Selective Microbial Cell Filtration for Rapid Analyte Isolation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current molecular diagnostics methods struggle to achieve high sensitivity, particularly in applications with low analyte concentrations, such as direct blood sepsis pathogen detection, liquid biopsies for circulating tumor cells, and water analytics, due to limitations in sample enrichment and detection techniques.
Innovation Solution
A method using selective filtering and lysis solutions to enrich analytes from larger sample volumes, followed by lysis and elution through specific filters, enabling improved sensitivity and efficiency in nucleic acid and protein detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If pathogen enrichment by blood culturing is used, then detection sensitivity is improved, but time consumption increases significantly (24-72 hours)
Solution Approach 1:
The patent extracts the pathogen enrichment function from the time-consuming blood culturing process by using selective filtration to directly capture pathogens from blood samples, eliminating the 24-72 hour incubation period while maintaining detection sensitivity
Solution Approach 2:
The patent performs preliminary pathogen capture through selective filtration before detection, preparing the sample in advance by concentrating pathogens on filter membranes, which enables rapid downstream processing and eliminates the need for extended culturing time
2Measurement precision
If antibodies are used for pathogen enrichment, then detection sensitivity is improved, but storage stability and cost increase
Solution Approach 1:
The patent replaces expensive, unstable antibodies with disposable filter membranes that have pathogen-capturing properties integrated into their structure, eliminating storage stability issues and reducing costs while maintaining enrichment capability
Solution Approach 2:
The patent uses porous filter membranes with specific pore sizes and surface properties to physically capture and concentrate pathogens directly from the sample, providing a stable, antibody-free enrichment approach that improves storage stability
3Measurement precision
If centrifugation is used for pathogen enrichment, then detection sensitivity is improved, but instrument size and complexity increase
Solution Approach 1:
The patent extracts the pathogen enrichment function from complex centrifugation systems by using simple filtration, removing the need for bulky centrifuges and complex fluidics while achieving equivalent or superior enrichment performance
Solution Approach 2:
The patent replaces the mechanical centrifugation system with a passive filtration system that uses pressure differentials and surface properties for pathogen capture, eliminating moving parts and reducing instrument complexity
4Measurement precision
If larger sample volumes are processed, then detection sensitivity is improved, but processing time and complexity increase
Solution Approach 1:
The patent uses porous filter membranes with optimized pore sizes and large surface areas to efficiently capture pathogens from large sample volumes in a single pass, enabling high sensitivity without increasing processing complexity
Solution Approach 2:
The patent transitions from linear processing to a two-dimensional filtration approach by using filter membranes with large surface areas, allowing parallel capture of pathogens across the entire membrane surface, which efficiently handles large sample volumes without proportionally increasing complexity
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
Enhances assay sensitivity and reduces time and cost by processing larger sample volumes, facilitating rapid and accurate detection of pathogens and biomolecules.
Implementation Method 1
filtering the first lysate through a filter having a pore size that retains the intact microbial cells
Data Source
AI summary
Disclosed are methods for isolating an analyte from a sample. In some aspects, the methods are for selectively isolating a microbial cell analyte, such as a nucleic acid, from a sample containing or suspected of containing mammalian cells. The selective isolation method includes selective lysis of the mammalian cells and filtration of the resulting lysate through a filter that retains intact microbial cells, followed by on-filter lysis of the retained microbial cells to release the microbial cell analyte. The released analyte is then eluted from the filter. In other aspects, the methods utilize on-filter lysis of a sample containing intact cells (e.g., microbial cells) to release the analytes, followed by elution of the released analytes from the filter by passing an immiscible liquid through the filter. The isolated analytes may be analyzed using a suitable assay depending on the type of analyte molecule. Also disclosed are fluidic systems and lysis solutions that may be used for isolating an analyte according to the disclosed methods.