Method for inline bilayer capacitance monitoring
AssigneeRoche Sequencing Solutions, Inc.
InventorAshraf Wahba
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Abstract
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.
Claims18
A method of detecting a state of a lipid membrane in a cell of a nanopore based sequencing chip, comprising:
- applying an alternating current (AC) voltage across a lipid membrane disposed between a working electrode and a counter electrode, the lipid membrane electrically coupled with a capacitor, wherein the AC voltage alternates between a first voltage and a second voltage;
- periodically sampling a voltage across the capacitor;
- determining a change in the sampled voltage across the capacitor in response to a monitoring signal, wherein the monitoring signal is a change in the AC voltage with a magnitude that is less than the difference between the first voltage and the second voltage;
- detecting a state of the lipid membrane based on the determined change in the sampled voltage across the capacitor in response to the monitoring signal;
- comparing the change in the sampled voltage across the capacitor against one or more predetermined thresholds, and
- detecting the state of the lipid membrane based on the comparisons against the one or more predetermined thresholds, wherein the state of the lipid membrane is selected from the group consisting of:
- a lipid membrane with more than two lipid molecule layers, a lipid bilayer, and a ruptured lipid bilayer.
A system for detecting a state of a lipid membrane in a cell of a nanopore based sequencing chip, comprising:
- a capacitor;
- a working electrode electrically coupled to the capacitor;
- a counter electrode;
- a surface configured to support a lipid membrane between the working electrode and the counter electrode such that the lipid membrane is electrically coupled with the capacitor;
- an alternating current (AC) voltage source configured to apply an AC voltage to the counter electrode, wherein the AC voltage alternates between a first voltage and a second voltage;
- an analog measurement circuitry configured to periodically sample a voltage across the capacitor;
- and
- a processor or a circuitry configured to:
- determine a change in the sampled voltage across the capacitor in response to a monitoring signal, wherein the monitoring signal is a change in the AC voltage with a magnitude that is less than the difference between the first voltage and the second voltage;
- detect a state of the lipid membrane based on the determined change in the sampled voltage across the capacitor in response to the monitoring signal;
- compare the change in the sampled voltage across the capacitor against one or more predetermined thresholds;
- and
- detect the state of the lipid membrane based on the comparisons against the one or more predetermined thresholds, wherein the state of the lipid membrane is selected from the group consisting of:
- a lipid membrane with more than two lipid molecule layers, a lipid bilayer, and a ruptured lipid bilayer.
Dependencies are inferred from the claim text.