CN203772786U - Chip type interdigital array electrode impedance sensor - Google Patents
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- CN203772786U CN203772786U CN201420178754.1U CN201420178754U CN203772786U CN 203772786 U CN203772786 U CN 203772786U CN 201420178754 U CN201420178754 U CN 201420178754U CN 203772786 U CN203772786 U CN 203772786U
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- 239000011521 glass Substances 0.000 claims abstract description 22
- 238000003491 array Methods 0.000 claims description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 229910052697 platinum Inorganic materials 0.000 claims description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229920005573 silicon-containing polymer Polymers 0.000 claims description 2
- 238000012544 monitoring process Methods 0.000 abstract description 8
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- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 6
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 6
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 3
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- 238000005459 micromachining Methods 0.000 description 2
- 229920002120 photoresistant polymer Polymers 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
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- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 239000003684 drug solvent Substances 0.000 description 1
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- 229910052719 titanium Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The utility model discloses a chip type interdigital array electrode impedance sensor. The chip type interdigital array electrode impedance sensor comprises a glass culture dish, an impedance sensitive element, a glass slide, a cell micro-culture cavity, an array switch, an impedance analyzer and a processor, wherein the glass slide is arranged in the glass culture dish; the impedance sensitive element is arranged on the glass slide; the cell micro-culture cavity is arranged above a region of the impedance sensitive element; the impedance sensitive element is connected with the array switch; the array switch, the impedance analyzer and the processor are connected with one another in sequence. The sensor can be used for monitoring states of single cells and multiple cells and the influences of external stimulation on cells.
Description
Technical field
The utility model relates to cell detection field, is specifically related to the interdigital array electrode impedance transducer of a kind of chip type that cell behavior is detected.
Background technology
Traditional biological detection method comprises biochemistry and immunology detection, as adopted fluorochrome label method can detect various features albumen; Adopt MTT/XTT colorimetric method for determining cytoactive etc.Above-mentioned traditional biochemistry detection method need to be carried out mark to sample to be tested, cannot monitor the pilot process state of cell; On the other hand, said method is terminal test, can not carry out in real time cell, dynamic monitoring.
The rise of biological electronics provides new technological means for traditional cell detection.A kind of typical case's application is that cell is cultivated on metal microelectrode, by detecting impedance variation value, realizes cell state and the monitoring of outside stimulus to impact cell, and the method is called cell impedance detection.Cell impedance detection as a kind of in real time, non-intrusion type, without mark, detection means easy and simple to handle, progressively become efficient analysis tool of biomedical sector, have broad application prospects.
Impedance transducer produces excitation source without external optical system, does not need complicated processing of circuit unit to carry out frequency feedback processing, therefore, can realize the microminaturization of system.In conjunction with micromachining technology and technique, can realize the integrated of impedance transducer and micro-fluidic chip, parallel high flux is detected becomes possibility.
Employing has the metal electrode of micro-meter scale as the detecting electrode of impedance transducer, and impedance transducer can be monitored the physiological status of microelectrode near zone cell, and is converted to the formal output of impedance spectrum.Impedance Z
fas the function of frequency, can obtain by following formula: Z
f=V
f/ I
f, wherein, V
ffor being applied to the driving voltage on detecting electrode, I
ffor flowing through the electric current of electrode; Another kind of form is to adopt electric current as driving source, by lock-in amplifier monitoring voltage, changes.
Although have some both at home and abroad about utilizing cell impedance detection technology to study the report of cell behavior, but exist pick-up unit integrated level low, response sensitivity is low---and only can react whole cell response in whole culture chamber, cannot accurately measure the problems such as certain cell behavior.Therefore be badly in need of a kind ofly studying unicellular and high sensitivity cell impedance analysis system many cells behavior simultaneously.
Utility model content
In view of this, the purpose of this utility model is to provide and the utility model proposes the interdigital array electrode impedance transducer of a kind of chip type, and this sensor can be realized unicellular and cellulous state and the monitoring of environmental stimuli to impact cell.
The utility model is achieved through the following technical solutions, and the interdigital array electrode impedance transducer of chip type comprises glass culture dish, impedance sensitive element, microslide, the micro-culture chamber of cell, array switch, electric impedance analyzer and processor; Described microslide is arranged in glass culture dish, and described impedance sensitive element is arranged on microslide, and the micro-culture chamber of described cell is arranged on the region at impedance sensitive element place; Described impedance sensitive element is connected with array switch, and described array switch, electric impedance analyzer, processor connect successively.Described electric impedance analyzer is realized the measurement of wide frequency ranges internal impedance value; Described processor is realized collection, analytic method of data etc.
