Nanopore Sequencing Shift Register Parallel Signal Transfer
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Solution Overview
Problem
Current sequencing methods, such as nanopore-based techniques, face challenges with low current intensity and high capacitance, leading to low throughput and noise interference, which limits the efficiency and speed of biopolymer sequencing.
Innovation Solution
The integration of image sensor technology principles, specifically using shift registers like CCDs, to parallelize the sequencing of multiple biopolymers, enabling simultaneous signal collection and noise-free charge transfer, with optional amplification stages for enhanced signal strength.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nanopore-based sequencing methods are used to detect building blocks, then sequence information can be obtained, but the current intensity is low and capacitance is high, leading to noise interference and low throughput
Solution Approach 1:
The patent divides the sequencing task into multiple parallel channels, each with its own nanopore and measurement circuit. Instead of sequencing one biopolymer at a time, multiple biopolymers are sequenced simultaneously in parallel, thereby increasing throughput while maintaining measurement precision in each channel
Solution Approach 2:
The patent combines multiple nanopore measurement circuits into a single integrated system with shared control and readout electronics. This merging approach enables parallel sequencing of multiple biopolymers while reducing overall system complexity and improving productivity
2Measurement precision
If tunneling current measurement is used to detect nucleotides, then sequence information can be obtained, but the low current intensity and high capacitance require complex preamplifiers, increasing device complexity
Solution Approach 1:
The patent introduces a charge-coupled device (CCD) as an intermediary between the nanopore measurement circuits and the readout electronics. The CCD acts as a buffer that transfers charge signals with high fidelity while isolating the sensitive nanopore measurements from the complex amplification circuitry, thereby reducing device complexity
Solution Approach 2:
The patent uses the CCD to create temporary copies of the charge signals from multiple nanopore channels before readout. This copying mechanism allows parallel signal acquisition without requiring complex simultaneous amplification circuits, simplifying the overall device architecture
3Productivity
If multiple biopolymers are sequenced in parallel, then throughput increases, but signal noise and interference increase, reducing measurement precision
Solution Approach 1:
The patent assigns dedicated nanopore and measurement circuit pairs to each biopolymer being sequenced, creating isolated measurement channels. This segmentation prevents cross-talk and interference between parallel sequencing operations, maintaining measurement precision while enabling high throughput
Solution Approach 2:
The CCD serves as an intermediary that buffers and isolates signals from multiple parallel nanopore channels before they are read out. This mediation prevents noise and interference from propagating between channels, allowing accurate simultaneous measurement of multiple biopolymers
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 increases sequencing efficiency, allowing for fast and simultaneous sequencing of multiple biopolymers with improved resolution and reduced noise, enabling sequencing to be completed in under an hour with high accuracy.
Implementation Method 1
Individual building blocks of the biopolymer may be analyzed by the nanopore as a result of a change in the pore resistance as the building blocks pass through
Implementation Method 2
Alternatively, a tunneling current may be measured in the nanopore, the tunneling current occurring only when the biopolymer passes through
Implementation Method 3
Each sequence signal is transferred in parallel into a shift register... allowing for fast and simultaneous sequencing of multiple biopolymers with improved resolution and reduced noise
Data Source
AI summary
The invention relates to a method and a corresponding arrangement for sequencing at least two biopolymers (6), wherein for each biopolymer (6) a sequence signal is picked up by a respective measured variable pickup on the basis of the sequence of the biopolymer (6), the sequence signals are transferred to a shift register (16) and buffer-stored therein, the buffer-stored sequence signals are transferred from the shift register (16) sequentially to an evaluation device (26) and evaluated therein. Each sequence signal is preferably produced here by means of a nanopore arrangement (10). A corresponding sequencing arrangement (11) has the measured variable pickups and the shift register (16) integrated in it, preferably in an electrical circuit, that is to say on a sensor array, for example. Each sequence signal can be amplified here by a preamplifier (14) prior to transfer to the shift register (16). The transfer of the output signal (A) to the evaluation device (24) can comprise the amplification of the signal by an output amplifier (24) and/or at least one EMCCD stage (32).