In Situ Formation of Gold Nanoparticles Decorated Ti₃C₂ MXenes Nanoprobe for Highly Sensitive Electrogenerated Chemiluminescence Detection of Exosomes and Their Surface Proteins

Abstract

In this work, an ultrasensitive electrogenerated chemiluminescence (ECL) biosensor for exosomes and their surface proteins was developed by the in situ formation of gold nanoparticles (AuNPs) decorated Ti3C2 MXenes hybrid with aptamer modification (AuNPs-MXenes-Apt). In this strategy, the exosomes were efficiently captured on an exosome recognized CD63 aptamer modified electrode interface. Meanwhile, in situ formation of gold nanoparticles on single layer Ti3C2MXenes with aptamer (MXenes-Apt) modification was obtained, in which MXenes acted as both reductants and stabilizer, and no additional reductant and stabilizer involved. The in situ formed AuNPs-MXenes-Apt hybrid not only presented highly efficient recognition of exosomes specifically, but also provide naked catalytic surface with high electrocatalytic activity of gold nanoparticles with predominated (111) facets that significantly improved the ECL signal of luminol. In this way, a highly sensitive ECL biosensor for exosomes detection was constructed ascribing to the synergistic effects of large surface area, excellent conductivity, and catalytic effects of the AuNPs-MXenes-Apt. The detection limit is 30 particles μL–1 for exosomes derived from HeLa cell line, which was over 1000 times lower than that of conventional ELISA method and the linear range was from 102 particles μL–1 to 105 particles μL–1. This ECL sensing platform possessed high selectivity toward exosomes and their surface proteins derived different kinds of tumor cell lines (HeLa cells, OVCAR cells and HepG2 cells), and enabled sensitive and accurate detection of exosomes from human serum, which implied that the ECL biosensor provided a feasible, sensitive, and reliable tool for exosomes detection in exosomes-related clinical diagnostic.

Recent Progress on the Isolation and Detection Methods of Exosomes

“…Many scholars [58] have realized the detection of exosomes by CD63 aptamer with good detection results. Zhang and his colleagues [59] used gold nanoparticle modified by Ti3C2 and CD63 aptamer to construct a hypersensitive electrochemiluminescence sensor for exosomes and their surface proteins. In this strategy, not only exosomes were specifically and efficiently recognized, but also bare catalytic surfaces of gold nanoparticles with high electrocatalytic activity were provided.…”

“… The principle of detecting exosomes based on Ti3C2 MXenes biosensor ECL modified by in situ formation of gold nanoparticles [59] …”

“…The principle of detecting exosomes based on Ti3C2 MXenes biosensor ECL modified by in situ formation of gold nanoparticles. [59] magnetoresistance (GMR) biosensors, [66] click-chemistry, [67] and luminescent resonant energy transfer (LRET). [68] Tan's group [69] used the specific binding between exosomes surface proteins and aptamers to cause color changes.…”

Additive Manufacturable Materials for Electrochemical Biosensor Electrodes

“…[98] To date, they have been functionalized with antibodies, DNA, enzymes, and aptamers, to impart features such as enhanced sensitivity or selectivity. [99][100][101][102][103] As Mxenes possess a large surface area, there is potential for immobilization of large amounts of biological molecules.…”

A Solid‐State Electrochemiluminescence Sensor Based on Novel Two‐Dimensional Ti3C2 MXene

“…[12] In most ECL sensing platforms, MXene was employed as signal amplifier and catalytical probes to construct the active transducer surfaces. [13] For example, Liu's group combined the multilayer MXene with Nafion membrane to improve the electron transfer capacity of pure Nafion and developed the label-free single-nucleotide mismatch discrimination based on the solid-state ECL platform. [14] Dai et al utilized the MXene as carriers to load the ECL coreactant of black phosphorous quantum dots and luminophore of Ru(dcbpy) 3 2 + to develop the self-enhanced exosomes sensing.…”