CN106929403A - A kind of blood-brain barrier analogue means for medicament high flux screening - Google Patents
A kind of blood-brain barrier analogue means for medicament high flux screening Download PDFInfo
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- CN106929403A CN106929403A CN201710245124.XA CN201710245124A CN106929403A CN 106929403 A CN106929403 A CN 106929403A CN 201710245124 A CN201710245124 A CN 201710245124A CN 106929403 A CN106929403 A CN 106929403A
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- 239000003814 drug Substances 0.000 title claims abstract description 32
- 230000008499 blood brain barrier function Effects 0.000 title claims abstract description 30
- 210000001218 blood-brain barrier Anatomy 0.000 title claims abstract description 30
- 230000004907 flux Effects 0.000 title claims abstract description 27
- 238000012216 screening Methods 0.000 title claims abstract description 27
- 239000000017 hydrogel Substances 0.000 claims abstract description 25
- 238000004113 cell culture Methods 0.000 claims description 67
- 239000007788 liquid Substances 0.000 claims description 15
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 10
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 10
- 210000002744 extracellular matrix Anatomy 0.000 claims description 10
- 238000007789 sealing Methods 0.000 claims description 5
- 210000004027 cell Anatomy 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 abstract description 13
- 210000003668 pericyte Anatomy 0.000 abstract description 9
- 238000004088 simulation Methods 0.000 abstract description 7
- 235000015097 nutrients Nutrition 0.000 description 5
- 210000004748 cultured cell Anatomy 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 2
- 239000012930 cell culture fluid Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2503/00—Use of cells in diagnostics
- C12N2503/02—Drug screening
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
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Abstract
A kind of blood-brain barrier analogue means for medicament high flux screening disclosed by the invention, including multiple simulated experiment units, each described simulated experiment unit include the first incubator and the second incubator, and the first incubator is located on the second incubator；Magnetic hydrogel layer is additionally provided between first incubator and the second incubator；Positive electrode is provided with first incubator, negative electrode is provided with the second incubator, positive electrode is connected with negative electrode by wire, and ohmmeter is additionally provided between positive electrode and negative electrode；Magnetic force control is additionally provided with below second incubator.A kind of blood-brain barrier analogue means for medicament high flux screening of the invention, is controlled magnetic hydrogel and to produce stretcher strain using magnetic force control, and pericyte flexible and central nervous system treatment medicament high flux screening is carried out simultaneously in simulation blood-brain barrier；The present apparatus is simple and compact for structure, safe and practical, can be used for the screening of medicine for central nervous system, it is easy to promote.
Description
Technical field
The invention belongs to biomedical in-vitro simulated equipment technical field, it is related to a kind of blood for medicament high flux screening
Brain barrier analogue means.
Background technology
Blood-brain barrier is the barrier that central nervous system treatment medicine must be faced.Pericyte is the important set of blood-brain barrier
Into part, it influences the function of blood-brain barrier by the change of controllable blood-brain barrier mechanics microenvironment of stretching.Blood-brain barrier body
External model is widely used in the screening of central nervous system treatment medicine, but there is no that can to simulate pericyte flexible and while enter now
The blood-brain barrier analogue means of row central nervous system treatment medicament high flux screening.
The content of the invention
Object of the present invention is to provide a kind of blood-brain barrier analogue means for medicament high flux screening, solve
Simulation pericyte is flexible and carries out the problem of central nervous system treatment medicament high flux screening simultaneously.
The technical solution adopted in the present invention is：A kind of blood-brain barrier analogue means for medicament high flux screening, bag
Multiple simulated experiment units are included, each described simulated experiment unit includes the first incubator and the second incubator, the first incubator
On the second incubator；Magnetic hydrogel layer is additionally provided between first incubator and the second incubator；In first incubator
Be provided with positive electrode, negative electrode be provided with the second incubator, positive electrode is connected with negative electrode by wire, positive electrode and negative electrode it
Between be additionally provided with ohmmeter；Magnetic force control is additionally provided with below second incubator.
The features of the present invention is also resided in,
The first cell culture chamber of bottom opening is provided with first incubator, open-topped is provided with the second incubator
Two cell culture chambers, magnetic hydrogel layer is located between first cell culture chamber and the second cell culture chamber, the first culture
Device top is provided with liquid filling hole, and liquid filling hole is connected with the first cell culture chamber.
Extracellular matrix layer is provided between first cell culture chamber and the second cell culture chamber, extracellular matrix layer is located at magnetic
On property hydrogel layer.
Second cell culture chamber includes the first cell culture chamber and the second cell culture chamber, the first cell culture chamber and second
Baffle plate is provided between cell culture chamber, the first cell culture chamber bottom surface is higher than the bottom surface of the second cell culture chamber, the training of the first cell
The bottom surface for supporting room is provided with microexamination hole.
