Nanopore Cell Overhang Structure for Compact Bidirectional Sensing
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Solution Overview
Problem
Current 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, making it difficult to scale the technology for larger arrays.
Innovation Solution
The solution involves eliminating the operational amplifier and on-chip capacitor by allowing the voltage across the nanopore to decay over time, utilizing the capacitance associated with the membrane and working electrode to achieve bidirectional measurements and reduce chip size, while adjusting the ratio of membrane and electrochemical capacitance for optimal performance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If operational amplifier and on-chip capacitor are used for voltage measurement, then measurement accuracy is maintained, but cell footprint and chip area increase significantly
Solution Approach 1:
The patent removes the operational amplifier and on-chip capacitor from the cell circuitry, extracting these components entirely from the measurement system. Instead, it uses the inherent capacitance of the membrane and working electrode, along with the decay characteristics of the voltage signal, to achieve measurements without requiring these additional area-intensive components.
Solution Approach 2:
The system utilizes the natural capacitance of the membrane and working electrode, and the inherent decay behavior of the voltage signal across the nanopore, to perform measurements. The membrane and electrode serve dual purposes: their primary function plus providing the capacitance needed for voltage measurement, eliminating the need for separate measurement components.
2Adaptability or versatility
If traditional circuitry with operational amplifier is used, then bidirectional measurements can be performed, but device complexity and area increase
Solution Approach 1:
The operational amplifier is completely removed from the system. The patent achieves bidirectional measurements by utilizing the decay characteristics of the voltage signal and the inherent capacitance of the system components, rather than requiring an operational amplifier to enable the measurement functionality.
Solution Approach 2:
The membrane and working electrode serve multiple functions: their primary electrochemical function plus providing the capacitance necessary for voltage measurements. This multi-functionality eliminates the need for separate dedicated measurement components, reducing overall device complexity.
3Productivity
If number of cells is increased for larger arrays, then sequencing capacity increases, but measurement inaccuracies due to offset and noise are exacerbated
Solution Approach 1:
By removing the operational amplifier, the patent eliminates the primary source of offset and noise that would be amplified and propagated across multiple cells. The measurement system relies on passive decay characteristics that are inherently more stable and less prone to drift and noise accumulation.
Solution Approach 2:
The system uses the decay characteristics of the voltage signal as a natural feedback mechanism. By measuring how the voltage decays over time and using this information to calculate the voltage across the nanopore, the system achieves accurate measurements without requiring active feedback control circuits that would add complexity and noise.
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 stability, allowing for the scaling of nanopore-based sequencing chips to include millions of cells without performance issues, while maintaining accurate bidirectional measurements.
Implementation Method 1
a working electrode with a larger base surface area than the lipid bilayer base surface area. The ratio of the membrane capacitance to the electrochemical capacitance associated with the working electrode can be adjusted to provide an optimized RC time constant for a particular application
Implementation Method 2
The ratio of the membrane capacitance to the electrochemical capacitance associated with the working electrode can be adjusted to provide an optimized RC time constant
Data Source
AI summary
A nanopore cell includes a conductive layer and a working electrode disposed above the conductive layer and at the bottom of a well into which an electrolyte may be contained, such that at least a portion of a top base surface area of the working electrode is exposed to the electrolyte. The nanopore cell further includes a first insulating wall disposed above the working electrode and surrounding a lower section of a well, and a second insulating wall disposed above the first insulating wall and surrounding an upper section of the well, forming an overhang above the lower section of the well. The upper section of the well includes an opening that a membrane may span across, and wherein a base surface area of the opening is smaller than the at least a portion of the top base surface area of the working electrode that is exposed to the electrolyte.