CN115096945A - Micro-needle array electrode for detecting myocardial cell electric signals and preparation method thereof - Google Patents
Micro-needle array electrode for detecting myocardial cell electric signals and preparation method thereof Download PDFInfo
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Abstract
The invention relates to the technical field of biomedicine, in particular to a micro-needle array electrode for detecting myocardial cell electric signals and a preparation method thereof. This a micropin array electrode for detecting cardiac muscle cell signal of telecommunication owing to be equipped with a plurality of micropin electrode unit, and micropin electrode unit includes stratum basale, metal level, insulating layer and PDMS porous membranous layer, and because the needle body is transparent material in the stratum basale, the light transmissivity is good, is convenient for observe under the microscope and pasteurization, more is fit for the cell culture. The insulating layer is arranged to cover the auxiliary metal wires in the metal layer on the base layer, so that current can be prevented from being formed between the auxiliary metal wires on the base, and interference on potential detection is avoided. Because a single myocardial cell can cover two connecting electrodes in the electrode pair, the conduction speed of an electric signal in the cell can be calculated by detecting the electric signal between the two connecting electrodes, and further the surface voltage and the electrical impedance of the single cell can be accurately detected.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a micro-needle array electrode for detecting myocardial cell electric signals and a preparation method thereof.
Background
The potential of the myocardial cell comprises a resting potential and an action potential during excitation, wherein when the myocardial cell is at rest, the potential outside the membrane is positive, and the potential inside the membrane is negative; when the myocardial cells are excited, the potentials of the myocardial cells are reversely polarized, namely the potential outside the membrane temporarily becomes negative, and the potential inside the membrane temporarily becomes positive; the cardiomyocytes then return to the original polarization state, i.e. repolarization or repolarization. The electrophysiological state of the myocardial cells can be accurately grasped by detecting the action potential of the myocardium. The function of the myocardial cells can be effectively evaluated by detecting the indexes of the myocardial cell internal/external signal conduction velocity, transmembrane voltage, electrical impedance and the like.
Currently, microneedle array electrodes have been widely used in the fields of biology and medicine. Microneedle electrodes are typically of micron size. In actual use, the microneedle electrode penetrates through or contacts with a measured object, the measured object cannot be damaged due to the tiny size of the microneedle, and the array microneedle electrode can simultaneously contact with a plurality of measured objects, so that the measured objects can be detected in a high-flux manner.
However, the existing microneedle electrodes cannot monitor the state of cells in real time, and cannot detect signal transduction inside the cells, the surface voltage of the single cell membrane, and the electrical impedance.
Disclosure of Invention
Technical problem to be solved
In view of the above disadvantages and shortcomings of the prior art, the present invention provides a microneedle array electrode for detecting electrical signals of cardiomyocytes and a method for manufacturing the same, which can detect the state of cells in real time and can detect signal conduction, surface voltage of single cell and electrical impedance in the cells.
(II) technical scheme
In order to achieve the purpose, the invention adopts the main technical scheme that:
the embodiment of the invention provides a microneedle array electrode for detecting myocardial cell electric signals, which is arranged on a PCB (printed circuit board), and comprises a plurality of microneedle electrode units arranged in an array manner; the micro-needle electrode unit sequentially comprises a substrate layer, a metal layer, an insulating layer and a PDMS porous film layer; the base layer comprises a base and two pairs of micro-needle electrode pairs arranged on the base, a pad is arranged on the base, each pair of micro-needle electrode pairs comprises two needle bodies, the needle bodies are made of transparent materials, the metal layer is sprayed on the base layer to form an auxiliary metal wire on the base and form a connecting electrode at the top end of each needle body, the connecting electrode is communicated with one end of the auxiliary metal wire, the other end of the auxiliary metal wire is connected with the pad, and a single cardiac muscle cell can cover the connecting electrodes at the top ends of the two needle bodies simultaneously; the insulating layer sets up on the stratum basale and exposes the top and the pad of needle body, and PDMS porous membrane layer covers on the insulating layer.
