Hydrogel-Based Sequencing for Lower Reagent Waste
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Solution Overview
Problem
Existing high-throughput sequencing methods face challenges in achieving cost reduction while maintaining sequencing efficiency and accuracy, with Flowcell solutions being costly due to high reagent consumption and Dip sequencing solutions risking reagent quality and chip drying.
Innovation Solution
A hydrogel-based sequencing method that supports both Flowcell and open sequencing systems, reducing reagent loss and preventing drying, using reversible thermogel polymers to manage nucleotide incorporation and removal in gel states, allowing for single-use reagents and simplified fluid management.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If Flowcell solution is used to achieve high reagent replacement ratio, then sequencing efficiency is improved, but reagent cost increases
Solution Approach 1:
The patent employs disposable hydrogel beads that are inexpensive and single-use, eliminating the need for expensive reusable Flowcell components. Each bead contains all necessary reagents for a complete sequencing reaction cycle, and after use, the entire bead is discarded, avoiding reagent loss and contamination issues associated with reusable systems.
Solution Approach 2:
The sequencing reaction is segmented into discrete functional units within individual hydrogel beads. Each bead acts as an independent reaction chamber containing specific reagents for particular steps (nucleotide incorporation, label removal, etc.), allowing parallel processing of multiple beads simultaneously while maintaining reagent integrity and reducing overall consumption.
2Loss of substance
If Dip sequencing solution is used to reduce reagent cost, then reagent cost decreases, but chip drying and quality risk increase
Solution Approach 1:
The hydrogel beads function as flexible, hydrophilic micro-chambers that maintain a controlled aqueous environment. The hydrogel matrix prevents evaporation and drying of reagents by maintaining its gel state, while still allowing necessary diffusion of molecules. This eliminates the chip drying problem inherent in Dip sequencing while maintaining cost effectiveness through reagent reuse within the bead.
Solution Approach 2:
The hydrogel bead acts as an intermediary structure between the sequencing chip and the reagents. It provides a stable, moisture-retaining microenvironment that prevents direct exposure of the chip to drying conditions, while facilitating reagent delivery and reaction completion. The bead can be removed after use, avoiding contamination of the chip.
3Measurement precision
If complex fluids and temperature control are used in Flowcell, then sequencing accuracy is maintained, but device complexity increases
Solution Approach 1:
The hydrogel beads are designed to be self-regulating and self-contained. The hydrogel matrix automatically maintains appropriate humidity and temperature conditions for the reactions without requiring external control systems. The beads perform all necessary functions (reagent containment, reaction facilitation, product release) autonomously, eliminating complex fluid handling and temperature control apparatus.
Solution Approach 2:
The patent utilizes changes in hydrogel bead properties (such as swelling, shrinking, or phase transitions) in response to environmental conditions to control reaction progression. These intrinsic parameter changes of the hydrogel material itself provide the necessary control mechanisms without requiring external devices, simplifying the overall system while maintaining reaction accuracy.
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
The method effectively reduces reagent costs and maintains sequencing accuracy by minimizing reagent waste and avoiding drying issues, supporting both traditional and open sequencing systems.
Implementation Method 1
at least one of steps (1) and (3) is performed in gel state
Implementation Method 2
using reversible thermogel polymers to manage nucleotide incorporation and removal in gel states
Data Source
AI summary
Provided is a hydrogel-based sequencing method suitable for a flowcell sequencing system and also supporting open-source sequencing system, and which can effectively reduce costs while ensuring sequencing efficiency and accuracy.