the microfluidic channel connecting the right heart and brain.Understandably, in some embodiments, can increase or reduce chamber and biological support to construct more or less organoid, such as: do not construct skin and/or do not construct skeletal muscle etc., or other organoid of structure further.
Fig. 3 shows the structure of biological support 3.As shown in Figure 3, biological support 3 is the crisscross stereochemical structures with biomaterial structure.Biomaterial comprises nutriment and relevant cell, nutriment prioritizing selection gelatin and sodium alginate.Particularly, biological support 3 containing cell and nutriment can be printed with biological 3D printer.In Fig. 3, a component of 6 expression biological supports 3.
Fig. 4 schematically illustrates the structure of some embodiment micro-fluidic chip systems.With reference to Fig. 4, this micro-fluidic chip system comprises: above-mentioned micro-fluidic chip, two fluid pumps 400, control device 500.Two fluid pumps 400 connect with the pump interface 1,1 ' of described micro-fluidic chip, concrete, a fluid pump (pump 1) connects with a pair pump interface in the microfluidic channel being connected the left heart and brain, and another fluid pump (pump 2) connects to pump interface with another in the microfluidic channel being connected the right heart and brain.Control device 500 is electrically connected with described fluid pump 400, and to regulate and control the running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs.Here two fluid pumps 400 and control device 500 combine, and simulate the actuating unit of left and right heart respectively, and control device 500 regulates and controls the rotating speed of fluid pump 400 for regulating and controlling liquid circulation velocity in chip, according to the actual requirements can choice for use list 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.More specifically, when being applied to drug screening, comprising:
Cytotrophy liquid is full of, injection of medicine in corresponding chamber 101 in the class blood circulation system of described micro-fluidic chip;
Start fluid pump 400, promote described liquid at class blood circulation system internal circulation flow; And
The organoid that monitoring is relevant, carries out drug efficacy study.
Described comprises to the step of injection of medicine in corresponding chamber 101: the inlet 4 opening this chamber; From this inlet 4 injection of medicine; Then this inlet 4 is closed.
The organoid that described monitoring is relevant, the step of carrying out drug efficacy study comprises: close fluid pump 400, the sample extracting organoid from the inlet 4 of this organoid place chamber 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 system), simulate human organ and blood circulation system.The running status that Cardiac Power mechanism regulates and controls fluid in chip apparatus is simulated by fluid pump 400 and control device 500, the medicine carried is delivered to each organoid, and simulate the operation of blood in human body in fluid circulation, the organoid relevant by Real-Time Monitoring carries out drug efficacy study, thus reaches the objects such as drug screening.
The micro-fluidic chip system of some embodiments can realize the drug effect ringing of an organoid, and the influencing each other of multiple organoid metabolic drug.Concrete, by one or more for infusion of medicine organoid, under the effect of fluid pump 400, medicine enters class blood circulation system after organoid metabolism, act in multiple organoid, again enter class blood circulation system, thus the metabolism of medicine one-level, secondary metabolism or multistage metabolism can be realized, thus can provide convenient for researchs such as drug effect reaction and cell tolerances.
The present invention is that drug research, screening and exploitation provide new thinking and countermeasure, significantly reduces fund and time cost simultaneously.
Claims (9)
1. a micro-fluidic chip, is characterized in that, the inside of described micro-fluidic chip comprises:
Some chambers (101), each chamber has independently inlet (4);
Some biological supports (3), correspondence is arranged in described some chambers, forms the some organoids corresponding with some organs of human body; And
Some microfluidic channel (2), correspondence is arranged between corresponding organoid, form the class blood circulation system identical with blood circulation system between human organ, at least one microfluidic channel is disconnected and channel end upon opening arranges pump interface (1,1 ').
2. micro-fluidic chip according to claim 1, it is characterized in that, described micro-fluidic chip is from up to down made up of cover plate (100), intermediate plate (200) and the stacked sealing of base plate (300), described some chambers (101) take shape in described base plate, and described some microfluidic channel take shape in described intermediate plate.
3. micro-fluidic chip according to claim 2, is characterized in that, the microfluidic channel (2) taking shape in described intermediate plate is narrow slit.
