Electrophoretic Molecular Communication With Piecewise Constant Electric Field.

This paper studies a novel electrophoretic molecular communication (EMC) framework utilizing a piecewise constant electric field. EMC is a particular type of molecular communication that exploits electric fields to induce the movement of charged particles to enhance communication performance. Our previous work proposed an EMC framework utilizing a time-varying electric field that exponentially changes; however, the field with such a complicated shape might be challenging to be implemented in practice. Thus, this paper proposes a new EMC approach exploiting a piecewise constant electric field that can be readily implemented via, e.g., an on/off switch method. We formulate two optimization problems to design the electric field based on different objectives: minimizing a mean squared error and minimizing a bit interval. The solutions of each, such as optimal on-off timings and corresponding strengths of the constant electric fields, are obtained through the Lagrange multiplier approach and the geometric programming, respectively. The Monte Carlo simulation results verify that the proposed piecewise constant electric field significantly reduces the bit error rate relative to the constant field benchmark while performing less well, but not significantly, than the exponential field benchmark.

Bacterial Receiver Prototype for Molecular Communication Using Rhamnose Operon in a Microfluidic Environment.

Bacterial populations are promising candidates for the development of the receiver and transmitter nanomachines for molecular communication (MC). A bacterial receiver is required to uptake the information molecules and produce the detectable molecules following a regulation mechanism. We have constructed a novel bacterial MC receiver using an inducible bacterial L-rhamnose-regulating operon. The proposed bacterial receiver produces green fluorescent protein (GFP) in response to the L-rhamnose information molecules following a quite fast regulation mechanism. To fabricate the receiver, the bacterial population has been transformed using a plasmid harboring L-rhamnose operon genes and gene expressing GFP in a microfluidic environment. We mathematically model the reception process of information molecules and characterize the model parameters by comparing the simulation results of the model in the employed microfluidic environment and the data obtained from the experimental setup. Based on the experimental results, the receiver is able to switch between different low and high concentrations. This work paves the way for the fabrication and modeling of any bacterial operon-based receiver with any proteins rather than GFP. Further, our experimental results indicate that the proposed bacterial receiver has a faster response to information molecules compared to the previous bacterial receiver based on the quorum sensing (QS) process.

On Mathematical Analysis of Active Drug Transport Coupled With Flow-Induced Diffusion in Blood Vessels.

Blood vessels are flow-induced diffusive molecular channels equipped with transport mechanisms across their walls for conveying substances between the organs in the body. Mathematical modeling of the blood vessel as a molecular transport channel can be used for the characterization of the underlying processes and higher-level functions in the circulatory system. Besides, the mathematical model can be utilized for designing and realizing nano-scale molecular communication systems for healthcare applications including drug delivery systems. In this paper, a continuous-time Markov chain framework is proposed to simply model active transport mechanisms e.g. transcytosis, across the single-layered endothelial cells building the inner vessel wall. Correspondingly, a general homogeneous boundary condition over the vessel wall is introduced. Coupled with the derived boundary condition, the flow-induced diffusion problem in an ideal vessel structure with a cylindrical shape is accurately formulated which takes into account variation in all three dimensions. The corresponding concentration Green's function is analytically derived in terms of a convergent infinite series. Particle-based simulation results confirm the proposed analysis. Also, the effects of system parameters on the concentration Green's function are examined.

Modeling of Modulated Exosome Release From Differentiated Induced Neural Stem Cells for Targeted Drug Delivery.

A novel implantable and externally controllable stem-cell-based platform for the treatment of Glioblastoma brain cancer has been proposed to bring hope to patients who suffer from this devastating cancer type. Induced Neural Stem Cells (iNSCs), known to have potent therapeutic effects through exosomes-based molecular communication, play a pivotal role in this platform. Transplanted iNSCs demonstrate long-term survival and differentiation into neurons and glia which then fully functionally integrate with the existing neural network. Recent studies have shown that specific types of calcium channels in differentiated neurons and astrocytes are inhibited or activated upon cell depolarization leading to the increased intracellular calcium concentration levels which, in turn, interact with mobilization of multivesicular bodies and exosomal release. In order to provide a platform towards treating brain cancer with the optimum therapy dosage, we propose mathematical models to compute the therapeutic exosomal release rate that is modulated by cell stimulation patterns applied from the external wearable device. This study serves as an initial and required step in the evaluation of controlled exosomal secretion and release via induced stimulation with electromagnetic, optical and/or ultrasonic waves.

