Microreactors & Microfluidics in Chemistry: a Review
Owing to its operation on the micro-scale, microfluidics presents high surface-area-to-volume ratios to allow for rapid heat and mass transfer and make them ideal for efficient and safe chemical reactions that can be precisely controlled and monitored.
1. Microfluidics in chemistry: an introduction
The emergence of microfluidics in recent decades has provided unprecedented precision in continuous flow technology, giving new capabilities to a wide range of fields, from biological analysis and chemical synthesis, to optics and information technology . Microfluidic devices (see figure 1) – made from polymers, glass, silicon, metal, and other materials – manipulate small volumes of fluids through geometrically controlled environments, often separated into distinct subunits, such as reactors, mixers, and detectors . Microfluidics owes its distinct advantages in these fields to some fundamental characteristics. It is characterized by laminar flows (see figure 2), or those with a low Reynolds number (Re, indicating the relative importance of inertial forces to viscous forces in a fluid), which helps eliminate any back-mixing in the system that may be caused by fluid turbulence . Figure 3 shows a schematic illustrating the diffusion-based mixing that the laminar flow in microfluidic devices facilitates.
Figure 2 : Schlieren image of the flow of air above a candle in a still room. The flow begins as a laminar flow near the base of the plume but soon transitions to turbulent flow, providing a good visualization of the different flow regimes at varying Reynolds numbers. Image from Hargather et al. “Background-oriented schlieren visualization of heating and ventilation: HVAC-BOS.” 
Figure 3 : Schematic showing the laminar flow of fluid streams X and Y beside each other, whereby the only mixing that occurs is by diffusion. The time of contact of the two streams dictates the amount of mixing that occurs. Image from Beebe et al. “Physics and applications of microfluidics in biology.” 
While microfluidics has been longer established in biological research areas, such as cell culture research , polymerase chain reaction (PCR) diagnostic tools, and even the simulation of entire organ systems , its application to chemistry is far more recent and less developed . Though this may be the case, there exist inherent advantages of microfluidics in its applications in chemistry, primarily based on the scale-dependent processes of heat and mass transfer . The small length scales result in high surface-area-to-volume ratios, which allow for greater thermal homogeneity across the reaction site and rapid heat transfers, whereas the laminar flow regime can result in diffusion-controlled reactions of compounds at the interface of two fluid streams . This review intends on providing an overview of the application of microfluidics in chemistry (i.e. microreactors), including an elaboration of its advantages, its current uses in industry and academia, challenges it faces, and its future potential. There are some outstanding reviews in literature of chemical synthesis using microfluidics, such as “The past, present and potential for microfluidic reactor technology in chemical synthesis” by Elvira et al. and this review relies on many of the sources presented there.
Figure 4 : Images showing the formation of water droplets in oil due to specially designed channel geometry in a microfluidic device. (a) shows the water being forced through the channel with thinner streams of fluid present in the narrow channel pinch points. (b) shows the water in the pinch points becoming unstable and beginning to break the continuity of the water, after the flow of water is stopped. (c) shows the formation of the monodisperse water droplets that result. Image from Wu et al. “Droplet formation in microchannels under static conditions.” 
2. Microfluidics in chemistry: advantages
2.1. Small reagent volumes microreactor and footprint
As one may expect when working with significantly smaller volumes of materials – as one does with microfluidics when compared to bulk-batch chemical reactions (see figure 5) – substantial cost savings can be made. This could be the case when working with reagents of limited availability or excessive cost, or especially true when the chemical reactions being performed are for the purpose of gathering information rather than synthesizing a useable end-product. The precise and targeted nature of microreactors can enable acquisition of the same amount of information as, or indeed more information than, their bulk system counter parts by using far smaller reagent quantities . The small size of microreactors also provides the very practical advantage of having a smaller footprint than conventional flow reactors, and smaller yet than macroscale reactors , due in part to the smaller heat-exchange equipment needed for the more efficient microfluidic heat transfers . Figure 6 provides an example of a chemical synthesis reaction performed at the small scale available with microfluidics.
Figure 5 : Illustration of a standard non-continuous batch reactor, whereby reagents are added to the reactor, left to react while being stirred by an impeller, then the product is extracted at the end of the process. Image from Lichtarowicz “Chemical reactors.” Online at:
2.2. Selectivity of microreactors
As is often the case with chemical and biological reactions, multiple products can be generated from a given set of reagents dependent on the local conditions of the reaction. With the control over these conditions granted by microfluidics, such as temperature and residence-time , individual compounds among multiple that could be produced by a given reaction can thus be selectively produced with high degrees of precision.
