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Exploiting Electrostatic Interaction for Highly Sensitive Detection of Tumor-Derived Extracellular Vesicles by an
Siddharth Sourabh Sahu1, Sara Cavallaro2, Petra Hååg3
1Department of Electrical Engineering, The Ångström Laboratory, Uppsala University, 75121 Uppsala, Sweden.
ACS Applied Materials & Interfaces
|September 2, 2021
Summary
This study enhances biosensor sensitivity for small extracellular vesicle (sEV) membrane protein detection using electrostatic charge. The optimized biosensor achieved a low limit of detection, enabling clinical application for cancer biomarker monitoring.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Analytical Chemistry
Background:
- Small extracellular vesicles (sEVs) are crucial biomarkers for disease diagnosis.
- Current biosensor technologies face limitations in detecting low concentrations of sEVs and their surface proteins.
- Improving detection sensitivity is vital for the clinical utility of sEV-based diagnostics.
Purpose of the Study:
- To develop and optimize a streaming current-based biosensor for enhanced detection sensitivity of sEV membrane proteins.
- To investigate the effect of sensor surface functionalization on electrostatic charge and detection performance.
- To validate the optimized biosensor for profiling cancer-associated proteins on sEVs from cell lines and patient samples.
Main Methods:
- Utilized theoretical investigation and experimental approaches to exploit electrostatic charge contrast for enhanced detection.
- Modulated sensor surface zeta potential through various chemical functionalization schemes (-16.0 to -32.8 mV).
- Determined optimal functionalization for maximum sensitivity and validated using sEVs from NSCLC cell lines and patient fluids, profiling CD9, EGFR, and PD-L1.
Main Results:
- Achieved a 2-order of magnitude improvement in detection sensitivity across different functionalization schemes.
- Reached a limit of detection (LOD) of 4.9 × 10^6 particles/mL for CD9 using the optimized surface.
- Successfully profiled CD9, EGFR, and PD-L1 on sEVs from NSCLC cell lines and patient samples, showing changes after treatment and in disease.
Conclusions:
- The developed electrostatic charge-based approach significantly enhances streaming current biosensor sensitivity for sEV membrane protein detection.
- The optimized biosensor demonstrates robust performance for profiling key cancer biomarkers (CD9, EGFR, PD-L1) on sEVs.
- This method holds significant promise for sensitive and specific clinical applications in cancer diagnostics and monitoring.
