CN102337211A - Cell culture device - Google Patents
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- CN102337211A CN102337211A CN2011102466835A CN201110246683A CN102337211A CN 102337211 A CN102337211 A CN 102337211A CN 2011102466835 A CN2011102466835 A CN 2011102466835A CN 201110246683 A CN201110246683 A CN 201110246683A CN 102337211 A CN102337211 A CN 102337211A
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Abstract
The invention relates to a cell culture device, which comprises fixing base plates and a cell culture system, a light control system and an electrode system which are fixed on the fixing base plates. The cell culture device adopts a special structure of a microfluidic technology to realize culturing of nerve cells, for example, the nerve cells can grow in a cell culture chamber, while axons can only grow in nerve conduits, the nerve cells in the cell culture chamber through the axons in the nerve conduits to constitute nerve loops, and the reproductivity and the controlling force of a cell growth area are relatively strong; the adjustment and the control with high spatiotemporal resolution are performed on the nerve cells through laser, the selectivity and the specificity are strong, and the excitement and the inhibition of the nerve cells can be realized; the nerve loops are excited through the electrode system to carry out auxiliary adjustment and control, the behavior and the function of the nerve loops are monitored in a real-time manner, the spatiotemporal resolution is high, and the adjustment and control as well as detection results are reliable.
Description
[technical field]
The present invention relates to neural engineering field, relate in particular to a kind of cell culture apparatus based on microflow control technique.
[background technology]
Along with the continuous rising of nervous system disorders sickness rate, its research is become focus just gradually.Yet, because neural complicacy makes that in neural some problem of live body (in vivo) research, especially the exploration for neural loop and neural plasticity is very difficult.Under this condition, external (the in vitro) of neurocyte cultivates just becomes a kind of comparatively ideal method.Can make the contact of setting up rule between the neurocyte through vitro culture, three-dimensional contact complicated between the neurone is reduced to two dimension, make its observation and research be more prone to.
The external cultured method of traditional neurocyte is the growth of regulating and control neurocyte through chemical conversion treatment (Chemically pattemed surface), physics microtexture structure (Physical structure) or strength of solution gradient (Solution gradients) cultivating on the matrix; Make it to form neural loop, regulate and control neurocyte through functional electrostimulation (Functional electrical stimulation) or regional perfusion (Local perfusion) then.
Wherein, chemical conversion treatment is through chemical process the cell cultures matrix surface to be processed into the biocompatibility interface with definite shape, thereby attracts neurocyte at these region growings; It is through micro-processing technology that the physics microtexture makes up, and the cell cultures matrix surface is processed into the interface with certain microtexture, and the guiding neurocyte is grown in the designated area; The strength of solution gradient is the growth of cell in certain zone that affect the nerves of the concentration through control biologically active substance (like polypeptide, albumen).Functional electrostimulation is to be used for clinical a kind of control methods at present, in for treatment of diseases such as essential tremor, parkinsonism and myodystonias, has played better action.
Yet to form neural loop, the circulation ratio of cellular growth area and control are relatively poor relatively through chemical conversion treatment, physics microtexture make up or the chemical concentrations gradient is regulated and control neurocyte growth, thereby the circulation ratio of testing is relatively poor.Though functional electrostimulation has excellent temporal resolution, its spatial resolution is relatively poor, and does not possess selectivity and specificity, the difficult inhibition that realizes neurocyte.Though regional perfusion has higher spatial resolution, dabbling position randomness is bigger, is difficult to accurately control, and circulation ratio is relatively poor; In addition, the temporal resolution of regional perfusion is relatively poor, can't satisfy electric physiological requirement.Therefore, traditional lacking, a kind ofly can be used for neuronal cell cultures simultaneously, and neural loop makes up, and the cell culture apparatus of regulating and control, detecting under than high-spatial and temporal resolution (Spatiotemporal resolution).