Figure 6 : Microfluidic reactor used for the synthesis of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Note the subunits of the device labelled accordingly. As can be seen, the entire footprint of the device is hardly larger than a coin. Image from Lee et al. “Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.” 
2.3. Rapid, safe reactions in microreactors
In regards to relative reaction times of microfluidic reactors and bulk reactors, there are a few fundamental things limiting the ability to make a direct comparison in all respects. Bulk reactions are often performed with more time than would be necessary to reach the equilibrium point of the reaction, in order to ensure that the desired reaction has reached completion . Microreactors, on the other hand, can more easily be optimized and closely monitored (see figure7) to not run for any longer than is necessary to reach the reaction endpoint, and are accordingly reported to have greater space-time yields than bulk reactors . Thus, even if the rate of rate-limited reactions is unchanged, microfluidic reactors will allow for more efficient, and consequently more rapid chemical processes. The rate of mass-limited reactions,on the other hand, will increase in the small characteristic dimensions of microreactors due to the significance that diffusive effects have in this domain, and consequently have the same or greater effect of increasing chemical process speeds .
Figure 7 : 3D plots of Raman intensity of a microfluidic device designed to synthesize ethyl acetate at Raman bands of 893 cm-1 (a) and 882 cm-1(b). The position of reagents (acetic acid and ethanol) can be closely monitored with this technique at locations of interest, such as the T-junction presented here. Image from Fletcher et al. “Monitoring of chemical reactions within microreactors using an inverted Raman microscopic spectrometer.” .
Furthermore, chemical reactions in microfluidic devices can be performed with more inherent safety than before and with the ability to handle high pressures and temperatures at small scales . By virtue of the fact that only small volumes of reagents are used in microreactors, reactions that are particularly reactive, explosive or toxic can be mitigated with relative ease . Additionally, exothermic reactions can be more safely performed due to the high surface-area-to-volume ratios and the rapid heat transfer that it entails , .
2.4. Scale-out potential of microreactors
In contrast to the scaling up of microreactors (i.e. increasing their characteristic dimensions for increased production), the true strength of microfluidics comes in “scaling out” these systems (see figure 8). Instead of increasing the size of microreactors, scaling out simply denotes the increase of the number of microreactors in order to produce a parallel network. The advantage comes from the fact that by using multiple reactors of the same size, the chemistry performed in each one remains the same at any level of scaling out . This approach also allows for the ease of transferring the use of the same reactors between research and industrial applications, as will be elaborated on further below .
2.5. Green chemistry with microreactors
Microfluidics from a sustainability point of view should not be overlooked, and is an aspect that is particularly attractive to industry due to the cost reductions that often go hand in hand with sustainability . Here the characteristic high surface-area-to-volume ratios exhibited in microfluidics again proves to be beneficial, reducing the amount of energy required to efficiently meet thermal requirements of the reaction (see figure 9) . And as discussed above, the increased selectivity of microfluidic reactions can allow for the exclusion of undesirable reaction products, as well as the more effective recycling of useful reagents with less filtering, resulting in minimal reagent consumption and minimal clean-up .
Figure 9 : an infrared image of the microthermal control unit for a PCR microfluidic device, measuring 5.2mm x 5.2mm, demonstrating the highly localized heat control, and thus energy savings that can be achieved using microfluidics. Image from Wang et al. “A miniaturized quantitative polymerase chain reaction system for DNA amplification and detection.” 
3. Microfluidics in chemistry: disadvantages
3.1. Microfluidics as enabling or replacing
While it is undoubted that microfluidics technology can enable a wide range of chemical processes, its primary barrier in its more universal implementation lies primarily in just that: it is viewed as an enabling technology, perhaps more than a replacing technology. Much of the development of microfluidic techniques in chemistry stem from applications that are considerably difficult or hazardous at larger scales , where the use of microreactors can bypass certain limitations that exist in conventional process conditions . On the other hand, for reactions that are not problematically hazardous or for those dominated by slow reaction rates (rather than being limited by the rate of heat or mass transfer),  the advantages granted by microfluidics becomes less apparent or in fact non-existent. Similarly, those reactions that take advantage of bulk forces like gravity and buoyancy (such as distillation, centrifugation and phase separation) may be better suited to large scale operation than integration with microfluidics . Even when the microfluidic approach to certain processes is advantageous in terms of speed, throughput, and analytical efficiency, if there lies no obvious constraint in existing practices, then few have chosen to adopt microfluidics in lieu of the familiar ease of using conventional techniques . Thus the challenge for microfluidics lies in attaining the recognition from the research and industrial communities that microfluidic techniques are applicable and superior in a greater range of areas than those in which they are currently being used.
