CN110367979A - It is a kind of to record and regulate and control based on nanometer pin electrode flexible microfluidic control device and preparation method thereof for brain tissue electric signal - Google Patents
It is a kind of to record and regulate and control based on nanometer pin electrode flexible microfluidic control device and preparation method thereof for brain tissue electric signal Download PDFInfo
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- CN110367979A CN110367979A CN201910777277.8A CN201910777277A CN110367979A CN 110367979 A CN110367979 A CN 110367979A CN 201910777277 A CN201910777277 A CN 201910777277A CN 110367979 A CN110367979 A CN 110367979A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/25—Bioelectric electrodes therefor
- A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
- A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y35/00—Methods or apparatus for measurement or analysis of nanostructures
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/0209—Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
- A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
Abstract
The invention belongs to microfluidic control technical fields, it is specific open a kind of based on nanometer pin electrode flexible microfluidic control device, there is the cell culture container of through-hole among including nanoneedle sensor and made of PDMS module, nanoneedle sensor includes hollow gold nanometer pin electrode array, snakelike flexible wire, to electrode, and hollow gold nanometer pin electrode array is packaged by insulating layer, hollow gold nanometer pin electrode array is placed in the bottom of cell culture apparatus and practically corresponds to lead to the hole site, and gold nano needle side upward and have part from the bottom of through-hole expose.The micro fluidic device has preferable biocompatibility, has expanded thinking for the selection of nerve electrode material；Hollow gold nanometer pin electrode array surface product is big simultaneously, and density is high, and size is small, and stable, high s/n ratio neural recording may be implemented；It can be adapted with biological tissue, good biocompatibility, suitable for implanting, have a good application prospect, in addition, it can be realized simultaneously intracellular recording, high-flux parallel record and records in body tissue.
Description
Technical field
The invention belongs to microfluidic control technical field, in particular to a kind of base recorded for brain tissue electric signal with regulation
In nanometer pin electrode flexible microfluidic control device and preparation method thereof.
Background technique
Human brain neuron is numerous, and the connection and working mechanism studied between neuron are comprehensive to Alzheimer is treated
The neurodegenerative diseases important in inhibiting such as disease, Huntingdon syndrome, parkinsonism.Brain machine interface (Brain-
Machine interface, BMI) it is a part important in neural engineering, as directly logical between brain and external equipment
Believe access, by combining various new techniques, the development of artificial limb and novel input equipment can be promoted.It is most important in brain machine interface
Building block be nerve electrode, in order to monitor neuron sending rapid, high volume signal, and keep the stabilization of signal, one
It causes, is accurate, preparation integrated level is high, and function admirable, the good electrode of biocompatibility has very important researching value.Pass through
The outer change in electric intracellular for monitoring brain, heart cell helps deep to understand brain and cardiac life behavior and its biology
Basis and the exploitation for serving biomedical research and disease treatment technology.
Brain tissue electric signal is mainly derived from the action potential of nerve cell, and the record of action potentials of cells needs to consider more
Aspect factor:
1) signal quality, including signal amplitude and signal-to-noise ratio record electric signal intracellular with having highly sensitive and high-resolution
Ability, while guaranteeing that device noise is smaller.
2) high s/n ratio signal can be provided by monitoring action potential intracellular, and signal peak spectrum can reflect that more details act
Current potential, and intracellular signal detection also ensure detection signal be originated from it is unicellular, for accurate signal record possibility is provided.
3) the high-throughput biological vital tissue network epineural cell electric signal that simultaneously and concurrently records is distributed, drafting organ,
The space time information of tissue and cellular network.
Traditional extracellular recording method, generallys use that multiple electrode array (such as microelectrode, field-effect tube array) is non-to invade
Entering property sensing detection technology is, it can be achieved that high-throughput record with prolonged bioelectrical signals.Metal fibril electrode is used for greatly earliest
The long-term record of brain is generally made of materials such as tungsten wire, nickel filament, platinumiridio silks；Insulating materials is wrapped up such as except tip in outside
Teflon, polyimides and Parylene can pay close attention to single neuron and study crawler behavior when animal regains consciousness.Gold
Category fibril electrode can record the activity of a large amount of neurons simultaneously after electrod-array is made, and extract more useful informations,
The multidate information of gyrus road interaction can be captured on multiple temporal and space scale.Fibril electrode manufacture craft is simple, is implanted into
Conveniently, with certain flexibility, but each passage consistency of the metal fibril electrode of multichannel is poor, and metal fibril electricity
Pole array take up space it is larger, to disorganization than more serious when implantation.In addition, extracellular signal recording technique cannot be used for born of the same parents
The record of interior electric signal.There are close relationship in extracellular electric signal quality and cell-electrode couple state, relative position, and
And these conditions are difficult to control, to greatly influence the consistency of signal quality and interchannel signal.
