Nanopore Sequencer Real-Time Genomic Analysis
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Solution Overview
Problem
Current nucleic acid sequencing technologies are limited by their inability to perform real-time analysis, require lengthy sample preparation, have high operation costs, and are non-portable, making it difficult for field workers to conduct genomic analysis, especially during outbreaks, leading to delayed decision-making with significant safety and economic impacts.
Innovation Solution
A nanopore-based sequencer system that uses a 2-nm nanopore array fabricated through nanopantography, allowing for real-time, portable, and cost-effective genomic analysis without the need for prior sample amplification, capable of identifying molecules directly and operating in extreme conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional sequencing technologies are used, then sequencing can be performed with existing methods, but real-time analysis capability is lost and turnaround time increases to days or weeks
Solution Approach 1:
The patent replaces conventional mechanical/chemical sequencing methods with nanopore-based detection. The nanopore sensor directly detects nucleic acid sequences as they pass through the pore, eliminating the need for complex amplification and chemical reaction steps, thereby enabling real-time analysis and reducing turnaround time from days/weeks to hours.
Solution Approach 2:
The patent changes the detection parameter from indirect chemical signals to direct electrical current measurements. By monitoring ionic current changes as nucleic acids translocate through the nanopore, the system achieves real-time detection without requiring time-consuming amplification protocols, thus improving analysis speed and reducing loss of time.
2Measurement precision
If bio-nanopore technology is used, then real-time analysis with high accuracy is achieved, but device lifetime is reduced to several hours to days
Solution Approach 1:
The patent acknowledges that bio-nanopores have short lifetimes but achieves acceptable device operation by using arrays of nanopores where individual pores are replaced or regenerated. The system uses disposable or replaceable nanopore modules that can be quickly exchanged, maintaining continuous operation while preserving the high measurement precision of bio-nanopore technology.
Solution Approach 2:
The patent implements a system where depleted or degraded nanopores are discarded and replaced with fresh ones. The flow cell design allows for easy replacement of nanopore-containing modules, enabling the system to maintain high sequencing accuracy over extended periods by continuously refreshing the nanopore population rather than attempting to preserve individual pores indefinitely.
3Duration of action of stationary object
If solid state nanopores are used, then device robustness and lifetime are improved, but manufacturing capability is insufficient to produce required arrays
Solution Approach 1:
The patent divides the nanopore array fabrication process into separate stages: first creating master templates using conventional lithography, then using those templates to generate arrays of nanopores through self-assembly or replication processes. This segmentation allows existing manufacturing capabilities to produce the required 256x256 arrays by breaking down the complex fabrication into manageable steps.
Solution Approach 2:
The patent introduces intermediate template structures that bridge conventional lithography and final nanopore formation. These templates serve as mediators that can be fabricated with existing tools and then used to define the precise locations and dimensions of nanopores in arrays, making the manufacturing process compatible with current semiconductor industry capabilities.
4Ease of manufacture
If conventional lithography is used, then manufacturing with existing tools is possible, but 2-nm feature size precision is not achieved
Solution Approach 1:
The patent transitions from planar 2D lithography to 3D nanopore formation by creating holes through thick membranes using a combination of top-down patterning and bottom-up self-assembly. This dimensional transition allows the use of conventional lithography for pattern definition while achieving sub-2-nm precision through the vertical dimension of membrane thickness and self-organized pore formation.
Solution Approach 2:
The patent performs preliminary patterning at a larger scale using conventional lithography to define the locations where nanopores will form, then uses subsequent self-assembly or focused ion beam processes to create the precise 2-nm features. This preliminary action allows existing lithography tools to contribute to the final precision without requiring them to directly create the sub-2-nm features themselves.
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 rapid, accurate, and cost-effective genomic analysis, reducing turnaround time and false-positive error rates, allowing for swift decision-making and on-site identification of bio-agents, with the potential for widespread applications in various industries and fields.
Implementation Method 1
As a molecule in a sample under test is translocated through a nanoscale pore, various electrical characteristics can be observed and utilized to identify the molecule under test
Data Source
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Figure 2A~2B
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AI summary
An apparatus and method for performing analysis and identification of molecules have been presented. In one embodiment, a portable molecule analyzer includes a sample input/output connection to receive a sample, a nanopore-based sequencing chip to perform analysis on the sample substantially in real-time, and an output interface to output result of the analysis.