[summary of the invention]
Based on this, be necessary to provide a kind of and can be used for neuronal cell cultures simultaneously, neural loop makes up, and at the cell culture apparatus of regulating and control, detecting than under the high-spatial and temporal resolution.
A kind of cell culture apparatus comprises: fixed base plate and be located at cell culture system, light regulator control system and the electrode system on the fixed base plate; Cell culture system comprises cell culture chamber and is communicated with the nerve trachea of the confession neural axon growth of cell culture chamber; The light regulator control system places the nerve trachea top to be used for the culture in the nerve trachea is carried out the light stimulus regulation and control; Electrode system is common to mutually with nerve trachea culture in the nerve trachea is carried out assistant regulating and controlling, and the behavior and the function of neural loop detected in real time.
Be applied to such scheme; Preferably, this cell culture apparatus also comprises the drug infusion system that is fixed on the fixed base plate, and the drug infusion system comprises drug infusion pond, drug catheter and waste liquid pool; The drug infusion pond links to each other with waste liquid pool through drug catheter, and drug catheter is connected with nerve trachea.
Be applied to such scheme and combination thereof, preferred, wherein electrode system comprises external contact, lead and electrode points, and external contact links to each other with electrode points through lead, and nerve trachea communicates with electrode points.
Be applied to such scheme and combination thereof, preferred, wherein electrode points deposits the impedance that electro-conductive material is used to reduce electrode points through electrochemical method, and electrode points is modified with enzyme compound through the enzyme technique for fixing and is used to gather biochemical signals.
Be applied to such scheme and combination thereof, preferred, wherein electrode system is formed on the fixed base plate through the mode of sputter or photoetching.
Be applied to such scheme and combination thereof, preferred, wherein the light stimulus position of light regulator control system is corresponding with the position of electrode points.
Be applied to such scheme and combination thereof, preferred, wherein the light regulator control system comprises LASER Light Source, optical fiber interface, optical fiber and is used to control the waveguide of laser light beam guiding and diameter, and waveguide links to each other with LASER Light Source through optical fiber, optical fiber interface.
Be applied to such scheme and combination thereof, preferred, wherein electrode system comprises a plurality of external one to one contacts, lead and electrode points; A plurality of external contacts center on fixed base plate uniform distribution all around; A plurality of leads and electrode points form electrod-array, and corresponding, the light regulator control system comprises the waveguide of a plurality of different diameters; A plurality of waveguides form waveguide arrays, in the waveguide array in the position of waveguide and the electrod-array electrode points position corresponding one by one; Be provided with micro-fluidic switch in electrod-array, waveguide array and the drug catheter.
Be applied to such scheme and combination thereof, preferred, wherein the width of nerve trachea is 1～10 μ m, and length is 100～1000 μ m; Waveguide directly through being 1～10 μ m.
Be applied to such scheme and combination thereof, preferred, wherein cell culture system comprises two groups of cell culture chambers; Every group of cell culture chamber that comprises two connections; Be communicated with through 4 nerve tracheas between two groups of cell culture chambers, the diameter of nerve trachea is 5 μ m, and length is 900 μ m; Electrode system axially is provided with 16 square-shaped electrode points successively along each nerve trachea, and the length and width of electrode points are 5 μ m, between the axial electrode points of each nerve trachea at a distance of 50 μ m; The light regulator control system comprises 16 waveguides, and the diameter of waveguide is 2 μ m; The drug infusion system comprises a plurality of drug catheters that are communicated with the nerve trachea quadrature.
Be applied to such scheme and combination thereof, preferred, wherein the light regulator control system comprises LASER Light Source, optical fiber interface, branch interface and optical fiber, and optical fiber links to each other with LASER Light Source through dividing interface, optical fiber interface.
Be applied to such scheme and combination thereof, preferred, wherein electrode system comprises a plurality of external one to one contacts, lead and electrode points; A plurality of external contacts center on fixed base plate uniform distribution all around; A plurality of leads and electrode points form electrod-array, and corresponding, the light regulator control system comprises a plurality of different diameter fibers; A plurality of optical fiber form fiber arrays, in the fiber array in the position of optical fiber and the electrod-array electrode points position corresponding one by one; Be provided with micro-fluidic switch in electrod-array, waveguide array and the drug catheter.