The conventional method of endocellular electricity signal record is patch clamp technique, is chiefly used in patch-clamp single unit recording equipment
Glass electrode is a kind of electrode applied earliest, and using glass capillary high-temperature drawn, tip laterally can generally achieve micro-
Rice magnitude, capillary front end can enter the corresponding potential record of cell membrane progress, perfusion electrolysis among capillary when in use
Liquid, rear end are connected using the Ag/AgCl wire immersed in the electrolytic solution with external circuit.Current clamp technique energy record standard is moved
Make electric potential signal, and voltage clamp technology can also record ion channel response, is the basis for understanding electrical excitation type cell behavior.So
And the flux of manual patch-clamp is lower, operating process complicated and time consumption, operation causes biggish injury to cell, leads to not grow
The electricity physiological signal (< 2 hours) of Shi Jilu cell.Automatic patch clamp technique can ground multiple cells are carried out in unicellular one by one
Signal record, but they can not be recorded in multiple cells simultaneously, carry out the research of cellular network record.
The continuous development of micro-nano sensing detection technology provides huge potentiality for the research recorded in body bioelectrical signals.
There are two main classes at present for the method for unicellular intracellular signal record at present, active (field-effect tube) and passive (electrical-conductive nanometer electrode)
Nanosensor array.
In order to effectively carry out intracellular signal record, Harvard University's Lieber development in laboratory is based on nano wire nanotube
Field-effect tube, assist nanometer interface to enter cell interior by modification lipid, realize electric signal intracellular record.Such active biography
Sensor will not be influenced by cell-device sealing impedance, therefore can obtain the action potential signal of high quality.However due to receiving
Rice material crystals tube sensor processing is complicated, limits senser element large-scale processing efficiency and success rate, it is difficult to realize record
The electric signal intracellular of high-flux cell.
With the development of microelectronic processing technique, the integrated level of electrode is higher and higher, and integrated form nerve microelectrode array is such as
The photoetching process that two-dimensional surface is carried out on silicon wafer processes the multiple electrod-arrays that integrate of record point, may be implemented pair
It is recorded while nerve signal, while the electrod-array of random two-dimensional structure can be processed, conveniently adapt to some specific brain structures
Or neuron.Furthermore the three-dimensional that three-dimensional assembling such as Univ Utah USA's bioengineering dept is developed is carried out to the electrode of plane
Silicon pin electrode, Utah (Utah) electrode are insulation, the needle point of each needle by thicker silicon wafer to manufacture, between adjacent silicon needle
It covers platinum or other metal materials with good conductivity, needle leg is insulated by materials such as polyimides, realize super
Highdensity electrod-array, can be to be implanted at a high speed, to reduce the influence in implantation process to record performance.Current most of use
It is all based on hard substrate in the nano-sensor of record intracellular, the mechanical stress between biological tissue mismatches, and can aggravate
Organize the inflammatory reaction caused, it is difficult to effectively be coupled, be limited its application in living animal with the tissue of living animal
The research in body electro physiology.
Summary of the invention
The purpose of the present invention is overcome the deficiencies in the prior art, disclose a kind of for brain tissue electric signal record and regulation
Based on nanometer pin electrode flexible microfluidic control device and preparation method thereof, which has preferable biocompatibility, is
Thinking has been expanded in the selection of nerve electrode material；Its hollow gold nanometer pin electrode array surface product is big simultaneously, and density is high, size
It is small, it may be implemented to stablize, the neural recording of high s/n ratio；The electrode of the micro fluidic device is integrated on a flexible substrate, can be with
It is adapted with biological tissue, good biocompatibility has a good application prospect, suitable for implanting in addition, it can be same
Shi Shixian intracellular recording, high-flux parallel are recorded and are recorded in body tissue.
