CN209098695U - Gut ischmia-reperfusion causes the bionical micro-fluidic chip of remote organ damage in a kind of analogue body - Google Patents
Gut ischmia-reperfusion causes the bionical micro-fluidic chip of remote organ damage in a kind of analogue body Download PDFInfo
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Abstract
The utility model discloses the bionical micro-fluidic chip that Gut ischmia-reperfusion in a kind of analogue body causes remote organ damage, it is characterized by: the chip includes glass substrate (1), PDMS piece (2) at being sequentially arranged above of glass substrate (1), polycarbonate perforated membrane (3) and upper PDMS piece (4), the downward Intestinal epithelial cells culture pond (5) of opening direction is offered on the upper PDMS piece (4), and culture solution exchange pond (6) is then offered on lower PDMS piece (2), it is identical that the cross section of described while Intestinal epithelial cells culture pond (5) and culture solution exchange pond (6) is formed by figure, and the two is overlapped in the longitudinal direction, the polycarbonate perforated membrane (3) is located between Intestinal epithelial cells culture pond (5) and culture solution exchange pond (6).
Description
Technical field
The utility model relates to field of cell culture, Gut ischmia-reperfusion causes remote organ damage in especially a kind of analogue body
The bionical micro-fluidic chip of wound.
Background technique
Gut ischmia-reperfusion (Intestinal ischemia/reperfusion, II/R) damage refers to that a variety of causes is led
The enteron aisle blood supply of cause is interrupted or is reduced, recovery blood supply makes the pathophysiological process that intestinal tract injury is further aggravated again, is surgery
Common clinical danger phase in practice.Intestine ischemia and reperfusion is a chain reaction, to the influence of general body state
Through the damage and destruction considerably beyond enteron aisle part, it is considered to be cause systemic inflammatory response syndrome (SIRS) and multiple organ function
Can distress syndrome (MODS) one of important initiating agent, the hepatic disorder and acute lung injury caused is clinically most
For common complication and the important cause of death.
The mechanism that Gut ischmia-reperfusion causes multiple organ injury is complicated, and numerous clinical researches show during II/R, lacks
Anoxemia can lead to Intestinal epithelial cells atrophy, apoptosis, and function of intestinal mucosa barrier in patient is lost, and move intestinal bacterium and endotoxin
Position to whole body, the activation of Monocytes/Macrophages system generates a series of cell factors and inflammatory mediator, furthermore intestinal tissue anoxic
The reactive oxidants intermediary factor (ROI) of generation can also be applied directly to by internal blood circulation is far apart organ and causes to damage
Wound.
Liver is that the enteron aisle that portalsystem directly converges adjoins organ, this Anatomy and histology feature determines it more
Damage vulnerable to II/R.A large amount of inflammatory mediator, ROS and bacteriotoxin enter blood by the intestinal wall destroyed when II/R, via door
Venous system reaches liver, exceeds liver Kupffer cell Scavenging activity, further activates inflammatory factor, discharge harmful enzyme body
And medium, cause hepatocellular injury, necrosis and apoptosis.Meanwhile a large amount of endotoxins and inflammatory factor further pass through blood circulation to
Whole body is sent out, and neutrophil leucocyte (PMNs) is made to assemble and activate in intrapulmonary, generates and release ROS, one side are damaged in Pulmonary Vascular
Chrotoplast increases vasopermeability, causes pulmonary edema, on the other hand thin by oxidative cell membrane lipid coup injury pulmonary parenchyma
Born of the same parents make the extensive apoptosis of alveolar epithelial cells, necrosis and collapse, cause diffusivity injury of lungs.
The research in the field at present is based on experiment in vivo, but experiment in vivo disturbing factor is more, is unfavorable in cellular water
The biological mechanisms such as flat observation and the variation of detection associated signal paths, inflammatory factor release.Further, since Gut ischmia-reperfusion causes
In remote organ damage process, it is related to a variety of cells of organs, physiological structure is complicated and needs special fluid microenvironment, conventional bulk
Outer cell culture processes are difficult to realize above-mentioned bionical effect, therefore there is an urgent need to one kind for the cause of vitro study Gut ischmia-reperfusion
The bionical micro flow control chip device of remote organ damage.
Summary of the invention
The utility model is to propose that intestine ischemia is again in a kind of analogue body to solve above-mentioned deficiency present in the prior art
Perfusion causes the bionical micro-fluidic chip of remote organ damage.The external Combined culture of various kinds of cell may be implemented in the chip, dynamic
It monitors Intestinal epithelial cells hypoxia-reoxygenation, release inflammatory factor and further influences liver cell and alveolar epithelial cells biology
Behavior and mechanism, while can be applied to screening drug, analysis drug effect and drug target, it is provided in vitro to study the disease
Research platform.
