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Fluid nanoporous microinterface enables multiscale-enhanced affinity interaction for tumor-derived extracellular

Qi Niu1,2, Jiafeng Gao1,3, Kaifeng Zhao1

  • 1Institute of Molecular Medicine, Department of Oncology, Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

Proceedings of the National Academy of Sciences of the United States of America
|October 28, 2022
PubMed
Summary

This study introduces FluidporeFace, a novel microfluidic chip for highly efficient isolation and ultrasensitive detection of tumor-derived extracellular vesicles (T-EVs). This technology enhances T-EV detection sensitivity for improved cancer diagnostics.

Keywords:
extracellular vesiclefluid interfacemicrofluidicsmultivalentsupported lipid bilayers

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Diagnostics

Background:

  • Tumor-derived extracellular vesicles (T-EVs) are crucial biomarkers for cancer diagnosis and treatment.
  • Low abundance and nanoscale size of T-EVs limit current isolation efficiency and detection sensitivity.
  • Existing methods struggle with effective interfacial affinity reactions for T-EVs.

Purpose of the Study:

  • To develop a microfluidic device for efficient isolation and ultrasensitive detection of T-EVs.
  • To engineer a multiscale-enhanced affinity reaction for improved T-EV capture.
  • To demonstrate the potential of this technology for clinical applications in liquid biopsies.

Main Methods:

  • Fabrication of a fluid nanoporous microinterface (FluidporeFace) using supported lipid bilayers (SLBs) on nanoporous herringbone microstructures.
  • Utilizing microscale herringbone patterns to enhance mass transfer of T-EVs.
  • Leveraging nanoscale nanoporousity for improved T-EV and interface contact.
  • Employing fluid SLBs for multivalent binding and increased affinity.

Main Results:

  • FluidporeFace achieved a limit of detection of 10 T-EVs μL⁻¹.
  • The device demonstrated ultrasensitive detection of T-EVs.
  • PD-L1 expression levels on isolated T-EVs successfully distinguished cancer patients from healthy donors.
  • An approximately 83-fold increase in binding affinity was observed compared to non-fluid interfaces.

Conclusions:

  • The FluidporeFace device offers a highly efficient strategy for T-EV isolation and detection.
  • This multiscale interfacial reaction approach significantly enhances biosensor performance.
  • The technology holds promise for expanding liquid biopsy applications, particularly for low-abundance targets.