Be applied to such scheme and combination thereof, preferred, wherein the width of nerve trachea is 1～10 μ m, and length is 100～1000 μ m; Optical fiber directly through being 1～10 μ m.
Be applied to such scheme and combination thereof, preferred, wherein cell culture system comprises two groups of cell culture chambers; Every group of cell culture chamber that comprises two connections; Be communicated with through 4 nerve tracheas between two groups of cell culture chambers, the diameter of nerve trachea is 5 μ m, and length is 900 μ m; Electrode system axially is provided with 16 square-shaped electrode points successively along each nerve trachea, and the length and width of electrode points are 5 μ m, between the axial electrode points of each nerve trachea at a distance of 50 μ m; The light regulator control system comprises 16 optical fiber, and the diameter of optical fiber is 2 μ m; The drug infusion system comprises a plurality of drug catheters that are communicated with the nerve trachea quadrature.
Be applied to such scheme and combination thereof, preferred, wherein the material of fixed base plate is glass, silicon or silicon-dioxide; The material of cell culture chamber and nerve trachea is the transparent dimethoxysiloxane of gathering.
This cell culture apparatus is realized the cultivation of neurocyte through the ad hoc structure of microflow control technique; Can be grown in the cell culture chamber like neurocyte; And aixs cylinder can only be grown in the nerve trachea; Neurocyte in the culturing room constitutes neural loop through the aixs cylinder in the nerve trachea, and the circulation ratio of cellular growth area and control are stronger relatively; Through laser neurocyte is carried out the regulation and control of high-spatial and temporal resolution again, selectivity and high specificity can be realized the excited and inhibition to neurocyte; Through the electrode system stimulation neural loop is carried out assistant regulating and controlling, and the behavior and the function of neural loop detected in real time, spatial and temporal resolution is high, and regulation and control and detected result are reliable.
[description of drawings]
Fig. 1 is the cell culture apparatus structural representation of an embodiment;
Fig. 2 is a cell culture system structural representation in Fig. 1 embodiment;
Fig. 3 is electrod-array and a nerve trachea distribution schematic diagram in Fig. 1 embodiment;
Fig. 4 is cell culture system and a drug infusion system distribution schematic diagram in Fig. 1 embodiment;
Fig. 5 is nerve trachea and a drug catheter distribution schematic diagram in Fig. 1 embodiment;
Fig. 6 is light regulator control system and a cell culture system distribution schematic diagram in Fig. 1 embodiment;
Fig. 7 is the light regulator control system and the cell culture system distribution schematic diagram of another embodiment.
[embodiment]
Mainly combine accompanying drawing and specific embodiment pair cell culture apparatus to do further detailed explanation below.
As shown in Figure 1, the cell culture apparatus 100 of a preferred implementation comprises: fixed base plate 110, cell culture system 120, electrode system 130, drug infusion system 140 and light regulator control system (figure does not show).Wherein, cell culture system 120, electrode system 130, drug infusion system 140 and light regulator control system are fixed on the fixed base plate 110.
Fixed base plate 110 can be made up of mechanically resistant material, mainly plays support fixation.The material that can select for use has glass, silicon and silicon-dioxide etc.The fixed base plate 110 of this embodiment is the square glass base plate.In other embodiments, fixed base plate 110 can also adopt other materials such as silicon or made of silicon dioxide, and shape also is not limited to square, can also be circle etc.
