Abstract
Ultrasmall inorganic nanoparticles (sub-5 nm) have unique biomedical advantages due to rapid clearance, enhanced imaging contrast, and potent therapeutic properties. However, current synthesis methods are limited by low throughput, polydispersity, and reliance on harsh conditions such as organic solvents or high temperatures. We report a scalable, single-step aqueous synthesis using a confined impinging jet mixer (CIJM) that produces size-controlled, clinically relevant nanoparticles, including silver sulfide, silver telluride, cerium oxide, and iron oxide, under ambient conditions. The resulting nanoparticles are homogeneous, stable, and preserve their functional biological properties. We demonstrate consistent performance across scales, establishing the CIJM as a versatile and reproducible method for producing ultrasmall inorganic nanoparticles suitable for clinical translation and high-throughput biomedical applications.
Data availability
The authors confirm that the data supporting the findings of this study are available within Zenodo at [https://doi.org/10.5281/zenodo.17592975](https:/doi.org/10.5281/zenodo.17592975) .
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Acknowledgements
The authors would like to acknowledge the staff of the Electron Microscopy Resource Lab, especially S. Molugu, B. Zhou, and I. Martynyuk, for their assistance in acquiring transmission electron micrographs. We also thank E. Blankemeyer for his assistance with micro-CT imaging. Additionally, we thank D. Burney for his assistance with ICP-OES and we would like to thank S. Szewczyk for his assistance with XRD. Finally, we thank the Materials Characterization Core at Drexel University, especially D. Barbash, for his assistance with XPS experiments.
Disclosures
DPC and ADAM are named as inventors on patent applications concerning silver-based contrast agents. They also hold stock in Daimroc Imaging, a company that is seeking to commercialize such agents. DPC and HK are named as inventors on patent applications concerning iron oxide-based nanoparticles. DI is named as an inventor on patent applications concerning methods of microfluidic nanoparticle production.
Funding
The authors gratefully acknowledge support from the NIH via R01 CA291880 (DPC), R01-EB036942 (DPC) and R01-DE025848 (HK).
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The project was designed by A.K., H.K., and D.P.C. The experiments for data acquisition performed by A.K., M.G., H.H., K.L.L.R., N.P., K.M., D.N.R.B., P.S.M., A.R.H., P.S., Z.X., J.K., H.K., and D.P.C. Data analysis was performed by A.K., M.G, H.H., K.L.L.R., N.P., A.D.A.M., D.I., H.K., and D.P.C. A.K and D.P.C. wrote the manuscript. All authors were involved in the approval of the manuscript.
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DPC and ADAM are named as inventors on patent applications concerning silver-based contrast agents. They also hold stock in Daimroc Imaging, a company that is seeking to commercialize such agents. DPC and HK are named as inventors on patent applications concerning iron oxide-based nanoparticles. DI is named as an inventor on patent applications concerning methods of microfluidic nanoparticle production.
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Kian, A.C., Gupta, M., Hong, H. et al. Scalable flow synthesis of ultrasmall inorganic nanoparticles for biomedical applications via a confined impinging jet mixer. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41509-z
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DOI: https://doi.org/10.1038/s41598-026-41509-z