Preferably, the needle body is in a revolving body structure, and the distance between the central axes of the needle bodies in each pair of microneedle electrode pairs is 30-50 μm.
Preferably, the base and the needle body in the basal layer are both made of high-light-transmission glass.
Preferably, the needle body is a cylinder having a diameter of 7-10 μm.
Preferably, the insulating layer is made of polyimide.
Preferably, the bonding pad is connected with a port on a parallel flat cable on the PCB board through a lead; the PCB is provided with a plurality of reference electrodes, and the reference electrodes are connected with ports on serial cables on the PCB.
The invention also provides a preparation method of the micro-needle array electrode for detecting the myocardial cell electric signal, which comprises the following steps;
s1: selecting a high-light-transmission glass sheet with the thickness of 500 mu m and 4 inches as a base of the substrate layer;
s2: sequentially cleaning the base with acetone, pure water, absolute ethyl alcohol and pure water for at least 5 minutes;
s3: spin-coating a layer of photoresist on one surface of the base, forming a substrate layer with a needle body by etching by using a mask, and removing the redundant photoresist;
s4: sequentially cleaning the basal layer with the needle bodies by using absolute ethyl alcohol and pure water for not less than 5 minutes, and airing for 1 hour after cleaning to obtain a dry basal layer;
s5: forming a conductive layer on the surface of the dried substrate layer through a magnetron sputtering metal layer, wherein the thickness of the conductive layer is 150nm, so that a connecting electrode is arranged at the top end of the needle body, and an auxiliary metal wire is arranged on the base;
s6: spin-coating an insulating material on the conducting layer except the top end of the pin body and the position of the pad on the base, so that the thickness of the insulating material is not more than 2 mu m, and forming an insulating layer after baking;
s7: and covering the PDMS porous film layer on the insulating layer to form the microneedle array electrode.
Preferably, step S7 includes the following steps;
s71: preparing a PDMS prepolymer solution, removing bubbles in a vacuum box, wherein the vacuum degree during extraction is-15 kPa, and the extraction time is not less than 30 minutes;
s72: spin-coating a layer of PDMS prepolymer on the insulating layer to make the thickness of the PDMS prepolymer not more than 20 μm, covering the PDMS prepolymer with a male mold with a conical structure in a reversed manner, and curing at 85 deg.C for 2 hr;
s73: and taking down the male die, cutting off the redundant PDMS film by using a knife, aligning and covering the PDMS film on the substrate layer under a microscope, and exposing the top end of the needle body and the pad of the base to obtain the microneedle array electrode.
Preferably, step S8 is also included;
s8: and connecting the bonding pads on the micro-needle array electrodes with the ports of the parallel flat cables on the PCB in a one-to-one correspondence manner through the conducting wires.
(III) advantageous effects
The beneficial effects of the invention are:
the microneedle array electrode for detecting the myocardial cell electric signals is provided with the plurality of microneedle electrode units, each microneedle electrode unit comprises the basal layer, the metal layer, the insulating layer and the PDMS porous film layer, and the needle body in the basal layer is made of the transparent material, so that the light transmission is good, the observation and the high-temperature sterilization under a microscope are facilitated, and the microneedle array electrode is more suitable for cell culture. The insulating layer is arranged to cover the auxiliary metal wires in the metal layer on the base layer, so that current can be prevented from being formed between the auxiliary metal wires on the base, and interference on potential detection is avoided. And because a single myocardial cell can cover the two connecting electrodes in the electrode pair, and the conduction speed of the electrical signal in the cell can be calculated by detecting the electrical signal between the two connecting electrodes, the micro-needle array electrode for detecting the electrical signal of the myocardial cell can accurately detect the surface voltage and the electrical impedance of the single cell.
