CN102337211B - Cell culture device - Google Patents
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- CN102337211B CN102337211B CN 201110246683 CN201110246683A CN102337211B CN 102337211 B CN102337211 B CN 102337211B CN 201110246683 CN201110246683 CN 201110246683 CN 201110246683 A CN201110246683 A CN 201110246683A CN 102337211 B CN102337211 B CN 102337211B
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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, so 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 desirable method.Can make the contact of setting up rule between the neurocyte by vitro culture, three-dimensional contact complicated between the neurone is reduced to two dimension, so that its observation and research are more prone to.
The method of traditional external cultivation of neurocyte is to regulate and control the growth of neurocyte by chemical conversion treatment (Chemically pattemed surface), physics microtexture structure (Physical structure) or strength of solution gradient (Solution gradients) at the cultivation matrix, make it to form neural loop, then regulate and control neurocyte by functional electrostimulation (Functional electrical stimulation) or regional perfusion (Local perfusion).
Wherein, chemical conversion treatment is by chemical process the cell cultures matrix surface to be processed into the biocompatible surface with definite shape, thereby attracts neurocyte at these region growings; It is by 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 concentration growth of cell in certain area that affect the nerves by control biologically active substance (such as polypeptide, albumen).Functional electrostimulation is to be used at present clinical a kind of control methods, has played preferably effect in the treatment for diseases such as essential tremor, parkinsonism and myodystonias.
Yet to form neural loop, the circulation ratio of cellular growth area is relative with control relatively poor by chemical conversion treatment, physics microtexture make up or the chemical concentrations gradient is regulated and control neurocyte growth, thereby the circulation ratio of experiment is relatively poor.Although 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.Although regional perfusion has higher spatial resolution, the position randomness of perfusion is larger, 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 simultaneously neuronal cell cultures, 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 electrode system on the fixed base plate; Cell culture system comprises cell culture chamber and is communicated with the nerve trachea for 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 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 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 by 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, wire and electrode points, and external contact links to each other with electrode points by wire, and nerve trachea communicates with electrode points.
Be applied to such scheme and combination thereof, preferred, wherein electrode points deposits electro-conductive material for reducing the impedance of electrode points by electrochemical method, and electrode points is modified with enzyme compound for gathering biochemical signals by the enzyme technique for fixing.
Be applied to such scheme and combination thereof, preferred, wherein electrode system is formed on the fixed base plate by 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 that LASER Light Source, optical fiber interface, optical fiber reach the waveguide that is used for control laser light beam guiding and diameter, and waveguide links to each other with LASER Light Source by optical fiber, optical fiber interface.
Be applied to such scheme and combination thereof, preferably, wherein electrode system comprises a plurality of one to one external contact, wire and electrode points, a plurality of external contacts evenly distribute around fixed base plate, a plurality of wires 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 by 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 electric limits 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; 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, minute interface and optical fiber, and optical fiber links to each other with LASER Light Source by a minute interface, optical fiber interface.
Be applied to such scheme and combination thereof, preferably, wherein electrode system comprises a plurality of one to one external contact, wire and electrode points, a plurality of external contacts evenly distribute around fixed base plate, a plurality of wires and electrode points form electrod-array, and corresponding, the light regulator control system comprises the optical fiber of a plurality of different diameters, 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 by 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 electric limits 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; 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 transparent poly-dimethoxysiloxane.
This cell culture apparatus is realized the cultivation of neurocyte by the ad hoc structure of microflow control technique, can be grown in the cell culture chamber such as neurocyte, and aixs cylinder can only be grown in the nerve trachea, neurocyte in the culturing room consists of neural loop by the aixs cylinder in the nerve trachea, and the circulation ratio of cellular growth area and control are relatively strong; By 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; By the electrode system stimulation neural loop is carried out assistant regulating and controlling, and 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 cell culture system structural representation in Fig. 1 embodiment;
Fig. 3 is electrod-array and nerve trachea distribution schematic diagram in Fig. 1 embodiment;
Fig. 4 is cell culture system and Drug Infusion system distribution schematic diagram in Fig. 1 embodiment;
Fig. 5 is nerve trachea and drug catheter distribution schematic diagram in Fig. 1 embodiment;
Fig. 6 is light regulator control system and cell culture system distribution schematic diagram in Fig. 1 embodiment;
Fig. 7 is light regulator control system and the cell culture system distribution schematic diagram of another embodiment.
