Department of Applied Physics, Yale University, New Haven, CT, USA.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013 Nov-Dec;5(6):629-45. doi: 10.1002/wnan.1235. Epub 2013 Jul 29.
Field-effect transistor-based biosensors (bioFETs) have shown great promise in the field of fast, ultra-sensitive, label-free detection of biomolecules. Reliability and accuracy, when trying to measure small concentrations, is of paramount importance for the translation of these research devices into the clinical setting. Our knowledge and experience with these sensors has reached a stage where we are able to identify three main aspects of bioFET sensing that currently limit their applications. By considering the intrinsic device noise as a limitation to the smallest measurable signal, we show how various parameters, processing steps and surface modifications, affect the limit of detection. We also introduce the signal-to-noise ratio of bioFETs as a universal performance metric, which allows us to gain better insight into the design of more sensitive devices. Another aspect that places a limit on the performance of bioFETs is screening by the electrolyte environment, which reduces the signal that could be potentially measured. Alternative functionalization and detection schemes that could enable the use of these charge-based sensors in physiological conditions are highlighted. Finally, the binding kinetics of the receptor-analyte system are considered, both in the context of extracting information about molecular interactions using the bioFET sensor platform and as a fundamental limitation to the number of molecules that bind to the sensor surface at steady-state conditions and to the signal that is generated. Some strategies to overcome these limitations are also proposed. Taken together, these performance-limiting issues, if solved, would bring bioFET sensors closer to clinical applications.
场效应晶体管生物传感器(bioFET)在快速、超灵敏、无标记生物分子检测领域显示出巨大的潜力。在尝试测量小浓度时,可靠性和准确性对于将这些研究设备转化为临床环境至关重要。我们对这些传感器的了解和经验已经达到了一个阶段,我们能够确定当前限制它们应用的三个主要方面的 bioFET 传感。通过将固有器件噪声视为可测量最小信号的限制,我们展示了各种参数、处理步骤和表面修饰如何影响检测限。我们还引入了 bioFET 的信噪比作为通用性能指标,这使我们能够更好地了解更灵敏器件的设计。限制 bioFET 性能的另一个方面是电解质环境的筛选,这会降低潜在可测量的信号。突出了能够在生理条件下使用这些基于电荷的传感器的替代功能化和检测方案。最后,考虑了受体-分析物系统的结合动力学,既包括使用 bioFET 传感器平台提取有关分子相互作用的信息,也包括在稳态条件下结合到传感器表面的分子数量以及产生的信号的基本限制。还提出了一些克服这些限制的策略。综上所述,如果这些性能限制问题得到解决,bioFET 传感器将更接近临床应用。