4. micro-fluidic chip according to claim 1, is characterized in that: described some organoids comprise brain, lung, heart, liver, spleen, stomach, small intestine, large intestine and kidney, and described pump interface is arranged at the microfluidic channel connecting heart.
5. micro-fluidic chip according to claim 4, is characterized in that, described some organoids also comprise skeletal muscle and/or skin.
6. micro-fluidic chip according to claim 1, is characterized in that, described biological support is the crisscross stereochemical structure with biomaterial structure.
7. a micro-fluidic chip system, is characterized in that, described micro-fluidic chip system comprises:
Micro-fluidic chip in claim 1 to 6 described in any one;
Fluid pump (400), connects with the pump interface (1,1 ') of described micro-fluidic chip; And
Control device (500), is electrically connected with described fluid pump, and to regulate and control the running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs.
8. an application for micro-fluidic chip system, described micro-fluidic chip system comprises:
Micro-fluidic chip in claim 1 to 6 described in any one;
Fluid pump (400), connects with the pump interface (1,1 ') of described micro-fluidic chip; And
Control device (500), is electrically connected with described fluid pump, and to regulate and control the running status of fluid in micro-fluidic chip, simulation blood in human body in fluid circulation runs;
Described application comprises:
Cytotrophy liquid is full of, to corresponding chamber (101) interior injection of medicine in the class blood circulation system of described micro-fluidic chip;
Start fluid pump (400), promote described liquid at class blood circulation system internal circulation flow; And
The organoid that monitoring is relevant, carries out drug efficacy study.
9. the application of micro-fluidic chip system according to claim 8, is characterized in that,
Describedly to comprise to the step of injection of medicine in corresponding chamber: the inlet (4) opening this chamber; From this inlet injection of medicine; Close this inlet;
The organoid that described monitoring is relevant, the step of carrying out drug efficacy study comprises: close fluid pump, and the sample extracting organoid from the inlet of this organoid place chamber detects.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510221090.1A CN104826676B (en) | 2015-05-04 | 2015-05-04 | Micro-fluidic chip, system and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510221090.1A CN104826676B (en) | 2015-05-04 | 2015-05-04 | Micro-fluidic chip, system and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104826676A true CN104826676A (en) | 2015-08-12 |
| CN104826676B CN104826676B (en) | 2016-08-24 |
Family
ID=53805084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510221090.1A Expired - Fee Related CN104826676B (en) | 2015-05-04 | 2015-05-04 | Micro-fluidic chip, system and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104826676B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105170205A (en) * | 2015-09-19 | 2015-12-23 | 大连理工大学 | Bionic chip constructed based on micro-fluidic chip technology |
| CN107955781A (en) * | 2016-10-14 | 2018-04-24 | 中国科学院大连化学物理研究所 | The liver of metabolic process-kidney system in aids drug body based on micro-fluidic chip |
| 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 |
| CN109310889A (en) * | 2016-04-27 | 2019-02-05 | 微型工厂 | It eliminates the unusual smell the system of effect for evaluating in vitro |
| CN110042077A (en) * | 2019-04-22 | 2019-07-23 | 清华-伯克利深圳学院筹备办公室 | A kind of high-throughput cultural method of organoid sphere |
| CN114414531A (en) * | 2022-01-30 | 2022-04-29 | 福州大学 | In-situ on-line detection method and device for metabolic molecules of organoid |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US20080261288A1 (en) * | 2007-03-29 | 2008-10-23 | Gonda Steve R | Micro-Organ Device |
| US20120135452A1 (en) * | 2009-07-29 | 2012-05-31 | Cornell University | Microfluidic device for pharmacokinetic-pharmacodynamic study of drugs and uses thereof |
| 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 |
| KR101468001B1 (en) * | 2014-05-21 | 2014-12-02 | 경북대학교 산학협력단 | Microfluidics-based tissue chip comprising three-dimensional porous nanofiber structure and preparation method thereof |
-
2015