Diffusive Molecular Communication in Biological Cylindrical Environment.

Diffusive molecular communication (DMC) is one of the most promising approaches for realizing nano-scale communications in biological environments for healthcare applications. In this paper, a DMC system in biological cylindrical environment is considered, inspired by blood vessel structures in the body. The internal surface of the cylinder boundary is assumed to be covered by the biological receptors which may irreversibly react with hitting molecules. Also, the information molecules diffusing in the fluid medium are subject to a degradation reaction and flow. The concentration Green's function of diffusion in this environment is analytically derived which takes into account asymmetry in all radial, axial, and azimuthal coordinates. Employing obtained Green's function, information channel between transmitter and transparent receiver of DMC is characterized. To evaluate the DMC system in the biological cylinder, a simple on-off keying modulation scheme is adopted and corresponding error probability is derived. The particle-based simulation results confirm the proposed analysis. Also, the effect of different system parameters on the concentration Green's function are examined. Our results reveal that the degradation reaction and the boundary covered by biological receptors may be utilized to mitigate intersymbol interference and outperform the corresponding error probability.

Comprehensive Reactive Receiver Modeling for Diffusive Molecular Communication Systems: Reversible Binding, Molecule Degradation, and Finite Number of Receptors.

This paper studies the problem of receiver modeling in molecular communication systems. We consider the diffusive molecular communication channel between a transmitter nano-machine and a receiver nano-machine in a fluid environment. The information molecules released by the transmitter nano-machine into the environment can degrade in the channel via a first-order degradation reaction and those that reach the receiver nano-machine can participate in a reversible bimolecular reaction with receiver receptor proteins. Thereby, we distinguish between two scenarios. In the first scenario, we assume that the entire surface of the receiver is covered by receptor molecules. We derive a closed-form analytical expression for the expected received signal at the receiver, i.e., the expected number of activated receptors on the surface of the receiver. Then, in the second scenario, we consider the case where the number of receptor molecules is finite and the uniformly distributed receptor molecules cover the receiver surface only partially. We show that the expected received signal for this scenario can be accurately approximated by the expected received signal for the first scenario after appropriately modifying the forward reaction rate constant. The accuracy of the derived analytical results is verified by Brownian motion particle-based simulations of the considered environment, where we also show the impact of the effect of receptor occupancy on the derived analytical results.

Ion Channel Based Bio-Synthetic Modulator for Diffusive Molecular Communication.

In diffusion-based molecular communication (DMC), a transmitter nanomachine is responsible for signal modulation. Thereby, the transmitter has to be able to control the release of the signaling molecules employed for representing the transmitted information. In nature, an important class of control mechanisms for releasing molecules from cells utilizes ion channels which are pore-forming proteins across the cell membrane. The opening and closing of the ion channels is controlled by a gating parameter. In this paper, an ion channel based modulator for DMC is proposed which controls the rate of molecule release from the transmitter by modulating a gating parameter signal. Exploiting the capabilities of the proposed modulator, an on-off keying modulation technique is introduced and the corresponding average modulated signal, i.e., the average release rate of the molecules from the transmitter, is analyzed. However, since the modulated signal is random in nature, it may deviate from its average. Therefore, the concept of modulator noise is introduced and the statistics of the modulated signal are investigated. Finally, by assuming a simple transparent receiver, the performance of the proposed on-off keying modulation format is studied. The derived analytical expressions for the average modulated signal are confirmed with particle based simulations. Our numerical results reveal that performance estimates of DMC systems obtained based on the assumption of instantaneous molecule release at the transmitter may substantially deviate from the performance achieved with practical modulators.