In Diffusive Molecular Communication (DMC), information is transmitted by diffusing molecules. Synaptic signaling, as a natural implementation of this paradigm, encompasses functional components that, once understood, can facilitate the development of synthetic DMC systems. To unleash this potential, however, a thorough understanding of the synaptic communication channel based on biophysical principles is needed. Since synaptic transmission critically depends also on non-neural cells, such understanding requires the consideration of the so-called tripartite synapse. In this paper, we develop a comprehensive channel model of the tripartite synapse encompassing a three-dimensional, finite-size spatial model of the synaptic cleft, molecule uptake at the presynaptic neuron and at glial cells, reversible binding to individual receptors at the postsynaptic neuron, and spillover to the extrasynaptic space. Based on this model, we derive analytical time domain expressions for the channel impulse response (CIR) of the synaptic DMC system and for the number of molecules taken up at the presynaptic neuron and at glial cells, respectively. These expressions provide insight into the impact of macroscopic physical channel parameters on the decay rate of the CIR and the reuptake rate, and reveal fundamental limits for synaptic signal transmission induced by chemical reaction kinetics and the channel geometry. Adapted to realistic parameters, our model produces plausible results when compared to previous experimental and simulation studies and we provide results from particle-based computer simulations to further validate the analytical model. The proposed comprehensive channel model admits a wide range of synaptic configurations making it suitable for the investigation of many practically relevant questions, such as the impact of glial cell uptake and spillover on signal transmission in the tripartite synapse.

In Diffusive Molecular Communication (DMC), information is transmitted by diffusing molecules. Synaptic signaling is a natural implementation of this paradigm. It is responsible for relaying information from one neuron to another, but also provides support for complex functionalities, such as learning and memory. Many of its features are not yet understood, some are, however, known to be critical for robust, reliable neural communication. In particular, some synapses feature a re-uptake mechanism at the presynaptic neuron, which provides a means for removing neurotransmitters from the synaptic cleft and for recycling them for future reuse. In this paper, we develop a comprehensive channel model for synaptic DMC encompassing a spatial model of the synaptic cleft, molecule re-uptake at the presynaptic neuron, and reversible binding to individual receptors at the postsynaptic neuron. Based on this model, we derive an analytical time domain expression for the channel impulse response (CIR) of the synaptic DMC system. Our model explicitly incorporates macroscopic physical channel parameters and can be used to evaluate the impact of re-uptake, receptor density, and channel width on the CIR of the synaptic DMC system. Furthermore, we provide results from particlebased computer simulation, which validate the analytical model. The proposed comprehensive channel model for synaptic DMC systems can be exploited for the investigation of challenging problems, like the quantification of the inter-symbol interference between successive synaptic signals and the design of synthetic neural communication systems.

Nanoparticle drug carriers play an important role in facilitating efficient targeted drug delivery, i.e., improving treatment success and reducing drug costs and side effects. However, the mobility of nanoparticle drug carriers poses a challenge in designing drug delivery systems. Moreover, healing results critically depend on the rate and time duration of drug absorption. Therefore, in this paper, we aim to design a controlled-release drug delivery system with a mobile drug carrier that minimizes the total amount of released drugs while ensuring a desired rate of drug absorption during a prescribed time period. We model the mobile drug carrier as a mobile transmitter, the targeted diseased cells as an absorbing receiver, and the channel between the transceivers as a time-variant channel since the carrier mobility results in a time-variant absorption rate of the drug molecules. Based on this, we develop a molecular communication (MC) framework to design the controlled-release drug delivery system. In particular, we develop new analytical expressions for the mean, variance, probability density function, and cumulative distribution function of the channel impulse response (CIR). Equipped with the statistical analysis of the CIR, we design and evaluate the performance of the controlled-release drug delivery system. Numerical results show significant savings in the amount of released drugs compared to a constant-release rate design and reveal the necessity of accounting for drug carrier mobility for reliable drug delivery.

