Formation and calibration of nanopore sequencing cells
AssigneeRoche Sequencing Solutions, Inc.
InventorsMorgan Mager, John Mannion
Life of this patent
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Abstract
Improved multi-cell nanopore-based sequencing chips and methods can employ formation, characterization, calibration, and/or normalization techniques. For example, various methods may include one or more steps of performing physical checks of cell circuitry, forming and characterizing a lipid layer on the cells, performing a zero point calibration of the cells, forming and characterizing nanopores on the lipid layers of each cell, performing a sequencing operation to accumulate sequencing signals from the cells, normalizing those sequencing signals, and determining bases based on the normalized sequencing signals.
Claims20
A system comprising:
- a plurality of sequencing cells, each sequencing cell comprising a nanopore;
- a signal generator that applies a signal across the nanopores of the plurality of sequencing cells;
- and
- electrical circuitry coupled with the signal generator and the plurality of sequencing cells, the electrical circuitry configured to:
- apply a first voltage across the nanopore of each sequencing cell while the nanopore is in an unthreaded state and measure an open channel voltage for each sequencing cell;
- after a molecule is inserted into nanopore of each sequencing cell so that the nanopore is in a threaded state, apply a second voltage across the nanopore of each sequencing cell while the nanopore is in the threaded state and measure a first voltage signal for each sequencing cell;
- normalize the first voltage signal for each sequencing cell with the corresponding open channel voltage for each sequencing cell;
- and
- determine an identity of at least a portion of the molecule based on the normalized first voltage signal.
A method of calibrating a sequencing chip including a plurality of sequencing cells, each sequencing cell comprising a nanopore, the method comprising:
- applying a first voltage across the nanopore of each sequencing cell while the nanopore is in an unthreaded state and measuring an open channel voltage for each sequencing cell;
- inserting a molecule into nanopore of each sequencing cell so that the nanopore is in a threaded state;
- applying a second voltage across the nanopore of each sequencing cell while the nanopore is in the threaded state and measuring a first voltage signal for each sequencing cell;
- normalizing the first voltage signal for each sequencing cell with the corresponding open channel voltage for each sequencing cell;
- and
- determining an identity of at least a portion of the molecule based on the normalized first voltage signal.
Dependencies are inferred from the claim text.