CN104490385A - Needle type microelectrode array - Google Patents
Needle type microelectrode array Download PDFInfo
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- CN104490385A CN104490385A CN201410759822.8A CN201410759822A CN104490385A CN 104490385 A CN104490385 A CN 104490385A CN 201410759822 A CN201410759822 A CN 201410759822A CN 104490385 A CN104490385 A CN 104490385A
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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
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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
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
- A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
- A61B5/685—Microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0504—Subcutaneous electrodes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/065—Light sources therefor
- A61N2005/0651—Diodes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0662—Visible light
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Abstract
The invention discloses a needle type microelectrode array, which successively comprises a lower-layer substrate, a lower metal layer, a lower insulation layer, an optical waveguide layer, an upper insulation layer, an upper metal layer and an upper substrate layer from bottom to top, wherein the optical waveguide layer is provided with an optical waveguide channel which is divided into five parts from one part, and the end part of the optical waveguide channel is used a site for photostimulation and optical recording; the upper metal layer and the lower layer metal are respectively provided with eight electrode points, and electrode leads and eight bonding pads corresponding to the electrode points; each electrode point is led out by the electrode lead corresponding to the electrode point; the electrode lead is connected with the corresponding bonding pad; each electrode point can be independently used as the site for electric stimulus and electric recording. According to the needle type microelectrode array, the integration, the microminiaturization and the intellectualization of a signal acquisition system can be realized, and the needle type microelectrode array can be used for simultaneously recording the electrical activity of cells and fluorescent protein expression which is under photostimulation. According to the needle type microelectrode array, biological information and electric information can be tightly combined so as to explain and stimulate neural activities in organisms.
Description
Technical field
The present invention relates to a kind of pin type microelectrode array, photoelectricity stimulation and record can be carried out simultaneously.
Background technology
Each process of organism response external event and process information, all needs the combined effect of many neurocytes.Electrophysiology activity is the major way of neurocyte transmission of information, and its waveform, amplitude, frequency not only have expressed the physiological status of single neurocyte itself, also carries between cell colony and links up mutual relevant information.Therefore, the bioelectrical activity of colony's neurocyte is carried out to the detection of high accuracy, high flux, real-time, contribute to understanding neurocyte state, function and interaction mechanism, thus to the pathogeny of some disease of research, nerve signal transmission and drug reaction etc., there is important scientific meaning and medical value.
Traditional Electrophysiology detects main employing glass microelectrode and tinsel Technology of Microelectrodes.Glass microelectrode is positioned, in cell membrane or on cell membrane, to be applicable to the research of unicellular bioelectrical activity and ion channel in cell membrane, and tracer signal amplitude is comparatively large, but location is complicated, cannot carry out multiple recording simultaneously.The outer electrical activity of tinsel microelectrode recording born of the same parents, can multiple recording, but number of electrodes is limited, and between electrode, relative position easily departs from, and spatial resolution is low.Therefore these two kinds traditional recording electrodes can not meet clinical and scientific research and detected demand.
In addition in recent years, along with the proposition of photogene technological concept, more and more higher to the requirement of electrode.Photogene technology refers to that one utilizes genetics technology to make cellular expression photaesthesia albumen, and then a kind of light wave of specific wavelength that utilizes is to disturb neurocyte, thus the technology that realization controls the optics of cell.Brain research worker utilizes a kind of special gene therapy in conjunction with photogene technology, can open or close the brain cell that some has high specific.Utilize photogene technical controlling cellular activity, have not damaged, non-intruding, spatial and temporal resolution high, quantitatively can repeat, use the advantages such as simple, just obtaining applying more and more widely.And current optoelectronic pole is made up of single fiber waveguide and electrod-array, fiber waveguide and electrode are still released state, and cannot realize integration, spatial resolution is lower.
Along with the development of microelectromechanical systems (MEMS) technology, many novel microelectrode arrays utilizing micro fabrication to prepare are there is.These microelectrode arrays are by the same base integrated for dozens or even hundreds of electro physiology sense channel, electrode size, spacing concordance are good, and volume is little, and spatial resolution is high, can various forms be prepared into, be applicable in animal body respectively or the multi-channel synchronous record of isolated cells electricity physiological signal.In addition, such microelectrode can combine with various nano-modified technology easily, thus improves microelectrode performance, meets the needs of its biocompatibility, long-lasting and signal to noise ratio.
Summary of the invention
For the defect that prior art exists, the object of this invention is to provide a kind of pin type microelectrode array, for realizing electrographic recording (Spike and LFP), electricity irritation (direct current) and photostimulation (micron order LED) simultaneously, may be used for chronic implantation experiment, to realize the integrated, microminiaturized and intelligent of signal acquiring system.