- 2015-05-04 CN CN201510221090.1A patent/CN104826676B/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080261288A1 (en) * | 2007-03-29 | 2008-10-23 | Gonda Steve R | Micro-Organ Device |
| 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 |
| US20120135452A1 (en) * | 2009-07-29 | 2012-05-31 | Cornell University | Microfluidic device for pharmacokinetic-pharmacodynamic study of drugs and uses thereof |
| 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 |
| KR101468001B1 (en) * | 2014-05-21 | 2014-12-02 | 경북대학교 산학협력단 | Microfluidics-based tissue chip comprising three-dimensional porous nanofiber structure and preparation method thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105170205A (en) * | 2015-09-19 | 2015-12-23 | 大连理工大学 | Bionic chip constructed based on micro-fluidic chip technology |
| CN109310889A (en) * | 2016-04-27 | 2019-02-05 | 微型工厂 | It eliminates the unusual smell the system of effect for evaluating in vitro |
| CN109310889B (en) * | 2016-04-27 | 2019-12-13 | 微型工厂 | System for in vitro assessment of efficacy of odor removal |
| CN107955781A (en) * | 2016-10-14 | 2018-04-24 | 中国科学院大连化学物理研究所 | The liver of metabolic process-kidney system in aids drug body based on micro-fluidic chip |
| 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 |
| CN110042077A (en) * | 2019-04-22 | 2019-07-23 | 清华-伯克利深圳学院筹备办公室 | A kind of high-throughput cultural method of organoid sphere |
| CN114414531A (en) * | 2022-01-30 | 2022-04-29 | 福州大学 | In-situ on-line detection method and device for metabolic molecules of organoid |
| CN114414531B (en) * | 2022-01-30 | 2023-07-28 | 福州大学 | In-situ on-line detection method and device for organoid metabolic molecules |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104826676B (en) | 2016-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104826676A (en) | Microfluidic chip, microfluidic chip system and applications of microfluidic chip system | |
| CN107022482B (en) | The interconnection of multiple perfusion engineered tissue buildings and Miniature biochemical analysis instrument, multiple miniature formula design modules and its application | |
| Rogal et al. | Integration concepts for multi-organ chips: how to maintain flexibility?! | |
| US10023832B2 (en) | Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multi-microformulators and applications of the same | |
| US20170137768A1 (en) | Modular platform for tissue integrated cell culture | |
| EP3119870B1 (en) | Dynamic multi organ plate | |
| CN105170205B (en) | Bionic chip constructed based on micro-fluidic chip technology | |
| CN107312711A (en) | A kind of self-loopa tissue/organ chip apparatus and preparation method thereof | |
| van der Linden et al. | A multilayer microfluidic platform for the conduction of prolonged cell-free gene expression | |
| Dehne et al. | Human body-on-a-chip systems | |
| Sung | In silico modeling of endocrine organ-on-a-chip systems | |
| CN104046564A (en) | Physiological environment-imitating mechanical stimulation type biological reactor system | |
| CN114085775A (en) | Bionic enterohepatic microfluidic cell culture-drug screening integrated chip | |
| CN212077076U (en) | Micro-fluidic experimental board | |
| US11712696B2 (en) | Drug screening platform simulating hyperthermic intraperitoneal chemotherapy | |
| CN104593258B (en) | A kind of device for setting up said three-dimensional body tissue | |
| Hajari et al. | A numerical study on tumor-on-chip performance and its optimization for nanodrug-based combination therapy | |
| Große-Elshoff | Getting continuous recirculating flow on a 3D blood vessel-on-chip integrated on a fluidic circuit board | |
| CN211972366U (en) | Micro-fluidic experimental board | |
| US11969727B2 (en) | Tumor microenvironment on chip | |
| CN214529079U (en) | Micro-fluidic bionic model | |
| CN203433726U (en) | Blood circulation analog module apparatus | |
| Lopez et al. | A programmable and configurable multi-port System-on-Chip for stimulating electrokinetically-driven microfluidic devices | |
| CN114437932A (en) | Microfluidic chip and system of multi-placenta vascular anastomosis model and using method | |
| Mau | Bioautomation–Re-engineering human body system controls |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
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 |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160824 |