Single phase microreactor for the continuous, high-temperature synthesis of <4¿nm superparamagnetic iron oxide nanoparticles

The reproducibility of key nanomaterial features is essential in nanomedicine applications where small changes of physical characteristics often lead to a very different behavior. In this regard, continuous microreactors are often advocated as a means to achieve highly precise synthesis of nanomaterials. However, when the synthesis must take place at high temperatures the use of these devices becomes restricted in terms of materials and practical problems (e.g. plugging of microchannels). Here we present the continuous synthesis of ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs) through a polyol-based process at high temperatures (>200 °C). The microfluidic reactor designed allows SPION production at residence times under 1 min, was able to work continuously for 8 h without channel blockage and reached high production yields by coupling microreactors using stacked plates. The effect of operating conditions was optimized to produce homogeneous particles with a narrow particle size distribution. In summary, the microreactor developed in this work enables easy-to scale up, reproducible continuous production of SPIONs

Perspective Article: Flow Synthesis of Functional Materials

Continuous-flow synthesis of specific functional materials is now seen as a reliable synthesis approach that gives consistent product properties. This perspective article aims to survey recent work in some of the relevant areas and to identify new domains where flow synthesis of functional materials can be better than the conventional synthesis methods. It also emphasizes the need for developing high-throughput integrated synthesis and screening systems for almost all functional materials so that laboratory-scale recipes can be transformed into reliable manufacturing processes. New areas relevant to functional materials which have remained unexplored in flow synthesis are also highlighted

Emulsion characterization via microfluidic devices : A review on interfacial tension and stability to coalescence

Emulsions have gained significant importance in many industries including foods, pharmaceuticals, cosmetics, health care formulations, paintings, polymer blends and oils. During emulsion generation, collisions can occur between newly-generated droplets, which may lead to coalescence between the droplets. The extent of coalescence is driven by properties of dispersed and continuous phases, e.g. density, viscosity, ion strength and pH, and system conditions, e.g. temperature, pressure or any external applied forces. In addition, the diffusion and adsorption behaviors of emulsifiers which govern the dynamic interfacial tension of the forming droplets, the surface potential, and the duration and frequency of the droplet collisions, contribute to the overall rate of coalescence. An understanding of these complex behaviors, particularly those of interfacial tension and droplet coalescence during emulsion generation, is critical for the design of an emulsion with desirable properties and the optimization of the processing conditions. However, in many cases, the time scales over which these phenomena occur are extremely short, typically a fraction of a second, which makes their accurate determination by conventional analytical methods extremely challenging. In the past few years, with advances in microfluidic technology, many attempts have demonstrated that microfluidic systems, characterized by micrometer-size channels, can be successfully employed to precisely characterize these properties of emulsions. In this review, current applications of microfluidic devices to determine the equilibrium and dynamic interfacial tension during the droplet formation, and to investigate the coalescence stability of dispersed droplets applicable to the processing and storage of emulsions, are discussed.Peer reviewe

Review: Electric field driven pumping in microfluidic device

Pumping of fluids with precise control is one of the key components in a microfluidic device. The electric field has been used as one of the most popular and efficient nonmechanical pumping mechanism to transport fluids in microchannels from the very early stage of microfluidic technology development. This review presents fundamental physics and theories of the different microscale phenomena that arise due to the application of an electric field in fluids, which can be applied for pumping of fluids in microdevices. Specific mechanisms considered in this report are electroosmosis, AC electroosmosis, AC electrothermal, induced charge electroosmosis, traveling wave dielectrophoresis, and liquid dielectrophoresis. Each phenomenon is discussed systematically with theoretical rigor and role of relevant key parameters are identified for pumping in microdevices. We specifically discussed the electric field driven body force term for each phenomenon using generalized Maxwell stress tensor as well as simplified effective dipole moment based method. Both experimental and theoretical works by several researchers are highlighted in this article for each electric field driven pumping mechanism. The detailed understanding of these phenomena and relevant key parameters are critical for better utilization, modulation, and selection of appropriate phenomenon for efficient pumping in a specific microfluidic application

Quantum optical signatures of coherent vibronic dynamics in bio-inspired light harvesting systems

