Microfluidic Filter for Nucleic Acid Concentration and Amplification
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Solution Overview
Problem
Conventional methods for detecting antibiotic resistances in infectious diseases are time-consuming and require multiple laborious steps, especially when dealing with low concentrations of pathogens in large sample volumes, making it difficult to efficiently concentrate and amplify nucleic acids for diagnostics.
Innovation Solution
A method involving a microfluidic system where a biological sample is introduced into a separating system with a filter, allowing sample constituents to be separated and amplified directly on the filter, eliminating the need for separate extraction and reducing the number of work steps, using PCR for nucleic acid amplification with filter modification to prevent reagent retention and improve results.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional multi-step purification methods are used, then nucleic acid purity is improved, but processing time and operational complexity increase
Solution Approach 1:
The patent combines multiple separate work steps (filtration, cell lysis, nucleic acid purification, and PCR amplification) into a single integrated microfluidic system. The filter serves multiple functions: it concentrates cells from large sample volumes, enables direct lysis with buffer, and allows PCR reagents to access nucleic acids without requiring transfer to separate tubes. This merging eliminates time-consuming manual operations while maintaining nucleic acid purity through controlled buffer compositions that prevent contamination.
Solution Approach 2:
The microfluidic system is segmented into distinct functional zones within a single chip: a filtration zone for cell concentration, a lysis zone with chaotropic buffer for cell disruption and nucleic acid release, and a PCR zone for amplification. Each zone performs its function in-situ without requiring sample transfer, thus maintaining purity while reducing processing time and operational steps.
2Manufacturing precision
If multiple manual work steps are performed, then nucleic acid quality is improved, but automation difficulty increases
Solution Approach 1:
All manual operations (filtration, lysis, purification, amplification) are merged into a single automated microfluidic device. The system requires only sample loading and final analysis, with all intermediate steps occurring automatically within the chip. This integration dramatically reduces automation difficulty while preserving nucleic acid quality through controlled chemical environments in each functional zone.
Solution Approach 2:
The microfluidic system performs self-service by automatically conducting filtration, cell lysis, and nucleic acid amplification without manual intervention. Buffer flows automatically through the filter containing cells, chaotropic buffer automatically lyses cells and releases nucleic acids, and PCR reagents automatically access and amplify the nucleic acids. This self-service capability enables full automation while maintaining high nucleic acid quality through precisely controlled chemical conditions.
3Measurement precision
If large sample volumes are processed, then pathogen detection sensitivity is improved, but system size and complexity increase
Solution Approach 1:
The patent transitions from macro-scale processing to micro-scale integration by implementing all functions within a microfluidic chip. Large sample volumes (milliliters) are processed through a compact filter membrane, concentrating cells into a small volume that fits within the microfluidic system. This dimensional transition enables high sensitivity detection while maintaining a compact device footprint suitable for point-of-care applications.
Solution Approach 2:
A porous filter membrane is used to concentrate cells from large sample volumes. The porous structure allows buffer and small molecules to pass through while retaining cells on the membrane surface. This concentration step increases pathogen detection sensitivity by accumulating cells in a small volume, while the porous material itself occupies minimal space, avoiding increases in overall system size.
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 significantly reduces the number of steps and media required, saving time and cost, while achieving high efficiency in nucleic acid concentration and amplification, enabling rapid diagnostics even with low pathogen concentrations.
Implementation Method 1
introducing the sample into a separating system having at least one filter; accumulating the sample constituents containing in the sample by separating off the sample constituents on the filter
Implementation Method 2
using PCR for nucleic acid amplification with filter modification to prevent reagent retention and improve results
Data Source
AI summary
A method is disclosed for concentrating sample constituents and for multiplying nucleic acids from a biological sample which are containing in the sample constituents. The nucleic acids are amplified on the same filter on which the sample constituents are also separated off.