Label free, biomimetic sensors for hormones and neurotransmitters

从人体细胞分泌的激素和神经递质等分子的异常调节导致广泛的衰弱状况，包括成瘾，抑郁症，糖尿病和许多其他疾病。 了解激素和神经递质分泌的正常和异常调节的一个主要挑战是无法在这些分子从细胞释放时以足够的选择性和灵敏度测量它们。 该研究项目旨在通过开发一种新的仿生传感器平台来克服这一挑战，该平台可以测量各种重要的激素和神经递质的分泌，这些激素和神经递质具有生物学意义，但使用现有方法无法充分检测。进行这种测量的能力使研究界能够更好地理解并最终纠正激素和神经递质调节的潜在生化机制。 该项目为亚利桑那大学的本科生和研究生提供了教育和跨学科研究的机会（西班牙裔服务机构）和Yavapai社区学院，从而帮助建立一个多元化的科学，技术，工程和数学劳动力。传感器的开发，能够检测各种单一的化合物，以及同时释放的多种化合物，对于绝大多数激素和神经肽以及许多神经递质来说， 该研究项目解决了对激素和神经递质的新的无标记测量策略的迫切需要，通过开发基于新的传感器换能器概念的新型电生理传感器，该传感器易于修改以检测广泛的重要生化分析物。 这些电生理传感器由蛋白质转换器组成，其在分析物结合时产生高增益电信号，包括离子通道蛋白或离子通道偶联受体蛋白。传感器被嵌入到一个超稳定的脂质膜，集成到一个微量移液管架构。 除了单个分析物传感器之外，正在开发由多个不同的传感器元件组成的传感器，这些传感器能够量化多种分析物。 该传感器平台为开发具有高空间和时间分辨率的高灵敏度和选择性传感器提供了一种模块化方法。该项目的重点是仿生电生理传感器的开发和表征，重点是影响传感器功能和性能的关键变量。这项工作的目标是脂质膜和蛋白质转换器的优化，多分析物传感器的设计和模型细胞系统的性能评估。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

Abnormal regulation of molecules such as hormones and neurotransmitters that are secreted from cells in the human body leads to a wide range of debilitating conditions, including addiction, depression, diabetes and many others. A major challenge in understanding the normal and abnormal regulation of hormone and neurotransmitter secretion is the inability to measure these molecules with sufficient selectivity and sensitivity as they are released from cells. This research project aims to overcome this challenging by developing a new biomimetic sensor platform that can measure the secretion of a wide range of important hormones and neurotransmitters that are biologically important, but that cannot be detected adequately using currently existing methods. The capability to make such measurements enables the research community to better understand, and ultimately correct, the underlying biochemical mechanisms in hormone and neurotransmitter regulation. The project provides educational and interdisciplinary research opportunities for undergraduate and graduate students at the University of Arizona (a Hispanic Serving Institution) and Yavapai Community College, thereby helping to build a diverse science, technology, engineering and mathematics workforce.The development of sensors that are capable of detecting various single chemical compounds, as well as multiple chemical compounds released simultaneously, from cells has proven challenging for the vast majority of hormones and neuropeptides, and many neurotransmitters. This research project addresses the critical need for new, label-free measurement strategies for hormones and neurotransmitters by developing a novel class of electrophysiological sensors based upon a new sensor transducer concept that is readily modified to enable detection of a wide range important biochemical analytes. These electrophysiological sensors are comprised of protein transducers that generate a high-gain electrical signal upon analyte binding, including ion channel proteins or ion channel-coupled receptor proteins. The transducers are embedded in an ultrastable lipid membrane that is integrated into a micropipette architecture. In addition to single analyte sensors, sensors comprised of multiple, differing sensor elements that enable quantification of multiple analytes are being developed. This sensor platform provides a modular approach for developing highly sensitive and selective sensors with high spatial and temporal resolution. The project focuses on development and characterization of biomimetic electrophysiological sensors with emphasis on key variables that affect sensor function and performance. The work targets optimization of lipid membranes and protein transducers, the design of multianalyte sensors and performance evaluation in model cellular systems.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.