For arriving above-mentioned purpose, the present invention adopts following technical scheme:
A kind of pin type microelectrode array, comprises lower floor's substrate, lower metal layer, lower insulating barrier, light waveguide-layer, upper insulating barrier, upper metal level and upper strata substrate from bottom to top successively; Described light waveguide-layer is provided with the Light guiding channel being divided into five by, and its end is as the site of photostimulation and optical recording; Described upper metal level and lower metal layer are respectively equipped with contact conductor and eight pads of eight electrode points and correspondence thereof; Each electrode points is drawn by the contact conductor of its correspondence, and contact conductor is connected with corresponding pad, and each electrode points all can separately as electricity irritation and electrographic site.
The electrode points diameter of described upper metal level and lower metal layer is 15 μm, and surface is coated with platinum.This is because Cerebral Cortex Neuronal Cells diameter about 10 μm ~ 20 μm, both ensure cell energy coated electrode, and allowed again an electrode only contact a neurocyte as far as possible, reduce the crosstalk between signal.
The contact conductor of described upper metal level and lower metal layer and the material of pad are gold, and the live width of contact conductor is 5 μm, and pad size is the square of 30 μm × 30 μm.
Described upper strata substrate, lower floor's substrate and upper and lower insulating barrier all adopt Sapphire Substrate.
The path channels being divided into five 25 μm × 25 μm by the path channels of a 25 μm × 125um of described light waveguide-layer.
Be 100um for the beeline between electricity irritation and electrographic site.Be 100um for the beeline between photostimulation and the site of optical recording.For electricity irritation and electrographic site round the site for photostimulation and optical recording.
The needle point angle of electrode needle is 60 degree.The length of electrode needle is 4mm, width 400 μm, thickness 75 μm.
Compared with prior art, the present invention has following outstanding substantive distinguishing features and significant advantage:
Pin type microelectrode array of the present invention, can realize the integrated, microminiaturized of signal acquiring system and intellectuality, can be used for recording simultaneously cell electrical activity and under photostimulation and fluorescent protein expression.Bio information and electrical information can be combined closely by it, thus can explain and encourage the neural activity in organism.
Accompanying drawing explanation
Fig. 1 is pin type Microelectrode array architecture schematic diagram of the present invention.
Fig. 2 is upper basal layer schematic diagram.
Fig. 3 is upper metal level schematic diagram.
Fig. 4 is upper and lower insulating barrier schematic diagram.
Fig. 5 is light waveguide-layer schematic diagram.
Fig. 6 is lower metal layer schematic diagram.
Fig. 7 is lower basal layer schematic diagram.
Detailed description of the invention
Below in conjunction with accompanying drawing, embodiments of the invention are described further.
As shown in Figures 1 to 7, a kind of pin type microelectrode array, comprises lower floor's substrate, lower metal layer, lower insulating barrier, light waveguide-layer, upper insulating barrier, upper metal level and upper strata substrate from bottom to top successively; Described light waveguide-layer is provided with the Light guiding channel being divided into five by, and its end is as the site of photostimulation and optical recording; Described upper metal level and lower metal layer are respectively equipped with contact conductor and eight pads of eight electrode points and correspondence thereof; Each electrode points is drawn by the contact conductor of its correspondence, and contact conductor is connected with corresponding pad, and each electrode points all can separately as electricity irritation and electrographic site.
The electrode points diameter of described upper metal level and lower metal layer is 15 μm, and surface is coated with platinum.
The contact conductor of described upper metal level and lower metal layer and the material of pad are gold, and the live width of contact conductor is 5 μm, and pad size is the square of 30 μm × 30 μm.
Described upper strata substrate, lower floor's substrate and upper and lower insulating barrier all adopt Sapphire Substrate.
The path channels being divided into five 25 μm × 25 μm by the path channels of 25 μm × 125 μm of described light waveguide-layer.
It is 100 μm for the beeline between electricity irritation and electrographic site.It is 100 μm for the beeline between photostimulation and the site of optical recording.For electricity irritation and electrographic site round the site for photostimulation and optical recording.
The needle point angle of electrode needle is 60 degree; The length of electrode needle is 4mm, width 400 μm, thickness 75 μm.
Pin type microelectrode array in the present embodiment is prepared by following steps:
1, lower floor's base treatment:
(1), lower floor's substrate photoetching light through hole, electrode points, contact conductor and pad, and to etch;
(2), sputtering method spraying plating platinum forms lower metal layer;
(3) plasma-enhanced chemical vapor deposition method, is utilized to make lower insulating barrier;
(4) glass and insulating barrier bonding method, is utilized to make waveguide paths;
2, upper strata base treatment:
(1), upper strata substrate photoetching light through hole, electrode points, contact conductor and pad, and to etch;
(2), sputtering method spraying plating platinum forms metal level;
(3), the substrate of plasma-enhanced chemical vapor deposition upper strata is applied;
(4) glass and insulating barrier bonding method, is utilized to make waveguide paths;
3, levels substrate split encapsulating.
