PFI-TT: Development of a Single-Molecule Electronic Biosensor

这个PFI项目更广泛的影响/商业潜力是为生物医学研究创造一种新型的生物传感器。生物传感器是研究分子如何相互结合的关键工具。蛋白质、抗体、多肽、DNA链和药物都以对人类健康至关重要的方式相互结合和释放；对这些结合相互作用的研究对于发现新药、检测疾病和理解我们自己的生物学至关重要。更好的生物传感器带来更好的健康结果，该项目开发的原型生物传感器旨在揭示目前所有其他类型的生物传感器所隐藏的分子相互作用。拟议的项目将利用生物传感研究的最新创新来实现这一目标。具体来说，电子固态生物传感器已经成功商业化；兼容的单分子电子学已被证明对生物化学活动的精确测量是有用的。该项目的技术目标将是一个概念验证混合设备，将传统的集成传感与互补的单分子结合动力学电子监测结合在一起。这种同时集成和单分子监测的结合在任何商用传感器中都不存在，但它为突破所有集成生物传感器面临的基本限制提供了新的机会。具体来说，该项目假设合并后的数据将扩展生物传感器的有效动态范围，并有助于消除假阳性和假阴性结果。如果成功，这种类型的混合传感器可以建立一个新的范例，在传感器中利用单分子数据，更好地为生物学、医疗保健和制造业的最终用户提供信息。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this PFI project is to create a new type of biosensor for biomedical research. Biosensors are key tools in the study of how molecules bind to each other. Proteins, antibodies, peptides, DNA strands, and medicines all bind and release each other in ways that are critical for human health; and the study of these binding interactions is critical to finding new medicines, detecting diseases, and understanding our own biology. Better biosensors lead to better health outcomes, and the prototype biosensor developed by this project aims to reveal molecular interactions that are presently hidden to all other types of biosensors currently in use.The proposed project will achieve this goal using recent innovations in biosensing research. Specifically, electronic, solid-state biosensors have been successfully commercialized; and compatible single-molecule electronics have been proven to be useful for precision measurements of biochemical activity. The technical objective of this project will be a proof-of-concept hybrid device that combines conventional ensemble sensing side-by-side with complementary, electronic monitoring of single-molecule binding kinetics. This combination of simultaneous ensemble and single-molecule monitoring does not exist in any commercial sensor, but it provides new opportunities to break through fundamental limitations faced by all ensemble biosensors. Specifically, the project hypothesizes that the combined data will extend the biosensor's effective dynamic range and help eliminate false positive and false negative results. If successful, this type of hybrid sensor could establish a new paradigm where single-molecule data are leveraged in sensors generally to better inform end users in biology, healthcare, and manufacturing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.