A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Abstract A number of nanomachines that cooperatively communicate and share molecular information in order to achieve specific tasks is envisioned as a nanonetwork. Due to the size and capabilities of nanomachines, the traditional communication paradigms cannot be used for nanonetworks in which network nodes may be composed of just several atoms or molecules and scale on the orders of few nanometers. Instead, molecular communication is a promising solution approach for the nanoscale communication paradigm. However, molecular communication must be thoroughly investigated to realize nanoscale communication and nanonetworks for many envisioned applications such as nanoscale body area networks, and nanoscale molecular computers. In this paper, a simulation framework (NanoNS) for molecular nanonetworks is presented. The objective of the framework is to provide a simulation tool in order to create a better understanding of nanonetworks and facilitate the development of new communication techniques and the validation of theoretical results. The NanoNS framework is built on top of core components of a widely used network simulator (ns-2). It incorporates the simulation modules for various nanoscale communication paradigms based on a diffusive molecular communication channel. The details of NanoNS are discussed and some functional scenarios are defined to validate NanoNS. In addition to this, the numerical analyses of these functional scenarios and their experimental results are presented. The validation of NanoNS is shown via comparative evaluation of these experimental and numerical results. <s> BIB001 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> In molecular communication, information is encoded and transmitted as a pattern of molecules or other very small information carriers (in this paper, vesicles are used). Nanoscale techniques, such as molecular motors or Brownian motion, are used to convey the vesicles from the transmitter to the receiver, where the transmitted message is deciphered. In this paper, the microchannel environment is considered, and the achievable information rates are compared between the use of Brownian motion and molecular motors, which are evaluated through simulation. Communication is viewed as a mass transfer problem, where messages are sent by transporting a number of vesicles from transmitter to receiver. Results are provided which suggest that active transport is best when the available number of vesicles is small, and Brownian motion is best when the number of vesicles is large. <s> BIB002 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Molecular communication is a promising technique for microchannel systems. In this paper, various microchannel molecular communication schemes are simulated and analyzed using information theory, including molecular motors and Brownian motion with drift. Results suggest Brownian motion with drift can deliver excellent performance, depending on the drift velocity. <s> BIB003 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Diffusion-based molecular communication is a promising bio-inspired paradigm to implement nanonetworks, i.e., the interconnection of nanomachines. The peculiarities of the physical channel in diffusion-based molecular communication require the development of novel models, architectures and protocols for this new scenario, which need to be validated by simulation. With this purpose, we present N3Sim, a simulation framework for diffusion-based molecular communication. N3Sim allows to simulate scenarios where transmitters encode the information by releasing molecules into the medium, thus varying their local concentration. N3Sim models the movement of these molecules according to Brownian dynamics, and it also takes into account their inertia and the interactions among them. Receivers decode the information by sensing the particle concentration in their neighborhood. The benefits of N3Sim are multiple: the validation of channel models for molecular communication and the evaluation of novel modulation schemes are just a few examples. <s> BIB004 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Nanonetworks are the interconnection of nanomachines and as such expand the limited capabilities of a single nanomachine. Several techniques have been proposed so far to interconnect nanomachines. For short distances (nm-mm ranges), researchers are proposing to use molecular motors and calcium signaling. For long distances (mm-m), pheromones are envisioned to transport information. In this work we propose a new mechanism for medium-range communications (nm-µm): flagellated bacteria. This technique is based on the transport of DNA-encoded information between emitters and receivers by means of a bacterium. We present a physical channel characterization and a simulator that, based on the previous characterization, simulates the transmission of a DNA packet between two nanomachines. <s> BIB005 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> a b s t r a c t Nanonetworking is a new interdisciplinary research area including nanotechnology, biotechnology, and ICT. In this paper, we present a novel simulation platform designed for modeling information exchange at nanoscales. This platform is adaptable to any kind of nano bearer, i.e. any mechanism used to transport information, such as electromagnetic waves or calcium ions. Moreover, it includes a set of configuration functions in order to adapt to different types of biological environments. In this paper, we provide a throughout description of the simulation libraries. In addition, we