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Molecular communication (MC) is a bio-inspired method of transmitting information using biochemical signals, promising for novel medical, agricultural, and environmental applications at the intersection of bio-, nano-, and communication technologies. Developing reliable MC systems for high-rate information transfer remains challenging due to the complex and dynamic nature of application environments and the physical and resource limitations of micro/nanoscale transmitters and receivers. Microfluidics can help overcome many such practical challenges by enabling testbeds that can replicate the application media with precise control over flow conditions. However, existing microfluidic MC testbeds face significant limitations in chemical signal generation with programmable signal waveforms, e.g., in terms of pulse width. To tackle this, we previously proposed a practical microfluidic MC transmitter architecture based on the hydrodynamic gating technique, a prevalent chemical waveform generation method. This paper reports the experimental validation and characterization of this method, examining its precision in terms of spatiotemporal control on the generated molecular concentration pulses. We detail the fabrication of the transmitter, its working mechanism and discuss its potential limitations based on empirical data. We show that the microfluidic transmitter is capable of providing precise, programmable, and reproducible molecular concentration pulses, which would facilitate the experimental research in MC.

Molecular Communications (MC) is a bio-inspired communication paradigm that uses molecules as information carriers, requiring unconventional transceivers and modulation/detection techniques. Practical MC receivers (MC-Rxs) can be implemented using field-effect transistor biosensor (bioFET) architectures, where surface receptors reversibly react with ligands. The time-varying concentration of ligand-bound receptors is translated into electrical signals via field effect, which is used to decode the transmitted information. However, ligand-receptor interactions do not provide an ideal molecular selectivity, as similar ligand types, i.e., interferers, co-existing in the MC channel, can interact with the same type of receptors. Overcoming this molecular cross-talk in the time domain can be challenging, especially when Rx has no knowledge of the interferer statistics or operates near saturation. Therefore, we propose a frequency-domain detection (FDD) technique for bioFET-based MC-Rxs that exploits the difference in binding reaction rates of different ligand types reflected in the power spectrum of the ligand-receptor binding noise. We derive the bit error probability (BEP) of the FDD technique and demonstrate its effectiveness in decoding transmitted concentration signals under stochastic molecular interference compared to a widely used time-domain detection (TDD) technique. We then verified the analytical performance bounds of the FDD through a particle-based spatial stochastic simulator simulating reactions on the MC-Rx in microfluidic channels., Comment: Submitted to the IEEE for possible publication. arXiv admin note: text overlap with arXiv:2301.01049

Molecular Communications (MC) is a bio-inspired paradigm for transmitting information using chemical signals, which can enable novel applications at the junction of biotechnology, nanotechnology, and information and communication technologies. However, designing efficient and reliable MC systems poses significant challenges due to the complex nature of the physical channel and the limitations of the micro/nanoscale transmitter and receiver devices. In this paper, we propose a practical microfluidic transmitter architecture for MC based on hydrodynamic gating, a widely utilized technique for generating chemical waveforms in microfluidic channels with high spatiotemporal resolution. We develop an approximate analytical model that can capture the fundamental characteristics of the generated molecular pulses, such as pulse width, pulse amplitude, and pulse delay, as functions of main system parameters, such as flow velocity and gating duration. We validate the accuracy of our model by comparing it with finite element simulations using COMSOL Multiphysics under various system settings. Our analytical model can enable the optimization of microfluidic transmitters for MC applications in terms of minimizing intersymbol interference and maximizing data transmission rate.

Molecular Communication (MC) is a bio-inspired communication paradigm utilizing molecules for information transfer. Research on this unconventional communication technique has recently started to transition from theoretical investigations to practical testbed implementations, primarily harnessing microfluidics and sensor technologies. Developing accurate models for input-output relationships on these platforms, which mirror real-world scenarios, is crucial for assessing modulation and detection techniques, devising optimized MC methods, and understanding the impact of physical parameters on performance. In this study, we consider a practical microfluidic MC system equipped with a graphene field effect transistor biosensor (bioFET)-based MC receiver as the model system, and develop an analytical end-to-end frequency-domain model. The model provides practical insights into the dispersion and distortion of received signals, thus potentially informing the design of new frequency-domain MC techniques, such as modulation and detection methods. The accuracy of the developed model is verified through particle-based spatial stochastic simulations of pulse transmission in microfluidic channels and ligand-receptor binding reactions on the receiver surface.

