Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> Methods are presented for determining those parameters of olfactory communication systems most closely related to the diffusion process. Four general cases of diffusion are considered: instantaneous release of the communicating substance in still air, continuous release in still air, continuous release from a moving source as in an odor trail, and continuous release in a wind. The techniques have been applied in the analysis of three real communication systems, involving an alarm substance, a recruitment trail, and a sex attractant respectively. It has been possible to demonstrate the effect of differing values of the parameters in fulfilling the design requirements of a particular system with respect to range of the signal, its rate of spread, and its persistence. <s> BIB001 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> This paper proposes a biological cell-based communication protocol to enable communication between biological nanodevices. Inspired by existing communication network protocols, our solution combines two molecular computing techniques (DNA and enzyme computing), to design a protocol stack for molecular communication networks. Based on computational requirements of each layer of the stack, our solution specifies biomolecule address encoding/decoding, error correction and link switching mechanisms for molecular communication networks. <s> BIB002 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> a b s t r a c t This paper describes a Bacteria-based Nanonetwork for communication between eukaryotic cell sized nano devices. The communication is achieved by the exchange of DNA molecules which are transported by bacteria guided by chemotaxis. First, the modules of the network are described and all the biological phenomena that support the basic communication steps are explained in detail. Then an analytical model is developed to assess the communication range and the network performance in terms of capacity and end-to-end delay by considering the available information about the biological mechanisms used. As there are no appropriate estimates of the propagation delay introduced by bacterial chemotaxis, our newly developed simulator is introduced which helps us to obtain the statistics on bacteria propagation. Finally, by combining the analytical model with the simulation results, a network performance in terms of end-to-end delay, capacity and end-to-end throughput is obtained which is 4 orders of magnitude higher than the other molecular communication approaches. <s> BIB003 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> Molecular communication is a promising paradigm for nanoscale networks. The end-to-end (including the channel) models developed for classical wireless communication networks need to undergo a profound revision so that they can be applied for nanonetworks. Consequently, there is a need to develop new end-to-end (including the channel) models which can give new insights into the design of these nanoscale networks. The objective of this paper is to introduce a new physical end-to-end (including the channel) model for molecular communication. The new model is investigated by means of three modules, i.e., the transmitter, the signal propagation and the receiver. Each module is related to a specific process involving particle exchanges, namely, particle emission, particle diffusion and particle reception. The particle emission process involves the increase or decrease of the particle concentration rate in the environment according to a modulating input signal. The particle diffusion provides the propagation of particles from the transmitter to the receiver by means of the physics laws underlying particle diffusion in the space. The particle reception process is identified by the sensing of the particle concentration value at the receiver location. Numerical results are provided for three modules, as well as for the overall end-to-end model, in terms of normalized gain and delay as functions of the input frequency and of the transmission range. <s> BIB004 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> We aimed to create an autonomous on-chip system that performs targeted delivery of lipid vesicles (liposomes) as nano- or microscale reactors using machinery from biological systems. Reactor-liposomes would be ideal model cargoes to realize biomolecular-motor-based biochemical analysis chips; however, there are no existing systems that enable targeted delivery of cargo-liposomes in an autonomous manner. By exploiting biomolecular-motor-based motility and DNA hybridization, we demonstrate that single-stranded DNA (ssDNA)-labeled microtubules (MTs), gliding on kinesin-coated surfaces, acted as cargo transporters and that ssDNA-labeled cargo-liposomes were loaded/unloaded onto/from gliding MTs without bursting at loading reservoirs/micropatterned unloading sites specified by DNA base sequences. Our results contribute to the development of an alternative strategy to pressure-driven or electrokinetic flow-based microfluidic devices. <s> BIB005 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> Abstract In this paper, we investigated approaches to form a self-organizing microtubule network. Microtubules are protein filaments naturally occurring in the aqueous environment of cells. A microtubule network connects multiple nano- or micro-scale objects (i.e., nanomachines). In the paper, we propose two approaches to form an in vitro microtubule network in a self-organizing manner. The first approach utilizes polymerization and depolymerization of microtubules. The second approach utilizes molecular motors to reorganize a microtubule network. In addition, we conducted preliminary in vitro experiments to investigate the feasibility of the proposed approaches. In the preliminary experiments, we observed that a few sender and receiver nanomachines were interconnected with the first approach, and that distinct topologies of microtubules were reorganized with the second approach. <s> BIB006 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <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> BIB007 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> The creation of orthogonal ‘AND’ logic gates by combining DNA-binding proteins into complex, layered circuits opens the way to the