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Continuous manufacturing technology and digitalization are going to have a strong impact on how chemicals (e.g., active pharmaceutical ingredients, APIs) are manufactured in the future. Recent developments, such as the implementation of process analytical technology (PAT), advanced data processing methods and the implementation of autonomous and data-rich experimentation, have contributed to this advancement.

Automated flow chemistry platforms have been established in both industrial and academic laboratories in past several years, In an ideal case, these platforms would design and plan their own synthetic route, self-optimize the reactions, build reaction models, identify all intermediates, discover new reactions and work 24/7, autonomously. The developed platforms are comprised of a hardware component (e.g., reactors, pumps and analytical instruments) and a software component (e.g., hardware control, experiment selection and data processing algorithms). In our labs the development of an automated flow chemistry platform started in 2018 and has been constantly improved over the following years. We strongly focus on real-time process analytics, data analysis and interaction of the control system with a range of different algorithms.

In this lecture the key aspects of implementing automated flow chemistry reactor platforms with real-time process analytics will be presented and the potential of these platforms to conduct self-optimization, automated reaction model building, dynamic experiments and implementing advanced process control strategies will be highlighted.

Peptides have become increasingly important as drugs and drug candidates. However, the conventional chemical peptide synthesis usually requires the use of an excess amount of expensive coupling agents and additives, making the process both expensive and wasteful. We have demonstrated micro-flow peptide synthesis using less wasteful, inexpensive, and highly active reagents. Our synthetic approach is based on the rapid and strong activation of carboxylic acid with the highly active reagent. Undesired reactions of highly active electrophile were suppressed by precise control of its residence time and reaction temperature, enabled by the microflow technologies. Microflow technologies not only enabled the development of less wasteful and low-cost synthetic processes for peptides but also gave us valuable insights into rapid reactions that can not be easily analyzed by conventional batch techniques.

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Our group has been working on the synthesis of nanoparticles using an inkjet mixing system, which is one of the clogging free micromixers. This talk will introduce some examples of synthesis of size and morphology controlled metal particles, polymer particles, and polymer capsules.

This talk will showcase the effective exploitation of continuous flow reactors for the safe generation of reactive intermediates using photochemical as well as thermal strategies. These will include azides, nitrenes, carbenes as well as benzynes that can be safely generated and consumed within the miniaturised flow environment en route to valuable chemical building blocks. Moreover, the strategic use of such flow approaches towards the discovery of new reactions and reactivity modes will be highlighted as an area with untapped potential in modern organic synthesis.

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This talk explores innovative approaches to continuous flow catalysis, focusing on the use of heterogeneous catalysts. Central to this work is the catalytic static mixer (CSM), a 3D-printed support coated with the active catalyst. This presentation will showcase continuous heterogeneous photocatalysis for CO2 upgrading. Additionally, new developments in continuous flow electrochemistry and plasma catalysis will be discussed, highlighting the ongoing efforts in reactor design and development within the team.

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After 10 years of accumulation of developing flow chemistry synthesis equipment and core modules, Ou Shisheng (Beijing) Technology Co., Ltd. launched a series of high-throughput instruments this year for rapidly screening and validating AI models. The platform accommodates homogeneous, heterogeneous, catalytic, photochemical, and electrochemical reactions. It can handle a wider range of reaction conditions, including low temperatures, high pressures, and corrosive materials, thus encompassing more reaction types. This accelerates AI data acquisition, improving AI model training, shortening R&D cycles, and enabling chemists to better utilize AI in their work.

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Mechanochemistry, which uses mechanical force to drive chemical reactions, offers a sustainable alternative to traditional methods by reducing energy use and minimizing waste. WAB-GROUP® is exploring this field through its advanced technologies, focusing particularly on the WAB IMPA°CT REACTOR®, a system that combines flow chemistry with bead milling. We evaluated key process parameters – such as heat transfer, residence time, and micro mixing efficiency – to assess the suitability of our equipment for mechanochemical applications. This presentation will provide an overview of characterization results and proposed optimization strategies, highlighting the benefits of bead mills for synthetic applications.

