Nanopore Sequencing Voltage Mode Circuitry Eliminates Op-Amp Drift
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Solution Overview
Problem
Current nanopore-based sequencing chips face challenges with measurement inaccuracies due to operational amplifier-induced voltage drift and noise, and the area-intensive circuitry required for maintaining constant voltage during current flow measurements, which becomes unfeasible as the number of cells increases.
Innovation Solution
A circuitry configuration that allows the voltage applied across the nanopore to vary over time, eliminating the need for operational amplifiers and reducing the footprint of each cell, while using an integrating capacitor and a reset signal to charge and discharge voltage, enabling bidirectional current measurements and reducing charge injection during measurement intervals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If operational amplifiers are used to maintain constant voltage during current flow measurements, then measurement stability is improved, but device complexity and area increase
Solution Approach 1:
The patent removes operational amplifiers from the circuitry, extracting the problematic component that caused voltage drift and noise. The constant voltage maintenance function is replaced by a simpler voltage source configuration that inherently provides stable voltage without requiring active feedback components, thereby reducing device complexity and area while maintaining measurement stability.
Solution Approach 2:
The voltage source is designed to self-regulate and maintain constant voltage across the nanopore without requiring external operational amplifiers for feedback control. The circuitry autonomously provides stable voltage conditions for current measurements, eliminating the need for complex active components and reducing overall device complexity.
2Productivity
If the number of cells in nanopore-based sequencing chips increases, then productivity is improved, but device complexity becomes unfeasible
Solution Approach 1:
The patent merges the voltage source and measurement circuitry into a more integrated configuration that reduces the footprint per cell. By combining functions and eliminating separate operational amplifier circuits in each cell, the overall circuitry area per nanopore is reduced, making it feasible to scale up to millions of cells while maintaining high sequencing capacity.
Solution Approach 2:
The simplified circuitry design uses universal components that can serve multiple functions across different cells. The voltage source and measurement circuitry are designed to be replicated efficiently across large numbers of cells, reducing the complexity burden when scaling from fewer to millions of cells.
3Stability of the object's composition
If operational amplifiers are used for voltage maintenance, then voltage stability is improved, but measurement precision deteriorates due to voltage drift and noise
Solution Approach 1:
The patent extracts operational amplifiers from the measurement circuit, removing the source of voltage drift and noise that degraded measurement precision. The remaining circuitry uses passive components and a simplified voltage source configuration that provides inherently stable voltage without the artifacts introduced by active feedback components.
Solution Approach 2:
The patent replaces expensive, complex operational amplifiers with simpler, more reliable voltage source circuitry that has fewer failure modes. The simplified design uses basic electronic components that are more stable and produce less noise, improving measurement precision while reducing device complexity.
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 enhances measurement accuracy by eliminating operational amplifier-related inaccuracies, allows for scalable nanopore-based sequencing chips with millions of cells, and maintains reliable bidirectional measurements, facilitating the analysis of molecules within nanopores.
Implementation Method 1
an integrating capacitor and a reset signal to charge and discharge voltage
Implementation Method 2
a nanopore-based sequencing chip comprises an array of cells, each cell comprising a nanopore and circuitry
Data Source
AI summary
A liquid voltage is applied to a first side of a lipid bilayer. The liquid voltage comprises a tag-reading period with a tag-reading voltage that tends to capture a tag into a nanopore in the lipid bilayer and an open-channel period with an open-channel voltage that tends to repel the tag. A pre-charging voltage source is connected to an integrating capacitor and a working electrode on a second side of the lipid bilayer during a pre-charging time period, such that the integrating capacitor and the working electrode are charged to a pre-charging voltage. The pre-charging voltage source is disconnected from the integrating capacitor and the working electrode during an integrating time period, such that a voltage of the integrating capacitor and a voltage of the working electrode may vary as a current flows through the nanopore. The pre-charging time period overlaps with a beginning portion of the tag-reading period.