The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.

The origins and the future of microfluidics

Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights.

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Reactions in Droplets in Microfluidic Channels

This critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration, automation and parallelization of (bio-)chemical assays (see S. Haeberle and R. Zengerle, Lab Chip, 2007, 7, 1094–1110, for an earlier review). In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the easy, fast, and cost-efficient implementation of different application-specific (bio-)chemical processes. In our review we focus on recent developments from the last decade (2000s). We start with a brief introduction into technical advances, major market segments and promising applications. We continue with a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations of every platform. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electrokinetics, electrowetting, surface acoustic waves, and dedicated systems for massively parallel analysis. This review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposability, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols (295 references).

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Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications

Recent years have seen considerable progress in the development of microfabricated systems for use in the chemical and biological sciences. Much development has been driven by a need to perform rapid measurements on small sample volumes. However, at a more primary level, interest in miniaturized analytical systems has been stimulated by the fact that physical processes can be more easily controlled and harnessed when instrumental dimensions are reduced to the micrometre scale. Such systems define new operational paradigms and provide predictions about how molecular synthesis might be revolutionized in the fields of high-throughput synthesis and chemical production.

https://www.gene-quantification.de/nature-review-3-lab-on-chip-2006.pdf

Control and detection of chemical reactions in microfluidic systems

Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow Until recently, however, the question, “Should we do this in flow?” has merely been an afterthought This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts

The Hitchhiker's Guide to Flow Chemistry

We present an integrated microfluidic system that achieves efficient mixing between two miscible liquid streams by introducing a gas phase, forming a segmented gas-liquid (slug) flow, and completely separating the mixed liquid and gas streams in a planar capillary separator. The recirculation motion associated with segmented flow enhances advection in straight microchannels without requiring additional fabrication steps. Instantaneous velocity fields are quantified by microscopic particle image velocimetry (muPIV). Velocities in the direction normal to the channel amount to approximately 30% of the bulk liquid velocity inside a liquid segment. This value depends only weakly on the length of a liquid segment. Spatial concentration fields and the extent of mixing (EOM) are obtained from pulsed-laser fluorescence microscopy and confocal scanning microscopy measurements. The mixing length is reduced 2-3-fold in comparison with previously reported chaotic micromixers that use three-dimensional microchannel networks or patterned walls. Segmented gas-liquid microflows allow mixing times to be varied over several orders of magnitude between milliseconds and second time scales.

Micromixing of miscible liquids in segmented gas-liquid flow.

Microreactor-based reaction optimization in organic chemistry—glycosylation as a challenge

Glycosylation reactions are performed rapidly over a wide range of conditions as an example of microreactor-based method optimization and process development in organic chemistry.

Microreactor-Based Reaction Optimization in Organic Chemistry — Glycosylation as a Challenge.

We describe flow visualization of gas-liquid flows in microchemical systems. The observations are summaries of new flow regime diagrams that provide new insight into the nature of flows (e.g., bubbly, slug, and channeling) and serve to guide the systematic design of gas-liquid microsystems. A case study of a dual-channel fluorination reactor illustrates the use of the flow regime understanding in establishing operating limits and the systematical design of multichannel devices.

Manish Jhunjhunwala

Papers

Micromixing of miscible liquids in segmented gas-liquid flow.

Microreactor-based reaction optimization in organic chemistry—glycosylation as a challenge

Microreactor-Based Reaction Optimization in Organic Chemistry — Glycosylation as a Challenge.

Gas-Liquid Flows in Microchemical Systems