Claims (9)
1. a pin type microelectrode array, is characterized in that, comprises lower floor's substrate, lower metal layer, lower insulating barrier, light waveguide-layer, upper insulating barrier, upper metal level and upper strata substrate from bottom to top successively; Described light waveguide-layer is provided with the Light guiding channel being divided into five by, and its end is as the site of photostimulation and optical recording; Described upper metal level and lower metal layer are respectively equipped with contact conductor and eight pads of eight electrode points and correspondence thereof; Each electrode points is drawn by the contact conductor of its correspondence, and contact conductor is connected with corresponding pad, and each electrode points all can separately as electricity irritation and electrographic site.
2. pin type microelectrode array according to claim 1, is characterized in that, the electrode points diameter of described upper metal level and lower metal layer is 15 μm, and surface is coated with platinum.
3. pin type microelectrode array according to claim 1, is characterized in that, the contact conductor of described upper metal level and lower metal layer and the material of pad are gold, and the live width of contact conductor is 5 μm, and pad size is the square of 30 μm × 30 μm.
4. pin type microelectrode array according to claim 1, is characterized in that, described upper strata substrate, lower floor's substrate and upper and lower insulating barrier all adopt Sapphire Substrate.
5. pin type microelectrode array according to claim 1, is characterized in that, the path channels being divided into five 25 μm × 25 μm by the path channels of 25 μm × 125 μm of described light waveguide-layer.
6. pin type microelectrode array according to claim 1, is characterized in that, is 100 μm for the beeline between electricity irritation and electrographic site.
7. pin type microelectrode array according to claim 1, is characterized in that, is 100 μm for the beeline between photostimulation and the site of optical recording.
8. pin type microelectrode array according to claim 1, is characterized in that, for electricity irritation and electrographic site round the site for photostimulation and optical recording.
9. pin type microelectrode array according to claim 1, is characterized in that, the needle point angle of electrode needle is 60 degree; The length of electrode needle is 4mm, width 400 μm, thickness 75 μm.
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| CN201410759822.8A CN104490385A (en) | 2014-12-12 | 2014-12-12 | Needle type microelectrode array |
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| CN201410759822.8A CN104490385A (en) | 2014-12-12 | 2014-12-12 | Needle type microelectrode array |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106308754A (en) * | 2016-09-18 | 2017-01-11 | 广东顺德中山大学卡内基梅隆大学国际联合研究院 | Implantable miniature LED neurological probe |
| CN107334471A (en) * | 2016-12-19 | 2017-11-10 | 中国科学院苏州生物医学工程技术研究所 | A kind of binary channels animal nerve unit signal record and synchronous stimulating system |
| 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 |
| CN109545884A (en) * | 2018-11-09 | 2019-03-29 | 中山大学 | A kind of integrated form can the atomic probe of injection type biological photoelectric and preparation method thereof |
| CN109567782A (en) * | 2017-09-28 | 2019-04-05 | 陈右颖 | It is combined with the nerve probe and its manufacturing method of optical waveguide |
| CN109820481A (en) * | 2019-02-22 | 2019-05-31 | 中国科学院半导体研究所 | Neural optoelectronic pole and preparation method thereof |
| CN110623655A (en) * | 2019-09-24 | 2019-12-31 | 中国科学院电子学研究所 | Implantable micro-nano electrode array chip for simulating weightless rat and preparation method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106308754A (en) * | 2016-09-18 | 2017-01-11 | 广东顺德中山大学卡内基梅隆大学国际联合研究院 | Implantable miniature LED neurological probe |
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| CN109567782A (en) * | 2017-09-28 | 2019-04-05 | 陈右颖 | It is combined with the nerve probe and its manufacturing method of optical waveguide |
| 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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| CN109545884A (en) * | 2018-11-09 | 2019-03-29 | 中山大学 | A kind of integrated form can the atomic probe of injection type biological photoelectric and preparation method thereof |
| CN109820481A (en) * | 2019-02-22 | 2019-05-31 | 中国科学院半导体研究所 | Neural optoelectronic pole and preparation method thereof |
| CN110623655A (en) * | 2019-09-24 | 2019-12-31 | 中国科学院电子学研究所 | Implantable micro-nano electrode array chip for simulating weightless rat and preparation method thereof |
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