CN208762505U - A kind of digitlization microarray organ chip - Google Patents
A kind of digitlization microarray organ chip Download PDFInfo
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- CN208762505U CN208762505U CN201820475403.5U CN201820475403U CN208762505U CN 208762505 U CN208762505 U CN 208762505U CN 201820475403 U CN201820475403 U CN 201820475403U CN 208762505 U CN208762505 U CN 208762505U
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- microarray
- digitlization
- organ chip
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Abstract
The utility model provides a kind of digitlization microarray organ chip, including top plate, PET film and bottom plate；Upper chamber is equipped in top plate, lower chambers are equipped in bottom plate, upper chamber is consistent with the shape of lower chambers, it is separated between upper chamber and lower chambers by PET film, the bottom chamber of bottom plate is arranged with the microarray hole for microballoon culture and digital measuring, input channel and output channel are connected on top plate, input channel and output channel are connected to upper chamber respectively.The utility model has the characteristics that bionical, high-throughput, cheap, has preferable prospect in terms of drug screening, disease modeling and the clinical applications such as cytotoxicity test.
Description
Technical field
The utility model relates to field of biotechnology, and in particular to a kind of digitlization microarray device based on microflow control technique
Official's chip and its application.
Background technique
" organ chip " technology be in microfluidic devices by way of continuous pouring culture living cells to simulate group
Knit the physiological function with organ.It can be grown for cell provide the intracorporal physical environment of simulation (hydrodynamic shear, cyclic strain and
Mechanical compression etc.), so that it is more really represented cell and organ.Liquid flowing can be controlled in organ chip, to enhance
The differentiation of many cell types and the long-term holding of function.Existing organ chip can use microflow control technique, microfabrication
Carry out three-dimensional microenvironment complicated in analogue body with biomaterial, such as cultivates the micro- blood of people in 3D institutional framework using microfluidic device
Endothelial cell simulates the microchannel of lymphatic vessel and blood vessel.The tumor phenotype observed in vivo can also be simulated, i.e.,
By necrotic cores, the gradient shape knot of internal stationary cell ring and external proliferative cell zone composition.
Digital assay is a kind of current accurate analysis system of high throughput, can be in microstructure to analytical unit point
It cuts and independently analyzes, there is the features such as high collimation, high duplication, can be used for improving the accurate analysis level of organ chip.Currently,
Digitlization medicine sorting platform is all based on 384 and 1536 orifice plates, but this method is limited to orifice plate number in precision, and can not
Realize 3D dynamic cultivation.Simultaneously, it is difficult to be further reduced the consumption of reagent, amount of pixels is limited to orifice plate number, is difficult to carry out liquid
The accurate distribution of body, and influenced by liquid evaporation.And the digital assay based on microflow control technique, there are mainly two types of moulds
Formula: microarray format and droplet mode.Digital assay based on droplet mode, it is difficult to produced by removing in cell growth process
Toxic metabolic substance, and addition nutriment, greatly limit research application of the droplet analysis platform in organ chip.Though
The blank of digital assay is so provided with the organ chip technology that micropore is basic microarray, but microarray organ core at present
Piece is all to retain in the chip to cell, agglomerating culture, all suffers from the lower defect of flux.
Therefore, develop a kind of digitlization microarray organ chip, by carrying out the culture of 3D microballoon and inspection in microporous matrix
It surveys, such 3D microballoon generates 3D sphere gel stent, can produce certain hole after freeze-drying by droplet generating principle, high throughput,
It can be cultivated after freeze-drying bracket adherent cell.Such method is the high-throughput preparation outside digitlization organ chip, is different from
The characteristics of existing organ chip is to retain in the chip to cell, agglomerating culture.The digitlization microarray organ chip
It is to be cultivated and detected after microballoon containing cell is directly injected into.The digitized microarray organ chip overcomes at present
There is the lower defect of the flux of organ chip, realizes high-throughput digital assay.The digitlization organ chip platform has
Precision is high, reproducible feature, can be in drug screening, and disease modeling, medical compounds optimization and cytotoxicity test need
Aspect is asked to play a role.
Utility model content
In view of this, providing one kind the technical problem to be solved by the present invention is to overcome the deficiencies of existing technologies
Digitize microarray organ chip, including top plate, PET film and bottom plate；The top plate includes liquid input, output channel, institute
State top plate, PET film forms upper chamber and forms lower chambers, the upper and lower cavity for adding cell culture fluid, the PET film and bottom plate
Room is separated by a floor PET film.The bottom plate is arranged with microarray hole, and the microarray hole is for microballoon culture and digitlization inspection
It surveys.
