WO2002099408A1 - Signal detecting sensor provided with multi-electrode - Google Patents
Signal detecting sensor provided with multi-electrode Download PDFInfo
- Publication number
- WO2002099408A1 WO2002099408A1 PCT/JP2002/005569 JP0205569W WO02099408A1 WO 2002099408 A1 WO2002099408 A1 WO 2002099408A1 JP 0205569 W JP0205569 W JP 0205569W WO 02099408 A1 WO02099408 A1 WO 02099408A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sensor
- electrode
- electrodes
- cell
- sensor according
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
- G01N33/48728—Investigating individual cells, e.g. by patch clamp, voltage clamp
Definitions
- the present invention relates to a sensor for measuring an electrophysiological property of a biological sample.
- the present invention also relates to a sensor device capable of artificially reconstructing a nerve cell network, a sensor device applicable to simple and high-speed drug screening, and an intercellular network analysis device and a drug screening device equipped with the sensor.
- a sensor device capable of artificially reconstructing a nerve cell network
- a sensor device applicable to simple and high-speed drug screening and an intercellular network analysis device and a drug screening device equipped with the sensor.
- Screening drugs has been performed by measuring the electrical activity of cells exposed to the drug.
- the electrical activity of cells is usually measured by a patch clamp method, a method using a fluorescent dye or a luminescence indicator, or the like.
- the patch clamp method is a method of electrically recording the transport of ions through a single channel protein molecule using a microscopic portion (patch) of the cell membrane attached to the tip of a micropit.
- Patch clamp is one of the few techniques in cell biology that allows one to study the function of a single protein molecule in real time (Molecular Biology of Cells, Third Edition, Garl and P u1 ishing, Inc., New York, 1994, Japanese edition, translated by Keiko Nakamura et al., 181-182, 1995, Kyoikusha).
- the electrical activity of cells can also be measured by combining luminescence indicators or fluorescent dyes that emit light in response to changes in the concentration of specific ions with the latest image processing methods (for example, by taking a fluorescent image of a cell with a CCD camera, etc.). Monitor the movement of ions within the cell).
- the patch clamp method requires special techniques such as micropipetting. In short, it is not suitable for high-speed screening of a large number of drug candidate compounds.
- a method using a fluorescent dye or the like can screen a large number of drug candidate compounds at high speed, but requires a step of staining cells. There was a disadvantage that the SZN ratio was poor due to bleaching. In cell potential measurement, a device that can obtain data of the same quality as the data obtained by the patch clamp method and that can be simply, quickly, and automatically like the fluorescent dye method is desired.
- the present invention is an improvement of the above-described conventional cell electrical activity measuring device, and a sensor capable of measuring the electrical activity of a large number of cells at once at a time and a signal transmission between subject cells. It is an object of the present invention to provide a device capable of detecting the same. Disclosure of the invention
- the present inventors have used micromachine technology to form minute holes in a substrate device with a diameter or a side of 0.5 to 5 mm, and to process a large number of samples at once with an accuracy close to the conventional patch clamp method.
- An electrophysiological measurement device that can be measured has been realized.
- the present invention relates to a sensor that includes a plurality of electrodes disposed on a substrate and separately measures each of signals generated by a biological sample held on each of the electrodes.
- Each of the electrodes includes a depression for holding a biological sample, a through hole communicating with the depression, and penetrating through the back surface of the substrate, an electrode portion, and a lead wire from the electrode portion.
- the samples held in each of the depressions are arranged so as to be electrically connected to each other.
- the signal is a signal responsive to a stimulus given to a biological sample held on one of the plurality of electrodes.
- each of the plurality of electrodes is arranged such that the centers thereof are spaced apart from each other by at least 20 m.
- the substrate is a silicon wafer, Teflon, polystyrene, poly force Made of a material selected from the group consisting of polyponate, polyethylene terephthalate, polyimide, acrylic, silicon rubber, PMDS, and elastomer.
- the electrode section is made of gold, platinum, silver chloride, silver, and platinum black. , Made from a material selected from the group consisting of ITO.
- the depression for holding the biological sample has a depth of 1 to 10111, an opening diameter of 10 to 50 im, and a diameter of the through hole of 2 to 1 ⁇ . ⁇ .
