EP1084404A1 - Apparatus for measuring the electrophysiological activity of a group of cells - Google Patents
Apparatus for measuring the electrophysiological activity of a group of cellsInfo
- Publication number
- EP1084404A1 EP1084404A1 EP99923355A EP99923355A EP1084404A1 EP 1084404 A1 EP1084404 A1 EP 1084404A1 EP 99923355 A EP99923355 A EP 99923355A EP 99923355 A EP99923355 A EP 99923355A EP 1084404 A1 EP1084404 A1 EP 1084404A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- measurement
- cells
- electrodes
- support
- electrode
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 230000000694 effects Effects 0.000 title claims description 7
- 238000005259 measurement Methods 0.000 claims abstract description 69
- 230000010412 perfusion Effects 0.000 claims abstract description 10
- 238000010438 heat treatment Methods 0.000 claims description 11
- 230000000638 stimulation Effects 0.000 claims description 7
- 238000001802 infusion Methods 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 230000006870 function Effects 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 4
- 230000008520 organization Effects 0.000 description 3
- 230000003321 amplification Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
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
- G01N33/4833—Physical analysis of biological material of solid biological material, e.g. tissue samples, cell cultures
- G01N33/4836—Physical analysis of biological material of solid biological material, e.g. tissue samples, cell cultures using multielectrode arrays
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
- C12M1/3407—Measure of electrical or magnetical factor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/46—Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2304/00—Chemical means of detecting microorganisms
- C12Q2304/80—Electrochemical detection via electrodes in contact with culture medium
Definitions
- the present invention relates to an apparatus for measuring the electrophysiological activity of a cell cluster.
- the cells are placed in a measuring device comprising an array of electrodes.
- Each electrode of this network comprises a stripped area in contact with the cluster of cells, a stripped area accessible from the outside of a container containing the cells, and an isolated area separating the two stripped areas.
- the structure of the container does not allow the cells to survive for a very long time.
- a user wishes to measure an electrophysiological activity of the cells, he puts power tips into contact with the electrodes concerned among the network of electrodes. This contact is made manually. This implies that it is particularly difficult to carry out measurements over a certain period of time or on several electrodes simultaneously.
- the present invention proposes to overcome these drawbacks by providing an apparatus which is simple to handle, which offers great flexibility of use and which can be totally managed remotely. This device also allows a long cell life, which allows measurements to be made over a long period.
- an apparatus as defined in the preamble and characterized in that it comprises a measurement card provided with a chamber receiving the cells to be analyzed and containing an array of electrodes, at least some of which are in contact with said cluster of cells comprising a connector formed of conductive tracks, each electrode of the electrode array being in contact with a conductive track of the connector, this connector being connected to an electronic measurement circuit arranged to transmit electrical signals to the at least one electrode of said array of electrodes and for receiving electrical signals from at least one of the electrodes.
- the electronic measurement circuit is connected to a measurement management system arranged to manage measurement parameters and to analyze the measurement signals.
- the apparatus advantageously comprises means for assigning to at least one electrode of the network of electrodes a function of measurement electrode and means for assigning to at least one electrode of the network of electrodes a function of stimulation electrode.
- the card is preferably placed in a support and the connector is integral with said support.
- This support is advantageously made of metal.
- the support cooperates with heating means arranged to heat the measurement card.
- the measurement card advantageously cooperates with an perfusion device arranged to perfuse said cluster of cells.
- the management system comprises means for controlling the infusion device and the heating means. It also includes remote control means.
- the apparatus advantageously comprises display means preferably comprising a camera.
- FIG. 1 is an overview of the apparatus according to the present invention.
- FIG. 2 is a view of a measurement card used with the device of FIG. 1,
- FIG. 3 is a sectional view of the measurement card of Figure 2.
- FIG. 4 is a schematic view of a particular embodiment of the invention.
- the apparatus 10 essentially comprises a support 11 in which is placed a measurement card 12, an infusion device 13, heating means 14, an electronic measurement circuit 15 and a measurement management system 16 comprising for example a computer 17 and a screen 18.
- the support 11 essentially consists of a fixed part 19 in which the measurement card 12 is placed, and of a mobile part 20.
- the card measurement essentially comprises a chamber 21 provided with an inlet 22 and an outlet 23 and containing the cells to be analyzed, a removable cover 24 serving to close the chamber, and an array of electrodes 25.
- the electrodes forming this array have a first part 26 disposed in the chamber so as to be able to be brought into contact with certain cells of the cluster of cells, and a second part 27 disposed outside the chamber.
- the mobile part 20 of the support is integral with a flexible electronic circuit formed by a network of conductive tracks, one end of which is in contact with a respective electrode of the measurement card.
