Nanopore Sequencing Circuit for pA Current Variation Measurement
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Solution Overview
Problem
Existing nanopore sequencing technologies face challenges in accurately measuring small electrical current variations in the pA range due to insufficient sensitivity of commonly used analog-to-digital converters.
Innovation Solution
A circuit design that dynamically adjusts the analog-to-digital conversion range to focus on measuring the AC component of the electrical signal by pre-charging a feedback capacitor and shifting the signal baseline, allowing for precise measurement of small current variations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If commonly used analog-to-digital converters are used to measure electrical current variations, then the device complexity is low, but the measurement precision is insufficient for pA range currents
Solution Approach 1:
The patent implements dynamic range adjustment of the analog-to-digital converter based on the magnitude of the measured current. The system automatically switches between different ADC ranges (e.g., 0-10 nA, 0-100 pA, 0-10 pA) depending on the baseline current level, allowing high precision measurement of small current variations without requiring an overly complex fixed high-precision converter throughout all operating conditions.
Solution Approach 2:
The system changes the operating parameters of the measurement circuit by adjusting the feedback resistor values and ADC reference voltages based on the detected current magnitude. This allows the same hardware to operate in different precision modes, achieving pA-range measurement capability when needed while maintaining simpler operation during normal conditions.
2Measurement precision
If the full electrical signal is measured directly, then the device complexity is low, but the measurement precision for small AC components is insufficient
Solution Approach 1:
The patent extracts and isolates the AC component from the total electrical signal by subtracting the baseline DC current measurement from the total current measurement. This separation allows the system to focus measurement precision resources solely on the small AC variations (pA range) rather than the full signal range, improving detection sensitivity for nucleotide identification.
Solution Approach 2:
The measurement process is segmented into distinct phases: baseline DC current measurement, total current measurement, and AC component calculation. This temporal and functional segmentation allows each phase to be optimized independently, with the DC component providing context for the AC variation measurement.
3Adaptability or versatility
If a fixed analog-to-digital conversion range is used, then the device complexity is low, but the adaptability to different current ranges is insufficient
Solution Approach 1:
The system dynamically adjusts the ADC input range based on real-time current measurements. The controller monitors the baseline current level and automatically selects the appropriate ADC range (e.g., switching between high-range and low-range modes), enabling the device to adapt to varying current conditions without requiring multiple fixed converter circuits.
Solution Approach 2:
The measurement circuit is designed to perform multiple functions across different current ranges using a single universal architecture. By incorporating switchable feedback resistors and dynamic range settings, the same circuit can accurately measure currents from nA down to pA ranges, eliminating the need for separate specialized converters for each range.
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
Enhances the resolution and accuracy of nanopore sequencing by isolating and digitizing the AC component of the electrical signal, improving the readout resolution and temporal precision for nucleotide identification.
Implementation Method 1
a feedback capacitor connected between the input terminal and the output terminal of the analog-to-digital converter
Data Source
AI summary
In one aspect, the disclosed technology relates to systems and methods for sequencing polynucleotides. In one embodiment, the disclosed system for sequencing polynucleotides includes: a sequencing cell comprising a nanopore for sensing a polynucleotide; an electronic circuit configured to measure an electrical response in the sequencing cell, the electronic circuit comprising a feedback capacitor; and a current source operably connected to the electronic circuit via a gate.