According to the preparation method of the microneedle array electrode for detecting the myocardial cell electric signals, the prepared microneedle array electrode is provided with the plurality of microneedle electrode units, each microneedle electrode unit comprises the basal layer, the metal layer, the insulating layer and the PDMS porous film layer, and the needle body in the basal layer is made of the transparent material, so that the light transmission is good, the observation and the high-temperature sterilization under a microscope are facilitated, and the microneedle array electrode is more suitable for cell culture. The insulating layer is arranged to cover the auxiliary metal wires in the metal layer on the base layer, so that current can be prevented from being formed between the auxiliary metal wires on the base, and interference on potential detection is avoided. And because a single myocardial cell can cover the two connecting electrodes in the electrode pair, and the conduction speed of the electrical signal in the cell can be calculated by detecting the electrical signal between the two connecting electrodes, the micro-needle array electrode for detecting the electrical signal of the myocardial cell can accurately detect the surface voltage and the electrical impedance of the single cell.
Drawings
Fig. 1 is a schematic structural view of a microneedle array electrode according to the present invention;
fig. 2 is an enlarged view of a portion a in fig. 1;
FIG. 3 is a schematic view of the structure of the micro-needle array electrode and the PCB board of the present invention;
fig. 4 is a schematic structural diagram of a PDMS porous membrane.
[ description of reference ]
1: a microneedle array electrode; 11: a microneedle electrode unit; 111: a needle body; 112: connecting the electrodes; 113: an auxiliary metal line; 114: a pad;
2: a PCB board; 21: parallel connection of flat cables; 22: a reference electrode; 23: and (4) serial bus lines.
Detailed Description
In order to better understand the above technical solutions, exemplary embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the invention are shown in the drawings, it should be understood that the invention may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
Example one
As shown in fig. 1 and fig. 3, an embodiment of the present invention provides a microneedle array electrode 1 for detecting an electrical signal of a cardiac muscle cell, where the microneedle array electrode 1 is arranged on a PCB 2, and the microneedle array electrode 1 includes a plurality of microneedle electrode units 11 arranged in an array.
As shown in fig. 2, the microneedle electrode unit 11 sequentially includes a substrate layer, a metal layer, an insulating layer, and a PDMS porous film layer, the substrate layer includes a base and two pairs of microneedle electrodes disposed on the base, a pad is disposed on the base, each pair of microneedle electrodes includes two needles 111, the needles 111 are made of transparent material, the metal layer is sprayed on the substrate layer to form an auxiliary metal wire 113 on the base, and a connection electrode 112 is formed on the top end of the needle 111, the connection electrode 112 is communicated with one end of the auxiliary metal wire 113, the other end of the auxiliary metal wire 113 is connected to the pad 114, a single cardiomyocyte can cover the connection electrodes 112 on the top ends of the two needles 111 at the same time, the insulating layer is disposed on the substrate layer and exposes the top end of the needle 111 (i.e., exposes the connection electrode 112) and the pad 114, and the PDMS porous film layer covers the insulating layer of the needle. It should be noted that the arrangement of the auxiliary metal lines 113 is designed according to actual requirements. It should be noted that PDMS is polydimethylsiloxane.
The micro-needle array electrode 1 for detecting the electrical signal of the myocardial cell provided by the embodiment is provided with a plurality of micro-needle electrode units 11, the micro-needle electrode units 11 comprise a basal layer, a metal layer, an insulating layer and a PDMS porous film layer, and the needle body 111 in the basal layer is made of a transparent material, so that the light transmission is good, the observation and the high-temperature sterilization under a microscope are convenient, and the micro-needle array electrode is more suitable for cell culture. The insulating layer is arranged to cover the auxiliary metal wires in the metal layer on the base layer, so that current can be prevented from being formed between the auxiliary metal wires on the base, and interference on potential detection is avoided. And because a single myocardial cell can cover the two connecting electrodes 112 in the electrode pair, and the conduction speed of the electrical signal in the cell can be calculated by detecting the electrical signal between the two connecting electrodes 112, the microneedle array electrode 1 for detecting the electrical signal of the myocardial cell can accurately detect the surface voltage and the electrical impedance of the single cell.
