Xavier Casadevall i Solvas

The past, present and potential for microfluidic reactor technology in chemical synthesis

The past two decades have seen far-reaching progress in the development of microfluidic systems for use in the chemical and biological sciences. Here we assess the utility of microfluidic reactor technology as a tool in chemical synthesis in both academic research and industrial applications. We highlight the successes and failures of past research in the field and provide a catalogue of chemistries performed in a microfluidic reactor. We then assess the current roadblocks hindering the widespread use of microfluidic reactors from the perspectives of both synthetic chemistry and industrial application. Finally, we set out seven challenges that we hope will inspire future research in this field.

Mapping of Fluidic Mixing in Microdroplets with 1 μs Time Resolution Using Fluorescence Lifetime Imaging

Microdroplets generated in microfluidic channels hold great promise for use as substrates in high-throughput chemical and biological analysis. These water-in-oil compartments can serve as isolated reaction vessels, and since they can be generated at rates in excess of 1 kHz, thousands of assays can be carried out quickly and reproducibly. Nevertheless, sampling the large amount of information generated from these platforms still remains a significant challenge. For example, considering the high droplet generation rates and velocities, reproducibility and micrometer resolution are challenging requirements that must be fulfilled. Herein we combine confocal fluorescence lifetime imaging microscopy with a statistical implementation that permits the analysis of mixing phenomena within microdroplets with a temporal resolution of 1 mus. Importantly, such exquisite resolution is only possible as a result of the large number of droplets sampled and their high structural reproducibility.

Microfluidic-Based Droplet and Cell Manipulations Using Artificial Bacterial Flagella

Herein, we assess the functionality of magnetic helical microswimmers as basic tools for the manipulation of soft materials, including microdroplets and single cells. Their ability to perform a range of unit operations is evaluated and the operational challenges associated with their use are established. In addition, we also report on interactions observed between the head of such helical swimmers and the boundaries of droplets and cells and discuss the possibilities of assembling an artificial swimming microorganism or a motorized cell.

Microfluidic evaporator for on-chip sample concentration.

We present a simple technique for the concentration of liquid samples in microfluidic devices applicable for single or multiple-phase configurations. The strategy consists of capturing the sample of interest within microfluidic traps and breaking its continuity by the introduction of a gas phase, which is also used to evaporate it.

Fluorescence detection methods for microfluidic droplet platforms

The development of microfluidic platforms for performing chemistry and biology has in large part been driven by a range of potential benefits that accompany system miniaturisation. Advantages include the ability to efficiently process nano- to femoto- liter volumes of sample, facile integration of functional components, an intrinsic predisposition towards large-scale multiplexing, enhanced analytical throughput, improved control and reduced instrumental footprints.1 In recent years much interest has focussed on the development of droplet-based (or segmented flow) microfluidic systems and their potential as platforms in high-throughput experimentation.2-4 Here water-in-oil emulsions are made to spontaneously form in microfluidic channels as a result of capillary instabilities between the two immiscible phases. Importantly, microdroplets of precisely defined volumes and compositions can be generated at frequencies of several kHz. Furthermore, by encapsulating reagents of interest within isolated compartments separated by a continuous immiscible phase, both sample cross-talk and dispersion (diffusion- and Taylor-based) can be eliminated, which leads to minimal cross-contamination and the ability to time analytical processes with great accuracy. Additionally, since there is no contact between the contents of the droplets and the channel walls (which are wetted by the continuous phase) absorption and loss of reagents on the channel walls is prevented. Once droplets of this kind have been generated and processed, it is necessary to extract the required analytical information. In this respect the detection method of choice should be rapid, provide high-sensitivity and low limits of detection, be applicable to a range of molecular species, be non-destructive and be able to be integrated with microfluidic devices in a facile manner. To address this need we have developed a suite of experimental tools and protocols that enable the extraction of large amounts of photophysical information from small-volume environments, and are applicable to the analysis of a wide range of physical, chemical and biological parameters. Herein two examples of these methods are presented and applied to the detection of single cells and the mapping of mixing processes inside picoliter-volume droplets. We report the entire experimental process including microfluidic chip fabrication, the optical setup and the process of droplet generation and detection.