Please join Fig. 2, the cell culture system 120 of this embodiment comprises two groups of totally 4 cell culture chambers 122.Be communicated with through main pipe 124 between every group of cell culture chamber.Main pipe 124 between two groups is communicated with through 4 nerve tracheas 126 that are located on the main pipe 124.Nerve trachea 126 is communicated with two main pipes 124, thereby two groups of cell culture chambers 122 can be communicated with through nerve trachea 126.Cell culture chamber 122 and nerve trachea 126 are mainly used in control and the growth of guiding neurocyte and the formation of connection between the neurocyte and neural loop.Can research model as required design the nerve trachea 126 of different size, the width of nerve trachea 126 is 1～10 μ m, and length is 100～1000 μ m.Preferably; The width of the nerve trachea of this embodiment is 5 μ m, and length is 900 μ m, and the nerve trachea 126 of this design can guarantee that neurocyte can not enter into nerve trachea 126; And have only aixs cylinder in nerve trachea 126, to grow, thereby can obtain orderly neural network.
The transparent ventilation property of cell culture system 120 preferred flexible is material preferably, like Zylox etc.The cell culture system of this embodiment adopts the dimethoxysiloxane (PDMS) of gathering with high hydrophobicity to make.For making neurocyte better growth in cell culture chamber 122, the internal surface of the cell culture chamber 122 of this embodiment, main pipe 124 and nerve trachea 126 can carry out biocompatibility through technology such as surface graft, surface coatings, self-assemblies layer by layer to be handled.In addition, before cell cultures, the internal surface of cell culture chamber 122, main pipe 124 and nerve trachea 126 further can also encapsulate processing, as poly-lysine encapsulate, ln encapsulates etc.
Please combine Fig. 1 and Fig. 3, electrode system 130 comprises external contact 132, lead 134 and electrode points 136.External contact 132 is connected with electrode points 136 through lead 134, each external contact 132 corresponding electrode points 136.A plurality of external contacts 132 evenly are provided with around fixed base plate 110, and a plurality of leads 134 and electrode points 136 form electrod-array.Every limit of the fixed base plate 110 of this embodiment is provided with 16 external contacts 132.For further facilitating use, the design of external contact 132 makes it can be directly connected on the general electrophysiologicalmeasurements measurements instrument carries out electrophysiologicalmeasurements measurements, like the electrophysiologicalmeasurements measurements appearance of U.S. Plexon company and German MEA company.Nerve trachea 126 axially be aligned in sequence with the electrod-array that forms by 16 leads 134 and square-shaped electrode point 136, the length and width of each electrode points 136 are 5 μ m, 50 μ m at interval between per two electrode points 136.Nerve trachea 126 communicates with electrode points 136, thereby electrod-array can carry out the electrophysiologicalmeasurements measurements and the electric pulse stimulation of high-spatial and temporal resolution to the culture in the nerve trachea 126.
Preferably, the electrode system 130 of this embodiment is the surface that is formed on fixed base plate 110 through the mode of sputter or photoetching.The material of lead 134 and electrode points 136 can be in gold, platinum, iridium oxide, titanium nitride, conductive polymers, the carbon-based material a kind of or two or more.In actual use; Electrode system 130 can be used as a kind of auxiliary control methods; Electrod-array can carry out the functional electric impulse stimulation to neurocyte; Strength of electric field through changing in microenvironment comes the growth of neurocyte is induced, and can study neural loop and neural plasticity.For reducing the contact impedance of electrode points 136, strengthen the SNR of electricity physiological signal, can be through the surface deposition decorative material of electrochemical method, like iridium oxide, conductive polymers or carbon-based material etc. in electrode points 136.After the electrode points 136 of iridium oxide material is carried out the modification of carbon-based material, can be with the impedance reduction by 50%～90% of electrode points 136 under the survey frequency of 1KHz, the background noise of the electricity physiological signal that obtains is little, and SNR is high.Further; Can use enzyme technique for fixing counter electrode point 136 to carry out the fixedly modification of enzyme compound; To constitute biosensor the microenvironment around the aixs cylinder is detected; The signal that detects comprises the concentration, amino acid concentration, ionic concn, oxygen concn, temperature, pH value of neurotransmitter etc., thereby obtains the variation of neurotransmitter, L-glutamic acid and the important ionic concn of aixs cylinder in regulation process, and the changing conditions of important indicators such as oxygen, temperature and pH in the environment.For example can counter electrode point 136 carry out after tyrosine oxidase modifies; Can obtain neurotransmitter Dopamine HCL transmitter; Adopt this Dopamine HCL transmitter can be implemented in and implement in the certain space scope to detect the dopamine concentration that the aixs cylinder position discharges, thereby can study the function of neural loop.