In this embodiment, the needle body 111 is a revolving structure, specifically, the needle body 111 is a cylinder, and the diameter of the cylinder is 7-10 μm. Of course, the needle body 111 may be a vertebral body. The distance between the central axes of the needle bodies 111 in each pair of microneedle electrode pairs is 30-50 μm. The needle body 111 and the base are made of high-light-transmission glass, and the base is made of glass. The needle body 111 is made of high-light-transmission glass, has higher hardness than stainless steel or plastic, has good light transmission, is convenient for observation under a microscope and high-temperature sterilization, and is more suitable for cell culture.
Wherein, PDMS has better biocompatibility, which is beneficial to the induced two-dimensional adherent growth of the myocardial cells. In addition, the PDMS porous membrane layer can be replaced, so that the influence of extracellular secretion on the growth of cells is avoided. The insulating layer is made of polyimide.
The auxiliary metal wires 113 of the microneedle electrode unit 11 correspond to the bonding pads 114 one by one, the bonding pads 114 are connected with ports on the parallel flat cable 21 on the PCB through wires, meanwhile, a plurality of reference electrodes 22 are arranged on the PCB 2, the reference electrodes 22 are connected with ports on the serial flat cable 23 on the PCB 2, and the spare terminal pins on the PCB 2 are respectively connected with the peripheral signal acquisition circuit. Of course, the interface on the serial bus 23 can be directly connected to a computer or other device for reading the signal measured by the connecting electrode 112 and the electrical signal measured by the reference electrode 22.
When the micro-needle array electrode 1 is used for detecting the electrical signal of the cardiac muscle cell, the cardiac muscle cell is planted on the porous membrane in a two-dimensional adherent manner, the cardiac muscle cell is spread on a pair of micro-needle electrodes, a current value is given to the connecting electrode 112 on one needle body 111, the signal of the connecting electrode 112 on the other needle body 111 is measured, and the conduction rate, transmembrane voltage and electrical impedance of the signal in (among) the cardiac muscle cell are obtained through calculation. And because the microneedle array electrode 1 is provided with a plurality of microneedle electrode units 11, when cells are planted in an adherent manner to reach a certain density, at least one myocardial cell can completely cover the pair of microneedle electrodes, and an electric signal of a single myocardial cell can be detected. Meanwhile, since the microneedle array comprises the microneedle electrode units 11, the signal conduction rate between two myocardial cells on a plurality of pairs of microneedle electrodes can be measured, and the signal conduction in (among) the myocardial cells can be detected at high flux at the same time. Because the reference electrode 22 is arranged on the PCB 2, the detected electric signal can be compared with the reference signal, and the signal of the myocardial cell can be accurately obtained, thereby improving the detection accuracy. In addition, since the needle 111 has a diameter of several micrometers, it is less harmful to cells when it is combined with the cell surface.
Example two
In this embodiment, the microneedle array electrode 1 has a rectangular structure with a size of 2cm × 2cm, and includes 60 microneedle electrode units 11, and a plurality of microneedle electrode units 11 may be provided according to actual requirements. Each microneedle electrode unit 11 is provided with two pairs of microneedle electrodes, each pair of microneedle electrodes comprises two needle bodies 111, each needle body 111 is a cylinder with a diameter of 7 μm, the height of the cylinder is 21 μm, and the distance between the central axes of the two cylinders is 35 μm. Wherein, the material of cylinder is high printing opacity glass, is convenient for observe the cell growth state. The thickness of the base was 500. mu.m.
As shown in fig. 4, the porous membrane is made of PDMS and has a conical structure, and the PDMS has good biocompatibility and high transmittance, and can be used for growth and observation of cells. The porous membrane has a porous structure, the aperture is 8 microns, two holes are in a pair, the center distance of the pair of holes is 35 microns, the thickness of the porous membrane is not more than 20 microns, and the porous membrane corresponds to the needle bodies 111 on the micro needle electrode pairs one by one.