design of programmable integrated circuits in synthetic biology. <s> BIB008 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> Linear and nonlinear piezoelectric devices are introduced to continuously recharge the batteries of the pacemakers by converting the vibrations from the heartbeats to electrical energy. The power requirement of a pacemaker is very low. However, after few years, patients require another surgical operation just to replace their pacemaker battery. Linear low frequency and nonlinear mono-stable and bi-stable energy harvesters are designed according to the especial signature of heart vibrations. The proposed energy harvesters are robust to variation of heart rate and can meet the power requirement of pacemakers. <s> BIB009 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications. <s> BIB010 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> The study of thermoelectric energy harvesting on people presented in this paper shows that although power generation is affected by many factors such as ambient temperature, wind speed, clothing thermal insulation, and a person's activity, it does not directly depend on metabolic rate as shown in the experiment. The relevant thermal properties of humans measured at different ambient conditions are reported. Several thermopiles are either attached with a strap directly to the skin or integrated into garments in different locations on human body, and power generation is extensively studied at different ambient conditions. Textile covering thermopiles is found not to essentially decrease power generation. Therefore, a hidden energy harvester is integrated into an office-style shirt and tested on people in real life. It generated power in 5–0.5 mW range at ambient temperatures of 15 $^{\circ}{\rm C}$ –27 $^{\circ}{\rm C}$ , respectively. The thermoelectric shirt with such an energy harvester produces more energy during nine months of use (if worn 10 h/day) than the energy stored in alkaline batteries of the same thickness and weight. <s> BIB011 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> With much advancement in the field of nanotechnology, bioengineering, and synthetic biology over the past decade, microscales and nanoscales devices are becoming a reality. Yet the problem of engineering a reliable communication system between tiny devices is still an open problem. At the same time, despite the prevalence of radio communication, there are still areas where traditional electromagnetic waves find it difficult or expensive to reach. Points of interest in industry, cities, and medical applications often lie in embedded and entrenched areas, accessible only by ventricles at scales too small for conventional radio waves and microwaves, or they are located in such a way that directional high frequency systems are ineffective. Inspired by nature, one solution to these problems is molecular communication (MC), where chemical signals are used to transfer information. Although biologists have studied MC for decades, it has only been researched for roughly 10 year from a communication engineering lens. Significant number of papers have been published to date, but owing to the need for interdisciplinary work, much of the results are preliminary. In this survey, the recent advancements in the field of MC engineering are highlighted. First, the biological, chemical, and physical processes used by an MC system are discussed. This includes different components of the MC transmitter and receiver, as well as the propagation and transport mechanisms. Then, a comprehensive survey of some of the recent works on MC through a communication engineering lens is provided. The survey ends with a technology readiness analysis of MC and future research directions. <s> BIB012 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> Living subjects (i.e., humans and animals) have abundant sources of energy in chemical, thermal, and mechanical forms. The use of these energies presents a viable way to overcome the battery capacity limitation that constrains the long-term operation of wearable/implantable devices. The intersection of novel materials and fabrication techniques offers boundless possibilities for the benefit of human health and well-being via various types of energy harvesters. This review summarizes the existing approaches that have been demonstrated to harvest energy from the bodies of living subjects for self-powered electronics. We present material choices, device layouts, and operation principles of these energy harvesters with a focus on in vivo applications. We discuss a broad range of energy harvesters placed in or on various body parts of human and animal models. We conclude with an outlook of future research in which the integration of various energy harvesters with advanced electronics can provide a new platform for the development of novel technologies for disease diagnostics, treatment, and prevention. <s> BIB013 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> B. Physical Design of MC-Tx <s> Internet of Things (IoT) is a perfect candidate to realize efficient observation and management for Smart City concept. This requires deployment of large number of wireless devices. However, replenishing batteries of thousands, maybe millions of devices may be hard or even impossible. In order to solve this problem, Internet of Energy Harvesting Things (IoEHT) is proposed. Although the first studies on IoEHT focused on energy harvesting (EH) as an auxiliary power provisioning method, now completely battery-free and self-sufficient systems are envisioned. Taking advantage of diverse sources that the concept of Smart City offers helps us to fully appreciate the capacity of EH. In this way, we address the primary shortcomings of IoEHT; availability, unreliability, and insufficiency by the Internet of Hybrid EH Things (IoHEHT). In this paper, we survey the various EH opportunities, propose an hybrid EH system, and discuss energy and data management issues for battery-free operation. We mathematically prove advantages of hybrid EH compared to single source harvesting as well. We also point out to hardware requirements and present the open research directions for different network layers specific to IoHEHT for Smart City concept. <s> BIB014
