Bio-Protocol Watermarking on Digital Microfluidic Biochips

Advancements in digital microfluidic biochip (DMFB) technologies are paving the way for low-cost and automated platforms for implementing bio-protocols. However, the deployment of DMFBs outside of controlled settings will make them vulnerable to intellectual property (IP) theft. Bio-protocol development requires large investments for cross-domain innovations in biochemical analysis, microfluidics, and cyberphysical systems. We propose a watermarking technique for bio-protocol IP protection-a first in microfluidics-that hierarchically embeds a secret signature across these domains. Such a signature can be exclusively attributed to the owner (like a hash). The proposed solution takes into account the inherent variability in domain-specific parameters such as mixing ratio, sensor calibration, and incubation time. We describe watermarking techniques of varying complexities for different bio-protocol steps. These include watermarking for bio-protocol synthesis parameters and the cyberphysical systems control path parameters. A watermarking scheme based on integer linear programming is proposed for the sample-preparation step of a bio-protocol. The practicality of our solution is demonstrated through case studies involving an immunoassay and several mixing ratios required in the sample-preparation process of bio-protocols. The effectiveness of this approach is evaluated through various security metrics: proof of ownership score, the probability of successful tampering of the watermark, and the probability of coincidence. We also analyze the integrity of the watermark against various possible attacks: brute force search, the insertion of a new watermark, and the watermarking of more parameters.