Molecular Communications (MC) underpins signaling in biological systems, enabling information transfer through biochemical molecules. The prospect of engineering this natural communication mechanism has inspired the Internet of Bio-Nano Things (IoBNT) applications, which rely on heterogeneous collaborative networks of natural and engineered biological devices, as well as artificial micro/nanomachines. A key attribute of natural MC systems is their adaptability, ensuring accurate information transmission in dynamic, time-varying biochemical environments. Therefore, integrating biological adaptation techniques into artificial MC networks, which are expected to operate in various biochemical environments, such as inside human body, is essential for robust and biocompatible IoBNT applications. This study explores the design of bio-inspired adaptive MC receivers capable of tuning their response functions for maintaining optimal detection performance in scenarios with time-varying received signals. The proposed receiver architectures are based on ligand-receptor interactions, with adaptivity achieved by modifying the sigmoidal-shaped ligand-receptor response curve in response to fluctuations in received signal statistics. The performance of these adaptive receivers is evaluated across a range of MC scenarios, including those with stochastic background interference, inter-symbol interference (ISI), and degrading enzymes, which involve time-varying scaling or shifting of received signals. Numerical results demonstrate the significant improvement in detection performance provided by adaptive receivers in dynamic MC scenarios.

A key challenge in Molecular Communications (MC) is low data transmission rates, which can be addressed by channel multiplexing techniques. One way to achieve channel multiplexing in MC is to leverage the diversity of different molecule types with respect to their receptor binding characteristics, such as affinity and kinetic binding/unbinding rates. In this study, we propose a practical multiplexing scheme for MC, which is based on the diversity of ligand-receptor binding affinities. This method requires only a single type of promiscuous receptor on the receiver side, capable of interacting with multiple ligand types. We analytically derive the mean Bit Error Probability (BEP) over all multiplexed MC channels as a function of similarity among ligands in terms of their receptor affinities, the number of receptors, the number of multiplexed channels, and the ratio of concentrations encoding bit-1 and bit-0. We investigate the impact of each design parameter on the performance of multiplexed MC system.

Internet of Bio-Nano Things (IoBNT) is a transformative communication framework, characterized by heterogeneous networks comprising both biological entities and artificial micro/nano-scale devices, so-called Bio-Nano Things (BNTs), interfaced with conventional communication networks for enabling innovative biomedical and environmental applications. Realizing the potential of IoBNT requires the development of new and unconventional communication technologies, such as molecular communications, as well as the corresponding transceivers, bio-cyber interfacing technologies connecting the biochemical domain of IoBNT to the electromagnetic domain of conventional networks, and miniaturized energy harvesting and storage components for the continuous power supply to BNTs. Graphene and related materials (GRMs) exhibit exceptional electrical, optical, biochemical, and mechanical properties, rendering them ideal candidates for addressing the challenges posed by IoBNT. This perspective article highlights recent advancements in GRM-based device technologies that are promising for implementing the core components of IoBNT. By identifying the unique opportunities afforded by GRMs and aligning them with the practical challenges associated with IoBNT, particularly in the materials domain, our aim is to accelerate the transition of envisaged IoBNT applications from theoretical concepts to practical implementations, while also uncovering new application areas for GRMs.

