Abstract

Herein, we reported a new dynamic light scattering (DLS) immunosensing technology for the rapid and sensitive detection of glycoprotein N-terminal pro-brain natriuretic peptide (NT-proBNP). In this design, the boronate affinity recognition based on the interaction of boronic acid ligands and cis-diols was introduced to amplify the nanoparticle aggregation to enable highly sensitive DLS transduction, thereby lowering the limit of detection (LOD) of the methodology. After covalently coupling with antibodies, magnetic nanoparticles (MNPs) were employed as the nanoprobes to selectively capture trace amount of NT-proBNP from complex samples and facilitate DLS signal transduction. Meanwhile, silica nanoparticles modified with phenylboronic acid (SiO2@PBA) were designed as the crosslinking agent to bridge the aggregation of MNPs in the presence of target NT-proBNP. Owing to the multivalent and fast affinity recognition between NT-proBNP containing cis-diols and SiO2@PBA, the developed DLS immunosensor exhibited charming advantages over traditional immunoassays, including ultrahigh sensitivity with an LOD of 7.4 fg mL−1, fast response time (< 20 min), and small sample consumption (1 μL). The DLS immunosensor was further characterized with good selectivity, accuracy, precision, reproducibility, and practicability. Collectively, this work demonstrated the promising application of the designed boronate affinity amplified-DLS immunosensor for field or point-of-care testing of cis-diol-containing molecules.Graphical

Highlights

  • Heart failure (HF) is one of the most common cardiovascular diseases, which often adversely affects cardiovascular health and has become a major cause of death in humans [1]

  • Working principle of the developed dynamic light scattering (DLS) immunosensor for NT‐proBNP Scheme 1 describes the working principle of the developed DLS immunosensor for the quantitative detection of NT-proBNP, wherein magnetic nanoparticles (MNPs)@monoclonal antibody (mAb) was employed for magnetic enrichment of target analytes and DLS signal transduction, and ­SiO2@PBA was designed as crosslinkers to amplify the crosslinking aggregation of MNPs

  • When NT-proBNP was present in the sample solution, target glycoprotein was selectively captured by the MNP@mAb to form the immunocomplex of MNP@ mAb-NT-proBNP

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Summary

Introduction

Heart failure (HF) is one of the most common cardiovascular diseases, which often adversely affects cardiovascular health and has become a major cause of death in humans [1]. Diagnosis of HF contributes to timely intervention, treatment, and prognosis. N-terminal probrain natriuretic peptide (NT-proBNP) has been considered as a clinically recognized biomarker for early diagnosis of HF [2]. Ultrasensitive detection for NT-proBNP is crucial for accurate clinical diagnosis and prognosis to reduce the hospitalization and mortality rates. Versatile immunoassay approaches have been reported to improve the determination of NT-proBNP, including colorimetric, fluorescent, electrochemical, field effect transistor, photoelectrochemical, electrochemiluminescence, and surface-enhanced Raman scattering [4,5,6,7,8,9,10]. Current methods succeed in achieving the specific detection of NT-proBNP, they are still compromised by insufficient sensitivity, long response time, large sample consumption and limited use in the field of point-of-care (POC) testing

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