Further, can open or close corresponding electrode point 136 targetedly in each electrod-array, optionally nerve trachea 126 carried out partial electric pulse stimulation through micro-fluidic switch is set.
Please combine Fig. 1, Fig. 4 and Fig. 5, drug infusion system 140 comprises drug infusion pond 142, drug catheter 144 and waste liquid pool 146.Drug infusion pond 142 links to each other with waste liquid pool 146 through drug catheter 144.Drug catheter 144 is connected with nerve trachea 126, can be to the capable medicine irritation of advancing by leaps and bounds of the microenvironment axis in the nerve trachea 126.Used medicine can be neurotrophic factor, neurotransmitter, amino acid or gene (like photaesthesia type protein gene etc.) etc.The drug infusion system 140 of this embodiment comprises 9 drug catheters 144.9 drug catheters 144 are communicated with nerve trachea 126 quadratures.Adopt a plurality of drug catheters 144 to carry out the multiple spot medicine irritation or to carry out high-throughout drug screening aixs cylinder, drug release is even, and experimental result is reliable.Further, in each drug catheter 144 micro-fluidic switch can be set, through micro-fluidic switch opens or close corresponding drug catheter, can carry out medicine irritation to the aixs cylinders in the nerve trachea 126 targetedly.
As shown in Figure 6, light regulator control system 150 is located at the top of cell culture system 120.Light regulator control system 150 comprises LASER Light Source (figure does not show), optical fiber interface 152, optical fiber 154 and is used to control the guiding of laser light beam and the waveguide 156 of diameter.Waveguide 156 links to each other with LASER Light Source through optical fiber 154, optical fiber interface 152.The laser that LASER Light Source is sent in waveguide 156 imports in the nerve trachea 126, and aixs cylinder etc. is carried out the light stimulus regulation and control.In implementation process, LASER Light Source mainly sends blueness (wavelength=472nm) or yellow (laser of wavelength=593nm), blueness or yellow laser import in the nerve trachea 126 through optical fiber 154 and waveguide 156 and shine.Because blueness or yellow laser only work to the cell that has imported the photaesthesia gene, so this light regulator control system 150 has cell-specific, and can effectively excited or inhibition neurone.Before making, need the photaesthesia gene be transferred in the neurone with associated loop through special promotor and express with light regulator control system 150.Wherein, the excitatory channel protein gene is Channelrhodopsin-2 (ChR2), and inhibition type channel protein gene is Helorhodopsin (NpHR).Light regulator control system 150 has the neurone of photaesthesia gene that light stimulus is provided through changeing in optical fiber 154 and the waveguide 156 neuralward conduits, causes neuronic excitement or inhibition thus.Express the neurone that the excitatory channel protein gene is arranged with the blue light stimulation, with such neurone of excitement; And stimulate expression that the neurone of inhibition type channel protein gene is arranged with gold-tinted, will suppress such neurone.Just can regulate and control neural circuit through excited or inhibition, thus the research of being correlated with.Because light regulator control system 150 has cell-specific, this photaesthesia gene neuromodulation technology has higher spatial and temporal resolution.
