Life is a non‐equilibrium state of matter maintained at the expense of energy. Nature uses predominantly chemical energy stored in thermodynamically activated, but kinetically stable, molecules. These high‐energy molecules are exploited for the synthesis of other biomolecules, for the activation of biological machinery such as pumps and motors, and for the maintenance of structural order. Knowledge of how chemical energy is transferred to biochemical processes is essential for the development of artificial systems with life‐like processes. Here, we discuss how chemical energy can be used to control the structural organization of organic molecules. Four different strategies have been identified according to a distinguishable physical‐organic basis. For each class, one example from biology and one from chemistry are discussed in detail to illustrate the practical implementation of each concept and the distinct opportunities they offer. Specific attention is paid to the discussion of chemically fueled non‐equilibrium self‐assembly. We discuss the meaning of non‐equilibrium self‐assembly, its kinetic origin, and strategies to develop synthetic non‐equilibrium systems.

The naked eye detection of single molecules in a complex mixture is the ultimate detection limit. Since a single molecule is unable to generate a strong enough signal, sensing methodologies able to reach that limit by necessity need to rely on signal amplification. This tutorial review describes various molecular approaches towards signal amplification in which a single analyte molecule affects the properties of a multitude of reporter molecules. Sensing by advanced instrumentation or changes in the physical properties of materials are excluded. The review is divided into four parts (catalysts, macromolecules, metal surfaces and supramolecular aggregates) depending on the species responsible for generating reporter molecules. Although on first sight apparently very diverse in nature, the majority of approaches rely on two key concepts: catalysis and multivalency. The ability of a catalyst to convert a multitude of substrate molecules into product (defined by the turn over number) makes a catalyst an intrinsic signal amplifier in case the chemical conversion of the substrate is accompanied by a measurable change in physical properties. For sensing purposes, catalytic activity must depend on the interaction between the analyte and the catalyst. Sensing using multivalent structures such as polymers and functionalized nanoparticles relies on the ability of a single analyte molecule to affect the properties of a multitude of reporter molecules collected in the multivalent structure. Chemical sensing systems will be discussed with detection limits that indeed go down to a few molecules and can rival the best biological assays. It will be shown that the most sensitive methods rely on a cascade of amplification mechanisms.