Controlled droplet microfluidic systems for multistep chemical and biological assays

Abstract

Droplet microfluidics is a relatively new and rapidly evolving field of science focused on studying the hydrodynamics and properties of biphasic flows at the microscale, and on the development of systems for practical applications in chemistry, biology and materials science. Microdroplets present several unique characteristics of interest to a broader research community. The main distinguishing features include (i) large numbers of isolated compartments of tiny volumes that are ideal for single cell or single molecule assays, (ii) rapid mixing and negligible thermal inertia that all provide excellent control over reaction conditions, and (iii) the presence of two immiscible liquids and the interface between them that enables new or exotic processes (the synthesis of new functional materials and structures that are otherwise difficult to obtain, studies of the functions and properties of lipid and polymer membranes and execution of reactions at liquid-liquid interfaces). The most frequent application of droplet microfluidics relies on the generation of large numbers of compartments either for ultrahigh throughput screens or for the synthesis of functional materials composed of millions of droplets or particles. Droplet microfluidics has already evolved into a complex field. In this review we focus on 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip. 'Controlled droplet microfluidics' can be regarded as a group of methods capable of addressing and manipulating droplets in series. The functionality and complexity of controlled droplet microfluidic systems can be positioned between digital microfluidics (DMF) addressing each droplet individually using 2D arrays of electrodes and ultrahigh throughput droplet microfluidics focused on the generation of hundreds of thousands or even millions of picoliter droplets that cannot be individually addressed by their location on a chip.

Droplet and Microchamber‐Based Digital Loop‐Mediated Isothermal Amplification (dLAMP)

“…Initially, droplet microfluidics is applied to generate droplets with size‐monodispersity, which have a wide range of applications, such as food, cosmetics, and drug encapsulation . Recently, droplet microfluidics is further enhanced and functionalized, extending its applications to biochemical analyses, including digital nucleic acid amplifications such as dLAMP . Using droplet microfluidics, the well‐mixed nucleic acid samples and LAMP reagents are emulsified by oils with stabilizing surfactants .…”

Inner Surface Design of Functional Microchannels for Microscale Flow Control

“…Microfluidic devices are miniaturized fluid handling systems, regulating small amount of fluids travelling through networks consisting of tiny channels with diameter typically ranging from tens to hundreds of micrometers . Microfluidic systems require small volumes of reagents and render fast response due to their increased surface area and shortened diffusion paths, so in a vision, they promise to offer cheaper and faster equipment capable of most chemical and biological analysis while saving time and footprints . However, before that, challenges more than simply scaling down conventional equipment are presented, and among those the efficient regulation of the motion of microfluidic flows is listed.…”

A Microfluidic Strategy for Controllable Generation of Water‐in‐Water Droplets as Biocompatible Microcarriers

“…Droplet microfluidic has been utilized as a versatile tool in chemical, biological, and materials science research due to its remarkable advantages of generating and manipulating discrete droplets in high‐throughput and controllable manners . The isolated compartments with tiny volumes and large specific surface areas are ideal microreactors, transporters, and mixers for microscale experiments . Droplet microfluidic offers a large number of applications in small molecule detection, drug screening, single‐cell analysis, functional microparticles fabrication, tissue engineering, etc.…”

“…Currently, droplet microfluidic is mainly based on water‐in‐oil (W/O) system, in which the organic reagents are used as continuous phase . However, the system is limited by the addition of the oil phase and/or surfactants in some biochemical and materials science applications, such as fabrication of cell‐laden microgels and new functional materials and structures, which requires extensive postprogressing (e.g., demulsification steps) to remove oil phase due to the toxic nature or disturbance to subsequent steps of it. Meanwhile, the waste organic reagents and/or surfactants are not environmentally digestible and need to be treated professionally before discharge.…”