In order to reach above-mentioned technical purpose, the present invention is realized by following technical scheme:
The system based on nanometer pin electrode flexible microfluidic control of the present invention recorded for brain tissue electric signal with regulation
Preparation Method, preparation step are:
(1) hollow gold nanometer pin electrode array is prepared；
(2) hollow gold nanometer pin electrode array is connected to electrode by conducting wire to be formed into a loop, and to hollow gold nanometer
Pin electrode array is packaged；
(3) it prepares nanoneedle sensor: PDMS module is made using dimethyl silicone polymer, by PDMS module making in
Between have the cell culture container of through-hole, hollow gold nanometer pin electrode array is placed in the bottom of through-hole, nanoneedle side is upward；It is logical
It can be used for cultivating cell in hole, rat nerve cell cultivated on nano-electrode array, to realize that brain tissue records.
(4) the CV curve of scanning nano needle sensor: if hollow gold nanometer pin electrode array is connect well with conducting wire, CV
Curve current peak is larger, and current peak, which reduces, if poor contact even disappears；
(5) noise level of nanoneedle sensor is assessed；
(6) flexible test is carried out to nanoneedle sensor, evaluates it and stretches electric property under torsional deformation state:
As the further improvement of above-mentioned technology, the step (1) prepare hollow gold nanometer pin electrode array include with
Lower specific steps:
(11) polycarbonate membrane is selected, one layer of gold is sputtered on polycarbonate membrane；
(12) electrochemical deposition technique is used, has the polycarbonate membrane of gold to be placed in electrochemical workstation and three above-mentioned sputtering
In electrode work system, using copper sheet as working electrode, Ag/AgCl electrode is reference electrode, and platinum filament is to electrode, to contain chlorine gold
The electroplate liquid progress electro-deposition of acid, potassium sulfate, sulfuric acid, potassium chloride generates hollow Au nano needle arrays, and the electroplate liquid is 0.1mM
Gold chloride, 10mM potassium sulfate, 1mM sulfuric acid and 1mM potassium chloride mixed solution；
(13) followed by O2Plasma etching falls the polycarbonate membrane of part, exposes diameter 100nm, length 1.5-2 μ
The gold nano needle construction of m.
As the further improvement of above-mentioned technology, in the step (2), the conducting wire used is snakelike flexible wire.
As the further improvement of above-mentioned technology, in the step (2), packaging method is in hollow gold nanometer needle electricity
The back side spin coating SU-8 photoresist of pole array is packaged as insulating layer.
As the further improvement of above-mentioned technology, in the step (5), the noise level of nanoneedle sensor is carried out
Assessment specifically includes: being analyzed by circuit system the frequency spectrum measured, assesses the noise level of sensor；
As the further improvement of above-mentioned technology, the step (6) carries out flexible test, evaluation to nanoneedle sensor
It stretches electric property under torsional deformation state, and nanoneedle sensor is specifically carried out to different degrees of stretching torsional deformation,
Then its CV curve is scanned, whether logical over-current judging conducting wire has disconnection.
It is recorded with regulation for brain tissue electric signal based on nanometer pin electrode flexible microfluidic the invention also discloses above-mentioned
Nanometer pin electrode flexible microfluidic control device made from the preparation method of control, including nanoneedle sensor and made of PDMS module
There is a cell culture container of through-hole in centre, and the nanoneedle sensor includes that hollow gold nanometer pin electrode array, snakelike flexibility are led
Line, to electrode, three's forming circuit, and being packaged by insulating layer hollow gold nanometer pin electrode array, the hollow Jenner
Rice pin electrode array is placed in the bottom of PDMS module and practically corresponds to the lead to the hole site of cell culture apparatus, and has nanoneedle
Side upward and have part from the bottom of through-hole expose.
