User:Mitchell Kaiser/sandbox draft

Droplet-based microfluidic methods have been adopted as a method of chemical synthesis. Droplets act as individual reaction chambers protected from contamination through device fouling by the continuous phase. Benefits of synthesis using this regime (compared to batch processes) include high throughput, continuous experiments, low waste, portability, and a high degree of synthetic control.^[1] Some examples of possible syntheses are the creation of semiconductor microspheres^[2] and nanoparticles^[3]. Generally, reactions are limited to one-step synthesis, as more complex synthesis require multiple additions of reagents to the droplet. This results in excess material which must be removed by splitting the droplet so that the excess is separated from the reaction chamber. ^[1][4] To ensure careful monitoring of reactions, techniques like laser-based spectroscopy, NMR spectroscopy, microscopy, mass spectrometry, electrochemical detection, absorbance detection, and chemiluminescent detection are used. Often, measurements are taken at different points along the microfluidic device to monitor the progress of the reaction.^[1]

Increased rate of reactions using micro-droplets are seen in the aldol reaction of silyl enol ethers and aldehydes. Using droplet based a microfluidic device, reaction times were shortened to twenty minutes versus the twenty-four hours required for a batch process.^[5] Other experimenters were able to show a high selectivity of cis-stilbene to the thermodynamically favored trans-stilbene compared to the batch reaction, showing the high degree of control afforded by micro-reactor droplets. This stereocontrol is beneficial to the pharmaceutical industry.^[6] For instance, L-Methotrexate, a drug used in chemotherapy, is more readily absorbed than the D isomer. These and the other benefits of microfluidics can be scaled up by using larger channels to allow more droplets to pass or by increasing droplet size^[7]. Adjusting the rate of flow of the carrier and disperse phase at a t-junction tunes the size of droplets created. Droplet size is limited by the need to maintain the concentration and stability of microdroplets^[5]. Thus, increased channel size becomes attractive due to the ability to create and transport a large number of droplets and increasing throughput.^[7] In larger channels, dispersion of droplets^[8] and stability of droplets^[9] become a concern. These steps maximize droplet throughput in generation and transportation. In order to maximize reaction throughput, thorough mixing of droplets to expose the greatest possible number of reagents is necessary to ensure the maximum amount of starting materials react.^[7] This can be accomplished by using a windy channel to facilitate turbulent flow within the droplets.^[10]

A significant complication in chemical synthesis using micro-droplets is the limitation of the number of reagent additions.^[1] Adding reagents generally results in an increased droplet size. Excess liquid must be separated from the droplet in order to maintain the droplet volume. One method of reagent addition without changing the volume of the droplet is achieved by dissolving amphipathic substances in the continuous phase and having an additional inlet for the solution where reagent addition is desired. The dissolved reagent diffuses into the reaction droplet without changing the droplet volume. Diffusion time is less than five seconds in this method.^[11] Reagents can also be added in multiple droplet fusion steps^[12] or by picoinjection^[13]. In this case, droplets must be enriched. This can be done by producing aqueous droplets in a continuous phase that is a mixture of oil and dimethyl carbonate (DMC). Water will dissolve into the DMC, shrinking the droplet and increasing the concentration of reagents.^[14]