CN102360007A - Well-type neurochip and preparation method thereof - Google Patents
Well-type neurochip and preparation method thereof Download PDFInfo
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- CN102360007A CN102360007A CN2011101725635A CN201110172563A CN102360007A CN 102360007 A CN102360007 A CN 102360007A CN 2011101725635 A CN2011101725635 A CN 2011101725635A CN 201110172563 A CN201110172563 A CN 201110172563A CN 102360007 A CN102360007 A CN 102360007A
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Abstract
The invention discloses a well-type neurochip and a preparation method thereof, belonging to the technical field of in vitro electrophysiological measurement equipment for nerves. The neurochip comprises a chip unit and a culture chamber, and the chip unit comprises a substrate, metal lead wires microelectrodes, an insulating layer and neural wells. The preparation method for the neurochip comprises the following steps: sputtering a gold coating on the substrate to form a metal lead wire layer; forming the insulating layer by using the method of plasma enhanced chemical vapor deposition; applying reactive ion etching on the insulating layer so as to allow the microelectrodes to be exposed; electroplating platinum-black on the microelectrodes; preparing polydimethylsiloxane dies over the microelectrodes, injecting a chitosan solution into the dies, carrying out freeze drying on the dies to obtain porous well type walls, and tearing off the polydimethylsiloxane dies to form the chip unit; allowing the culture chamber and the chip unit to be in seamless connection. According to the invention, a chitosan network structure of neural well walls allows neurites to pass through but does not allow nerve cells to pass through; therefore, the neurochip in the invention can be used for positioning electrophysiological measurement of nerve cells.
Description
Technical field
The invention belongs to neuron soma dispatch from foreign news agency physiological measurement device technical field, be specifically related to a kind of well type neuro chip and preparation method thereof.
Background technology
Neuro chip is meant can be at neurocyte, tissue or system level hyperchannel, detect the micro device general name of neuroelectricity physiological signal or neurotransmitter in real time; The plane neuro chip is 1972 by people such as Thomas report the earliest, is used to write down in vitro culture cardiac muscle cell's electrical activity.
But this neuro chip faces a problem: the neurocyte of in vitro culture can stick in the substrate at random; Be not to be accurately positioned on the electrode; Cause the attaching property of most of cell and electrode relatively poor or distance is arranged, so electro photoluminescence might occur on the different parts of different cells with electrical signal detection.Because the spatial relation of extracellular electrode record electric signal pair cell and electrode is very responsive; Cause the electric signal amplitude (particularly the neural network to early development stage writes down) often less than normal that obtains; Shape is also complicated, so be unfavorable for the software sorting of electric signal and confirm corresponding neurocyte.Therefore, if can provide a kind of method with celluar localization on recording electrode, with the detection performance that strengthens chip greatly and enlarge its scope of application.The method of present common control celluar localization mainly contains two kinds.A kind of method is through chemical modification method, utilizes the attaching property difference of cell on different materials, realizes celluar localization.Second method is to make structures such as miniature pit, groove through micro-processing method.
The present invention is intended to utilize micro-machined method to make a kind of well type neuro chip; Mode through the neural well of preparation above electrode strengthens the detection performance of neuro chip, guarantees when wherein its borehole wall can allow nervous process to pass through that cell space is positioned at the electrode top.
Summary of the invention
The object of the present invention is to provide a kind of neuro chip that can satisfy man-to-man related, the small-sized neural network bioelectrical activity of research between electrode and the neurocyte.
The present invention also aims to provide the preparation method of above-mentioned neuro chip.
A kind of well type neuro chip, this neuro chip is made up of chip unit and culture chamber; Chip unit is by substrate, metal lead wire, microelectrode, insulation course and neural well construction; Substrate is a glass; Metal lead wire is a gold; Microelectrode array is arranged in the substrate, and the diameter of microelectrode is between 10 μ m～50 μ m, and microelectrode array is a dot matrix; Microelectrode quantity is 4～128; Spacing between microelectrode and the microelectrode is 100 μ m～500 μ m, and the platinum black processing is carried out on the microelectrode surface, and insulation course is SiO
2And Si
3N
4Mixolimnion; The corresponding microelectrode of each neural well; The wall of neural well is made up of chitosan multi-porous network, and porosity is greater than 90%, and the aperture is between 1 μ m～5 μ m.
Connected mode between culture chamber and chip unit is seamless link.