The integration of continuous-flow technology and photochemistry holds significant potential for applications in pharmaceuticals and agrochemicals; however, achieving precise control and real-time monitoring remains a critical challenge. In this study, we developed a highly automated, multi-stage continuous-flow reaction platform that innovatively integrates in-situ bromine generation, photocatalytic bromination, quenching, water–oil separation, and photodebromination reactions. This integration enabled the rapid, continuous synthesis of trifloxystrobin intermediates, achieving a conversion rate of 98.6%, overall yield of 94.2% and purity of 98.9% within just 12.9 minutes. Concurrently, we designed a Dynamic Tracking Reference Continuous Calorimeter (DTRCC) to precisely and reliably monitor reaction heat in real time, thereby providing robust thermodynamic data for the reaction process. Furthermore, by combining microfluidic technology with advanced machine learning algorithms, we significantly enhanced the accuracy of thermal measurement and automatic data correction, effectively reducing measurement error to below 0.5%. The developed integrated platform demonstrates substantial advantages in rapid continuous synthesis, precise real-time monitoring, and accurate data correction, offering essential technological support for the industrial application of continuous-flow chemistry.

Microfluidic plasmas so far reported mostly follow the classical approach, which is to have microchannel creating a microfluidic environment that allows to exert process intensification, being amplified by plasma as co-enabling concept. Similarly, microwave-amplified flow chemistry has been concepted. The new approach reported here uses the plasma processing itself to generate in-situ a microreaction zone. Gas-liquid plasmas often use a high-velocity gas stream or gaseous jet. High-velocity liquid jets actually are used to shape microchannels in metals (water jet cutting). Thus, what about using the energy of high-velocity plasma gas jets to shape “channel-free microreaction zones” during the plasma process? Three concepts have been invented and designed as process. A plasma microjet penetrates deeply into a liquid microvolume, squeezing almost all liquid out of the milli-vessel centre. A stagnant layer of about 2 mm thickness remains, and it has been determined that reaction herein is governed by diffusion, despite being surrounded by highly turbulent gas and liquid flows. Using two plasma microjets, instead of one, and setting the liquid volume somewhat larger, allows to form a virulent convective layer above the stagnant layer. Now, the microjet functions as ‘pumping engine’ to create directed convection towards the reaction zone, in the centre of the milli-vessel. Microturbulence at the gas-liquid interface intensifies the chemical reaction. As third concept, a plasma bubble reactor has been investigated. Through about 250 micrometer nozzles in a hollow cylinder, micro-bubbles of a diameter ranging 1.9-3.3 mm micrometers are formed, which stay attached up to 100 ms to the cylinder outer wall. In this time, plasma is effective to generate activated species. Their absorption in the liquid volume is intensified by cavitation that the plasma ultrasound causes. All three channel-free, in-situ microreactor concepts demonstrated significant increase in conversion for the formation of nitrates in aqueous solution from air plasma; with application as fertilizers.

This presentation starts by exploring two examples of recent collaborative work aimed at increasing lab efficiency and throughput through digital lab workflows. The second part explores exciting new synthetic routes published recently by Vapourtec customers.

Experience the next stage of flow chemistry with automated, real-time molecular insight. Paeonia Innovations presents its next-generation compact mid-infrared (mid-IR) spectrometer, purpose built for continuous flow applications. Designed for seamless integration into flow systems, this advanced platform delivers uninterrupted, in-line monitoring of reaction kinetics, conversion, and product formation, which eliminates the need for off-line sampling and accelerates development of new products.

Beyond monitoring, the system offers real-time analysis of residence time distribution (RTD) to support reactor optimization and scale-up. Through a series of compelling case studies, we will demonstrate how integrated mid-IR sensing enables smarter process control, faster development, and deeper chemical understanding, empowering researchers and industry professionals to rethink what’s possible in flow chemistry and automated synthesis.

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Africa has a variety of formulation companies; however the active pharmaceutical ingredients (APIs) are generally imported, making medications unaffordable to many patients in developing countries.

When micro reactor technology and flow chemistry was introduced it was seen as a research and development tool, however it is now being used to produce large quantities of product, especially in Asia.

To this effect, we are working on developing local drug manufacturing capacity in Africa using continuous flow technology, with the goal of lowering the cost of drugs, improving drug accessibility and ultimately improving Africa’s health. A selection of cases studies will be presented.