Chemical and Biological Dynamics Using Droplet-Based Microfluidics

Recent years have witnessed an increased use of droplet-based microfluidic techniques in a wide variety of chemical and biological assays. Nevertheless, obtaining dynamic data from these platforms has remained challenging, as this often requires reading the same droplets (possibly thousands of them) multiple times over a wide range of intervals (from milliseconds to hours). In this review, we introduce the elemental techniques for the formation and manipulation of microfluidic droplets, together with the most recent developments in these areas. We then discuss a wide range of analytical methods that have been successfully adapted for analyte detection in droplets. Finally, we highlight a diversity of studies where droplet-based microfluidic strategies have enabled the characterization of dynamic systems that would otherwise have remained unexplorable.

Utilization of electroactive polymer actuators in micromixing and in extended-life biosensor applications

Polypyrrole (PPy)-based microactuators hold a promise for a wide variety of engineering applications from robotics and microassembly to biosensors and drug delivery systems. The main advantages of using PPy/Au actuator structures (vs competing solid-state actuator technologies) include ease of fabrication, low actuation energy, and large motion range of microactuators. We present advances in two areas of application - in the extended-life biosensor platform and in micromixers.

Au/PPy Actuators for Active Micromixing and Mass Transport Enhancement

We developed a new micromixer based on Gold/Polypyrrole (Au/PPy) bilayer act uators. Several actuators (length x width from 10 x 1 mm to 380 x 38 µm) were tested at frequencies up to 3 Hz. Chronoamperometric experiments (in the mass transport-limited regime) with a Redox sensor implemented in front of the actuators were run. Differential mass transport effects with or without the activation of the actuators were recorded for several systems. In addition, numerical simulations of a DNA hybridization reaction under the effect of different configurations of these devices were carried out, and their effect on reaction rate increase was studied.

Dynamic wetting in microfluidic droplet formation

The extent to which the carrier fluid wets the walls of a microchannel is crucial in the droplet formation process for segmented flow microfluidic applications and can be influenced by the use of surfactants. Surfactants dynamically modify the microchannel surface leading to stabilization of the two phase interface, affecting the droplet formation process. An experimental study of the influence of hydrophobic surfactant (Span 80) during the formation of water-inoil droplets in a T-shaped microchannel geometry is presented and the wetting properties of the microchannel walls were characterized. The range of data to be analyzed on the microscale is estimated from the macroscopic interfacial tension and contact angle measurements. The critical micelle concentration (CMC) level at the microscale was estimated by observing the trend of droplet length variation with concentration of surfactant in a microchannel. Microchannels used in this work were fabricated using softlithography methods and bonded using a custom-made plasma bonding setup that does not require an ultra high vacuum chamber and hence saves the fabrication cost.

Hydrodynamics in Cell Studies

Hydrodynamic phenomena are ubiquitous in living organisms and can be used to manipulate cells or emulate physiological microenvironments experienced in vivo. Hydrodynamic effects influence multiple cellular properties and processes, including cell morphology, intracellular processes, cell–cell signaling cascades and reaction kinetics, and play an important role at the single-cell, multicellular, and organ level. Selected hydrodynamic effects can also be leveraged to control mechanical stresses, analyte transport, as well as local temperature within cellular microenvironments. With a better understanding of fluid mechanics at the micrometer-length scale and the advent of microfluidic technologies, a new generation of experimental tools that provide control over cellular microenvironments and emulate physiological conditions with exquisite accuracy is now emerging. Accordingly, we believe that it is timely to assess the concepts underlying hydrodynamic control of cellular microenvironments and their applications and provide some perspective on the future of such tools in in vitro cell-culture models. Generally, we describe the interplay between living cells, hydrodynamic stressors, and fluid flow-induced effects imposed on the cells. This interplay results in a broad range of chemical, biological, and physical phenomena in and around cells. More specifically, we describe and formulate the underlying physics of hydrodynamic phenomena affecting both adhered and suspended cells. Moreover, we provide an overview of representative studies that leverage hydrodynamic effects in the context of single-cell studies within microfluidic systems.