Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> A new class of convolutional codes called turbo-codes, whose performances in terms of bit error rate (BER) are close to the Shannon limit, is discussed. The turbo-code encoder is built using a parallel concatenation of two recursive systematic convolutional codes, and the associated decoder, using a feedback decoding rule, is implemented as P pipelined identical elementary decoders. > <s> BIB001 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Precise control over the release of drug from devices implanted in the body, such as quantity, timing, is highly desirable in order to optimise drug therapy. In this paper, the research on electrically-responsive drug delivery is reviewed. Electrically-controllable drug release from polyelectrolyte hydrogels has been demonstrated in vitro and in vivo (in rats). Pulsatile drug release profiles, in response to alternating application and removal of the electric field have been achieved. Responsive drug release from hydrogels results from the electro-induced changes in the gels, which may deswell, swell or erode in response to an electric field. The mechanisms of drug release include ejection of the drug from the gel as the fluid phase synereses out, drug diffusion along a concentration gradient, electrophoresis of charged drugs towards an oppositely charged electrode and liberation of the entrapped drug as the gel complex erodes. Electrically-responsive drug release is influenced by a number of factors such as the nature of the drug and of the gel, the experimental set-up, magnitude of the electric field etc. In this paper, electrically-responsive hydrogels, response of gels to an electric field and electrically-stimulated drug release are discussed. <s> BIB002 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Abstract Molecular communication enables nanomachines to exchange information with each other by emitting molecules to their surrounding environment. Molecular nanonetworks are envisioned as a number of nanomachines that are deployed in an environment to share specific molecular information such as odor, flavor, or any chemical state. In this paper, using the stochastic model of molecular reactions in biochemical systems, a realistic channel model is first introduced for molecular communication. Then, based on the realistic channel model, we introduce a deterministic capacity expression for point-to-point, broadcast, and multiple-access molecular channels. We also investigate information flow capacity in a molecular nanonetwork for the realization of efficient communication and networking techniques for frontier nanonetwork applications. The results reveal that molecular point-to-point, broadcast, and multiple-access channels are feasible with a satisfactorily high molecular communication rate, which allows molecular information flow in nanonetworks. Furthermore, the derived molecular channel model with input-dependent noise term also reveals that unlike a traditional Gaussian communication channel, achievable capacity is affected by both lower and upper bounds of the channel input in molecular communication channels. <s> BIB003 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> In this paper, we consider molecular communication, with information conveyed in the time of release of molecules. These molecules propagate to the transmitter through a fluid medium, propelled by a positive drift velocity and Brownian motion. The main contribution of this paper is the development of a theoretical foundation for such a communication system; specifically, the additive inverse Gaussian noise (AIGN) channel model. In such a channel, the information is corrupted by noise that follows an IG distribution. We show that such a channel model is appropriate for molecular communication in fluid media. Taking advantage of the available literature on the IG distribution, upper and lower bounds on channel capacity are developed, and a maximum likelihood receiver is derived. Results are presented which suggest that this channel does not have a single quality measure analogous to signal-to-noise ratio in the additive white Gaussian noise channel. It is also shown that the use of multiple molecules leads to reduced error rate in a manner akin to diversity order in wireless communications. Finally, some open problems are discussed that arise from the IG channel model. <s> BIB004 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Communication via diffusion of molecules is an effective method for transporting information in nanonetworks. In this paper, novel modulation techniques called Concentration Shift Keying (CSK) and Molecule Shift Keying (MSK) are proposed for coding and decoding information of the so-called messenger molecule concentration waves in nanonetworks. The first technique, CSK, modulates the information via the variation in the concentration of the messenger molecules whereas MSK utilizes different types of messenger molecules to represent the information. Using simulation, the performance of these modulation techniques is evaluated in terms of susceptibility to noise and transmission power requirements. The new techniques achieve high channel capacity values, in particular, the MSK technique exhibits more robustness against noise and requires less power. <s> BIB005 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Abstract Currently, Communication via Diffusion (CvD) is one of the most prominent systems in nanonetworks. In this paper, we evaluate the effects of two major interference sources, Intersymbol Interference (ISI) and Co-channel Interference (CCI) in the CvD system using different modulation techniques. In the analysis of this paper, we use two modulation techniques, namely Concentration Shift Keying (CSK) and