Apparatus and method for chronic measurement of monophasic action potentials
First Claim
1. A method for measurement of monophasic action potentials from an excitable tissue including a plurality of cells, the method comprising the steps of:
- providing at least one sensing electrode adjacent to or in contact with a portion of said excitable tissue and at least one reference electrode in proximity to said at least one sensing electrode;
intermittently inducing a transient depolarization in at least some of said cells adjacent said sensing electrode, said depolarization lasting for a first time interval; and
measuring a signal representing the potential difference between said sensing electrode and said reference electrode within at least part of said first time interval.
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Accused Products
Abstract
Apparatus and methods adapted for in vivo chronic measurement of cardiac monophasic action potentials (MAPs). The methods include, inter alia, providing a sensing electrode in contact with cardiac tissue and a reference electrode in proximity to the sensing electrode, intermittently inducing a transient localized depolarization or transient injury-like electrical currents in at least some of the cells of the cardiac tissue underlying or adjacent to the sensing electrode and measuring the potential difference between the sensing electrode and the reference electrode during at least part of the duration of the depolarization or injury-like currents. Other methods for inducing depolarization or injury-like currents in the tissue include, inter alia, localized membrane electroporation, localized electrostatic production of depolarization using voltage clamp to produce a signal representative of MAPs, localized tissue heating, localized application of ultrasound and localized irradiation with light. The apparatus and methods may also be applied for non-chronic measurement of cardiac monophasic action potentials and for measurement of monophasic action potentials from other non-cardiac excitable tissues.
240 Citations
96 Claims
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1. A method for measurement of monophasic action potentials from an excitable tissue including a plurality of cells, the method comprising the steps of:
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providing at least one sensing electrode adjacent to or in contact with a portion of said excitable tissue and at least one reference electrode in proximity to said at least one sensing electrode; intermittently inducing a transient depolarization in at least some of said cells adjacent said sensing electrode, said depolarization lasting for a first time interval; and measuring a signal representing the potential difference between said sensing electrode and said reference electrode within at least part of said first time interval. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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25. A method for measurement of a signal representing monophasic action potentials of an excitable tissue including a plurality of cells, the method comprising the steps of:
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providing a sensing electrode adjacent to or in contact with a portion of said excitable tissue and a reference electrode in proximity to said sensing electrode; intermittently inducing a transient depolarization and injury-like currents in at least some of said cells of said excitable tissue adjacent said sensing electrode by clamping the potential difference between said sensing electrode and said reference electrode at a value sufficient to electrostatically modify the electrical charge distribution across at least portions of the membranes of said at least some of said cells, said clamping lasting for a first time interval; and measuring the clamping current required to maintain said value of said potential difference within at least part of said first time interval to obtain said signal. - View Dependent Claims (26, 27)
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28. A method for measurement of signals representing monophasic action potentials from an excitable tissue including a plurality of cells, the method comprising the steps of:
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providing at least one sensing electrode adjacent to or in contact with a portion of said excitable tissue and at least one reference electrode in proximity to said sensing electrode; intermittently inducing a depolarization and injury-like currents in at least some of said cells of said excitable tissue adjacent said at least one sensing electrode by clamping the potential difference between said at least one sensing electrode and said at least one reference electrode at a value sufficient to electrostatically modify the electrical charge distribution across at least portions of the membranes of said at least some of said cells, said clamping lasting for a first time interval; and measuring the clamping current required to maintain said value of said potential difference within at least part of said first time interval to obtain at least one of said signals. - View Dependent Claims (29, 30)
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31. A method for measurement of signals representing monophasic action potentials from an excitable tissue, the method comprising the steps of:
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providing at least one sensing electrode adjacent to or in contact with a portion of said excitable tissue and at least one reference electrode in proximity to said at least one sensing electrode; clamping the potential difference between said at least one sensing electrode and said at least one reference electrode at a first value; measuring the clamping current required to maintain said first value of said potential difference to obtain biphasic or polyphasic signals representing biphasic or polyphasic action potentials in said excitable tissue; increasing said potential difference to a second value sufficient to obtain substantially monophasic signals representing said monophasic action potentials; maintaining said second value for a time interval sufficient for measuring at least one of said substantially monophasic signals; and measuring the clamping current required to maintain said second value of said potential difference to obtain at least one of said substantially monophasic signals. - View Dependent Claims (32, 33, 34)