A kind of preparation method of well type neuro chip, carry out according to following steps:
(1) selects SiO
2Glass is substrate, at sputter one deck on glass
Golden film, utilize lift-off technology to form electrode and pin configuration;
(2) in the substrate that step (1) forms, use the plasma enhanced chemical vapor deposition method to form SiO
2-Si
3N
4-SiO
2The insulation course of sandwich type does from bottom to top
Thick SiO
2Layer,
Thick SiN
4The layer with
Thick SiO
2Layer;
(3) in the position of electrode, the insulation course of sandwich type is applied reactive ion etching, expose electrode;
The electrode that (4) will expose is electroplated platinum black through electrochemical plating;
(5) on step (4) basis, spin coating photoresist SU-8 2050 on base material, above each electrode, etching a diameter then is that 50 μ m～150 μ m, height are the SU-8 cylindrical cavity of 30 μ m～70 μ m;
(6) be that 10: 1 mixed is even with dimethyl siloxane and SYGARD 184 elastomer silicones according to mass ratio at ambient temperature; Pour in the above-mentioned sample; Make the dimethyl silicone polymer liquid level exceed SU-8 2050 upper surfaces 200 μ m-1000 μ m, in 60 ℃, solidified 2～3 hours then; Above-mentioned sample is put into plasma generator, utilize the oxygen plasma oxidation to dispose SU-8 2050, above electrode, forming diameter is that 50 μ m～150 μ m, height are the dimethyl silicone polymer mould of the cylindrical protrusion of 30 μ m～70 μ m;
(7) shitosan being dissolved in mass concentration is in 2% the acetum, forms mass concentration and be 2% chitosan solution; Add mass concentration therein and be 0.25% glutaraldehyde, stir crosslinked; Then it is injected in the dimethyl silicone polymer mould of step (6) formation; It was implanted under-196 ℃～-80 ℃ the environment pre-freeze more than 12 hours; With its freeze drying, form porous chitosan well type wall then;
(8) remove the dimethyl silicone polymer mould, form the well structure of forming by the porous chitosan wall;
(9) with the material of step (8) gained, in the NaOH of 0.1M solution, soaked 2-7 hour, then it being immersed in mass concentration is in 1%～2% sodium borohydride solution 6 hours, secondary freeze drying is processed chip unit;
(10) will not have the glass culture chamber at the end, and use silicone resin itself and the seamless adhesion of chip unit.
Beneficial effect of the present invention: the invention has the advantages that neural well construction can fetter pericaryon; The shitosan reticulate texture of its neural well wall can allow nervous process to pass through; But neurocyte can not pass through, and can be used for neurocyte location electrophysiologicalmeasurements measurements.Realized between electrode and the neurocyte man-to-man relatedly, can a beneficial tools be provided for the small-sized neural network research of in vitro culture.
Description of drawings
Fig. 1 is the sectional view of well type neuro chip electrode zone;
Among the figure, 101-SiO
2Substrate glasses, 102-gold electrode and gold wire, 103-SiO
2/ Si
3N
4/ SiO
2The insulation course of sandwich structure, 104-platinum black, the neural well porous chitosan of 105-wall.
Embodiment
Below in conjunction with accompanying drawing and specific embodiment the present invention is further specified.
It is pure that the employed acetic acid of following examples, glutaraldehyde, NaOH, sodium borohydride, dimethyl siloxane are analysis; The deacetylation molecular weight of shitosan is greater than 85%, and molecular weight is about 200,000; All the other materials are commercially produced product.
Embodiment 1
The well type neuro chip of present embodiment is formed (as shown in Figure 1) by the chip unit and the culture chamber at a no end.Chip unit is by substrate, metal lead wire, microelectrode, insulation course and neural well construction; Substrate is a glass; Metal lead wire is a gold; Microelectrode array is arranged in the substrate, and the diameter of microelectrode is 50 μ m, and microelectrode array is a dot matrix, and microelectrode quantity is 16, and the spacing between microelectrode and the microelectrode is 500 μ m, and the platinum black processing is carried out on the microelectrode surface, and insulation course is SiO
2And Si
3N
4Mixolimnion; The corresponding microelectrode of each neural well; The wall of neural well is made up of chitosan multi-porous network, and porosity is greater than 90%, and the aperture is 5 μ m.
