OPTOELECTRONIC NANOWIRE PROBES FOR INVESTIGATION OF INTRA-CELLULAR PROCESSES

描述(由申请人提供) 摘要：我们建议组装具有光电和电学功能的纳米线设备，以前所未有的空间和时间分辨率探测细胞内和细胞间的动力学。电泵浦纳米线波导、激光器、发光二极管和光电探测器阵列及其作为纳米电极的功能将被用于以纳米级分辨率探测细胞器和其他亚细胞目标，并实时测量化学反应动力学、信号传播和由于局部释放的药物引起的反应，以及在任何相关长度尺度上发生的其他复杂现象。纳米线探测器阵列将在其尖端或表面使用荧光团、量子点、等离子体纳米晶体来功能化，以实现几乎任何类型的生物成像技术。使用通用的纳米线探针平台将导致开发一系列具有新功能的非常广泛的工具，以实现具有无标记技术的成像和电探测，该技术具有探测活细胞内任何所需空间域的独特能力。这些纳米线探针底物可以很容易地与AFM悬臂或传统纤维的尖端集成，然后可以与标准的3-D纳米定位系统、外部电路和光学显微镜相结合，以探测细胞内细胞器/组件的特定区域。例如，这些纳米线设备将被用来创建与海马神经元和神经元网络的新型纳米级接口，以研究神经元信号整合和网络功能，然后用于研究癫痫等疾病的病理生理学。将纳米线的光电和电学功能集成在一个共同的平台上，将导致新一代纳米系统在分子水平上探测活细胞的亚室，具有前所未有的灵敏度和选择性，这将彻底改变我们对这些生物系统的认识，并极大地帮助未来的药物发现。 与公共卫生相关：利用建议的光电和电学结合的纳米线探针，通过多路复用和纳米级分辨率检测实时可视化体外细胞内和细胞间过程的能力，将阐明新的化学和电化学过程和信号通路。对使用纳米线探针的亚细胞和细胞间过程的详细了解将有助于更好地了解整个细胞过程，并将有助于设计治疗大量疾病的新药，从而影响公众健康。

DESCRIPTION (Provided by the applicant) Abstract: We propose to assemble nanowire devices with optoelectronic and electrical functionalities to probe intra- and inter-cellular dynamics with unprecedented spatial and temporal resolution. Arrays of electrically pumped nanowire waveguides, lasers, light emitting diodes, and photodetectors combined along with their ability to function as nanoelectrodes will be utilized to probe organelles and other subcellular targets with nanoscale resolution and measure in real-time chemical reaction kinetics, signal propagation, and reactions due to a locally delivered drug, amongst other complex phenomena occurring over any relevant length scales. The arrays of nanowire probes will be functionalized with fluorophores, quantum dots, plasmonic nanocrystals, either at their tips or on their surfaces to enable almost any type of biological imaging technique. Using a general nanowire probe platform will lead to the development of a very broad set of tools with novel functionalities, to enable imaging and electrical probing with label-free techniques with the unique capability of probing any desired spatial domain within living cells. These nanowire-probe substrates can be easily integrated with AFM cantilevers or the tips of conventional fibers, which can then be combined with standard 3-D nanopositioning systems, external electrical circuitry, and optical microscopes to probe specific domains of intracellular organelles/components. As an example, these nanowire devices will be used to create novel nanoscale interfaces with neurons and neuronal networks in the hippocampus to study neuronal signal integration and network functioning and then utilized to investigate the pathophysiology of diseases such as epilepsy. The integration of optoelectronic and electrical functionalities of nanowires on a common platform would lead to a new generation of nanosystems with unprecedented sensitivity and selectivity in probing subcompartments of living cells at the molecular level, which could revolutionize our knowledge of these biological systems and tremendously aid in future drug discoveries. Public Health Relevance: The ability to visualize in vitro intra- and inter- cellular processes in real time with multiplexed and nanoscale resolution detection with the proposed combined optoelectronic and electrical nanowire probes will elucidate new chemical and electrochemical processes and signaling pathways. Detailed knowledge of suband inter- cellular processes using nanowire probes will lead to a much better understanding of overall cellular processes and will aid the design of new drugs for a large number of diseases thereby impacting public health.