A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Abstract In this study, nanoscale communication networks have been investigated in the context of binary concentration-encoded unicast molecular communication suitable for numerous emerging applications, for example in healthcare and nanobiomedicine. The main focus of the paper has been given to the spatiotemporal distribution of signal strength and modulation schemes suitable for short-range, medium-range, and long-range molecular communication between two communicating nanomachines in a nanonetwork. This paper has principally focused on bio-inspired transmission techniques for concentration-encoded molecular communication systems. Spatiotemporal distributions of a carrier signal in the form of the concentration of diffused molecules over the molecular propagation channel and diffusion-dependent communication ranges have been explained for various scenarios. Finally, the performance analysis of modulation schemes has been evaluated in the form of the steady-state loss of amplitude of the received concentration signals and its dependence on the transmitter–receiver distance. <s> BIB001 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <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> BIB002 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Nanonetworking is an emerging field of research, where nanotechnology and communication engineering are applied on a common ground. Molecular Communication (MC) is a bio-inspired paradigm, where Nanonetworks, i.e., the interconnection of devices at the nanoscale, are based on the exchange of molecules. Amongst others, diffusion-based MC is expected to be suitable for covering short distances (nm-µm). In this work, we explore the main characteristics of diffusion-based MC through the use of N3Sim, a physical simulation framework for MC. N3Sim allows for the simulation of the physics underlying the diffusion of molecules for different scenarios. Through the N3Sim results, the Linear Time Invariant (LTI) property is proven to be a valid assumption for the free diffusion-based MC scenario. Moreover, diffusion-based noise is observed and evaluated with reference to already proposed stochastic models. The optimal pulse shape for diffusion-based MC is provided as a result of simulations. Two different pulse-based coding techniques are also compared through N3Sim in terms of available bandwidth and energy consumption for communication. <s> BIB003 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Catala: El treball es una exploracio del canal de difusio molecular per nanoredes moleculars, en el qual s'identifica la resposta impulsional i en frequencia del canal, es comprova la seva linealitat i invariancia i s'extreuen les principals caracteristiques de comunicacio. S'avaluen diferents tecniques de modulacio. <s> BIB004 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Nanotechnology is enabling the development of devices in a scale ranging from one to a few hundred nanometers, known as nanomachines. How these nanomachines will communicate is still an open debate. Molecular communication is a promising paradigm that has been proposed to implement nanonetworks, i.e., the interconnection of nanomachines. Recent studies have attempted to model the physical channel of molecular communication, mainly from a communication or information-theoretical point of view. In this work, we focus on the diffusion-based molecular communication, whose physical channel is governed by Fick's laws of diffusion. We characterize the molecular channel following two complementary approaches: first, we obtain the channel impulse response, transfer function and group delay; second, we propose a pulse-based modulation scheme and we obtain analytical expressions for the most relevant performance evaluation metrics, which we also validate by simulation. Finally, we compare the scalability of these metrics with their equivalents in a wireless electromagnetic channel. We consider that these results provide interesting insights which may serve designers as a guide to implement future molecular nanonetworks. <s> BIB005 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <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> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Abstract A key research question in the design of molecular nano-communication networks is how the information is to be encoded and decoded. One particular encoding method is to use different frequencies to represent different symbols. This paper will investigate the decoding of such frequency coded signals. To the best of our knowledge, the current literature on molecular communication has only used simple ligand–receptor models as decoders and the decoding of frequency coded signals has not been studied. There are two key issues in the design of such decoders. First, the decoder must exhibit frequency selective behaviour which means that encoder symbol of a specific frequency causes a bigger response at the decoder than symbols of other frequencies. Second, the decoder must take into account inter-symbol interference which earlier studies on concentration coding have pointed out to be a major performance issue. In order to study the design of decoder, we propose a system of reaction–diffusion and reaction kinetic equations to model the system of encoder, channel and decoder. We use this model to show that enzymatic circuit of a particular inter-connection has frequency selective properties. We also explore how decoder can be designed to avoid inter-symbol interference. <s> BIB007 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Abstract Designing an optimum receiver for diffusion-based molecular communication in nano-networks needs a well justified channel model. In this paper, we present a linear and time invariant signal propagation model and an additive noise model for the diffusion-based molecular communication channel. These models are based on Brownian motion molecular statistics. Using these models, we develop the first optimal receiver design for diffusion-based molecular communication scenarios with and