The preparation method of this well type neuro chip, carry out according to following steps:
1) chip unit of preparation microelectrode array device
(1) used SiO
2Substrate cleans up;
(2) splash-proofing sputtering metal layer; Metal is Au, and thickness is
(3) measure dot matrix with the first mask plates photoetching, 4 * 4 matrix potential electrode, lead-in wire, and carry out etching; Wherein have 16 microelectrodes, the microelectrode diameter is 50 μ m, and electrode separation is 500 μ m;
(4) use the plasma-enhanced chemical vapor deposition insulation course, this layer structure is SiO
2 
-Si
3N
4 -SiO
2 
(5), use wet method, dry method to replace the etching insulation course with the second mask plates lithography measurements electrode;
(6) use constant flow method, in ultrasound environments, electroplate platinum black;
(7) scribing and the cleaning of removing photoresist;
(8) spin coating photoresist SU-8 2050 with three mask plates photoetching well structure, and carries out etching, and forming diameter is 100 μ m, and height is the SU-8 cylindrical cavity of 50 μ m;
(9) be that 10: 1 mixed is even with dimethyl siloxane and SYGARD 184 elastomer silicones according to mass ratio at ambient temperature, pour in the above-mentioned sample, in 60 ℃, solidified 2～3 hours then;
(10) above-mentioned sample is put into plasma generator, utilize the oxygen plasma oxidation to dispose SU-82050;
(11) shitosan being dissolved in mass concentration is in 2% the acetum, forms mass concentration and be 2% chitosan solution; Add mass concentration therein and be 0.25% glutaraldehyde, stir crosslinked; Chitosan solution is injected into has in the well type dimethyl silicone polymer mould, it is implanted pre-freeze under-196 ℃ the environment, then with its freeze drying;
(12) remove the dimethyl silicone polymer mould;
(13) with the material of gained, in the NaOH solution of 0.1M, soaked 2-7 hour, then it being immersed in quality is in 1%～2% sodium borohydride 6 hours, secondary freeze drying.
2) adhesion of cultivation cavity
Utilize no end culture chamber and the chip unit seamless link of silicone resin, guarantee that electrode and neural well are in the chamber glass material.
Embodiment 2
The well type neuro chip of present embodiment is made up of the chip unit and the culture chamber at a no end.Chip unit is by substrate, metal lead wire, microelectrode, insulation course and neural well construction; Substrate is a glass; Metal lead wire is a gold; Microelectrode array is arranged in the substrate, and the diameter of microelectrode is 30 μ m, and microelectrode array is a dot matrix, and microelectrode quantity is 32, and the spacing between microelectrode and the microelectrode is 300 μ m, and the platinum black processing is carried out on the microelectrode surface, and insulation course is SiO
2And Si
3N
4Mixolimnion; The corresponding microelectrode of each neural well; The wall of neural well is made up of chitosan multi-porous network, and porosity is greater than 90%, and the aperture is 3 μ m.
The preparation method of this well type neuro chip, carry out according to following steps:
1) chip unit of preparation microelectrode array device
(1) used SiO
2Substrate cleans up;
(2) splash-proofing sputtering metal layer; Metal is Au, and thickness is
(3) measure dot matrix with the first mask plates photoetching, 4 * 8 matrix potential electrode, lead-in wire, and carry out etching, and wherein having 32 electrodes, electrode diameter is 30 μ m, electrode separation is 300 μ m;
(4) use the plasma-enhanced chemical vapor deposition insulation course, this layer structure is SiO
2 
-Si
3N
4 
-SiO
2 
(5), use wet method, dry method to replace the etching insulation course with the second mask plates lithography measurements electrode;
(6) use constant flow method, in ultrasound environments, electroplate platinum black;
(7) scribing and the cleaning of removing photoresist;
(8) spin coating photoresist SU-8 2050 with three mask plates photoetching well structure, and carries out etching, and forming diameter is 50 μ m, and height is the SU-8 cylindrical cavity of 70 μ m;
(9) be that 10: 1 mixed is even with dimethyl siloxane and SYGARD 184 elastomer silicones according to mass ratio at ambient temperature, pour in the above-mentioned sample, in 60 ℃, solidified 2～3 hours then;
(10) above-mentioned sample is put into plasma generator, utilize the oxygen plasma oxidation to dispose SU-82050;
(11) shitosan being dissolved in mass concentration is in 2% the acetum, forms mass concentration and be 2% chitosan solution; Add mass concentration therein and be 0.25% glutaraldehyde, stir crosslinked; Chitosan solution is injected into has in the well type dimethyl silicone polymer mould, it is implanted pre-freeze under-196 ℃ the environment, then with its freeze drying;
(12) remove the dimethyl silicone polymer mould;
(13) with the material of gained, in the NaOH solution of 0.1M, soaked 2-7 hour, then it is immersed in mass concentration for being in 1%～2% sodium borohydride 6 hours, secondary freeze drying.