Magnetic force control includes housing, and housing upper surface is provided with through hole, and enclosure interior is provided with lifting platform, lifting platform upper surface
Projection is provided with, projection is located at immediately below through hole, and projection upper surface is provided with permanent magnet, threaded rod, screw thread are provided with vertically on lifting platform
Bar one end passes through the other end of lifting platform, threaded rod to pass through housing upper surface, and threaded rod is threadedly coupled with lifting platform, on lifting platform
Support bar is also provided with vertically, and support bar is fixed between housing upper and lower surface.
Airstrainer is provided with liquid filling hole.
Sealing gasket is provided between the surface that first incubator is in contact with the second incubator.
The beneficial effects of the invention are as follows, a kind of blood-brain barrier analogue means for medicament high flux screening, including multiple
Simulated experiment unit, each simulated experiment unit includes the first incubator, the second incubator and magnetic force control；By
Cultured cells in one incubator and the second incubator, using the first cell culture chamber in full second incubator of nutrient solution, will
Magnetic hydrogel layer is placed between the first cell culture chamber and the second cell culture chamber, by liquid filling hole to the first cell culture
Room irrigates the nutrient solution of central nervous system treatment medicine, controls magnetic hydrogel using magnetic force control and produces stretching to become
Shape, pericyte flexible and central nervous system treatment medicament high flux screening is carried out in simulation blood-brain barrier simultaneously；In addition, plus
Fluid apertures top is provided with dismantled and assembled air filter screen can prevent cell culture fluid to be contaminated；Set in the bottom surface of the second cell culture chamber
Microexamination hole is equipped with, convenient form and growing state to its inside cell is observed；By positive electrode, negative electrode and Europe
The setting of nurse table, can detect magnetic hydrogel layer both sides across transendothelial electrical resistance；The present apparatus is simple and compact for structure, safe and practical,
It is easy to spread.
Brief description of the drawings
Fig. 1 is that a kind of structure of the embodiment 1 of blood-brain barrier analogue means for medicament high flux screening of the invention is shown
It is intended to；
Fig. 2 is a kind of single mould of the embodiment 2 of blood-brain barrier analogue means for medicament high flux screening of the invention
The structural representation of draft experiment unit.
In figure, 1. the first incubator, 2. the first cell culture chamber, 3. the second incubator, 4. the second cell culture chamber, 5. magnetic
Property hydrogel layer, 6. extracellular matrix layer, 7. liquid filling hole, 8. positive electrode, 9. negative electrode, 10. ohmmeter, 11. magnetic force controls,
12. sealing gaskets；
The cell culture chambers of 4-1. first, the cell culture chambers of 4-2. second, 4-3. baffle plates, 4-4. microexaminations hole；
11-1. housings, 11-2. lifting platforms, 11-3. permanent magnets, 11-4. threaded rods, 11-5. support bars.
Specific embodiment
The present invention is described in detail with reference to the accompanying drawings and detailed description.
A kind of blood-brain barrier analogue means for medicament high flux screening of the invention, as shown in Figures 1 and 2, including it is many
Individual simulated experiment unit, each described simulated experiment unit includes the first incubator 1 and the second incubator 3, the first incubator 1
On the second incubator 3；Magnetic hydrogel layer 5 is additionally provided between first incubator 1 and the second incubator 3；First incubator 1
Inside be provided with positive electrode 8, negative electrode 9 be provided with the second incubator 3, positive electrode 8 is connected with negative electrode 9 by wire, positive electrode 8 and
Ohmmeter 10 is additionally provided between negative electrode 9；The lower section of the second incubator 3 is additionally provided with magnetic force control 11.
The first cell culture chamber 2 of bottom opening is provided with first incubator 1, open top is provided with the second incubator 3
The second cell culture chamber 4, magnetic hydrogel layer 5 be located at the cell culture chamber 4 of first cell culture chamber 2 and second between,
The top of first incubator 1 is provided with liquid filling hole 7, and liquid filling hole 7 is connected with the first cell culture chamber 2.
Extracellular matrix layer 6, extracellular matrix layer 6 are provided between first cell culture chamber 2 and the second cell culture chamber 4
On magnetic hydrogel layer 5.
Second cell culture chamber 4 includes the first cell culture chamber 4-1 and the second cell culture chamber 4-2, the first cell culture
Baffle plate 4-3 is provided between chamber 4-1 and the second cell culture chamber 4-2, the first cell culture chamber 4-1 bottom surfaces are higher than the second cell culture
The bottom surface of chamber 4-2, the bottom surface of the second cell culture chamber 4-2 is provided with microexamination hole 4-4.