Molecular communication (MC) is a new communication engineering paradigm where molecules are employed as information carriers. MC systems are expected to enable new revolutionary applications, such as sensing of target substances in biotechnology, smart drug delivery in medicine, and monitoring of oil pipelines or chemical reactors in industrial settings. As for any other kind of communication, simple yet sufficiently accurate channel models are needed for the design, analysis, and efficient operation of MC systems. In this paper, we provide a tutorial review on mathematical channel modeling for diffusive MC systems. The considered end-to-end MC channel models incorporate the effects of the release mechanism, the MC environment, and the reception mechanism on the observed information molecules. Thereby, the various existing models for the different components of an MC system are presented under a common framework and the underlying biological, chemical, and physical phenomena are discussed. Deterministic models characterizing the expected number of molecules observed at the receiver and statistical models characterizing the actual number of observed molecules are developed. In addition, we provide the channel models for time-varying MC systems with moving transmitters and receivers, which are relevant for advanced applications such as smart drug delivery with mobile nanomachines. For complex scenarios, where simple MC channel models cannot be obtained from first principles, we investigate the simulation- and experiment-driven channel models. Finally, we provide a detailed discussion of potential challenges, open research problems, and future directions in channel modeling for diffusive MC systems.

In this paper, we consider target detection in suspicious tissue via diffusive molecular communications (MCs). If a target is present, it continuously and with a constant rate secretes molecules of a specific type, so-called biomarkers, into the medium, which are symptomatic for the presence of the target. Detection of these biomarkers is challenging since due to the diffusion and degradation, the biomarkers are only detectable in the vicinity of the target. In addition, the exact location of the target within the tissue is not known. In this paper, we propose to distribute several reactive nanosensors (NSs) across the tissue such that at least some of them are expected to come in contact with biomarkers, which cause them to become activated. Upon activation, an NS releases a certain number of molecules of a secondary type into the medium to alert a fusion center (FC), where the final decision regarding the presence of the target is made. In particular, we consider a composite hypothesis testing framework where it is assumed that the location of the target and the biomarker secretion rate are unknown, whereas the locations of the NSs are known. We derive the uniformly most powerful (UMP) test for the detection at the NSs. For the final decision at the FC, we show that the UMP test does not exist. Hence, we derive a genie-aided detector as an upper bound on performance. We then propose two sub-optimal detectors and evaluate their performance via simulations.

Active transport such as fluid flow is sought in molecular communication to extend coverage, improve reliability, and mitigate interference. Flow models are often over-simplified, assuming one-dimensional diffusion with constant drift. However, diffusion and flow are usually encountered in three-dimensional bounded environments where the flow is highly non-uniform such as in blood vessels or microfluidic channels. For a qualitative understanding of the relevant physical effects inherent to these channels, based on the Péclet number and the transmitter-receiver distance, we study when simplified models of uniform flow and advection-only transport are applicable. For these two regimes, analytical expressions for the channel impulse response are derived and validated by particle-based simulation. Furthermore, as advection-only transport is typically overlooked and hence not analyzed in the molecular communication literature, we evaluate the symbol error rate for exemplary on-off keying as performance metric.

In this paper, we propose to use magnetic nanoparticles as information carriers for molecular communication. This enables the use of an external magnetic field to guide information-carrying particles towards the receiver. We show that the particle movement can be mathematically modeled as diffusion with drift. Thereby, we reveal that the key parameters determining the magnetic force are particle size and magnetic field gradient. As an example, we consider magnetic nanoparticle based communication in a bounded two-dimensional environment. For this model, we derive an analytical expression for the channel impulse response subject to fluid flow and magnetic drift. Numerical results, obtained by particle-based simulation, validate the accuracy of the derived analytical expressions. Furthermore, adopting the symbol error rate as performance metric, we show that using magnetic nanoparticles facilitates reliable communication, even in the presence of fluid flow.