- the biological sample is a nerve cell
- the nerve cell held by each of the electrodes reconfigures a network of nerve cells according to the arrangement of the plurality of electrodes.
- the stimulus is provided through at least one of the plurality of electrodes.
- the senor further includes a counter electrode for the electrode, and when the biological sample is a nerve cell, can fix the membrane potential of the nerve cell.
- the senor further includes a reference electrode.
- the reference electrode is a ring-shaped electrode having a diameter of 100 to 100 m made from a ribbon-shaped member having a line width of 1 to 100 / m.
- the electrode portion and the lead-out line are patterned on the back surface of the substrate and drawn out to the periphery of the substrate.
- the senor further includes means for holding the biological sample in close contact with the plurality of electrodes.
- the means for holding the biological sample in close contact is a suction line.
- the sensor includes means for controlling means for holding the biological sample in close contact.
- the present invention also provides the above sensor, cell accommodation means arranged on the sensor, means for maintaining the sensor in which the cell accommodation means is arranged under cell growth conditions,
- the present invention relates to an intercellular network analyzer, comprising: means for holding the sample in close contact with each electrode; means for obtaining an electric signal from each electrode of the sensor; and means for processing the electric signal.
- the present invention also relates to a sensor, a cell accommodating means arranged on the sensor, a means for maintaining the sensor in which the cell accommodating means is arranged under cell growth conditions, and a movement of the sensor in which the cell accommodating means is arranged High-speed drug screening comprising: means for performing the following steps: means for holding the sample in close contact with each electrode of the sensor; means for obtaining an electric signal from each electrode of the sensor; and means for processing the electric signal.
- High-speed drug screening comprising: means for performing the following steps: means for holding the sample in close contact with each electrode of the sensor; means for obtaining an electric signal from each electrode of the sensor; and means for processing the electric signal.
- the sensor of the present invention having the above configuration enables detection of noise accompanying opening and closing of ion channels, which was impossible with ordinary extracellular recording, and artificially reconstructed nerve cells on the sensor It also enabled analysis of signal transmission in networks.
- FIG. 1 is a diagram showing the measurement principle and structure of the sensor of the present invention in comparison with a conventional sensor using microelectrodes.
- the right side of FIG. 1 shows a part of the structure of the sensor of the present invention, and the left side of FIG. 1 shows a conventional sensor using microelectrodes.
- FIG. 2 is a plan view of the sensor of the present invention.
- FIG. 3 is a plan view, a cross-sectional view, and a rear view of the electrode, showing a plan view of the sensor of the present invention and an enlarged view of the structure of the electrode that is a part of the sensor.
- FIG. 4 is a plan view schematically showing a modified example of the sensor of the present invention, and a cross-sectional view of an electrode showing an enlarged structure of an electrode which is a part of the sensor.
- FIG. 5 is a cross-sectional view schematically showing a modified example of the sensor of the present invention.
- FIG. 6 is a sectional view schematically showing a modified example of the sensor of the present invention.
- FIG. 7 is a sectional view schematically showing a modified example of the sensor of the present invention.
- FIG. 8 is a schematic diagram showing the configuration of the intercellular network analysis device of the present invention.
- FIG. 9 is a diagram showing the results of tests performed using the cell potential measurement depiice of the present invention.
- FIG. 10 is a diagram showing the results of tests performed using the cell potential measuring device of the present invention.
- FIG. 11 is a diagram showing the results of tests performed using the cell potential measuring device of the present invention.
- FIGS. 1 to 11 indicate the following members, respectively.
- FIG. 1 schematically shows the principle of measurement by the sensor of the present invention and the outline of the electrode structure.
- a culture vessel is placed in a cylindrical vessel 2 arranged on a substrate 1 and accommodates a biological sample such as a cell.
- the left side of FIG. 1 shows an electrode structure provided with a conventional flat microelectrode 6 on which cells are placed, and the right side of FIG. 1 shows an example of the electrode structure of the present invention, which is located at the center of a cylindrical vessel 2.
- the test cell indicated by the ellipse is captured or held in the depression 3 which is a part of the cell holding means provided on the substrate 1.