Molecular Communications (MC) is a bio-inspired communication technique that uses molecules to encode and transfer information. Many efforts have been devoted to developing novel modulation techniques for MC based on various distinguishable characteristics of molecules, such as their concentrations or types. In this paper, we investigate a particular modulation scheme called Ratio Shift Keying (RSK), where the information is encoded in the concentration ratio of two different types of molecules. RSK modulation is hypothesized to enable accurate information transfer in dynamic MC scenarios where the time-varying channel characteristics affect both types of molecules equally. To validate this hypothesis, we first conduct an information-theoretical analysis of RSK modulation and derive the capacity of the end-to-end MC channel where the receiver estimates concentration ratio based on ligand-receptor binding statistics in an optimal or suboptimal manner. We then analyze the error performance of RSK modulation in a practical time-varying MC scenario, that is mobile MC, in which both the transmitter and the receiver undergo diffusion-based propagation. Our numerical and analytical results, obtained for varying levels of similarity between the ligand types used for ratio-encoding, and varying number of receptors, show that RSK can significantly outperform the most commonly considered MC modulation technique, concentration shift keying (CSK), in dynamic MC scenarios., Comment: 13 pages, 7 figures. arXiv admin note: substantial text overlap with arXiv:2205.13317

Molecular Communication (MC) is a bio-inspired communication modality that utilizes chemical signals in the form of molecules to exchange information between spatially separated entities. Pulse shaping is an important process in all communication systems, as it modifies the waveform of transmitted signals to match the characteristics of the communication channel for reliable and high-speed information transfer. In MC systems, the unconventional architectures of components, such as transmitters and receivers, and the complex, nonlinear, and time-varying nature of MC channels make pulse shaping even more important. While several pulse shaping methods have been theoretically proposed for MC, their practicality and performance are still uncertain. Moreover, the majority of recently proposed experimental MC testbeds that rely on microfluidics technology lack the incorporation of programmable pulse shaping methods, which hinders the accurate evaluation of MC techniques in practical settings. To address the challenges associated with pulse shaping in microfluidic MC systems, we provide a comprehensive overview of practical microfluidic chemical waveform generation techniques that have been experimentally validated and whose architectures can inform the design of pulse shaping methods for microfluidic MC systems and testbeds. These techniques include those based on hydrodynamic and acoustofluidic force fields, as well as electrochemical reactions. We also discuss the fundamental working mechanisms and system architectures of these techniques, and compare their performances in terms of spatiotemporal resolution, selectivity, system complexity, and other performance metrics relevant to MC applications, as well as their feasibility for practical MC applications., Comment: 14 pages, 11 figures

Molecular Communications (MC) is a bio-inspired communication technique that uses molecules to encode and transfer information. Many efforts have been focused on developing new modulation techniques for MC by exploiting distinguishable properties of molecules. In this paper, we investigate a particular modulation scheme where the information is encoded into the concentration ratio of two different types of molecules. To evaluate the performance of this so-called Ratio Shift Keying (RSK) modulation, we carry out an information theoretical analysis and derive the capacity of the end-to-end MC channel where the receiver performs ratio estimation based on ligand-receptor binding statistics in an optimal or suboptimal manner. The numerical results, obtained for varying similarity between the ligand types employed for ratio-encoding, and number of receptors, indicate that the RSK can outperform the concentration shift keying (CSK) modulation, the most common technique considered in literature, when the transmitter is power-limited. The results also indicate the potential advantages of RSK over other modulation methods under time-varying channel conditions, when the effects of the dynamic conditions are invariant to the type of the molecules.

Internet of Bio-Nano Things (IoBNT) is envisioned to be a heterogeneous network of nanoscale and biological devices, so called Bio-Nano Things (BNTs), communicating via non-conventional means, e.g., molecular communications (MC), in non-conventional environments, e.g., inside human body. The main objective of this emerging networking framework is to enable direct and seamless interaction with biological systems for accurate sensing and control of their dynamics in real time. This close interaction between bio and cyber domains with unprecedentedly high spatio-temporal resolution is expected to open up vast opportunities to devise novel applications, especially in healthcare area, such as intrabody continuous health monitoring. There are, however, substantial challenges to be overcome if the enormous potential of the IoBNT is to be realized. These range from developing feasible nanocommunication and energy harvesting techniques for BNTs to handling the big data generated by IoBNT. In this survey, we attempt to provide a comprehensive overview of the IoBNT framework along with its main components and applications. An investigation of key technological challenges is presented together with a detailed review of the state-of-the-art approaches and a discussion of future research directions.