In this paper, we consider mobile molecular communication (MC) systems which are expected to find application in several fields including targeted drug delivery and health monitoring. We develop a mathematical framework for modeling the time-variant stochastic channels of diffusive mobile MC systems. In particular, we consider a diffusive mobile MC system consisting of a pair of transmitter and receiver nano-machines suspended in a fluid medium with a uniform bulk flow, where we assume that either the transmitter or the receiver or both are mobile, and we model the mobility by Brownian motion. The transmitter and receiver nano-machines exchange information via diffusive signaling molecules. Due to the random movements of the transmitter and receiver nano-machines, the statistics of the channel impulse response (CIR) change over time. We derive closed-form expressions for the mean, the autocorrelation function (ACF), the cumulative distribution function (CDF), and the probability density function (PDF) of the time-variant CIR. Exploiting the ACF, we define the coherence time of the time-variant MC channel as a metric for characterization of the variations of the CIR. The derived CDF is employed for calculation of the outage probability of the system. We also show that under certain conditions, the PDF of the CIR can be accurately approximated by a Log-normal distribution. Based on this approximation, we derive a simple model for outdated channel state information (CSI). Moreover, we derive an analytical expression for the evaluation of the expected error probability of a simple detector for the considered MC system. In order to investigate the impact of CIR decorrelation over time, we compare the performances of a detector with perfect CSI knowledge and a detector with outdated CSI knowledge. The accuracy of the proposed analytical expressions is verified via particle-based simulation of the Brownian motion.

Instantaneous or statistical channel state information (CSI) is needed for most detection schemes developed for molecular communication (MC) systems. Since the MC channel changes over time, e.g., due to variations in the velocity of flow, the temperature, or the distance between transmitter and receiver, CSI acquisition has to be conducted repeatedly to keep track of CSI variations. Frequent CSI acquisition may entail a large overhead whereas infrequent CSI acquisition may result in a low CSI estimation accuracy. To overcome these challenges, we design codes which enable maximum likelihood sequence detection at the receiver without instantaneous or statistical CSI. In particular, assuming concentration shift keying modulation, we show that a class of codes, known as constant-composition (CC) codes, enables optimal CSI-free sequence detection at the expense of a decrease in data rate. We analyze the code rate, the error rate, and the average number of released molecules for the adopted CC codes. In addition, we study the properties of binary CC codes and balanced CC codes in further detail. Simulation results verify our analytical derivations and reveal that CC codes with CSI-free detection outperform uncoded transmission with optimal coherent and noncoherent detection.

In this paper, we consider a diffusive mobile molecular communication (MC) system consisting of a pair of mobile transmitter and receiver nano- machines suspended in a fluid medium, where we model the mobility of the nano-machines by Brownian motion. The transmitter and receiver nano-machines exchange information via diffusive signaling molecules. Due to the random movements of the transmitter and receiver nano-machines, the statistics of the channel impulse response (CIR) change over time. We introduce a statistical framework for characterization of the impulse response of time-variant MC channels. In particular, we derive closed-form analytical expressions for the mean and the autocorrelation function of the impulse response of the channel. Given the autocorrelation function, we define the coherence time of the time-variant MC channel as a metric that characterizes the variations of the impulse response. Furthermore, we derive an analytical expression for evaluation of the expected error probability of a simple detector for the considered system. In order to investigate the impact of CIR decorrelation over time, we compare the performances of a detector with perfect channel state information (CSI) knowledge and a detector with outdated CSI knowledge. The accuracy of the proposed analytical expression is verified via particle-based simulation of the Brownian motion.

Symbol synchronization refers to the estimation of the start of a symbol interval and is needed for reliable detection. In this paper, we develop a symbol synchronization framework for molecular communication (MC) systems where we consider some practical challenges which have not been addressed in the literature yet. In particular, we take into account that in MC systems, the transmitter may not be equipped with an internal clock and may not be able to emit molecules with a fixed release frequency. Such restrictions hold for practical nanotransmitters, e.g. modified cells, where the lengths of the symbol intervals may vary due to the inherent randomness in the availability of food and energy for molecule generation, the process for molecule production, and the release process. To address this issue, we propose to employ two types of molecules, one for synchronization and one for data transmission. We derive the optimal maximum likelihood (ML) symbol synchronization scheme as a performance upper bound. Since ML synchronization entails high complexity, we also propose two low-complexity synchronization schemes, namely a peak observation-based scheme and a threshold-trigger scheme, which are suitable for MC systems with limited computational capabilities. Our simulation results reveal the effectiveness of the proposed synchronization schemes and suggest that the end-to-end performance of MC systems significantly depends on the accuracy of symbol synchronization.