In some embodiments, the top plate, PET film, bottom plate are sequentially connected by ionic bond；The top plate offers
Liquid injection hole, drainage hole and note ball, gas vent, are communicated with liquid injection pipe and drain pipe, the note at the liquid injection hole and drainage hole
Note bulb and exhaust pipe are communicated at ball and gas vent.It is cell culture fluid perfusion chamber that the top plate, which has upper chamber,.
In some embodiments, PET film is equipped between the upper and lower chambers, aperture is 3 ~ 10 μm.
In some embodiments, the lower chambers are located at immediately below the film, and cross-sectional area is 1-3 cm2。
It in some embodiments, is micropore on the bottom plate, number is 200 ~ 10,000, and aperture is 100 ~ 300 μ
M, with a thickness of 100 ~ 200 μm.
In some embodiments, the epicoele chamber is U-shaped structure.
In some embodiments, the liquid injection hole aperture is 1-2 mm；The liquid discharge orifice aperture is 1-2 mm；Institute
Stating note ball aperture is 1-2 mm；The gas vent aperture is 1-2 mm；The liquid injection pipe caliber is 0.5-1 mm, length 8-
10 cm；The drain pipe caliber is 0.5-1 mm, and length is 8-10 cm；The note bulb caliber is 0.5-1 mm, and length is
1-2 cm；The exhaust pipe caliber is 0.5-1 mm, and length is 1-2 cm.
In some embodiments, the top plate and bottom plate are PDMS plate, and its side length is respectively 10-15 mm；It is described
The thickness of top plate and bottom plate is respectively 2-5 mm.
The utility model additionally provides a kind of application for digitizing microarray organ chip, which is characterized in that including following
Step:
S10: microballoon containing cell being injected into the bottom plate of the lower chambers, closes note ball and exhaust with clip
Hole stands 4 hours；
S20: will be in the cell culture fluid injection upper chamber；
S30: it is connected with peristaltic pump culture to microarray organ chip is digitized in S20 step, cultivates and after a certain period of time may be used
Carry out microarray analysis.
In some embodiments, when cell or microballoon being injected into digitlization microarray organ chip, sample introduction speed
For 0.5-2 mL/min.
A kind of digitlization microarray organ chip beneficial effect provided by the utility model is:
Digitlization microarray organ chip be micro-fluid chip, one piece several square centimeters of chips can to containing difference
The long-term cultivation that the microballoon of cell type is recycled, and a kind of platform of high throughput analysis can be carried out to its cell activity.This
It is that one kind can be used for drug screening, the Important Platform of disease modeling and Study of cytotoxicity.With bionical, high-throughput, cheap etc.
Feature.The digitlization microarray organ chip preferably simulated in vivo environment and can carry out high throughput analysis, possess huge city
Fieldization prospect.
In conclusion the utility model is in view of the problems of the existing technology, using the microarray on organ chip, establish
A kind of high-flux detection method.It the digitlization microarray organ chip and its applies in drug screening, disease modeling and cell
Toxotest etc. is with good application prospect.
Detailed description of the invention
It should be understood that the following drawings illustrates only some embodiments of the utility model, therefore it is not construed as
Restriction to range for those of ordinary skill in the art without creative efforts, can also basis
These attached drawings obtain other relevant attached drawings.
Fig. 1 is the structural decomposition diagram of utility model.
Fig. 2 is the constitutional diagram of the utility model.
Fig. 3 is the constitutional diagram of the utility model.
Drawing reference numeral explanation: top plate 1, liquid injection hole 1-1, drainage hole 1-2 infuse ball 1-3, gas vent 1-4, upper chamber 1-5,
Liquid injection pipe 1-6, drain pipe 1-7 infuse bulb 1-8, exhaust pipe 1-9, PET film 2-1, bottom plate 3, lower chambers 3-1, micropore 3-1-1.
Specific embodiment
The embodiments of the present invention are described below in detail, examples of the embodiments are shown in the accompanying drawings, wherein from beginning
Same or similar element or element with the same or similar functions are indicated to same or similar label eventually.Below by ginseng
The embodiment for examining attached drawing description is exemplary, it is intended to for explaining the utility model, and should not be understood as to the utility model
Limitation.
In the description of the present invention, it should be understood that term " length ", " width ", "upper", "lower", " preceding ",
The orientation or positional relationship of the instructions such as " rear ", "left", "right", "vertical", "horizontal", "top", "bottom" "inner", "outside" is based on attached
Orientation or positional relationship shown in figure, is merely for convenience of describing the present invention and simplifying the description, rather than indication or suggestion
Signified device or element must have a particular orientation, be constructed and operated in a specific orientation, therefore should not be understood as to this
The limitation of utility model.
