Channel Current Cheminformatics And Bioengineering Methods For Immunological Screening, Single-Molecule Analysis, And Single-Molecular-Interaction Analysis
First Claim
1. A method comprising receiving a blockade channel current signal carried by an ionic current flowing through a partially-blockaded nano-scale membrane channel defined by a membrane which partitions a conductive medium, exposing the channel to a test condition during ionic current flow while extracting from the blockade channel current signal, a set of one or more pattern features to establish over a period of time either a blockade channel current signal pattern or a change in the blockade channel current signal pattern.
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Accused Products
Abstract
Analytical tools and methods employing processing of channel current blockade measurements to detect or assess changes in environmental conditions generally, and more specifically, to detect and assess interactions between a blockade-producing auxiliary molecule in the channel and either the surrounding conductive medium generally or molecules in that conductive medium. The auxiliary molecule is disposed within the channel in order to generate a highly structured channel current blockade signal. The blockade signal resulting from inducing ionic current flow through the channel with auxiliary molecule present, is based on an auxiliary molecule chosen to be highly susceptible to modulation when the auxiliary molecule interacts with other molecules in the surrounding conductive medium, or when it otherwise is modified or affected at the molecular level by changes in the physical or chemical conditions of that surrounding medium. The tools and methods enable, amongst other things, candidate antibody screening, molecular affinity and bond strength analysis and detection of a variety of changes in test media, even at the molecular level.
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Citations
16 Claims
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1. A method comprising
receiving a blockade channel current signal carried by an ionic current flowing through a partially-blockaded nano-scale membrane channel defined by a membrane which partitions a conductive medium, exposing the channel to a test condition during ionic current flow while extracting from the blockade channel current signal, a set of one or more pattern features to establish over a period of time either a blockade channel current signal pattern or a change in the blockade channel current signal pattern.
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2. A method according to claim 2, further comprising
comparing the blockade channel current signal pattern, or the change in the blockade channel current signal pattern, to at least one blockade channel current signal pattern, or at least one change in the blockade channel current signal pattern, associated with at least one known condition, to thereby correlate the test condition with the known condition.
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10. A method for screening candidate agents for preventing pore formation, comprising
in a conductive medium, contacting a membrane with one of the candidate agents and then placing a membrane-permeabilizing agent in the presence of the membrane and the candidate agent under conditions which would permit pore formation in the membrane in the absence of the candidate agent, and introducing an ionic charge to the membrane in the conductive medium and measuring the time which passes from the moment the membrane-permeabilizing agent is placed in the presence of the membrane until pore formation in the membrane permits an ionic current to flow through the pore to be detected.
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11. A method for identifying an effective cytosolic antigen delivery mechanism for use in evoking a cytotoxic T Lymphocyte response in an organism challenged by one or more cytosolic virulence factors, comprising
introducing a single pore-forming toxin to a membrane so as to form at least one pore through which an ionic current may flow, and causing the current to flow through the pore to generate one or more signals indicative of at least one characteristic of antigen transmembrane transport.
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12. Apparatus comprising
a membrane which partitions a conductive medium, the membrane defining at least one nano-scale channel through which an ionic current may flow, the channel having disposed therein an auxiliary molecule which causes modulations in the ionic current when the ionic current flows through the channel, an ionic current source, a sensor for measuring the ionic current flowing through the channel and generating a blockade channel current signal, a computer system programmed and configured for receiving and processing the blockade channel current signal from the sensor to enable the extraction of a set of one or more pattern features.
Specification