Biomolecular Processor Time-of-Flight Sequencing
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Solution Overview
Problem
Current DNA sequencing technologies face challenges such as high costs, labor-intensive processes, and inefficiencies in detecting rare mutations and methylation events, particularly in clinical settings, due to limitations in nanopore technologies and fluorescence-based methods.
Innovation Solution
A biomolecular processor with bioreactor chambers and time-of-flight channels that use a cleaving enzyme to break down biopolymers into monomers or multimers, which are then identified by their flight time through nano-scale sensors, enabling efficient and automated nucleic acid sequencing without the need for amplification or fluorescence labeling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence-based sequencing methods are used, then sequencing can be performed, but the process becomes labor-intensive and costly
Solution Approach 1:
The system uses automated robotic arms to perform sample preparation, loading, and plate handling operations. The sequencing platform performs self-service by automatically preparing samples, loading them into sequencing chambers, and processing multiple plates sequentially without requiring manual intervention for each step, thereby reducing labor intensity while maintaining sequencing capability
Solution Approach 2:
The invention replaces manual mechanical operations with an automated robotic system. The robotic arm with automated pipetting mechanisms substitutes human hands for sample preparation, and the automated plate loading system replaces manual plate handling, thereby eliminating the labor-intensive aspects of fluorescence-based sequencing while preserving the detection capability
2Measurement precision
If conventional sequencing technologies are used, then nucleic acid sequences can be determined, but the process takes significant time and resources
Solution Approach 1:
The system segments the sequencing process into independent parallel operations. Multiple sequencing plates are processed simultaneously in separate chambers, and the robotic system can switch between different plates and samples without completing one entire sequencing run before starting another. This parallelization significantly reduces the total time required to determine multiple nucleic acid sequences while maintaining accuracy
Solution Approach 2:
The automated robotic system enables continuous operation by eliminating idle time between sequencing steps. The robotic arm continuously prepares samples, loads plates, and manages reagents without interruption, and the sequencing chambers operate continuously once initialized. This continuous useful action reduces the overall sequencing time compared to conventional batch processing while preserving sequence determination accuracy
3Measurement precision
If specialized equipment is used for each molecular assay, then specific genetic variations can be detected, but device complexity increases
Solution Approach 1:
The sequencing platform is designed as a universal system that can detect multiple types of genetic variations including SNPs, insertions, deletions, and methylation events using the same core sequencing technology. The system uses universal reagents and standardized protocols that work across different sample types and variation kinds, eliminating the need for specialized equipment for each assay type while maintaining high detection sensitivity through the fluorescence-based sequencing chemistry
Solution Approach 2:
Instead of having specialized equipment for each type of genetic variation detection, the invention inverts the approach by using a single universal sequencing platform that can detect all variation types. The system achieves this by using universal adapters and primers that work for all samples, and the sequencing chemistry inherently detects all variation kinds, thereby reducing device complexity from multiple specialized instruments to one multi-functional system
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 reduces sequencing costs and time, enhances sensitivity for detecting rare mutations and methylation events, and allows for accurate, real-time analysis of nucleic acid sequences, making it suitable for clinical applications.
Implementation Method 1
Each of the one or more time-of-flight channels has two or more sensors including at least (i) a first sensor contacting the one or more time-of-flight channels proximate to the input end of the one or more time-of-flight channels and (ii) a second sensor contacting the one or more time-of-flight channels proximate to the output end of the one or more time-of-flight channels
Implementation Method 2
a cleaving enzyme immobilized to the support structure and operatively positioned within said bioreactor chamber to cleave monomer or multimer units of a biopolymer molecule
Data Source
AI summary
The present invention relates to a device comprising a biomolecular processor. Each biomolecular processor has one or more bioreactor chambers defined by a solid substrate; a support structure within each bioreactor; a cleaving enzyme immobilized to the support structure and operatively positioned within the bioreactor chamber to cleave monomer or multimer units of a biopolymer molecule operatively engaged by the cleaving enzyme; and one or more time-of-flight channels formed in the solid substrate and fluidically coupled to said one or more bioreactor chambers. Each of the time-of-flight channels have two or more sensors including at least (i) a first sensor contacting the time-of-flight channel proximate to the input end of the channel and (ii) a second sensor contacting the time-of-flight channel proximate to the output end of channel. The present invention further relates to methods of sequencing and identifying biopolymer molecules using the device.