- the other end of the tracks of the network of conductive tracks is placed in a connector 28 fixed to the support.
- This support is advantageously made of metal so as to constitute a Faraday cage around the card.
- the chamber can also include a gas injection pipe 29 and a gas discharge pipe 30. This makes it possible to introduce a gas into the room.
- the support has a through hole 31 in its fixed part and a through hole 32 in its mobile part. These holes are aligned and arranged in such a way that the chamber of the measurement card is placed between the two holes when the support is closed.
- This support can be associated with lighting means and / or with display means 33.
- the display means can comprise a camera 34 and in particular a digital camera, so that it is possible either to observe the cells analyzed using a microscope or a magnifying glass, either to obtain an image on the screen 18 of the computer 17.
- the support also contains the heating means 14 as well as temperature control means 35.
- the heating means 14 can be produced in the form of an electrical resistance placed so as to heat an area of the support close to the cells to be analyzed. They can also be formed by channels made in the support itself and arranged to allow a circulation of hot air, generated by a fan associated with a heating resistance.
- the temperature control means 35 are linked to a thermostat 36 and include, for example, a thermostatic probe placed near the cells to be analyzed.
- the inlet 22 and the outlet 23 of the chamber are connected respectively to a flexible introduction tube and to a flexible evacuation tube.
- the introduction tube is connected to the perfusion device 13. This perfusion device makes it possible on the one hand, to deliver a nutritive liquid to the cells arranged in the card, and on the other hand, to administer a product to be tested to these cells.
- This perfusion device is formed by a support 37 containing one or more syringes 38, and pushers 39 actuating the pistons of the syringes independently.
- the movement of the pushers is managed by the measurement management system 16 so as to deliver the desired product, at a given instant or for a given duration, according to a certain quantity or a certain flow rate.
- a gas can be introduced into the gas injection pipe 29. It is also possible to generate a gas flow in the chamber by introducing a gas into the pipe 29 and evacuated by the gas evacuation pipe 30.
- Thermostat 36 makes it possible to define a given temperature or a change in temperature as a function of time. It is also managed by the measurement management system 16 and acts on the heating means.
- the electronic measurement circuit 15 is an interface box between the measurement management system 16 and the measurement card 12. This circuit allows in particular the amplification and the multiplexing of electrical signals moving between the card and the measurement system. two-way measurement management.
- This electronic measurement circuit includes means for amplifying the electrical signals flowing between the card and the management system. It also includes means for modifying the amplification factor, as well as the multiplexing order. These modifications can be made from the measurement management system 16, that is to say without acting mechanically on the electronic measurement circuit. It should be noted that the circuit can also be produced in the form of an electronic card integrated in the measurement management system 16.
- This measurement management system 16 includes the computer 17 which uses measurement management software specific to the desired application.
- This software makes it possible in particular to manage the operation of the perfusion device 13, the heating means 14 and the electronic measurement circuit 15. It also makes it possible to assign different functions to the electrodes.
- two electrodes are chosen as stimulation electrodes. An electrical signal is therefore sent from the electronic measurement circuit to these electrodes.
- Other electrodes for example eight electrodes among a total of forty electrodes forming the network, are used as measurement electrodes. An electrical signal from the card is therefore received by the electronic circuit.
- the electrodes used are chosen according to the organization of the tissue. It is also possible to reserve one or more electrodes as biosensors, in order to detect the presence and / or the concentration of a given product.
- the management system allows you to easily define all the parameters relating to the measurements made.
- the length, period and amplitude of the pulses can be defined.
- the stimulation can also be carried out by means of an external device, in which the various parameters can be programmed.
- the data for performing the measurements as well as the results of these measurements can be stored in a memory placed in the measurement management system 16. This allows this information to be stored for later analysis.
- FIG. 4 represents a "monobloc" version of the apparatus 10 of the invention.
- This device comprises a chassis 40 in which are arranged the support 11 receiving the measurement card 12, the perfusion device 13, the heating means 14, the thermostat 36, the electronic measurement circuit 15, the measurement management system 16 and the display means 33.
- the support 11 includes a drawer 41 which, when in the open position, allows the measurement card 12 to be placed and access to the infusion device 13. In the closed position of the drawer 41, the measurement card 12 is located in front of camera 34.
- the perfusion device 13 comprises peristaltic pumps 42.
- the embodiment in one-piece form is advantageous mainly by the fact that it is very compact.
- the present invention has a number of advantages over existing systems.
- the device is very simple to handle. Indeed, the positioning of the card in the support ensures an electrical connection of all the electrodes of the network.
