Lipid Bilayer Integrity Monitoring via AC Voltage Sampling
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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 flow and reduced yield due to the breakdown of the lipid bilayer during the testing process, resulting in inefficiencies and a lower percentage of cells with properly formed lipid bilayers and nanopores.
Innovation Solution
A non-destructive technique that uses an alternating current voltage with an intermediate monitoring phase to detect the state of the lipid bilayer without causing it to break down, employing an integrating capacitor and analog-to-digital converter to monitor voltage changes and determine the presence and integrity of the lipid bilayer, and disabling further electrical stimuli if the bilayer is ruptured.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a stimulus voltage is applied to test the lipid bilayer, then the state of the membrane can be detected, but the already properly formed lipid bilayer is destroyed
Solution Approach 1:
The patent applies periodic action by using alternating current (AC) voltage at a specific frequency (e.g., 1 kHz) to periodically stimulate the lipid bilayer. This periodic stimulation allows the membrane to respond reversibly without causing permanent damage, enabling repeated measurements while maintaining membrane integrity throughout the testing process.
Solution Approach 2:
The patent changes the electrical parameters by using AC voltage with specific frequency and amplitude characteristics, rather than applying DC voltage. The AC signal at 1 kHz frequency creates capacitive coupling that allows voltage measurement across the membrane without causing destructive electrochemical reactions or breakdown, thus maintaining both detection capability and membrane reliability.
2Measurement precision
If the lipid bilayer is destroyed by stimulus voltage, then detection can be performed, but a very high current flows and the system must re-form the bilayer which is time-consuming
Solution Approach 1:
By using periodic AC stimulation at 1 kHz, the system can repeatedly assess lipid bilayer formation without destroying the membrane. This eliminates the need for time-consuming re-formation processes after each detection attempt, significantly improving productivity while maintaining accurate detection capability throughout the entire measurement process.
3Measurement precision
If high current is applied to test the lipid bilayer, then the state can be determined, but the yield of properly formed lipid bilayers is reduced
Solution Approach 1:
The patent changes the electrical parameters from high-current DC to AC voltage at 1 kHz with appropriate amplitude. This parameter change allows accurate detection of lipid bilayer state through voltage measurement across the membrane while avoiding the destructive effects of high current, thus maintaining both detection accuracy and the yield of properly formed lipid bilayers.
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 increases the efficiency and yield of nanopore-based sequencing chips by accurately detecting lipid bilayer formation and integrity without causing damage, thereby improving the overall performance and reliability of the sequencing process.
Implementation Method 1
periodically sampling a voltage across an integrating capacitor
Data Source
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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). An intermediate change in the AC voltage is inserted between two magnitudes of the AC voltage. A change in the sampled voltage across the integrating capacitor in response to the 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.