Adjustable Bilayer Capacitance for Nanopore Sequencing

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Solution Overview

Problem

Nanopore-based sequencing chips face challenges with measurement inaccuracies due to operational amplifier offset and noise, and area-intensive circuitry, which become exacerbated as the number of cells increases, leading to significant measurement inaccuracies and detection errors.

Innovation Solution

The solution involves configuring the voltage applied across the nanopore to vary over time, eliminating the need for an operational amplifier and additional on-chip capacitors, allowing for bidirectional measurements and adjusting the capacitances associated with the membrane and working electrode to optimize system performance, thereby reducing chip size and improving measurement accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional operational amplifier circuitry is used in each cell, then voltage control and measurement can be performed, but the chip area becomes excessively large and measurement inaccuracies increase due to offset and noise

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidchip area
Core Design Contradiction:
Measurement precisionVSArea of stationary object

Solution Approach 1:

The patent extracts and removes the operational amplifier and additional on-chip capacitors from each cell, eliminating the sources of offset and noise that degrade measurement accuracy. This extraction also eliminates the area-intensive circuitry, allowing the chip to scale to millions of cells while maintaining measurement precision through alternative voltage control methods.

Inventive Principle:
Principle #2Taking out (Extraction)

2Productivity

If the number of cells is increased to improve sequencing capacity, then productivity increases, but measurement inaccuracies and detection errors become more significant

Engineering Contradiction:
Improvesequencing capacityVSAvoidmeasurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the capacitance function into two independent components: the membrane capacitance (Cmembrane) and the working electrode capacitance (Cworking electrode). This segmentation allows independent optimization of each component, enabling high cell counts for increased productivity while maintaining measurement accuracy through separate control and adjustment of each capacitance element.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the parameters of the capacitance structure by adjusting the base surface area of the membrane and the base surface area of the working electrode independently. This parameter adjustment enables optimization of measurement accuracy across varying cell counts, allowing the system to scale to millions of cells without degradation of measurement precision.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If additional on-chip capacitors are added to adjust capacitance, then measurement accuracy can be improved, but device complexity and chip area increase

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidcircuit complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent makes the membrane and working electrode structure serve multiple functions: it provides both the biological barrier function and the capacitance adjustment function. By making the base surface areas of these components adjustable, the system achieves capacitance control without requiring additional dedicated capacitor components, thereby reducing device complexity while maintaining measurement accuracy.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 significantly reduces the footprint of each cell, minimizes charge injection, and enhances measurement accuracy by eliminating offset inaccuracies, facilitating the scaling of nanopore-based sequencing chips to include millions of cells while maintaining precise molecular identification.

Implementation Method 1

adjusting the capacitances associated with the membrane and working electrode to optimize system performance

Methodology Applied
Scientific EffectCapacitance: Capacitance

Data Source

PatentUS10976302B2Adjustable bilayer capacitance structure for biomedical devices
Publication Date: 2021.04.13 ROCHE SEQUENCING SOLUTIONS INC
  • US10976302B2 patent drawing
  • US10976302B2 patent drawing
  • US10976302B2 patent drawing

AI summary

A nanopore sequencing device is disclosed. The nanopore sequencing device includes a working electrode. It further includes a dielectric layer, wherein a portion of the dielectric layer is disposed horizontally adjacent to the working electrode and a portion of the dielectric layer is disposed above and covering a portion of the working electrode, and wherein the dielectric layer forms a well having an opening above an uncovered portion of the working electrode. A base surface area of the working electrode is greater than a base surface area of the opening above the uncovered portion of the working electrode.