Untethering Electrophysiology in Vivo: An Optical Nanoscale Semiconductor Array f

描述(由申请人提供)：神经系统中信息处理的大规模并行性质要求同时和体内准确地感知和记录许多神经元的电活动。到目前为止，无论是在哺乳动物身上有系留的溶液，还是在有限程度上无系留的溶液中，这都是可能的，但在昆虫中是不可能的。基本的限制是神经探头的大小和重量。我们的提案呼吁开发基于光子晶体(PC)纳米腔激光器的纳米级神经探针，可以用于体内的自由神经传感和记录。探测器将由光学供电，并能够以预先指定的波长传输测量信号。在数百到数千个不同波长工作的这种探头阵列将允许人们并行和实时地记录和分析大量的神经活动。探测器将包括一个电场传感器，它可以调制光泵PC纳米腔激光器的输出功率或中心波长。传感器和纳米腔激光器都将被集成到III-V族化合物半导体薄膜中，该薄膜将在现代纳米制造工艺中制造。这一过程将使数以万计的新型设备能够以低成本并行生产。作为我们的试验床，我们将使用果蝇的早期嗅觉系统。当将探头插入苍蝇触角上感受器的底部时，该探头将获得由2-4个嗅觉感觉神经元将树突投射到该感受器所产生的局部ELD电位。然后，这个局部场势将被编码成由探测器上的纳米腔激光发出的光波。最后，将使用光学数据采集系统来捕获光波并解码局部场势。结合已经开发的精确气味传递和测量系统以及神经系统识别方面的理论进展，这种自由探头阵列将使我们对气味如何由嗅觉感觉神经元在时间和空间上代表进行异常详细的洞察，并有助于加深对高等大脑中枢气味信号处理的理解。此外，我们计划监测在自然环境中自由活动的嗅觉感觉神经元的神经活动。一个由20到30个纳米探测器组成的阵列将被插入天线中，并在自由光线下进行监测。考虑到纳米芯片半导体探针的尺寸和重量非常小，功能灵活，成本低，我们还设想它们将用于脊椎动物和无脊椎动物的各种感觉和运动系统中的非束缚神经传感和记录。 与公共健康相关：我们建议建立纳米级的光子设备，能够不受限制地记录果蝇早期嗅觉系统的神经活动。这些设备将使人们能够免费记录a y的神经活动对气味的反应 并将有助于加深对气味信号处理的理解，无论是在外周还是在更高的大脑中心。这反过来将帮助我们了解嗅觉障碍等疾病的神经基础，即无法感知气味。

DESCRIPTION (provided by applicant): The massively parallel nature of information processing in neural systems calls for an accurate sensing and recording of the electrical activity of many neurons simultaneously and in-vivo. Until now, this has been possible with both tethered and, to a limited extent, untethered solutions in mammals, but not in insects. The fundamental limitations were size and weight of neural probes. Our proposal calls for the development of nanoscale neural probes based on photonic crystal (PC) nanocavity lasers that can be used for untethered neural sensing and recording in-vivo. The probes will be optically powered and capable of transmitting measured signals at pre-specied wavelengths. An array of such probes operating at hundreds to thousands of dierent wavelengths will allow one to record and analyze massive amounts of neural activity in parallel and in real-time. The probes will include an electric field sensor that modulates either the output power or the center wavelength of an optically pumped PC nanocavity laser. Both the sensor and the nanocavity laser will be integrated into a III-V group compound semiconductor membrane that will be fabricated in a modern nanofabrication process. This process will enable a low-cost production of tens of thousands of novel devices in parallel. As our testbed, we will use the early olfactory system of the fruit fly Drosophila Melanogaster. When inserted at the base of a sensillum on the fly's antenna, the probe will pick up the local eld potential generated by 2-4 olfactory sensory neurons projecting their dendrites into that sensillum. This local field potential will then be encoded into a lightwave emitted by the nanocavity laser on the probe. Finally, an optical data acquisition system will be used to capture the lightwave and decode the local field potential. Combined with an already-developed system for precise odorant delivery and measurement as well as theoretical advances in neural system identication, an array of such untethered probes will give us an exceptionally detailed insight into how odorants are represented by olfactory sensory neurons both in time and space and will aid in developing a deeper understanding of odor signal processing in higher brain centers. Furthermore, we plan to monitor the neural activity of olfactory sensory neurons in freely moving ies in a natural environment. An array consisting of 20 to 30 nanoprobes will be inserted into the antennae and monitored in free ight. Given the extraordinarily small size and weight, flexible functionality and low cost of nanofabricated semiconductor probes, we also envision them being used for untethered neural sensing and recording in a wide variety of sensory and motor systems of both vertebrates and invertebrates. PUBLIC HEALTH RELEVANCE: We propose to build nanoscale photonic devices that would enable an untethered recording of neural activity in the early olfactory system of fruit flies. These devices will make it possible to record a y's neural activity in response to odorants in free ight and will aid in developing a deeper understanding of odor signal processing both in the periphery and in higher brain centers. This in turn will help us understand the neural basis of conditions such as anosmia, the inability to perceive odors.