Parallel Patch Clamp System for High-Throughput Ion Channel Analysis
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Solution Overview
Problem
Current patch clamp techniques face limitations in throughput, data consistency, and cost-effectiveness, particularly in recording electrophysiological signals, and struggle with accurately estimating electrophysiological parameters when compensation mechanisms are enabled, especially in automated systems.
Innovation Solution
A parallel patch clamp system with multiple apertures per well allows for high-throughput analysis by sealing multiple membranous samples across apertures, enabling current measurement through unsealed apertures, and includes a fluidics system for adding and washing solutions, which improves success rates and reduces costs by eliminating redundancy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple compounds are added and washed repeatedly to multiple wells with single cells, then data consistency and control responses are improved, but throughput is significantly reduced
Solution Approach 1:
The invention divides the measurement process into two independent segments: (1) control response measurement on a first well containing multiple cells, and (2) test compound measurement on a second well containing multiple cells. This segmentation allows control and test measurements to be performed in separate wells rather than requiring repeated additions and washes on the same well, thereby improving throughput while maintaining data consistency through the use of multiple cells per well for statistical robustness.
Solution Approach 2:
The invention transitions from a single-well sequential measurement approach to a multi-well parallel measurement approach. By using multiple wells (first well for control, second well for test) and multiple cells per well, the system adds spatial dimensionality to the measurement process, enabling simultaneous or near-simultaneous control and test measurements, thus resolving the contradiction between data consistency and throughput.
2Reliability
If redundancy is used to guarantee successful recordings, then reliability is improved, but cost per data point increases
Solution Approach 1:
The invention merges multiple cell recordings within the same well by using a multi-aperture substrate where multiple cells are recorded simultaneously from a single well. This combining approach achieves statistical robustness and high success rates without requiring redundant measurements across multiple wells, thereby reducing the cost per data point while maintaining reliability.
Solution Approach 2:
The invention uses homogeneous multi-cell populations in each well, where multiple cells are subjected to the same experimental conditions simultaneously. This homogeneity approach ensures consistent data quality and high success rates without the need for redundant heterogeneous measurements, reducing overall costs while maintaining reliability.
3Ease of operation
If single cell per well is used, then ease of operation is maintained, but throughput and success rate are limited
Solution Approach 1:
The invention makes the well multi-functional by enabling it to contain multiple cells that can all be recorded from simultaneously using a multi-aperture substrate. Each well serves as a universal recording unit that can accommodate multiple cells, maintaining operational simplicity while dramatically increasing throughput and success rates compared to single-cell-per-well approaches.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The system achieves increased success rates, improved data consistency, and reduced costs per data point, enabling high-throughput electrophysiological analysis and expanding applications to include ligand-gated ion currents, while maintaining accurate parameter estimation.
Implementation Method 1
an electric source configured to apply a voltage and/or a current between the extracellular and intracellular chambers
Implementation Method 2
the at least one aperture is sealed by the at least one membranous sample... wherein a portion of current travels through the unsealed aperture
Data Source
AI summary
A system for high-throughput analysis of membranous samples having ion channels including at least one membranous sample, a multi-compartment structure including an extracellular chamber, an opposing intracellular chamber and a partition separating the extracellular and intracellular chambers, the partition having a plurality of apertures fluidly and electrically coupling the extracellular and intracellular chambers, wherein at least one of the apertures is sealed by the at least one membranous sample, and another of the apertures is unsealed, a electric source configured to apply a current between the extracellular and intracellular chambers, wherein a portion of the current travels through the unsealed aperture, and a current sensor configured to measure the current between the extracellular and intracellular chambers. A method of using the system is also disclosed.