[embodiment]
The below mainly is described in further detail cell culture apparatus in conjunction with the drawings and the specific embodiments.
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 (not shown).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 of mechanically resistant material, mainly plays a part to support fixing.The material that can select has glass, silicon and silicon-dioxide etc.The fixed base plate 110 of present 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 refer to the drawing 2, the cell culture system 120 of present embodiment comprise two groups of totally 4 cell culture chambers 122.Be communicated with by main pipe 124 between every group of cell culture chamber.Main pipe 124 between two groups is communicated with by 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 by nerve trachea 126.Cell culture chamber 122 and nerve trachea 126 are mainly used in the growth of control and guidance neurocyte and the formation of the 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 present 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 only have 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 preferably material is made, such as silicon rubber etc.The cell culture system of present embodiment adopts the poly-dimethoxysiloxane (PDMS) 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 present embodiment, main pipe 124 and nerve trachea 126 can carry out biocompatibility by technology such as surface graft, surface coatings, layer by layer self-assemblies to be processed.In addition, before cell cultures, the internal surface of cell culture chamber 122, main pipe 124 and nerve trachea 126 further can also be coated with processing, and, ln coated such as poly-lysine is coated etc.
Please in conjunction with Fig. 1 and Fig. 3, electrode system 130 comprises external contact 132, wire 134 and electrode points 136.External contact 132 is connected with electrode points 136 by wire 134, each external contact 132 corresponding electrode points 136.A plurality of external contacts 132 evenly arrange around fixed base plate 110, and a plurality of wires 134 and electrode points 136 form electrod-array.Every limit of the fixed base plate 110 of present 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, such as the electrophysiologicalmeasurements measurements instrument of U.S. Plexon company and German MEA company.Nerve trachea 126 axially be aligned in sequence with the electrod-array that is formed by 16 wires 134 and square electric limit 136, the length and width of each electrode points 136 are 5 μ m, interval 50 μ m between per two electrode points 136.Nerve trachea 126 communicates with electrode points 136, thereby electrod-array can carry out to the culture in the nerve trachea 126 electrophysiologicalmeasurements measurements and the electric pulse stimulation of high-spatial and temporal resolution.
Preferably, the electrode system 130 of present embodiment is the surface that is formed on fixed base plate 110 by the mode of sputter or photoetching.The material of wire 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, come the growth of neurocyte is induced by the strength of electric field that changes in microenvironment, and can study neural loop and neural plasticity.For reducing the contact impedance of electrode points 136, strengthen the signal to noise ratio of electricity physiological signal, can be by the surface deposition decorative material of electrochemical method in electrode points 136, such as iridium oxide, conductive polymers or carbon-based material etc.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 signal to noise ratio is high.Further, can use the enzyme technique for fixing electrode points 136 to be carried out the fixedly modification of enzyme compound, to consist of 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 obtain the variation of neurotransmitter, L-glutamic acid and the important ionic concn of aixs cylinder in regulation process, and the changing conditions of the important indicators such as oxygen, temperature and pH in the environment.After for example can carrying out the tyrosine oxidase modification to electrode points 136, can obtain the neurotransmitter Dopamine Sensor, adopt this Dopamine Sensor to can be implemented in the dopamine concentration that examinations aixs cylinder position discharges in the certain space scope, thereby can study the function of neural loop.
