Genetic physical unclonable functions in human cells
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A physical unclonable function (PUF) is a physical entity that provides a measurable output that can be used as a unique and irreproducible identifier for the artifact wherein it is embedded. Popularized by the electronics industry, silicon PUFs leverage the inherent physical variations of semiconductor manufacturing to establish intrinsic security primitives for attesting integrated circuits. Owing to the stochastic nature of these variations, photolithographically manufactured silicon PUFs are impossible to reproduce (thus unclonable). Inspired by the success of silicon PUFs, we sought to create the first generation of genetic PUFs in human cells. We demonstrate that these PUFs are robust (i.e., they repeatedly produce the same output), unique (i.e., they do not coincide with any other identically produced PUF), and unclonable (i.e., they are virtually impossible to replicate). Furthermore, we demonstrate that CRISPR-engineered PUFs (CRISPR-PUFs) can serve as a foundational principle for establishing provenance attestation protocols.
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Biological physical unclonable functions exploit genetic differences in the process of engineering cell lines to provide robust, unique, and irreproducible identifying signatures of cells.
“Similarly, biological PUFs exploit genetic differences in the process of engineering cell lines to provide robust, unique, and irreproducible identifying signatures of cells [147].”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [147]
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Check your cultures! A list of cross‐contaminated or misidentified cell lines
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“For example, a major German cell repository has reported that 20% of its human cell line stocks were cross-contaminated with other cell lines (36), and the China Center for Type Culture Collection demonstrated that 85% of cell lines in their repository, supposedly established from primary isolates, were actually HeLa…”
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The history, landscape, and outlook of human cell line authentication and security
Harbut, E., Makris, Y., Pertsemlidis, A., & Bleris, L. (2024) · SLAS Discovery · doi:10.1016/j.slasd.2024.100194 · Cited by 8 · see citing works
Self-citation
- Authors
- Li, Y., Bidmeshki, M. M., Kang, T., Nowak, C. M., Makris, Y., & Bleris, L.
- Affiliations
- The University of Texas at Dallas (US)
- Corresponding author
- Makris, Yiorgos
- Bleris, Leonidas
- Venue
- Science Advances
- Published
- 2022-05-06
- Volume
- 8
- Issue
- 18
- Pages
- eabm4106-eabm4106
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC9067934
- OpenAlex
- W4229000547
- Cited by
- 12
- References
- 3
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Computer Science › Hardware and Architecture › Physical Unclonable Functions (PUFs) and Hardware Security
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Biological Computing
- Keywords
- physical unclonable functions, human cells, cell identity, biocomputing, biosecurity
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