- the choice of electrodes used is simply made on the management system 16.
- the images coming from the viewing camera are displayed on the screen 18. Therefore, it is possible, thanks to an adequate computer program, to assign a function at each electrode individually, by means of a pointer acting on the screen.
- the cells are isolated from the external environment which allows measurements to be made in a non-sterile environment.
- the support is advantageously made of metal. It therefore plays the role of Faraday cage, which avoids adding another Faraday cage.
- the entire device can also be adapted to the specific measurement cases to be carried out. This can occur if viewing by a particular lens is not necessary, or if the device is always used for the same type of measurement requiring specific conditions.
- measurement card for example in a microscope holder.
- An electric cable serving as an extension can connect the measurement card to the support 11, which allows this card to be used outside of its support.
- the number and arrangement of the electrodes can also be modified according to the needs of the analysis.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Food Science & Technology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Optics & Photonics (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- General Engineering & Computer Science (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9807595A FR2779525B1 (en) | 1998-06-08 | 1998-06-08 | APPARATUS FOR MEASURING THE ELECTROPHYSIOLOGICAL ACTIVITY OF A CLUSTER OF CELLS |
FR9807595 | 1998-06-08 | ||
PCT/CH1999/000244 WO1999064858A1 (en) | 1998-06-08 | 1999-06-04 | Apparatus for measuring the electrophysiological activity of a group of cells |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1084404A1 true EP1084404A1 (en) | 2001-03-21 |
Family
ID=9527464
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99923355A Withdrawn EP1084404A1 (en) | 1998-06-08 | 1999-06-04 | Apparatus for measuring the electrophysiological activity of a group of cells |
Country Status (7)
Country | Link |
---|---|
US (1) | US6730199B1 (en) |
EP (1) | EP1084404A1 (en) |
JP (1) | JP2004506868A (en) |
AU (1) | AU4028099A (en) |
FR (1) | FR2779525B1 (en) |
IL (1) | IL140175A (en) |
WO (1) | WO1999064858A1 (en) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8075570B2 (en) * | 2001-11-28 | 2011-12-13 | Aptus Endosystems, Inc. | Intraluminal prosthesis attachment systems and methods |
CN100372920C (en) * | 2003-06-27 | 2008-03-05 | 松下电器产业株式会社 | Instrument and system for pharmacologic measurement and well vessel used therein |
US7501301B2 (en) * | 2004-03-10 | 2009-03-10 | The Board Of Trustees Of The Leland Stanford Junior University | Low cost fabrication of microelectrode arrays for cell-based biosensors and drug discovery methods |
US7504069B2 (en) * | 2004-06-21 | 2009-03-17 | Wisconsin Alumni Research Foundation | Micro device for high resolution delivery and monitoring of stimuli to a biological object, in vitro |
KR101401711B1 (en) * | 2007-05-18 | 2014-05-30 | 메디메이트 홀딩 비.브이. | A Measurement Sample Handling Device with a Sealed, Solution-Filled Channel |
EP2218772A1 (en) * | 2009-02-09 | 2010-08-18 | Koninklijke Philips Electronics N.V. | Cardiomyocytes-containing device and method for manufacturing the same |
EP2601524B1 (en) * | 2010-08-05 | 2014-06-25 | Koninklijke Philips N.V. | Cardiomyocyte containing device, manufacturing method and measuring method |
RU171227U1 (en) * | 2015-06-09 | 2017-05-24 | Общество с ограниченной ответственностью "ВЕСТТРЭЙД ЛТД" | CAMERA FOR EXPRESS COMPLEX ELECTROKINETIC ANALYSIS |
US10914722B2 (en) * | 2017-02-24 | 2021-02-09 | Lawrence Livermore National Security, Llc | Sensor array and apparatus for simultaneous observation of tissue electrophysiology, contractility, and growth |
US11493472B2 (en) * | 2017-10-11 | 2022-11-08 | Sony Semiconductor Solutions Corporation | Sensor device and measurement apparatus |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4225410A (en) * | 1978-12-04 | 1980-09-30 | Technicon Instruments Corporation | Integrated array of electrochemical sensors |
WO1985002257A1 (en) * | 1983-11-10 | 1985-05-23 | Sentech Medical Corporation | Clinical chemistry analyzer |
US5810725A (en) * | 1993-04-16 | 1998-09-22 | Matsushita Electric Industrial Co., Ltd. | Planar electrode |