The study of quantum phenomena in biology has received significant attention in the last decade. One of the problems of most interest is the understanding of quantum effects during the first steps of photosynthesis. Ultrafast two-dimensional electronic spectroscopy has revealed that pigment-protein complexes responsible for light- harvesting and charge separation in photosynthetic organisms can support quantum coherent dynamics in the excited state, for up to few hundreds of femtoseconds. The leading hypothesis on the mechanisms supporting this coherent behaviour is quan- tum interactions between electronic and some specific vibrational motions in the excited state. This hypothesis, however, awaits unambiguous confirmation. Among the most powerful techniques to investigate the quantum behaviour of an emitter is the study of quantum optical properties of the light it emits. This thesis de- velops theoretical studies showing that frequency-filtered and time-resolved photon counting statistics of the light emitted by a prototype photosynthetic unit can give important insight into the quantum coherent nature and the mechanisms underlying excited state dynamics in single photosynthetic complexes. By developing a pertur- bative and efficient approach to the computation of frequency- and time- resolved photon correlation functions, we show that such correlations have the potential to give unambiguous signatures of coherence contributions to the steady state emis- sion. For a light-harvesting unit emitting in free space, the signatures of excited state coherence manifest themselves as non-trivial antibunching. This feature can- not be probed by measuring unfiltered photon correlations. We then consider the situation in which a prototype energy transfer unit is embedded in an optical cavity such that its emission rate is enhanced. In this case we observed a rich behaviour of the frequency-filtered, second-order photon correlations that allows a clear distinc- tion of coherence contributions, and their variation, depending of the electronic and vibrational interactions in the system of interest

Novel Synthesis Methods For the Production of Human Circulating Metabolites of Natural Products

Upon entering the body, any given xenobiotic can undergo metabolism which facilitates its excretion from the body. When metabolised, a compound typically has the same effects of the initial drug/nutraceutical, however this is not always the case and can significantly differ. The determination of these beneficial and toxicological effects is vital to allow for effective drug development and to increase current knowledge of nutraceuticals. This is because contradictory knowledge of their pharmacological effects is often found. Currently there is no method available that allows for the synthesis of these compounds in useable quantities (mg). This study aimed to provide a method that can be used to simply synthesise these metabolic products in sufficient amounts for further testing. Three different enzymes families (UGT1a1, SULT1a1 and CYP1a1) were immobilised via a silanization followed by a glutaraldehyde functionalization and tested. These were compared to a variety of different controls being excluding co-factor or enzyme from the system or immobilising an alternative unreactive enzyme towards the substrate. In each of the chapters it was determined that metabolite formation was only observed when both the correct enzyme and co-factor was available within the system. The true run for each enzyme was optimised at two different parameters: flow rate and temperature. For all three of the enzymes used the optimal temperature depicted in their recommended instructions was 37 °C. The UDP-glucuronosyl transferase immobilised device showed no significant difference at any of the three tested flow rates. However, temperature showed a significant difference oppositely to expected in which 37 °C yielded almost no product at all (97.9 ± 38.5 μM substrate remaining), and both room temperature and 30 °C yielded significant conversion (11.0 ± 8.0 μM and 0.0 ± 0.0 μM remaining respectively). The Sulfotransferase immobilised device also showed no significant difference between any of the three tested flow rates. Temperature also yielded the contrary results to that which was expected and almost no product at all was formed (81.3 ± 21.8 μM substrate remaining) and both room temperature and 30 °C yielded significant conversion (92.9 ± 7.2 and 92.2 ± 10.2 μM remaining respectively). The cytochrome P450 based device showed no significant difference between any of the three tested flow rates, the further parameters were not tested due to fluorescence interference issues and further testing is needed. The UGT and SULT devices were then compared to directly incubating both the substrate and co-factor with the enzyme. A 2-hour period for both methods yielded comparable results (0.22 ng in static conditions and 0.24 ng in flow conditions) but the formation of a complex biological matrix is not formed. Alongside this allowing the reaction to occur over a longer period of time (4 hours) the immobilised enzyme reactor continued to yield product in which the incubation method plateaued; leading to significantly higher metabolite formation (0.2 ng in static conditions and 0.47 ng in batch conditions). This data was not observed in the case of the CYP device due to a fluorescence interference observed in the effluent of the device preventing comparable measurements. With further optimisation or scaling up of these devices they will likely be viable for the synthesis of sufficient quantities of metabolite to allow for pharmacological testing, with an improvement on the currently available methods by bypassing the necessary complex separation, high costs and commonly observed low yields

Microwave-Assisted Synthesis of Supported Nanocatalysts: A route from nanoparticles to nanoclusters, from batch to continuous.