demonstrate their capabilities by modeling a section of a lymph node and the information transfer within it, which happens between antibody molecules produced by the immune system during the humoral immune response. <s> BIB006 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Nanonetworking is a new research field in which nanotechnology and communication engineering disciplines are employed to explore the possible communication mechanisms at nanoscale. Inspired by living organisms, molecular communication is one of the alternatives that can be used for communication between nanomachines. The research activities on molecular communication depend on simulations to verify and analyze the performance of proposed models. Due to the different channel characteristics, current simulation tools can not be used as is for nanonetworking. Simulation at nanoscale requires modeling of new communication paradigm, hence either existing tools need to be extended, or new tools need to be developed. Since molecular communication involves the modeling of large number of nanoscale objects, scalability of the simulation tool is another important concern. In this paper, we introduce dMCS, a distributed molecular communication simulator design. The proposed architecture is based on High Level Architecture (HLA), which is standardized under IEEE 1516. The results show that using the proposed architecture, it is possible to exploit different scalability options to shorten the execution time significantly. This enables modeling large and complex system simulations. <s> BIB007 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Abstract This paper presents a software platform, named BiNS2, able to simulate diffusion-based molecular communications with drift inside blood vessels. The contribution of the paper is twofold. First a detailed description of the simulator is given, under the software engineering point of view, by highlighting the innovations and optimizations introduced. Their introduction into the previous version of the BiNS simulator was needed to provide the functions for simulating molecular signaling and communication potentials inside bounded spaces. The second contribution consists of the analysis, carried out by using BiNS2, of a specific communication process happening inside blood vessels, the atherogenesis, which is the initial phase of the formation of atherosclerotic plaques, due to the abnormal signaling between platelets and endothelium. From a communication point of view, platelets act as mobile transmitters, endothelial cells are fixed receivers, sticky to the vessel walls, and the transmitted signal is made of bursts of molecules emitted by platelets. The simulator allows for the evaluation of the channel latency and the footprint on the vessel wall of the transmitted signal as a function of the transmitter distance from the vessels wall, the signal strength, and the receiver sensitivity. <s> BIB008 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Abstract Nanoscale communications is an emergent research topic with potential applications in many fields. In order to design nanomachines able to exploit the communication potentials of nanoscale environments, it is necessary to identify the basic communication mechanisms and the relevant parameters. In this paper, we show how system parameters can be derived by suitably matching the results of in vitro experiments with those obtained via simulations by using the BiNS2 simulator. In order to scale the simulation from micrometric settings, with timescale in the order of seconds, to real experiments lasting tens of minutes with millimetric size, we enhanced the BiNS2 simulator by introducing a space partition algorithm based on the octree. In this way, the simulator can exploit the high level of parallelism of modern multicore computer architectures. We have used this technique for simulating an experiment focused on the communication between platelets and endothelium through the diffusion of nanoparticles. Simulation results match experimental data, thus allowing us to infer useful information on the receiver operation. <s> BIB009 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Bacteria-based networks are formed using native or engineered bacteria that communicate at nano-scale. This definition includes the micro-scale molecular transportation system which uses chemotactic bacteria for targeted cargo delivery, as well as genetic circuits for intercellular interactions like quorum sensing or light communication. To characterize the dynamics of bacterial networks accurately, we introduce BNSim, an open-source, parallel, stochastic, and multiscale modeling platform which integrates various simulation algorithms, together with genetic circuits and chemotactic pathway models in a complex 3D environment. Moreover, we show how this platform can be used to model synthetic bacterial consortia which implement a XOR function and aggregate nearby bacteria using light communication. Consequently, the results demonstrate how BNSim can predict various properties of realistic bacterial networks and provide guidance for their actual wet-lab implementations. <s> BIB010 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Abstract In parallel to the developments in nano-scale machines and engineered cells, communication among them is getting more attention. The use of molecules to transfer information from one nanomachine to another is one of the mechanisms to build networks at the nano-scale. The research activities on communication models and performance evaluation of molecular communication heavily depend on simulations