CN107955788A - A kind of micro fluid dynamcis method on organ chip - Google Patents
A kind of micro fluid dynamcis method on organ chip Download PDFInfo
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- CN107955788A CN107955788A CN201610897999.3A CN201610897999A CN107955788A CN 107955788 A CN107955788 A CN 107955788A CN 201610897999 A CN201610897999 A CN 201610897999A CN 107955788 A CN107955788 A CN 107955788A
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- Prior art keywords
- fluid
- chip
- organ
- organ chip
- micro
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/16—Microfluidic devices; Capillary tubes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
Abstract
The present invention provides a kind of micro fluid dynamcis method on organ chip, belongs to microfluidic art.This method manipulates the forms of motion of organ chip upper fluid using control pump；Using forward, the rear alternate form of row, a kind of creeping flow is formed in the microchannel of organ chip, the double direction shear power of fluid can be presented using this creeping flow, increases fluid retention time in microchannel, increase fluid contact level product, obtain more preferable mixing effect of fluid.The driving method effect stability, can increase miniflow body function, the structure for realizing the organ chip of external simulated environment, microreactor, carries out application of drug evaluation etc. and be of great significance by the fluid in the form of wriggling in simulated organ.
Description
Technical field
Construction method and application process field the present invention relates to organ chip, and in particular to micro- on a kind of organ chip
Fluid driving method.
Background technology
Zoopery occupies particularly important position in modern medicine and biology, but funds and animal welfare
Also into the problem of being difficult to avoid.With reference to microflow control technique and bioscience technology, a kind of " organ chip " has been createed, can
The function of human organ is replicated with microchip, medical experiment is become more easy.
Microfluid based Lab on a chip is also known as chip lab or micro-fluidic chip, refers in the fields such as biological and chemical
The basic operation units such as involved sample preparation, reaction, separation, detection, cell culture, sorting, cracking integrate or baseset
Into on the chip to one piece several square centimeters (or even smaller), network is formed by microchannel, whole system is run through with controlled fluid,
To substitute a kind of technology of the various functions of conventional chemical or biology laboratory.Microfluidic chip technology is as a rapid hair
The science and technology that exhibition is got up, presents its unique advantage in biomedical sector, more because it is the same as cell size matching, ring
Border is close with physiological environment, more accurate manipulation is capable of providing on time and Spatial Dimension, is easy to real by flexible design
The features such as existing various kinds of cell functional study and as bionic of new generation and the Important Platform of cell research.Micro-fluidic chip
Architectural feature is various complicated microchannel networks.Microfluidic system need by these microchannel networks to microfluid
Operation realize various functions, such as the introducing of reagent, mixing, separation etc..Therefore, the fluid driving skill in microfluidic system
Art is to realize the key technology of micro-fluidic chip function.Microfluidic system drives fluid using various types of Micropumps, actual
Basic demand for Micropump in is：The flow of continuous-stable can be provided, accessory simple in structure, needing is few, grasps
Work is easy, it is low with operating cost to make.
The fluid driving method method of organ chip still at present, mostly using static, straight trip stream, recycle stream etc., yet there are no compacted
The form of dynamic stream.Alternately forward or moved ahead, the form of rear row alternately backward using forward, rear row, in the micro- logical of micro-fluidic chip
A kind of creeping flow is formed in road, the double direction shear power of fluid can be presented using this creeping flow, increases fluid in microchannel and stops
The time is stayed, increase fluid contact level product, obtains more preferable mixing effect of fluid.
At present, it is also more rare using the organ chip progress correlative study analysis of specialized fluids actuation techniques, in biology
Learning in research and medicine research and development has great application prospect.
The content of the invention
The object of the present invention is to provide a kind of micro fluid dynamcis method on organ chip, the organ core of this method structure
Piece simulated organ function more optimizes, and adds the function of fluid in microchannel, can be applied to organ chip or microreactor
The research such as structure, application of drug evaluation.
Micro fluid dynamcis method on organ chip provided by the invention, the application control pump manipulation fluid on organ chip
Method.
Micro fluid dynamcis method on organ chip provided by the invention, the organ chip are to be integrated in micro-fluidic chip
Functional cell is to simulate the chip of corresponding organ function.
Micro fluid dynamcis method on organ chip provided by the invention,：The control pump can carry out different parameters
Adjusting machine program setting, can manipulate fluid move ahead/irrigate, rear row/extraction.
Micro fluid dynamcis method on organ chip provided by the invention, the method for the manipulation fluid are to drive fluid
Move ahead and replace with rear row forward or the forward form replaced with rear row backward.
Micro fluid dynamcis method on organ chip provided by the invention, the program parameter, including flow velocity, the time,
Time out, intercycle, cycle-index etc..Wherein flow velocity can be negative value, represent row after fluid.
