Source: http://www.google.se/patents/US6132683?hl=sv
Timestamp: 2013-05-23 08:49:24
Document Index: 664109007

Matched Legal Cases: ['art 9', 'art 9', 'art 9', 'art 9', 'art 9', 'art 9', 'art 9']

Patent US6132683 - Cell potential measuring electrode and measuring apparatus using the same - Google PatentS�k Bilder Kartor Play YouTube Nyheter Gmail Drive Mer » Avancerad patents�kning | Webbhistorik | Logga in Avancerad patents�kning PatentThis invention relates to a low impedance cell potential measuring electrode assembly typically having a number of microelectrodes on an insulating substrate and having a wall enclosing the region including the microelectrodes. The device is capable of measuring electrophysiological activities of a monitored...http://www.google.se/patents/US6132683?utm_source=gb-gplus-sharePatent US6132683 - Cell potential measuring electrode and measuring apparatus using the same PublikationsnummerUS6132683 ATyp av kung�relseBeviljande Ans�kningsnummer09/220,981 Publiceringsdatum17 okt 2000 Registreringsdatum23 dec 1998 Prioritetsdatum23 dec 1998 UppfinnareRyuta OgawaHiroaki OkaKen ShimonoHirokazu SugiharaMakoto Taketani Ursprunglig innehavareMatsushita Electric Industrial Co., Ltd. USA-klassificering422/82.1204/412204/435204/403.1 Internationell klassificeringC12M1/34G01N33/487 Kooperativ klassningG01N33/4836C12M1/3407 Europeisk klassificeringG01N33/483C1C12M1/34BH�nvisningarCitat fr�n patent (8)Citat fr�n andra k�llor (8) H�nvisningar finns i f�ljande patent (38)Externa l�nkarUSPTO �verl�telse av �gander�tt till patent som har registrerats av USPTO EspacenetCell potential measuring electrode and measuring apparatus using the sameUS 6132683 A Sammanfattning This invention relates to a low impedance cell potential measuring electrode assembly typically having a number of microelectrodes on an insulating substrate and having a wall enclosing the region including the microelectrodes. The device is capable of measuring electrophysiological activities of a monitored sample using the microelectrodes while cultivating those cells or tissues in the in the region of the microelectrodes. The invention utilizes independent reference electrodes to lower the impedance of the overall system and to therefore lower the noise often inherent in the measured data. Optimally the microelectrodes are enclosed by a physical wall used for controlling the atmosphere around the monitored sample.
We claim as our invention: 1. A cell potential measuring electrode assembly suitable for measuring electrical potential in a neural sample comprising: a. a plurality of measurement microelectrodes insulated from each other and located on an insulating substrate in a measuring region, b. a plurality of reference electrodes located on said insulating substrate and isolated from each other in said measuring region, each of said plurality of reference electrodes having an impedance smaller than said each of said measurement electrodes when measured in an electrolyte covering said measuring region at 1 kHz, 50 mv.
4. The cell potential measuring electrode assembly of claim 2 wherein the area of said each of plurality of measurement microelectrodes is 4 the plurality of reference electrodes is 64 64
11. A cell potential measuring electrode comprising plural microelectrodes disposed on an insulating substrate, a conductive pattern for wiring of said microelectrodes, an electric contact connected to the end of said conductive pattern, an insulating film covering the surface of said conductive pattern, and a wall enclosing the region including the microelectrodes on the surface of said insulating film, being a cell potential measuring electrode for use in measurement of electrophysiological activities while cultivating cells or tissues in a region enclosed by said wall, wherein reference electrodes having a smaller impedance than the impedance of said microelectrodes are respectively disposed at plural positions located on said insulating substrate in the region enclosed by said wall and at a specific distance from the region of disposition of said microelectrodes, electric contacts are further connected between the conductive pattern for wiring of each reference electrode and the end of said conductive pattern, and the surface of the conductive pattern for wiring of said reference electrodes is covered with said insulating film.