Light regulator control system 150 can comprise a plurality of waveguides 156, waveguide directly can be 1～10 μ m.A plurality of waveguides 156 form waveguide array through micro-processing technology.Can incident laser be divided into the laser array with fixed size through waveguide array, can in waveguide array, add micro-fluidic switch simultaneously, can optionally carry out partial light stimulus, purpose is strong, and spatial and temporal resolution is high.The light stimulus site of waveguide 156 guided lasers is corresponding with the position of electrode points 136, thereby electrode points 136 can comparatively accurately be gathered the electricity physiological signal in light stimulus site targetedly.The light regulator control system 150 of this embodiment has 16 waveguides 156 in the axial distribution of every nerve trachea 126.The diameter of waveguide 156 is 2 μ m.16 waveguides 156 are corresponding with 16 electrode points 136.
In other embodiments, the light regulator control system can also substitute waveguide through different diameter fibers is set.As shown in Figure 7, the light regulator control system 250 in this embodiment comprises LASER Light Source (figure does not show), optical fiber interface 252, divides interface 254 and optical fiber 256.Optical fiber 256 links to each other with LASER Light Source through dividing interface 254, optical fiber interface 252.The diameter of optical fiber 256 can be 1～10 μ m.Preferably, the diameter of optical fiber is 2 μ m.The laser that optical fiber 256 directly sends LASER Light Source imports in the nerve trachea 126.A plurality of optical fiber 256 can form fiber array, can add micro-fluidic switch in the fiber array, optionally nerve trachea 126 are carried out partial light stimulus.
This cell culture apparatus 100 is realized the cultivation of neurocyte through the ad hoc structure of microflow control technique; Can be grown in the cell culture chamber 122 like neurocyte; And aixs cylinder can only be grown in the nerve trachea 126; Neurocyte in the cell culture chamber 122 constitutes neural loop through the aixs cylinder in the nerve trachea 126, and the circulation ratio of cellular growth area and control are stronger relatively; Through laser neurocyte is carried out the regulation and control of high-spatial and temporal resolution again, selectivity and high specificity can be realized the excited and inhibition to neurocyte; Through electrode system 130 stimulations neural loop is carried out assistant regulating and controlling, and the behavior and the function of neural loop detected in real time, spatial and temporal resolution is high, and regulation and control and detected result are reliable.
The above embodiment has only expressed several kinds of embodiments of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to claim of the present invention.Should be pointed out that for the person of ordinary skill of the art under the prerequisite that does not break away from the present invention's design, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with accompanying claims.
Claims (15)
1. a cell culture apparatus is characterized in that, comprising: fixed base plate and be located at cell culture system, light regulator control system and the electrode system on the said fixed base plate; Said cell culture system comprises cell culture chamber and is communicated with the nerve trachea of the confession neural axon growth of said cell culture chamber; Said smooth regulator control system places said nerve trachea top to be used for the culture in the nerve trachea is carried out the light stimulus regulation and control; Said electrode system is common to mutually with said nerve trachea culture in the nerve trachea is carried out assistant regulating and controlling, and the behavior and the function of neural loop detected in real time.
2. cell culture apparatus as claimed in claim 1; It is characterized in that; Also comprise the drug infusion system that is fixed on the said fixed base plate; Said drug infusion system comprises drug infusion pond, drug catheter and waste liquid pool, and said drug infusion pond links to each other with said waste liquid pool through said drug catheter, and said drug catheter is connected with said nerve trachea.
3. cell culture apparatus as claimed in claim 2 is characterized in that said electrode system comprises external contact, lead and electrode points, and said external contact links to each other with said electrode points through said lead, and said nerve trachea communicates with said electrode points.
4. cell culture apparatus as claimed in claim 3; It is characterized in that; Said electrode points deposits the impedance that electro-conductive material is used to reduce electrode points through electrochemical method, and said electrode points is modified with enzyme compound through the enzyme technique for fixing and is used to gather biochemical signals.
5. like claim 3 or 4 described cell culture apparatus, it is characterized in that said electrode system is formed on the said fixed base plate through the mode of sputter or photoetching.
6. cell culture apparatus as claimed in claim 4 is characterized in that, the light stimulus position of said smooth regulator control system is corresponding with the position of said electrode points.