Further, described impedance sensitive element is three groups of interdigital microelectrode arrays, described three groups of interdigital microelectrode array shapes triangular in shape are distributed on microslide, and the electrode of every group of interdigital microelectrode array is alternately connected with one of two buses of place electrod-array; A bus end of three groups of interdigital microelectrode arrays is connected to form common port by lead-in wire; Another bus of described three groups of interdigital microelectrode arrays is connected with corresponding connection gasket by lead-in wire respectively with common port.
Further, described interdigital microelectrode array is formed on microslide by miromaching.
Further, described interdigital microelectrode array is platinum electrode, and its thickness is 100nm, and the spacing of electrode and width are 10 μ m.
Further, described glass culture dish comprises the end and the lid matching with it of a flat circle plate-like, and the lid of glass culture dish covers as the chamber of the micro-culture chamber of cell,
Further, the cell micro-culture chamber of the micro-culture chamber of described cell for being built by dimethyl silicone polymer.。
Compared with prior art, the utlity model has following advantage:
1, the sensitive element of impedance transducer adopts the interdigital array metal electrode of micro-meter scale, by miromaching, is made in glass slide surface, has improved the degree of integration of sensor.
2, every group of interdigital microelectrode array is interconnected by two buses, the sensitivity that has greatly improved impedance detection; A bus end of three groups of circular interdigital microelectrode arrays is connected to form common port by lead-in wire, as with reference to electrode, improved sensor degree of integration, coordinate the use of array switch, can realize in this impedance sensing apparatus simultaneously cell state in 3 micro-culture chambers of cell harmless, dynamically, Real-Time Monitoring.
Accompanying drawing explanation
In order to make the purpose of this utility model, technical scheme and advantage clearer, below in conjunction with accompanying drawing, the utility model is described in further detail, wherein:
Fig. 1 is the interdigital array electrode impedance transducer of chip type structural representation;
Fig. 2 is the circular interdigital microelectrode array of three groups on microslide, connecting line and connection gasket distribution schematic diagram;
Fig. 3 is interdigital microelectrode array and interconnection thereof;
Fig. 4 is that the continuous dynamic monitoring human body of impedance transducer of the present invention tm cells is subject to after dexamethasone drug effect impedance curve map over time;
Wherein, 1, glass culture dish; 2, interdigital microelectrode array; 3, microslide; 4, the micro-culture chamber of cell; 5, array switch; 6, electric impedance analyzer; 7, processor; 8, bus; 9, common port; 10, connection gasket.
Embodiment
Below with reference to accompanying drawing, preferred embodiment of the present utility model is described in detail; Should be appreciated that preferred embodiment is only for the utility model is described, rather than in order to limit protection domain of the present utility model.
As shown in Figure 1, the interdigital array electrode impedance transducer of chip type, comprises glass culture dish 1, impedance sensitive element 2, microslide 3, the micro-culture chamber 4 of cell, array switch 5, electric impedance analyzer 6 and processor 7; Described microslide is arranged in glass culture dish, and described impedance sensitive element is arranged on microslide, and the micro-culture chamber of described cell is arranged on the region at impedance sensitive element place; Described impedance sensitive element is connected with array switch, and described array switch, electric impedance analyzer, processor connect successively.
As shown in Figure 2,3, described impedance sensitive element is three groups of interdigital microelectrode arrays, described three groups of interdigital microelectrode array shapes triangular in shape are distributed on microslide, and the electrode of every group of interdigital microelectrode array is alternately connected with one of two buses 8 of place electrod-array; A bus end of three groups of interdigital microelectrode arrays is connected to form common port 9 by lead-in wire; Another bus of described three groups of interdigital microelectrode arrays is connected with corresponding connection gasket 10 by lead-in wire respectively with common port.
Described interdigital microelectrode array is formed on microslide by miromaching.
Described interdigital microelectrode array is platinum electrode, and its thickness is 100nm, and the spacing of electrode and width are 10 μ m.
Described glass culture dish comprises the end and the lid matching with it of a flat circle plate-like, and the lid of glass culture dish is as the chamber lid of the micro-culture chamber of cell.