The technical solution of the utility model is: Gut ischmia-reperfusion causes the imitative of remote organ damage in a kind of analogue body
Raw micro-fluidic chip, it is characterised in that: the chip includes glass substrate 1, under being sequentially arranged above of glass substrate 1
PDMS piece 2, polycarbonate perforated membrane 3 and upper PDMS piece 4,
Offer the downward Intestinal epithelial cells culture pond 5 of opening direction on the upper PDMS piece 4, and lower PDMS piece 2
On then offer culture solution exchange pond 6, described while Intestinal epithelial cells culture pond 5 and culture solution exchange pond 6 cross section
It is identical to be formed by figure, and the two is overlapped in the longitudinal direction, it is thin that the polycarbonate perforated membrane 3 is located at intestinal mucosa epithelium
Between born of the same parents' culture pond 5 and culture solution exchange pond 6,
The upper inlet 7 and upper outlet 8 being connected with Intestinal epithelial cells culture pond 5 are additionally provided on upper PDMS piece 2,
It is then provided on lower PDMS piece 2 and exchanges the lower inlet 9 that pond 6 is connected with culture solution, it is separate that culture solution exchanges pond 6
Hepatocyte cultures pond 10, serpentine channel 11 and alveolar epithelial cells culture pond 12 are also disposed on the direction of lower inlet 9, and
Culture solution exchanges between pond 6 and hepatocyte cultures pond 10, between hepatocyte cultures pond 10 and serpentine channel 11 and serpentine channel
Be interconnected by microchannel between 11 and alveolar epithelial cells culture pond 12, at the same be additionally provided on lower PDMS piece 2 with
The end of the connected lower outlet 13 of alveolar epithelial cells culture pond 12, the lower outlet 13 is located at the surface of upper PDMS piece 4.
The utility model compared with the existing technology, has the advantages that
Bionical micro-fluidic chip disclosed in the utility model, can simulate in body Intestinal epithelial cells, liver cell
With alveolar epithelial cells biomimetic features and simulation blood circulation fluid environment Combined culture cavity, convenient for the intestines of dynamic detection culture
The inflammatory factor discharged after mucosa causes the feelings such as liver cell, alveolar epithelial cells damage, apoptosis with it is observed
Condition further analyzes relevant Cell. Mol mechanism, it can also be used to screen related drugs and action target spot, filled up from
Body studies the blank that Gut ischmia-reperfusion causes remote organ damage field.And its main material is PDMS, good biocompatibility,
And the translucency with elasticity and height, good leak tightness, the closed circulation for forming isolation air are constructed closer to physiology micro-loop
Border, and the indirect traditional training method contacted with air, are more conducive to intestinal epithelial cell anoxic in accurate analogue body
Reoxygenation process.Meanwhile the bionical micro-fluidic chip is for when detecting, reagent consumption to be considerably less than the inside and outside experiment of conventional bulk,
A large amount of research cost can be saved.And the manufacture craft of this chip is simple, and manufacturing cost is cheap, it can be said that it has
A variety of advantages, particularly suitable for promoting and applying in the art, wide market, significance of scientific research is great.
Detailed description of the invention
Fig. 1 is the side sectional view of the utility model embodiment.
Fig. 2 is the top view of upper PDMS piece in the utility model embodiment.
Fig. 3 is the top view of lower PDMS piece in the utility model embodiment.
Specific embodiment
Below in conjunction with Detailed description of the invention specific embodiment of the present utility model.It is as shown in Figure 1, Figure 2, Figure 3 shows: a kind of simulation
Internal Gut ischmia-reperfusion causes the bionical micro-fluidic chip of remote organ damage, including glass substrate 1, in the upper of glass substrate 1
Side is disposed with lower PDMS piece 2, polycarbonate perforated membrane 3 and upper PDMS piece 4,
Offer the downward Intestinal epithelial cells culture pond 5 of opening direction on the upper PDMS piece 4, and lower PDMS piece 2
On then offer culture solution exchange pond 6, described while Intestinal epithelial cells culture pond 5 and culture solution exchange pond 6 cross section
It is identical to be formed by figure, and the two is overlapped in the longitudinal direction, it is thin that the polycarbonate perforated membrane 3 is located at intestinal mucosa epithelium
Between born of the same parents' culture pond 5 and culture solution exchange pond 6,
The upper inlet 7 and upper outlet 8 being connected with Intestinal epithelial cells culture pond 5 are additionally provided on upper PDMS piece 2,
It is then provided on lower PDMS piece 2 and exchanges the lower inlet 9 that pond 6 is connected with culture solution, it is separate that culture solution exchanges pond 6
Hepatocyte cultures pond 10, serpentine channel 11 and alveolar epithelial cells culture pond 12 are also disposed on the direction of lower inlet 9, and
Culture solution exchanges between pond 6 and hepatocyte cultures pond 10, between hepatocyte cultures pond 10 and serpentine channel 11 and serpentine channel
Be interconnected by microchannel between 11 and alveolar epithelial cells culture pond 12, at the same be additionally provided on lower PDMS piece 2 with
The end of the connected lower outlet 13 of alveolar epithelial cells culture pond 12, the lower outlet 13 is located at the surface of upper PDMS piece 4.