Micro fluid dynamcis method on organ chip provided by the invention, the fluid driving method, driving fluid move ahead
When replacing forward or backward with rear row, program parameter setting as follows, flow velocity a, time b, 20 microseconds of pause, flow velocity-c, time d,
Suspend 20 microseconds, intercycle is above-mentioned all parameters, cycle-index e.The flow velocity of gained fluid is (a*b-c*d)/(b+d).a
>During c, fluid moves ahead, a<During c, row after fluid.
Micro fluid dynamcis method on organ chip provided by the invention, the fluid driving method, driving fluid move ahead
When replacing forward or backward with rear row, program parameter sets as follows, flow velocity a (1 μ L/h-120 μ L/h), time b (1s-30s), temporarily
Stop 20 microseconds, flow velocity-c (1 μ L/h-120 μ L/h), time d (1s-30s), suspend 20 microseconds, intercycle is above-mentioned all ginsengs
Number, cycle-index e (1-50000 times).The flow velocity of gained fluid is (a*b-c*d)/(b+d).a>During c, fluid moves ahead, a<During c,
Row after fluid.
Micro fluid dynamcis method on organ chip provided by the invention, forms a kind of in the microchannel of micro-fluidic chip
Creeping flow, the double direction shear power of fluid can be presented using this creeping flow, and this double direction shear power more meets for some thin
The microenvironment of born of the same parents in vivo, can advantageously promote the growth of cell, obtain more preferable cell function.Creeping flow can also increase
Fluid retention time in microchannel, increase fluid contact level product, obtains more preferable mixing effect of fluid, can be with medicinal application
Advantageously promote drug utilization.
Brief description of the drawings
Micro fluid dynamcis method effect on Fig. 1 organ chips of the present invention；The speed of tri- kinds of fluid applications of a；(1) straight trip stream
(1 μ L/min), (2) straight trip stream (0.5 μ L/min), (3) creeping flow (1 μ L/min)；The residence time of tri- kinds of fluid applications of b；.
Micro fluid dynamcis method effect on Fig. 2 organ chips of the present invention；(4) straight trip stream (1 μ L/min) more than 50% contaminates
Expect region (5) straight trip stream (1 μ L/min) more than 25% dye area (6) straight trip stream (1 μ L/min) viewing area (7) straight trip stream
(0.5 μ L/min) more than 50% dye area, (8) straight trip stream (0.5 μ L/min) more than 25% dye area, (9) straight trip stream
(0.5 μ L/min) viewing area, (10) creeping flow (1 μ L/min) more than 50% dye area, (11) creeping flow (1 μ L/min)
More than 25% dye area (12) creeping flow (1 μ L/min) viewing area.
The osmotic effect of micro fluid dynamcis method is applied on Fig. 3 organ chips of the present invention.A bilayer Transwell chips shine
Piece；B upper stratas chip channel configuration schematic diagram；C lower layer chip channel design schematic diagrames；D intestines chip entirety schematic top plan views；E intestines
Chip cross-sectional view；F fluorescein sodiums osmotic concentration-time graph；G fluorescein sodiums permeate total amount；
Wherein 13 upper strata chip channels, 14 porous membranes, 15 lower layer chip passages, 16 feeder connections of upper strata core, under 17
Layer chip channel entrance.
Embodiment
The following examples will be further described the present invention, but not thereby limiting the invention.
Embodiment 1
Micro fluid dynamcis method
Single channel micro-fluidic chip is made, channel design is long and straight type, 50 μ L of system.Water is full of in passage, use is red
Color dyestuff carries out perfusion, carries out the comparison of three kinds of perfusion modes.Set to control and pump parameter persistently to move ahead, flow velocity is 1 μ L/min；
Set to control and pump parameter persistently to move ahead, flow velocity is 0.5 μ L/min；Set and control pump parameter as flow velocity 1 μ L/min, time 9s,
Suspend 20 microseconds, flow velocity -1 μ L/min, time 3s, suspend 20 microseconds, cycle-index 10000 times, it is 0.5 μ to obtain fluid flow rate
L/min.Record time of the orchil by passage.As shown in Figure 1, there is creeping flow the shearing force of high flow rate and fluid to make
With, and the residence time with low flow velocity and speed.Its mixed effect is also more preferable compared with other two kinds of effects, as shown in Figure 2.Implement
Example 2
Permeability test
Two layers of micro-fluidic chip of Transwell is made, as shown in Fig. 3 a, b, c, d, e.The chip is by upper strata chip, lower floor
Chip and porous membrane composition, chip channel 13 connects upper strata chip channel entrance 16 to upper strata chip at the middle and upper levels, in lower layer chip
Lower layer chip passage 15 connects lower layer chip feeder connection 17, and upper strata chip channel 13 and lower layer chip passage 15 pass through porous filter
Film connects.
