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基于机器学习增强的印刷电路板上的石墨烯场效应晶体管生物芯片用于水中多种抗生素的超灵敏并行检测。

Graphene FET biochip on PCB reinforced by machine learning for ultrasensitive parallel detection of multiple antibiotics in water.

作者信息

Mukherjee P, Sen S, Das A, Kundu S, RoyChaudhuri C

机构信息

Department of Electronics & Telecommunication Engineering, Indian Institute of Engineering Science & Technology, Shibpur, Howrah, India.

Dr. Bholanath Chakraborty Memorial Fundamental Research Laboratory (under CCRH), Centre of Healthcare Science & Technology, Indian Institute of Engineering Science & Technology, Shibpur, Howrah, India.

出版信息

Biosens Bioelectron. 2025 Mar 1;271:117023. doi: 10.1016/j.bios.2024.117023. Epub 2024 Nov 30.

DOI:10.1016/j.bios.2024.117023
PMID:39647407
Abstract

Antibiotics like Ciprofloxacin (Cfx), tetracycline (Tet) and Tobramycin (Tob) are commonly used against a broad-spectrum of bacterial infection. Recent surge in their uptake through the presence of their residues in environmental water has been linked to increased antibiotic resistance. Conventional methods for antibiotic monitoring by gold standards like LC-MS though sensitive and reliable, are expensive, requires dedicated equipment and complex sample processing steps. In this context, nanoscale field-effect transistors (FETs) present significant advantages of rapid measurement and ultra-high sensitivity but the device-device variations in the transfer characteristics originating from the inherent fluctuations in fabrication protocol of 2D materials, lead to stochasticity in bioreceptor orientation and binding densities which limits their potential for ultrasensitive and reliable detection of multiple antibiotics in river water. Here, we introduce a distinctive approach for few femtomolar detection of Cfx, Tet and Tob simultaneously in river water by developing thermally reduced graphene oxide (TRGO) FET array on printed circuit board utilizing copper plated electrodes where multiple features extracted from sensor transfer characteristics are processed by machine learning models, trained with moderate calibration dataset. The demonstrated methodology detects 1 fM concentration of Cfx, Tet and Tob with satisfactory accuracy within 20 min, using XGBoost model. The achieved detection limit is three and two orders of magnitude lower than previous reports of multiple and single antibiotic detection respectively. The TRGO FET sensor array interfaced with an electronic readout imparts capability to track the concentration of antibiotic contaminants in various water sources and adopt necessary measures for safe drinking water.

摘要

环丙沙星(Cfx)、四环素(Tet)和妥布霉素(Tob)等抗生素通常用于对抗广谱细菌感染。近期,环境水体中这些抗生素残留的增加导致了抗生素耐药性的上升。尽管采用液相色谱 - 质谱等金标准方法进行抗生素监测灵敏可靠,但成本高昂,需要专用设备和复杂的样品处理步骤。在此背景下,纳米级场效应晶体管(FET)具有快速测量和超高灵敏度的显著优势,但由于二维材料制造工艺中固有的波动导致器件间转移特性存在差异,进而导致生物受体取向和结合密度的随机性,限制了其对河水中多种抗生素进行超灵敏和可靠检测的潜力。在此,我们介绍一种独特的方法,通过在印刷电路板上利用镀铜电极开发热还原氧化石墨烯(TRGO)FET阵列,同时对河水中的Cfx、Tet和Tob进行低至飞摩尔级别的检测。从传感器转移特性中提取的多个特征由机器学习模型进行处理,该模型使用适度的校准数据集进行训练。所展示的方法使用XGBoost模型在20分钟内以令人满意的准确度检测到1 fM浓度的Cfx、Tet和Tob。所实现的检测限分别比之前关于多种和单一抗生素检测的报告低三个和两个数量级。与电子读数接口的TRGO FET传感器阵列具备追踪各种水源中抗生素污染物浓度并采取必要措施确保饮用水安全的能力。

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