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Scalable flow synthesis of ultrasmall inorganic nanoparticles for biomedical applications via a confined impinging jet mixer
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  • Published: 26 February 2026

Scalable flow synthesis of ultrasmall inorganic nanoparticles for biomedical applications via a confined impinging jet mixer

  • Andrea C. Kian1,
  • Mahima Gupta2,
  • Heeju Hong3,
  • Kálery La Luz Rivera4,
  • Nil Pandey2,5,
  • Katherine J. Mossburg1,
  • Derick N. Rosario-Berrios2,
  • Portia S. N. Maidment2,
  • Andrew R. Hanna1,
  • Priyash Singh2,
  • Zhenting Xiang5,6,
  • Jay Kikkawa7,
  • David Issadore1,
  • Andrew D. A. Maidment2,
  • Hyun Koo1,5,6 &
  • …
  • David P. Cormode1,4,6,8 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biotechnology
  • Chemistry
  • Materials science
  • Nanoscience and technology

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).

Author information

Authors and Affiliations

  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA

    Andrea C. Kian, Katherine J. Mossburg, Andrew R. Hanna, David Issadore, Hyun Koo & David P. Cormode

  2. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    Mahima Gupta, Nil Pandey, Derick N. Rosario-Berrios, Portia S. N. Maidment, Priyash Singh & Andrew D. A. Maidment

  3. Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA

    Heeju Hong

  4. Department of Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, USA

    Kálery La Luz Rivera & David P. Cormode

  5. Divisions of Pediatric Dentistry & Community Oral Health, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Nil Pandey, Zhenting Xiang & Hyun Koo

  6. Center for Innovation & Precision Dentistry (CiPD), School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA

    Zhenting Xiang, Hyun Koo & David P. Cormode

  7. Department of Physics, University of Pennsylvania, Philadelphia, PA, USA

    Jay Kikkawa

  8. Department of Cardiology, University of Pennsylvania, Philadelphia, PA, USA

    David P. Cormode

Authors
  1. Andrea C. Kian
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  2. Mahima Gupta
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  3. Heeju Hong
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Contributions

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.

Corresponding author

Correspondence to David P. Cormode.

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Competing interests

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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  • Received: 15 November 2025

  • Accepted: 20 February 2026

  • Published: 26 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-41509-z

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Keywords

  • Microfluidics
  • Nanoparticles
  • Silver sulfide
  • Silver telluride
  • Cerium oxide
  • Iron oxide
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