Label free, biomimetic sensors for hormones and neurotransmitters

人体细胞分泌的激素和神经递质等分子的异常调节会导致各种各样的衰弱状况，包括成瘾、抑郁、糖尿病等。了解激素和神经递质分泌的正常和异常调节的主要挑战是无法以足够的选择性和灵敏度测量这些分子，因为它们从细胞中释放出来。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激素和神经递质的分泌，这些激素和神经递质在生物学上很重要，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中潜在的生化机制。该项目为亚利桑那大学（西班牙裔服务机构）和Yavapai社区学院的本科生和研究生提供教育和跨学科研究机会，从而帮助建立一支多样化的科学、技术、工程和数学劳动力队伍。对于绝大多数激素和神经肽以及许多神经递质来说，能够检测各种单一化合物以及同时从细胞中释放的多种化合物的传感器的发展具有挑战性。该研究项目通过开发基于新的传感器传感器概念的新型电生理传感器，解决了对激素和神经递质新的无标签测量策略的迫切需求，该传感器易于修改，可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传感器组成，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。换能器嵌入在一个集成到微移液管结构的超稳定脂质膜中。除了单个分析物传感器外，正在开发由多个不同传感器元件组成的传感器，这些传感器元件能够对多种分析物进行量化。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模块化方法。该项目侧重于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传感器的优化，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。

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.