Feasibility: An Artificial Electrocyte for Neuronal Observation & Interaction

描述(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其互动。该项目的重点是一种远程供电和控制的人造电细胞(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将其输送到目标位置。这类传感器可能会揭示神经信号传输及其病理性中断的前所未见的秘密细节。这台纳米机器将使用DNA“折纸”方法进行自我组装。使用这种方法，将建造一个跨度约500纳米(Nm)的平台，其所有机载组件将以2纳米的精度集成到设计位置。车载组件包括以脂质体为基础的人造电细胞。基本电荷转移单元是一个人工反应中心，与基于藜氨酸的氧化还原环路相连，该环路的功能是结合在脂质体壁上的光驱动质子泵。通过使用螺吡喃类光致变色活性分子打开壁中的质子通道，它在命令下被释放。能量和命令是通过光提供的，光由机载调谐等离子天线放大。据报道，这些纳米结构的入射光放大了数千倍。开发是以踏脚石的方式进行的，每个组件都被组装到平台上，并分别进行批量测试(溶液中)和详细测试(使用原子力显微镜、扫描显微镜和单分子电子学测量)。关键的里程碑是：(I)使用精确定位在天线计算的“热点”处的荧光分子来验证天线放大。(Ii)质子泵功能的化学验证(Iii)绝缘电细胞链的组装验证。(Iv)通过测量单链脂质体电细胞末端产生的电压来验证放电功能。(V)总装和试验。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型设备的尖端制造纳米仪器。光能人造电细胞可能成为显微外科手术和细胞培养、人类和细菌研究的一种新工具。事实上，这些纳米机器在体外应用于细胞集落的研究，本身就构成了推进细胞生物学的一种新颖而强大的工具。公共卫生相关性：传染病和退化性疾病在微观层面上通过人体细胞系统的崩溃而发展。因此，观察、理解和抗击疾病的最终方法是使用微观机器在同一水平上进行操作。这种纳米机器可以提供新的、侵入性较小的方法来执行脑深部刺激，并提供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.