Figure 10 : Examples of multiphase microfluidic applications using gas and liquids. (a) shows a schematic of a flow-focusing device to facilitate the formation of bubbles from a gaseous thread. (b) shows the production of foam of monodisperse bubbles using the flow-focusing method described. (c) shows the use of bubbles to enhance the mixing of two liquids. Image from Whitesides “The origin and future of microfluidics.” .
3.2. Multi-phase reactions with microfluidics
Multiphase reactions (those between solids, liquids, gases, etc. – see figure 10) have long presented challenges for microfluidics. The high surface-area-to-volume ratios inherent to microfluidic reactions present great potential advantages for multiphase reactions, but complications with the clogging of solid reagents, in particular, has been a concern . While more recent progress has been made in the synthesis of micro and nano particles through droplet-based microfluidics (see figure 11)  and of materials using non-Newtonian multiphase microfluidic systems , solutions for the operation of continuous flow reactions with relatively large solid particles remain difficult (i.e. particles in the size range of 0.01-0.1 times the channel diameter) . While heterogeneous catalysis (where the catalysis is of a different phase to the reagents, often a solid) remains less complicated in conventional reactors, systems have successfully been designed to immobilize solid catalysts to microchannel walls to perform three-phase hydrogenation reactions .
Figure 11 : Images showing the formation of iron oxide nanoparticles through the coalescence of iron chloride solution droplets with ammonium hydroxide droplets under the influence of an electric field applied by electrodes beside the channel. Image from Frenz et al. “Droplet-based microreactors for the synthesis of magnetic iron oxide nanoparticles.” .
3.3. Microfluidic chip materials
The choice of microfluidic chip material dominates its function . While this presents a variety of options to the operator, factors such as cost, complexity of fabrication, and suitability for involved reagents present distinct pros and cons for each type of material. For organic chemistry applications, chips made from polydimethylsiloxane (PDMS), commonly used due to their low cost and ease of prototyping, are not ideal for organic chemistry high-throughput industrial use, as organic solvents can swell of dissolve PDMS . Chips made of glass (see figure 12), poly(methylmethacrylate) (PMMA), cyclic olefin copolymer (COC), teflon, or fluorinated ethylene propylene (FEP), coupled with the development of lower cost fabrication techniques will likely allow for a greater range of chemical applications on longer timescales .
Figure 12 : Illustration showing the fabrication process of glass based microfluidic chips using wet etching and fusion bonding methods. Image from Lin et al. “A fast prototyping process for fabrication of microfluidic systems on soda-lime glass.” .
3.4. Other practical disadvantages of microfluidics in chemistry
An obvious limitation of working with individual, or small amounts of microfluidic reactors, is the production volume capability. When only very small amounts of reagents are involved only small amounts of product will consequently be produced. While this can be effectively side-stepped to some degree through the scaling out of microfluidic systems  (see section 2.4 “Scale-out potential of microfluidics”), this very physical limitation of working at micro-scales must not be overlooked.
Very similar to the limitations of microfluidics when using solid reagents (see section 3.2 “Multi-phase reactions with microfluidics”), when a reaction results in the precipitation of a solid, either a product or by-product, problems with particles aggregating on microchannel walls can cause blockages and catastrophic failure , . Thus the development of solutions, such as microchannel surface modification (see figure 13) and gas/liquid “slug-flow,” are necessary in order to realise flows with solid precipitates.
Figure 13 : Scanning electron microscope (SEM) image of colloidal silica particles synthesized in a microreactor whose walls were passivated with Polytetrafluoroethylene (PTFE) in order to prevent particle deposition. The scale bar represents 1µm. Image from Khan et al. “Microfluidic synthesis of colloidal silica” .
4. Microfluidics in chemistry: applications
Due to the numerous benefits of microfluidics discussed above, many stemming from the scale-dependent processes of heat and mass transfer, microreactors have found application in a variety of academic and industrial areas, such as the synthesis of nanomaterials , natural products , and various small molecule drugs and pharmaceuticals (see figure 14) , . While microfluidics up to this point have more commonly been used in an academic setting, their industrial use in growing. This section aims to provide an insight into the numerous applications adopted in research and industry that have expanded upon the fundamental advantages of microfluidics in chemistry outlined above.
Figure 14 : Microfluidic chip used for the synthesis of G protein-couple receptor-modulating compounds. Image from Rodrigues et al. “Accessing new chemical entities through microfluidic systems.” 