Magnetic force control 11 includes housing 11-1, and housing 11-1 upper surfaces are provided with through hole, lifting is provided with inside housing 11-1
Platform 11-2, lifting platform 11-2 upper surface are provided with projection, and projection is located at immediately below through hole, and projection upper surface is provided with permanent magnet 11-3,
Threaded rod 11-4 is provided with lifting platform 11-2 vertically, threaded rod 11-4 one end passes through lifting platform 11-2, and threaded rod 11-4's is another
Through housing 11-1 upper surfaces, threaded rod 11-4 is threadedly coupled with lifting platform 11-2, is also provided with branch on lifting platform 11-2 vertically at end
Strut 11-5, support bar 11-5 are fixed between the housing 11-1 upper and lower surfaces.
Airstrainer is provided with liquid filling hole 7.
Sealing gasket 12 is provided between the surface that first incubator 1 is in contact with the second incubator 3.
When using, as shown in Figures 1 and 2, the present apparatus includes multiple simulated experiment units, and each simulated experiment unit is wrapped
Include the first incubator 1, the second incubator 3 and magnetic force control 11；First incubator 1 is placed on the upper strata of the second incubator 3,
Sealing gasket 12, the bottom opening of the first cell culture chamber 2 and are provided between the contact surface of the first incubator 1 and the second incubator 3
The open top of two cell culture chambers 4 is relative, by magnetic hydrogel layer 5 and extracellular matrix layer 6 by the first cell culture chamber 2
Keep apart with the second cell culture chamber 4, by liquid filling hole 7 to the perfusion cultures liquid of the first cell culture chamber 2, filled using nutrient solution
It is full of the second cell culture chamber 4, the first cell culture chamber 4-1 in the first cell culture chamber 2, the second cell culture chamber 4 and
Cultured cells in two cell culture chamber 4-2；By adjusting the permanent magnet 11-3 in magnetic force control 11 with magnetic hydrogel layer 5
Distance makes the magnetic hydrogel layer 5 produce stretcher strain, and pericyte is flexible in simulation blood-brain barrier, by positive electrode 8, negative electricity
Pole 9 and the setting of ohmmeter 10, can detect the both sides of magnetic hydrogel layer 5 across transendothelial electrical resistance；Wherein the first incubator 1 and
Two incubators 3 are transparent polydimethyl siloxane material, and the magnetic force control in addition to permanent magnet 11-3 is transparent organic
Glass；By the way that by multiple simulated experiment units, carrying out experiment can carry out central nervous system treatment medicament high flux sieve simultaneously
Choosing.
Embodiment 1
As shown in figure 1, upper strata is 6 the first incubators 1 of series connection, intermediate layer is followed successively by extracellular matrix layer 6 and magnetic
Hydrogel layer 5, lower floor is 6 the second incubators 3 of series connection, and the magnetic force control of series connection is additionally provided with below the second incubator 3
11,6 block permanent magnet 11-3 are separately mounted on 6 projections of same lifting platform, and permanent magnet is controlled by same threaded rod 11-4
The lifting of 11-3, can be studied under the conditions of same magnetic force by such design, magnetic hydrogel layer is produced identical
Stretcher strain, pericyte flexible and various central nervous system treatment medicament high fluxes sieves are carried out in simulation blood-brain barrier simultaneously
Choosing.
Embodiment 2
As shown in Fig. 2 the present apparatus includes multiple separate simulated experiment units, each independent simulated experiment unit
Including the first incubator 1, the second incubator 3 and magnetic force control 11, also including being arranged on the first incubator 1 and the second culture
Extracellular matrix layer 6 and magnetic hydrogel layer 5 between device 3；Can be studied in different magnetic force conditions by such design
Under, magnetic hydrogel layer 5 is produced different stretcher strains, different retracted positions of pericyte and simultaneously in simulation blood-brain barrier
Carry out central nervous system treatment medicament high flux screening.
A kind of blood-brain barrier analogue means for medicament high flux screening of the invention has the following advantages：Including multiple moulds
Draft experiment unit, each simulated experiment unit includes the first incubator, the second incubator and magnetic force control；By first
Cultured cells in incubator and the second incubator, using the first cell culture chamber in full second incubator of nutrient solution, by magnetic
Property hydrogel layer is placed between the first cell culture chamber and the second cell culture chamber, by liquid filling hole to the first cell culture chamber
The nutrient solution of central nervous system treatment medicine is irrigated, magnetic hydrogel is controlled using magnetic force control and is produced stretcher strain,
In simulation blood-brain barrier pericyte flexible and central nervous system treatment medicament high flux screening is carried out simultaneously；In addition, liquid feeding
Hole top is provided with dismantled and assembled air filter screen can prevent cell culture fluid to be contaminated；Set in the bottom surface of the second cell culture chamber
There is microexamination hole, convenient form and growing state to its inside cell is observed；By positive electrode, negative electrode and ohm
The setting of table, can detect magnetic hydrogel layer both sides across transendothelial electrical resistance；The present apparatus is simple and compact for structure, safe and practical, easily
In popularization.