7. cell culture apparatus as claimed in claim 6; It is characterized in that; Said smooth regulator control system comprises LASER Light Source, optical fiber interface, optical fiber and is used to control the waveguide of laser light beam guiding and diameter that said waveguide links to each other with said LASER Light Source through optical fiber, optical fiber interface.
8. cell culture apparatus as claimed in claim 7 is characterized in that, said electrode system comprises a plurality of external one to one contacts, lead and electrode points; A plurality of external contacts center on said fixed base plate uniform distribution all around; A plurality of leads and electrode points form electrod-array, and corresponding, said smooth regulator control system comprises the waveguide of a plurality of different diameters; A plurality of said waveguides form waveguide arrays, in the said waveguide array in the position of waveguide and the said electrod-array electrode points position corresponding one by one; Be provided with micro-fluidic switch in said electrod-array, waveguide array and the said drug catheter.
9. cell culture apparatus as claimed in claim 8 is characterized in that, the width of said nerve trachea is 1～10 μ m, and length is 100～1000 μ m; Said waveguide directly through being 1～10 μ m.
10. cell culture apparatus as claimed in claim 9; It is characterized in that; Said cell culture system comprises two groups of cell culture chambers, and every group of cell culture chamber that comprises two connections is communicated with through 4 nerve tracheas between two groups of cell culture chambers; The diameter of said nerve trachea is 5 μ m, and length is 900 μ m;
Said electrode system axially is provided with 16 square-shaped electrode points successively along each nerve trachea, and the length and width of said electrode points are 5 μ m, between the axial electrode points of each nerve trachea at a distance of 50 μ m;
Said smooth regulator control system comprises 16 waveguides, and the diameter of said waveguide is 2 μ m;
Said drug infusion system comprises a plurality of drug catheters that are communicated with the nerve trachea quadrature.
11. the described cell culture apparatus of claim 6 is characterized in that, said smooth regulator control system comprises LASER Light Source, optical fiber interface, branch interface and optical fiber, and said optical fiber links to each other with said LASER Light Source through dividing interface, optical fiber interface.
12. cell culture apparatus as claimed in claim 11 is characterized in that, said electrode system comprises a plurality of external one to one contacts, lead and electrode points; A plurality of external contacts center on said fixed base plate uniform distribution all around; A plurality of leads and electrode points form electrod-array, and corresponding, said smooth regulator control system comprises a plurality of different diameter fibers; A plurality of said optical fiber form fiber arrays, in the said fiber array in the position of optical fiber and the said electrod-array electrode points position corresponding one by one; Be provided with micro-fluidic switch in said electrod-array, waveguide array and the said drug catheter.
13. cell culture apparatus as claimed in claim 12 is characterized in that, the width of said nerve trachea is 1～10 μ m, and length is 100～1000 μ m; Said optical fiber directly through being 1～10 μ m.
14. cell culture apparatus as claimed in claim 13; It is characterized in that; Said cell culture system comprises two groups of cell culture chambers, and every group of cell culture chamber that comprises two connections is communicated with through 4 nerve tracheas between two groups of cell culture chambers; The diameter of said nerve trachea is 5 μ m, and length is 900 μ m;
Said electrode system axially is provided with 16 square-shaped electrode points successively along each nerve trachea, and the length and width of said electrode points are 5 μ m, between the axial electrode points of each nerve trachea at a distance of 50 μ m;
Said smooth regulator control system comprises 16 optical fiber, and the diameter of said optical fiber is 2 μ m;
Said drug infusion system comprises a plurality of drug catheters that are communicated with the nerve trachea quadrature.
15. cell culture apparatus as claimed in claim 1 is characterized in that, the material of said fixed base plate is glass, silicon or silicon-dioxide; The material of said cell culture chamber and said nerve trachea is the transparent dimethoxysiloxane of gathering.
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| CN107758605A (en) * | 2016-08-16 | 2018-03-06 | 中国科学院上海微系统与信息技术研究所 | A kind of microelectrode array chip and preparation method thereof |
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