Integrated Calendar

Organ-on-chip technology aims to replace animal toxicity testing, but thus far demonstrated few advantages over traditional methods. Current methods to evaluate toxicity rely on end-point assays measuring tissue damage and cell death, resulting in limited kinetic and mechanistic information. We present the Tissue Dynamics platform capable of maintaining vascularized 3D liver, cardiac, and neural tissues for over a month in vitro. Tissues acquire physiological structure, physiological activity and show complex metabolic zonation. Tissue-embedded metabolic sensors for oxygen, glucose, lactate and glutamine permit the real-time quantification of intracellular fluxes and tissue level function. Change in metabolic function is the first indication of physiological stress, preceding any detectable damage. Using the Tissue Dynamics platform, we show a new CYP450-idependent mechanism of acetaminophen toxicity that may be responsible for clinically observed nephrotoxicity. We also show that troglitazone, a drug withdrawn from the market due to idiosyncratic toxicity, induces harmful metabolic changes at below the observed threshold for toxic damage. These metabolic changes may underlie troglitazone’s observed idiosyncratic toxicity. Our work marks the importance of tracing function in real-time, demonstrating specific advantages in predicative toxicology.

The mechanics of many natural systems is governed by localized sources of stresses. Examples include "plastic events" that occur in amorphous solids under external stress, defects formation in graphene, and force-dipoles applied by cells adhered to an elastic substrate. Recent developments in a geometric formulation of elasticity theory paved the way for a unifying mathematical description of such singular sources of stress, as “geometric charges". In this talk I will review basic results in this field, focusing on the geometry and mechanics of two-dimensional solid bodies. I will demonstrate the applicability of this approach in three different problems: mechanical metamaterials, mechanics of Kirigami, and wrinkle patterns in geometrically-incompatible elastic sheets.

The nano-impact technique is among the latest and most considerable advances in electrochemistry and enables the detection and characterisation of individual nanoparticles, viruses, and bacteria. Its significance particularly arises from the broad applicability and simplicity of the experimental set-up and procedure: An electrode is set in contact with a solution comprising a suspension of analyte particles and is biased versus the solution potential. By virtue of Brownian motion, individual analyte entities then stochastically impact on the electrode surface, where they give rise to transient currents, Faradaic or capacitive, and an analysis provides insight into the nature of the impacting entity as well as the prevalent reaction mechanism.
The talk commences with a broad overview of the nano-impact technique while particularly theoretical aspects are highlighted. We then turn to examples of theoretical work on stochastic processes and the feasibility of individual enzyme detection to illustrate topics that are currently researched. In the light of recent developments, the talk finally points out future challenges and opportunities in the theory of nano-impacts.