The oxidation of methylarenes is a crucial reaction for preparing fine chemicals such as aromatic aldehydes and aromatic acids. Conventional oxidation methods much rely on high-temperature and high-pressure conditions or hazardous reagents, leading to safety risks and environmental pollution. Electro-oxidation offers an alternative due to its advantages of high atomic economy and mild reaction conditions. Among different electro-oxidation approaches of methylarenes, indirect oxidation mediated by Co(II) in organic systems holds the potential to solve the problems. We therefore constructed a Co(II)-mediated indirect electro-oxidation system for methylarenes using acetic acid as the solvent, cobalt acetate as the electrochemical mediator, and n-Bu4NBF4 as the supporting electrolyte. Facing complex product distributions and selectivity control challenges, an AI algorithm was integrated to develop and optimize a selective electro-oxidation process, achieving a balance between product yield and energy consumption. A continuous-flow reaction platform centered on an electrochemical microreactor was further designed, enabling the electro-oxidation with high yield and selectively.

Aromatic nitration, a hazardously complex process, poses serious risks for nearly 200 years. Key challenges include the decoupling of reaction kinetics and transport behavior, the suppression of side reactions, and the improvement of process safety. Flow chemistry offers a powerful integrated tool for both mechanistic exploration and process intensification. By enhancing mass transfer and heat management in continuous flow systems and precisely controlling reaction conditions, a kinetic research methodology for aromatic nitration and kinetic models for typical nitration processes were established. For the first time, a mechanism for suppressing over-nitration side reactions through dynamic regulation of thermodynamic properties in continuous flow system was identified, significantly improving the selectivity of nitration reactions. Furthermore, by integrating the concept of countercurrent flow with flow chemistry principles, a novel microflow reaction mode and its corresponding optimization strategy were developed. This mode reduces the exothermic rate of the nitration reaction while simultaneously increasing the spatiotemporal conversion rate. The flow nitration strategy, combining the novel mechanism and microflow mode, has been successfully applied to various typical nitration processes. It provides a safer and more efficient nitration protocol with higher selectivity, demonstrating the advantages of the proposed strategy.

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This lecture outlines our efforts to develop safe, efficient, and scalable chemical processes for the transformation of biobased diols and aldehydes using continuous flow technology and predictive modeling. A selection of case studies will be presented, including the chlorination/dechlorination of glycerol toward glycidol and epichlorohydrin, the direct carbonation of glycidol with CO₂, dynamic covalent exchange reactions on polyols, and the nitration of furfural for the synthesis of nitrofuran pharmaceuticals. These examples illustrate how digital tools and integrated flow platforms can accelerate process development, reduce environmental impact, and improve reproducibility at scale.

Flow chemistry enables process intensification yet sometimes is amplified by a ‘co-enabler’. That might be a specific solvent (deep eutectic solvent, ionic liquid), catalyst (nano), energy induction (microwave, plasma, ultrasound), and so on. This talk reports about flow chemistry leaching with a green lixiviant, pyroligneous acid derived from biomass pyrolysis, as co-enabler that substitute conventional mineral based leaching agents, for e-waste recycling. Past environmental and cost evaluations of flow chemistry did not account on the ‘backpack’ of the co-enabler but focused on the flow chemistry itself. That might be an untapped opportunity to show societal value.

This work is, therefore, the first in providing a holistic view on the combined role of both the ‘enabler’ (flow chemistry) and co-enabler’ (green lixiviant) for critical metal recovery from e-waste. Life cycle assessment, LCA, and techno-economic analysis, TEA, have been performed for the manufacturing of the green lixiviant from biomass resources. The life cycle inventory (LCI) encompasses and compares the pre-processing and pyrolysis options of the biomass. Transportation scenarios have significant TEA&LCA-impact when considering distributed and centralised green lixiviant manufacturing. The inventories of the LCA and TEA are much expanded by integrating the flow chemistry process to leach ‘black mass’, industrial powder from spent lithium-ion batteries of e-waste. As this is a solid-liquid flow chemistry process, data were mined both from conventional flow chemistry reactors (capillaries, Corning) and also solid-carriage tailored ones (StoliChem). We will demonstrate how the choice of biomass (e.g. pine, bamboo) impacts the environmental profile of a flow chemistry (leaching) process on e-waste recycling.

