Benchtop Nucleic Acid Library Preparation Device Using CLC Thermal Chip
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Solution Overview
Problem
Current methods for nucleic acid library preparation for next-generation sequencing require high local concentrations of target molecules and involve labor-intensive, manual processes, making automation and miniaturization challenging, especially in small volumes.
Innovation Solution
A benchtop device employing composite liquid cell (CLC) technology with a thermal chip module, consumable reagent and sample cartridges, and a robotically controlled liquid handler to automate and miniaturize nucleic acid library preparation, including magnetic purification, enabling efficient production of nucleic acid libraries in small volumes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Extent of automation
If manual processes are used for nucleic acid library preparation, then flexibility and adaptability are maintained, but labor intensity increases and automation becomes challenging
Solution Approach 1:
The automated library preparation system is divided into discrete functional modules: a thermal cycler module for temperature-controlled reactions, a liquid handler for automated reagent dispensing, a magnetic bead purification system for DNA isolation, and a control system. Each module performs a specific function, allowing the complex automation task to be managed through modular components rather than a monolithic system.
Solution Approach 2:
The thermal cycler module serves multiple functions by performing different thermal protocols for various library preparation steps (fragmentation, end repair, adapter ligation, amplification) within a single device. The liquid handler can dispense multiple reagents and perform different liquid manipulation tasks, reducing the need for separate specialized devices for each function.
2Quantity of substance
If miniaturization is implemented to reduce reaction volumes, then reagent consumption decreases, but maintaining high local concentrations of target molecules becomes challenging
Solution Approach 1:
The system uses magnetic beads with high surface area to volume ratio to create localized zones of high nucleic acid concentration during purification. The thermal cycler module creates localized thermal gradients that enhance reaction efficiency in small volumes. The liquid handler employs precise pipetting techniques that maintain appropriate concentrations even in microliter-scale reactions by accurately controlling dispensing volumes.
Solution Approach 2:
The thermal cycler module dynamically changes temperature parameters through multiple cycling steps (denaturation at 95°C, annealing at 50-65°C, extension at 72°C) to optimize reaction conditions at each stage. The system adjusts thermal parameters to maintain effective reaction kinetics despite reduced reaction volumes, ensuring adequate local concentrations of reactants and products throughout the library preparation process.
3Productivity
If multiple library preparation steps are consolidated into a single device, then workflow efficiency improves, but device complexity increases
Solution Approach 1:
The system merges four distinct library preparation functions (thermal cycling, liquid handling, magnetic bead purification, and waste collection) into a single integrated device. The thermal cycler module, liquid handler, magnetic purification system, and fluidic waste management are combined in one instrument, allowing all library preparation steps to be performed sequentially without transferring samples between separate devices, thereby improving workflow efficiency.
Solution Approach 2:
The liquid handler serves as an intermediary component that coordinates between the thermal cycler module, magnetic bead purification system, and reagent storage. It automatically transfers liquids between modules, manages reagent dispensing, and synchronizes operations, reducing the need for complex mechanical linkages or direct integration between all modules while maintaining workflow efficiency.
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 device streamlines nucleic acid library preparation, automating processes to achieve high-quality libraries with minimal user intervention, suitable for next-generation sequencing, and capable of producing multiple libraries efficiently in a compact format.
Implementation Method 1
a thermal chip module configured to receive a composite liquid cell (CLC) reaction cartridge
Implementation Method 2
a thermal chip module configured to receive a composite liquid cell (CLC) reaction cartridge
Implementation Method 3
The device further comprises a magnetic nucleic acid library purification system
Data Source
AI summary
Complete nucleic acid library preparation devices are provided. Aspects of the devices include: a thermal chip module comprising multiple CLC reaction wells; one or more plate locations; a robotically controlled liquid handler configured to transfer liquid between the one or more plate locations and the thermal chip module; and a bulk reagent dispenser configured to access each CLC reaction well of the thermal chip module.