Fluidic Cartridge for Automated NGS Library Preparation
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Solution Overview
Problem
Current next-generation sequencing (NGS) library preparation is labor-intensive and requires multiple manual steps, including sample liquefaction, nucleic acid liberation, purification, quality and quantity assessment, and library preparation, with no existing protocol for direct, fast, and automated sample-to-NGS-ready library processing that concomitantly assesses nucleic acid quality and quantity.
Innovation Solution
A fluidic cartridge for automated processing of biological samples that integrates sample liquefaction, nucleic acid liberation and purification, and NGS library preparation, while also enabling concurrent or sequential qPCR analysis for quality control and target screening, using reagents for generating nucleic acid fragments and attaching oligonucleotide adapters for library preparation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Extent of automation
If manual processing steps are used for NGS library preparation, then flexibility and adaptability are maintained, but labor intensity and processing time increase significantly
Solution Approach 1:
The cartridge is divided into multiple functionally independent compartments (sample compartment, library preparation compartment, qPCR compartment) that can be processed automatically. Each compartment contains specific reagents and performs a discrete function, enabling automated high-throughput processing while maintaining modular flexibility for different sample types and library preparation protocols.
Solution Approach 2:
The cartridge design integrates multiple functions into a single platform: sample processing, nucleic acid liberation, library preparation, and qPCR analysis. This multi-functional integration enables one system to replace multiple separate manual operations, achieving automation without proportionally increasing overall system complexity.
2Productivity
If multiple separate steps are performed for nucleic acid purification and library preparation, then quality control is possible at each step, but processing time and resource consumption increase
Solution Approach 1:
The cartridge merges nucleic acid liberation, purification, and library preparation steps into a single integrated flow path. Nucleic acids are liberated in the sample compartment, purified through the same compartment, and directly transported to the library preparation compartment without intermediate manual handling or separate quality assessment steps, thereby accelerating processing while maintaining quality through built-in controls.
Solution Approach 2:
The system enables continuous processing by eliminating idle time between steps. As nucleic acids are liberated and purified in the sample compartment, they are immediately transported to the library preparation compartment where library construction begins without interruption. This continuous flow maximizes productivity and minimizes the time lost to sequential batch processing.
3Reliability
If NGS library preparation is performed without concomitant qPCR analysis, then workflow is simpler, but quality and quantity assessment delays result availability
Solution Approach 1:
The cartridge performs qPCR analysis in parallel with library preparation by allocating a dedicated qPCR compartment that receives and processes nucleic acid samples simultaneously with the library preparation compartment. This preliminary concurrent assessment provides quality and quantity data before sequencing without delaying the overall workflow, as both processes occur at the same time rather than sequentially.
4Measurement precision
If manual quality assessment steps are performed before library preparation, then accurate quality control is achieved, but the process becomes more labor-intensive and time-consuming
Solution Approach 1:
The cartridge enables self-service quality assessment through integrated qPCR analysis that automatically measures nucleic acid quality and quantity within the cartridge itself. The system performs its own quality control without requiring external manual assessment steps, thereby maintaining measurement precision while significantly improving ease of operation by eliminating separate quality control procedures from the workflow.
Data Source
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AI summary
The present invention generally-relates to cartridges for automated systems and automated methods for fully automated processing of biological samples to next-generation sequencing-ready nucleic acid libraries. In particular, the present invention concerns a fluidic cartridge comprising a compartment for receiving a biological sample, means for liberating and/or purifying nucleic acids from the received sample and for transporting said nucleic acids to a compartment wherein NGS library can be prepared from said nucleic acids using provided therein reagents. In a particular aspect, the present invention also concerns cartridges for automated systems and automated methods for preparing an NGS nucleic acid library from a biological sample simultaneously or sequentially with a qPCR assay performed on the same biological sample.