Multiaperture sample positioning and analysis system
First Claim
Patent Images
1. A multiaperture system for analyzing membranous samples, comprising:
- a carrier having a plurality of apertures;
at least two fluid compartments, separated by the carrier, and fluidically connected to one another, in the absence of a membranous sample, via at least one of the apertures, at least one fluid compartment including a suspension, and a substantially planar seal surface circling the aperture;
a membranous sample from the suspension, selected from the group consisting of cells, organelles, and vesicles, sealed across one of the plurality of apertures, wherein the seal between the sample and the carrier is tight enough so that the variance of leakage currents through the aperture during electrical measurements lies below the signals to be measured by a factor of 5–
10; and
at least two electrodes in electrical contact with at least one of the fluid compartments, wherein the electrodes are adapted to apply and/or measure at least one of an electrical potential and a current, across at least a portion of the membranous sample sealed across the one of the plurality of apertures within the seal surface.
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Abstract
Systems for positioning and/or analyzing samples such as cells, vesicles, cellular organelles, and fragments, derivatives, and mixtures thereof, for electrical and/or optical analysis, especially relating to the presence and/or activity of ion channels.
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Citations
97 Claims
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1. A multiaperture system for analyzing membranous samples, comprising:
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a carrier having a plurality of apertures; at least two fluid compartments, separated by the carrier, and fluidically connected to one another, in the absence of a membranous sample, via at least one of the apertures, at least one fluid compartment including a suspension, and a substantially planar seal surface circling the aperture; a membranous sample from the suspension, selected from the group consisting of cells, organelles, and vesicles, sealed across one of the plurality of apertures, wherein the seal between the sample and the carrier is tight enough so that the variance of leakage currents through the aperture during electrical measurements lies below the signals to be measured by a factor of 5–
10; andat least two electrodes in electrical contact with at least one of the fluid compartments, wherein the electrodes are adapted to apply and/or measure at least one of an electrical potential and a current, across at least a portion of the membranous sample sealed across the one of the plurality of apertures within the seal surface. - 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, 25, 26, 27, 28, 29, 30, 31, 32)
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33. A multiaperture system for analyzing membranous samples, comprising:
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a holder, a plurality of measurement sites disposed in the holder, each measurement site having a carrier that separates from one another two fluid compartments, the carrier containing an aperture that connects the two compartments, and a substantially planar seal surface circling the aperture; and a membranous mammalian-cell-sized sample, selected from the group consisting of cells, organelles, and vesicles, sealed across an aperture at one of the measurement sites within the seal surface, wherein the seal between the sample and the carrier is tight enough so that the variance of leakage currents through the aperture during electrical measurements lies below the signals to be measured by a factor of 5–
10; andwherein each compartment is in electrical contact with at least one electrode, the electrodes being adapted to apply and/or measure at least one of an electrical potential and a current, across at least a portion of the sample sealed across the aperture. - View Dependent Claims (34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48)
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49. A multiaperture system for analyzing membranous samples selected from the group consisting of cells, vesicles, and cellular organelles, comprising:
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a membranous mammalian-cell-sized sample, selected from the group consisting of cells, organelles, and vesicles; a carrier having a plurality of apertures and substantially planar seal surfaces circling respective apertures, wherein the sample is sealed across at least one of the apertures and within the respective seal surface; at least three fluid compartments, each fluid compartment connected to another of the at least three fluid compartments on an opposite side of the carrier via at least one of the apertures; and at least three electrodes, each electrode in electrical contact with at least one of the fluid compartment, wherein the electrodes are adapted to apply and/or measure at least one of an electrical potential and a current, across at least a portion of the at least one of the samples, alter it is sealed across the at least one of the apertures; wherein the fluid compartments and electrodes are separated on at least one side of the carrier to allow independent measurements; wherein the maximum diameter of the aperture at the seal surface is between about 0.3 μ
m and about 7 μ
m. - View Dependent Claims (50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80)
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81. A multiaperture system for analyzing membranous samples selected from the group consisting of cells, vesicles, and cellular organelles, comprising:
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a membranous mammalian-cell-sized sample, selected from the group consisting of cells, organelles, and vesicles; a holder; and a plurality of measurement sites disposed in the holder, each measurement site having a carrier that separates from one another two fluid compartments; wherein the carrier contains an aperture that connects the two compartments and a substantially planar seal surface circling the aperture, wherein the sample is sealed across the aperture and within the seal surface; wherein each compartment is in electrical contact with at least one electrode, the electrodes being adapted to measure at least one of an electrical potential and a current, across at least a portion of the sample, after the sample has been sealed across the aperture; and wherein the fluid compartments and electrodes are separated on at least one side of the carrier to allow independent measurements; wherein the maximum diameter of the aperture at the seal surface is between about 0.3 μ
m and about 7 μ
m. - View Dependent Claims (82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97)
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Specification