Molecule Shift Keying (MoSK) that we proposed in our previous paper. These techniques are suitable for the unique properties of messenger molecule concentration waves in nanonetworks. Using a two transmitting couple simulation environment, the channel capacity performances of the CvD system utilizing these modulation techniques are evaluated in terms of communication range, distance between interfering sources, physical size of devices, and average transmission power. <s> BIB006 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Molecular Communication (MC) is a communication paradigm based on the exchange of molecules. The implicit biocompatibility and nanoscale feasibility of MC make it a promising communication technology for nanonetworks. This paper provides a closed-form expression for the information capacity of an MC system based on the free diffusion of molecules, which is of primary importance to understand the performance of the MC paradigm. Unlike previous contributions, the provided capacity expression is independent from any coding scheme and takes into account the two main effects of the diffusion channel: the memory and the molecular noise. For this, the diffusion is decomposed into two processes, namely, the Fick's diffusion and the particle location displacement, which are analyzed as a cascade of two separate systems. The Fick's diffusion captures solely the channel memory, while the particle location displacement isolates the molecular noise. The MC capacity expression is obtained by combining the two systems as function of the diffusion coefficient, the temperature, the transmitter-receiver distance, the bandwidth of the transmitted signal, and the average transmitted power. Numerical results show that a few kilobits per second can be reached within a distance range of tenth of micrometer and for an average transmitted power around 1 pW. <s> BIB007 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> In the Molecular Communication (MC), molecules are utilized to encode, transmit, and receive information. Transmission of the information is achieved by means of diffusion of molecules and the information is recovered based on the molecule concentration variations at the receiver location. The MC is very prone to intersymbol interference (ISI) due to residual molecules emitted previously. Furthermore, the stochastic nature of the molecule movements adds noise to the MC. For the first time, we propose four methods for a receiver in the MC to recover the transmitted information distorted by both ISI and noise. We introduce sequence detection methods based on maximum a posteriori (MAP) and maximum likelihood (ML) criterions, a linear equalizer based on minimum mean-square error (MMSE) criterion, and a decision-feedback equalizer (DFE) which is a nonlinear equalizer. We present a channel estimator to estimate time varying MC channel at the receiver. The performances of the proposed methods based on bit error rates are evaluated. The sequence detection methods reveal the best performance at the expense of computational complexity. However, the MMSE equalizer has the lowest performance with the lowest computational complexity. The results show that using these methods significantly increases the information transmission rate in the MC. <s> BIB008 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> In order to understand information processing in neural circuits, it is necessary to detect both electrical and chemical signaling with high spatial and temporal resolution. Although the primary currency of neural information processing is electrical, many of the downstream effects of the electrical signals on the circuits that generate them are dependent on activity-dependent increases in intracellular calcium concentration. It is therefore of great utility to be able to record electrical signals in neural circuits at multiple sites, while at the same time detecting optical signals from reporters of intracellular calcium levels. We describe here a microfluidic multi-electrode array (MMEA) capable of high-resolution extracellular recording from brain slices that is optically compatible with calcium imaging at single cell resolution. We show the application of the MMEA device to record waves of spontaneous activity in developing cortical slices and to perform multi-site extracellular recordings during simultaneous calcium imaging of activity. The MMEA has the unique capability to simultaneously allow focal electrical and chemical stimuli at different locations of the surface of a brain slice. <s> BIB009 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Synthetic analog gene circuits can be engineered to execute logarithmically linear sensing, addition, ratiometric and power-law computations in living cells using just three transcription factors. <s> BIB010 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <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> BIB011 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> In this paper, we consider a molecular diffusion based communications link that can reliably transport data over-the-air. We show that the system can also reliably transport data across confined structural environments, especially in cases where conventional electromagnetic (EM) wave based systems may fail. In particular, this paper compares the performance of our proprietary molecular communication test-bed with Zigbee wireless sensors in a metal pipe network that does not act as a radio wave-guide. The paper first shows that a molecular-based communication link's performance is determined primarily by the delay time spread of the pulse response. The paper go on to show that molecular-based systems can transmit more reliably in complex and confined structural environments than conventional