- the cell holding means includes a depression 3 formed in the substrate 1, a through hole 7 communicating with the depression 3 through the opening 5, and a suction line (not shown).
- a measurement electrode 9 serving as signal detection means is disposed in the through hole 7.
- the measurement electrode 9 is connected to a signal detection unit (not shown) via the wiring 8.
- the through hole 7 forms a part of a suction part communicating with a suction means such as a suction pump and is connected to a cell suction means (not shown).
- a suction means such as a suction pump
- a cell suction means not shown.
- the unit of the structure including the above-described dent arranged on the substrate and the measurement electrode arranged in the through hole communicating with the dent is defined as “electrode” or “electrode structure”.
- electrode structure a device configuration that includes a substrate that supports it, a cell-accommodating member, and a lead wire connected to the electrode is defined as a “sensor”.
- a part of the cell is shown to fit into the opening of the depression 3. Since the cells and the substrate 1 are held in close contact with each other, electric signals generated from the cells do not leak into the culture solution 4.
- the conventional flat microelectrode shown on the left of Fig. 1 most of the electrical signals emitted from the cells leak into the culture solution 4 as indicated by the arrows in the figure, and the signal detection sensitivity Is significantly lower.
- a reference electrode is further provided as necessary, and the measurement electrode 9 measures an electric signal of a cell with reference to a reference potential applied to the reference electrode.
- the reference electrode is a wire made of a material such as gold, platinum, or silver monochloride having a cross section of about 100 to about 1000 im in diameter. And shape.
- one or more reference electrodes are provided per well as necessary, thereby improving the measurement accuracy of the cell potential.
- Such a sensor having one or more depressions is formed by conventional micromachining technology.
- FIG. 2 shows an example of an embodiment of the sensor of the present invention.
- FIG. 2 is a plan view of an example of an embodiment of the present invention.
- the electrodes provided with the depressions having the diameters of the openings of about 10 m are arranged in a matrix of 8 rows ⁇ 8 columns at the centers of about 20 m each. ing.
- Reference number 2 indicates the culture medium to be placed on the electrode and Is a container for accommodating cells.
- On the periphery of the board size 3 O mm x 30 mm), a total of 64 board terminal sections 10, which are derived from the measurement electrode of each electrode and are insulated from other electrodes or wiring, are provided. (The derivation line is not shown).
- FIG. 3 is an enlarged view showing an electrode structure according to an embodiment of the sensor of the present invention.
- each electrode has a recess 3 with an opening of about 10 // m in diameter
- the measuring electrode (also referred to herein as the electrode portion of the electrode) 9 is sputtered on the back of the substrate. It is patterned in the evening and the like, and is led out to the periphery of the substrate through the signal lead-out line 8.
- a through hole 7 having an opening diameter of about 3 m is provided.
- the three figures shown on the right side of Fig. 3 are enlarged views of one of the electrodes constituting the sensor.The part indicated by A surrounded by a dotted line on the left side of Fig.
- FIG. 7 is a plan view, a cross-sectional view along a straight line passing through the center of the depression 3, and a rear view.
- FIG. 4 also shows an example of an embodiment of the sensor of the present invention.
- the electrode is provided with one measurement electrode 9, one depression 3, and a through-hole 7, and the measurement electrode 9 is placed on the rear surface of the S ⁇ I substrate so as to contact the through-hole 7. It is patterned.
- a ring-shaped reference electrode 11 having a diameter of 100 ⁇ m and made of a lipon-shaped member having a line width of 100 im is arranged on a wall of a vessel for accommodating a biological sample.
- Figure 5 shows an example where the reference electrode is placed inside the vessel containing cells
- Figure 6 shows an example where the reference electrode is placed on part of the wall of the vessel containing cells and at the bottom of the vessel.
- the form and arrangement of the reference electrode can take a form appropriately selected according to the purpose of measurement and the biological sample to be measured.
- the reference electrode acts as a counter electrode to the measurement electrode and can fix the membrane potential of the retained cells (set the cell membrane potential to an arbitrary value).
