Molecular communication (MC) is envisioned to realize nanotheranostics as an emerging diagnostic tool to improve existing treatment modalities. Phase separation (PS) is a complex time-dependent process responsible for discrimination of two independent phases from a single homogeneous mixture. Recently, PS was revealed to be the fundamental mechanism behind formation and organization of the living cells. Inspired by PS mechanisms in nature, we establish a novel modulation scheme for MC which encodes the information in the dispersion of molecules diffusing in the environment. Hence, the diffusion distribution can be considered as carriers of molecules. To evaluate the performance of this communication scheme, a dual-carrier diffusion-division modulation (DDM) is adopted where each carrier can be effectively modeled by superposition of multiple independent phases. We derive the theoretical bit error rate (BER) of the proposed DDM scheme which is validated by particle-based simulation (PBS). Furthermore, performance of the multi-carrier DDM scheme is compared to the well-known on-off keying (OOK) modulation scheme (as the most relevant benchmark) and pulse-position modulation (PPM) scheme. It is shown that performance of the DDM-based MC system can be boosted by increasing the transmission power and/or using multiple carriers. Interestingly, the proposed DDM is a covert modulation scheme since any other receiver cannot decode the transmitted signal by just counting the number of received molecules unless having the shared key. Moreover, the DDM scheme requires a receiver that exploits the displacement distribution of the molecules inside the receiver to infer about the tranmitted bit. We strongly believe that this concept will introduce novel types of communication schemes more compatible with biological microenvironments. Also, this work establishes the foundation for more complex orthogonal multi-carrier DDM schemes which can potentially unlock novel cellular sensing mechanisms in biology.

Intercellular communication is crucial for organ function, with extracellular vesicles (EVs) acting as common messengers for almost all cells. This study proposes a novel EV-mediated intercellular communication system that uses a modulation technique regulated via altered intracellular-cytosolic calcium dynamics regulation. As a case study, intercellular communication within a cardiac muscle is considered with cardiomyocyte cells serving as transceivers. Through molecular communication theory, we propose a comprehensive model addressing EV release kinetics, propagation, degradation, and uptake. A linear time-invariant Poisson channel model is developed and closed-form expressions, verified through particle-based simulations, are derived for EV detection probabilities at the receiver. A closed-form bit error probability is derived and validated through Monte Carlo simulations. By selecting an optimal receiver threshold: 1) bit error rate (BER) in EV-mediated intercellular communication is robust against adverse effects from cardiac disorders, such as myocardial infarction; 2) transmitter design can be optimized by minimizing actuation signal amplitude and pulse width; 3) BER stays stable across heart rates for different distances, demonstrating the robustness of EV-mediated communication. This study enhances our ability to engineer precise and reliable intra-body cardiac communications, which may offer valuable applications for cardiovascular disease treatment, for example, the realization of biological lead-less multi-nodal pacemakers.

Treating brain diseases with therapeutic particles imposes significant challenges as particles are usually too large to traverse the gaps between endothelial cells in the blood-brain barrier (BBB). Focused ultrasound (FUS) for disruption of the BBB has been proposed as a remedy. However, the extent of disruption and the efficiency of the particle delivery to the regions of interest are highly dependent on FUS sonication parameters. This study investigates the effects of not only FUS sonication parameters but also the therapeutic particle admin-istration scheme by exploiting communication-theoretic channel modeling. Specifically, the particle pathways from blood vessels to hallmarked spots in the brain interstitial space are abstracted as a single-input-multiple-output (SIMO) channel. The channel outputs are then examined through the lenses of communication-theoretic measures such as channel gain, transmission efficiency, signal-to-noise ratio, and bit error ratio. The numerical results are displayed utilizing the available clinical data on six patients with brain cancer. The results show that the proposed approach could be exploited in future studies to maximize the efficacy of the treatment and minimize adverse effects.

This paper presents spatial diversity techniques applied to multiple-input multiple-output (MIMO) diffusion-based molecular communications (DBMC). Two types of spatial coding techniques, namely Alamouti-type coding and repetition MIMO coding are suggested and analyzed. In addition, we consider receiver-side equal-gain combining, which is equivalent to maximum-ratio combining in symmetrical scenarios. For numerical analysis, the channel impulse responses of a symmetrical 2 × 2 MIMO-DBMC system are acquired by a trained artificial neural network. It is demonstrated that spatial diversity has the potential to improve the system performance and that repetition MIMO coding outperforms Alamouti-type coding.