High-throughput electrophysiological measurement system
First Claim
1. Electrophysiological measurement apparatus, comprising:
- a multi-well plate having a plurality of fluid chambers, each configured to support a biological material to be measured;
a thin substrate having an array of apertures in alignment with the chambers of the multi-well plate, wherein the substrate is joined to the multi-well plate such that the chambers are open at the top and sealed at the bottom, except for the apertures, and wherein the diameter of the apertures is less than the diameter of the biological material, thereby enabling a high-resistance seal to be formed between the biological material in each chamber and a corresponding aperture;
a fluid plenum to receive the multi-well plate such that one side of the substrate is immersed;
a transfer device configured to move material into the fluid chambers of the multi-well plate while it is in contact with the fluid plenum;
a first electrode disposed in the fluid plenum;
at least one second electrode that can be selectively connected with and disconnected from the fluid chambers of the multi-well plate, wherein the second electrode disconnects from the fluid chambers when the transfer device moves material into the fluid chambers; and
electrophysiological measurement circuitry in electrical communication with the electrodes;
wherein the substrate is selected from the group consisting of polyethylene terephthalate (PET) and polyimide and further wherein the substrate has a glass coating at least in the region where the high-resistance seal is formed between the material and the substrate.
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Accused Products
Abstract
Systems, including apparatus and methods, for performing electrophysiological measurements on membranous samples, including living cells, isolated cell fragments (such as organelles), and/or artificial membranes (such as vesicles). The apparatus may include a high-throughput electrophysiological measurement system, and components thereof. This measurement system may include, among others, (1) a fluidics head for transferring samples and/or other compounds to a perforated measurement substrate, (2) a pressure-regulated plenum system for positioning samples on the substrate and subsequently forming a high-resistance electrical seal, (3) an activation system (such as a computer-controlled pulsed UV illumination module) for activating caged compounds, (4) an electronics head for applying and/or measuring voltage and/or current, and/or (5) a computer-controlled analysis system for collecting and/or analyzing data. The methods may include methods for performing high-throughput electrophysiological measurements on transporters and/or voltage or ligand-gated ion channels, sequentially and/or simultaneously.
163 Citations
44 Claims
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1. Electrophysiological measurement apparatus, comprising:
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a multi-well plate having a plurality of fluid chambers, each configured to support a biological material to be measured; a thin substrate having an array of apertures in alignment with the chambers of the multi-well plate, wherein the substrate is joined to the multi-well plate such that the chambers are open at the top and sealed at the bottom, except for the apertures, and wherein the diameter of the apertures is less than the diameter of the biological material, thereby enabling a high-resistance seal to be formed between the biological material in each chamber and a corresponding aperture; a fluid plenum to receive the multi-well plate such that one side of the substrate is immersed; a transfer device configured to move material into the fluid chambers of the multi-well plate while it is in contact with the fluid plenum; a first electrode disposed in the fluid plenum; at least one second electrode that can be selectively connected with and disconnected from the fluid chambers of the multi-well plate, wherein the second electrode disconnects from the fluid chambers when the transfer device moves material into the fluid chambers; and electrophysiological measurement circuitry in electrical communication with the electrodes; wherein the substrate is selected from the group consisting of polyethylene terephthalate (PET) and polyimide and further wherein the substrate has a glass coating at least in the region where the high-resistance seal is formed between the material and the substrate. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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16. Electrophysiological measurement apparatus, comprising:
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a multi-well plate having a plurality of fluid chambers, each configured to support a biological material to be measured; a thin substrate having an array of apertures in alignment with the chambers of the multi-well plate, wherein the substrate is joined to the multi-well plate such that the chambers are open at the top and sealed at the bottom, except for the apertures, and wherein the diameter of the apertures is less than the diameter of the biological material, thereby enabling a high-resistance seal to be formed between the biological material in each chamber and a corresponding aperture; a fluid plenum to receive the multi-well plate such that one side of the substrate is immersed; a first electrode disposed in the fluid plenum; at least one second electrode that can be connected with and disconnected from the fluid chambers of the multi-well plate; and electrophysiological measurement circuitry in electrical communication with the electrodes, wherein the substrate is a plastic substrate having a glass coating at least in the region where the high-resistance seal is formed between the material and the substrate, wherein the substrate is selected from the group consisting of polyethylene terephthalate (PET) and polyimide. - View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44)
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Specification