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Automated multistep synthesis remains challenging due to the complexity of organic reactions and downstream purification. We present a modular platform based on high-speed circulation flow (HSCF) reactors that combines the flexibility of batch with the efficiency of flow systems. This platform enables direct automation of batch-based literature protocols, including homo- and heterogeneous reactions, slow kinetics, and photochemical process, which without requiring re-optimization. Two configurations were demonstrated: an “all-in-one” setup with compact footprint enabled fully automated synthesis of Brexpiprazole (25g, top 200 best-selling small-molecule drugs in 2023), while an “integrated flow” setup achieved semi-continuous production of Esonarimod and other bioactive molecules at >10 g/day. This universal, scalable system offers a practical solution for on-demand synthesis of complex small molecules.

Cyclobutane-containing molecules are highly sought after in drug discovery due to their ability to impart conformational rigidity, enhance metabolic stability, and mimic bioactive conformations. However, their synthesis remains a significant challenge, owing to the inherent ring strain and the need for stringent stereocontrol. In this work, we present a flow-enabled approach to access a diverse library of β-cyclobutane amino acids (β-CBAAs) via photoinduced [2+2] cycloadditions of 2-pyrone and 2-pyridone derivatives. By developing and optimizing continuous and circulated flow photoreactor systems with high-intensity 310 nm UV LEDs, we achieved enhanced control, safety, and scalability compared to conventional batch photochemistry. This platform enabled efficient generation of key bicyclo[2.2.0] intermediates, which were further elaborated into structurally novel β-CBAAs. Our results highlight the power of combining photochemical reactivity with modern flow technologies to address long-standing synthetic challenges in strained molecule construction.

The FloW4all Resource Center, emerging from the Center for Integrated Technology and Organic Synthesis at the University of Liège, provides a dedicated platform to support the development and implementation of continuous flow processes for industrial applications. This presentation highlights successful collaboration models with industrial partners, demonstrating how expertise can accelerate process innovation. Three representative case studies will be presented, each showcasing a distinct type of chemical transformation and the specific reactor technology required for its optimal implementation. These examples illustrate how diverse reaction classes, ranging from fast, exothermic lithiation–addition steps to superheated or high-pressure conditions, demand tailored reactor designs and operating conditions. Together, they underline the importance of maintaining a broadly equipped facility capable of addressing varied process development needs, from microfluidic optimization to pilot-scale demonstration. The FloW4all model exemplifies how a center combining strong expertise in organic synthesis with advanced knowledge in flow chemistry can design synthetic routes and implement continuous processes that exploit the benefits of flow technology from the very beginning of development.

This talk highlights recent progress in using kinetic analysis and flow reactor design to improve the performance of photocatalytic and biocatalytic processes. In flow photocatalysis, large irradiation windows are often needed, but challenges such as scale-up and broad residence time distribution can limit efficiency. A global optimization approach can help guide reactor design to meet specific performance goals. In flow biocatalysis, enzyme deactivation is a key issue. Kinetic modeling provides valuable insights to design more stable and efficient systems. Case studies will be shared to show how combining kinetic modeling with optimization strategies can lead to more effective flow-based catalytic processes.

This presentation introduces continuous-flow recycling process of LIB-sourced critical metals. The rapid rise of e-waste is projected to reach 74 million tonnes by 2030 including a sharp increase in spent lithium-ion batteries (LIBs), expected to exceed 136,000 tonnes in Australia by 2036. Continuous-flow processing offers process efficiency, sustainability, and scalability for leaching and extraction of LIB-sourced critical metals like Co and Ni; thus, being a viable alternative to traditional batch processing. This study explores and integrates upstream leaching, and then, downstream extraction for the recovery of Co and Ni from industrial black mass derived from lithium battery composites. Our flow process concept, the Coiled Flow Inverter (CFI), intensifies by enhanced mass transfer via Dean forces using commercial continuous-flow reactors, at hand at different scales (Stoli-Chem, Corning, Amar). The bespoke challenge of the leaching process conducted is a proper conduct of the solid-liquid flow. CFD simulations revealed how solid–liquid flow slurries can change—from irregular (colliding) to regular (swarm) particle dynamics—that affects mixing and interfacial renewal; in analogy to the lift-up of bubble swarm flows in gas-liquid bubble columns. Batch leaching was optimised to completion within only 5 minutes at 70 °C, achieving ~98% Ni and ~40% Co recovery for a Ni-rich (55-wt%) LIB black mass. Similar results were obtained for Co-rich (63-wt%) LIB black mass; both masses are from industrial sources. With those achievements, the process is now switched from mineral acids to a bio-derived lixiviant from pinewood, produced by Xylogic Pty Ltd, a company of our co-author Kwong, for which we have assessed superior environmental metrics via circularity and LCA metrics.