EXAMPLE III
The invention also provides a preparation method of the micro-needle array electrode 1 for detecting the myocardial cell electric signal, which comprises the following steps;
s1: selecting a high-light-transmission glass sheet with the thickness of 500 mu m and 4 inches as a base of the substrate layer;
s2: sequentially cleaning the base with acetone, pure water, absolute ethyl alcohol and pure water for at least 5 minutes;
s3: spin-coating a layer of photoresist on one surface of the base, forming a substrate layer with the needle body 111 by etching through a mask, and removing redundant photoresist;
s4: sequentially cleaning the basal layer with the needle bodies 111 by using absolute ethyl alcohol and pure water for not less than 5 minutes, and airing for 1 hour after cleaning to obtain a dry basal layer;
s5: forming a conductive layer on the surface of the dried substrate layer by magnetron sputtering a metal layer, wherein the metal layer is made of gold, the thickness of the conductive layer is 150nm, the top end of the pin body 111 is provided with a connecting electrode 112, and the base is provided with an auxiliary metal wire 113;
s6: spin-coating insulating materials on the conducting layer except the top ends of the pin bodies 111 and the positions of the pads 114 on the base, so that the thickness of the insulating materials is not more than 2 mu m, and forming an insulating layer after baking;
s7: and covering the PDMS porous film layer on the insulating layer by a spin coating method to form the microneedle array electrode 1.
Wherein, step S7 includes the following steps;
s71: preparing PDMS prepolymer solution, removing bubbles in a vacuum box, wherein the vacuum degree is-15 kPa during extraction, and the extraction time is not less than 30 minutes;
s72: spin-coating a layer of PDMS prepolymer on the insulating layer to make the thickness of the PDMS prepolymer not more than 20 μm, covering the PDMS prepolymer with a male mold with a conical structure in a reversed manner, and curing at 85 deg.C for 2 hr;
s73: and (3) taking down the male die, cutting off the redundant PDMS film by using a knife, aligning and covering the PDMS film on the substrate layer under a microscope, and exposing the top end of the needle body 111 and the welding disc 114 of the base to obtain the microneedle array electrode 1.
S8: the bonding pads 114 on the microneedle array electrode 1 are correspondingly connected with the ports of the parallel flat cables 21 on the PCB board through the welding wires.
According to the preparation method of the microneedle array electrode 1 for detecting the myocardial cell electric signal, the prepared microneedle array electrode 1 is provided with the plurality of microneedle electrode units 11, the microneedle electrode units 11 comprise the basal layer, the metal layer, the insulating layer and the PDMS porous film layer, and the needle body 111 in the basal layer is made of transparent materials, so that the light transmission is good, observation and high-temperature sterilization under a microscope are facilitated, and the microneedle array electrode 1 is more suitable for cell culture. The insulating layer is arranged to cover the auxiliary metal wires in the metal layer on the base layer, so that current can be prevented from being formed between the auxiliary metal wires on the base, and interference on potential detection is avoided. And because a single myocardial cell can cover the two connecting electrodes 112 in the electrode pair, and the conduction speed of the electrical signal in the cell can be calculated by detecting the electrical signal between the two connecting electrodes 112, the microneedle array electrode 1 for detecting the electrical signal of the myocardial cell can accurately detect the surface voltage and the electrical impedance of the single cell.
In the present invention, unless otherwise expressly stated or limited, the terms "mounted," "connected," "secured," and the like are to be construed broadly and can, for example, be fixedly connected, detachably connected, or integrally formed; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium; either internal to the two elements or in an interactive relationship of the two elements. The specific meanings of the above terms in the present invention can be understood according to specific situations by those of ordinary skill in the art.
In the present invention, unless otherwise expressly stated or limited, a first feature may be "on" or "under" a second feature, and the first and second features may be in direct contact, or the first and second features may be in indirect contact via an intermediate. Also, a first feature "on," "above," and "over" a second feature may be directly or obliquely above the second feature, or simply mean that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature may be directly under or obliquely under the second feature, or may simply mean that the first feature is at a lower level than the second feature.