- a weak electric pulse for example, a polarization pulse of 100 Hz is applied between the reference electrode and the measurement electrode, so that the ion permeability of the cell membrane of the cell held in the well can be improved.
- FIG. 7 shows an embodiment of a sensor having a suction line 15 according to the present invention.
- the line 15 is formed in a suction line attachment 20 arranged on the back surface of the substrate, and is connected to a suction means (not shown) such as an aspirator to improve the adhesion between the cell and the electrode structure. I can do it.
- the suction line attachment 20 is typically made of a material such as acrylic, PMDS, or silicone rubber, and is adhered to the back surface of the substrate over the measurement electrode.
- FIG. 8 schematically shows a configuration example of an intercellular network analysis device or a high-speed drug screening device incorporating the above-described sensor of the present invention.
- the configuration in FIG. 8 is as follows.
- A This is a culture device that maintains the sensor equipped with cell storage means under cell growth conditions. Provide an environment suitable for the growth and maintenance of the biological sample to be tested.
- B Means for moving the sensor from the culture device, and carries this sensor into the signal detection device C.
- C Signal detection device. It comprises a means for injecting or discharging a test solution, such as a reagent dispensing multipipette, a sensor equipped with the above multielectrode, an aspirator, or a suction pump.
- D Signal derivation cable
- E Signal processor (computer).
- connection between the components described above can be performed using a means known in the art, and the details will not be described.
- An intercellular network device incorporating the above-described sensor according to the present invention includes: a sensor; a cell storage means disposed on the sensor; a means for maintaining cell growth conditions; and an electrode for each of the sensors. Means for holding the sample in close contact, means for obtaining an electric signal from each electrode of the sensor, and means for processing the electric signal may be provided.
- the intercellular network device may further include a stimulus applying unit for applying a current to an arbitrary electrode on the sensor, and a microscope or an imaging unit for displaying a state of cells cultured on the sensor.
- the cell holding means usually holds a solution for maintaining cells.
- the means for maintaining the above cell growth conditions usually maintains the environment for accommodating the cells at a temperature, humidity, pH and gas composition that are optimal for cell growth.
- the means for processing the electrical signal typically acquires signals from each electrode of the sensor.
- the high-speed drug screening apparatus incorporating the sensor according to the present invention includes: a sensor; a cell storage means disposed on the sensor; a means for maintaining cell growth conditions; and a sensor in which the cell storage means is disposed. Means for holding the sample in close contact with each electrode of the sensor, means for obtaining an electric signal from each electrode of the sensor, and means for processing the electric signal.
- the high-speed drug screening apparatus may further include means for injecting or discharging a solution into or from the cell storage container at an arbitrary position on the sensor.
- the cell storage means usually holds a solution for maintaining cells.
- the means for maintaining the cell growth conditions generally maintains the environment for accommodating the cells so that the temperature, humidity, pH, and gas composition are optimal for cell growth.
- the means for processing the electrical signal usually acquires the signal from each electrode of the sensor individually and performs statistical processing.
- Nervous cells were prepared from the rat cerebral cortex on the 17th day of embryogenesis, suspended in Dulbecco's modified medium, and 5X was applied to each of the sensor vessels with 64 electrodes and vessels shown in Fig. 3.
- An artificial nerve cell network was reconstituted on the sensor by adding 10 5 cells to a concentration of Zm 1 and culturing for 2 weeks.
- the sensor including the reconstructed nerve cell network was connected to one of the 64 electrodes (the electrode (5th row, 6th column) shown in Fig. 9) using the device shown in Fig. 8.
- a constant voltage stimulus 50 ⁇ V
- a constant voltage stimulus is applied to one cell on the sensor, and the transmission of that stimulus is detected by the remaining 63 electrodes to detect the cell potential.
- FIG. 9 shows the results.
- Figure 9 is a hard copy of the signal processing device (computer screen). As shown in FIG. 9, interlocking signal transmission was observed in the encircled channels, that is, 24 out of 63 electrodes, confirming that the nerve cell network was reconfigured.
- the reconstructed neuronal network as in Examples 1 and 2 was treated with 40 D NQX (6,7-D initroquin ox alin e-2,3 (1H, 4H) —dione) for 10 minutes. did.
