Continuous flow microfluidic device

Notably, two classes of microreactors exist, referring to applications in analysis, especially in the field of biochemistry and biology (e.g., continuous flow microfluidic devices, micro total analysis systems - (xTAS, etc.) or chemical engineering and chemistry. Although these fields are distinct, there are clear overlaps and common areas of development. 

Chen X, Cui D, Liu C, Li H, Chen J (2007) Continuous flow microfluidic device for cell separation, cell lysis and DNA purification. Anal Chim Acta 584(2) 237-243... 

Cummings EB (2003) Streaming dielectrophoresis for continuous-flow microfluidic devices. IEEE Eng Med Biol Mag 22 75-84... 

Since they feature permanently etched microchannels, continuous-flow microfluidic devices suffer from inherent difficulty in integrating and scaling them because the parameters that govern the flow field (e.g., pressure, fluid resistance, and electric field) vary along the flow path. 

A number of microfluidic circuits have been developed their principles of operation depend on the mechanism of fluid flow in the microchip. In this entry, we shall describe only the fluidic circuits used with pressure-driven flow and electrokinetically driven flow, as these are the two main pumping methods for continuous-flow microfluidic devices. Pressure-driven flow can be obtained by connecting the channel to a syringe pump or a compressed gas. Electroki-netic flow of an ionized electrolyte can be obtained by applying an electric field along the flow direction. 

Sethu P, Anahtar M, Moldawer LL, Tompkins RG, Toner M (2004) Continuous flow microfluidic device for rapid erythrocyte lysis. Anal Chem 76 ... 

Ramadan Q, Samper V, Poenar D, Liang Z, Yu C, Lim TM (2005) Simultaneous cell lysis and bead trapping in a continuous flow microfluidic device. Sens Actuators B 113 944-955... 

Continuous flow microfluidic device for rapid erythrocyte lysis. Anal Chem 76 6247-6253... 

Lab-on-a-chip systems have been previously demonstrated to have significant utility in the field of analytical chemistry.1 Lab-on-a-chip systems miniaturize standard bench-scale operations that are normally carried out in containers of the order of millilitres or litres to chip-scale operations in channels and droplets on the order of nanolitres to microlitres. The majority of lab-on-a-chip devices proposed thus far utilize micrometer-scale sealed channels. These sealed channels can then be used to separate, combine and mix chemical reagents in such a way as to recreate traditional wet chemistry protocols on a much smaller scale. When used in such a manner, these sealed channels are referred to as continuous flow microfluidic channels.2 4... 

To summarize, a lot of work has been done in the field of fluorination reactions in microfluidic devices. Concerning the deoxofluorination with hazardous DAST, the development of a process from laboratory to pilot plant scale with inline process analysis was nicely demonstrated. Later on, the scope of substrates and fluorinating agents was broadened and inline purifications were introduced on laboratory scale. Thus, the microfluidic devices were a good tool to establish substance libraries. In the case of radiolabeling with [ F] fluoride ions, the chapter focused on recent advances in continuous-flow microfluidic procedures. However, the miniaturization for a continuous processing of all necessary preparation steps remains a major challenge. 

Wang, H.-Y., Bhunia, A. K., and Lu, C. (2006). A microfluidic flow-through device for high throughput electrical lysis of bacterial cells based on continuous DC voltage. Biosens. Bioelectron. 22,582-588. 

In order to increase the efficiency of biocatalytic transformations conducted under continuous flow conditions, Honda et al. (2006, 2007) reported an integrated microfluidic system, consisting of an immobilized enzymatic microreactor and an in-line liquid-liquid extraction device, capable of achieving the optical resolution of racemic amino acids under continuous flow whilst enabling efficient recycle of the enzyme. As Scheme 42 illustrates, the first step of the optical resolution was an enzyme-catalyzed enantioselective hydrolysis of a racemic mixture of acetyl-D,L-phenylalanine to afford L-phenylalanine 157 (99.2-99.9% ee) and unreacted acetyl-D-phenylalanine 158. Acidification of the reaction products, prior to the addition of EtOAc, enabled efficient continuous extraction of L-phenylalanine 157 into the aqueous stream, whilst acetyl-D-phenylalanine 158 remained in the organic fraction (84—92% efficiency). Employing the optimal reaction conditions of 0.5 gl min 1 for the enzymatic reaction and 2.0 gl min-1 for the liquid-liquid extraction, the authors were able to resolve 240 nmol h-1 of the racemate. 

Qualitatively, the operation of the microfluidic flow-focusing system can be described in the following way. Two immiscible phases (e.g. Nitrogen and water, or water and oil) are delivered via their inlet channels to the flow-focusing junction. In this junction, one central inlet channel, that delivers the fluid-to-be-dispersed (e.g. Nitrogen to be dispersed into bubbles) ends upstream of a small constriction (an orifice). From the sides of the central channel, two additional ones terminate upstream of the orifice. These side channels deliver the continuous fluid (e.g. aqueous solution of surfactant). It is important that these continuous phase wets the walls of the microfluidic device preferentially. Otherwise - if the fluid-to-be-dispersed - wets the walls, the resulting flows are erratic [16] and it becomes virtually impossible to form bubbles (droplets) in a reproducible and controllable process. 

Figure 9. Formation of droplets in microfluidic flow-focusing devices. The micrographs on the left illustrate the process of formation of aqueous drops in an organic continuous fluid [S. Makulska, P. Garstecki, Institute of Physical Chemistry PAS]. The chart on the right shows the dependence of the volume of liquid droplets formed in a planar flow focusing device on the value of the capillary number (Adapted from Ref [24]).

---