Compared with prior art, the beneficial effects of the present invention are:
(1) flexible microfluidic control device of the present invention, gold nano needle are 3D structure, and surface area is big, small in size, can
Realize the neural recording of high s/n ratio, the efficiency of signal record is influenced by being electrically coupled to contact with battery with electrode surface, this
The density of electrode is high, and size is small, record cerebral nerve circuit it is movable during, can carry out accurately monitoring and fine
Control has the potentiality of stable recording signal out；
(2) there is extraordinary biocompatibility as electrode material using Au in the present invention, using nanoneedle minimally-invasive
The method of penetrating cell film so that electrode has the performance of record cell interior signal, while avoid as far as possible to cell activity and
The interference of behavior.
(3) in the present invention, since electrode to be integrated in flexible substrates prepared by PDMS, there is device good soft
Property, the mechanical stress between biological tissue more matches, in biocompatibility face with good prospect；
(4) present invention prepares flexible substrate metal nano needle array using micro-nano technology technology, while making independent correspondence
Sensing module and flexible circuit, may be implemented high-flux parallel record in vitro with the action potential in body cell.
Detailed description of the invention
The present invention is described in detail in the following with reference to the drawings and specific embodiments:
Fig. 1 is the structural schematic diagram (including nerve cell) of flexible microfluidic control device of the present invention；
Fig. 2 is nanoneedle sensor structure schematic diagram (including nerve cell) in the present invention；
Fig. 3 is hollow gold nanometer pin electrode array and snakelike flexible wire attachment structure schematic diagram in the present invention；
Fig. 4 is the SEM phenogram of nanoneedle.
Specific embodiment
As shown in Figure 1 to Figure 3, the invention discloses record and regulate and control based on nanometer pin electrode for brain tissue electric signal
The nanometer pin electrode flexible microfluidic control device of flexible microfluidic control, including nanoneedle sensor 10 and made of PDMS it is intermediate have it is logical
The cell culture container 20 in hole 21, the nanoneedle sensor 10 are led including hollow gold nanometer pin electrode array 11, snakelike flexibility
Line 12, to electrode 13, three's forming circuit, and being packaged by insulating layer to hollow gold nanometer pin electrode array 11 is described
Hollow gold nanometer pin electrode array 11 is placed in the bottom of cell culture apparatus 20 and part and corresponds to 21 position of through-hole, and has nanoneedle
Side upward and have part from the bottom of through-hole 21 expose.
The preparation method of nanometer pin electrode flexible microfluidic control of the present invention, preparation step be,
(1) hollow gold nanometer pin electrode array 11 is prepared:
(11) polycarbonate membrane 111 is selected, one layer of gold is sputtered on polycarbonate membrane 111；
(12) electrochemical deposition technique is used, has the polycarbonate membrane 111 of gold to be placed in electrochemical workstation above-mentioned sputtering
In three electrode work systems, using copper sheet as working electrode, Ag/AgCl electrode is reference electrode, and platinum filament is to electrode, to contain
The electroplate liquid progress electro-deposition of gold chloride, potassium sulfate, sulfuric acid, potassium chloride generates hollow Au nano needle arrays 11；
(13) followed by O2Plasma etching falls the polycarbonate membrane 111 of part, exposes diameter 100nm, length
1.5-2 μm of gold nano needle construction.
(2) hollow gold nanometer pin electrode array 11 is connected by snakelike flexible wire 12 to electrode 13, to be formed into a loop,
And hollow gold nanometer pin electrode array 11 is packaged, packaging method is the back side in hollow gold nanometer pin electrode array 11
Spin coating SU-8 photoresist is packaged as insulating layer.
(3) prepare nanoneedle sensor 10: PDMS module is made using dimethyl silicone polymer, by PDMS module making at
There is the cell culture container 20 of through-hole 21 in centre, and hollow gold nanometer pin electrode array 11 is placed in the bottom of cell culture container 20
And corresponding to the position of through-hole 21, nanoneedle side upward, makes part hollow gold nano pin electrode array 11 from 21 bottom of through-hole
Expose, can be used for cultivating cell in through-hole 21, rat nerve cell is cultivated on hollow gold nanometer pin electrode array 11, thus real
Existing brain tissue record, while uncured PDMS glue bond will be used between PDMS module and the substrate 100 of nanoneedle, in cell
Cell is cultivated in the through-hole 21 of culture vessel 20, electric signal record uses Ag/AgCl electrode as reference electrode.