4.1. Hazardous reactions with microreactors
As mentioned above, the relatively small length scales and amounts of chemical material involved with microfluidics significantly mitigates the risk surrounding hazardous materials and exothermic reactions. Reactions with these hazardous characteristics are difficult to scale to an industrial level with conventional batch reactors. With this in mind, a study performed and compared life-cycle assessments of the conversion of m-bromoanisole into m-anisaldehyde (a highly exothermic two-step conversion) in both continuous microreactors and semi-continuous batch reactors, finding that the m-anisaldehyde yield decreased with reactor size and in fact, the cryogenic systems required by the macro-scale reactors could be dispensed with due to the superior heat-transfer characteristics of the microreactors .
By similar reasoning, microfluidics have been found to be extremely useful in the synthesis of radiochemicals. Radiotracers for positron emission tomography (PET) exhibit short half-lives, and thus high radioactivity, meaning they must be synthesized rapidly, and in a shielded environment in order to maintain activity for diagnostic use . Microreactors, with their fast and easily contained reactions, have consequently become very effective at the synthesis of PET tracers (see figure 15) , . In addition to performing reactions that are difficult to perform with conventional means, another element driving wider scale industrial use of microfluidics is their development to be used for reactions that would otherwise be impossible. Such was the case in the development of microreactors for the selective fluorination and perfluoronation of organic compounds .
Figure 15 : MicroCT image of PET radiotracers synthesized with a microfluidic reactor being used in vivo (in a mouse). Image from Lee et al. “Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.” 
4.2. Reaction optimization with microreactors
Due to their rapid response times to programmed changes in the microfluidic environment, microreactors are ideal for performing reaction optimizations. A reaction optimization can, for example, consist of mapping the reaction phase space, by varying reaction factors, such as temperature, reagent concentration, and residence time, then rapidly sampling product formation in near to real time in order to determine a reaction’s optimum conditions (see figure 16) .
Figure 16 : a microfluidic reactor used for reaction optimization where reaction temperature, reagent concentration and residence time were varied to determine optimum reaction conditions for glycosylation reactions. ashows the entire chip made of silicon and Pyrex. bshows the design of the chip, employing three inlets for the donor, acceptor, and activator, which are subsequently mixed and allowed to react, with quenchant being added towards the end of the reaction. Image from Ratner et al. “Microreactor-based reaction optimization in organic chemistry – glycosylation as a challenge.”
4.3. Commercialization of microfluidics
The continuing growth in commercially available microfluidic devices  has helped bridge the gap between academic research and industrial application in relevant fields. The commercial availability of microfluidic devices allows researchers to access this powerful technology without the technical skills and experience needed to fabricate the devices themselves. Furthermore, any chemical processes that are developed with microfluidics in an academic setting can easily be scaled out, as mentioned above, for industrial use simply by virtue of the fact that the same commercially available microfluidic platforms can be used in both settings .
The extended capabilities of microreactors when compared to traditional laboratory techniques also helps narrow the gap between research and industry. For example, multiphase homogeneously catalysed reactions are usually studied at relatively low temperatures and pressures in order to facilitate the ease of these processes in a small setting, whereas similar techniques in industry are performed at high temperatures and pressures in order to make these processes more economical . Microreactors present the capability of working at similarly high temperatures and pressures to those used in industry, but at a small scale that would otherwise be difficult to achieve in a laboratory setting .
4.4. Droplet-based microfluidics
The more recent development of droplet-based microfluidics has significantly influenced chemical synthesis, micro and nano fabrication, and synthetic biology . This alternative method of microfluidic processes involves splitting a fluid stream into small, discrete droplets, and provides the added benefits of removing the effects of Taylor dispersion and the subsequently increased ease of droplet transport (see figure 17) . Reactions performed in droplets have been shown to have significantly affected reaction kinetics, showing increased equilibrium and forward rate constants as the droplet radius decreased . Droplet-based techniques, by isolating reactions from the microfluidic channel walls, can also prevent microfluidic channel fouling, a problem that can sometimes occur in continuous flow methods .
Figure 17 : Schematic of microfluidic droplet generation methods. Common hydrodynamic formation methods are (top to bottom) T-junction, flow-focusing, and co-flow setups. Common externally driven methods involve (top to bottom) involve the use of electromagnetic valves and pneumatic micropumps. Image from Mashaghi et al. “Droplet microfluidics: a tool for biology, chemistry and nanotechnology.” 