without inter-symbol interference. We evaluate the performance of our proposed receiver by investigating the bit error rate for small and large transmission rates. <s> BIB008 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> In this paper for the first time ever a comprehensive analysis of the sampling-based optimum signal detection in diffusion-based binary concentration-encoded molecular communication (CEMC) system has been presented. A generalized amplitude shift keying (ASK) based CEMC system has been considered in diffusion-based noise and inter-symbol interference (ISI) conditions. We present an optimum receiver architecture of sampling-based signal detection, address the critical issues in signal detection, and evaluate its performance in terms of sampling number, communication range, and transmission data rate. ISI produced by the residual molecules deteriorates the performance of the CEMC system significantly, which is further deteriorated when the communication distance and/or the transmission data rate increase(s). The proposed receiver architecture can also be used to detect multilevel (M-ary) amplitude modulated signals by increasing the alphabet size and changing the modulation format. <s> BIB009 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> In this paper, a generalized strength-based signal detection model for Concentration-Encoded Molecular Communication (CEMC) has been presented. The generalized strength-based signal detection problem in diffusion-based CEMC system has been investigated in the presence of both diffusion noise and intersymbol interference (ISI). Amplitude-shift keying (ASK)-modulated CEMC system has been considered with impulsive transmission scheme. The receiver for optimum signal detection has been developed theoretically and explained with both analytical and simulation results of binary signal detection. It is found that the receiver thus developed can detect the CEMC symbols; however, the performance of the receiver is influenced by two main factors, namely, communication range and transmission data rate. Correspondingly, the bit error rate (BER) performance of the receiver thus developed is further evaluated under various communication ranges and transmission data rates through extensive simulation experiments. <s> BIB010 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> In this paper, we propose three novel modulation techniques, i.e., concentration-based, molecular-type-based, and molecular-ratio-based, using isomers as messenger molecules for nano communication networks via diffusion. To evaluate achievable rate performance, we compare the proposed techniques with conventional insulin-based concepts under practical scenarios. Analytical and numerical results confirm that the proposed modulation techniques using isomers achieve higher data transmission rate performance than the insulin based concepts. We also investigate the tradeoff between messenger sizes and modulation orders and provide guidelines for selecting from among several possible candidates. <s> BIB011 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Nanonetworks, the interconnection of nanosystems, are envisaged to greatly expand the applications of nanotechnology in the biomedical, environmental and industrial fields. However, it is still not clear how these nanosystems will communicate among them. This work considers a scenario of Diffusion-based Molecular Communication (DMC), a promising paradigm that has been recently proposed to implement nanonetworks. In a DMC network, transmitters encode information by the emission of molecules which diffuse throughout the medium, eventually reaching the receiver locations. In this scenario, a pulse-based modulation scheme is proposed and two techniques for the detection of the molecular pulses, namely, amplitude detection and energy detection, are compared. In order to evaluate the performance of DMC using both detection schemes, the most important communication metrics in each case are identified. Their analytical expressions are obtained and validated by simulation. Finally, the scalability of the obtained performance evaluation metrics in both detection techniques is compared in order to determine their suitability to particular DMC scenarios. Energy detection is found to be more suitable when the transmission distance constitutes a bottleneck in the performance of the network, whereas amplitude detection will allow achieving a higher transmission rate in the cases where the transmission distance is not a limitation. These results provide interesting insights which may serve designers as a guide to implement future DMC networks. <s> BIB012 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <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> BIB013 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Bacterial populations housed in microfluidic environments can serve as transceivers for molecular communication, but the data-rates are extremely low (e.g., 10-5 bits per second.). In this work, genetically engineered Escherichia coli bacteria were maintained in a microfluidic device where their response to a chemical stimulus was examined over time. The bacteria serve as a communication receiver where a simple modulation such as on-off keying (OOK) is achievable, although it suffers from very poor data-rates. We explore an alternative communication strategy called time-elapse communication (TEC) that uses the time period between signals to encode information. We identify the limitations of TEC under practical non-zero error conditions and propose an advanced communication strategy called smart time-elapse communication (TEC-SMART) that achieves over a 10x improvement in data-rate over OOK. We derive the capacity of TEC and provide a theoretical maximum data-rate that can be achieved. <s> BIB014 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Abstract Molecular communications is emerging as a promising paradigm for nanoscale communications in nanotechnology. Though still at an early stage, research efforts have been devoted and various molecular communication systems have been