(4) cyclic voltammetric method (CV) is used, in K3Fe(CN)6In solution, the CV curve of scanning nano needle sensor leads to
Cross the connection that experiment electric current judges hollow gold nanometer pin electrode array 11 Yu snakelike flexible wire 12 (i.e. substrate back electrode):
If hollow gold nanometer pin electrode array 11 is connect well with snakelike flexible wire 12, CV curve current peak is larger, if contact
Bad then current peak, which reduces, even to disappear；
(5) noise level of nanoneedle sensor 10 is assessed: the frequency spectrum measured is divided by circuit system
Analysis, assesses the noise level of sensor；
(6) flexible test is carried out to nanoneedle sensor 10, evaluates it and stretch electric property under torsional deformation state, will receives
Rice needle sensor 10 carries out different degrees of stretching torsional deformation, then scans its CV curve, whether leads to over-current judging conducting wire
There is disconnection, in the case where stretching torsional deformation state, serpentine-shaped circuit distribution, device are observed by optical microscopy and scanning electron microscope
The integrality and reliability of part are good, under isolated cells and the environmental condition of tissue cultures, to the period each in longer cycle
Data be collected, measurement obtains sensor electrical performance and has good stability.
It is described in detail below by way of two specific embodiments:
Embodiment one:
It is simulated using rat nerve cell.Rat tissue is transferred to 0 DEG C of balanced salt solution and cleaned and is shredded, is used
Clostridiopetidase A and trypsase repeat digestion 1-14 times, and the DMEM culture medium for containing fetal calf serum (FBS) is added, and collect single-cell suspension
Liquid.Centrifugation is resuspended cell, filters off other cells.Sensor surface is modified using containing Fibronectin solution, improves the patch of cell
It is attached.It can be 37 DEG C with the electric signal of start recording nerve cell, cell culture condition after cultivating 8h, 5%CO2。
The rat nerve cell line cultivated on hollow gold nanometer pin electrode array 11 shows normal growth, microscope imaging
Show that the nerve cell grown on nano-electrode array shows the form similar to plane domain in rhythmicity hopping process
Cell is handled after the cells are fixed using critical point drying, and obtains nanoneedle and nerve using focused ion beam incising cell
The cross section of cell is observed using scanning electron microscope (SEM), shows nerve growth on nano-electrode.
Embodiment two:
By neuronal cell cultures in the top of hollow gold nanometer pin electrode array 11, Ag/AgCl reference electrode is placed in carefully
In born of the same parents' culture solution, using goldstandard patch clamp technique synchronous recording with the action potential of cell, with the nanoneedle in the present invention
The signal contrast that sensor 10 records, the shape of signal is similar, the electric signal that the hollow gold nanometer pin electrode array 11 records
Signal-to-noise ratio is typically larger than 100.
Nerve cell is recorded in the cerebral cortex of anaesthetised rat model specific brain area, Ag/AgCl reference electrode is put
It is placed in tissue non-electrical zone of action, makes the attaching of nanoneedle sensor 10 Yu tissue tight, records multichannel electrical signal, analysis is each
Channel signal amplitude, provides the basic parameters such as rate at time-histories, and each interchannel tracer signal is with uniformity, passes through long Shi Duoci
Electric signal analysis is recorded, single channel different time tracer signal is with uniformity.
Nanometer pin electrode flexible microfluidic control device of the present invention has good biocompatibility, is nerve electrode material
Thinking has been expanded in the selection of material；The nanoneedle uses 3D structure, and surface area is big, and density is high, and size is small (as shown in Figure 4), can
Stablized with realizing, the neural recording of high s/n ratio；Due to nanometer pin electrode is integrated in flexible substrates can be with biological tissue
It is adapted, good biocompatibility has a good application prospect suitable for implanting；Can be realized simultaneously intracellular recording,
High-flux parallel is recorded and is recorded in body tissue.
It is all that the present invention is not departed to various changes or modifications of the invention the invention is not limited to above embodiment
Spirit and scope, if these modification and variations belong within the scope of claim and equivalent technologies of the invention, then this hair
It is bright to also imply that comprising these modification and variations.
