Feasibility: An Artificial Electrocyte for Neuronal Observation & Interaction

描述（由申请人提供）：这项工作的长期目标是开发纳米机器技术，用于在细胞水平上观察人体并与人体互动。该项目的重点是一个远程供电和控制的人工电细胞（电器官细胞），能够执行高精度的神经刺激。同样的机器也可以用作纳米传感器，通过化学标签或在手术干预期间传递到其目标。这种传感器可能揭示出以前从未见过的神经信号传输及其病理中断的细节。纳米机器将使用DNA“折纸”方法进行自组装。通过这种方法，将构建一个500纳米（nm）量级的平台，其所有机载组件都以2纳米的精度集成到其设计位置。机载组件包括基于脂质体的人工电细胞。基本的电荷转移单元是与基于喹啉的氧化还原环偶联的人工反应中心，所述氧化还原环用作并入脂质体壁中的光驱动质子泵。它通过使用螺吡喃基光致变色活性分子打开壁中的质子通道来释放。电力和命令是通过光提供的，光由机载调谐等离子体天线放大。已经报道了这些纳米结构的入射光的三倍放大。开发过程以垫脚石的方式进行，每个组件都组装到平台上，并分别进行批量（溶液）和详细（使用原子力显微镜，扫描显微镜和单分子电子测量）测试。主要里程碑是：（i）使用精确定位在天线计算“热点”的荧光分子来验证天线放大。(ii)质子泵功能的化学验证（iii）绝缘电池链组装的验证。(iv)通过测量单链脂质体电解质末端产生的电压验证放电功能。(v)最终组装和测试。即使这十年没有看到体内纳米机器的出现，为实现这一目标而开发的技术也有许多其他近期的生物科学应用。DNA自组装过程可以应用于在现有微器件的尖端上制造纳米仪器。这种光动力的人工电细胞有望成为显微外科手术和人体及细菌细胞培养研究的新工具。事实上，这些纳米机器在体外应用于细胞集落的研究，本身就构成了一个新的和强大的工具，为细胞生物学的进步。 公共卫生相关性：传染病和退行性疾病通过在微观水平上破坏身体的细胞系统而进展。因此，观察、理解和对抗疾病的最终方法是使用微观机器在同一水平上操作。这种纳米机器可以提供新的、侵入性更小的方法来进行深部脑刺激，并提供有关导致多发性硬化症的神经表面损伤的详细数据。

DESCRIPTION (provided by applicant): The long-term objective of this work is to develop nano-machine technology for observing and interacting with the human body at the cellular level. The project's focus is a remotely powered and controlled artificial electrocyte (electric-organ cell) able to perform high precision neuro-stimulation. The same machine could also be used as a nano-sensor that would be delivered to its target by chemical tags or during surgical intervention. Such sensors may reveal never before seen intimate details of the transmission of neural signals and of their pathological interruption. The nano-machine will be self-assembled using the DNA "origami" approach. With this method a platform of the order of 500 nanometers (nm) across will be built with all its onboard components integrated into their designed locations with 2 nm precision. The on-board components include a liposome-based artificial electrocyte. The basic charge transfer unit is an artificial reaction center coupled to a quinoine-based redox loop that functions as a photodriven proton pump incorporated in the liposome wall. It is discharged on command by the opening of proton channels in the wall using a spiropyran-based photochromically active molecule. The power and command is provided through light that is amplified by on-board tuned plasmonic antennas. Thousand-fold amplification of the incident light has been reported for these nanostructures. The development proceeds in a stepping-stone approach where every component is assembled onto the platform and tested individually both in bulk (in solution) and in detail (using Atomic Force Microscopy, Scanning Microscopy and Single Molecule Electronics measurements). The key milestones are: (i) Verification of antenna amplification using a fluorescent molecule precisely positioned at the antenna's calculated "hot spot". (ii) Chemical verification of proton pump function (iii) Verification of assembly of insulated electrocyte chain. (iv) Verification of discharge function by measuring the voltage developed at the end of a single-chain liposome electrocyte. (v) Final assembly and test. Even if this decade does not see the advent of the in vivo nano-machine, the technology developed working towards this goal has many other near-term bio-science applications. The DNA self-assembly process can be applied to the manufacture of nano-instruments on the tips of existing micro-devices. The light-powered artificial electrocyte could become a new tool in micro-surgery and in the study of cell cultures, human and bacterial. In fact, the in vitro applications of these nano-machines to the study of cell colonies would, in itself, constitute a novel and powerful tool for the advancement of cellular biology. PUBLIC HEALTH RELEVANCE: Infectious and degenerative diseases progress through the breakdown of the body's cellular systems at the microscopic level. Therefore, the ultimate way to observe, understand and combat disease is to operate at the same level using microscopic machines. Such nanomachines could offer new, less intrusive methods to perform deep brain stimulation as well as provide detailed data on the nerve surface damage leading to Multiple Sclerosis.