2) adhesion of cultivation cavity
Utilize no end culture chamber and the chip unit seamless link of silicone resin, guarantee that electrode and neural well are in the chamber glass material.
Embodiment 3
The well type neuro chip of present embodiment is made up of the chip unit and the culture chamber at a no end.Chip unit is by substrate, metal lead wire, microelectrode, insulation course and neural well construction; Substrate is a glass; Metal lead wire is a gold; Microelectrode array is arranged in the substrate, and the diameter of microelectrode is 30 μ m, and microelectrode array is a dot matrix, and microelectrode quantity is 19, and the spacing between microelectrode and the microelectrode is 200 μ m, and the platinum black processing is carried out on the microelectrode surface, and insulation course is SiO
2And Si
3N
4Mixolimnion; The corresponding microelectrode of each neural well; The wall of neural well is made up of chitosan multi-porous network, and porosity is greater than 90%, and the aperture is 4 μ m.
The preparation method of this well type neuro chip, carry out according to following steps:
1) chip unit of preparation microelectrode array device
(1) used SiO
2Substrate cleans up;
(2) splash-proofing sputtering metal layer; Metal is Au, and thickness is
(3) with the first mask plates photoetching hexagon potential electrode dot matrix, lead-in wire, and carry out etching.Wherein have 19 electrodes, electrode diameter is 30 μ m, and electrode separation is 200 μ m;
(4) use the plasma-enhanced chemical vapor deposition insulation course, this layer structure is SiO
2 
-Si
3N
4 
-SiO
2
(5), use wet method, dry method to replace the etching insulation course with the second mask plates lithography measurements electrode;
(6) use constant flow method, in ultrasound environments, electroplate platinum black;
(7) scribing and the cleaning of removing photoresist;
(8) spin coating photoresist SU-8 2050 with three mask plates photoetching well structure, and carries out etching, and forming diameter is the SU-8 cylindrical cavity that 150 μ m height are about 30 μ m;
(9) be that 10: 1 mixed is even with dimethyl siloxane and SYGARD 184 elastomer silicones according to mass ratio at ambient temperature, pour in the above-mentioned sample, in 60 ℃, solidified 2～3 hours then;
(10) above-mentioned sample is put into plasma generator, utilize the oxygen plasma oxidation to dispose SU-82050;
(11) shitosan being dissolved in mass concentration is in 2% the acetum, forms mass concentration and be 2% chitosan solution; Add mass concentration therein and be 0.25% glutaraldehyde, stir crosslinked; Chitosan solution is injected into has in the well type dimethyl silicone polymer mould, it is implanted pre-freeze under-120 ℃ the environment, more than 12 hours; Then with its freeze drying;
(12) remove the dimethyl silicone polymer mould;
(13) with the material of gained, in the NaOH solution of 0.1M, soaked 2-7 hour, then it is immersed in mass concentration for being in 1%～2% sodium borohydride 6 hours, secondary freeze drying.
2) adhesion of cultivation cavity
Utilize no end culture chamber and the chip unit seamless link of silicone resin, guarantee that electrode and neural well are in the chamber glass material.
Embodiment 4
The well type neuro chip of present embodiment is made up of the chip unit and the culture chamber at a no end.Chip unit is by substrate, metal lead wire, microelectrode, insulation course and neural well construction; Substrate is a glass; Metal lead wire is a gold; Microelectrode array is arranged in the substrate, and the diameter of microelectrode is 10 μ m, and microelectrode array is a dot matrix, and microelectrode quantity is 64, and the spacing between microelectrode and the microelectrode is 100 μ m, and the platinum black processing is carried out on the microelectrode surface, and insulation course is SiO
2And Si
3N
4Mixolimnion; The corresponding microelectrode of each neural well; The wall of neural well is made up of chitosan multi-porous network, and porosity is greater than 90%, and the aperture is 2 μ m.