In the description herein, the description of the terms "one embodiment," "some embodiments," "an embodiment," "an example," "a specific example" or "some examples" or the like, means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it should be understood that the above embodiments are illustrative and not restrictive, and that those skilled in the art may make changes, modifications, substitutions and alterations to the above embodiments without departing from the scope of the present invention.
Claims (9)
1. The micro-needle array electrode is used for detecting myocardial cell electric signals and is characterized by being arranged on a PCB (printed circuit board), and comprising a plurality of micro-needle electrode units which are arranged in an array manner;
the micro-needle electrode unit sequentially comprises a substrate layer, a metal layer, an insulating layer and a PDMS porous membrane layer;
the basal layer comprises a base and two pairs of micro-needle electrode pairs arranged on the base, a welding disc is arranged on the base, each pair of micro-needle electrode pairs comprises two needle bodies, the needle bodies are made of transparent materials, the metal layer is sprayed on the basal layer so as to form an auxiliary metal wire on the base and form a connecting electrode at the top end of each needle body, the connecting electrode is communicated with one end of each auxiliary metal wire, the other end of each auxiliary metal wire is connected with the welding disc, and a single myocardial cell can cover the connecting electrodes at the top ends of the two needle bodies simultaneously;
the insulation layer is arranged on the base layer and exposes the top end of the needle body and the pad, and the PDMS porous film layer covers the insulation layer.
2. A microneedle array electrode for detecting an electrical signal of a cardiac myocyte as set forth in claim 1, wherein:
the needle body is of a revolving body structure, and the distance between the central axes of the needle body in each pair of micro-needle electrode pairs is 30-50 mu m.
3. A microneedle array electrode for detecting an electrical signal of a cardiac myocyte as set forth in claim 1, wherein:
the base and the needle body in the substrate layer are made of high-light-transmission glass.
4. A microneedle array electrode for detecting an electrical signal of a cardiac myocyte as set forth in claim 1, wherein:
the needle body is a cylinder, and the diameter of the cylinder is 7-10 mu m.
5. A microneedle array electrode for detecting an electrical signal of a cardiac myocyte as set forth in claim 1, wherein:
the insulating layer is made of polyimide.
6. A microneedle array electrode for detecting an electrical signal of a cardiac myocyte as set forth in claim 1, wherein:
the bonding pad is connected with a port on a parallel flat cable on the PCB through a lead;
and the PCB is provided with a plurality of reference electrodes, and the reference electrodes are connected with ports on serial cables on the PCB.
7. The preparation method of the micro-needle array electrode for detecting the myocardial cell electric signal is characterized by comprising the following steps: comprises the following steps;
s1: selecting a high-light-transmission glass sheet with the thickness of 500 mu m and 4 inches as a base of the substrate layer;
s2: sequentially cleaning the base by using acetone, pure water, absolute ethyl alcohol and pure water for not less than 5 minutes;
s3: spin-coating a layer of photoresist on one surface of the base, forming a substrate layer with a needle body by etching by using a mask, and removing redundant photoresist;
s4: sequentially cleaning the basal layer with the needle bodies by using absolute ethyl alcohol and pure water for not less than 5 minutes, and airing for 1 hour after cleaning to obtain a dry basal layer;
s5: forming a conductive layer on the surface of the dried substrate layer through a magnetron sputtering metal layer, wherein the thickness of the conductive layer is 150nm, so that a connecting electrode is arranged at the top end of the needle body, and an auxiliary metal wire is arranged on the base;
s6: spin-coating an insulating material on the conducting layer except the top end of the pin body and the position of the pad on the base, so that the thickness of the insulating material is not more than 2 mu m, and baking to form an insulating layer;
s7: and covering a PDMS porous film layer on the insulating layer to form the microneedle array electrode.
