Multi-layer Asymmetric Membrane for Pathogen Detection

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Solution Overview

Problem

Current methods for detecting waterborne pathogens in environmental samples are often slow, expensive, and require sophisticated equipment, making them unsuitable for point-of-use field testing or low-resource settings, especially when dealing with low concentrations of pathogens.

Innovation Solution

A multi-layer asymmetric membrane system that filters samples to concentrate and detect pathogens by trapping them in micropores while allowing other constituents to pass through nanochannels, enabling rapid and cost-effective digital quantification and single-cell analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If culture-based detection methods are used, then detection accuracy is improved, but detection time increases to days

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The detection system segments the sample into numerous microreactors (droplets or chambers), each capable of independent amplification and detection. This parallel processing approach maintains high detection accuracy while reducing overall detection time by performing multiple reactions simultaneously rather than sequentially.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system performs preliminary enrichment and concentration of target pathogens in the sample before the actual detection step. By pre-concentrating the targets in a smaller volume, the subsequent amplification and detection processes are accelerated, reducing total detection time while maintaining accuracy.

Inventive Principle:
Principle #10Preliminary action

2Loss of time

If quantitative real-time PCR is used, then detection time is reduced to hours, but equipment cost and complexity increase

Engineering Contradiction:
Improvedetection timeVSAvoidequipment complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The invention employs disposable microfluidic chips or assay cartridges that integrate sample processing, amplification, and detection functions. These single-use devices eliminate the need for expensive, complex instrumentation while maintaining rapid detection capabilities, as each chip is self-contained and requires no sophisticated equipment for operation.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The system replaces complex mechanical amplification systems with isothermal amplification methods that occur at constant temperature, eliminating the need for thermal cyclers and complex temperature control mechanisms. This substitution maintains rapid detection while significantly reducing equipment complexity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If droplet-based microfluidics is used, then detection sensitivity is improved, but sample volume requirement increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsample volume
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The system nests multiple levels of partitioning within the sample processing workflow, creating hierarchical structures of droplets within chambers or compartments. This nested architecture allows extreme concentration of targets in minimal volumes while maintaining detection sensitivity, as each nested level further concentrates the sample without requiring proportionally larger total volumes.

Inventive Principle:
Principle #7Nested doll (Nesting)

4Quantity of substance

If bulk sample loading is used, then sample processing capacity is improved, but processing time increases to hours or days

Engineering Contradiction:
Improvesample processing capacityVSAvoidprocessing time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The system segments the bulk sample into numerous parallel microreaction channels or droplets, allowing simultaneous processing of large sample volumes. This segmentation enables high throughput capacity while maintaining rapid processing times, as multiple samples are processed in parallel rather than sequentially through a single channel.

Inventive Principle:
Principle #1Segmentation

5Measurement precision

If multiple pre-treatment steps are used, then detection accuracy is improved, but operational complexity increases

Engineering Contradiction:
Improvedetection accuracyVSAvoidoperational complexity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The invention merges multiple pre-treatment steps (filtration, concentration, purification, and lysis) into a single integrated microfluidic device or assay cartridge. This consolidation maintains detection accuracy by performing all necessary pre-treatments, but eliminates the need for multiple separate operational steps, significantly reducing user complexity and making the assay accessible to non-experts.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The integrated pre-treatment device performs multiple functions (filtration, concentration, purification, and lysis) within a single universal platform that can handle various sample types. This multi-functional design maintains high detection accuracy across different applications while requiring only a single device and protocol, reducing operational complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS20210180116A1Assay using multi-layer membrane to detect microbiological target and method of manufacturing multi-layer membrane
Publication Date: 2021.06.17 CALIFORNIA INST OF TECH
  • US20210180116A1 patent drawing
  • US20210180116A1 patent drawing
  • US20210180116A1 patent drawing

AI summary

A membrane, method and system are disclosed for rapid, sensitive and precise detection of an agent suspected of being present in a sample. The agent may be a cell or microorganism, e.g., a single pathogenic bacteria, and the sample may be small, e.g., milliliters of unprocessed environmental water. The sample is processed by filtering it through an asymmetric membrane having multiple layers. One layer has microchannels for capturing the agent and another layer has nanochannels for passing particles smaller than the agent. Amplification reagents, such as loop-mediated isothermal amplification (LAMP) reagents, are load onto membrane so that the microchannels act as nanoreactors, creating quantifiable amplicons within the pores on the exposed surface of the membrane in response to captured agent. The amplicons may be imaged and counted using a fluorescent camera. The membrane is capable of agent capture, concentration, purification, partition, lysis and digital LAMP without off-membrane sample treatments.