4.5. Photochemistry with microreactors
Organic photochemistry presents the potential for more sustainable chemical synthesis processes. By achieving selective transformations with high chemical and quantum yields , and in many cases requiring no chemical catalysts or activating groups , organic photochemistry effectively addresses the principles if green chemistry . Current technologies, however, most often involve energy-demanding mercury lamps, and batch reactors, with difficulty in coupling parameters such as hydrodynamics, radiative transfer, mass transfer, and photochemical kinetics present many process limitations with these methods . Continuous flow microreactor technology, on the other hand, in addition to the advantages offered for chemical processes in general, introduce further benefits to photochemistry, including more precise and efficient control of irradiation time and more effective light penetration , . For example, in the continuous flow investigation of the [2+2]-cycloadditions of cyclopentene and 2,3-dimethylbut-2-ene to furanone using UVC light (see figure 18), it was found that the use of microreactors resulted in faster conversions and improved product qualities when compared to their batch analogues .
5. Microfluidics in chemistry: conclusions
Microfluidics has made significant developments since its emergence in the early 1990s, and has come a long way toward fulfilling early predictions made about its potential. Owing to its operation on the micro-scale, microfluidics presents high surface-area-to-volume ratios to allow for rapid heat and mass transfer and make them ideal for efficient and safe chemical reactions that can be precisely controlled and monitored. The adoption of microfluidics for chemistry-based purposes (i.e. in the form of microreactors) has seen slower uptake than for its biological sciences counterparts, but the qualities that make microfluidics highly advantageous for biology also apply to chemistry. Indeed, the potential for microfluidics in chemistry has been widely demonstrated in research settings and have seen increased use in industrial settings thanks to the ease with which microreactors can be scaled out, especially as off-the-shelf microfluidic tools become more and more accessible and sophisticated. They have been shown to be particularly useful for hazardous chemical reactions that can become difficult or impossible at larger scales, but beyond that have shown that most chemical reactions can be performed with increased efficiency using microfluidics.
More recent advances in chemical microfluidics have focused primarily on droplet-based techniques, creating the possibility of generating highly monodisperse droplets on chips, merging and breaking them, manipulating their geometry, chemical contents, and internal flow profiles, all with in situ monitoring . These techniques are becoming ever more complex, with demonstrations of double or triple emulsion microstructures being formed by forcing droplets into larger droplets (see figure 19) . The obvious next step is to transform these primarily proof-of-concept demonstrations into further productive applications.
Figure 19 : Optical micrograph images of a range of highly monodisperse triple emulsions featuring a controlled number of inner and middle droplets, generated with an extended capillary microfluidic device. Shown with scale bar of 200µm. Image from Chu et al. “Controllable Monodisperse Multiple Emulsions.” .
Although there is still work to be done before microfluidics may become a more universal feature in laboratories and industrial centers, the primary barrier it faces may in fact be that the benefits it provides to some chemical processes, though very real and accepted, are not pronounced enough to warrant the overhaul of conventional methods and practices. Perhaps through a combination of further development of these microfluidic tools and wider recognition of their potential as they are used more and more, microfluidics in chemistry will be commonplace and change the way that research and industry are performed.
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 G. M. Whitesides, “The origins and the future of microfluidics.,” Nature, vol. 442, no. 7101, pp. 368–73, 2006.
 T. Rodrigues, P. Schneider, and G. Schneider, “Accessing new chemical entities through microfluidic systems,” Angew. Chemie – Int. Ed., vol. 53, no. 23, pp. 5750–5758, 2014.
 K. S. Elvira, X. C. i Solvas, R. C. R. Wootton, and A. J. DeMello, “The past, present and potential for microfluidic reactor technology in chemical synthesis,” Nat. Chem., vol. 5, no. 11, pp. 905–915, 2013.
 F. K. Balagaddé, L. You, C. L. Hansen, F. H. Arnold, and S. R. Quake, “Long-term monitoring of bacteria undergoing programmed population control in a microchemostat.,” Science (80-. )., vol. 309, no. 5731, pp. 137–140, 2005.
 R. S. Ramsey and J. M. Ramsey, “Generating Electrospray from Microchip Devices Using Electroosmotic Pumping Generating Electrospray from Microchip Devices Using Electroosmotic Pumping,” Anal. Chem., 1997.
 M. Johnson, C. Li, B. Rasnow, P. Grandsard, H. Xing, and A. Fields, “Converting a protease assay to a Caliper® format LabChip system,” JALA – J. Assoc. Lab. Autom., 2002.
 H. Yin and D. Marshall, “Microfluidics for single cell analysis,” Curr Opin Biotechnol, 2012.
 C. L. Hansen, E. Skordalakes, J. M. Berger, and S. R. Quake, “A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion.,” Proc. Natl. Acad. Sci. U. S. A., 2002.