- a constant voltage stimulus was applied to one cell on the sensor, and the transmission of that stimulus was detected with the remaining 63 electrodes, and a response was observed at any of the electrodes. None (Fig. 11). This indicates that DNQX completely blocked the synaptic-mediated response to constant voltage stimulation.
- the sensor of the present invention can measure signal transmission in an artificially reconstructed neural cell network. Moreover, The sensor of the present invention has made it possible to measure the opening and closing frequency of the voltage-sensitive ion channel of a cell by fixing the membrane potential of the cell. Industrial applicability
- a sensor that can easily and quickly measure the electrical activity of a large number of cells at a time, and a device that can also detect signal transmission between subject cells.
- the device of the present invention overcomes the drawbacks of the conventional patch-clamp method that requires advanced technology and the fluorescent dye method that has many test steps and low SZN ratio.
- an apparatus capable of screening drug candidate compounds easily and at high speed is provided, and the time required for conventional drug screening can be dramatically reduced.
- this device automatically collects data and processes signals without the need for advanced special techniques, anyone can easily measure cell potential.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003502479A JP3570715B2 (ja) | 2001-06-05 | 2002-06-05 | マルチ電極を備えた信号検出用センサ |
EP02733327A EP1406086A4 (en) | 2001-06-05 | 2002-06-05 | SIGNAL DETECTION SENSOR WITH MULTI-ELECTRODE |
US10/479,938 US7006929B2 (en) | 2001-06-05 | 2002-06-05 | Signal detecting sensor provided with multi-electrode |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001-170340 | 2001-06-05 | ||
JP2001170340 | 2001-06-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002099408A1 true WO2002099408A1 (en) | 2002-12-12 |
Family
ID=19012275
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2002/005569 WO2002099408A1 (en) | 2001-06-05 | 2002-06-05 | Signal detecting sensor provided with multi-electrode |
Country Status (4)
Country | Link |
---|---|
US (1) | US7006929B2 (ja) |
EP (1) | EP1406086A4 (ja) |
JP (1) | JP3570715B2 (ja) |
WO (1) | WO2002099408A1 (ja) |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006129798A (ja) * | 2004-11-08 | 2006-05-25 | Onchip Cellomics Consortium | 細胞チップおよび細胞改変方法および細胞制御方法 |
JP2006521550A (ja) * | 2003-03-29 | 2006-09-21 | キネティック リミテッド | 化合物を分析するための方法及びシステム |
WO2006130990A2 (en) * | 2005-06-10 | 2006-12-14 | Neurosilicon (1145990 Alberta Ltd.) | Detecting electrical activity and assessing agents for the ability to influence electrical activity in neuronal cell networks |
JP2008518594A (ja) * | 2004-11-05 | 2008-06-05 | ウニベルジテート・オスナブリユツク | 細胞特性を測定するための装置および方法 |
JP2009085624A (ja) * | 2007-09-27 | 2009-04-23 | Nippon Telegr & Teleph Corp <Ntt> | 電気的活動刺激計測方法および電気的活動刺激計測装置 |
US7736477B2 (en) | 2004-08-25 | 2010-06-15 | Panasonic Corporation | Probe for measuring electric potential of cell |
US7927474B2 (en) | 2005-12-20 | 2011-04-19 | Panasonic Corporation | Cell electrophysiological sensor |
US8030059B2 (en) | 2003-11-21 | 2011-10-04 | Panasonic Corporation | Apparatus for measuring extracellular potential |
US8071363B2 (en) | 2006-05-25 | 2011-12-06 | Panasonic Corporation | Chip for cell electrophysiological sensor, cell electrophysiological sensor using the same, and manufacturing method of chip for cell electrophysiological sensor |