18. A cell potential measuring electrode of claim 11, wherein the area of said microelectrodes is 4 and the area of said reference electrodes is 64 64
23. A cell potential measuring apparatus comprising: a cell placement device having a cell potential measuring electrode in any one of claims 11 to 22, and a contact metal for contacting with its electric contact, and including an electrode holder for fixing said insulating substrate by sandwiching from above and beneath, a signal processor connected electrically to said cell placement device for processing voltage signals generated between each microelectrode and reference electrode of said cell potential measuring electrode by the activity of cells or tissues cultivated in a region enclosed by a wall, and an optical device for magnifying and observing optically the cells or tissues cultivated in the region enclosed by said wall.
The cell culture system 40 usually includes a temperature controller 41, a culture fluid circulation device 42, and a feeder 43 for supplying, e.g., a mixed gas of air and carbon dioxide. The cell culture system 40 may instead be made up of a commercial microincubator, a temperature controller, and CO.sub.2 cylinder. The microincubator can be used to control in a temperature range of 0 to 50 element and is applicable to the liquid feed rate of 3.0 ml/min or less and gas flow rate of 1.0 liter/min or less. Or, a microincubator incorporating a temperature controller may be used.
FIG. 3 shows the details of the glass substrate. The size of the glass substrate for constituting the cell potential measuring electrode (integrated multiple electrode) 2 may be 1.1 mm in thickness and about 50 mm square. In the central part of the glass substrate, 64 microelectrodes 11 are formed in a matrix form of 8 insulated from each other and from the reference electrodes. A conductive pattern 12 for wiring is connected to each microelectrode 11. The microelectrode 11 may be about 50 microns square and the distance between centers of adjacent electrodes is about 150 microns. The depicted 64 microelectrodes 11 are therefore shown in a matrix form of 8 side of the formed rectangular region is about 1.1 mm.
An electrical connection is made in the same way. The holders 3, 4 are typically polymeric. The step portion is used to hold the edge of the integrated multiple electrode 2 and the rectangular opening are formed in the central part. The upper holder 3 is provided with a pair of fasteners 8 and 17 pieces holders 3, 4 sandwiching and fixing the integrated multiple electrode 2 is shown in FIG. 6(A), its side view (section B--B) in FIG. 6(B), and its perspective back view in FIG. 7. As clear from these diagrams, the fastener 8 is supported by and rotates about shaft pins 8a on two confronting sides of the upper holder 3. As shown in FIG. 7, grooves 4a are formed in two confronting sides of the back side of the lower holder 4. Protrusions 8b of the fastener 8 are fitted in grooves 4a and the upper and lower holders 3, 4 are fixed firmly in a state of sandwiching the integrated multiple electrode 2.
A total of 68 contact metal fittings 9 provided on the upper holder 3 to correspond to the electric contacts 7 of the integrated multiple electrode 2 may be formed by processing elastic and conductive metal plates such as a Be/Cu spring alloy, plated with Ni and Au. The metal fittings 9 have a sectional shape as shown in FIG. 8. That is, it consists of a pin 9a, its base part 9b, and a movable contact part 9d extending from the base part 9b through a curved part 9c. In such structure, the movable contact part 9d can be elastically dislocated from the base part 9b. In the upper holder 3, holes for inserting the pin 9a of the contact metal fitting 9, and grooves for fitting the base part 9b are formed in 68 (17 positions.
As shown in FIG. 12, eight microelectrodes in one row are used as reference electrodes and seven measuring electrodes each are correlated to each of the reference electrodes, so that the potential can be measured simultaneously at 7 as measuring electrodes, i.e., by using eight microelectrodes in one row as reference electrodes, the loss of measuring sites is about 12% as compared with the case of using all 64 or 63 pieces as measuring electrodes. However, even when seven measuring electrodes are used with one reference electrode, the noise is still quite large. It is quite difficult to detect a small change in cell potential from the noise.
In order to set the impedance of the reference electrodes to be sufficiently smaller than the impedance of the microelectrodes, the area of the reference electrodes is preferably 4 to 25 times (particularly preferably 16 times) the area of the microelectrodes. As a specific example, the area of each of the microelectrodes is preferably between about 4 each of the reference electrodes is preferably between about 64
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