Water is full of in the chip channel of upper strata, perfusion is carried out using 10mg/mL fluorescein sodiums dyestuff, is changed to after 25 μ L
Water.Three kinds of perfusion modes of upper strata chip application.Set to control and pump parameter persistently to move ahead, flow velocity is 1 μ L/min；Setting control pump
For parameter persistently to move ahead, flow velocity is 0.5 μ L/min；It is flow velocity 1 μ L/min, time 9s to control pump parameter calmly, suspends 20 microseconds, stream
Speed -1 μ L/min, time 3s, suspend 20 microseconds, cycle-index 10000 times, it is 0.5 μ L/min to obtain fluid flow rate..Lower floor's core
Piece passage perfusion rate is 10 μ L/h.Liquid in lower layer chip passage is collected per 30min, it is dense using microplate reader detection fluorescein sodium
Degree.As illustrated in figure 3f, there is the permeability of high flow rate, and the time of penetration with low flow velocity using creeping flow.Its osmotic effect
Also it is more preferable compared with other two kinds of effects, as shown in figure 3g, the permeability of higher is obtained using creeping flow.
Claims (6)
1. a kind of micro fluid dynamcis method on organ chip, it is characterised in that：The application control pump manipulation stream on organ chip
The forms of motion of body.
2. the micro fluid dynamcis method on a kind of organ chip as claimed in claim 1, it is characterised in that：The organ chip
To be integrated with functioning cell in micro-fluidic chip to simulate the chip of corresponding organ function.
3. the micro fluid dynamcis method on a kind of organ chip as claimed in claim 1, it is characterised in that：The control pump energy
Enough using program carry out parameter adjusting, can manipulate fluid move ahead/irrigate, rear row/extraction.
4. the micro fluid dynamcis method on a kind of organ chip as claimed in claim 1, it is characterised in that：The manipulation fluid
Forms of motion be that driving fluid moves ahead the form replaced with rear row forward or backward.
5. the micro fluid dynamcis method on a kind of organ chip as claimed in claim 3, it is characterised in that the program parameter,
Including flow velocity, time, time out, intercycle, cycle-index；Wherein flow velocity can be negative value, represent row after fluid.
6. the micro fluid dynamcis method on a kind of organ chip as claimed in claim 4, it is characterised in that before the driving fluid
When row is replaced forward or backward with rear row, program parameter setting as follows, flow velocity a, time b, suspend 20 microseconds, flow velocity-c, time
D, suspends 20 microseconds, intercycle is above-mentioned all parameters, and cycle-index e, the flow velocity of gained fluid is (a*b-c*d)/(b+
d)；a>During c, fluid moves ahead, a<During c, row after fluid.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610897999.3A CN107955788A (en) | 2016-10-14 | 2016-10-14 | A kind of micro fluid dynamcis method on organ chip |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610897999.3A CN107955788A (en) | 2016-10-14 | 2016-10-14 | A kind of micro fluid dynamcis method on organ chip |
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| CN107955788A true CN107955788A (en) | 2018-04-24 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111269830A (en) * | 2018-12-05 | 2020-06-12 | 中国科学院大连化学物理研究所 | Multi-organ chip based on microfluidic technology and application thereof |
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| CN1683560A (en) * | 2005-03-07 | 2005-10-19 | 上海百傲科技有限公司 | Device and method for accelerating biological chip micro fluid reaction |
| WO2010057078A2 (en) * | 2008-11-14 | 2010-05-20 | The Brigham And Women's Hospital, Inc. | Method and system for generating spatially and temporally controllable concentration gradients |
| CN103981096A (en) * | 2014-05-27 | 2014-08-13 | 东南大学 | Two-layer cell culture system organ chip and preparation method thereof |
| CN104741157A (en) * | 2010-09-14 | 2015-07-01 | 加利福尼亚大学董事会 | Device for isolating cells from heterogeneous solution using microfluidic trapping vortices |
| CN104826676A (en) * | 2015-05-04 | 2015-08-12 | 清华大学深圳研究生院 | Microfluidic chip, microfluidic chip system and applications of microfluidic chip system |
-
2016
- 2016-10-14 CN CN201610897999.3A patent/CN107955788A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1683560A (en) * | 2005-03-07 | 2005-10-19 | 上海百傲科技有限公司 | Device and method for accelerating biological chip micro fluid reaction |
| WO2010057078A2 (en) * | 2008-11-14 | 2010-05-20 | The Brigham And Women's Hospital, Inc. | Method and system for generating spatially and temporally controllable concentration gradients |
| CN104741157A (en) * | 2010-09-14 | 2015-07-01 | 加利福尼亚大学董事会 | Device for isolating cells from heterogeneous solution using microfluidic trapping vortices |
| CN103981096A (en) * | 2014-05-27 | 2014-08-13 | 东南大学 | Two-layer cell culture system organ chip and preparation method thereof |
| CN104826676A (en) * | 2015-05-04 | 2015-08-12 | 清华大学深圳研究生院 | Microfluidic chip, microfluidic chip system and applications of microfluidic chip system |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111269830A (en) * | 2018-12-05 | 2020-06-12 | 中国科学院大连化学物理研究所 | Multi-organ chip based on microfluidic technology and application thereof |
| CN111269830B (en) * | 2018-12-05 | 2022-07-15 | 中国科学院大连化学物理研究所 | Multi-organ chip based on microfluidic technology and application thereof |
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Application publication date: 20180424 |