Biochemical Sensors based on Single-Molecule Nanoelectronic Devices

在几十年极度小型化的基础上，电子设备正在成为一种单分子表征的创新技术，这种技术基于纳米级电子电路，能够捕获单个分子，并实时记录其结构和化学活动。在分子生物学中，监测孤立分子的能力尤其受到追捧，以表征蛋白质和核酸之间的相互作用，而不会因为集合平均而丢失信息。通过提出的研究计划，我将设计原创性的单分子生物正极电子器件，并扩大它们的应用，以获得关于生化机制的新知识，并开发创新的生物分析和生物物理仪器。纳米电子平台在表征生物分子方面具有特殊的优势，这将使先进的单分子测量能够在具有特殊空间和时间分辨率的生物兼容解决方案中实现。具体地说，拟议的研究计划围绕三个项目进行：DNA中的电荷传输(目标1)、酶催化活性(目标2)和生物标志物检测(目标3)。我将使用一种高度跨学科的实验方法来解决这些问题，结合化学、生物化学、固态物理和电气工程的策略和技术。特别是，这项研究将为学生提供电气测量、纳米制造、生物连接方案、显微镜、编程和数据分析方面的高级培训。 拟议的生物节点电子传感器研究计划旨在基于电子学在成本、便携性和放大方面的独特优势，为生物分析和生物物理技术的深刻扩展奠定基础。与芯片上实验室的设计相结合，它为组装负担得起、紧凑和多功能的分析和诊断试剂盒打开了大门，而此时基于基因组的个性化医学的兴起有望带来大量针对患者的生物标志物。它还为科学家开启了创新和强大的手段，以收集关于生物分子过程的大量数据，从而对生物分子的动力学及其在癌症和免疫疾病等复杂疾病中的作用产生独特的看法。由于所有这些原因，人们可以预期电子传感器的发展将对生物化学、生物物理学和生物医学实践产生革命性的影响。

Building on decades of extreme miniaturization, electronic devices are emerging as an innovative technology for single-molecule characterization, based on nanoscale electronic circuits able to capture individual molecules and record their structural and chemical activity in real time. The ability to monitor isolated molecules is particularly sought-after in molecular biology to characterize interactions between proteins and nucleic acids without loss of information due to ensemble averaging. Through the proposed research program, I will design original single-molecule bionanoelectronic devices, and expand their application to gain new knowledge on biochemical mechanisms and to develop innovative bioanalytical & biophysical instrumentation. Nanoelectronic platforms have specific advantages for the characterization of biomolecules that will enable advanced single-molecule measurements in biocompatible solutions with exceptional spatial and temporal resolutions. Specifically, the proposed research program is articulated around three projects: charge transport in DNA (Aim 1), enzyme catalytic activity (Aim 2) and biomarker detection (Aim 3). I will address these using an experimental approach that is highly interdisciplinary, combining strategies and techniques from chemistry, biochemistry, solid-state physics and electrical engineering. In particular, this research will provide students with advanced training in electrical measurements, nanofabrication, bioconjugation protocols, microscopy, programming and data analysis. The proposed research program on bionanoelectronic sensors aims to set the grounds for a profound expansion of bioanalytical and biophysical technology, based on the distinct advantages of electronics in terms of cost, portability and scale-up. Combined with lab-on-a-chip design, it opens the door to assembling affordable, compact and multi-purpose analysis and diagnosis kits, at the time when the rise of genome-based personalized medicine promises a deluge of patient-specific biomarkers. It also unlocks innovative and powerful means for scientists to collect a formidable amount of data on biomolecular processes, and thus generate a unique view of the dynamics of biomolecules and their role in complex diseases such as cancer and immunological disorders. For all these reasons, one can expect the development of electronic sensors to initiate a transformative impact on biochemistry, biophysics and biomedical practice.