Microfluidic MRPS-Fluorescence Sensing for Correlated Nanoparticle Analysis
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Solution Overview
Problem
Existing technologies struggle to accurately measure the size, concentration, and single-particle fluorescence of nanoparticles in complex, heterogenous samples, particularly when particles are polydispersed in size or heterogeneous in material properties, as they rely on indirect methods that yield misleading results and lack particle-to-particle correlation.
Innovation Solution
A combined microfluidic resistive pulse sensing and fluorescence device that includes an optics module, cartridge interface, and fluids module, utilizing a multi-axis positioning system and modular fiber optics to enable simultaneous measurement of particle size, concentration, and fluorescence, with flexible alignment and high sensitivity to fluorescence light.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If indirect methods are used to measure nanoparticle size and concentration, then measurement process is simplified, but measurement precision deteriorates yielding misleading results
Solution Approach 1:
The patent combines two measurement modalities (fluorescence detection and resistive pulse sensing) into a single integrated device. The fluorescence module detects fluorescently labeled nanoparticles while the MRPS module measures electrical resistance changes, allowing simultaneous acquisition of size, concentration, and optical properties through direct measurement rather than indirect inference
Solution Approach 2:
The patent replaces indirect optical measurement methods with direct electrical resistance-based measurement for size determination. The MRPS technique measures nanoparticle size by detecting changes in electrical resistance as particles pass through a constriction, providing direct and accurate size measurement without relying on optical scattering models or calibration curves
2Measurement precision
If conventional fluorescence measurement is used, then particle subpopulations can be identified, but alignment complexities and photobleaching increase
Solution Approach 1:
The patent uses fluorescent labels as intermediaries to tag specific nanoparticle subpopulations of interest. These fluorescent markers allow selective identification and tracking of target particles (such as exosomes or specific cellular components) without requiring complex alignment procedures, as the fluorescence detection is performed through standard optical paths
Solution Approach 2:
The patent employs resistive pulse sensing as a periodic measurement technique where nanoparticles are driven through a sensing constriction one by one under applied voltage. This periodic passage through the detection zone minimizes exposure time to excitation light, thereby reducing photobleaching while maintaining high measurement precision
3Measurement precision
If simultaneous measurement of size and fluorescence is implemented, then particle-to-particle correlation is achieved, but device complexity increases
Solution Approach 1:
The patent integrates fluorescence detection and resistive pulse sensing modules within a single microfluidic device, allowing simultaneous measurement of both optical properties (fluorescence intensity) and physical properties (size via electrical resistance) of the same nanoparticle population. This merging enables direct particle-to-particle correlation without requiring separate measurements or complex synchronization
Solution Approach 2:
The patent designs a multi-functional device that performs multiple measurement tasks (fluorescence detection, size measurement via MRPS, and concentration determination) using a single integrated system. The microfluidic platform serves as a universal carrier that handles sample flow, electrical sensing, and optical detection, reducing overall system complexity despite the multiple measurement capabilities
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 provides accurate and quantitative measurements of nanoparticle size, concentration, and fluorescence by correlating MRPS and fluorescence signals, reducing photobleaching and alignment complexities, and enabling high sensitivity and ease of use.
Implementation Method 1
microfluidic resistive pulse sensing
Implementation Method 2
fluorescence detection
Data Source
AI summary
The devices and methods disclosed herein relate to combined microfluidic resistive pulse sensing and fluorescence to accurately and quantitatively measuring the size, concentration and single-particle fluorescence of nanoparticles in complex, heterogenous samples. The devices include an optics module, a cartridge interface, and a fluids module.