The Internet of Everything (IoE) is a recently introduced information and communication technology (ICT) framework promising for extending the human connectivity to the entire universe, which itself can be regarded as a natural IoE, an interconnected network of everything we perceive. The countless number of opportunities that can be enabled by IoE through a blend of heterogeneous ICT technologies across different scales and environments and a seamless interface with the natural IoE impose several fundamental challenges, such as interoperability, ubiquitous connectivity, energy efficiency, and miniaturization. The key to address these challenges is to advance our communication technology to match the multi-scale, multi-modal, and dynamic features of the natural IoE. To this end, we introduce a new communication device concept, namely the universal IoE transceiver, that encompasses transceiver architectures that are characterized by multi-modality in communication (with modalities such as molecular, RF/THz, optical and acoustic) and in energy harvesting (with modalities such as mechanical, solar, biochemical), modularity, tunability, and scalability. Focusing on these fundamental traits, we provide an overview of the opportunities that can be opened up by micro/nanoscale universal transceiver architectures towards realizing the IoE applications. We also discuss the most pressing challenges in implementing such transceivers and briefly review the open research directions. Our discussion is particularly focused on the opportunities and challenges pertaining to the IoE physical layer, which can enable the efficient and effective design of higher-level techniques. We believe that such universal transceivers can pave the way for seamless connection and communication with the universe at a deeper level and pioneer the construction of the forthcoming IoE landscape.

Molecular Communications (MC) is a bio-inspired communication technique that uses molecules to transfer information among bio-nano devices. In this paper, we focus on the detection problem for biological MC receivers employing ligand receptors to infer the transmitted messages encoded into the concentration of molecules, i.e., ligands. In practice, receptors are not ideally selective against target ligands, and in physiological environments, they can interact with multiple types of ligands at different reaction rates depending on their binding affinity. This molecular cross-talk can cause a substantial interference on MC. Here we consider a particular scenario, where there is non-negligible concentration of interferer molecules in the channel, which have similar receptor-binding characteristics with the information molecules, and the receiver employs single type of receptors. We investigate the performance of four different detection methods, which make use of different statistics of the ligand-receptor binding reactions: instantaneous number of bound receptors, unbound time durations of receptors, bound time durations of receptors, and combination of unbound and bound time durations of receptors within a sampling time interval. The performance of the introduced detection methods are evaluated in terms of bit error probability for varying strength of molecular interference, similarity between information and interferer molecules, number of receptors, and received concentration difference between bit-0 and bit-1 transmissions. We propose synthetic receptor designs that can convert the required receptor statistics to the concentration of intracellular molecules, and chemical reaction networks that can chemically perform the computations required for detection., Comment: 17 pages, 10 figures

Bio-inspired molecular communications (MC), where molecules are used to transfer information, is the most promising technique to realise the Internet of Nano Things (IoNT), thanks to its inherent biocompatibility, energy-efficiency, and reliability in physiologically-relevant environments. Despite a substantial body of theoretical work concerning MC, the lack of practical micro/nanoscale MC devices and MC testbeds has led researchers to make overly simplifying assumptions about the implications of the channel conditions and the physical architectures of the practical transceivers in developing theoretical models and devising communication methods for MC. On the other hand, MC imposes unique challenges resulting from the highly complex, nonlinear, time-varying channel properties that cannot be always tackled by conventional information and communication tools and technologies (ICT). As a result, the reliability of the existing MC methods, which are mostly adopted from electromagnetic communications and not validated with practical testbeds, is highly questionable. As the first step to remove this discrepancy, in this study, we report on the fabrication of a nanoscale MC receiver based on graphene field-effect transistor biosensors. We perform its ICT characterisation in a custom-designed microfluidic MC system with the information encoded into the concentration of single-stranded DNA molecules. This experimental platform is the first practical implementation of a micro/nanoscale MC system with nanoscale MC receivers, and can serve as a testbed for developing realistic MC methods and IoNT applications., Comment: References fixed

