Lipid Bilayer Monitoring Using AC Response in Nanopore Cells
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Solution Overview
Problem
Existing methods for forming lipid bilayers in nanopore based sequencing chips are destructive and inefficient, leading to reduced yield and efficiency due to the breakdown of already formed bilayers during the detection process.
Innovation Solution
A non-destructive technique using an AC voltage source and integrating capacitor to monitor delta voltage changes (ΔVADC) at the lipid bilayer, allowing for the detection of formed bilayers without causing damage, and separating cells with and without bilayers for targeted lipid-thinning stimulus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional destructive methods are used to detect lipid bilayer formation, then detection can be achieved, but the bilayers are broken down and yield is reduced
Solution Approach 1:
The patent replaces destructive mechanical/electrical testing methods with a non-destructive AC impedance measurement technique. By applying small AC voltage signals and measuring the resulting current through the bilayer, the system can detect bilayer formation without causing breakdown, thus maintaining both measurement capability and chip yield.
Solution Approach 2:
The patent changes the measurement parameters by using small amplitude AC voltage signals instead of large DC voltages. This parameter change allows detection of bilayer formation (through impedance changes) without exceeding the breakdown threshold of the bilayer, thereby preventing destruction while maintaining detection sensitivity.
2Difficulty of detecting and measuring
If electrical stimulus is applied to detect bilayer formation, then detection is enabled, but the bilayer stability is compromised
Solution Approach 1:
The patent applies partial action by using small AC voltage signals that are sufficient to generate detectable impedance changes but insufficient to cause bilayer breakdown. This partial stimulation enables detection while preserving bilayer stability.
Solution Approach 2:
The patent uses periodic AC voltage signals instead of continuous DC stimulation. The periodic nature allows measurement of impedance characteristics during specific phases of the AC cycle when the bilayer is most stable, improving detection sensitivity while minimizing cumulative damage.
3Loss of time
If conventional bilayer monitoring is used, then formation can be tracked, but time is lost due to destruction and reform cycles
Solution Approach 1:
The patent enables continuous monitoring of bilayer formation without interruption by using non-destructive AC impedance measurements. The bilayer remains intact throughout the monitoring process, allowing continuous data collection and eliminating the need to stop and reform bilayers, thus reducing time loss and improving process reliability.
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
Increases the efficiency and yield of nanopore based sequencing chips by ensuring proper bilayer formation without destruction, facilitating improved fluid flow and enhancing overall chip performance.
Implementation Method 1
A non-destructive technique using an AC voltage source and integrating capacitor to monitor delta voltage changes (ΔVADC) at the lipid bilayer
Data Source
AI summary
A method of detecting a lipid bilayer formed in a cell of a nanopore based sequencing chip is disclosed. An integrating capacitor is coupled with a lipid membrane, wherein the lipid membrane is between a working electrode and a counter electrode. An alternating current (AC) voltage is applied to the counter electrode. A voltage across the integrating capacitor is periodically sampled by an analog-to-digital converter (ADC). A change in the sampled voltage across the integrating capacitor in response to a change in the AC voltage is determined. Whether the lipid membrane comprises a lipid bilayer is detected based on the determined change in the sampled voltage across the integrating capacitor in response to the change in the AC voltage.