US8202439B2 (en) | 2002-06-05 | 2012-06-19 | Panasonic Corporation | Diaphragm and device for measuring cellular potential using the same, manufacturing method of the diaphragm |
US8232084B2 (en) | 2002-06-05 | 2012-07-31 | Panasonic Corporation | Device for measuring extracellular potential and method of manufacturing device |
US8314466B2 (en) | 2007-09-11 | 2012-11-20 | Panasonic Corporation | Silicon structure, method for manufacturing the same, and sensor chip |
US8318477B2 (en) | 2005-06-07 | 2012-11-27 | Panasonic Corporation | Cellular electrophysiological measurement device and method for manufacturing the same |
US8445263B2 (en) | 2006-07-06 | 2013-05-21 | Panasonic Corporation | Device for cellular electrophysiology sensor, cellular electrophysiology sensor using the device, and method for manufacturing the cellular electrophysiology sensor device |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4449519B2 (ja) * | 2004-03-22 | 2010-04-14 | パナソニック株式会社 | 細胞外電位測定デバイスおよびその製造方法 |
WO2007047989A2 (en) * | 2005-10-19 | 2007-04-26 | Duke University | Electrode systems and related methods for providing therapeutic differential tissue stimulation |
JP4582146B2 (ja) * | 2006-05-17 | 2010-11-17 | パナソニック株式会社 | 細胞電位測定デバイスとそれに用いる基板、細胞電位測定デバイス用基板の製造方法 |
FR2904872B1 (fr) * | 2006-08-09 | 2008-10-10 | Neuroservice Sarl | Appareil pour la mesure des variations de potentiel membranaire extracellulaire au moyen de microelectrodes |
US8460921B2 (en) * | 2006-09-18 | 2013-06-11 | University Of North Texas | Multinetwork nerve cell assay platform with parallel recording capability |
EP2343550B1 (en) * | 2009-12-30 | 2013-11-06 | Imec | Improved microneedle |
KR101631479B1 (ko) | 2014-01-07 | 2016-06-20 | 한국과학기술연구원 | 세포 스페로이드의 전기적 특성을 분석하기 위한 전극 구조체 |
JP6086412B1 (ja) | 2015-12-22 | 2017-03-01 | 日本航空電子工業株式会社 | 電気化学測定方法、電気化学測定装置及びトランスデューサ |
US20220365019A1 (en) * | 2021-05-14 | 2022-11-17 | Taiwan Semiconductor Manufacturing Company Ltd. | Fluid sensor system |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0678889A (ja) * | 1992-09-04 | 1994-03-22 | Matsushita Electric Ind Co Ltd | 一体化複合電極 |
JPH06296595A (ja) * | 1993-04-16 | 1994-10-25 | Matsushita Electric Ind Co Ltd | 一体化複合電極 |
JPH08122326A (ja) * | 1994-10-24 | 1996-05-17 | Fujitsu Ltd | 膜電位固定方法及びその装置 |
JPH09289886A (ja) * | 1996-04-25 | 1997-11-11 | Shimadzu Corp | 細胞膜電位検出装置 |
WO1999028037A1 (de) * | 1997-12-03 | 1999-06-10 | Micronas Gmbh | Vorrichtung zum messen physiologischer parameter |
JPH11187865A (ja) * | 1997-12-25 | 1999-07-13 | Matsushita Electric Ind Co Ltd | 細胞電位測定電極及びこれを用いた測定装置 |
WO1999064559A2 (fr) * | 1998-06-08 | 1999-12-16 | Haenni Claude | Dispositif de culture de cellules organiques et d'etude de leur activite electrophysiologique et membrane utilisee dans un tel dispositif |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4264728A (en) * | 1979-08-17 | 1981-04-28 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Indirect microbial detection |
US5178161A (en) * | 1988-09-02 | 1993-01-12 | The Board Of Trustees Of The Leland Stanford Junior University | Microelectronic interface |
US5378343A (en) * | 1993-01-11 | 1995-01-03 | Tufts University | Electrode assembly including iridium based mercury ultramicroelectrode array |
US5387329A (en) * | 1993-04-09 | 1995-02-07 | Ciba Corning Diagnostics Corp. | Extended use planar sensors |
US6193864B1 (en) * | 1996-05-16 | 2001-02-27 | Sendx Medical, Inc. | Locking sensor cartridge with integral fluid ports, electrical connections, and pump tube |
US5981268A (en) * | 1997-05-30 | 1999-11-09 | Board Of Trustees, Leland Stanford, Jr. University | Hybrid biosensors |
