Nucleic Acid Sequencing System with Modular Substrate Arrays
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Solution Overview
Problem
Current genetic sequencing techniques are time-intensive and costly, limiting their efficiency and reliability in determining nucleotide sequences for DNA and RNA analysis.
Innovation Solution
The development of a method and system for nucleic acid sequencing that involves automated cycles of nucleotide detection and quality evaluation, using a substrate-based array system with fluidics and imaging to improve throughput and accuracy, allowing for real-time adjustment of sequencing procedures based on detected parameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If automated sequencing systems with substrate-based arrays are used, then productivity and throughput are improved, but device complexity increases
Solution Approach 1:
The sequencing system is divided into independently removable modules: a sample preparation module, a sequencing module with substrate array, and a detection module. Each module can be independently operated, maintained, and replaced, reducing the complexity burden on the entire system while maintaining high throughput capability.
Solution Approach 2:
The substrate-based array system is designed to accommodate multiple sample types and sequencing chemistries through universal binding sites and standardized protocols. This multi-functionality allows a single complex system to perform diverse sequencing tasks, improving productivity without requiring separate specialized equipment for each application.
2Reliability
If real-time quality evaluation and adaptive adjustment are implemented, then reliability and data quality are improved, but device complexity and operational complexity increase
Solution Approach 1:
The system incorporates real-time quality evaluation that monitors sequencing parameters and provides feedback to automatically adjust reaction conditions, imaging parameters, and cycle timing. This closed-loop control improves reliability by detecting and correcting deviations during sequencing without requiring complex manual intervention systems.
Solution Approach 2:
The sequencing system performs self-diagnosis and self-adjustment through automated quality control algorithms that evaluate data quality metrics and modify subsequent sequencing cycles accordingly. This self-service capability enhances reliability while minimizing the need for complex external control systems.
3Productivity
If multiple samples are sequenced simultaneously, then productivity is improved, but measurement precision and data quality control become more difficult
Solution Approach 1:
The substrate array is designed with spatially resolved detection zones that allow independent quality evaluation and parameter optimization for each sample location. This local quality control ensures that data from multiple parallel samples maintains consistent precision despite variations in individual sample conditions.
Solution Approach 2:
The system dynamically adjusts sequencing parameters such as nucleotide concentration, incubation time, and imaging exposure based on real-time quality metrics for each sample. This parameter optimization maintains measurement precision across multiple simultaneous samples by adapting to local conditions at each array position.
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 enhances the speed and reliability of nucleic acid sequencing, reducing costs and improving the quality of genomic data by enabling continuous and simultaneous sequencing of multiple samples with adaptive quality control and process optimization.
Implementation Method 1
each nucleotide type is tagged with a fluorescent tag or dye that permits analysis of the nucleotide attached at a particular site to be determined by analysis of image data
Data Source
AI summary
A technique for sequencing nucleic acids in an automated or semi-automated manner is disclosed. Sample arrays of a multitude of nucleic acid sites are processed in multiple cycles to add nucleotides to the material to be sequenced, detect the nucleotides added to sites, and to de-block the added nucleotides of blocking agents and tags used to identify the last added nucleotide. Multiple parameters of the system are monitored to enable diagnosis and correction of problems as they occur during sequencing of the samples. Quality control routines are run during sequencing to determine quality of samples, and quality of the data collected.