Pro-Inflammatory Cytokines and Soluble Cellular Adhesion Molecules as Activating Triggers for Nanorobots

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Pro-Inflammatory Cytokines and Soluble Cellular
Adhesion Molecules as Activating Triggers for
Nanorobots Lior Rosen1, Adriano Cavalcanti2,
Moshe Rosenfeld1 and Shmuel Einav1 1Faculty of
Engineering, Tel-Aviv University, Tel-Aviv,
Israel 2Electrical and Computer Eng. School,
Unicamp, Campinas, Brazil.
INTRODUCTION
RESULTS
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• 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.

sVCAM-1 Levels and Blood Temperature Distributions
Rupture-prone site at distal edge
Rupture-prone site at proximal edge
sVCAM-1 Mass Fraction
sVCAM-1 Mass Fraction

• 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.

Temperature (C0)
Temperature (C0)
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.

•  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.

Rupture-prone site at distal edge
Rupture-prone site at proximal edge
SUMMARY

• 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.