EP0978716B1 (de) * | 1998-08-01 | 2006-10-04 | ENDRESS + HAUSER WETZER GmbH + Co. KG | Vorrichtung und Verfahren zur Entnahme eines vorbestimmbaren Volumens einer Probe eines Mediums |
US6682649B1 (en) * | 1999-10-01 | 2004-01-27 | Sophion Bioscience A/S | Substrate and a method for determining and/or monitoring electrophysiological properties of ion channels |
DE19948473A1 (de) * | 1999-10-08 | 2001-04-12 | Nmi Univ Tuebingen | Verfahren und Vorrichtung zum Messen an in einer flüssigen Umgebung befindlichen Zellen |
US6484045B1 (en) * | 2000-02-10 | 2002-11-19 | Medtronic Minimed, Inc. | Analyte sensor and method of making the same |
-
2002
- 2002-06-05 WO PCT/JP2002/005569 patent/WO2002099408A1/ja not_active Application Discontinuation
- 2002-06-05 EP EP02733327A patent/EP1406086A4/en not_active Withdrawn
- 2002-06-05 JP JP2003502479A patent/JP3570715B2/ja not_active Expired - Lifetime
- 2002-06-05 US US10/479,938 patent/US7006929B2/en not_active Expired - Lifetime
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0678889A (ja) * | 1992-09-04 | 1994-03-22 | Matsushita Electric Ind Co Ltd | 一体化複合電極 |
JPH06296595A (ja) * | 1993-04-16 | 1994-10-25 | Matsushita Electric Ind Co Ltd | 一体化複合電極 |
JPH08122326A (ja) * | 1994-10-24 | 1996-05-17 | Fujitsu Ltd | 膜電位固定方法及びその装置 |
JPH09289886A (ja) * | 1996-04-25 | 1997-11-11 | Shimadzu Corp | 細胞膜電位検出装置 |
WO1999028037A1 (de) * | 1997-12-03 | 1999-06-10 | Micronas Gmbh | Vorrichtung zum messen physiologischer parameter |
JPH11187865A (ja) * | 1997-12-25 | 1999-07-13 | Matsushita Electric Ind Co Ltd | 細胞電位測定電極及びこれを用いた測定装置 |
WO1999064559A2 (fr) * | 1998-06-08 | 1999-12-16 | Haenni Claude | Dispositif de culture de cellules organiques et d'etude de leur activite electrophysiologique et membrane utilisee dans un tel dispositif |
Non-Patent Citations (1)
Title |
---|
HIROKAZU SUGIHARA, YASUSHI KOBAYASHI, MAKOTO TAKETANI: "Saibo den'i sokutei system oyobi daino hishitsu hattatsu katei kenkyu heno oyo", NATIONAL TECHNICAL REPORT, vol. 42, no. 2, 1996, pages 112 - 119, XP002955024 * |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8232084B2 (en) | 2002-06-05 | 2012-07-31 | Panasonic Corporation | Device for measuring extracellular potential and method of manufacturing device |
US8202439B2 (en) | 2002-06-05 | 2012-06-19 | Panasonic Corporation | Diaphragm and device for measuring cellular potential using the same, manufacturing method of the diaphragm |
JP2006521550A (ja) * | 2003-03-29 | 2006-09-21 | キネティック リミテッド | 化合物を分析するための方法及びシステム |
US8247218B2 (en) | 2003-11-21 | 2012-08-21 | Panasonic Corporation | Extracellular potential sensing element, device for measuring extracellular potential, apparatus for measuring extracellular potential and method of measuring extracellular potential by using the same |
US8030059B2 (en) | 2003-11-21 | 2011-10-04 | Panasonic Corporation | Apparatus for measuring extracellular potential |
US7736477B2 (en) | 2004-08-25 | 2010-06-15 | Panasonic Corporation | Probe for measuring electric potential of cell |
JP2008518594A (ja) * | 2004-11-05 | 2008-06-05 | ウニベルジテート・オスナブリユツク | 細胞特性を測定するための装置および方法 |
JP4585280B2 (ja) * | 2004-11-08 | 2010-11-24 | 一般社団法人オンチップ・セロミクス・コンソーシアム | 細胞チップおよび細胞改変方法および細胞制御方法 |
JP2006129798A (ja) * | 2004-11-08 | 2006-05-25 | Onchip Cellomics Consortium | 細胞チップおよび細胞改変方法および細胞制御方法 |
US8318477B2 (en) | 2005-06-07 | 2012-11-27 | Panasonic Corporation | Cellular electrophysiological measurement device and method for manufacturing the same |