Claims (9)
1. recording the preparation method based on nanometer pin electrode flexible microfluidic control with regulation, preparation step for brain tissue electric signal
Suddenly it is:
(1) hollow gold nanometer pin electrode array is prepared；
(2) hollow gold nanometer pin electrode array is connected to electrode by conducting wire to be formed into a loop, and to hollow gold nanometer needle electricity
Pole array is packaged；
(3) it prepares nanoneedle sensor: PDMS module is made using dimethyl silicone polymer, PDMS module making is had at centre
Hollow gold nanometer pin electrode array is placed in the bottom of through-hole by the cell culture container of through-hole, and nanoneedle side is upward；In through-hole
It can be used for cultivating cell, rat nerve cell cultivated on nano-electrode array, to realize that brain tissue records.
(4) the CV curve of scanning nano needle sensor, comments the connection of hollow gold nanometer pin electrode array and conducting wire
Estimate；
(5) noise level of nanoneedle sensor is assessed；
(6) flexible test is carried out to nanoneedle sensor, evaluates it and stretches electric property under torsional deformation state.
2. according to claim 1 record for brain tissue electric signal and regulate and control based on nanometer pin electrode flexible microfluidic control
Preparation method, it is characterised in that:
The step (1) prepare hollow gold nanometer pin electrode array comprising the following specific steps
(11) polycarbonate membrane is selected, one layer of gold is sputtered on polycarbonate membrane；
(12) electrochemical deposition technique is used, has the polycarbonate membrane of gold to be placed in electrochemical workstation and three electrodes above-mentioned sputtering
In work system, using copper sheet as working electrode, Ag/AgCl electrode is reference electrode, platinum filament be to electrode, with containing gold chloride,
The electroplate liquid progress electro-deposition of potassium sulfate, sulfuric acid, potassium chloride generates hollow Au nano needle arrays；
(13) followed by O2Plasma etching falls the polycarbonate membrane of part, exposes gold nano needle construction.
3. according to claim 2 record for brain tissue electric signal and regulate and control based on nanometer pin electrode flexible microfluidic control
Preparation method, it is characterised in that: in step (12), the electroplate liquid be 0.1mM gold chloride, 10mM potassium sulfate, 1mM sulfuric acid
With the mixed solution of 1mM potassium chloride.
4. according to claim 2 record for brain tissue electric signal and regulate and control based on nanometer pin electrode flexible microfluidic control
Preparation method, it is characterised in that: in step (12), the diameter 100nm of the gold nano needle construction of exposing, 1.5-2 μm of length.
5. according to claim 1 record for brain tissue electric signal and regulate and control based on nanometer pin electrode flexible microfluidic control
Preparation method, it is characterised in that: in the step (2), the conducting wire used is snakelike flexible wire.
6. according to claim 1 record for brain tissue electric signal and regulate and control based on nanometer pin electrode flexible microfluidic control
Preparation method, it is characterised in that: in the step (2), packaging method is the back side in hollow gold nanometer pin electrode array
Spin coating SU-8 photoresist is packaged as insulating layer.
7. according to claim 1 record for brain tissue electric signal and regulate and control based on nanometer pin electrode flexible microfluidic control
Preparation method, it is characterised in that: in the step (5), to the noise level of nanoneedle sensor carry out assessment specifically include:
The frequency spectrum measured is analyzed by circuit system, assesses the noise level of sensor.
8. according to claim 1 record for brain tissue electric signal and regulate and control based on nanometer pin electrode flexible microfluidic control
Preparation method, it is characterised in that: the step (6) to nanoneedle sensor carry out flexible test, evaluate its stretch distortion become
Nanoneedle sensor is specifically carried out different degrees of stretching torsional deformation, then scans its CV by electric property under shape state
Whether curve, logical over-current judging conducting wire have disconnection.