to verify the proposed models. The existing simulation tools for computer networking can not be directly used for molecular communication due to different communication model and channel characteristics of the fluid environment and the carrier wave properties. Simulation of molecular communication requires modeling the new communication paradigm that comprises different options for encoding, transmission, propagation, reception, and decoding. It should consider possible architectural design options and performance evaluation of molecular communication networks. Since molecular communication involves the modeling of large number of nano-scale objects, the scalability of the simulation tool is another important concern. In this paper, we introduce a simulator design that aims at fulfilling important design issues of the molecular communication model, focusing on scalability. High Level Architecture (HLA), which is standardized under IEEE 1516, is used to design and develop a distributed simulation tool for molecular communication. The results show that different scalability options can be used to benefit from additional processing power to shorten the execution time. This also enables modeling large systems, which may not be possible otherwise. <s> BIB011 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Abstract In this paper, a strength-based optimum signal detection scheme for binary concentration-encoded molecular communication (CEMC) system has been presented. In CEMC, a single type of information molecule is assumed to carry the information from the transmitting nanomachine (TN), through the propagation medium, to the receiving nanomachine (RN) in the form of received concentration of information molecules at the location of the RN. We consider a pair of nanomachines communicating by means of on–off keying (OOK) transmission protocol in a three-dimensional ideal (i.e. free) diffusion-based unbounded propagation environment. First, based on stochastic chemical kinetics of the reaction events between ligand molecules and receptors, we develop a mathematical receiver model of strength-based detection scheme for OOK CEMC system. Using an analytical approach, we explain the receiver operating characteristic (ROC) curves of the receiver thus developed. Finally, we propose a variable threshold-based detection scheme and explain its communication range and rate dependent characteristics. We show that it provides an improvement in the communication ranges compared to fixed threshold-based detection scheme. (Part of this paper has been peer-reviewed and published in BWCCA-2012 conference in Victoria, BC, 12–14 November, 2012 [20] .) <s> BIB012 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Diffusion-based molecular communication is a promising bio-inspired paradigm to implement nanonetworks, i.e., the interconnection of nanomachines. The peculiarities of the physical channel in diffusion-based molecular communication require the development of novel models, architectures and protocols for this new scenario, which need to be validated by simulation. N3Sim is a simulation framework for nanonetworks with transmitter, receiver, and harvester nodes using Diffusion-based Molecular Communication (DMC). In DMC, transmitters encode the information by releasing molecules into the medium, thus varying their local concentration. N3Sim models the movement of these molecules according to Brownian dynamics, and it also takes into account their inertia and the interactions among them. Harvesters collect molecules from the environment to reuse them for later transmissions. Receivers decode the information by sensing the particle concentration in their neighborhood. The benefits of N3Sim are multiple: the validation of channel models for DMC and the evaluation of novel modulation schemes are just a few examples. <s> BIB013 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> E. Simulation Tools <s> Abstract The research activities on Molecular Communication via Diffusion (MCvD) that can interconnect nanomachines, heavily depend on simulations to verify and evaluate the new communication paradigm. The existing simulation tools cannot be directly used for MCvD systems since the diffusion channel has different characteristics compared to classical communication channels. In an MCvD system, diffusion and demodulation processes have their own constraints and characteristics due to the impossibility of sending a negative number of molecules, the random movement of molecules, and a reception process of molecules that determines the signal. Therefore, a custom end-to-end MolecUlar CommunicatIoN (MUCIN) simulator for MCvD systems is presented. Compared to other simulators available in the literature, MUCIN simulator is an end-to-end simulator that considers first hitting process for the signal reception. It supports 1-D to 3-D environments, sending consecutive symbols, imperfect molecule reception, extendable modulation, and filtering modules. MUCIN simulator source code is available under BSD licensing for contributors from the nanonetworking community. Following the simulator analysis, a case study of inter-symbol-interference mitigation that utilizes the decision in one previous slot is introduced. The contribution of this paper is twofold; one is the modeling and the development of an end-to-end MCvD simulator, the other is the performance evaluation of the proposed inter-symbol interference filtering and demodulation techniques. <s> BIB014
