Transverse AC Electrophoresis for High-Throughput Particle Mobility Sizing
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Solution Overview
Problem
Existing methods for characterizing particle electrophoretic mobility, particularly in microfluidic systems, suffer from low signal-to-noise ratios, longer processing times, and lower sample throughput, with challenges such as bubble formation, surface adsorption, and particle aggregation, which affect the precision and reproducibility of measurements.
Innovation Solution
A novel microfluidic transverse AC electrophoresis (TrACE) technique using low-frequency AC electrophoresis and particle tracking velocimetry (PTV) in a microfluidic channel, employing a single pair of electrodes to create a high electric field orthogonal to the flow direction, allowing for precise measurement of electrophoretic mobility and size determination of particles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single-particle measurement techniques are used, then specific characteristics of each particle can be recorded, but the signal-to-noise ratio is low and processing time is long
Solution Approach 1:
The patent applies alternating current (AC) electrophoresis with frequencies ranging from 1 Hz to 10 kHz to induce periodic oscillation of particles in the electric field. This periodic action enables rapid measurement of electrophoretic mobility through oscillation amplitude and phase analysis, dramatically reducing processing time compared to traditional single-particle methods while maintaining measurement precision
Solution Approach 2:
The patent replaces traditional mechanical particle manipulation methods with acoustic radiation forces generated by surface acoustic waves (SAW). This substitution enables non-contact, label-free particle manipulation and focusing, improving signal-to-noise ratio and reducing measurement time by eliminating mechanical interference and sample preparation steps
2Measurement precision
If capillary electrophoresis is used, then electrophoretic mobility can be measured, but surface adsorption and particle aggregation occur affecting reproducibility
Solution Approach 1:
The patent extracts particles from the confining capillary environment and measures them in a open microchannel filled with buffer solution. This extraction eliminates surface adsorption issues inherent to capillary walls and prevents particle aggregation, thereby improving measurement reproducibility while maintaining electrophoretic mobility measurement accuracy
Solution Approach 2:
The patent introduces surface acoustic waves as an intermediary mechanism to manipulate and focus particles without direct contact with surfaces. The SAWs create acoustic radiation forces that position particles in the measurement zone without requiring surface interactions, eliminating adsorption effects and improving measurement reliability
3Productivity
If ensemble measurement techniques are used, then large numbers of particles can be measured in parallel, but single particle correlation and sorting capabilities are lost
Solution Approach 1:
The patent segments the measurement process by first focusing multiple particles into a narrow band using acoustic radiation forces, then measuring their electrophoretic mobility individually as they pass through the detection zone. This segmentation enables simultaneous processing of multiple particles while maintaining single-particle measurement precision and correlation capabilities
Solution Approach 2:
The patent adds the dimension of acoustic field manipulation to the traditional electrophoresis setup. By using surface acoustic waves to focus and position particles in the vertical dimension while maintaining horizontal flow, the system achieves multiplexed measurement capability without sacrificing single-particle analysis precision
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
TrACE enables multiplexed single-particle characterization with increased throughput, reduces noise and processing time, and avoids bubble formation, providing accurate electrophoretic mobility and size measurements for a variety of particles, including thermally sensitive biological samples.
Implementation Method 1
determining an electrophoretic mobility associated with a particle, based at least in part on passing the particle through a transverse alternating force microfluidic channel
Implementation Method 2
a plurality of electrodes oriented transverse to the microfluidic channel, the plurality of electrodes comprising an alternating current (AC) electric field
Implementation Method 3
determining a size of the particle based at least in part on one of Brownian motion of the particle
Data Source
AI summary
A method, comprising: determining electrophoretic mobility associated with a particle in a transverse alternating force microfluidic channel; determining a size of the particle based at least in part on one of Brownian motion of a particle or one or more images of the particle. A system comprising: a microfluidic channel; a plurality of electrodes oriented transverse to the microfluidic channel, the plurality of electrodes comprising an alternating electric field; and a classification system configured to: determine one or more of the following: an electrophoretic mobility associated with a particle in the transverse AC microfluidic channel and/or determine, based at least in part on the electrophoretic motion, and size from image analysis or Brownian motion of a particle or one or more images of the particle, particle shape, particle deformability, for recognition of surface characteristics, such as assaying for receptors and ligands, and to perform electroporation.