US 11,530,443 B2 · Non-destructive bilayer monitoring using measurement of bilayer response to electrical stimulus

Abstract

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.

Claims17

Dependent claims

A method of detecting whether a membrane has thinned in a cell of a nanopore based sequencing chip, comprising:

applying an alternating current (AC) voltage across a membrane disposed between a working electrode and a counter electrode, the membrane electrically coupled with a capacitor;
periodically sampling a voltage across the capacitor;
determining a change in the sampled voltage across the capacitor in response to a change in the AC voltage;
and
detecting that the membrane has been thinned at least partially into a thin membrane based on the determined change in the sampled voltage across the capacitor in response to the change in the AC voltage, wherein the thin membrane has a thickness that allows a nanopore to insert into the thin membrane and form an electrical path between the working electrode and the counter electrode.

2 more elements

A system for detecting whether a membrane has thinned 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 membrane between the working electrode and the counter electrode such that the membrane is electrically coupled with the capacitor;
an alternating current (AC) voltage source configured to apply an AC voltage to the counter electrode;
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 change in the AC voltage;
and
detect whether the membrane has been thinned at least partly into the thin membrane based on the determined change in the sampled voltage across the capacitor in response to the change in the AC voltage.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/892,212Filed 3 Jun 2020 · continuation

Priority

30 Mar 2016

Published

US 2020/0291468 A117 Sep 2020

Granted

20 Dec 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification4 codes

C12Q 1/6869
Involving nucleic acids: methods for sequencing
G01N 33/48721
By electrical means: investigating individual macromolecules, e.g. by translocation through nanopores
C12Q
Measuring or testing processes involving enzymes, nucleic acids or microorganisms
G01N
Investigating or analysing materials by determining their chemical or physical properties

Family

Application15/085,700Parent of this continuation · filed 30 Mar 2016

Application16/186,894Parent of this continuation · filed 12 Nov 2018

US 10,155,979 B2Parent of this continuation · filed 18 Dec 2018

US 2020/0291468 A1Pre-grant publication · published 17 Sep 2020

US 10,683,543 B2Parent of this continuation

US 2017/0283866 A1Published application

US 2019/0144934 A1Published application

US 11,530,443 B2This patent

From the US filing history. Foreign family members aren’t listed.

Non-destructive bilayer monitoring using measurement of bilayer response to electrical stimulus

Life of this patent

Non-destructive bilayer monitoring using measurement of bilayer response to electrical stimulus

Life of this patent

Abstract

Claims17