WO2006130990A3 (en) * | 2005-06-10 | 2007-05-10 | Neurosilicon 1145990 Alberta L | Detecting electrical activity and assessing agents for the ability to influence electrical activity in neuronal cell networks |
WO2006130990A2 (en) * | 2005-06-10 | 2006-12-14 | Neurosilicon (1145990 Alberta Ltd.) | Detecting electrical activity and assessing agents for the ability to influence electrical activity in neuronal cell networks |
US7927474B2 (en) | 2005-12-20 | 2011-04-19 | Panasonic Corporation | Cell electrophysiological sensor |
US8071363B2 (en) | 2006-05-25 | 2011-12-06 | Panasonic Corporation | Chip for cell electrophysiological sensor, cell electrophysiological sensor using the same, and manufacturing method of chip for cell electrophysiological sensor |
US8445263B2 (en) | 2006-07-06 | 2013-05-21 | Panasonic Corporation | Device for cellular electrophysiology sensor, cellular electrophysiology sensor using the device, and method for manufacturing the cellular electrophysiology sensor device |
US8314466B2 (en) | 2007-09-11 | 2012-11-20 | Panasonic Corporation | Silicon structure, method for manufacturing the same, and sensor chip |
US8816450B2 (en) | 2007-09-11 | 2014-08-26 | Panasonic Corporation | Fibrous projections structure |
JP2009085624A (ja) * | 2007-09-27 | 2009-04-23 | Nippon Telegr & Teleph Corp <Ntt> | 電気的活動刺激計測方法および電気的活動刺激計測装置 |
Also Published As
Publication number | Publication date |
---|---|
EP1406086A1 (en) | 2004-04-07 |
JP3570715B2 (ja) | 2004-09-29 |
JPWO2002099408A1 (ja) | 2004-09-16 |
EP1406086A4 (en) | 2007-10-31 |
US7006929B2 (en) | 2006-02-28 |
US20040167723A1 (en) | 2004-08-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP3570715B2 (ja) | マルチ電極を備えた信号検出用センサ | |
US20030113833A1 (en) | Device for measuring extracellular potential, method of measuring extracellular potential by using the same and apparatus for quickly screening drug provided therewith | |
EP1300678B1 (en) | Extracellular recording integrated composite electrode | |
JPWO2009038079A1 (ja) | 細胞測定容器、細胞外電位測定方法、薬品検査方法 | |
US20050231186A1 (en) | High throughput electrophysiology system | |
US7594984B2 (en) | Apparatus and method for measuring activity signals of biological samples | |
US20050237065A1 (en) | Compartment-arrayed probe for measuring extracellular electrical potential and method of measuring pharmacological effect using the same | |
JPH0862209A (ja) | 細胞電位測定装置 | |
JP2003532116A (ja) | 電気化学的センシング | |
US7326384B2 (en) | Method and apparatus for detecting physicochemical changes emitted by biological sample | |
CN112673252A (zh) | 使用基于chemfet传感器阵列的系统进行细胞分析 | |
Eiler et al. | Application of a thin-film transistor array for cellular-resolution electrophysiology and electrochemistry | |
Wu et al. | New acid biosensor for taste transduction based on extracellular recording of PKD channels | |
EP1398625A1 (en) | Extracellular recording electrode | |
EP3591377B1 (en) | Electrochemical determination of the permeability of biological membranes and cellular layers | |
US20050227139A1 (en) | Device and methods for carring out electrical measurements on membrane bodies | |
JP2004020238A (ja) | 生体反応計測チップ、およびそれを用いた生体反応測定方法および装置 | |
Picollo et al. | The definitive version is available at | |
JP3182127U (ja) | 細胞外電位計測装置及び方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2003502479 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10479938 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002733327 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2002733327 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2002733327 Country of ref document: EP |