Doretto Daniel S, Corsato Paula C R, Silva Christian O, Pessoa James C, Vieira Luis C S, de Araújo William R, Shimizu Flávio M, O Piazzetta Maria H, Gobbi Angelo L, S Ribeiro Iris R, Lima Renato S
Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
Institute of Chemistry, University of Campinas, Campinas, São Paulo 13083-970, Brazil.
ACS Sens. 2025 Feb 28;10(2):773-784. doi: 10.1021/acssensors.4c02298. Epub 2024 Nov 29.
Despite the potentialities of electrochemical sensors, these devices still encounter challenges in devising high-throughput and accurate drug susceptibility testing. The lack of platforms for providing these analyses over the preclinical trials of drug candidates remains a significant barrier to developing medicines. In this way, ultradense electrochemical chips are combined with machine learning (ML) to enable high-throughput, user-friendly, and accurate determination of the viability of 2D tumor cells (breast and colorectal) aiming at drug susceptibility assays. The effect of doxorubicin (anticancer drug model) was assessed through cell detachment electrochemical assays by interrogating Ru(NH) with square wave voltammetry (SWV). This positive probe is presumed to imply sensitive monitoring of the on-sensor cellular death because of its electrostatic preconcentration in the so-called nanogap zone between the electrode surface and adherent cells. High-throughput assays were obtained by merging fast individual SWV measurements (9 s) with the ability of chips to yield analyses of Ru(NH) in series. The approach's applicability was demonstrated across two analysis formats, drop-casting and microfluidic assays. One should also mention that fitting a multivariate descriptor from selected input data via ML proved to be essential to providing accurate determinations (98 to 104%) of cell viability and half-maximal lethal concentration of the drug. The achieved results underscore the potential of the method in steering electrochemical sensors toward enabling high-throughput drug screening in practical applications.
尽管电化学传感器具有诸多潜力,但这些设备在设计高通量且准确的药敏试验方面仍面临挑战。在候选药物的临床前试验中,缺乏能够提供这些分析的平台仍然是药物研发的一个重大障碍。通过这种方式,超密集电化学芯片与机器学习(ML)相结合,旨在实现针对药敏试验的二维肿瘤细胞(乳腺癌和结肠直肠癌)活力的高通量、用户友好且准确的测定。通过用方波伏安法(SWV)检测Ru(NH),通过细胞脱离电化学分析评估了阿霉素(抗癌药物模型)的效果。由于其在电极表面和贴壁细胞之间的所谓纳米间隙区域中的静电预富集,这种阳性探针被认为意味着对传感器上细胞死亡的灵敏监测。通过将快速的单个SWV测量(9秒)与芯片对Ru(NH)进行系列分析的能力相结合,获得了高通量分析。该方法的适用性在两种分析形式,即滴铸法和微流控分析中得到了证明。还应提及的是,通过机器学习从选定的输入数据中拟合多变量描述符对于准确测定细胞活力(98%至104%)和药物的半数致死浓度至关重要。所取得的结果强调了该方法在引导电化学传感器实现实际应用中的高通量药物筛选方面的潜力。