Further, can open or close targetedly corresponding electrode points 136 by micro-fluidic switch is set in each electrod-array, optionally nerve trachea 126 be carried out local electric pulse stimulation.
Please in conjunction with 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 by 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 (such as photaesthesia type protein gene etc.) etc.The Drug Infusion system 140 of present 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, by 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 (not shown), optical fiber interface 152, optical fiber 154 and is used for the guiding of control laser light beam and the waveguide 156 of diameter.Waveguide 156 links to each other with LASER Light Source by 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 is mainly sent blueness (wavelength=472nm) or yellow (laser of wavelength=593nm), blueness or yellow laser import in the nerve trachea 126 by 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 effectively excitement or inhibitory neuron.Before making with light regulator control system 150, need to be transferred to neurone with associated loop in by special promotor the photaesthesia gene and express.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 by turning in optical fiber 154 and the waveguide 156 neuralward conduits, causes thus neuronic excitement or inhibition.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 by 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 by micro-processing technology.The laser of incident can be divided into the laser array with fixed size by waveguide array, can add micro-fluidic switch simultaneously in waveguide array, can optionally carry out local 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 gather the electricity physiological signal in light stimulus site targetedly.The light regulator control system 150 of present 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 by the optical fiber that different diameter is set.As shown in Figure 7, the light regulator control system 250 in the present embodiment comprises LASER Light Source (not shown), optical fiber interface 252, minute interface 254 and optical fiber 256.Optical fiber 256 links to each other with LASER Light Source by a minute 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 local light stimulus.
This cell culture apparatus 100 is realized the cultivation of neurocyte by the ad hoc structure of microflow control technique, can be grown in the cell culture chamber 122 such as neurocyte, and aixs cylinder can only be grown in the nerve trachea 126, neurocyte in the cell culture chamber 122 consists of neural loop by the aixs cylinder in the nerve trachea 126, and the circulation ratio of cellular growth area and control are relatively strong; By 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; By electrode system 130 stimulations neural loop is carried out assistant regulating and controlling, and 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 embodiment 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 without departing from the inventive concept of the premise, 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 claims.
Claims (11)
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 electrode system on the described fixed base plate; Described cell culture system comprises cell culture chamber and is communicated with the nerve trachea for neural axon growth of described cell culture chamber; Described smooth regulator control system places described nerve trachea top to be used for the culture in the nerve trachea is carried out the light stimulus regulation and control; Described electrode system is common to mutually with described nerve trachea culture in the nerve trachea is carried out assistant regulating and controlling, and behavior and the function of neural loop detected in real time; Described electrode system comprises external contact, wire and electrode points, and described external contact links to each other with described electrode points by described wire, and described nerve trachea communicates with described electrode points; Described electrode points deposits electro-conductive material for reducing the impedance of electrode points by electrochemical method, and described electrode points is modified with enzyme compound for gathering biochemical signals by the enzyme technique for fixing; The light stimulus position of described smooth regulator control system is corresponding with the position of described electrode points; Described smooth regulator control system comprises LASER Light Source, optical fiber interface, optical fiber and is used for the waveguide of control laser light beam guiding and diameter that described waveguide links to each other with described LASER Light Source by optical fiber, optical fiber interface.
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 described fixed base plate, described Drug Infusion system comprises drug infusion pond, drug catheter and waste liquid pool, described drug infusion pond links to each other with described waste liquid pool by described drug catheter, and described drug catheter is connected with described nerve trachea.
3. cell culture apparatus as claimed in claim 1 is characterized in that, described electrode system is formed on the described fixed base plate by the mode of sputter or photoetching.
4. cell culture apparatus as claimed in claim 2, it is characterized in that, described electrode system comprises a plurality of one to one external contact, wire and electrode points, a plurality of external contacts evenly distribute around described fixed base plate, a plurality of wires and electrode points form electrod-array, and corresponding, described smooth regulator control system comprises the waveguide of a plurality of different diameters, a plurality of described waveguides form waveguide arrays, in the described waveguide array in the position of waveguide and the described electrod-array electrode points position corresponding one by one; Be provided with micro-fluidic switch in described electrod-array, waveguide array and the described drug catheter.
