Continuous flow production of bioactive ceria quantum dots: New paradigms to the effect of process parameters on surface oxygen vacancy tuning

Precisely monitored nucleation-growth kinetics for governing the size, surface chemistry, and sought-after attributes of quantum dots (QDs) for large-scale manufacturing remains a formidable challenge. This study evinces the importance of ultrafast mixing and high heating rates for rapid nucleation, particularly in synthesizing monodispersed QDs with enriched surface defects. Recently, cerium oxide (CeO2) nanostructures have gained prominence in antioxidant therapy owing to the co-existence of Ce3+ and Ce4+. However, current batch processes lack scalability, reproducibility, and control over the reaction kinetics, key for fine-tuning the surface defect-driven properties of CeO2 nanostructures. Addressing this knowledge gap, we demonstrate a unique, sustainable, continuous flow platform that allows simultaneous engineering of surface oxygen vacancies (VO●) and regulates the size of L arginine functionalized CeO2 QDs (VO●-rich L-arg-CeO2 QDs). Introduction of the helical coil reactor regulated by dean vortices yields monodispersed QDs with enhanced Ce3+/Ce4+ ratio and VO● at the surface. Through various experimental methodologies, we showed how adjusting temperature, flowrate, and pH enables achieving the desirable size (3 nm), thereby bestowing an optimal surface Ce3+ and VO● fractions, pivotal for size-dictated photo-response, physiochemical properties, and biofunctionality of the QDs. The abundant surface VO● (72%) entails narrowing of the band gap (~ 2.5 eV), resulting in unprecedented photothermal response (ΔT = 19.7±0.6°C) and photoluminescence, features not typically found in defect-free conventional CeO2 nanostructures. With a strategic combination of process parameters, the defect-rich material system displayed excellent biocompatibility (95.6%), and antioxidant efficacy on human keratinocyte (HaCaT) cells, and long-term stability (ζ = -29±1.5 mV) in suspensions, even after 120 days. This economical, high throughput continuous flow platform for fabricating biofunctionalized VO●-rich L-arg-CeO2 QDs outperforms conventional batch processes, opening numerous possibilities for lab-to-clinic translation in the fight against oxidative stress-related disorders.