EM-based systems. The paper then utilizes empirical data to find relationships between the received radio signal strength, the molecular pulse spread, data rate (0.1 bits/s) and the structural propagation environment. <s> BIB012 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Biological computation is a major area of focus in synthetic biology because it has the potential to enable a wide range of applications. Synthetic biologists have applied engineering concepts to biological systems in order to construct progressively more complex gene circuits capable of processing information in living cells. Here, we review the current state of computational genetic circuits and describe artificial gene circuits that perform digital and analog computation. We then discuss recent progress in designing gene networks that exhibit memory, and how memory and computation have been integrated to yield more complex systems that can both process and record information. Finally, we suggest new directions for engineering biological circuits capable of computation. <s> BIB013 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Molecular communications, where molecules are used to encode, transmit, and receive information, are a promising means of enabling the coordination of nanoscale devices. The paradigm has been extensively studied from various aspects, including channel modeling and noise analysis. Comparatively little attention has been given to the physical design of molecular receiver and transmitter, envisioning biological synthetic cells with intrinsic molecular reception and transmission capabilities as the future nanomachines. However, this assumption leads to a discrepancy between the envisaged applications requiring complex communication interfaces and protocols, and the very limited computational capacities of the envisioned biological nanomachines. In this paper, we examine the feasibility of designing a molecular receiver, in a physical domain other than synthetic biology, meeting the basic requirements of nanonetwork applications. We first review the state-of-the-art biosensing approaches to determine whether they can inspire a receiver design. We reveal that the nanoscale field effect transistor-based electrical biosensor technology (bioFET) is particularly a useful starting point for designing a molecular receiver. Focusing on bioFET-based molecular receivers with a conceptual approach, we provide a guideline elaborating on their operation principles, performance metrics, and design parameters. We then provide a simple model for signal flow in silicon nanowire FET-based molecular receiver. Finally, we discuss the practical challenges of implementing the receiver and present the future research avenues from a communication theoretical perspective. <s> BIB014 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules at the same site for the most efficient feedback regulation. Here, we address this challenge with an organic electronic multifunctional device that is capable of chemical stimulation and electrical sensing at the same site, at the single-cell scale. Conducting polymer electrodes recorded epileptiform discharges induced in mouse hippocampal preparation. The inhibitory neurotransmitter, γ-aminobutyric acid (GABA), was then actively delivered through the recording electrodes via organic electronic ion pump technology. GABA delivery stopped epileptiform activity, recorded simultaneously and colocally. This multifunctional “neural pixel” creates a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents. <s> BIB015 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Molecular communication (MC) is the most promising communication paradigm for nanonetwork realization since it is a natural phenomenon observed among living entities with nanoscale components. Since MC significantly differs from classical communication systems, it mandates reinvestigation of information and communication theoretical fundamentals. The closest examples of MC architectures are present inside our own body. Therefore, in this paper, we investigate the existing literature on intrabody nanonetworks and different MC paradigms to establish and introduce the fundamentals of molecular information and communication science. We highlight future research directions and open issues that need to be addressed for revealing the fundamental limits of this science. Although the scope of this development encompasses wide range of applications, we particularly emphasize its significance for life sciences by introducing potential diagnosis and treatment techniques for diseases caused by dysfunction of intrabody nanonetworks. <s> BIB016 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Abstract Drug delivery systems (DDS) are engineered methods to enable the targeted delivery of therapeutic agents at the right rate and location while minimizing the undesired side effects. The recent advances in bioengineering and nanotechnology make it possible to design molecular compounds with specific sizes, shapes, structures and chemical properties to improve the drug uptake and minimize its side effects. Despite all of this progress, overcoming the biological barriers to drug delivery remains challenging. Observing the parallels between the delivery of drugs and the delivery of data, a new paradigm in communication systems research, called molecular communication (MC), has been devised to approach this problem. This paper presents the state-of-the-art, challenges and research opportunities in studying DDS through the MC paradigm. First, the constituting elements of a DDS are presented, highlighting the contributions from MC research. Second, an overview is given of the novel modeling approaches based on communication theory and several simulation platforms applicable