Claims (7)
1. a kind of blood-brain barrier analogue means for medicament high flux screening, it is characterised in that including multiple simulated experiment lists
Unit, each described simulated experiment unit includes the first incubator (1) and the second incubator (3), and first incubator (1) is located at
On second incubator (3)；Magnetic water-setting is additionally provided between first incubator (1) and second incubator (3)
Glue-line (5)；It is provided with first incubator (1) in positive electrode (8), second incubator (3) and is provided with negative electrode (9), institute
State positive electrode (8) to be connected by wire with the negative electrode (9), be additionally provided between the positive electrode (8) and the negative electrode (9)
Ohmmeter (10)；Magnetic force control (11) is additionally provided with below second incubator (3).
2. a kind of blood-brain barrier analogue means for medicament high flux screening according to claim 1, it is characterised in that
It is provided with first incubator (1) in first cell culture chamber (2) of bottom opening, second incubator (3) and is provided with top
Second cell culture chamber (4) of portion opening, magnetic hydrogel layer (5) positioned at first cell culture chamber (2) with it is described
Between second cell culture chamber (4), the first incubator (1) top is provided with liquid filling hole (7), the liquid filling hole (7) and first
Cell culture chamber (2) is connected.
3. a kind of blood-brain barrier analogue means for medicament high flux screening according to claim 2, it is characterised in that
Extracellular matrix layer (6), the cell are provided between first cell culture chamber (2) and second cell culture chamber (4)
Extracellular matrix layer (6) is on magnetic hydrogel layer (5).
4. a kind of blood-brain barrier analogue means for medicament high flux screening according to claim 3, it is characterised in that
Second cell culture chamber (4) includes the first cell culture chamber (4-1) and the second cell culture chamber (4-2), and described first is thin
Baffle plate (4-3), the first cell culture chamber (4- are provided between born of the same parents' culture chamber (4-1) and second cell culture chamber (4-2)
1) bottom surface is higher than the bottom surface of the second cell culture chamber (4-2), and the bottom surface of second cell culture chamber (4-2) is provided with micro- sight
Examine hole (4-4).
5. a kind of blood-brain barrier analogue means for medicament high flux screening according to claim 4, it is characterised in that
The magnetic force control (11) includes housing (11-1), and housing (11-1) upper surface is provided with through hole, the housing (11-1)
Inside is provided with lifting platform (11-2), and lifting platform (11-2) upper surface is provided with projection, under the projection is located at the through hole just
Side, the projection upper surface is provided with permanent magnet (11-3), threaded rod (11-4) is provided with vertically on the lifting platform (11-2), described
Threaded rod (11-4) one end passes through the other end of lifting platform (11-2), the threaded rod (11-4) to pass through housing (11-1) upper table
Face, the threaded rod (11-4) is threadedly coupled with lifting platform (11-2), and support bar is also provided with vertically on the lifting platform (11-2)
(11-5), the support bar (11-5) is fixed between the housing (11-1) upper and lower surface.
6., according to a kind of blood-brain barrier analogue means for medicament high flux screening that one of claim 2-5 is described, it is special
Levy and be, airstrainer is provided with the liquid filling hole (7).
7. a kind of blood-brain barrier analogue means for medicament high flux screening according to claim 6, it is characterised in that
Sealing gasket (12) is provided between the surface that first incubator (1) is in contact with second incubator (3).
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710245124.XA CN106929403A (en) | 2017-04-14 | 2017-04-14 | A kind of blood-brain barrier analogue means for medicament high flux screening |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710245124.XA CN106929403A (en) | 2017-04-14 | 2017-04-14 | A kind of blood-brain barrier analogue means for medicament high flux screening |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105593358A (en) * | 2013-09-05 | 2016-05-18 | 伯尔尼大学 | Device for in-vitro modelling in-vivo tissues of organs |
| US20160326477A1 (en) * | 2013-12-20 | 2016-11-10 | Jose FERNANDEZ-ALCON | Organomimetic devices and methods of use and manufacturing thereof |
| CN206768114U (en) * | 2017-04-14 | 2017-12-19 | 西安医学院 | Magnetic control high-flux medicaments sifting blood-brain barrier analogue means |
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2017
- 2017-04-14 CN CN201710245124.XA patent/CN106929403A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105593358A (en) * | 2013-09-05 | 2016-05-18 | 伯尔尼大学 | Device for in-vitro modelling in-vivo tissues of organs |
| US20160326477A1 (en) * | 2013-12-20 | 2016-11-10 | Jose FERNANDEZ-ALCON | Organomimetic devices and methods of use and manufacturing thereof |
| CN206768114U (en) * | 2017-04-14 | 2017-12-19 | 西安医学院 | Magnetic control high-flux medicaments sifting blood-brain barrier analogue means |
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Application publication date: 20170707 |