The main drawbacks of the traditional batch chemical processes are the excessive energy consumption, the variable product quality, the limited scaled‐up and the poor efficiency. The European Training Network for Continuous Sonication and Microwave Reactors (ETN‐COSMIC) aims to support the transition of the chemical industry from batch to continuous flow technologies with the investigation of alternative no contact energy sources, such as ultrasounds and microwaves. The current PhD work targets the development of high efficient nanocatalysts suitable for heterogeneous catalytic reactions, focusing on the effects of microwaves and continuous flow reactors. This thesis covers the following aspects to successfully design the synthesis reactor and the final high efficient nanocatalysts:‐ Development of a method to accurately control the temperature in microwave-heated continuous flow microreactor for the synthesis of metallic nanoparticles.‐ Definition of the optimum heating patterns for the synthesis of metallic nanoclusters.‐ Development of a synthesis procedure, based on microwave heating, for the in-situ synthesis of metallic nanoclusters on catalytic supports.‐ Testing of catalytic activity.The thesis is structured in five experimental chapters. In chapter 2, it is introduced the microwave‐heated continuous flow reactor used in this PhD research, benchmarking its efficiency with a common silver nanoparticles procedure that is carried out in a batch‐type reactor comparing a conventional heating mode, such as an oil bath, and the alternative electromagnetic heating. An accurate investigation of the temperature mapping, performed by integrating simulated and experimental results, confirmed that microwaves guarantee a higher heating rate and consequently higher synthesis yield. Furthermore, the different heating profile counteracts the wall fouling and then, improves the quality of the final product. In chapter 3, the optimization of the heating pattern for the production of ultra-small nanocatalysts was conducted in a batch‐type process, evidencing the effects of the nucleation rate on the size distribution of the resulting nanoparticles. A detailed analysis of the temperature profile evidenced that the quality of the final product may increase by adopting a rapid selective heating rate, function of the microwave irradiation power. The quality of the produced nanomaterials was remarkable not only for their high activity in the tested conditions but also for their long‐term stability which is more than 18‐months. The nanoparticles produced were deposited into mesoporous SBA‐15, obtaining the first catalyst B-AgNPs@SBA-15, and its activity was tested using the hydrogenation of 4‐Nitrophenol with sodium borohydride, comparing the developed nanosystem with literature results.In chapter 4, the process was switched to continuous flow, including a rapid quenching step. The nanoclusters were uniformly supported over the mesoporous channels of SBA‐15, and the catalyst C-AgNCs@SBA-15 was tested for alkynes’ hydrogenation. The high density of uncoordinated Ag atoms was responsible for the high activity observed, confirming that supported nanoclusters may represent a bridge between low active nanoparticles and unrecoverable silver salts. In chapter 5, an alternative reactor for in‐situ nucleation of silver nanoclusters was introduced with the purpose of increasing the loading yield, lowering the metal loss. The clusters size was still reduced and the synthesis yield was higher than 90%. The higher metal loading may play a crucial role in accelerate some catalytic reaction, as demonstrated by the hydrogenation of 4‐Nitrophenol. Furthermore, the nanocatalyst synthesized confirmed its usefulness for a wide range of C≡C cyclization and its morphological and catalytic stability was proved after one year of storage. To conclude, the scalability of the batch method was evaluated moving from 100 mg to 1 g of catalyst, in 2 minutes synthesis time.Finally, chapter 6 is focused on the production of bimetallic nanoclusters, which may present interesting and fascinating properties. The continuous flow reactor was properly modified to allow a dual‐step reducing process, and bimetallic structures were synthesized, investigating the effects of residence time and temperature profile. The bimetallic nanoclusters were directly synthesized on the carbon support in the continuous flow, maximizing the synthesis yield and optimizing clusters distribution.<br /