High-Throughput Quantification of Nanoparticle Degradation Using Computational Microscopy and Its Application to Drug Delivery Nanocapsules

Aniruddha Ray, Shuoran Li, Tatiana Segura, Aydogan Ozcan

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Design and synthesis of degradable nanoparticles are very important in drug delivery and biosensing fields. Although accurate assessment of nanoparticle degradation rate would improve the characterization and optimization of drug delivery vehicles, current methods rely on estimating the size of the particles at discrete points over time using, for example, electron microscopy or dynamic light scattering (DLS), among other techniques, all of which have drawbacks and practical limitations. There is a significant need for a high-throughput and cost-effective technology to accurately monitor nanoparticle degradation as a function of time and using small amounts of sample. To address this need, here we present two different computational imaging-based methods for monitoring and quantification of nanoparticle degradation. The first method is suitable for discrete testing, where a computational holographic microscope is designed to track the size changes of protease-sensitive protein-core nanoparticles following degradation, by periodically sampling a subset of particles mixed with proteases. In the second method, a sandwich structure was utilized to observe, in real-time, the change in the properties of liquid nanolenses that were self-assembled around degrading nanoparticles, permitting continuous monitoring and quantification of the degradation process. These cost-effective holographic imaging based techniques enable high-throughput monitoring of the degradation of any type of nanoparticle, using an extremely small amount of sample volume that is at least 3 orders of magnitude smaller than what is required by, for example, DLS-based techniques.
Original languageEnglish (US)
Pages (from-to)1216-1224
Number of pages9
JournalACS Photonics
Issue number5
StatePublished - May 2 2017
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: The Ozcan Research Group at UCLA gratefully acknowledges the support of the Presidential Early Career Award for Scientists and Engineers (PECASE), the Army Research Office (ARO; W911NF-13-1-0419 and W911NF-13-1-0197), the ARO Life Sciences Division, the National Science Foundation (NSF) CBET Division Biophotonics Program, the NSF Emerging Frontiers in Research and Innovation (EFRI) Award, the NSF EAGER Award, the NSF INSPIRE Award, NSF Partnerships for Innovation: Building Innovation Capacity (PFI:BIC) Program, Office of Naval Research (ONR), the National Institutes of Health (NIH), the Howard Hughes Medical Institute (HHMI), Vodafone Americas Foundation, the Mary Kay Foundation, Steven & Alexandra Cohen Foundation, and KAUST. This work is based upon research performed in a laboratory renovated by the National Science Foundation under Grant No. 0963183, which is an award funded under the American Recovery and Reinvestment Act of 2009 (ARRA). The authors also acknowledge Alborz Feizi for his help with the LabVIEW code, Derek Tseng for his help with the production of 3D CAD images, and Dr. Euan McLeod for his help with the particle sizing code. The Segura Laboratory gratefully acknowledges the funding from the National Institutes of Health R01-NS079691.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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