The utility model utilizes miromaching to make metal microelectrode array as the sensitive element of cell impedance detection, utilizes PDMS to build the micro-culture chamber of cell, and cell is cultivated on interdigital microelectrode array.By connection gasket, apply a faint sinusoidal excitation, due to the high-insulativity (10 of cell membrane
-7s/m), cell produces inhibition by the distribution to electrode surface electric field during adherent growth on microelectrode.When Growth of Cells, division, propagation, apoptosis or when being subject to drug effect and causing corresponding metamorphosis, by the transformed value of Impedance measurement, can indirectly reflect the physiological status of cell.The preparation method of the utility model impedance transducer is as follows:
Selection is of a size of the glass slide of 75mm * 25mm as dielectric base material, utilizes the lift-off technique in micromachining technology to make impedance sensitive element thereon---interdigital microelectrode array and extension line, connection gasket etc.First microslide is cleaned and dried through standard technology; Rotary coating S1813 photoresist in glass substrate material; Photoetching, development form three groups of circular interdigital microelectrode arrays, connecting line and connection gasket graphics fields on microslide; The Titanium that electron beam evaporation formation thickness is 20nm is as adhesion layer; The metal platinum that the thickness of evaporation formation is thereon 100nm is again as sensing electrode layer; In acetone, dissolve photoresist, obtain the sensitive element that contains metal microelectrode.
Prepare the micro-culture chamber of cell: PDMS matrix is mixed by the mass ratio of 10:1 with hardening agent, and the degassed processing of uniform stirring prepares PDMS prepolymer after 1 hour.Utilize PDMS prepolymer to make three cavitys that internal diameter is 1cm.Utilize PDMS prepolymer to be attached to three groups of circular interdigital microelectrode array corresponding positions 3 micro-culture chambers of cell, after PDMS prepolymer cures, can realize the unidirectional type bonding of cavity and glass slide, thereby form three independently Growth of Cells spaces.
Microslide containing interdigital microelectrode array is placed in to double dish, by lead-in wire, connection gasket is drawn with array switch and is connected.The outer testing system of impedance transducer only comprises an electric impedance analyzer, by switch arrays can implement device in the Real-Time Monitoring of cell state in 3 micro-culture chambers of cell.
Use-case: the microslide containing interdigital microelectrode array preparing is invaded and steeped half an hour with alcohol, then clean up with deionized water, dry up with nitrogen, be placed in double dish.In three micro-culture chambers of cell, inject 100mL cell culture fluid, be placed on cell culture incubator interior after standing 5 minutes, in three micro-culture chambers of cell, add concentration is the human body tm cells suspending liquid of 100cell/ μ L simultaneously; Then in three culture chambers, adding respectively 100mL concentration is dexamethasone (DEX) drug solvent and the cell culture fluid of 10-8mol/L, 10-7mol/L.By electric impedance analyzer, in frequency, be under 40kHz condition, cell impedance variation value to be monitored for a long time, experimental result as shown in Figure 4.
The foregoing is only preferred embodiment of the present utility model, be not limited to the utility model, obviously, those skilled in the art can carry out various changes and modification and not depart from spirit and scope of the present utility model the utility model.Like this, if within of the present utility model these are revised and modification belongs to the scope of the utility model claim and equivalent technologies thereof, the utility model is also intended to comprise these changes and modification interior.
Claims (6)
1. the interdigital array electrode impedance transducer of chip type, is characterized in that: comprise glass culture dish (1), impedance sensitive element (2), microslide (3), the micro-culture chamber of cell (4), array switch (5), electric impedance analyzer (6) and processor (7); Described microslide is arranged in glass culture dish, and described impedance sensitive element is arranged on microslide, and the micro-culture chamber of described cell is arranged on the region at impedance sensitive element place; Described impedance sensitive element is connected with array switch, and described array switch, electric impedance analyzer, processor connect successively.
2. the interdigital array electrode impedance transducer of chip type according to claim 1, it is characterized in that: described impedance sensitive element is three groups of interdigital microelectrode arrays, described three groups of interdigital microelectrode array shapes triangular in shape are distributed on microslide, and the electrode of every group of interdigital microelectrode array is alternately connected with one of two buses (8) of place electrod-array; A bus end of three groups of interdigital microelectrode arrays is connected to form common port (9) by lead-in wire; Another bus of described three groups of interdigital microelectrode arrays is connected with corresponding connection gasket (10) by lead-in wire respectively with common port.
3. the interdigital array electrode impedance transducer of chip type according to claim 2, is characterized in that: described interdigital microelectrode array is formed on microslide by miromaching.
4. the interdigital array electrode impedance transducer of chip type according to claim 2, is characterized in that: described interdigital microelectrode array is platinum electrode, and its thickness is 100nm, and the spacing of electrode and width are 10 μ m.
5. the interdigital array electrode impedance transducer of chip type according to claim 1, is characterized in that: described glass culture dish comprises the end and the lid matching with it of a flat circle plate-like, and the lid of glass culture dish is as the chamber lid of the micro-culture chamber of cell.
