NRI: Design of nanorobotics based on iron-palladium alloy nanohelicses for a new diagnosis and treatment of cancer

纳米螺旋被认为是设计一组新型合成纳米致动器和传感器及其组合的一种新的有吸引力的构件元件，即纳米机器人，具有广泛的应用前景；生物医学、纳米医学、医药合成关键催化剂、能源器件（电池、太阳能电池等）关键电极、软物质机器人手近距离触觉传感器。如果纳米螺旋具有机械柔韧性，并由磁场控制的磁性活性材料制成，那么这种磁性活性纳米螺旋可以被设计成一种新的机器人系统，用于诊断和治疗难以治疗的癌症。所提出的纳米机器人具有多种功能；(1)由于“螺旋弹簧”的形状，在磁引导下游泳；(2)具有柔性纳米螺旋的纳米机器人在外加磁场和梯度下的机械振动，从而由于机械应力负载而杀死癌细胞；(3)纳米机器人的磁性活性材料还可以作为磁共振成像增强剂，从而在纳米机器人附着在癌细胞部位时精确定位。可以通过磁共振成像进行识别。本文采用化学工艺路线合成了铁-钯合金纳米螺旋；铝-硅模板和电镀制备固态铁-钯合金纳米螺旋。这种铁-钯合金纳米螺旋比我们之前设计的铁-钯合金宏观弹簧尺寸小，在外加磁梯度下表现出快速的振动。我们发现宏观铁钯合金弹簧的关键科学机理是一种新的驱动机制（混合机制），一组链式反应；施加磁梯度、磁力，应力诱导马氏体相由奥氏体相转变为马氏体相，从而在极短的时间内快速致动。本文建立了分子动力学模型，模拟了恒定磁场作用下铁钯合金纳米螺旋的另一种致动机制。我们还合成了另一种由铁-钯合金圆柱形头（头）和纳米螺旋组成的纳米机器人，其中铁-钯合金头可以用铁头代替，因此，铁头和铁-钯合金螺旋结合的纳米机器人可能更有效地服务于纳米机器人概念。本次NSF项目的目标是：(1)利用纳米机器人在磁场下证明假说驱动的机械应力诱导癌细胞凋亡；(2)建立磁性纳米机器人的最佳导航控制；(3)通过体外实验证明纳米机器人在癌症诊断和治疗中的有效性。为了实现上述目标，我们在三年的时间内提出了以下五个任务：任务a：磁性纳米螺旋及其纳米机器人的高产加工（Taya）任务b：铁钯合金纳米螺旋的纳米结构和性能表征（Taya）任务c：建模工作（Kuga/Taya）任务d：含有细胞凋亡研究溶液的纳米机器人的生产（Takao/Taya）任务e：应用磁场/梯度下磁性纳米机器人的体外实验（Lee/Kuga）。本建议的更广泛的影响是，所提出的基于磁性纳米螺旋的纳米机器人，导致开辟了上面讨论的新应用。我们计划将研究结果纳入教育，即：华盛顿大学现有的主动和传感材料及其集成系统研究生课程和暑期教育项目。本NSF项目的智力意义在于：(1)建立纳米机器人关键构件铁-钯纳米螺旋、复合磁头和铁-钯合金纳米螺旋的高产加工路线；(2)研究磁性纳米螺旋的混合驱动机制是否实现；(3)构建纳米机器人导航精确控制的内聚模型。（iv）验证机械应力载荷诱导细胞死亡的假设；(v)设计适合纳米机器人精确导航的亥姆霍兹线圈系统。

Nanohelix is considered a new and attractive building block element for designing a set of new synthetic nano-actuators and -sensors and combination of them, namely nanorobotics which has broader applications; biomedicine, nanomedicine, key catalyst for synthesis of pharmaceutical medicine, key electrodes for energy devices (battery, solar cells, etc), and proximity tactile sensor of soft-matter robotic hands. If the nanohelix is mechanically flexible and made of magnetically active material, which is controlled under applied magnetic field, such magnetically active nanohelix can be designed into a new robotics system for diagnosis and treatment of difficult-to-treat cancers. The proposed nanorobotics can have multi-functions; (i) swimming under magnetic guidance, thanks to the shape of "helical spring", (ii) mechanical vibrations of the nanorobotics with flexible nanohelix under applied magnetic field and gradient, thus, killing cancer cells due to mechanical stress loading, and (iii) magnetically active material for nanorobotics plays also as a magnetic resonance imaging enhancer, thus, accurate locations of the nanorobots if they are attached to cancer cell sites, can be identified by the magnetic resonance imaging. We recently synthesized iron-palladium alloy nanohelices by using chemistry processing route; alumina-silica template and electroplating to make solid-state iron-palladium alloy nanohelices. This iron-palladium alloy nanohelix is down-sizing from our previous design of macro-iron-palladium alloy spring which exhibited the fast vibrations under applied magnetic gradient. The key scientific mechanism associated with the macro-iron-palladium alloy spring, which we discovered is a new actuation mechanism (hybrid mechanism), a set of chain-reactions; applied magnetic gradient, magnetic force, stress induced martensite phase from austensite phase, resulting in fast-actuation within a very short time. We recently made molecular dynamics modelling to simulate another actuator mechanism of iron-palladium alloy nanohelices under applied "constant" magnetic field. We also synthesized another nanorobot which is composed of iron-palladium alloy cylindrical head (head) and nanohelix where we can replace the iron-palladium alloy head by an iron head, thus, the nanorobot based on the combination of iron head and iron-palladium alloy helix may serve more effective nanorobot concept. The goals of the proposed NSF project are multi-fold: (1) to prove the hypothesis driven mechanical stress-induced apoptosis of cancer cells by using the nanorobots under magnetic field, (2) to establish the optimum navigation control of the magnetic nanorobots and (3) to demonstrate the effectiveness of the nanorobots for cancer diagnosis and treatment using in vitro experiment. To achieve the above goals, we propose the following five tasks over a three-year period:Task-A: High-yield processing of magnetic nanohelices and their nanorobots (Taya)Task-B: Characterization of the nanostructure and properties of iron-palladium alloy nanohelices (Taya)Task-C: Modeling work (Kuga/Taya)Task-D: Production of nanorobots containing solution for apoptosis study (Takao/Taya)Task-E: In vitro experiment for magnetic nanorobots under applied magnetic field/gradient (Lee/Kuga)The broader impact of this proposal is that the proposed nanorobots based on magnetic nanohelices, leading to opening up new applications discussed above. We plan to incorporate the results into education,i.e., into the existing graduate course on active and sensing materials and their integrated systems and educational summer program at University of Washington. The intellectual significances of this NSF project are: (i) to establish high-yield processing route for key building block element of nanorobots, i.e. iron-palladium nanohelices, and combined magnetic head and iron-palladium alloy nanohelix , (ii) to study if the hybrid mechanism of actuation in magnetic nanohelix is realized, (iii) to construct a cohesive model for an accurate control of nanorobots navigation, (iv) to test the hypothesis of mechanical stress loading-induced cell death and (v) to design Helmholtz coil system tailored for accurate navigation of nanorobots.