Microflow process integration

In their pioneering work, Jensen et al. demonstrated that photochemical transformation can be carried out in a microfabricated reactor [37]. The photomicroreactor had a single serpentine-shaped microchannel (having a width of 500 pm and a depth of 250 or 500 pm, and etched on a silicon chip) covered by a transparent window (Pyrex or quartz) (Scheme 4.25). A miniature UV light source and an online UV analysis probe were integrated to the device. Jensen et al. studied the radical photopinacolization of benzophenone in isopropanol. Substantial conversion of benzophenone was observed for a 0.5 M benzophenone solution in this microflow system. Such a high concentration of benzophenone would present a challenge in macroscale reactors. This microreaction device provided an opportunity for fast process optimization by online analysis of the reaction mixture. 

Several academic partners and Siemens Medical Solutions USA Inc. (Molecular Imaging) in Culver City, USA, made the synthesis of an [18F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose in an integrated microfluidic device (see Figure 5.1) [21]. Five sequential processes were made, and they are [18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange and hydrolytic deprotection. The half-life of [lsF]fluorine (t1/2 = llOmin) makes rapid synthesis of doses essential. This is one of the first examples of an automated multistep synthesis in microflow fashion. 

Figure 3.54 Conceptual view of integrated microflow system employing FPW pumps, mixer, process sensor and insonicator to produce ultrasound-assisted chemical reactions. Heater would be deposited metal or polysilicon meanderline formed on a surface of the chamber.

Many researchers have studied the interfacial science and technology of laminar flow in microfluidics [8]. Interfacial polymerization and the subsequent formation of solid micro structures, such as membranes and fibers in a laminar flow system, are very interesting techniques because the bottom-up method through polymerization is suitable for the formation of miniature structures in a microspace [3]. The development of such microstructure systems plays an important role for the integration of various microfluidic operations and microchemical processing [9]. For instance, membrane formation in a microchannel and further modification has a strong potential for useful functions such as microseparation, microreaction and biochemical analysis [8-10]. Here, we will introduce several reports on polyamide and protein membrane formation through interfadal polycondensation in a microflow. 

Realization of a flow sensor depends on its specific application. Overall, the spatial and transient resolution and the compatibility of the sensor within the desired device are of major concern [6]. In addition, the protection of the fluids and components demands a reduction in the thermal crossover from the flow sensor. The microflow sensors are usually automatically integrated with the microchannel during the fabrication process. The sensing element should be a resistor that has a resistance with high temperature sensitivity [2, 4, 9]. The heater of the sensor is often fabricated from a platinum or polysilicon resistor and acts as a microheater while the upstream and downstream temperature sensors are made from either polysilicon resistors or thermopiles. Such materials have excellent chemical resistance, hiocompatihUity, and high TCR [9]. 

This is necessary both for process control as well as the reliabihty of the system. The integration of sensors into the microreactor or building a multisensor module for the four functions of state is easy for a microreactor made of sUicon. For the process pressure, the piezoresistive principle is used often. With diEFerential pressure measurements, the flow rate can be determined. Alternatively, calorimetric principles are used widely. These are easy to implement technically, but a calibration is needed for eatii new medium. The most robust sensors are the Coriolis mass flow sensors. In process engineering, they are very common, but in terms of micro process engineering, there is still a need for research. In Ref. [26], sensors of this type are described. Ref [25] is a good summary of other microflow sensors. For measurement of temperature, there are many equivalent principles but will not be discussed here. Substantially, it is more difficult to measure the concentration in the reactor. In addition to optical principles, the impedance spectroscopy is often used. See Ref [27-31] for more details. 

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