We present a droplet-based microfluidic technology that enables high-throughput screening of single mammalian cells. This integrated platform allows for the encapsulation of single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil and enables the digital manipulation of these reactors at a very high-throughput. Here, we validate a full droplet screening workflow by conducting a droplet-based cytotoxicity screen. To perform this screen, we first developed a droplet viability assay that permits the quantitative scoring of cell viability and growth within intact droplets. Next, we demonstrated the high viability of encapsulated human monocytic U937 cells over a period of 4 days. Finally, we developed an optically-coded droplet library enabling the identification of the droplets composition during the assay read-out. Using the integrated droplet technology, we screened a drug library for its cytotoxic effect against U937 cells. Taken together our droplet microfluidic platform is modular, robust, uses no moving parts, and has a wide range of potential applications including high-throughput single-cell analyses, combinatorial screening, and facilitating small sample analyses.

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Droplet microfluidic technology for single-cell high-throughput screening

Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

https://iopscience.iop.org/article/10.1088/0034-4885/75/1/016601/pdf

Droplet based microfluidics

This critical review discusses the current understanding of the formation, transport, and merging of drops in microfluidics. We focus on the physical ingredients which determine the flow of drops in microchannels and recall classical results of fluid dynamics which help explain the observed behaviour. We begin by introducing the main physical ingredients that differentiate droplet microfluidics from single-phase microfluidics, namely the modifications to the flow and pressure fields that are introduced by the presence of interfacial tension. Then three practical aspects are studied in detail: (i) The formation of drops and the dominant interactions depending on the geometry in which they are formed. (ii) The transport of drops, namely the evaluation of drop velocity, the pressure-velocity relationships, and the flow field induced by the presence of the drop. (iii) The fusion of two drops, including different methods of bridging the liquid film between them which enables their merging.

/pdf/dynamics-of-microfluidic-droplets-4g9dmgil4o.pdf

Dynamics of microfluidic droplets.

Droplet‐Based Microreactors for the Synthesis of Magnetic Iron Oxide Nanoparticles

Small-scale mixing is of uttermost importance in bio- and chemical analyses using micro TAS (total analysis systems) or lab-on-chips. Many microfluidic applications involve chemical reactions where, most often, the fluid diffusivity is very low so that without the help of chaotic advection the reaction time can be extremely long. In this article, we will review various kinds of mixers developed for use in microfluidic devices. Our review starts by defining the terminology necessary to understand the fundamental concept of mixing and by introducing quantities for evaluating the mixing performance, such as mixing index and residence time. In particular, we will review the concept of chaotic advection and the mathematical terms, Poincare section and Lyapunov exponent. Since these concepts are developed from nonlinear dynamical systems, they should play important roles in devising microfluidic devices with enhanced mixing performance. Following, we review the various designs of mixers that are employed in applications. We will classify the designs in terms of the driving forces, including mechanical, electrical and magnetic forces, used to control fluid flow upon mixing. The advantages and disadvantages of each design will also be addressed. Finally, we will briefly touch on the expected future development regarding mixer design and related issues for the further enhancement of mixing performance.

G. Cristobal

Papers

Mixing characterization inside microdroplets engineered on a microcoalescer