to the study of drug delivery systems are presented. Finally, lessons are drawn from the efforts of the MC community on this research topic and future research opportunities and challenges are discussed. <s> BIB017 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> In recent years, progresses in nanotechnology have established the foundations for implementing nanomachines capable of carrying out simple but significant tasks. Under this stimulus, researchers have been proposing various solutions for realizing nanoscale communications, considering both electromagnetic and biological communications. Their aim is to extend the capabilities of nanodevices, so as to enable the execution of more complex tasks by means of mutual coordination, achievable through communications. However, although most of these proposals show how devices can communicate at the nanoscales, they leave in the background specific applications of these new technologies. Thus, this paper shows an overview of the actual and potential applications that can rely on a specific class of such communications techniques, commonly referred to as molecular communications. In particular, we focus on health-related applications. This decision is due to the rapidly increasing interests of research communities and companies to minimally invasive, biocompatible, and targeted health-care solutions. Molecular communication techniques have actually the potentials of becoming the main technology for implementing advanced medical solution. Hence, in this paper we provide a taxonomy of potential applications, illustrate them in some detail, along with the existing open challenges for them to be actually deployed, and draw future perspectives. <s> BIB018 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> Synthetic DNA is durable and can encode digital data with high density, making it an attractive medium for data storage. However, recovering stored data on a large-scale currently requires all the DNA in a pool to be sequenced, even if only a subset of the information needs to be extracted. Here, we encode and store 35 distinct files (over 200 MB of data), in more than 13 million DNA oligonucleotides, and show that we can recover each file individually and with no errors, using a random access approach. We design and validate a large library of primers that enable individual recovery of all files stored within the DNA. We also develop an algorithm that greatly reduces the sequencing read coverage required for error-free decoding by maximizing information from all sequence reads. These advances demonstrate a viable, large-scale system for DNA data storage and retrieval. <s> BIB019 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s>  <s> In this paper, we propose using mobile nanosensors (MNSs) for early stage anomaly detection. For concreteness, we focus on the detection of cancer cells located in a particular region of a blood vessel. These cancer cells produce and emit special molecules, so-called biomarkers, which are symptomatic for the presence of anomaly, into the cardiovascular system. Detection of cancer biomarkers with conventional blood tests is difficult in the early stages of a cancer due to the very low concentration of the biomarkers in the samples taken. However, close to the cancer cells, the concentration of the cancer biomarkers is high. Hence, detection is possible if a sensor with the ability to detect these biomarkers is placed in the vicinity of the cancer cells. Therefore, in this paper, we study the use of MNSs that are injected at a suitable injection site and can move through the blood vessels of the cardiovascular system, which potentially contain cancer cells. These MNSs can be activated by the biomarkers close to the cancer cells, where the biomarker concentration is sufficiently high. Eventually, the MNSs are collected by a fusion center (FC), where their activation levels are read and exploited to declare the presence of anomaly. We analytically derive the biomarker concentration in a network of interconnected blood vessels as well as the probability mass function of the MNSs’ activation levels and validate the obtained results via particle-based simulations. Then, we derive the optimal decision rule for the FC regarding the presence of anomaly assuming that the entire network is known at the FC. Finally, for the FC, we propose a simple sum detector that does not require knowledge of the network topology. Our simulations reveal that while the optimal detector achieves a higher performance than the sum detector, both proposed detectors significantly outperform a benchmark scheme that uses fixed nanosensors at the FC. <s> BIB020
infrastructure  ,  . In that respect, MC is promising for novel applications especially towards information and communication technology (ICT)-based early diagnosis and treatment of diseases, such as continuous health monitoring, smart drug delivery, artificial organs, and lab-on-a-chips BIB016 , BIB018 (see Fig. 1(a) ). It bears a significant potential as an alternative to conventional wireless communication in environments where the latter may fail, e.g., intrabody medium  and confined channels like pipe networks BIB011 , BIB012 . Discrete nature of information carrying agents, i.e., molecules, and peculiarities arising from the nanophysical and biochemical processes, and computational and energy-based limitations of communicating nanomachines give rise to novel challenges that cannot be always tackled by the conventional ICT methods, which are mostly tailored for electromagnetic means of communications with macroscale components. This requires rethinking of the existing ICT tools and devising new ones for MC in the light of envisioned applications and considering especially available material and fabrication