MC uses molecules for information transfer unlike the traditional communication systems that rely on electromagnetic (EM) and acoustic waves. Therefore, the physical design of MC-Tx significantly differs from the traditional transmitters. The key components of an MC-Tx is illustrated in Figure  2 . The first element in MC-Tx is the information source that represents either a bit-wise information generated by a BIB012 or through biocompatible micro-scale processors, or via synthetic genetic circuits BIB008 . In case of biological Tx architectures, processing units performing logic gates and memory functions in the form of synthetic genetic circuits can be embedded into cells BIB008 , BIB010 . Inside the processing unit, the first step is to represent analog or digital information with the least number of bits possible through source coding. Then, channel coding block introduces extra bits to make data transmission more robust against error-prone MC channels. After the coding step, digital information is transformed into an analog molecular signal according to a predetermined modulation scheme. There are various modulation schemes proposed for MC by using molecular concentration, type of molecules or time of molecule release. The detailed discussion of modulation techniques for MC can be found in Section II-C. The processing unit controls IM release according to the data being transmitted and the modulation scheme. IM molecules are provided from IM generator/container, which can be realized as either a reservoir containing genetically engineered bacteria to produce IM molecules on demand, or a container with limited supply of IM molecules. There are two types of molecule release mechanisms BIB001 : instant release, where certain number of molecules (in mol) are released to the medium at the same time, and continuous release, where the molecules are released with a constant rate over a certain period of time (mol/s). Instant release can be modeled as an impulse symbol, while continuous release can be considered as a pulse wave. According to application requirements and channel conditions, one of the release mechanisms can be more favorable. Bit-wise communications, for example, require rapid fade-out of IMs from the channel as these molecules will cause ISI for the next symbol, thus, instant release is more promising. In addition, alarm signals for warning plants and other insects can favor continuous release to increase detection probability and reliability. MC-Tx architecture also shows dependency on propagation channel. There are three main propagation channels that can be exploited by MC: free diffusion, flow-assisted propagation, and motor-powered propagation BIB012 , BIB003 . Diffusion is the movement of molecules from high concentration to low concentration with random steps. This process requires no external energy and the molecules travel with the thermal energy of the medium, e.g., liquid or air. Diffusion process can be modeled with the Fick's law, i.e., a partial differential equation calculating the changes in molecular concentration in a medium, as where c is the molecule concentration, and D is the diffusion coefficient, which depends on the temperature, pressure and viscosity of the medium. Calcium signaling between cells and propagation of neurotransmitters in synaptic cleft are good examples of biological systems utilizing diffusion for molecular information transfer. Diffusion-based MC provides short range information transfer in the order of micrometers BIB012 . Second type of MC channel is flow-assisted propagation, in which molecules propagate via both diffusion and flow, such as flow in the blood stream and air flow created by wind. Flow-assisted propagation can be modeled with the advectiondiffusion equation, which is represented as where v is the velocity vector for the flow in the medium. The diffusion case, flow-assisted propagation does not require any external energy source, and uses the thermal energy that exists in the propagation medium. Communication range of flow-assisted propagation can reach up to several meters as in hormonal communications in the blood stream and communications via pheromone between plants BIB012 . Lastly, motor-powered propagation includes molecular motors and bacteria with flagella, e.g., E. coli. Molecular motorpowered microtubules, also known as walkway-based architectures BIB004 , BIB002 , use predefined microtubules with motor proteins, which carry IMs from one end to other end of the tube. Motor proteins such as Kinesis consume external energy in the form of adenosine triphosphate (ATP) to move IMs in microtubules with the diameters of 20-30nm BIB005 , BIB006 . This motion can be mathematically represented as BIB012  where x is the location of the molecule inside the microtubule, v avg is the average speed of molecules moving via molecular motors, and ∆t is the time step. Molecular motors enable medium range molecular communication up to a millimeter BIB004 . In addition, BIB003 , BIB007 propose a nanonetwork architecture in which engineered bacteria with flagella is utilized to carry IMs for medium range MC (µm-mm). As in the molecular motor case, bacteria consume energy for movement via flagella. The processing unit in MC-Tx may require a power source for performing coding and modulation operations especially in the nanomaterial-based MC-Txs. Battery-powered devices suffer from limited-lifetime and random battery depletions, i.e., unexpected exhaustion of sensor battery due to hardware or software failure, that significantly affect the reliability of systems that rely on MC. Therefore, MC-Tx unit is required to operate as a self-sustaining battery-less device by harvesting energy from its surrounding. For this purpose, energy harvesting (EH) from various sources, such as solar, mechanical, chemical, can be utilized in MC-Tx architectures. Hybrid energy harvesting techniques can be employed as well to increase the output power reliability BIB014 . Concerning the intrabody and body area applications, human body stands as a vast source of energy BIB013 , which has been exploited to power biomedical devices and implants in many ways, e.g., thermoelectric EH from body heat BIB011 , vibrational EH from heartbeats BIB009 , and biochemical EH from perspiration  . Nevertheless, design and implementation of EH methods at micro/nanoscales for MC still stand as important open research issues in the literature.