Automation and flow control for particle manipulation

In recent years, several new methods have been developed to precisely manipulate small particles using optical, electric, acoustic, magnetic, or fluidic fields. Automated fluidic trapping has emerged as a particularly powerful method to control colloidal particles, cells, or single polymers using only fluid flow. Here, we discuss recent advances in the automation of particle manipulation, focusing on flow-based and electric field-based methods. Broadly, automated flow control enables the precise manipulation of multiple freely suspended particles using gentle flow, thereby enabling new directions in chemical and biological systems.

Introduction

Recent advances in automation have enabled the development of several new methods for manipulating small particles in solution. In general, particle trapping methods rely on an external force field (optical, magnetic, electric, acoustic, fluidic) to control particle position or suppress the thermal fluctuations of small Brownian particles [1, 2, 3, 4,5^••]. Single-beam optical traps (known as laser tweezers) [1] can stably confine particles without active feedback control due to the nature of the gradient restoring force [1,6]. On the other hand, most trapping methods rely on active feedback control to suppress thermal motion and control particle position in solution [5^••]. Broadly speaking, particle trapping methods have enabled transformative studies across science and engineering, with a handful of examples including measurement of RNA hairpin folding energy in strongly non-equilibrium regimes [7], direct observation of single molecule polymer dynamics [8], directed assembly of colloidal particles into two-dimensional (2D) crystals [9], conformational dynamics of single proteins such as G protein-coupled receptors [10^•], and detailed studies of vesicle dynamics in defined flows [11^•,12].

Despite the popularity of optical traps and magnetic tweezers, these methods are generally limited to trapping particles with specific material properties (e.g. index of refraction, magnetic susceptibility). In particular, optical traps may not be suitable for long-time trapping of biological specimens due to local heating or photo-induced damage [13]. In contrast, methods such as electrokinetic traps [14^•,15] and hydrodynamic traps [15,5^••] confine particles in solution without restrictions on the intrinsic material properties of trapped particles. Moreover, electric field and flow-based traps generally rely on model predictive or model-free controllers [16] to manipulate particles using active feedback control. Electrokinetic traps manipulate particles using a combination of electrophoretic forces and electro-osmotic flows [4,17,18^••] and have been used for numerous studies in single-molecule biophysics and nanoscience. However, electric field-based methods generally require the use of strong electric fields and field gradients that can perturb trapped chemical or biological samples.

In recent years, automated flow control has emerged as a simple, potent, and non-perturbative method for trapping particles in free solution [5^••,15]. The Stokes trap allows for the simultaneous manipulation of Brownian particles using only fluid flow [5^••]. In this article, we provide an overview of recent advances in particle trapping methods relying on automation and feedback control, focusing on flow-based traps and electrokinetic traps. We discuss the strengths, limitations, and practical considerations of these methods while considering applications to several chemical and biological systems, with a major focus on flow-based trapping. Overall, automated flow control holds strong potential to enable new fundamental studies in science and engineering.