Non-destructive Lipid Bilayer Monitoring via AC Capacitance
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Solution Overview
Problem
The existing methods for determining whether a lipid bilayer is properly formed in a nanopore-based sequencing chip are often destructive, leading to a high current short-circuit condition and reduced yield due to the destruction of the lipid bilayer during the stimulus voltage testing process, which is both time-consuming and inefficient.
Innovation Solution
A method involving an integrating capacitor coupled with a lipid membrane between a working electrode and a counter electrode, applying an alternating current voltage, and periodically sampling the voltage across the capacitor to detect changes, allowing for non-destructive monitoring of the lipid bilayer state without applying further electrical stimuli if it has ruptured.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If stimulus voltage is applied to test lipid bilayer formation, then formation status can be determined, but the lipid bilayer may be destroyed causing short-circuit condition
Solution Approach 1:
The patent changes the electrical parameters by using AC voltage instead of DC voltage, and by controlling the voltage magnitude to be below the rupture threshold. This allows continuous monitoring without destroying the lipid bilayer, resolving the contradiction between detection capability and bilayer integrity.
Solution Approach 2:
The patent implements periodic sampling of the voltage across the integrating capacitor at regular intervals. This periodic measurement approach allows continuous monitoring of lipid bilayer formation status without applying continuous destructive voltage, enabling detection while preserving bilayer integrity.
2Measurement precision
If destructive testing method is used to determine lipid bilayer formation, then formation status can be detected, but time is lost due to bilayer destruction and re-formation
Solution Approach 1:
The patent applies preliminary gentle AC voltage stimulation before the lipid bilayer is fully formed to detect formation status. This preliminary non-destructive testing avoids the need for destructive testing and subsequent re-formation, significantly reducing time loss.
Solution Approach 2:
The patent implements feedback control by continuously monitoring the voltage across the integrating capacitor and adjusting the stimulation protocol based on detected changes. When lipid bilayer formation is detected, the system provides feedback to stop or reduce stimulation, preventing destruction and avoiding re-formation time loss.
3Measurement precision
If high current flows due to lipid bilayer destruction, then short-circuit condition occurs, but yield of functional cells is reduced
Solution Approach 1:
The patent applies partial action by using voltage magnitudes that are sufficient for detection but below the threshold that causes bilayer rupture. This controlled partial stimulation detects lipid bilayer formation without causing destruction and subsequent short-circuit conditions, preserving functional cell yield.
Solution Approach 2:
The patent converts the potentially harmful high current effect into a beneficial detection signal by using the capacitive coupling effect. The integrating capacitor converts voltage changes into measurable current signals that indicate lipid bilayer formation, avoiding direct harmful current flow through the bilayer.
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
This approach enables efficient and non-destructive detection of lipid bilayer formation and rupture, improving the yield and robustness of nanopore-based sequencing chips by preventing damage to already formed lipid bilayers and facilitating the formation of new bilayers in subsequent trials.
Implementation Method 1
coupling a lipid membrane with an integrating capacitor
Implementation Method 2
applying an alternating current (AC) voltage to the counter electrode; periodically sampling a voltage across the integrating capacitor
Data Source
AI summary
A method of detecting a state of a lipid membrane in a cell of a nanopore based sequencing chip is disclosed. A lipid membrane is coupled with an integrating capacitor, 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 an intermediate change in the AC voltage is determined. A state of the lipid membrane is determined based on the determined change in the sampled voltage across the integrating capacitor in response to the intermediate change in the AC voltage.