Molecular fingerprinting of biological nanoparticles with a label-free optofluidic platform

Nat Commun. 2024 May 15;15(1):4109. doi: 10.1038/s41467-024-48132-4.

Abstract

Label-free detection of multiple analytes in a high-throughput fashion has been one of the long-sought goals in biosensing applications. Yet, for all-optical approaches, interfacing state-of-the-art label-free techniques with microfluidics tools that can process small volumes of sample with high throughput, and with surface chemistry that grants analyte specificity, poses a critical challenge to date. Here, we introduce an optofluidic platform that brings together state-of-the-art digital holography with PDMS microfluidics by using supported lipid bilayers as a surface chemistry building block to integrate both technologies. Specifically, this platform fingerprints heterogeneous biological nanoparticle populations via a multiplexed label-free immunoaffinity assay with single particle sensitivity. First, we characterise the robustness and performance of the platform, and then apply it to profile four distinct ovarian cell-derived extracellular vesicle populations over a panel of surface protein biomarkers, thus developing a unique biomarker fingerprint for each cell line. We foresee that our approach will find many applications where routine and multiplexed characterisation of biological nanoparticles are required.

MeSH terms

  • Biomarkers / analysis
  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods
  • Cell Line, Tumor
  • Extracellular Vesicles / chemistry
  • Extracellular Vesicles / metabolism
  • Female
  • Holography / methods
  • Humans
  • Lipid Bilayers / chemistry
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods
  • Microfluidics / instrumentation
  • Microfluidics / methods
  • Nanoparticles* / chemistry