Microfluidic Nanoparticle Sizing and Sorting for Single-Particle Detection
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Solution Overview
Problem
Conventional flow cytometers and sorters lack the sensitivity and throughput for analyzing and sorting sub-cellular organelles and nanoscale biological nanoparticles, while existing concentration methods are time-consuming, costly, and prone to contamination.
Innovation Solution
A microfluidic chip system for illuminating and detecting biological nanoparticles on a particle-by-particle basis, using a microfluidic chip with constriction regions and detectors to measure light intensity, allowing for rapid size determination and sorting based on hydrodynamic diameter.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional flow cytometers are used for cell sorting, then broad range biological research applications are enabled, but sensitivity and throughput are insufficient for nanoscale biological nanoparticles
Solution Approach 1:
The invention segments the detection process by analyzing nanoparticles one-by-one as they flow through the microfluidic channel, rather than analyzing bulk samples. This single-particle analysis approach enables high sensitivity detection of nanoscale objects while maintaining high throughput through continuous flow processing
Solution Approach 2:
The invention transitions from conventional bulk flow analysis to microfluidic single-file flow analysis, adding the dimension of spatial confinement at the microscale. This enables individual nanoparticle detection while maintaining high flow rates through the narrow channel, resolving the sensitivity-throughput tradeoff
2Quantity of substance
If ultracentrifugation is used for bionanoparticle concentration, then concentration is achieved, but the process requires 4-5 hours and specialized expensive equipment
Solution Approach 1:
The invention replaces the mechanical ultracentrifugation system (requiring 200,000-fold gravity) with a microfluidic system that uses controlled fluid flow and optical detection. This substitution eliminates the need for expensive centrifugation equipment and reduces concentration time from hours to minutes
Solution Approach 2:
The invention changes the detection parameters from bulk optical measurements to single-particle optical measurements in a microfluidic environment. This enables detection of concentrated nanoparticles without requiring the extreme centrifugal forces of ultracentrifugation, achieving concentration in minutes rather than hours
3Quantity of substance
If ultracentrifugation is used for bionanoparticle concentration, then concentration is achieved, but contamination occurs due to lack of specificity
Solution Approach 1:
The invention applies local quality by using specific capture coatings (such as antibodies or streptavidin) at specific locations on the microfluidic channel surface. This localized specific binding enables selective capture of target nanoparticles while excluding non-target materials, achieving high purity concentration without contamination
4Reliability
If beads coated with capturing coatings are used for bionanoparticle capture, then specific capture is achieved, but downstream analysis requires release from beads causing decreased yield and accuracy
Solution Approach 1:
The invention extracts the capture function from separate beads and integrates it directly into the microfluidic channel wall through surface coatings. This eliminates the need for bead-based capture and subsequent release steps, allowing nanoparticles to be captured specifically and then analyzed directly in-flow without yield loss or damage from bead detachment
5Reliability
If bead-based capture is used for bionanoparticles, then capture is achieved, but expensive equipment and frequent manual handling are required
Solution Approach 1:
The invention merges the capture function, the analysis function, and the flow system into a single integrated microfluidic device. The capture coatings are built into the channel walls, eliminating the need for separate bead preparation, manual handling, and complex bead-based protocols, thereby reducing equipment complexity and operational burden
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
Enables high-throughput, accurate sizing and sorting of biological nanoparticles with single-nanoparticle sensitivity, reducing contamination and operational complexity.
Implementation Method 1
illuminating in the at least one microfluidic channel at least one biological nanoparticle from the portion of the plurality of biological nanoparticles on a particle-by-particle basis; detecting a light intensity emitted from the at least one biological nanoparticle
Data Source
AI summary
The present disclosure relates to methods, systems, and devices for performing analyses of biological nanoparticles. More specifically, the present disclosure relates to methods, systems, and devices for performing single biological nanoparticle size determination on a sample while the biological nanoparticle is in transit through a microfluidic chip. In other aspects, the present disclosure relates to methods, systems, and devices for selectively capturing biological nanoparticles on a coated planar surface, the capturing being facilitated by centrifugation.