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Transmitter and Receiver Architectures for Molecular Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design With Modulation, Coding, and Detection Techniques This article focuses on the design of transmitters and receivers for molecular communication (MC). It also reviews existing literature on transmitter and receiver architectures for realizing MC, including both nanomaterial-based nanomachines and/or biological entities. By MURAT KUSCU , Student Member IEEE,ERGIN DINC , Member IEEE, BILGESU A. BILGIN , Member IEEE,HAMIDEH RAMEZANI , Student Member IEEE, AND OZGUR B. AKAN , Fellow IEEE ABSTRACT | Inspired by nature, molecular communications ing novel device architectures and communication methods (MC), i.e., the use of molecules to encode, transmit, and compatible with MC constraints. To that end, various transmit- receive information, stands as the most promising communica- ter and receiver designs for MC have been proposed in the tion paradigm to realize the nanonetworks. Even though there literature together with numerable modulation, coding, and has been extensive theoretical research toward nanoscale detection techniques. However, these works fall into domains MC, there are no examples of implemented nanoscale MC of a very wide spectrum of disciplines, including, but not networks. The main reason for this lies in the peculiarities limited to, information and communication theory, quantum of nanoscale physics, challenges in nanoscale fabrication, physics, materials science, nanofabrication, physiology, and and highly stochastic nature of the biochemical domain of synthetic biology. Therefore, we believe it is imperative for the envisioned nanonetwork applications. This mandates develop- progress of the field that an organized exposition of cumulative knowledge on the subject matter can be compiled. Thus, to fill this gap, in this comprehensive survey, we review the existing Manuscript received November 5, 2018; revised March 13, 2019; accepted literature on transmitter and receiver architectures toward April 30, 2019. Date of publication May 30, 2019; date of current version July 19, realizing MC among nanomaterial-based nanomachines and/or 2019. This work was supported in part by the European Research Council (ERC) Projects MINERVA under Grant ERC-2013-CoG #616922 and MINERGRACE under biological entities and provide a complete overview of mod- Grant ERC-2017-PoC #780645. (Corresponding author: Murat Kuscu.) ulation, coding, and detection techniques employed for MC. M. Kuscu, E. Dinc, B. A. Bilgin,andH. Ramezani are with the Electrical Engineering Division, Internet of Everything (IoE) Group, Department of Moreover, we identify the most significant shortcomings and Engineering, University of Cambridge, Cambridge CB3 0FA, U.K. (e-mail: challenges in all these research areas and propose potential [email protected]; [email protected]; [email protected]; [email protected]). O. B. Akan is with the Electrical Engineering Division, Internet of Everything solutions to overcome some of them. (IoE) Group, Department of Engineering, University of Cambridge, Cambridge CB3 0FA, U.K., and also with the Next-generation and Wireless Communications KEYWORDS | Coding; detection; Internet of Bio-Nano Laboratory (NWCL), Department of Electrical and Electronics Engineering, Koc University, 34450 Istanbul, Turkey (e-mail: [email protected]). Things (IoBNT); modulation; molecular communications (MCs); nanonetworks; receiver; transmitter. Digital Object Identifier 10.1109/JPROC.2019.2916081 0018-9219 © 2019 IEEE. Translations and content mining are permitted for academic research only. Personal use is also permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information. 1302 PROCEEDINGS OF THE IEEE | Vol. 107, No. 7, July 2019 Kuscu et al.: Transmitter and Receiver Architectures for MCs I. INTRODUCTION the transmitted molecules propagate through passive dif- fusion along concentration gradients. This is the most Molecular communications (MC) is a bioinspired com- widely utilized MC configuration in the literature, as the munication method that uses molecules for encoding, propagation of molecules does not necessitate additional transmitting, and receiving information, in the same way complexity or energy consumption. Moreover, diffusion is by which the living cells communicate [1]. MC is inher- the main molecular transport mechanism in many of the ently biocompatible, energy-efficient, and robust in physi- widespread natural MC systems, such as synaptic commu- ological conditions. Therefore, it has emerged as the most nication, quorum sensing, and Ca2+ signaling. However, promising method to realize nanonetworks and Internet of throughout this review, we also partly cover other MC Bio-Nano Things (IoBNT), which defines the artificial net- configurations, such as diffusion-based MC with the addi- works of nanoscale functional units, such as nanobiosen- tional flow, microfluidic MC, bacteria conjugation-based sors and engineered bacteria, integrated with the Internet MC, and molecular-motor powered MC, while discussing infrastructure [1], [2]. In that respect, MC is promising the physical design approaches for MC-Tx/Rx. for novel applications, especially toward information and We first investigate the fundamental requirements for communication technology (ICT)-based early diagnosis the physical design of microscale/nanoscale MC-Tx and and treatment of diseases, such as continuous health mon- MC-Rx, such as those regarding the energy and molecule itoring, smart drug delivery, artificial organs, and lab-on-a- consumption, computational complexity, and operating chip [3], [4] [see Fig. 1(a)]. It bears a significant potential conditions. In light of these requirements, we cover the as an alternative to conventional wireless communications, two design approaches, namely, the nanomaterial-based especially in those environments where the latter may fail, approach enabled by the newly discovered nanomateri- such as intrabody medium [5] and confined channels such als, e.g., graphene, and the biological approach enabled as pipe networks [6], [7]. However, the discrete nature of by the synthetic biology tools. For nanomaterial-based information-carrying agents (i.e., molecules), peculiarities MC-Tx, we investigate architectures based on microflu- arising from the nanophysical and biochemical processes, idics, stimuli-responsive hydrogels, and nanoporous struc- and computational and energy-based limitations of com- tures, whereas for biological MC-Tx, we particularly focus municating nanomachines give rise to novel challenges. on transmission schemes based on bacterial-conjugation, This necessitates rethinking conventional ICT tools and virus transmission, genetic circuit-regulated protein trans- devising new ones for MC in light of envisioned IoBNT mission, and enzyme-regulated Ca2+ transmission. For applications. nanomaterial-based MC-Rx, although we mostly focus on MC has been extensively studied from various aspects the nanoscale field-effect-transistor biosensor (bioFET)- over the last decade. The research efforts are mainly cen- based designs, we also discuss receiver architectures that tered around developing information theoretical models are widely utilized in initial macroscale MC experiments. of MC channels [8], devising modulation and detection Toward the biological design of MC-Rx, we provide a brief techniques [9], [10], and system theoretical modeling of review of synthetic biology tools that are available for MC applications [11]. For the physical design of MC trans- sampling and decoding molecular messages. mitter (MC-Tx) and MC receiver (MC-Rx), mainly, two In this paper, we also provide an overview of the approaches have been envisioned: biological architectures modulation, coding, and detection methods proposed for based on engineered bacteria enabled by synthetic biology MC. Modulation techniques in MC fundamentally differ and nanomaterial-based architectures that are conceptu- from that in conventional electromagnetic (EM) commu- ally visualized in Fig. 1(b) [1]. However, none of these nications, as the modulated entities, i.e., molecules, are approaches could be realized yet, and thus, there is no discrete in nature and the developed techniques should implementation of any artificial microscale/nanoscale MC be robust against highly time-varying characteristics of system to date. As a result, the overall MC literature mostly the MC channel, as well as the inherently slow nature of relies on assumptions isolating the MC channel from the the propagation mechanisms. We cover MC modulation physical processes regarding the transceiving operations, techniques that encode information into the concentration, leading to a plethora of ICT techniques, feasibility, and type, ratio, release time, and release order of molecules, performance of which could not be validated. as well as the base sequences of nucleotides. We also Our objective in this paper is to help close the gap review the MC channel coding techniques that over- between theory and practice in the MC research by pro- come the extremely noisy and intersymbol interference viding a comprehensive account of the recent proposals (ISI)-susceptible nature of MC channels via introducing for the physical design of MC-Tx/Rx and the state-of- the redundant bits. Our review covers MC-specific chan- the-art theoretical studies covering modulation, coding, nel coding methods, such as the ISI-free coding scheme and detection techniques.
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