6. the interdigital array electrode impedance transducer of chip type according to claim 1, is characterized in that: the cell micro-culture chamber of the micro-culture chamber of described cell for being built by dimethyl silicone polymer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201420178754.1U CN203772786U (en) | 2014-04-14 | 2014-04-14 | Chip type interdigital array electrode impedance sensor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201420178754.1U CN203772786U (en) | 2014-04-14 | 2014-04-14 | Chip type interdigital array electrode impedance sensor |
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| CN (1) | CN203772786U (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104849322A (en) * | 2015-04-22 | 2015-08-19 | 中国农业大学 | Impedance biosensor and bio-impedance detection analysis method |
| CN106047678A (en) * | 2016-05-20 | 2016-10-26 | 江苏大学 | Cell activity detection method and device based on impedance spectroscopy |
| CN108037159A (en) * | 2017-11-02 | 2018-05-15 | 江苏大学 | A kind of cytoactive detection method and device based on impedance spectrum integration feature |
| CN108896642A (en) * | 2018-05-11 | 2018-11-27 | 江苏大学 | A kind of interdigital electrode cell activity impedance transducer refers to gap experimental rig and method |
| WO2018234238A1 (en) * | 2017-06-21 | 2018-12-27 | Institut für Bioprozeß- und Analysentechnik e.V. | Multi-electrode field for impedance measurement on adherent cells |
| CN110982682A (en) * | 2019-11-20 | 2020-04-10 | 东南大学 | High-throughput cell detection system based on passive wireless technology |
| CN111272819A (en) * | 2020-02-21 | 2020-06-12 | 中山大学 | Interdigital arrangement conductive nanotube sensing device for detecting multi-element activity of myocardial cells |
| CN111304083A (en) * | 2020-03-10 | 2020-06-19 | 中国科学院苏州生物医学工程技术研究所 | Cell culture chip and method for monitoring cell state thereof |
| CN111655325A (en) * | 2017-12-18 | 2020-09-11 | 丹·萨克斯 | Devices, systems, and methods for therapeutic muscle stimulation |
| CN115586227A (en) * | 2022-09-30 | 2023-01-10 | 北京大学 | Chemotherapy drug quantitative screening method based on remote cloud diagnosis integrated sensing device |
-
2014
- 2014-04-14 CN CN201420178754.1U patent/CN203772786U/en not_active Expired - Lifetime
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104849322A (en) * | 2015-04-22 | 2015-08-19 | 中国农业大学 | Impedance biosensor and bio-impedance detection analysis method |
| CN104849322B (en) * | 2015-04-22 | 2017-10-24 | 中国农业大学 | A kind of impedance biosensor and bio-impedance determination method |
| CN106047678A (en) * | 2016-05-20 | 2016-10-26 | 江苏大学 | Cell activity detection method and device based on impedance spectroscopy |
| CN106047678B (en) * | 2016-05-20 | 2018-04-24 | 江苏大学 | A kind of cytoactive detection method and apparatus based on Measured By Impedance Spectroscopy |
| WO2018234238A1 (en) * | 2017-06-21 | 2018-12-27 | Institut für Bioprozeß- und Analysentechnik e.V. | Multi-electrode field for impedance measurement on adherent cells |
| CN108037159A (en) * | 2017-11-02 | 2018-05-15 | 江苏大学 | A kind of cytoactive detection method and device based on impedance spectrum integration feature |
| CN108037159B (en) * | 2017-11-02 | 2019-12-03 | 江苏大学 | A kind of cytoactive detection method and device based on impedance spectrum integral feature |
| CN111655325A (en) * | 2017-12-18 | 2020-09-11 | 丹·萨克斯 | Devices, systems, and methods for therapeutic muscle stimulation |
| CN108896642A (en) * | 2018-05-11 | 2018-11-27 | 江苏大学 | A kind of interdigital electrode cell activity impedance transducer refers to gap experimental rig and method |
| CN110982682A (en) * | 2019-11-20 | 2020-04-10 | 东南大学 | High-throughput cell detection system based on passive wireless technology |
| CN110982682B (en) * | 2019-11-20 | 2022-07-29 | 东南大学 | High-throughput cell detection system based on passive wireless technology |
| CN111272819A (en) * | 2020-02-21 | 2020-06-12 | 中山大学 | Interdigital arrangement conductive nanotube sensing device for detecting multi-element activity of myocardial cells |
| CN111304083A (en) * | 2020-03-10 | 2020-06-19 | 中国科学院苏州生物医学工程技术研究所 | Cell culture chip and method for monitoring cell state thereof |
| CN111304083B (en) * | 2020-03-10 | 2024-02-09 | 中国科学院苏州生物医学工程技术研究所 | Cell culture chip and method for monitoring cell state thereof |
| CN115586227A (en) * | 2022-09-30 | 2023-01-10 | 北京大学 | Chemotherapy drug quantitative screening method based on remote cloud diagnosis integrated sensing device |
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Granted publication date: 20140813 |