Nanopore Pulse Control Circuit for Fast Sequencing Signals
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Solution Overview
Problem
Existing nanopore sensors face challenges in applying microsecond-scale pulses due to the limited time response of trans-impedance amplifiers, leading to signal distortion and inefficiency in sequencing biopolymers.
Innovation Solution
A nanopore sensor system with a command node, amplifier, and a switch driven by a clock pulse to ground the amplifier's inverting input, allowing precise application of short duration pulses to translocate polynucleotides or polypeptides through the nanopore well.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If short duration pulses (microseconds or nanoseconds) are applied to translocate polynucleotide through nanopore well, then sequencing precision and translocation control are improved, but signal distortion occurs due to limited amplifier time response
Solution Approach 1:
The system separates the pulse generation function from the amplification function. The command node generates short duration pulses directly at the nanopore well, while the trans-impedance amplifier processes the resulting current signal. This segmentation allows the pulse width to be determined by the command node (enabling precise sub-microsecond control) while the amplifier only needs to handle the slower current response, avoiding the contradiction between short pulse duration and amplifier bandwidth limitations.
Solution Approach 2:
The nanopore well acts as an intermediary element between the applied voltage pulse and the measured current signal. The command node applies voltage pulses to translocate the polynucleotide through the nanopore well, and the trans-impedance amplifier converts the resulting ionic current changes into measurable voltage signals. This intermediary mechanism allows decoupling of the fast voltage pulse generation from the slower current measurement process.
2Measurement precision
If high gain (10^9 V/A or higher) is used in trans-impedance amplifier for nanopore sequencing, then signal sensitivity is improved, but bandwidth is limited and settling time increases to 100 μs or more
Solution Approach 1:
The system divides the signal processing into two distinct stages: (1) voltage pulse generation and application at the command node, and (2) current-to-voltage conversion at the trans-impedance amplifier. This segmentation allows the amplifier to operate at high gain for sensitivity without requiring fast response, because the critical fast timing functions are handled by the command node's voltage output rather than the amplifier.
Solution Approach 2:
The system dynamically separates the time-critical functions from the sensitivity-critical functions. The command node handles the dynamic, time-critical voltage pulse generation with sub-microsecond precision, while the trans-impedance amplifier handles the static, sensitivity-critical current amplification. This dynamic functional separation resolves the contradiction between speed and sensitivity requirements.
3Quantity of substance
If typical trans-impedance amplifier configuration is used with high gain, then signal amplification is sufficient for detection, but fast pulse application becomes challenging due to slow settling time
Solution Approach 1:
The system segments the functionality between command node and amplifier: the command node is responsible for fast voltage pulse generation and application, while the trans-impedance amplifier is responsible for current signal amplification. This segmentation eliminates the conflict between requiring fast pulse response and high gain amplification, as each component performs its specialized function without compromise.
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
Enables accurate and efficient sequencing of biopolymers with reduced signal noise by ensuring pulse integrity and timing precision.
Implementation Method 1
a switch disposed between the amplifier and the nanopore sensor, wherein the switch is driven by a clock pulse and configured to ground an inverting input of the amplifier
Implementation Method 2
a command node connected directly to the nanopore sensor, wherein the command node is configured to apply a potential across the nanopore sensor and a command pulse
Implementation Method 3
it can provide a channel for an ionic electrical current through the nanopore well
Implementation Method 4
an amplifier with a feedback loop coupled to the nanopore sensor
Data Source
AI summary
Sequencing systems and methods are provided that include a nanopore sensor that includes a cis well associated with a cis electrode and a trans well associated with a trans electrode, a membrane separating the cis well and the trans well, and a nanopore well embedded in the membrane providing a channel through the membrane; a command node connected directly to the nanopore sensor. The command node is configured to apply a potential across the nanopore well and a command pulse. The system further includes an amplifier with a feedback loop coupled to the nanopore sensor and a switch disposed between the amplifier and the nanopore sensor. The switch is driven by a clock pulse and configured to ground an inverting input of the amplifier.