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Bisphenol-A polycarbonate (BPA-PC), widely used in consumer and industrial applications, can be depolymerized using a mixture of ethylene glycol and a catalyst into bisphenol-A (BPA) for the synthesis of new plastics. Quantitative depolymerization of BPA-PC into BPA was achieved in a coiled flow inverter (CFI, i.d. 2 mm, o.d. 3 mm) reactor, enabling superior performance compared to batch operation.

Scale-up of microreactor-based flow chemistry has attracted growing interest. Generally, the small feature size of a microreactor enables not only process intensification but also low throughput. Herein, design of macro-microreactor is reported to allow for both similar or even stronger microscale effect and lower pressure-drop in contrast to a microreactor. The characteristic sizes of the macro-microreactors are expanded into more than 3,000 μm by incorporating the optimized internals. The macro-microreactor could be applied in organic and polymer reactions and separations.

The development of pH-universal electrocatalysts for the oxygen evolution reaction (OER) is vital for future energy conversion. Here, we presents a data-driven approach combining a Bayesian optimization with plasma surface engineering to construct a RuO₂/W-Co₃O₄ composite catalyst. The material was synthesized via a four-step strategy involving hydrothermal growth, plasma treatment, impregnation, and calcination. By leveraging Bayesian optimization, we efficiently navigated the complex parameter space to identify optimal conditions with minimal experimental runs. The resulting catalyst exhibited uniform dispersion of active species and remarkable OER performance across acidic, neutral, and alkaline solution environments. This study not only demonstrates the power of AI-assisted synthesis optimization but also offers a reproducible, scalable route toward high-performance, pH-universal electrocatalysts. This approach provides valuable insights into the relationship between synthesis conditions and catalytic function, paving the way for rational catalyst design in flow-compatible electrochemical energy systems.

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Professor Volker Hessel is key opinion leader in the Flow Chemistry Field and is Applying Research from his Group into Important Problems for Space Flight and Commercialization in Space.

This presentation introduces a digital twin (DT) framework for lettuce growth across extreme environments—from Earth-based climate stress to future extreme conditions in space agriculture. Future climate (Climate 2050) and space extremes can only be modeled. This is why this study designed a ‘physical-twin couple’, measuring real-time weather data from six climate zones, and repeated these in a growth chamber; “virtually changing from one climate to other” every week. Various machine learning (ML) models (regressors) were validated to predict the biomass from lettuce growth; meaning these ML models can applied for above mentioned future studies. This study is one step towards our recently achieved full-loop autonomous digital twin; a holistic methodology for numerous space applications. Real-time monitoring via camera-based feedback loop sends program-binarized data over IoT to an ML program. This informs Multi-Agent Generative Systems (MAGS) to assist autonomous decision-making. MAGS-DT are one foundational step toward resilient food production for long-term space missions.

Securing a reliable food supply is a cornerstone for sustaining human life beyond Earth. This work explores how lunar regolith could serve as a local source of essential nutrients—phosphorus (P) and potassium (K)—to reduce reliance on Earth-based transport. Using acid leaching on lunar regolith simulants, we evaluated the impact of reaction time, temperature, and acid type, with ICP-MS confirming nutrient concentrations. Results reveal that oxalic acid dramatically boosts P recovery, while K extraction remains consistent across acids, and simulants with higher basalt content performed best. These insights advance in-situ resource utilization strategies, bringing us closer to closed-loop agricultural systems for future lunar habitats.