9. being received made from the preparation method according to any one of claims 1 to 8 based on nanometer pin electrode flexible microfluidic control
Rice pin electrode flexible microfluidic control device, it is characterised in that: have among including nanoneedle sensor and made of PDMS module logical
The cell culture container in hole, the nanoneedle sensor include hollow gold nanometer pin electrode array, snakelike flexible wire, to electricity
Pole, three's forming circuit, and hollow gold nanometer pin electrode array is packaged by insulating layer, the hollow gold nanometer needle electricity
Pole array is placed in the bottom of cell culture apparatus and practically corresponds to lead to the hole site, and gold nano needle side upward and have part from
Expose the bottom of through-hole.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111289819A (en) * | 2020-04-09 | 2020-06-16 | 中山大学 | Integrated recording regulation and control system for measuring intracellular electric signals by myocardial cell electroporation |
| CN111568474A (en) * | 2020-04-22 | 2020-08-25 | 中国电子科技集团公司第四十九研究所 | Paper-pasted sweat sensor with sweat collection and collection structure |
| CN113884554A (en) * | 2021-10-27 | 2022-01-04 | 中国科学院过程工程研究所 | Method for preparing size-controllable nano needle type electrode |
| CN114544721A (en) * | 2022-02-24 | 2022-05-27 | 中山大学 | Flexible micro-nano electrode sensor and preparation method thereof |
| CN115248238A (en) * | 2022-07-09 | 2022-10-28 | 浙江大学杭州国际科创中心 | Nano trap microelectrode array device and controllable preparation method and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104720788A (en) * | 2014-12-25 | 2015-06-24 | 北京联合大学 | Evaluation system and method for vital sign monitoring device |
| CN107462511A (en) * | 2017-07-13 | 2017-12-12 | 中山大学 | Pass through the device of nano-electrode An arrayed recording endocellular electricity signal |
| CN108376618A (en) * | 2018-03-27 | 2018-08-07 | 西南交通大学 | Polyaniline/phytic acid conductive hydrogel and preparation method thereof and flexible super capacitor |
| US20180355297A1 (en) * | 2016-01-04 | 2018-12-13 | King Abdullah University Of Science And Technology | Nanoneedles for intracellular applications |
| CN109030597A (en) * | 2018-06-20 | 2018-12-18 | 中山大学 | Hollow Nano needle-graphene composite material sensor and its application |
| CN109097752A (en) * | 2018-08-02 | 2018-12-28 | 中山大学 | A kind of hollow Nano needle preparation method based on electrodeposition process |
-
2019
- 2019-08-22 CN CN201910777277.8A patent/CN110367979A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104720788A (en) * | 2014-12-25 | 2015-06-24 | 北京联合大学 | Evaluation system and method for vital sign monitoring device |
| US20180355297A1 (en) * | 2016-01-04 | 2018-12-13 | King Abdullah University Of Science And Technology | Nanoneedles for intracellular applications |
| CN107462511A (en) * | 2017-07-13 | 2017-12-12 | 中山大学 | Pass through the device of nano-electrode An arrayed recording endocellular electricity signal |
| CN108376618A (en) * | 2018-03-27 | 2018-08-07 | 西南交通大学 | Polyaniline/phytic acid conductive hydrogel and preparation method thereof and flexible super capacitor |
| CN109030597A (en) * | 2018-06-20 | 2018-12-18 | 中山大学 | Hollow Nano needle-graphene composite material sensor and its application |
| CN109097752A (en) * | 2018-08-02 | 2018-12-28 | 中山大学 | A kind of hollow Nano needle preparation method based on electrodeposition process |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111289819A (en) * | 2020-04-09 | 2020-06-16 | 中山大学 | Integrated recording regulation and control system for measuring intracellular electric signals by myocardial cell electroporation |
| CN111289819B (en) * | 2020-04-09 | 2022-04-12 | 中山大学 | Integrated recording regulation and control system for measuring intracellular electric signals by myocardial cell electroporation |
| CN111568474A (en) * | 2020-04-22 | 2020-08-25 | 中国电子科技集团公司第四十九研究所 | Paper-pasted sweat sensor with sweat collection and collection structure |
| CN113884554A (en) * | 2021-10-27 | 2022-01-04 | 中国科学院过程工程研究所 | Method for preparing size-controllable nano needle type electrode |
| CN114544721A (en) * | 2022-02-24 | 2022-05-27 | 中山大学 | Flexible micro-nano electrode sensor and preparation method thereof |
| CN115248238A (en) * | 2022-07-09 | 2022-10-28 | 浙江大学杭州国际科创中心 | Nano trap microelectrode array device and controllable preparation method and application thereof |
| CN115248238B (en) * | 2022-07-09 | 2024-04-02 | 浙江大学杭州国际科创中心 | Nano trap microelectrode array device and controllable preparation method and application thereof |
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Application publication date: 20191025 |