Gut ischmia-reperfusion causes the bionical micro-fluidic chip of remote organ damage in the analogue body of the utility model embodiment
The course of work it is as follows: glass substrate 1, lower PDMS piece 2, polycarbonate perforated membrane 3 and upper PDMS piece 4 are in turn connected into first
Integral structure, then pipeline of the connection with peristaltic pump at the upper inlet 7 of upper PDMS piece 4, passes through the upward PDMS piece 4 of peristaltic pump
On Intestinal epithelial cells culture pond 5 in inject CaCO2 cell suspension, so that it is transported to Intestinal epithelial cells culture pond 5
In;Also connection has the pipeline of peristaltic pump at the lower inlet 9 of lower PDMS piece 2, passes through the culture on the downward PDMS piece 2 of peristaltic pump
Liquid exchanges pond 6 and injects HepG2 cell, and connection has the pipeline of peristaltic pump at lower outlet 13, by peristaltic pump to alveolar epithelium
A549 cell is injected in cell culture insert 12 forms bionical micro-fluidic chip after above-mentioned three kinds of cells are adherent;
Carry out Intestinal ischemia simulated operation when, by upper inlet 7 into Intestinal epithelial cells culture pond injection with
The anoxic culture solution of nitrogen displacement oxygen, and be discharged by upper outlet 8, the anoxic culture of Intestinal epithelial cells is carried out, with mould
Intend internal Intestinal ischemia process, while lower inlet 9 injects normal culture solution, and passes sequentially through hepatocyte cultures pond 10, snakelike logical
Road 11 and alveolar epithelial cells culture pond 12 are eventually by lower 13 discharge of outlet, the life of liver and lungs when simulating Intestinal ischemia
Reason state;After anoxic 8h, then with normal oxygen-containing culture solution replacement anoxic culture solution continuation reoxygenation culture 16-24h, oxygen-containing culture solution
Chip is injected by top-level entries 7, training is penetrated by polycarbonate perforated membrane 3 in Intestinal epithelial cells culture pond 5
Nutrient solution exchanges in pond 6, and it is finally logical to pass sequentially through hepatocyte cultures pond 10, serpentine channel 11 and alveolar epithelial cells culture pond 12
13 discharge of outlet is crossed down, in the process, upper outlet 8 and lower inlet 9 are blocked, anoxic culture solution is one-way flow, thus real
The now simulation to liver and lung injury pathologic process is caused after internal Intestinal ischemia Reperfu- sion.
Claims (1)
1. Gut ischmia-reperfusion causes the bionical micro-fluidic chip of remote organ damage in a kind of analogue body, it is characterised in that: described
Chip includes glass substrate (1), PDMS piece (2), polycarbonate perforated membrane at being sequentially arranged above of glass substrate (1)
(3) and upper PDMS piece (4),
Offer the downward Intestinal epithelial cells culture pond (5) of opening direction on the upper PDMS piece (4), and lower PDMS piece
(2) culture solution exchange pond (6), described while Intestinal epithelial cells culture pond (5) and culture solution exchange pond (6) are then offered on
To be formed by figure identical in cross section, and the two is overlapped in the longitudinal direction, and the polycarbonate perforated membrane (3) is located at intestines
Between mucosal epithelial cells culture pond (5) and culture solution exchange pond (6),
The upper inlet (7) and upper outlet being connected with Intestinal epithelial cells culture pond (5) are additionally provided on upper PDMS piece (4)
(8),
It is then provided on lower PDMS piece (2) and exchanges the lower inlet (9) that pond (6) is connected with culture solution, culture solution exchanges pond (6)
Hepatocyte cultures pond (10), serpentine channel (11) and alveolar epithelial cells are also disposed on direction far from lower inlet (9)
Culture pond (12), and culture solution exchanges between pond (6) and hepatocyte cultures pond (10), hepatocyte cultures pond (10) and serpentine channel
(11) it is interconnected by microchannel between and between serpentine channel (11) and alveolar epithelial cells culture pond (12), together
When the lower outlet (13) being connected with alveolar epithelial cells culture pond (12), the lower outlet are additionally provided on lower PDMS piece (2)
(13) end is located at the surface of upper PDMS piece (4).
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI709645B (en) * | 2019-07-29 | 2020-11-11 | 國立屏東科技大學 | Biochip that simulates the intestinal environment |
CN112403542A (en) * | 2020-11-05 | 2021-02-26 | 清华大学 | Micro-fluidic chip for quantitatively researching biofilm and manufacturing method thereof |
-
2018
- 2018-10-29 CN CN201821753208.0U patent/CN209098695U/en active Active
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI709645B (en) * | 2019-07-29 | 2020-11-11 | 國立屏東科技大學 | Biochip that simulates the intestinal environment |
CN112403542A (en) * | 2020-11-05 | 2021-02-26 | 清华大学 | Micro-fluidic chip for quantitatively researching biofilm and manufacturing method thereof |
CN112403542B (en) * | 2020-11-05 | 2021-09-28 | 清华大学 | Micro-fluidic chip for quantitatively researching biofilm and manufacturing method thereof |
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