 W. J. Duncanson, T. Lin, A. R. Abate, S. Seiffert, R. K. Shah, and D. a Weitz, “Microfluidic synthesis of advanced microparticles for encapsulation and controlled release.,” Lab Chip, 2012.
 M. J. Hargather and G. S. Settles, “Background-oriented schlieren visualization of heating and ventilation flows: HVAC-BOS,” Hvac&R Res., 2011.
 D. J. Beebe, G. a Mensing, and G. M. Walker, “Physics and applications of microfluidics in biology.,” Annu. Rev. Biomed. Eng., vol. 4, pp. 261–286, 2002.
 H. Andersson and A. Van den Berg, “Microfluidic devices for cellomics: A review,” Sensors Actuators, B Chem., vol. 92, no. 3, pp. 315–325, 2003.
 C. Zhang, J. Xu, W. Ma, and W. Zheng, “PCR microfluidic devices for DNA amplification,” Biotechnology Advances. 2006.
 M. T. Guo, A. Rotem, J. a. Heyman, and D. a. Weitz, “Droplet microfluidics for high-throughput biological assays,” Lab Chip, 2012.
 R. L. Hartman, J. P. McMullen, and K. F. Jensen, “Deciding whether to go with the flow: Evaluating the merits of flow reactors for synthesis,” Angew. Chemie – Int. Ed., vol. 50, no. 33, pp. 7502–7519, 2011.
 W. G. Schwalbe Thomas, Autze Volker, “Chemical synthesis in microreactors,” Chimia (Aarau)., 2002.
 P. S. Dittrich and A. Manz, “Lab-on-a-chip: microfluidics in drug discovery.,” Nat. Rev. Drug Discov., vol. 5, no. 3, pp. 210–218, 2006.
 L. Wu, G. P. Li, W. Xu, and M. Bachman, “Droplet formation in microchannels under static conditions,” Appl. Phys. Lett., vol. 89, no. 14, pp. 20–23, 2006.
 J. R. Goodell et al., “Development of an automated microfluidic reaction platform for multidimensional screening: Reaction discovery employing bicyclo[3.2.1]octanoid scaffolds,” J. Org. Chem., 2009.
 N. Zaborenko, M. W. Bedore, T. F. Jamison, and K. F. Jensen, “Kinetic and scale-up investigations of epoxide aminolysis in microreactors at high temperatures and pressures,” Org. Process Res. Dev., 2011.
 L. Saias, J. Autebert, L. Malaquin, and J.-L. Viovy, “Design, modeling and characterization of microfluidic architectures for high flow rate, small footprint microfluidic systems.,” Lab Chip, 2011.
 M. Ozdemir, A. Koşar, O. Demir, C. Ozenel, and O. Bahcivan, “Thermal-hydraulic, exergy and exergy-economic analysis of micro heat sinks at high flow rates.,” Proc. 10th ASME Bienn. Conf. Eng. Syst. Des. Anal., pp. 710–713, 2010.
 T. Asai, A. Takata, Y. Ushiogi, Y. Iinuma, A. Nagaki, and J. Yoshida, “Switching Reaction Pathways of Benzo b thiophen-3-yllithium and Benzo b furan-3-yllithium Based on High-resolution Residence-time and Temperature Control in a Flow Microreactor,” Chem. Lett., vol. 40, no. 4, pp. 393–395, 2011.
 C.-C. Lee et al., “Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.,” Science, 2005.
 T. Illg, V. Hessel, P. Lçb, and J. C. Schouten, “Continuous synthesis of tert-butyl peroxypivalate using a single-channel microreactor equipped with orifices as emulsification units,” ChemSusChem, vol. 4, no. 3, pp. 392–398, 2011.
 P. D. I. Fletcher, S. J. Haswell, and X. Zhang, “Monitoring of chemical reactions within microreactors using an inverted Raman microscopic spectrometer,” Electrophoresis, vol. 24, no. 18, pp. 3239–3245, Sep. 2003.
 J. Baek, P. M. Allen, M. G. Bawendi, and K. F. Jensen, “Investigation of indium phosphide nanocrystal synthesis using a high-temperature and high-pressure continuous flow microreactor,” Angew. Chemie – Int. Ed., vol. 50, no. 3, pp. 627–630, 2011.
 J. Pelleter and F. Renaud, “Facile, fast and safe process development of nitration and bromination reactions using continuous flow reactors,” Org. Process Res. Dev., 2009.
