Continuous Flow Drug Manufacturing in Africa
Paul Watts, Distinguished Professor and Research Chair, Nelson Mandela University, South Africa

While Africa has a variety of companies that formulate medicines it has very little active pharmaceutical ingredient (API) manufacturing, with the consequence that these need to be imported. This results in increased drug costs, making medications unaffordable to most patients in Africa.  Economic, social and political stresses have been witnessed all over the world during the COVID-19 pandemic. In particular, drug shortages and inaccessibility is one of the many results of disruption of supply chains due to the shutdown of manufacturing activity, as well as export restrictions and bans by other countries. 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 examples will be presented.

Intensification and Electrification of Flow Chemistry
Thomas Wirth, Professor, Cardiff University, United Kingdom

The advantages of increased mixing of biphasic reaction mixtures in flow offers great potential compared to conventional flask techniques, especially when combined with microwave irradiation or phase transfer catalysis. The presentation will also illustrate that metal-catalyzed reactions and enzyme-promoted transformations can be performed advantageously in biphasic systems. The development of a microreactor for electrochemistry including several applications will be discussed.

Novel Microfluidic Platforms for Scale-Up Production and Autonomous Self-Optimization
Dong Pyo Kim, Yonsan Chaired Professor, Pohang University of Science And Technology (POSTECH), Korea South

Flow chemistry in the confined microfluidic space enables easy up-scaling production at precise controlled conditions. In the talk, we show the assembly of 16 numbering-up 3D printed metal microreactor to render high productivity up to 20 g for 10 min operation of subsecond ultrafast chemistry. And, hexagon-shaped 3D printed polymer module of photomicroreactor with solar concentrator leaded to facile assembly into serial and radial reconfiguration for high throughput of synthesis. In addition, for scalable production of emulsions, compact 3D printed droplet generator was devised by array of 40 drop-makers with a 3D void geometry and a flow distributor, producing microgels and microparticles. Finally, we explore ultrafast flow chemistry by autonomous self-optimizing platform that accelerates the optimization and screening of complex chemistry.

Organic Synthesis Enabled by Catalytic Flow Methods
Shu Kobayashi, Professor, The University of Tokyo, Japan

In synthesis, flow methods have several advantages over batch methods in terms of environmental compatibility, efficiency, and safety. Wastes derived from work-up processes can be minimized or omitted altogether by performing organic transformations in flow. Equipment for chemical manufacturing can be designed to be smaller, which would enable significant savings in space and costs. In addition, the differences between batch and flow reactors, which are the large surface to volume ratios and the rapid mixing/quenching of reagents, should make chemical productions safer and more efficient. While continuous-flow practices have been adopted in the petrochemical and bulk chemical industries, its applications in fine chemical production have been limited. It was believed that synthesis by flow methods could be applicable for the production of simple gasses such as ammonia, but was difficult to apply to the preparation of complex molecules such as active pharmaceutical ingredients (APIs). This lecture will discuss recent advances in organic synthesis enabled by continuous-flow methods. In particular, the development of heterogeneous catalysts in multi-step continuous-flow reactions (sequential flow reactions) for the synthesis of complex organic molecules will be highlighted.

It's a Machines World: Challenges and Opportunities in Automated Polymer Synthesis
Tanja Junkers, Professor, School of Chemistry, Polymer Reaction Design group, Monash University, Australia

Contemporary macromolecular chemistry has matured to a point where virtually any polymer structure can be synthesized via combinations of controlled polymerization approaches, post-polymerization modification and efficient ligation strategies. Still, often large hurdles have to be overcome to take the next step in research, that is being able to provide such complex materials reliably on significant scale for use in advanced applications. A solution to this problem is to make use of continuous flow synthesis techniques. Flow reactors are associated with high reproducibility, intrinsically simple reaction scale-up and improved product qualities due to significant reduction of side reactions. Being an established method especially in the pharmaceutical chemistry domain, full potential with regards to macromolecular synthesis did not unfold until very recently. Among others, the benefits of using online-monitoring, reactor automation and machine-learning will be discussed and the development of fully autonomous based reactor systems presented. Also polymer self-assembly itself can largely benefit from flow operation, and first advances in this area will be presented. The potential of flow chemistry for preparative macromolecular chemistry will be discussed and explored on the example of polymerization. Further, the possibility to build reactor cascades and the advantages of online-monitoring will be highlighted. Machine-assisted synthesis of polymers is shown to be superior in accuracy in synthesis. Generally, the introduction of smart algorithms in synthesis control opens avenues into the digital chemistry space, and challenges and opportunities in this realm will be discussed.

Flow Synthesis of Phosphorus Nanocomposites for Controlled Fertilizer Release and Wheat Growth
Volker Hessel, Professor,, The University of Adelaide, Australia

Flow chemistry has shown distinct advantages in the synthesis of nanomaterials. Here, we investigate flow chemistry for the synthesis of nanofertilizers which has been so far less reported in literature. New generations of P fertilizer have been developed in batch synthesis. In 2020, Hessel et al. proposed a process for leaching phosphorus from mimicked moon crust using a re-entrance flow microfluidic device and using this to fertilize lettuce in “space greenhouses”, and recycling phosphate from lettuce root via burning in a furnace.
 
In this research, a coiled inverted flow system, was used to prepare a slow released P-containing fertilizer and this system also allowed the direct adsorption of low molecular weight organic acid anions (LMWOAs). Citrate ions, as the chosen LMWOAs, were incorporated with the above prepared phosphorus fertiliser to form a compound fertilizer capable of releasing nutrients in a slow manner and reducing the P binding sites in P deficient soil. The nutrient performance was investigated in a model soil mixture. The system allowed the one-stage production of LMWOAs adsorbed apatite with the maximum adsorption capacity of 0.19 gcitrate.gaptite-1 in a continuous manner. The presence of citrate ions in the prepared material increased the P availability in the model soil mixture by 2.6 times compared to commercial apatite. After 14 days of application, about 57% of P in the prepared fertilizer was released into the soil solution.  

We will also report about an extension of the approach here towards nanoencapsulation by chitosan and using more innovative continuous-flow reactor equipment, including the Corning and StoliFlow reactors. We will compare the wheat growth efficiency of the flow-made phosphorus nanofertilizers with plasma-made nitrogen (carbon dot and solution-based) fertilizers, which we also prepare.