Restricted diffusion is a common feature of many physicochemical, biological, and industrial processes. Nuclear magnetic resonance techniques are often used to survey the atomic or molecular motion in confining media by applying inhomogeneous magnetic fields to encode the trajectories of spin-bearing particles. The diversity and complexity of diffusive NMR phenomena, observed in experiments, result from the specific properties of reflected Brownian motion. Here the focus is on the mathematical aspects of this stochastic process, their physical interpretations, and their practical applications. The main achievements in this field, from Hahn’s discovery of spin echoes to present-day research, are presented in a unified mathematical language. A long-standing problem of restricted diffusion under arbitrary magnetic field is reformulated in terms of multiple correlation functions of the reflected Brownian motion. Many classical results are retrieved, extended, and critically discussed.

Most biochemical reactions in living cells rely on diffusive search for target molecules or regions in a heterogeneous overcrowded cytoplasmic medium. Rapid rearrangements of the medium constantly change the effective diffusivity felt locally by a diffusing particle and thus impact the distribution of the first-passage time to a reaction event. Here, we investigate the effect of these dynamic spatiotemporal heterogeneities onto diffusion-limited reactions. We describe a general mathematical framework to translate many results for ordinary homogeneous Brownian motion to heterogeneous diffusion. In particular, we derive the probability density of the first-passage time to a reaction event and show how the dynamic disorder broadens the distribution and increases the likelihood of both short and long trajectories to reactive targets. While the disorder slows down reaction kinetics on average, its dynamic character is beneficial for a faster search and realization of an individual reaction event triggered by a single molecule.

Diffusion-mediated surface phenomena are crucial for human life and industry, with examples ranging from oxygen capture by lung alveolar surface to heterogeneous catalysis, gene regulation, membrane permeation, and filtration processes. Their current description via diffusion equations with mixed boundary conditions is limited to simple surface reactions with infinite or constant reactivity. In this Letter, we propose a probabilistic approach based on the concept of boundary local time to investigate the intricate dynamics of diffusing particles near a reactive surface. Reformulating surface-particle interactions in terms of stopping conditions, we obtain in a unified way major diffusion-reaction characteristics such as the propagator, the survival probability, the first-passage time distribution, and the reaction rate. This general formalism allows us to describe new surface reaction mechanisms such as for instance surface reactivity depending on the number of encounters with the diffusing particle that can model the effects of catalyst fooling or membrane degradation. The disentanglement of the geometric structure of the medium from surface reactivity opens far-reaching perspectives for modeling, optimization, and control of diffusion-mediated surface phenomena.

Textbook concepts of diffusion-versus kinetic-control are well-defined for reaction-kinetics involving macroscopic concentrations of diffusive reactants that are adequately described by rate-constants—the inverse of the mean-first-passage-time to the reaction-event. In contradiction, an open important question is whether the mean-first-passage-time alone is a sufficient measure for biochemical reactions that involve nanomolar reactant concentrations. Here, using a simple yet generic, exactly solvable model we study the effect of diffusion and chemical reaction-limitations on the full reaction-time distribution. We show that it has a complex structure with four distinct regimes delineated by three characteristic time scales spanning a window of several decades. Consequently, the reaction-times are defocused: no unique time-scale characterises the reaction-process, diffusion- and kinetic-control can no longer be disentangled, and it is imperative to know the full reaction-time distribution. We introduce the concepts of geometry- and reaction-control, and also quantify each regime by calculating the corresponding reaction depth.

We study the residence and local times for a Brownian particle confined by reflecting boundaries, and propose a general solution to the problem of finding the related probability distribution. Its Fourier transform (characteristic function) and Laplace transform (survival probability) are obtained in a compact matrix form involving the Laplace operator eigenbasis. Explicit combinatorial relations are derived for the moments, and the probability distribution is shown to be nearly Gaussian when the exploration time is long enough. When the eigenbasis (or a part of it) is known, the numerical computation of the residence time distributions is straightforward and accurate. The present approach can also be applied to investigate other functionals of reflected Brownian motion describing, in particular, restricted diffusion in an external field or potential (e.g., nuclei diffusing in an inhomogeneous magnetic field). Theoretical results for the local times are confronted with Monte Carlo simulations on the unit interval, disk, and sphere.

We derive a general exact formula for the mean first passage time (MFPT) from a fixed point inside a planar domain to an escape region on its boundary. The underlying mixed Dirichlet-Neumann boundary value problem is conformally mapped onto the unit disk, solved exactly, and mapped back. The resulting formula for the MFPT is valid for an arbitrary space-dependent diffusion coefficient, while the leading logarithmic term is explicit, simple, and remarkably universal. In contrast to earlier works, we show that the natural small parameter of the problem is the harmonic measure of the escape region, not its perimeter. The conventional scaling of the MFPT with the area of the domain is altered when diffusing particles are released near the escape region. These findings change the current view of escape problems and related chemical or biochemical kinetics in complex, multiscale, porous or fractal domains, while the fundamental relation to the harmonic measure opens new ways of computing and interpreting MFPTs.