DE4400955C2 (en) * | 1993-12-23 | 1999-04-01 | Fraunhofer Ges Forschung | Adhesion-controllable surface structure |
US5563067A (en) * | 1994-06-13 | 1996-10-08 | Matsushita Electric Industrial Co., Ltd. | Cell potential measurement apparatus having a plurality of microelectrodes |
AUPM851694A0 (en) * | 1994-09-30 | 1994-10-27 | Barsamian, Sergei T | New methods for diagnosis, detection of cell abnormalities and morphology of living systems |
US5981268A (en) * | 1997-05-30 | 1999-11-09 | Board Of Trustees, Leland Stanford, Jr. University | Hybrid biosensors |
-
1998
- 1998-06-08 FR FR9807595A patent/FR2779525B1/en not_active Expired - Fee Related
-
1999
- 1999-06-04 JP JP2000553802A patent/JP2004506868A/en active Pending
- 1999-06-04 AU AU40280/99A patent/AU4028099A/en not_active Abandoned
- 1999-06-04 IL IL14017599A patent/IL140175A/en not_active IP Right Cessation
- 1999-06-04 WO PCT/CH1999/000244 patent/WO1999064858A1/en active Application Filing
- 1999-06-04 US US09/701,904 patent/US6730199B1/en not_active Expired - Fee Related
- 1999-06-04 EP EP99923355A patent/EP1084404A1/en not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of WO9964858A1 * |
Also Published As
Publication number | Publication date |
---|---|
IL140175A (en) | 2005-05-17 |
JP2004506868A (en) | 2004-03-04 |
WO1999064858A1 (en) | 1999-12-16 |
IL140175A0 (en) | 2002-02-10 |
US6730199B1 (en) | 2004-05-04 |
AU4028099A (en) | 1999-12-30 |
FR2779525B1 (en) | 2000-10-13 |
FR2779525A1 (en) | 1999-12-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6032071A (en) | Skin examination device | |
WO1999064858A1 (en) | Apparatus for measuring the electrophysiological activity of a group of cells | |
EP1866637B1 (en) | Body fluid testing component for analyte detection | |
EP0198759B1 (en) | Apparatus for the measurement of the luminosity of the skin | |
US4930872A (en) | Imaging with combined alignment fixturing, illumination and imaging optics | |
FR2762908A1 (en) | METHOD AND DEVICE FOR OBTAINING A COMPENSATED ANALOG SIGNAL FROM AN OUTPUT SIGNAL OF A THERMOELECTRIC DEVICE | |
FR2656925A1 (en) | HUMIDITY SENSOR AND MEASURING INSTALLATION COMPRISING A PLURALITY OF SUCH SENSORS. | |
FR2779443A1 (en) | ORGANIC CELL CULTURE AND STUDY OF THEIR ELECTROPHYSIOLOGICAL ACTIVITY AND MEMBRANE DEVICE USED IN SUCH A DEVICE | |
JPH10232199A (en) | Method and program for operating chemical sensor | |
US20030139672A1 (en) | Apparatus and methods for analysing epithelial tissue histology | |
CA1117787A (en) | Apparatus used to measure the quantity of sebum secreted by the skin | |
De Jong et al. | Identification of bladder wall layers by Raman spectroscopy | |
EP1660895A1 (en) | Anechoic chamber with direct observation of the electromagnetic behaviour of a tool to be studied | |
EP0273296B1 (en) | Apparatus for the photometric analysis of liquid samples | |
EP4380451A1 (en) | Device, system and method for biometric electrode testing | |
Anand et al. | Shade matching in fixed prosthodontics using instrumental color measurements and computers | |
EP1247144B1 (en) | Method and installation for determining the physical properties of an object | |
CA2055592A1 (en) | Papillameter | |
FR2664380A1 (en) | Multipurpose measurement apparatus | |
FR3066690A1 (en) | SYSTEM AND METHOD FOR ANALYSIS OF SKIN CHARACTERISTICS COMPRISING AN OPTICAL PROBE | |
CA2206273C (en) | Skin examination device | |
FR2894667A1 (en) | Object, e.g. tooth, colorimetry measuring system, has central processing and controlling unit calculating color represented by colorimetry coordinates from sequence of color images for certain points or preset zones of object's surface | |
EP0494834A1 (en) | Method and device for measuring the impedance of a biological body | |
FR2894666A1 (en) | SYSTEM FOR OPTICALLY MEASURING THE COLORIMETRY OF AN OBJECT | |
FR2649882A1 (en) | Device for measuring and analysing the vital human parameters |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20001223 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES GB IT LI NL SE |
|
17Q | First examination report despatched |
Effective date: 20021018 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BIO CELL-INTERFACE S.A. |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: STOPPINI, LUC Inventor name: HAENNI, CLAUDE |
|
17Q | First examination report despatched |
Effective date: 20021018 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20080710 |