In the present invention, it is limited unless there are specific, in the utility model description, PET film pore diameter range can be into
Row is adjusted, and size can be 3 ~ 10 μm, while it should be understood that material can as digitlization microarray organ microarray biochip
For PDMS, but it is not limited to PDMS, can also be PMMA or other can be carved or hollow out is that the material with the big small-bore of correspondence is equal
For this patent institute protection scope.In addition, term " upper chamber ", " lower chambers " are used for description purposes only, and should not be understood as indicating
Or it implies relative importance or implicitly indicates indicated technical characteristic.
In the present invention unless specifically defined or limited otherwise, the arts such as term " connected ", " connection ", " fixation "
Language shall be understood in a broad sense, for example, it may be being fixedly connected, may be a detachable connection, or integral；It can be mechanical connect
It connects, is also possible to be electrically connected；It can be directly connected, can also can be in two elements indirectly connected through an intermediary
The interaction relationship of the connection in portion or two elements.It for the ordinary skill in the art, can be according to specific feelings
Condition understands the concrete meaning of above-mentioned term in the present invention.
Embodiment
Referring to Fig. 1, the utility model provides a kind of digitlization microarray organ chip, including top plate, PET film and bottom
Plate；The top plate includes liquid input, output channel, and the top plate, PET film form upper chamber and be used to add cell culture fluid,
The PET film and bottom plate form lower chambers, and the upper and lower chambers is separated by one layer of PET film.The bottom plate is arranged with microarray hole,
The microarray hole is used for microballoon culture and digital measuring.
It is above-mentioned, it is to be understood that digitlization microarray organ chip is micro-fluid chip, at one piece several square centimeters
The long-term cultivation that chip can recycle the microballoon containing different cell types, and its cell activity can be carried out high-throughput
A kind of platform of analysis can be used for drug screening, disease modeling and Study of cytotoxicity.The chip has bionical, high-throughput, honest and clean
The features such as valence.The digitlization microarray organ chip preferably simulated in vivo environment and can carry out high throughput analysis, possess huge
Market-oriented prospect.
In conclusion the utility model is in view of the problems of the existing technology, using the microarray on organ chip, establish
A kind of high-flux detection method.It the digitlization microarray organ chip and its applies in drug screening, disease modeling and cell
Toxotest etc. is with good application prospect.
In the utility model embodiment, the top plate, PET film, bottom plate are sequentially connected by ionic bonding；The top plate
Liquid injection hole, drainage hole and note ball, gas vent are offered, is communicated with liquid injection pipe and drain pipe at the liquid injection hole and drainage hole,
Note bulb and exhaust pipe are communicated at the note ball and gas vent.
In the utility model embodiment, PET film is equipped between the upper and lower chambers, aperture is 3 μm.
In the utility model embodiment, the upper chamber is U-shaped structure, and cross-sectional area is 1 cm2.The structure is available
Perfusion and constant flow in culture medium, are conducive to mass exchange and long-term cultivation.
In the utility model embodiment, the liquid injection hole aperture is 1 mm；The liquid discharge orifice aperture is 1 mm；Institute
Stating note ball aperture is 1 mm；The gas vent aperture is 1 mm；The liquid injection pipe caliber is 1 mm, and length is 10 cm；It is described
Drain pipe caliber is 1 mm, and length is 10 cm；The note bulb caliber is 1 mm, length 1cm；The exhaust pipe caliber is 1
Mm, length are 2 cm.The structure can be used for adding culture medium and microballoon respectively, be conducive to the fixation and culture of microballoon.
In the utility model embodiment, the top plate and bottom plate are PDMS plate, and its side length is respectively 1.2 cm；Institute
The thickness for stating top plate and bottom plate is followed successively by 2mm.
It is micropore on the bottom plate, number 10,000, aperture is 100 μm, thick in the utility model embodiment
Degree is 100 μm.Since the structure of micropore designs, when in use, the structure of the utility model can achieve the unit time 10,000
A flux compares and is commonly used for lower than 100 flux of product in the prior art, and analysis efficiency is greatly improved.
The utility model additionally provides a kind of application for digitizing microarray organ chip, comprising the following steps:
S10: microballoon containing cell being injected into the bottom plate of the lower chambers, closes note ball and exhaust with clip
Hole stands 4 hours；
S20: will be in the cell culture fluid injection upper chamber；
S30: microarray organ chip will be digitized in S20 step and be connected with peristaltic pump culture, and cultivated and after a certain period of time may be used
Carry out microarray analysis.
It is understood that miniflow syringe pump, autosampler or manual injector can be used in step S10 by collection
Microballoon is injected into the digitlization microarray organ chip 1.
It is understood that after step S30 cell activation assay can be carried out to microarray.
It is to be appreciated that the chip can directly detect the microballoon in micro array structure, this kind of detection mode
As in situ detection.