The preparation method of this well type neuro chip, carry out according to following steps:
1) chip unit of preparation microelectrode array device
(1) used SiO
2Substrate cleans up;
(2) splash-proofing sputtering metal layer; Metal is Au, and thickness is
(3) measure dot matrix with the first mask plates photoetching, 8 * 8 matrix potential electrode, lead-in wire, and carry out etching; Wherein have 64 electrodes, electrode diameter is 10 μ m, and electrode separation is 100 μ m;
(4) use the plasma-enhanced chemical vapor deposition insulation course, this layer structure is SiO
2 
-Si
3N
4 
-SiO
2 
(5), use wet method, dry method to replace the etching insulation course with the second mask plates lithography measurements electrode;
(6) use constant flow method, in ultrasound environments, electroplate platinum black;
(7) scribing and the cleaning of removing photoresist;
(8) spin coating photoresist SU-8 2050 with three mask plates photoetching well structure, and carries out etching, and forming diameter is the SU-8 cylindrical cavity that 150 μ m height are about 70 μ m;
(9) be that 10: 1 mixed is even with dimethyl siloxane and SYGARD 184 elastomer silicones according to mass ratio at ambient temperature, pour in the above-mentioned sample, in 60 ℃, solidified 2～3 hours then;
(10) above-mentioned sample is put into plasma generator, utilize the oxygen plasma oxidation to dispose SU-82050;
(11) shitosan being dissolved in mass concentration is in 2% the acetum, forms mass concentration and be 2% chitosan solution; Add mass concentration therein and be 0.25% glutaraldehyde, stir crosslinked; Chitosan solution is injected into has in the well type dimethyl silicone polymer mould, it is implanted pre-freeze under-150 ℃ the environment, more than 12 hours, then with its freeze drying;
(12) remove the dimethyl silicone polymer mould;
(13) with the material of gained, in the NaOH solution of 0.1M, soaked 2-7 hour, then it being immersed in mass concentration is in 1%～2% sodium borohydride 6 hours, secondary freeze drying.
2) adhesion of cultivation cavity
Utilize no end culture chamber and the chip unit seamless link of silicone resin, guarantee that electrode and neural well are in the chamber glass material.
Embodiment 5
The well type neuro chip of present embodiment is made up of the chip unit and the culture chamber at a no end.Chip unit is by substrate, metal lead wire, microelectrode, insulation course and neural well construction; Substrate is a glass; Metal lead wire is a gold; Microelectrode array is arranged in the substrate, and the diameter of microelectrode is 10 μ m, and microelectrode array is a dot matrix, and microelectrode quantity is 32, and the spacing between microelectrode and the microelectrode is 100 μ m, and the platinum black processing is carried out on the microelectrode surface, and insulation course is SiO
2And Si
3N
4Mixolimnion; The corresponding microelectrode of each neural well; The wall of neural well is made up of chitosan multi-porous network, and porosity is greater than 90%, and the aperture is 3 μ m.
The preparation method of this well type neuro chip, carry out according to following steps:
1) chip unit of preparation microelectrode array device
(1) used SiO
2Substrate cleans up;
(2) splash-proofing sputtering metal layer; Metal is Au, and thickness is
(3) with the first mask plates photoetching, 4 * 4+4 * 4 double-matrix potential electrode dot matrix, lead-in wire, and carry out etching; Wherein have 32 electrodes, electrode diameter is 10 μ m, and electrode separation is 100 μ m in the same rectangular lattice, and two matrix centre distances are 3000 μ m;
(4) use the plasma-enhanced chemical vapor deposition insulation course, this layer structure is SiO
2 
-Si
3N
4 
-SiO
2 
(5), use wet method, dry method to replace the etching insulation course with the second mask plates lithography measurements electrode;
(6) use constant flow method, in ultrasound environments, electroplate platinum black;
(7) scribing and the cleaning of removing photoresist;
(8) spin coating photoresist SU-8 2050 with three mask plates photoetching well structure, and carries out etching, and forming diameter is 50 μ m, and height is the SU-8 cylindrical cavity of 30 μ m;
(9) be that 10: 1 mixed is even with dimethyl siloxane and SYGARD 184 elastomer silicones according to mass ratio at ambient temperature, pour in the above-mentioned sample, in 60 ℃, solidified 2～3 hours then;
(10) above-mentioned sample is put into plasma generator, utilize the oxygen plasma oxidation to dispose SU-82050;
(11) shitosan being dissolved in mass concentration is in 2% the acetum, forms mass concentration and be 2% chitosan solution; Add mass concentration therein and be 0.25% glutaraldehyde, stir crosslinked; Chitosan solution is injected into has in the well type dimethyl silicone polymer mould, it is implanted pre-freeze under-196 ℃ the environment, then with its freeze drying.
