GEMSEC, Genetically Engineered Materials Science and Engineering Center, Materials Science and Engineering, University of Washington, 302 Roberts Hall, Seattle, WA, 98195, USA.
Small. 2014 Apr 24;10(8):1505-13, 1504. doi: 10.1002/smll.201302188. Epub 2014 Mar 26.
Direct molecular detection of biomarkers is a promising approach for diagnosis and monitoring of numerous diseases, as well as a cornerstone of modern molecular medicine and drug discovery. Currently, clinical applications of biomarkers are limited by the sensitivity, complexity and low selectivity of available indirect detection methods. Electronic 1D and 2D nano-materials such as carbon nanotubes and graphene, respectively, offer unique advantages as sensing substrates for simple, fast and ultrasensitive detection of biomolecular binding. Versatile methods, however, have yet to be developed for simultaneous functionalization and passivation of the sensor surface to allow for enhanced detection and selectivity of the device. Herein, we demonstrate selective detection of a model protein against a background of serum protein using a graphene sensor functionalized via self-assembling multifunctional short peptides. The two peptides are engineered to bind to graphene and undergo co-assembly in the form of an ordered monomolecular film on the substrate. While the probe peptide displays the bioactive molecule, the passivating peptide prevents non-specific protein adsorption onto the device surface, ensuring target selectivity. In particular, we demonstrate a graphene field effect transistor (gFET) biosensor which can detect streptavidin against a background of serum bovine albumin at less than 50 ng/ml. Our nano-sensor design, allows us to restore the graphene surface and utilize each sensor in multiple experiments. The peptide-enabled gFET device has great potential to address a variety of bio-sensing problems, such as studying ligand-receptor interactions, or detection of biomarkers in a clinical setting.
直接分子检测生物标志物是一种很有前途的方法,可用于诊断和监测许多疾病,也是现代分子医学和药物发现的基石。目前,生物标志物的临床应用受到现有间接检测方法的灵敏度、复杂性和低选择性的限制。一维和二维电子纳米材料,如碳纳米管和石墨烯,分别作为传感基底具有独特的优势,可用于简单、快速和超灵敏地检测生物分子结合。然而,仍需要开发多功能方法来对传感器表面进行功能化和钝化,以提高器件的检测和选择性。在这里,我们使用通过自组装多功能短肽功能化的石墨烯传感器,证明了针对血清蛋白背景的模型蛋白的选择性检测。这两种肽被设计为与石墨烯结合,并以有序的单分子膜的形式在基底上共同组装。虽然探针肽显示出生物活性分子,但钝化肽可防止非特异性蛋白质吸附到器件表面,从而确保了目标的选择性。特别是,我们展示了一种石墨烯场效应晶体管(gFET)生物传感器,它可以在低于 50ng/ml 的浓度下检测链霉亲和素,而背景为牛血清白蛋白。我们的纳米传感器设计允许我们恢复石墨烯表面并在多个实验中使用每个传感器。基于肽的 gFET 器件具有解决各种生物传感问题的巨大潜力,例如研究配体-受体相互作用,或在临床环境中检测生物标志物。