Label-Free Multivariate Biophysical Phenotyping-Activated Acoustic Sorting at the Single-Cell Level
Peixian Li1, Ye Ai1
1Pillar of Engineering Product Development, Singapore University of Technology and Design, Singapore 487372, Singapore.
Analytical Chemistry
|February 18, 2021
Summary
This study introduces a novel method for label-free, high-throughput single-cell sorting using acoustic waves. It enables precise separation of cells based on their unique electrical and mechanical properties, improving cell purification without molecular markers.
Area of Science:
- Biophysics
- Cell Biology
- Microfluidics
Background:
- Cellular electrical and mechanical properties serve as label-free biomarkers.
- Accurate isolation of specific cell types from heterogeneous samples is crucial for further analysis.
- Current cell sorting lacks the ability to separate cells based on multivariate biophysical phenotypes at the single-cell level.
Purpose of the Study:
- To develop a label-free, high-throughput method for single-cell sorting based on multivariate biophysical phenotypes.
- To demonstrate the capability of acoustic sorting activated by combined electrical and mechanical cell characterization.
- To address the limitations of current cell purification techniques that rely on specific molecular biomarkers.
Main Methods:
- Implemented single-cell electrical impedance characterization using differential sensing electrodes.
- Determined mechanical phenotypes by analyzing cell transit time through microconstrictions from impedance signals.
- Developed a real-time algorithm to process impedance signals and trigger focused surface acoustic waves for cell sorting.
Main Results:
- Demonstrated label-free acoustic single-cell sorting based on individual electrical or mechanical phenotypes.
- Successfully sorted live MCF-7 cells from a mixed population with high throughput (>100 cells/s) and purity (~91.8%) using combined phenotyping.
- Validated the system's ability to perform multivariate biophysical phenotyping for cell sorting.
Conclusions:
- The developed microfluidic system enables high-throughput, label-free single-cell sorting based on multivariate biophysical properties.
- This technology offers a solution for cell purification challenges where specific molecular biomarkers are absent.
- The method advances cell characterization and isolation for various biological and medical applications.


