Biocompatible optical physically unclonable function hydrogel microparticles for on-dose authentication

Mengmeng Zhang, Aparna Raghunath, An Zhao, Huseyin Burak Eral*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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On-dose authentication (ODA) enhances security by incorporating customized molecular or micro-tags into each pill, preventing counterfeit products in genuine packages. ODA's security relies on tag non-replication and non-reverse engineering. Combining ODA with graphical Physical Unclonable Functions (PUF) promises maximum security. PUF uses intrinsic micro or nanoscale randomness as a unique ‘fingerprint’. However, current graphical PUFs have limitations like specific illumination requirements and the use of toxic materials, restricting their use in pharmaceuticals. In this study, we propose a novel approach called on-dose PUF. This method involves embedding microspheres randomly within micro biocompatible hydrogel particles. We showcase two distinct types of such on-dose PUFs. The first type utilizes randomly distributed superparamagnetic colloids (SPC) of identical diameters, while the second type utilizes vortexed sunflower oil drops of various diameters. The diameter and coordinates of the microspheres serve as input for generating cryptographic keys. A universal circle identification and binning program is used for extracting this information. One advantage of this approach is that it enables imaging using white light illumination and low-magnification microscopy, as color and signal intensity information are not crucial. This method enables patients to verify their medication by using their mobile phones from home. To assess the performance of the proposed on-dose PUF, we conducted canonical investigations on the single-diameter system. This system can only generate one layer of cryptographic keys, making it potentially more vulnerable than the multiple-diameter system. However, the single-diameter system successfully passed NIST Statistical tests and exhibited sufficient randomness, ideal bit uniformity, Hamming distance, and device uniqueness. Furthermore, we found that the encoding capacity of the single-diameter system was 9.2×1018, providing ample labeling potential.

Original languageEnglish
Article numbere22895
Number of pages11
Issue number1
Publication statusPublished - 2024


Funding Information:
This work is part of the research program open technology scheme with project number P80384 , which is financed by the Dutch Research Council (NWO). Mengmeng Zhang was supported by a scholarship granted by the China Scholarship Council (CSC, Grant No. 201808370175 ).


  • Anti-counterfeiting
  • Biocompatible
  • Colloid
  • Emulsion
  • Hydrogel
  • On-dose authentication
  • Optical PUF
  • Physical unclonable function


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