proposed. However, each proposed system possesses a specific structure to achieve communications in its own way. To our best knowledge, no unified system description exists so far. In this paper, we propose an abstract system structure called an event-driven system ; a significant group of molecular communication systems can be classified into such an abstract form. We define event-driven systems and further show that, for these systems, there is a signaling scheme called asynchronous information embedding which carries additional information while at the same time keeping the original communication mechanisms uninfluenced. Instead of investigating asynchronous information embedding in full generality, we consider synchronous type-based systems as a demonstrative example which still captures most of the features. For such type-based systems, we develop an approximation method for obtaining the channel capacity as a general performance measure. Numerical results are provided to show the capacity gain of asynchronous information embedding. <s> BIB015 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> B. Modulation Techniques <s> Molecular communication (MC) aims to develop a promising bio-inspired communication paradigm for nanotechnology, in which molecules are used to encode, transmit, and receive information. One of the main challenges in MC is the intersymbol interference (ISI) caused by the nature of the diffusion channel. The most popular solution to reduce the effects of ISI in MC is to keep the symbol duration as long as possible and reduce the number of molecules that can be received in subsequent symbol durations. On the other hand, a long symbol duration leads to a very low data rate, even for very short distances. Furthermore, due to the size of the nano-scale machines, production of energy becomes an essential problem. In this paper, an ISI mitigation technique for diffusion-based molecular communication channels, titled Molecular Transition Shift Keying (MTSK) is proposed in order to increase the data rate via suppressing the negative impact of the ISI on communication quality. MTSK employs multiple molecule types and the energy efficient extended version of MTSK with power adjustment (MTSK-PA) makes use of the residual molecules in the channel to reduce the ISI that would otherwise contribute to the ISI. It is shown via computer simulations that both MTSK and MTSK-PA outperforms the standard modulation techniques proposed in the literature. <s> BIB016
Modulation is the process of varying one or more properties the carrier signal according to the transmission symbol. In essence, transmission symbols are encoded in changes of the properties of the carrier signal. In traditional radio based wireless communication systems, the carrier of information is electromagnetic waves. Radio waves are sinusoidal signals that can be presented mathematically as where A is the amplitude of the sinusoidal, f is the frequency, and φ is the phase. The amplitude effects the peak to peak height of the sinusoidal, the frequency effects the number of cycles per seconds, and the phase effects the amount of shift from the origin. Information can be modulated on the amplitude, the phase, the frequency, or any combination of these parameters. Figure 11 (a) demonstrates the modulation of binary data (0 and 1) using amplitude, frequency, and phase. In molecular communication, the carriers of information are very tiny information particles (e.g., molecules). In this scheme information can be modulated on the following properties of the information particles. • Number of Particles: Information can be encoded in the number of information particles released. If the number of information particles that are released is very large (e.g., at macroscales), concentration (i.e., the number of particles per unit volume) could be used instead of the number of particles. In general, modulating information in the number of information particles is very similar to amplitude modulation in radio communication. For example, increasing the number of photons in an optical channel, increases the intensity and hence the amplitude of the signal. • Type of Particles: It is possible to encode information in the type (or structure) of information particles released. For example, two types of molecules could be used to encode two bits of information. This can be compared to frequency modulation from traditional radio communication. Changing the frequency of an electromagnetic wave changes its properties. For example, visible light has a higher frequency than radio waves and interacts differently with matter. As another example, in a multiuser environment filters could isolate a specific frequency band of the signal which belongs to a specific user. Similarly, in molecular communication specific detectors could be used to detect a specific signaling molecule belonging to a specific user. • Time of Release: Information can be encoded in the time of release of information particles. This can be compared with phase modulation in a traditional communication scheme. For example, information can be encoded in the time interval between two consecutive transmissions. Figure 11 (b) demonstrates the modulation of binary data (0 and 1) using the number of molecules (concentration), the type of molecules, and their release timing. Just like radio based communication, it is also possible to use any combination of these modulation schemes. It must be noted that the analogy used here between amplitude and number of particles, frequency and type of particles, phase and time of release is not literal. In the rest of this section we survey some of the recent work on modulation techniques for molecular communication. One of the first works that considered modulation in molecular communication was BIB001 . In this work the authors considered two different modulation schemes for the diffusion based propagation channels. In the first modulation scheme, a binary bit-0 was represented by concentration zero and the bit 1 by concentration Q. This modulation scheme is similar to on-off-keying from traditional telecommunication. In