Inspired by Nature, molecular communications (MC), i.e., use of molecules to encode, transmit and receive information, stands as the most promising communication paradigm to realize nanonetworks. Even though there has been extensive theoretical research towards nanoscale MC, there are no examples of implemented nanoscale MC networks. The main reason for this lies in the peculiarities of nanoscale physics, challenges in nanoscale fabrication and highly stochastic nature of biochemical domain of envisioned nanonetwork applications. This mandates developing novel device architectures and communication methods compatible with MC constraints. To that end, various transmitter and receiver designs for MC have been proposed in literature together with numerable modulation, coding and detection techniques. However, these works fall into domains of a very wide spectrum of disciplines, including but not limited to information and communication theory, quantum physics, materials science, nanofabrication, physiology and synthetic biology. Therefore, we believe it is imperative for the progress of the field that, an organized exposition of cumulative knowledge on subject matter be compiled. Thus, to fill this gap, in this comprehensive survey we review the existing literature on transmitter and receiver architectures towards realizing MC amongst nanomaterial-based nanomachines and/or biological entities, and provide a complete overview of modulation, coding and detection techniques employed for MC. Moreover, we identify the most significant shortcomings and challenges in all these research areas, and propose potential solutions to overcome some of them.

Molecular Communications (MC) uses molecules as information carriers between nanomachines. MC channel in practice can be crowded with different types of molecules, i.e., ligands, which can have similar binding properties causing severe cross-talk on ligand receptors. Simultaneous sensing of multiple ligand types provides opportunities for eliminating interference of external molecular sources and multi-user interference (MUI), and developing new multiple access techniques for MC nanonetworks. In this paper, we investigate channel sensing methods that use only a single type of receptors and exploit the amount of time receptors stay bound and unbound during ligand-receptor binding reaction to concurrently estimate the concentration of multiple types of ligands. We derive the Cram\'er-Rao Lower Bound (CRLB) for multi-ligand estimation, and propose practical and low-complexity suboptimal estimators for channel sensing. We analyze the performance of the proposed methods in terms of normalized mean squared error (NMSE), and show that they can efficiently estimate the concentration of ligands up to $10$ different types with an average NMSE far below $10^{-2}$. Lastly, we propose a synthetic receptor design based on modified kinetic proofreading (KPR) scheme to sample the unbound and bound time durations, and a Chemical Reaction Network (CRN) to perform the required computations in synthetic cells.

Molecular communication (MC) is a bio-inspired communication method based on the exchange of molecules for information transfer among nanoscale devices. Although MC has been extensively studied from various aspects, limitations imposed by the physical design of transceiving units have been largely neglected in the literature. Recently, we have proposed a nanobioelectronic MC receiver architecture based on the nanoscale field effect transistor-based biosensor (bioFET) technology, providing noninvasive and sensitive molecular detection at nanoscale while producing electrical signals at the output. In this paper, we derive analytical closed-form expressions for the capacity and capacity-achieving input distribution for a memoryless MC channel with a silicon nanowire (SiNW) FET-based MC receiver. The resulting expressions could be used to optimize the information flow in MC systems equipped with nanobioelectronic receivers., Comment: To be presented at IEEE EMBC 2016, Orlando, FL, USA

Seamless connection of molecular nanonetworks to macroscale cyber networks is envisioned to enable the Internet of Bio-NanoThings, which promises for cutting-edge applications, especially in the medical domain. The connection requires the development of an interface between the biochemical domain of molecular nanonetworks and the electrical domain of conventional electromagnetic networks. To this aim, in this paper, we propose to exploit field effect transistor based biosensors (bioFETs) to devise a molecular antenna capable of transducing molecular messages into electrical signals. In particular, focusing on the use of SiNW FET-based biosensors as molecular antennas, we develop deterministic and noise models for the antenna operation to provide a theoretical framework for the optimization of the device from communication perspective. We numerically evaluate the performance of the antenna in terms of the Signal-to-Noise Ratio (SNR) at the electrical output., Comment: to appear in Proc. IEEE WF-IoT 2015, Milan, Italy, Dec. 2015

Molecular communications (MC), where molecules are used to encode, transmit, and receive information, is 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 nanoscale field effect transistor based electrical biosensor technology (bioFET) is a particularly 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 (SiNW) FET-based molecular receiver. Lastly, we discuss the practical challenges of implementing the receiver and present the future research avenues from a communication theoretical perspective.