 S. J. Haswell and P. Watts, “Green chemistry: synthesis in micro reactors,” Green Chem., vol. 5, no. 2, pp. 240–249, 2003.
 J. ichi Yoshida, Flash Chemistry: Fast Organic Synthesis in Microsystems. 2008.
 N. Kockmann, M. Gottsponer, B. Zimmermann, and D. M. Roberge, “Enabling continuous-flow chemistry in microstructured devices for pharmaceutical and fine-chemical production,” in Chemistry – A European Journal, 2008.
 M. Nobis and D. M. Roberge, “Mastering ozonolysis: Production from laboratory to ton scale in continuous flow,” Chim. Oggi, 2011.
 B. Pieber and C. O. Kappe, “Direct aerobic oxidation of 2-benzylpyridines in a gas–liquid continuous-flow regime using propylene carbonate as a solvent,” Green Chem., 2013.
 C. Wiles, P. Watts, and S. J. Haswell, “Clean and selective oxidation of aromatic alcohols using silica-supported Jones’ reagent in a pressure-driven flow reactor,” Tetrahedron Lett., 2006.
 J.-H. Wang et al., “A miniaturized quantitative polymerase chain reaction system for DNA amplification and detection,” Sensors Actuators B Chem., vol. 141, no. 1, pp. 329–337, 2009.
 K. Geyer, T. Gustafsson, and P. H. Seeberger, “Developing continuous-flow microreactors as tools for synthetic chemists,” Synlett. 2009.
 D. T. Chiu et al., “Small but Perfectly Formed? Successes, Challenges, and Opportunities for Microfluidics in the Chemical and Biological Sciences,” Chem, vol. 2, no. 2, pp. 201–223, 2017.
 J. P. McMullen and K. F. Jensen, “Integrated microreactors for reaction automation: new approaches to reaction development.,” Annu. Rev. Anal. Chem. (Palo Alto. Calif)., 2010.
 L. Frenz, a El Harrak, M. Pauly, S. Bégin-Colin, a D. Griffiths, and J.-C. Baret, “Droplet-based microreactors for the synthesis of magnetic iron oxide nanoparticles,” Angew. Chemie – Int. Ed., 2008.
 K. S. K. and Y. Z. Yong Ren, “Synthesis of Functional Materials by Non-Newtonian Microfluidic Multiphase System.”
 R. L. Hartman, “Managing solids in microreactors for the upstream continuous processing of fine chemicals,” Org. Process Res. Dev., vol. 16, no. 5, pp. 870–887, 2012.
 J. Kobayashi, “A Microfluidic Device for Conducting Gas-Liquid-Solid Hydrogenation Reactions,” Science (80-. )., vol. 304, no. 5675, pp. 1305–1308, 2004.
 K. Ren, J. Zhou, and H. Wu, “Materials for microfluidic chip fabrication,” Acc. Chem. Res., vol. 46, no. 11, pp. 2396–2406, 2013.
 J. P. Rolland, R. M. Van Dam, D. A. Schorzman, S. R. Quake, and J. M. DeSimone, “Solvent-Resistant Photocurable ‘Liquid Teflon’ for Microfluidic Device Fabrication,” J. Am. Chem. Soc., 2004.
 G. Du, Q. Fang, and J. M. J. den Toonder, “Microfluidics for cell-based high throughput screening platforms-A review,” Analytica Chimica Acta. 2016.
 L. Che-Hsin, L. Gwo-Bin, L. Yen-Heng, and C. Guan-Liang, “A fast prototyping process for fabrication of microfluidic systems on soda-lime glass,” J. Micromechanics Microengineering, 2001.
 C. Wiles and P. Watts, “Recent advances in synthetic micro reaction technology,” Chem. Comm., no. 23, pp. 443–467, 2006.
 S. A. Khan, A. Günther, M. A. Schmidt, and K. F. Jensen, “Microfluidic synthesis of colloidal silica,” Langmuir, vol. 20, no. 20, pp. 8604–8611, 2004.
 J. P. Knowles, L. D. Elliott, and K. I. Booker-Milburn, “Flow photochemistry: Old light through new windows,” Beilstein J. Org. Chem., vol. 8, no. Figure 1, pp. 2025–2052, 2012.
 T. W. Phillips, I. G. Lignos, R. M. Maceiczyk, A. J. deMello, and J. C. deMello, “Nanocrystal synthesis in microfluidic reactors: where next?,” Lab Chip, 2014.
