In this paper we describe a novel method of manufacturing shape-controlled calcium alginate gel microparticles in a microfluidic device. Both manufacturing shape-controlled microparticles and synthesizing hydrogel microparticles could be performed simultaneously in the microfluidic device. The novel microfluidic device comprised of two individual flow-focusing channels and a synthesizing channel was successfully applied as a continuous microfluidic reactor to synthesize gel microparticles with size and shape control. By passive control based on the microchannel geometric confinement and liquid-phase flow rates, we succeeded in producing monodisperse sodium alginate microparticles with diverse shapes (such as plugs, disks, microspheres, rods, and threads) in the flow-focusing channels of the microfluidic device. The shape and size of the sodium alginate microparticles could be tuned by adjusting the flow rates of the various streams. Further stages of the chemical reaction could be initiated by mixing sodium alginate microparticles and calcium chloride (CaCl2) solution in the synthesizing channel. The shapes of the sodium alginate microparticles could be permanently preserved by the synthesis of calcium alginate gel microparticles. The preparation conditions of size- and shape-controlled calcium alginate microparticles and influence factors were studied.

We have developed an all-electronic digital microfluidic device for microscale chemical synthesis in organic solvents, operated by electrowetting-on-dielectric (EWOD). As an example of the principles, we demonstrate the multistep synthesis of ½ 18 FFDG, the most common radiotracer for positron emission tomography (PET), with high and reliable radio-fluorination efficiency of ½ 18 FFTAG (88 AE 7%, n ¼ 11) and quantitative hydrolysis to ½ 18 FFDG (>95%, n ¼ 11). We furthermore show that batches of purified ½ 18 FFDG can successfully be used for PET imaging in mice and that they pass typical quality control requirements for human use (including radiochemical purity, residual solvents, Kryptofix, chemical purity, and pH). We report statistical repeatability of the radiosynthesis rather than bestcase results, demonstrating the robustness of the EWOD microfluidic platform. Exhibiting high compatibility with organic solvents and the ability to carry out sophisticated actuation and sensing of reaction droplets, EWOD is a unique platform for performing diverse microscale chemical syntheses in small volumes, including multistep processes with intermediate solvent-exchange steps. molecular imaging | PET probes | synthetic chemistry | lab on a chip | on-chip chemistry T he use of micro-reaction technology in chemistry has grown tremendously over the past several years (1), due primarily to the highly precise control of reaction conditions that is possible through rapid mixing and heat transport, leading to improved reaction speeds and selectivity compared to macroscale approaches (2). Additional advantages include straightforward scale-up of production without changing conditions, and increased safety in dangerous syntheses due to the minute amounts of reagents within the reactor at any given time. A further advantage of microfluidics is the ability to perform reactions in extremely small volumes, which is valuable for many applications, especially when working with scarce reagents, such as isolated proteins or natural products, products of long synthetic pathways, or short-lived radiolabeled radioisotopes where the needed mass quantities are extremely low (3).Myriad microfluidic platforms have been explored for chemical reactions that can be classified into three basic formats: (i) flow-through (or continuous flow), (ii) droplet or slug, or (iii) batch. In flow-through systems, streams of two or more reagents are mixed and reacted by flowing through a residence time unit held at a constant temperature or immersed in a fixed microwave field. Continuous liquid-liquid extraction and other processes have been developed to enable multistep reactions where different solvents are required in different steps (4). Droplet and slug systems are a variant of flow-through systems, in which individual droplets or slugs (with volumes down to tens of nanoliters) are separated by an immiscible carrier fluid, each acting as an isolated batch microreactor and enabling vastly reduced reaction volumes. Screening assays and optimization studies...

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Droplet generation and droplet-based microreactor are realized by a facile microfluidic device. The relative concentrations of reactants could be well controlled by adjusting the flow rates without bringing reagents into prior contact; this new method shows considerable advantages for the control and rapid mixing of reagents with no dispersion.

We demonstrate a new approach to impedance measurement on digital microfluidics chips for the purpose of simple, sensitive, and accurate volume and liquid composition measurement. Adding only a single series resistor to existing AC droplet actuation circuits, the platform is simple to implement and has negligible effect on actuation voltage. To accurately measure the complex voltage across the resistor (and hence current through the device and droplet), the designed system is based on software-implemented lock-in amplification detection of the voltage drop across the resistor which filters out noise, enabling high-resolution and low-limit signal recovery. We observe picoliter sensitivity with linear correlation of voltage to volume extending to the microliter volumes that can be handled by digital microfluidic devices. Due to the minimal hardware, the system is robust and measurements are highly repeatable. The detection technique provides both phase and magnitude information of the real-time current flowing through the droplet for a full impedance measurement. The sensitivity and resolution of this platform enables it to distinguish between various liquids which, as demonstrated in this paper, could potentially be extended to quantify solute concentrations, liquid mixtures, and presence of analytes.