the second scheme, the concentration of information particles was varied according to a sinusoidal signal with a given frequency, and it is assumed information can be encoded in the amplitude and the frequency of this sinusoidal. In BIB002 two new modulation schemes were proposed for diffusion based propagation channels. One was based on the number of molecules, where transmission symbols were encoded in the number of information particles released by the transmitter. This modulation scheme is termed concentration shift-keying (CSK). The second modulation scheme was molecular typed based modulation, where the transmission symbols were encoded in the type of the information particles released. The authors named this modulation scheme molecular shift keying (MoSK), and they proposed hydrofluorocarbon based information particles as an example for this type of modulation. The results were then extended in BIB006 , where the authors considered the effects of co-channel inference in a two-sender, two-receiver system. In BIB003 , BIB004 first concentration based modulation (i.e., modulation based on the number of particles) in diffusion based propagation channels was considered using different pulse shapes at the receiver. Using computer simulations, it was shown that the optimal transmission pulse is a spike. Based on this conclusion, the authors assumed pulse trains were used for modulation. They then presented two different pulse based approaches: pulse amplitude modulation (PAM), and pulse position modulation (PPM). In PAM a transmission bit-1 was represented by a pulse at the beginning of the bit interval, and transmission bit-0 was represented with no pulse. In PPM, a bit interval was divided in to two equal halves, and transmission bits-1 and 0 were represented by a pulse in the first or the second half, respectively. In  a novel modulation technique based on CSK that utilizes two different molecule types is proposed. Proposed modulation technique takes advantage of constructive ISI while mitigating the destructive ISI by changing the molecule type just for the bit-1 those are followed by bit-0. Therefore, consecutive bits of bit-1 are detected more correctly due to accumulating ISI molecules and the ISI on bits of bit-0 are reduced due to usage of different molecule type. This technique is named molecular transition shift keying (MTSK). In BIB016 they extended the MTSK with power adjustment capability for energy efficiency. In BIB007 a receiver circuit was proposed for frequency shift-keying-modulation presented in BIB001 . For frequency detection, an enzymatic circuit consisting of a number of interconnected chemical reaction cycles was proposed. The circuit was then modeled using reaction-diffusion equations and reaction kinetics equations, which were all partial or ordinary differential equations. The feasibility of the detection scheme was then verified using simulations. In BIB008 an optimal receiver for MoSK modulation proposed in BIB002 , was designed. The receiver was optimal in the sense that it minimized the probability of error according to the maximum a-posteriori (MAP) criterion. To do this the authors first showed that for diffusion based propagation, the channel is linear and time invariant. They then used this assumption to derive the optimal receiver design. Similarly, in BIB009 , BIB010 optimal receiver was derived for binary concentration modulation scheme using MAP criterion. In BIB011 , the authors proposed aldohexose isomers as an effective information particle, specially for in-body molecular communication. As they pointed out the information-carrying isomers must be selected carefully such that they would not be harmful as the isomers proposed in BIB002 . The authors considered isomer based CSK, and isomer based MoSK. They also presented a new modulation scheme which they called isomer-based ratio shift keying (IRSK). In this scheme the information was encoded in the ratio of two isomers (i.e., the radio of two information particles). In BIB005 , the binary concentration modulation scheme presented in BIB001 was reformulated as a pulse based modulation. For the peak-shaped channel response of this modulation scheme, the authors provided expressions for the peak's max, peak's width at half max, and peak's max delay. In BIB012 , they extended the results slightly by providing an expression for the energy of the impulse response. In BIB013 the authors considered receiver design for on-offkeying modulation scheme based on maximum a posteriori (MAP), and maximum likelihood criterion. To do this the authors considered the continuous diffusion equation and considered the random propagation as noise. Using some simplifying assumptions it was shown that this noise is Gaussian. The sequential detection in the presence of ISI was then achieved by considering the equivalent problem of estimating the state of a finite-state machine. In BIB014 a new modulation scheme called time-elapse communication (TEC) was proposed for very slow networks such as on-chip bacterial communication. In TEC information was encoded in the time interval between two consecutive pulses (i.e., two consecutive pulses of information particle transmission). The authors showed the feasibility of this technique for communication through bacterial fluorescence. In this setup information particles were released from the transmitter in an on-chip device, where they propagated using microflows until they arrived at the reception chamber. The reception chamber contained bacteria that would produce fluorescence light in proportion to the concentration of information particles. The authors showed that TEC can outperform on-off-keying when techniques such as differential coding was used. In BIB015 the authors considered diffusion based molecular communication, where a hybrid modulation scheme based on type and time of release of particles was proposed. This type of modulation was asynchronous, and could achieve higher information rates than the type based or timing based approach. To derive their models, the authors presented their modulation scheme as an event-driven system.