 J. C. Pastre, D. L. Browne, and S. V. Ley, “Flow chemistry syntheses of natural products.,” Chem. Soc. Rev., 2013.
 A. Adamo et al., “On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system,” Science (80-. )., 2016.
 D. Kralisch and G. Kreisel, “Assessment of the ecological potential of microreaction technology,” Chem. Eng. Sci., 2007.
 B. Seok Moon et al., “Highly efficient production of [18F]fallypride using small amounts of base concentration,” Appl. Radiat. Isot., 2010.
 S. Kealey et al., “Microfluidic reactions using [11C]carbon monoxide solutions for the synthesis of a positron emission tomography radiotracer.,” Org. Biomol. Chem., 2011.
 R. D. Chambers and R. C. H. Spink, “Microreactors for elemental fluorine,” Chem. Commun., 1999.
 D. M. Ratner, E. R. Murphy, M. Jhunjhunwala, D. a Snyder, K. F. Jensen, and P. H. Seeberger, “Microreactor-based reaction optimization in organic chemistry–glycosylation as a challenge.,” Chem. Commun. (Camb)., 2005.
 L. R. Volpatti and A. K. Yetisen, “Commercialization of microfluidic devices,” Trends Biotechnol., vol. 32, no. 7, pp. 347–350, 2014.
 J. Keybl and K. F. Jensen, “Microreactor system for high-pressure continuous flow homogeneous catalysis measurements,” Ind. Eng. Chem. Res., vol. 50, no. 19, pp. 11013–11022, 2011.
 E. R. Murphy, J. R. Martinelli, N. Zaborenko, S. L. Buchwald, and K. F. Jensen, “Accelerating reactions with microreactors at elevated temperatures and pressures: Profiling aminocarbonylation reactions,” Angew. Chemie – Int. Ed., vol. 46, no. 10, pp. 1734–1737, 2007.
 S. Mashaghi, A. Abbaspourrad, D. A. Weitz, and A. M. van Oijen, “Droplet microfluidics: A tool for biology, chemistry and nanotechnology,” TrAC – Trends Anal. Chem., vol. 82, pp. 118–125, 2016.
 S. Haeberle et al., “Microfluidic platforms for lab-on-a-chip applications,” Lab Chip, 2007.
 A. Fallah-Araghi et al., “Enhanced chemical synthesis at soft interfaces: A universal reaction-adsorption mechanism in microcompartments,” Phys. Rev. Lett., 2014.
 A. M. Nightingale, T. W. Phillips, J. H. Bannock, and J. C. de Mello, “Controlled multistep synthesis in a three-phase droplet reactor.,” Nat. Commun., 2014.
 T. Aillet, K. Loubière, O. Dechy-Cabaret, and L. Prat, “Microreactors as a Tool for Acquiring Kinetic Data on Photochemical Reactions,” Chem. Eng. Technol., vol. 39, no. 1, pp. 115–122, Jan. 2016.
 K. Loubière, M. Oelgemöller, T. Aillet, O. Dechy-Cabaret, and L. Prat, “Continuous-flow photochemistry: A need for chemical engineering,” Chem. Eng. Process. Process Intensif., vol. 104, pp. 120–132, Jun. 2016.
 P. Anastas and N. Eghbali, “Green Chemistry: Principles and Practice,” pp. 301–312, 2009.
 E. E. Coyle and M. Oelgemöller, “Micro-photochemistry: photochemistry in microstructured reactors. The new photochemistry of the future?,” Photochem. Photobiol. Sci., vol. 7, no. 11, pp. 1313–1322, 2008.
 Y. Su, N. J. W. Straathof, V. Hessel, and T. Noël, “Photochemical transformations accelerated in continuous-flow reactors: Basic concepts and applications,” Chem. – A Eur. J., vol. 20, no. 34, pp. 10562–10589, 2014.
 S. Bachollet, K. Terao, S. Aida, Y. Nishiyama, K. Kakiuchi, and M. Oelgemöller, “Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor,” Beilstein J. Org. Chem., vol. 9, no. Scheme 1, pp. 2015–2021, 2013.
 T. Fukuyama, Y. Kajihara, Y. Hino, and I. Ryu, “Continuous Microflow [2 + 2] Photocycloaddition Reactions Using Energy-saving Compact Light Sources,” J. Flow Chem., vol. 1, no. 1, pp. 40–45, 2011.
 R. K. Shah et al., “Designer emulsions using microfluidics,” Mater. Today, vol. 11, no. 4, pp. 18–27, Apr. 2008.
 L.-Y. Chu, A. S. Utada, R. K. Shah, J.-W. Kim, and D. A. Weitz, “Controllable Monodisperse Multiple Emulsions,” Angew. Chemie, vol. 119, no. 47, pp. 9128–9132, 2007.