Gutiérrez-Sanz Óscar, Andoy Nesha M, Filipiak Marcin S, Haustein Natalie, Tarasov Alexey
BioMed X Innovation Center , 69120 Heidelberg, Germany.
Institute for Physical Chemistry, Universität Heidelberg , 69120 Heidelberg, Germany.
ACS Sens. 2017 Sep 22;2(9):1278-1286. doi: 10.1021/acssensors.7b00187. Epub 2017 Aug 30.
Transistor-based biosensors fulfill many requirements posed upon transducers for future point-of-care diagnostic devices such as scalable fabrication and label-free and real-time quantification of chemical and biological species with high sensitivity. However, the short Debye screening length in physiological samples (<1 nm) has been a major drawback so far, preventing direct measurements in serum. In this work, we demonstrate how tailoring the sensing surface with short specific biological receptors and a polymer polyethylene glycol (PEG) can strongly enhance the sensor response. In addition, the sensor performance can be dramatically improved if the measurements are performed at elevated temperatures (37 °C instead of 21 °C). With this novel approach, highly sensitive and selective detection of a representative immunosensing parameter-human thyroid-stimulating hormone-is shown over a wide measuring range with subpicomolar detection limits in whole serum. To the best of our knowledge, this is the first demonstration of direct immunodetection in whole serum using transistor-based biosensors, without the need for sample pretreatment, labeling, or washing steps. The presented sensor is low-cost, can be easily integrated into portable diagnostics devices, and offers a competitive performance compared to state-of-the-art central laboratory analyzers.
基于晶体管的生物传感器满足了未来即时诊断设备对换能器提出的许多要求,比如可扩展制造以及对化学和生物物质进行无标记实时高灵敏度定量分析。然而,生理样本中较短的德拜屏蔽长度(<1 nm)一直是目前的一个主要缺点,阻碍了在血清中的直接测量。在这项工作中,我们展示了如何通过用短的特异性生物受体和聚合物聚乙二醇(PEG)对传感表面进行定制,来显著增强传感器响应。此外,如果在较高温度(37°C而非21°C)下进行测量,传感器性能可以得到显著改善。通过这种新方法,在全血清中,在宽测量范围内展示了对代表性免疫传感参数——人促甲状腺激素的高灵敏度和选择性检测,检测限达到亚皮摩尔级别。据我们所知,这是首次使用基于晶体管的生物传感器在全血清中进行直接免疫检测,无需样品预处理、标记或洗涤步骤。所展示的传感器成本低,可轻松集成到便携式诊断设备中,并且与最先进的中心实验室分析仪相比具有竞争力的性能。