Pro-Inflammatory Cytokines and Soluble Cellular Adhesion Molecules as Activating Triggers for Nanorobots Lior Rosen 1, Adriano Cavalcanti 2, Moshe Rosenfeld 1 and Shmuel Einav 1 1 Faculty of Engineering, Tel-Aviv University, Tel-Aviv, Israel 2 Electrical and Computer Eng. School, Unicamp, Campinas, Brazil. Ongoing developments in molecular fabrication, computation, sensors and motors will enable the manufacturing of nanorobots – nanoscale biomolecular machine systems. An elevated transcardiac gradient of soluble adhesion molecules (such as sVCAM-1) and pro-inflammatory cytokines (such as IL-6) may reflect the endothelial dysfunction of a coronary artery, and may be a predictive index of coronary atherosclerosis progression. It is well documented that a significant temperature heterogeneity exists over plaque surfaces, as inflamed plaques are hotter. 1 MODEL ASSUMPTIONS 2-D Axisymmetric models of stenosed LAD coronary arteries with varying diameter stenosis (20%, 50%, 90%) are being investigated. The inlet flow profile in the LAD coronary artery serves as an inlet boundary condition. Nanorobots are assumed to be equipped with chemical sensors, able to detect time-gradients in concentrations of specific molecules, and time-gradients of temperature. When a predefined threshold is exceeded, the nanorobot is activated. Nanorobots flow mainly in a near wall region (“The nanorobot freeway”). IL-6 and sVCAM-1 are being shed from rupture-prone sites of the vulnerable plaque. Various wall temperature profiles are simulated, according to lesion macrophage and inflammatory cells density. 2 INTRODUCTION OBJECTIVES Constituting a novel simulation approach, intended to be a platform for the design and research of nanorobots control. Establishing the triggering and control strategy for nanorobots in the coronary arteries, using clinical data regarding the distribution of IL-6, sVCAM-1, and the wall temperature in patients with acute coronary artery disease. Defining a range of nanorobot activation trigger values, which would fit to various clinical cases. METHODS Using CFD (Computational Fluid Dynamics), the locations and velocities of each injected nanorobot have been computed, as well as the temperatures, cytokines and soluble adhesion molecules concentrations the nanorobot is exposed to. CFD simulation output data is transferred to the NCD simulator to serve as the operating environment of the nanorobots. The NCD (Nanorobot Control Design) is a nanorobot-level simulator, providing analysis of nanorobot locomotion assuming various on- board sensors, motors and control tactics, including interactions with obstacles. The simulator also generates a visual display of the 3D environment. 3 Velocity (Cm/sec) The present work, of combining a precise physical simulation to establish the environment in which nanorobots would inhabit, with nanorobot control design simulator capable of modeling behavior, has been shown to be of an extreme potential for exploration of techniques, strategies, and nanorobot mobility considerations. An activating trigger based on both molecule concentrations and temperature time-gradients has been defined. This trigger may be implemented by foreseeable technology. This triggering approach can minimize the energy required for a nanorobot to reach the inflammation source, activating it close to the target. A delimited range of activation trigger values was defined and shown to fit different cases of rupture-prone sites of vulnerable plaques. The results can assist in future design of nanorobot sensors. Future work would include analysis of the nanorobots locomotion to the lesion after trigger activation, and also additional optimization and statistical framework. 5 SUMMARY RESULTS sVCAM-1 Levels and Blood Temperature Distributions Rupture-prone site at proximal edge Rupture-prone site at distal edge Trigger Activation Approaches for trigger activation include analyzing time- gradients of temperature and molecules concentration, as they change during nanorobot locomotion. The trigger has been defined as a function of concentration and temperature time- gradients, utilizing their correlation around the lesion. Activation occurs when a predefined threshold is exceeded. Temperature (C 0) sVCAM-1 Mass Fraction 4 Temperature (C 0 ) Rupture-prone site at proximal edge Rupture-prone site at distal edge