外泌体由于与亲代具有高度同源性，可以反映病理生理状态，在临床诊断中具有重要意义。然而，外泌体的定量和分类检测仍面临灵敏度低、操作复杂的挑战。在这项研究中，我们开发了一种基于硅纳米线场效应晶体管生物传感器（Si-NW Bio-FET）的电学和无标记方法，以高灵敏度直接检测外泌体。首先，通过仿真研究了德拜长度对 Si-NW Bio-FET 检测的影响。模拟结果表明，随着德拜长度的增加，距Si-NW表面一定距离的带电粒子对Si-NW产生的电响应更大。制备了在纳米线上用特异性抗体 CD81 修饰的 Si-NW Bio-FET，然后用于检测细胞系来源的外泌体，在 0.01 × PBS 中实现了 1078 个颗粒/mL 的低检测限 (LOD)。此外，分别用特异性抗体CD9、CD81和CD63修饰的Si-NW Bio-FET用于区分三种不同状态（对照组、脂多糖（LPS）炎症）的人早幼粒细胞白血病（HL-60）细胞系来源的外泌体组和LPS罗米地辛（FK228）药物治疗组），这与纳米流式细胞术一致。这项研究提供了一种无需标记即可直接定量外泌体的高度灵敏方法，表明其作为疾病监测和药物指导工具的潜力。版权所有 © 2024。由 Elsevier B.V. 出版。

Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction.Copyright © 2024. Published by Elsevier B.V.