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35. Apparatus for measurement of monophasic action potentials from an excitable tissue including a plurality of cells, the apparatus comprising:
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at least one probe electrode placeable adjacent to or in contact with a portion of said excitable tissue; at least one reference electrode placeable proximate said at least one probe electrode; an electroporating unit electrically connected to said at least one probe electrode and said at least one reference electrode for controllably applying to at least some of said cells subjacent said at least one probe electrode electrical current pulses suitable for causing electroporation of cell membranes of said at least some of said cells; and an amplifier unit electrically connected to said at least one probe electrode and to said at least one reference electrode for providing an output signal representing the potential difference between said probe electrode and said reference electrode. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44)
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45. Apparatus for measurement of monophasic action potentials from an excitable tissue including a plurality of cells, the apparatus comprising:
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at least one sensing electrode placeable adjacent to or in contact with a portion of said excitable tissue for sensing the potential of said portion; at least one reference electrode placeable proximate said at least one sensing electrode for sensing a reference potential; at least one electroporating electrode adjacent to said sensing electrode, said at least one electroporating electrode is placeable adjacent said portion of said excitable tissue or in contact with a part thereof; and an electroporating unit electrically connected to said at least one electroporating electrode for controllably applying to at least some of said cells adjacent said at least one electroporating electrode electrical current pulses suitable for causing electroporation of cell membranes of said at least some of said cells. - View Dependent Claims (46, 47)
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48. Apparatus for measurement of monophasic action potentials from an excitable tissue including a plurality of cells, the apparatus comprising:
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a probe electrode placeable adjacent to or in contact with a portion of said excitable tissue; a reference electrode disposed proximate said probe electrode; and a voltage clamp unit electrically connected to said probe electrode and to said reference electrode for intermittently clamping the potential difference between said probe electrode and said reference electrode at a value sufficient to electrostatically modify the electrical charge distribution across at least portions of the membranes of said at least some of said cells to generate injury-like currents in at least some of said cells adjacent said probe electrode, and for providing a signal representing the clamping current required to maintain said value of said potential difference, said signal includes at least one of said monophasic action potentials. - View Dependent Claims (49, 50, 51, 52, 53, 54, 55, 56, 57)
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58. Apparatus for measurement of monophasic action potentials from an excitable tissue including a plurality of cells, the apparatus comprising:
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at least one probe electrode placeable adjacent to or in contact with a portion of said excitable tissue; at least one reference electrode disposed proximate said at least one probe electrode; and a voltage clamping unit electrically connected to said at least one probe electrode and to said at least one reference electrode for intermittently clamping the potential difference between said at least one probe electrode and said at least one reference electrode at a value sufficient to electrostatically modify the electrical charge distribution across at least portions of the membranes of said at least some of said cells to induce a transient depolarization in at least some of said cells adjacent said at least one probe electrode, and for providing a signal representing the clamping current required to maintain said value of said potential difference, said signal includes at least one of said monophasic action potentials.
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59. Apparatus for measurement of monophasic action potentials from an excitable tissue including a plurality of cells, the apparatus comprising:
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at least one sensing electrode placeable adjacent to or in contact with a portion of said excitable tissue; at least one reference electrode disposed proximate said at least one probe electrode; a controllable depolarizing unit for intermittently inducing a transient depolarization in at least some of said plurality of cells of said portion; and an amplifier unit electrically connected to said at least one sensing electrode and to said at least one reference electrode for providing an output signal representing the potential difference between said at least one probe electrode and said at least one reference electrode. - View Dependent Claims (60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96)
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Specification