Molecular communication has its own characteristics, which differ from a traditional RF-based communication paradigm. Therefore, research activities on molecular communication heavily depend on simulations to verify and evaluate the new communication solutions. The existing simulation tools, however, cannot be directly used for molecular communication systems since molecular channel has different characteristics compared to classical communication channels. Therefore, proper simulators are required to precisely track the behavior of information-carrying molecules within a realistic environment. We provide a comparison matrix in Table II for the molecular communication simulators in the literature. In BIB011 and BIB007 , high level architecture (HLA) based, distributed simulations for molecular communication were proposed and the authors analyzed the speed up with the parallelism. Akkaya et al. mostly focused on confined space and parallelism gain while not considered the effect of consecutive symbols in their simulator, dMCS. In BIB001 , NanoNS simulation platform was introduced and it is based on the well-known NS-2 simulation platform and was written in C++ and Tcl. In NanoNS, the communication system was not considered as an end-to-end system and the authors focused on physical channel properties with considering one-shot signal. The multi-particle lattice gas automata algorithm was implemented in NanoNS, which divided the propagation medium into lattice sides. Thus, the exact particle position was not evaluated. In NanoNS, the reaction process, that describes the molecular interaction between nodes and molecules, was modeled as: NoReaction, Berg, and Gillespie. In BIB012 , amplitude-based modulations were analyzed via custom simulator. The molecules, however, constituted a signal not just once, since they continued free diffusion even though they reacted with the receptors. In BIB004 , N3Sim simulation framework was introduced and the reception process at the receiver site was similar to the model in BIB012 . In N3Sim, molecules can go in and out of the receiver without any resistance; i.e., the receiver is transparent to the molecules BIB013 . In both of the simulators, transmissions were done from a point source while in reality the transmitter nodes have a volume and they reflect the emitted molecules. N3Sim, is a Java package that simulates particle diffusion in a 2-D environment, with an ongoing evolution to 3-D diffusion models (currently 3-D simulations are possible only under specific conditions  ). The reception process takes place by counting the particles located within a given area close to any receiver node each time step, without implementing any specific receptor model. N3Sim can model propagation phenomena also by taking into account specific laws for handling electrostatic, inertia forces, and particle collisions. A simulation tool, BINS, for nanoscale biological networks was developed for simulating information exchange at nanoscale BIB006 . BINS is adaptable to any kind of nano bearer. In BIB006 , the authors provided a throughout description of the simulation libraries and demonstrated their capabilities by modeling a section of a lymph node and the information transfer within it. Their simulator supports 3-D space, receptor dynamics including affinity, different carriers, lifetime for molecules, tracking each molecule, collisions, and mobile receiver nodes. BINS was upgraded to BINS2, which offers new features to simulate bounded environments. Using the BINS2 simulator, propagation in blood vessels was analyzed in BIB008 and in vitro experiments were simulated in BIB009 . The authors simulated an experiment that focused on the communication between platelets and endothelium through the diffusion of nanoparticles BIB009 . They verified the simulation results with the experimental data. In BIB014 , the MolecUlar CommunicatIoN (MUCIN) simulator for molecular communication via diffusion systems was presented. MUCIN simulator is an end-to-end simulator that considers first hitting process for the signal reception. It supports 1-D to 3-D environments, sending consecutive symbols, imperfect molecule reception, extendable modulation, and filtering modules. MUCIN simulator was developed in MATLAB and it is available in MATLAB file exchange central. In BIB010 , open source bacteria networks simulator BNSim was introduced. BNSim supports parallel multi scale stochastic modeling, chemical signaling pathways inside each bacterium, movement in 3-D environments, and chemotaxis. Similarly, in BIB005 the authors proposed medium-range point-to-point molecular communication that was based on the transport of DNAencoded information between emitters and receivers by means of a bacterium. Gregori et al. presented the channel characterization and a simulator for the communication channel. The proposed communication scheme was as follows: first, the DNA message was introduced inside the bacterium cytoplasm. Then, the bacterium was released into the environment that in turn followed its natural instincts and propelled itself to a particular receiver, which was continuously releasing attractant particles to the environment. Finally, in the last step, the reception and decoding of the DNA message was done by exchanging the genetic material between the bacterium and the final destination. In BIB002 , BIB003 a simulation environment for molecular communication in confined environments was presented. The environment, which could be used for Monte Carlo simulations, captured both diffusion based propagation and active transport propagation using stationary kinesin and microtubule filaments. For the diffusion propagation, it was assumed that the collision of information particles with the channel walls are elastic.