The Chorioallantoic Membrane Model: A 3D in vivo Testbed for Design and Analysis of MC Systems

TL;DR

The paper addresses the gap between theoretical molecular communications concepts and practical in vivo validation by introducing the chorioallantoic membrane CAM as a flexible 3D in vivo MC testbed. It proposes an approximate closed‑loop diffusion–advection model for the CAM vascular system, derived from the Aris‑Taylor dispersion framework and extended to a wrapped normal distribution on a finite loop, and validates it against particle‑based simulations. An experimental study using the fluorescent dye ICG demonstrates the ability to fit the model to CAM injection–distribution dynamics across multiple eggs, yielding physically plausible estimates for $D_ ext{eff}$, $v_ ext{eff}$, $L_ ext{eff}$, and $d_ ext{rx}$. The results support CAM as a realistic testbed for MC system design and optimization, while highlighting areas for future work such as time‑varying flow, absorption, and multi‑RX scenarios that reflect more complex in vivo environments.

Abstract

Molecular Communications (MC) research is increasingly focused on applications within the human body, such as health monitoring and drug delivery. These applications require testing in realistic and living environments. Thus, advancing experimental MC research to the next level requires the development of in vivo experimental testbeds. In this paper, we introduce the Chorioallantoic Membrane ( CAM ) model as a versatile 3D in vivo MC testbed. The CAM is a highly vascularized membrane formed in fertilized chicken eggs and has gained significance in various research fields, including bioengineering, cancer research, and drug development. Its versatility, reproducibility, and realistic biological properties make the CAM model perfectly suited for next-generation MC testbeds, facilitating the transition from proof-of-concept systems to practical applications. We provide a comprehensive introduction to the CAM model, its properties, and its applications in practical research. Additionally, we present a characterization of the CAM model as an MC system. As a preliminary experimental study, we investigate the distribution of fluorescent molecules in the closed-loop vascular system of the CAM model. We also derive an approximate analytical model for the propagation of molecules in closed-loop systems, and show that the proposed model is able to approximate molecule propagation in the CAM model.

Figures (10)

• Figure 1: Schematic illustration of the CAM model consisting of the chicken embryo, the yolk bag, and the CAM established. Furthermore, a tumor is engrafted on the CAM (Created with BioRender.com).
• Figure 2: Snapshots of the distribution of fluorescent molecules in the vascular system of the CAM model directly after injection via a syringe (left) and after a few seconds fully distributed (right).
• Figure 3: CAM model for tumor and distribution studies. Left: ICG injection into CAM vessels at $t = 0~min$ and distribution in the vascular system. Right: ICG is accumulated in tumor tissue after $\sim \!15~min$Ettner2024.
• Figure 4: Interpretation of the CAM model as closed-loop MC system with TX, e.g., a syringe or a tumor, several nRX, e.g., yolk bag, organs, tumor tissue, and several sRX (Created with BioRender.com).
• Figure 5: Application-dependent specializations of system in Fig. \ref{['fig:cam-mc']}. (a): Study molecule distribution and accumulation, yolk bag and organs are RX. (b): Study molecule accumulation in tumors, engrafted tumor tissue is the RX, and the yolk bag and organs are part of the channel. (c): Anomaly detection or monitoring tasks, engrafted tumor tissue is the TX (Created with BioRender.com).