8. A method of manufacturing a microneedle array electrode for detecting an electrical signal of a cardiac myocyte according to claim 7, wherein: the step S7 includes the following steps;
s71: preparing a PDMS prepolymer solution, removing bubbles in a vacuum box, wherein the vacuum degree during extraction is-15 kPa, and the extraction time is not less than 30 minutes;
s72: spin-coating a layer of PDMS prepolymer on the insulating layer so that the thickness of the PDMS prepolymer is not more than 20 μm, covering a male mold with a conical structure on the PDMS prepolymer in a reversed way, and curing at the temperature of 85 ℃ for 2 hours;
s73: and taking down the male die, cutting off the redundant PDMS film by using a knife, aligning and covering the PDMS film on the substrate layer under a microscope, and exposing the top end of the needle body and the bonding pad of the base to obtain the microneedle array electrode.
9. A method of manufacturing a microneedle array electrode for detecting an electrical signal of a cardiac myocyte according to claim 7, wherein: further comprising step S8;
s8: and correspondingly connecting the bonding pads on the microneedle array electrode with the ports of the parallel flat cables on the PCB one by one through leads.
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| CN202210748191.4A CN115096945A (en) | 2022-06-22 | 2022-06-22 | Micro-needle array electrode for detecting myocardial cell electric signals and preparation method thereof |
| PCT/CN2023/083939 WO2023246212A1 (en) | 2022-06-22 | 2023-03-26 | Microneedle array electrode used for measuring myocardial cell electrical signals and manufacturing method therefor |
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| CN202210748191.4A CN115096945A (en) | 2022-06-22 | 2022-06-22 | Micro-needle array electrode for detecting myocardial cell electric signals and preparation method thereof |
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| WO2023246212A1 (en) * | 2022-06-22 | 2023-12-28 | 中国人民解放军陆军军医大学 | Microneedle array electrode used for measuring myocardial cell electrical signals and manufacturing method therefor |
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| CN102680526A (en) * | 2012-05-16 | 2012-09-19 | 清华大学 | Single cell array microchip and manufacturing, electrical measurement and electroporation methods thereof |
| CN104531524A (en) * | 2014-12-11 | 2015-04-22 | 国家纳米科学中心 | Micro-needle tip array chip for cell electroporation and application of micro-needle tip array chip |
| KR101978600B1 (en) * | 2018-02-19 | 2019-05-14 | 단국대학교 산학협력단 | Method for manufacturing micro probe electrode device with template |
| CN114469113A (en) * | 2021-12-31 | 2022-05-13 | 北京大学 | Multi-channel flexible microneedle electrode and preparation method |
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| KR101618923B1 (en) * | 2013-04-30 | 2016-05-18 | 단국대학교 산학협력단 | Micro-Tip Electrode and Method of forming the same |
| CN109171718B (en) * | 2018-08-03 | 2020-11-20 | 北京大学 | Microneedle electrode array device |
| CN112631425B (en) * | 2020-12-21 | 2022-03-22 | 上海交通大学 | Microneedle array type brain-computer interface device and preparation method thereof |
| CN115096945A (en) * | 2022-06-22 | 2022-09-23 | 中国人民解放军陆军军医大学 | Micro-needle array electrode for detecting myocardial cell electric signals and preparation method thereof |
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| CN102680526A (en) * | 2012-05-16 | 2012-09-19 | 清华大学 | Single cell array microchip and manufacturing, electrical measurement and electroporation methods thereof |
| CN104531524A (en) * | 2014-12-11 | 2015-04-22 | 国家纳米科学中心 | Micro-needle tip array chip for cell electroporation and application of micro-needle tip array chip |
| KR101978600B1 (en) * | 2018-02-19 | 2019-05-14 | 단국대학교 산학협력단 | Method for manufacturing micro probe electrode device with template |
| CN114469113A (en) * | 2021-12-31 | 2022-05-13 | 北京大学 | Multi-channel flexible microneedle electrode and preparation method |
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| WO2023246212A1 (en) * | 2022-06-22 | 2023-12-28 | 中国人民解放军陆军军医大学 | Microneedle array electrode used for measuring myocardial cell electrical signals and manufacturing method therefor |
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