It is to be appreciated that under the microballoon on digitlization microarray organ chip in micro array structure is rinsed from chip
Come, then the process detected is ex situ detection.
In the utility model embodiment, when microballoon or cell are injected into digitlization microarray organ chip 1, into
Sample speed is 1 mL/min.
The above descriptions are merely preferred embodiments of the present invention, is not intended to limit the utility model, for this
For the technical staff in field, various modifications and changes may be made to the present invention.It is all in the spirit and principles of the utility model
Within, any modification, equivalent replacement, improvement and so on should be included within the scope of protection of this utility model.
Claims (9)
1. a kind of digitlization microarray organ chip, it is characterised in that: including top plate, PET film and bottom plate；It is equipped in top plate upper
Chamber is equipped with lower chambers in bottom plate, and upper chamber is consistent with the shape of lower chambers, between upper chamber and lower chambers by PET film every
It opens, the bottom chamber of bottom plate is arranged with the microarray hole for microballoon culture and digital measuring, is connected with input pipe on top plate
Road and output channel, input channel and output channel are connected to upper chamber respectively.
2. a kind of digitlization microarray organ chip as described in claim 1, it is characterised in that: the top plate, PET film, bottom
Plate is sequentially connected by ionic bond, and the aperture of PET film is 3~10 μm.
3. a kind of digitlization microarray organ chip as described in claim 1, it is characterised in that: input channel includes liquid injection pipe
With note bulb, output channel includes drain pipe and exhaust pipe.
4. a kind of digitlization microarray organ chip as described in claim 1, it is characterised in that: open respectively at the both ends of upper chamber
If liquid injection hole and drainage hole, liquid injection hole are connected to liquid injection pipe, drainage hole is connected to drain pipe；Be also provided on top plate note ball and
Gas vent, note ball are connected to note bulb, and gas vent is connected to exhaust pipe, and note ball is connected to liquid injection hole, gas vent and drain
Hole connection.
5. a kind of digitlization microarray organ chip as claimed in claim 2, it is characterised in that: the microarray hole is located at
Below the PET film, shared total cross-sectional area is 1-3cm2。
6. a kind of digitlization microarray organ chip as claimed in claim 4, it is characterised in that: the bottom plate is equipped with micro-
Hole, number are 200~10000,100~300 μm of aperture, with a thickness of 100~200 μm.
7. a kind of digitlization microarray organ chip as claimed in claim 4, it is characterised in that: the upper chamber is U-shaped knot
Structure, the two sides of U-shaped structure are respectively used to that ball and liquid injection hole and gas vent will be infused and drainage hole is respectively communicated with.
8. a kind of digitlization microarray organ chip as claimed in claim 4, it is characterised in that: the aperture of the liquid injection hole is
1-2mm；The aperture of the drainage hole is 1-2mm；The aperture of the note ball is 1-2mm；The gas vent aperture is 1-2mm；
The liquid injection pipe caliber is 0.5-1mm, length 8-10cm；The drain pipe caliber is 0.5-1mm, length 5-10cm；Institute
Stating note bulb caliber is 0.5-1mm, length 1-2cm；The exhaust pipe caliber is 0.5-1mm, length 1-2cm.
9. a kind of digitlization microarray organ chip as claimed in claim 2, it is characterised in that: the top plate and bottom plate are
The PDMS plate of square, and its side length is respectively 10-15mm；The thickness of the top plate and bottom plate is respectively 2-5mm.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201820475403.5U CN208762505U (en) | 2018-04-04 | 2018-04-04 | A kind of digitlization microarray organ chip |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201820475403.5U CN208762505U (en) | 2018-04-04 | 2018-04-04 | A kind of digitlization microarray organ chip |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108641931A (en) * | 2018-04-04 | 2018-10-12 | 浙江大学 | A kind of digitlization microarray organ chip and its application |
| CN110257249A (en) * | 2019-07-19 | 2019-09-20 | 东北大学 | A kind of micro-fluidic chip and administration cultural method for tumour cell dimensional culture |
| CN110556046A (en) * | 2019-08-09 | 2019-12-10 | 西安交通大学 | Dual-network structure three-dimensional tissue model and perfusion integrated preparation method thereof |
-
2018
- 2018-04-04 CN CN201820475403.5U patent/CN208762505U/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108641931A (en) * | 2018-04-04 | 2018-10-12 | 浙江大学 | A kind of digitlization microarray organ chip and its application |
| CN110257249A (en) * | 2019-07-19 | 2019-09-20 | 东北大学 | A kind of micro-fluidic chip and administration cultural method for tumour cell dimensional culture |
| CN110556046A (en) * | 2019-08-09 | 2019-12-10 | 西安交通大学 | Dual-network structure three-dimensional tissue model and perfusion integrated preparation method thereof |
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