Instantaneous or statistical channel state information (CSI) is needed for most detection schemes developed in the molecular communication (MC) literature. Since the MC channel changes, e.g., due to variations in the velocity of flow, the temperature, or the distance between transmitter and receiver, CSI acquisition has to be conducted repeatedly to keep track of CSI variations. Frequent CSI acquisition may entail a large overhead whereas infrequent CSI acquisition may result in a low CSI estimation quality. To cope with these issues, we design codes which facilitate maximum likelihood sequence detection at the receiver without instantaneous or statistical CSI. In particular, assuming concentration shift keying modulation, we show that a class of codes, referred to as strongly constant-weight (SCW) codes, enables optimal CSI-free sequence detection at the cost of decreasing the data rate. For the proposed SCW codes, we analyze the code rate and the error rate. Simulation results verify our analytical derivations and reveal that the proposed CSI-free detector for SCW codes outperforms the baseline coherent and non-coherent detectors for uncoded transmission.

In this paper, 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. 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. The accuracy of the derived analytical result is verified with a Brownian motion particle-based simulation of the environment.

In molecular communication (MC) systems, the expected number of molecules observed at the receiver over time after the instantaneous release of molecules by the transmitter is referred to as the channel impulse response (CIR). Knowledge of the CIR is needed for the design of detection and equalization schemes. In this paper, we present a training-based CIR estimation framework for MC systems which aims at estimating the CIR based on the observed number of molecules at the receiver due to emission of a sequence of known numbers of molecules by the transmitter. In particular, we derive maximum likelihood (ML) and least sum of square errors (LSSE) estimators. We also study the Cramer Rao (CR) lower bound and training sequence design for the considered system. Simulation results confirm the analysis and compare the performance of the proposed estimation techniques with the CR lower bound.

In molecular communication (MC) systems, the expected number of molecules observed at the receiver over time after the instantaneous release of molecules by the transmitter is referred to as the channel impulse response (CIR). Knowledge of the CIR is needed for the design of detection and equalization schemes. In this paper, we present a training-based CIR estimation framework for MC systems, which aims at estimating the CIR based on the observed number of molecules at the receiver due to emission of a sequence of known numbers of molecules by the transmitter. Thereby, we distinguish two scenarios depending on whether or not statistical channel knowledge is available. In particular, we derive maximum likelihood and least sum of square errors estimators, which do not require any knowledge of the channel statistics. For the case, when statistical channel knowledge is available, the corresponding maximum a posteriori and linear minimum mean square error estimators are provided. As performance bound, we derive the classical Cramer Rao (CR) lower bound, valid for any unbiased estimator, which does not exploit statistical channel knowledge, and the Bayesian CR lower bound, valid for any unbiased estimator, which exploits statistical channel knowledge. Finally, we propose the optimal and suboptimal training sequence designs for the considered MC system. Simulation results confirm the analysis and compare the performance of the proposed estimation techniques with the respective CR lower bounds.

This paper studies a three-node network in which an intermediate nano-transceiver, acting as a relay, is placed between a nano-transmitter and a nano-receiver to improve the range of diffusion- based molecular communication. Motivated by the relaying protocols used in traditional wireless communication systems, we study amplify-and- forward (AF) relaying with fixed and variable amplification factor for use in molecular communication systems. To this end, we derive a closed-form expression for the expected end-to-end error probability. Furthermore, we derive a closed-form expression for the optimal amplification factor at the relay node for minimization of an approximation of the expected error probability of the network. Our analytical and simulation results show the potential of AF relaying to improve the overall performance of nano-networks.

In this paper, we consider a two-hop molecular communication network consisting of one nanotransmitter, one nanoreceiver, and one nanotransceiver acting as a relay. We consider two different schemes for relaying to improve the range of diffusion-based molecular communication. In the first scheme, two different types of messenger molecules are utilized at the relay node for transmission and detection. In the second scheme, we assume that there is only one type of molecule available to be used as an information carrier. We identify self-interference as the performance-limiting effect for the second relaying scheme. Self-interference occurs when the relay must detect the same type of molecule that it also emits. Furthermore, we consider two relaying modes analogous to those used in wireless communication systems, i.e., full-duplex and half-duplex. In particular, while our main focus is on full-duplex relaying, half-duplex relaying is employed as a means to mitigate self-interference. In addition, we propose the adaptation of the decision threshold as an effective mechanism to mitigate self-interference at the relay for full-duplex transmission. We derive closed-form expressions for the expected error probability of the network for both considered relaying schemes.