5. cell culture apparatus as claimed in claim 4 is characterized in that, the width of described nerve trachea is 1 ~ 10 μ m, and length is 100 ~ 1000 μ m; The diameter of described waveguide is 1 ~ 10 μ m.
6. cell culture apparatus as claimed in claim 5, it is characterized in that, described cell culture system comprises two groups of cell culture chambers, every group of cell culture chamber that comprises two connections, be communicated with by 4 nerve tracheas between two groups of cell culture chambers, the diameter of described nerve trachea is 5 μ m, and length is 900 μ m;
Described electrode system axially is provided with 16 square electric limits successively along each nerve trachea, and the length and width of described electrode points are 5 μ m, between the axial electrode points of each nerve trachea at a distance of 50 μ m;
Described smooth regulator control system comprises 16 waveguides, and the diameter of described waveguide is 2 μ m;
Described Drug Infusion system comprises a plurality of drug catheters that are communicated with the nerve trachea quadrature.
7. cell culture apparatus claimed in claim 2 is characterized in that, described smooth regulator control system comprises LASER Light Source, optical fiber interface, minute interface and optical fiber, and described optical fiber links to each other with described LASER Light Source by a minute interface, optical fiber interface.
8. cell culture apparatus as claimed in claim 7, it is characterized in that, described electrode system comprises a plurality of one to one external contact, wire and electrode points, a plurality of external contacts evenly distribute around described fixed base plate, a plurality of wires and electrode points form electrod-array, and corresponding, described smooth regulator control system comprises the optical fiber of a plurality of different diameters, a plurality of described optical fiber form fiber arrays, in the described fiber array in the position of optical fiber and the described electrod-array electrode points position corresponding one by one; Be provided with micro-fluidic switch in described electrod-array, waveguide array and the described drug catheter.
9. cell culture apparatus as claimed in claim 8 is characterized in that, the width of described nerve trachea is 1 ~ 10 μ m, and length is 100 ~ 1000 μ m; The diameter of described optical fiber is 1 ~ 10 μ m.
10. cell culture apparatus as claimed in claim 9, it is characterized in that, described cell culture system comprises two groups of cell culture chambers, every group of cell culture chamber that comprises two connections, be communicated with by 4 nerve tracheas between two groups of cell culture chambers, the diameter of described nerve trachea is 5 μ m, and length is 900 μ m;
Described electrode system axially is provided with 16 square electric limits successively along each nerve trachea, and the length and width of described electrode points are 5 μ m, between the axial electrode points of each nerve trachea at a distance of 50 μ m;
Described smooth regulator control system comprises 16 optical fiber, and the diameter of described optical fiber is 2 μ m;
Described Drug Infusion system comprises a plurality of drug catheters that are communicated with the nerve trachea quadrature.
11. cell culture apparatus as claimed in claim 1 is characterized in that, the material of described fixed base plate is glass, silicon or silicon-dioxide; The material of described cell culture chamber and described nerve trachea is transparent poly-dimethoxysiloxane.
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| CN103173355A (en) * | 2013-04-18 | 2013-06-26 | 中国医学科学院生物医学工程研究所 | Cell culture incubator with low-level laser environment |
| CN107758605B (en) * | 2016-08-16 | 2020-01-31 | 中国科学院上海微***与信息技术研究所 | microelectrode array chips and its preparing process |
| CN112662554B (en) * | 2020-12-31 | 2022-11-04 | 北京工业大学 | Microfluidic platform, preparation method and application thereof |
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| CN1439432A (en) * | 2003-03-21 | 2003-09-03 | 东华大学 | Nervous duct and membrane with fixed nerve regeneration promoting agent with surface modified by plasma and their preparations |
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