A Metal Chelator as a Plasmonic Signal‐Generation Superregulator for Ultrasensitive Colorimetric Bioassays of Disease Biomarkers

Abstract

Enzyme‐based assays have been widely applied in clinical diagnosis for decades. However, the intrinsic limitations of enzymes, such as low operation stability, mediocre sensitivity, and high cost in production and purification, heavily constrain their detection application. Here, an enzyme‐free assay is reported that relies on the strong chelating capability of ethylenediamine tetraacetic acid disodium salt (EDTA•2Na, the chelator) for Au3+ ions, in which the cheap EDTA•2Na labeled by targeting moieties can selectively regulate the growth of plasmonic gold nanoparticles (AuNPs) at the target site subjecting to the concentration of analyte in samples. Independent of ambient temperature and unstable H2O2, EDTA•2Na perform superregulation in AuNPs plasmonic signal generation with distinct tonality and outstanding reliability. Upon integrating with silica nanoparticles as the signal amplifying platform, EDTA•2Na‐regulated bioassay can lead to detection‐sensitivity enhancements exceeding three orders of magnitude in protein detection, compared with the gold‐standard assay. The limit of detection of the HBsAg and alpha fetoprotein (AFP) pushes down to 2.6 × 10−15 and 2.5 × 10−19 g mL−1, respectively. EDTA•2Na‐regulated bioassay is also challenged in the clinical serum sample detection and a good consistency is found with the chemiluminescence immunoassay method in clinics.

Nanotechnology for Hepatocellular Carcinoma: From Surveillance, Diagnosis to Management

“…To overcome the problem of low detection sensitivity and interference of conventional serum immunoassays, several enhanced immunoassays using biosensor or Raman spectra detection have been performed. [ 42–45 ] Duan et al. applied a biosensor array integrated with nanopore, and the array was based on a microchip for label free and multiplexed detection of cancer‐related biomarker proteins using charge modulation ion current rectification.…”

Applications of nanotechnology in virus detection, tracking, and infection mechanisms

“…The detection sensitivity of EDTA•2Na regulated bioassay was enhanced by three orders of magnitude with incorporation of silica‐NPs. (Zhao, Piao, Peng, Wang, Gao, et al, 2018).…”

Silica-Based Nanoframeworks Involved Hepatocellular Carcinoma Theranostic

“…To overcome the deficiency of enzyme-based immunoassays that depend on the enzyme catalytic activity, which are determined by thermophilic scope and stability, an enzyme-free metal sequestration of a complexing agent to dominate the gold nanoparticle generation (called Scadge) strategy was carried out ( Zhao et al, 2018 ). The detection signals originated from the in situ generated gold nanoparticles (AuNPs) that were regulated by the metal chelator ethylenediaminetetraacetic acid disodium salt (EDTA·2Na).…”

“…(B,D) Practical detection of HBsAg by naked-eye visualization and (C,E) plotting absorbance values of AuNPs collected at 550 nm versus varying concentrations of HBsAg based on (B,C) Scadge-Diag and (D,E) SiO 2 NPs-amplified Scadge-Diag, respectively. Reprinted with permission from Zhao et al (2018) . Copyright (2018) John Wiley and Sons.…”