Ultrasensitive Analysis of Exosomes Using a 3D Self-Assembled Nanostructured SiO₂ Microfluidic Chip

Abstract

Conventional microfluidics with a solid mixer for exosome detection is constrained by the low binding efficiency of the solid−liquid boundary effects and reduced sensitivity of individual markers. Here, we report a 3D-SiO 2 porous chip that combines nanoscale porous characteristics and multiple exosome specific markers to greatly improve the sensitivity for biosensing. The lower limit of detection was 220 particles/μL exosomes in PBS. We applied the 3D-SiO 2 porous chip for prostate cancer (PCa) staging in mice and early detection of clinical PCa patients. The developed method could significantly differentiate the different stages of PCa in mice and improve the early detection rate in clinical patients. Expression of multiple specific markers in clinical serum samples identified disease fingerprints, alongside histological results, which supports the potential application of exosomes as a noninvasive surrogate biopsy for PCa.

Microfluidics‐based molecular profiling of tumor‐derived exosomes for liquid biopsy

“…Similarly, a 3D-SiO 2 porous herringbone chip was constructed by Li et al through CSA technology for the multiplexed surface specific markers detection. 146 In this method, Tim-4 antibody-involved immunoaffinity was used to capture exosomes, and the biotinylated antibodies with the assistance of signal amplification strategy were applied to the detection of the four surface proteins (EpCAM, PSMA, and CD81). Clinical samples from prostate cancer staging and tumor-derived exosomes were analyzed by the 3D-SiO 2 porous chip with desirable sensitivity and specificity, respectively.…”

Emerging integrated SERS-microfluidic devices for analysis of cancer-derived small extracellular vesicles

“…5D). 83 They simulated the fluid flow in their device and reported that presence of SiO 2 nanostructures (as compared to only herringbone structure) reduced fluid stagnation near the surface which subsequently led to enhanced affinity capture of sEVs through increased particle-surface interaction.…”

Latest advances and perspectives of liquid biopsy for cancer diagnostics driven by microfluidic on-chip assays

“…5A). 100 They immobilized SiO 2 nanoparticles modified with Tim4 antibody in herringbone-shaped channels to capture exosomes. The captured exosomes were incubated with biotinylated detection antibody (anti-EpCAM, anti-PSMA, and anti-CD81).…”