technologies, which basically set the limitations. MC has been extensively studied from various aspects over the last decade. The research efforts are mainly centered around developing information theoretical models of MC channels BIB007 , BIB003 , devising modulation and detection techniques BIB005 , BIB008 , and system-theoretical modeling of MC applications BIB017 , BIB020 . For the physical design of MC transmitter (Tx) and receiver (Rx), mainly two approaches have been envisioned: biological architectures based on engineered bacteria enabled by synthetic biology, and nanomaterial-based architectures, as shown in Fig. 1(b)  . However, none of these approaches could be realized yet, and thus, there is no implementation of any artificial micro/nanoscale MC system to date. As a result, the overall MC literature mostly relies on assumptions isolating the MC channel from the physical processes regarding the transceiving operations, leading to a plethora of ICT techniques, feasibility and performance of which could not be validated. Our objective in this paper is to tackle this discrepancy between the theory and practice by providing a comprehensive account of the recent proposals for the physical design of MC-Tx/Rx and the state-of-the-art in the theoretical MC research covering modulation, coding and detection techniques. We provide an overview of the opportunities and challenges regarding the implementation of Tx/Rx and corresponding ICT techniques which are to be built on these devices. Although we mostly focus on diffusion-based MC in this review, we also partly cover other MC configuration, such as MC with flow, microfluidic MC, bacteria conjugation-based MC, and molecular-motor powered MC. We first investigate the fundamental requirements for the physical design of micro/nanoscale MC-Tx and MC-Rx, e.g., those regarding the energy and molecule consumption, computational complexity and operating conditions. In light of these requirements, both of the design approaches previously proposed for MC-Tx/Rx, i.e., artificial Tx/Rx designs enabled by the discovery of new nanomaterials, e.g., graphene, and biological Tx/Rx architectures based on the engineering tools provided by synthetic biology, are covered. The literature on physical design of micro/nanoscale artificial MC-Tx is almost nonexistent, except for a few approaches focusing on standalone drug delivery systems BIB002 and microfluidic neural interfaces with chemical stimulation capabilities BIB009 , BIB015 , which, however, do not address the communication theoretical challenges of MC. Therefore, regarding the MC-Tx architecture, we mostly investigate and propose several potential research directions towards nanomaterialbased implementation of MC-Tx based on recent advancements in nanotechnology, novel materials and microfluidics. We will particularly focus on the utilization of nanoporous graphene membranes in microfluidic settings to control the release of information molecules through electric field. For the design of artificial MC-Rx, we will focus on nanomaterialbased biosensing approaches, as a biosensor and an MC-Rx have similar functionality, i.e., both of them aim to detect the physical characteristics of molecules in an environment. Previously in BIB014 , the structure and performance of available biosensing approaches, i.e., electrical, optical and chemical sensing, are studied to evaluate their feasibility as an artificial MC receiver. It is shown that field effect transistor (FET)-based biosensors (bioFETs) satisfy the requirements of an MC receiver, i.e., nanoscale dimension, in-situ, label free, continuous and selective detection of information carriers. Thus, in this paper, we mostly focus on the operation principles of bioFETs and their main design parameters that must be selected to optimize performance of the device as an MC-Rx. We review the possible types of bioreceptors, e.g., natural receptor proteins, aptamer/DNAs, which act as the interface between the MC channel and the receiver. We also study available options for the nanomaterials, e.g., silicon nanowire (SiNW) and graphene, used as the transducer channel, and evaluate their feasibility and potential to be a part of MC receiver in terms of mechanical, electrical and chemical properties and associated fabrication challenges. We then provide an overview of studies focusing on the modeling and performance evaluation of bioFETs from MC perspective. Regarding biological architectures, there are more opportunities enabled by the synthetic biology tools in engineering bacteria with artificial MC-Tx/Rx functionalities. Biological device architectures, in general, have the advantage of biocompatibility, a necessary condition for many MC applications within healthcare and Internet of Bio-Nano Things (IoBNT) paradigm  , as well as availability of already existing molecular machinery for sensing, transmitting and propagation at micro/nanoscale, all of which are prone to be utilized for MC nanonetworking. In terms of Tx architectures, biological-based approaches also prove advantageous thanks to the capability of harnessing transmitter molecules or synthesizing them from readily available molecules, which resolves the reservoir problem. Biological architectures considered in this review include the use of genetically engineered flagellated bacteria, e.g., E. coli and viruses as encapsulated carriers of information, e.g., RNA or DNA, bacteria with engineered gene circuits for protein-based communication and Ca ++ circuits for hor-monal communication, as well as other mechanisms such as microtubule networks and biological-nanomaterial hybrid approaches. For biological receivers, synthetic biology tools allow performing complex digital and analog computations for detection BIB010 , integrate computation and