(12) remove the dimethyl silicone polymer mould;
(13) with the material of gained, in the NaOH solution of 0.1M, soaked 2-7 hour, then it is immersed in mass concentration for being in 1%～2% sodium borohydride 6 hours, secondary freeze drying.
2) adhesion of cultivation cavity
Utilize no end culture chamber and the chip unit seamless link of silicone resin, guarantee that electrode and neural well are in the chamber glass material.
Claims (3)
1. a well type neuro chip is characterized in that this neuro chip is made up of chip unit and culture chamber; Chip unit is by substrate, metal lead wire, microelectrode, insulation course and neural well construction; Substrate is a glass; Metal lead wire is a gold; Microelectrode array is arranged in the substrate, and the diameter of microelectrode is between 10 μ m～50 μ m, and microelectrode array is a dot matrix; Microelectrode quantity is 4～128; Spacing between microelectrode and the microelectrode is 100 μ m～500 μ m, and the platinum black processing is carried out on the microelectrode surface, and insulation course is SiO
2And Si
3N
4Mixolimnion; The corresponding microelectrode of each neural well; The wall of neural well is made up of chitosan multi-porous network, and porosity is greater than 90%, and the aperture is between 1 μ m～5 μ m.
2. according to the said a kind of well type neuro chip of claim 1, it is characterized in that the connected mode between culture chamber and chip unit is seamless link.
3. the preparation method of well type neuro chip according to claim 1 is characterized in that, carries out according to following steps:
(1) selects SiO
2Glass is substrate, at sputter one deck on glass
Golden film, utilize lift-off technology to form electrode and pin configuration;
(2) in the substrate that step (1) forms, use the plasma enhanced chemical vapor deposition method to form SiO
2-Si
3N
4-SiO
2The insulation course of sandwich type does from bottom to top
Thick SiO
2Layer,
Thick SiN
4The layer with
Thick SiO
2Layer;
(3) in the position of electrode, the insulation course of sandwich type is applied reactive ion etching, expose electrode;
The electrode that (4) will expose is electroplated platinum black through electrochemical plating;
(5) on step (4) basis, spin coating photoresist SU-8 2050 on base material, above each electrode, etching a diameter then is that 50 μ m～150 μ m, height are the SU-8 cylindrical cavity of 30 μ m～70 μ m;
(6) be that 10: 1 mixed is even with dimethyl siloxane and SYGARD 184 elastomer silicones according to mass ratio at ambient temperature; Pour in the above-mentioned sample; Make the dimethyl silicone polymer liquid level exceed SU-8 2050 upper surfaces 200 μ m-1000 μ m, in 60 ℃, solidified 2～3 hours then; Above-mentioned sample is put into plasma generator, utilize the oxygen plasma oxidation to dispose SU-8 2050, above electrode, forming diameter is that 50 μ m～150 μ m, height are the dimethyl silicone polymer mould of the cylindrical protrusion of 30 μ m～70 μ m;
(7) shitosan being dissolved in mass concentration is in 2% the acetum, forms mass concentration and be 2% chitosan solution; Add mass concentration therein and be 0.25% glutaraldehyde, stir crosslinked; Then it is injected in the dimethyl silicone polymer mould of step (6) formation; It was implanted under-196 ℃～-80 ℃ the environment pre-freeze more than 12 hours; With its freeze drying, form porous chitosan well type wall then;
(8) remove the dimethyl silicone polymer mould, form the well structure of forming by the porous chitosan wall;
(9) with the material of step (8) gained, in the NaOH of 0.1M solution, soaked 2-7 hour, then it being immersed in mass concentration is in 1%～2% sodium borohydride solution 6 hours, secondary freeze drying is processed chip unit;
(10) will not have the glass culture chamber at the end, and use silicone resin itself and the seamless adhesion of chip unit.
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| CN105420105A (en) * | 2015-12-25 | 2016-03-23 | 北京工业大学 | Biochip and manufacturing method thereof |
| CN108254414A (en) * | 2018-03-09 | 2018-07-06 | 国家纳米科学中心 | A kind of flexible in vitro micro- raceway groove microelectrode array integrated chip and its preparation method and application |
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