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基于阻抗的中和抗体检测生物传感器及其在SARS-CoV-2感染中的应用

Impedance-Based Neutralizing Antibody Detection Biosensor with Application in SARS-CoV-2 Infection.

作者信息

Manshadi Mohammad K D, Mansoorifar Amin, Chiao Jung-Chih, Beskok Ali

机构信息

Mechanical Engineering Department, Southern Methodist University, Dallas, Texas75275, United States.

Electrical and Computer Engineering Department, Southern Methodist University, Dallas, Texas75275, United States.

出版信息

Anal Chem. 2023 Jan 17;95(2):836-845. doi: 10.1021/acs.analchem.2c03193. Epub 2023 Jan 2.

Abstract

Although safe and efficacious coronavirus disease-2019 (COVID-19) vaccines are available, real protective immunity is revealed by the serum COVID-19 neutralizing antibody (NAb) concentration. NAbs deactivate the virus by attaching to the viral receptor-binding domain (RBD), which interacts with angiotensin-converting enzyme 2 (ACE2) on the human cell. This paper introduces inexpensive, rapid, sensitive, and quantifiable impedance-based immunosensors to evaluate the NAb. The sensor limit of detection is experimentally determined in different buffer dilutions using bovine IgG-anti-bovine IgG interaction. The dominance of AC electrokinetic transport and molecular diffusion in the sensor is investigated using scaling analysis and numerical simulations. The results demonstrated that the sensor detection mechanism is mainly based on the diffusion of the biomolecules onto the electrode surface. After evaluating the sensor working principles, viral RBD buffers, including different NAb concentrations, are applied to the sensor, immobilized with the human ACE2 (hACE2). Results demonstrate that the sensor is capable of NAb detection in the analytical measuring interval between 45 ng/mL and 185 ng/mL. Since the present sensor provides fast test results with lower costs, it can be used to assess the NAb in people's blood serum before receiving further COVID vaccine doses.

摘要

尽管已有安全有效的2019冠状病毒病(COVID-19)疫苗,但血清COVID-19中和抗体(NAb)浓度才能揭示真正的保护性免疫。中和抗体通过附着于病毒受体结合域(RBD)使病毒失活,该受体结合域与人细胞上的血管紧张素转换酶2(ACE2)相互作用。本文介绍了用于评估中和抗体的基于阻抗的廉价、快速、灵敏且可定量的免疫传感器。使用牛IgG-抗牛IgG相互作用,在不同缓冲液稀释度下通过实验确定传感器的检测限。使用标度分析和数值模拟研究了传感器中交流电动传输和分子扩散的主导作用。结果表明,传感器的检测机制主要基于生物分子在电极表面的扩散。在评估了传感器的工作原理后,将包括不同中和抗体浓度的病毒RBD缓冲液应用于固定有人类ACE2(hACE2)的传感器。结果表明,该传感器能够在45 ng/mL至185 ng/mL的分析测量区间内检测中和抗体。由于本传感器能以较低成本提供快速检测结果,因此可用于在人们接种更多剂COVID疫苗之前评估其血清中的中和抗体。

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