memory BIB013 and enable continuously keep track of individual receptor states, as naturally done by living cells. In this paper, we provide a review of available studies on the use of genetic circuits for implementing MC receiver architectures. The major challenge in use of genetic circuits for implementing MC-Tx/Rx functionalities in engineered bacteria arises from the fact that information transmission in biological cells is through molecules and biochemical reactions. This results in nonlinear inputoutput behaviors with system-evolution-dependent stochastic effects that are needed to be comprehensively studied to evaluate the performance of the device. This paper will present a brief account of these challenges and opportunities regarding the use of biological architectures. We also provide an overview of the communication techniques proposed for MC. In particular, we will cover modulation, coding and detection methods. Modulation techniques in MC fundamentally differ from that in conventional EM communications, as the modulated entities, i.e., molecules, are discrete in nature and the developed techniques should be robust against highly time-varying characteristics of the MC channel, as well as inherently slow nature of the propagation mechanisms. Exploiting the observable characteristics of molecules, researchers have proposed to encode information into the concentration, e.g., concentration shift keying (CSK) BIB006 , molecule type, e.g., molecule shift keying (MoSK) BIB005 , and molecule release time, e.g., release time shift keying (RTSK) BIB004 . However, the proposed modulation schemes generally suffer from low data rates as it is not practical to use modulation schemes with high number of symbols due to intersymbol interference (ISI), detection sensitivity and selectivity problems. Therefore, in this paper, we also investigate two new research directions that can potentially alleviate these problems: (1) utilization of DNA/RNA as carrier molecules such that nucleotide strands differing in physical properties, e.g., length, dumbbell hairpins, short sequence motifs/labels and orientation, can enable transmitting high number of symbols that can be selectively received, (2) encoding large amount of information into the base sequences of DNAs, i.e., Nucleotide Shift-Keying (NSK) BIB019 , to boost the data rate up to the order of Mbps such that MC can compete with traditional wireless communication systems. Another fundamental aspect of MC is coding. In a communication system coding is done at two stages, source coding and channel coding. Source coding is related to the structure of information to be transmitted, which has so far not been discussed in MC literature, and is not covered in this review. On the other hand, various channel coding schemes have been applied to MC channels with the hope of error correction. However, conventional channel coding schemes developed for classical EM-wave based communications are incompatible with nanoscale MC in many aspects. To start with, channel characteristics are very different, where diffusive channels suffer extremely from ISI, which causes high bit error rates (BERs). Novel codes that specifically handle with ISI need to be developed for mitigation of these errors. Moreover, in general, energy is a scarce resource for communicating agents in a nanonetwork, requiring implementation of low complexity codes with low computational cost, which renders the application of state-of-the-art codes, such as Turbo codes BIB001 , unfeasible. Consequently, many researchers have focused on simpler block codes, such as Hamming codes  , whereas some have devised novel channel codes specifically for MC. In this review, we give a comprehensive account of these channel codes. Detection is by far the most studied aspect of MC in the literature, but there are still many open issues mainly because of the unavailability of any MC-Rx implementation that can validate the developed methods. This lack of physical models for realistic devices has led the researchers to make simplifying assumptions about the sampling process, receiver geometry and channel and reception noise. Depending on the type of these assumptions, we investigate MC detection methods under two categories: detection with passive/absorbing receivers and detection with reactive receivers. We provide a qualitative comparison of these methods in terms of considered channel and receiver characteristics, complexity, type of required channel state information (CSI), and performance. In summary, this paper provides design guidelines for the physical implementation of MC-Tx/Rxs, an overview of the state-of-the-art MC methods on transceiving molecular messages, and a detailed account of the challenges and future research directions. We believe that this comprehensive review will help researchers to overcome the major bottleneck resulting from the long-standing discrepancy between theory and practice in MC, which has, so far, severely impeded the innovation in this field linked with huge societal and economic impact. The remainder of this paper is organized as follows. In Section II, we investigate the design requirements of an MCTx, and review the physical design options for nanomaterialbased and biological MC-Tx architectures with an overview of state-of-the-art MC modulation and coding techniques. We focus on the opportunities for the physical design of an MC-Rx in Section II, where we also provide a comprehensive review of the existing MC detection schemes for passive, absorbing and reactive receivers. In Section IV, we outline the challenges and future research directions towards the implementation of MC Tx/Rxs, and the development of the corresponding coding, modulation, and detection techniques. Finally, we conclude the paper in Section V.