Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> A single-molecule method for sequencing DNA that does not require fluorescent labelling could reduce costs and increase sequencing speeds. An exonuclease enzyme might be used to cleave individual nucleotide molecules from the DNA, and when coupled to an appropriate detection system, these nucleotides could be identified in the correct order. Here, we show that a protein nanopore with a covalently attached adapter molecule can continuously identify unlabelled nucleoside 5'-monophosphate molecules with accuracies averaging 99.8%. Methylated cytosine can also be distinguished from the four standard DNA bases: guanine, adenine, thymine and cytosine. The operating conditions are compatible with the exonuclease, and the kinetic data show that the nucleotides have a high probability of translocation through the nanopore and, therefore, of not being registered twice. This highly accurate tool is suitable for integration into a system for sequencing nucleic acids and for analysing epigenetic modifications. <s> BIB001 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <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> BIB002 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <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> BIB003 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> Nanopore sequencing has the potential to become a direct, fast, and inexpensive DNA sequencing technology. The simplest form of nanopore DNA sequencing utilizes the hypothesis that individual nucleotides of single-stranded DNA passing through a nanopore will uniquely modulate an ionic current flowing through the pore, allowing the record of the current to yield the DNA sequence. We demonstrate that the ionic current through the engineered Mycobacterium smegmatis porin A, MspA, has the ability to distinguish all four DNA nucleotides and resolve single-nucleotides in single-stranded DNA when double-stranded DNA temporarily holds the nucleotides in the pore constriction. Passing DNA with a series of double-stranded sections through MspA provides proof of principle of a simple DNA sequencing method using a nanopore. These findings highlight the importance of MspA in the future of nanopore sequencing. <s> BIB004 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <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> BIB005 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <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> BIB006 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <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> BIB007 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> Molecular communication is a promising nanoscale communication paradigm that enables nanomachines to exchange information by using molecules as communication carrier. Up to now, the molecular communication channel between a transmitter nanomachine (TN) and a receiver nanomachine (RN) has been modeled as either concentration channel or timing channel. However, these channel models necessitate exact time synchronization of the nanomachines and provide a relatively low communication bandwidth. In this paper, the Molecular ARray-based COmmunication (MARCO) scheme is proposed, in which the transmission order of different molecules is used to convey molecular information without any need for time synchronization. The MARCO channel model is first theoretically derived, and the intersymbol interference and error probabilities are obtained. Based on the error probability, achievable communication rates are analytically obtained. Numerical results and performance comparisons reveal that MARCO provides significantly higher communication rate, i.e., on the scale of 100 Kbps, than the previously proposed molecular communication models without any need for synchronization. More specifically, MARCO can provide more than 250 Kbps of molecular communication rate if intersymbol time and internode distance are set to 2 μs and 2 nm, respectively. <s> BIB008 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <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> BIB009 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> Molecular communication in nanonetworks is an emerging communication paradigm that uses molecules as information carriers. In molecule shift keying (MoSK), where different types of molecules are used for encoding, transmitter and receiver complexities increase as the modulation order increases. We propose a modulation technique called depleted MoSK (D-MoSK) in which, molecules are released if the information bit is 1 and no molecule is released for 0. The proposed scheme enjoys reduced number of the types of molecules for encoding. Numerical results show that the achievable rate is considerably higher and symbol error rate (SER) performance is better in the proposed technique. <s> BIB010 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> This work studies communication over diffusion- based molecular timing (DBMT) channels. The transmitter {\em simultaneously} releases {\em multiple} small information particles, where the information is encoded in the time of release. The receiver decodes the transmitted information based on the random time of arrival of the information particles, which is represented as an additive noise channel. For a DBMT channel, without flow, this noise follows the L\'evy distribution. Under this channel model, the maximum- likelihood (ML) detector is derived and shown to have high computational complexity. It is further shown that for {\em any} additive noise channel with $\alpha$-stable noise, $\alpha < 1$, such as the DBMT channel, a linear receiver is {\em not able to take advantage} of the release of multiple information particles. Thus, instead of the common low-complexity linear approach, a new detector, which is based on the first arrival (FA) among all the transmitted particles, is derived. Numerical simulations indicate that for a small to medium number of released particles, the performance of the FA detector is very close to the performance of the ML detector. <s> BIB011 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> In this paper, a simple memory limited transmitter for molecular communication is proposed, in which information is encoded in the emission rate of the molecules. Taking advantage of memory, the proposed transmitter reduces the ISI problem by properly adjusting its emission rate, which can be interpreted as water-filling on the expected interference. The error probability of the proposed scheme is derived and the result is compared with the error probability of the optimal transmitter obtained by dynamic programming methods. Furthermore, for the special case of channel with one symbol memory, a tight lower bound on error probability is derived. Numerical results show that the performance of introduced transmitter is near optimal. Simplicity is the key feature of the presented communication system: the transmitter follows a simple rule, the receiver is a simple threshold decoder, and only one type of molecule is used to convey the information. <s> BIB012 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> Abstract We report on a strong capacity boost in storing digital data in synthetic DNA. In principle, synthetic DNA is an ideal media to archive digital data for very long times because the achievable data density and longevity outperforms today's digital data storage media by far. On the other hand, neither the synthesis, nor the amplification and the sequencing of DNA strands can be performed error-free today and in the foreseeable future. In order to make synthetic DNA available as digital data storage media, specifically tailored forward error correction schemes have to be applied. For the purpose of realizing a DNA data storage, we have developed an efficient and robust forwarderror-correcting scheme adapted to the DNA channel. We based the design of the needed DNA channel model on data from a proof-of-concept conducted 2012 by a team from the Harvard Medical School [1]. Our forward error correction scheme is able to cope with all error types of today's DNA synthesis, amplification and sequencing processes, e.g. insertion, deletion, and swap errors. In a successful experiment, we were able to store and retrieve error-free 22 MByte of digital data in synthetic DNA recently. The found residual error probability is already in the same order as it is in hard disk drives and can be easily improved further. This proves the feasibility to use synthetic DNA as longterm digital data storage media. <s> BIB013 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> We study diversity in one-shot communication over molecular timing channels. In the considered channel model the transmitter simultaneously releases a large number of information particles, where the information is encoded in the time of release. The receiver decodes the information based on the random time of arrival of the information particles. We characterize the asymptotic exponential decrease rate of the probability of error as a function of the number of released particles. We denote this quantity as the system diversity gain, as it depends both on the number of particles transmitted as well as the receiver detection method. Three types of detectors are considered: the maximumlikelihood (ML) detector, a linear detector, and a detector that is based on the first arrival (FA) among all the transmitted particles. We show that for random propagation characterized by right-sided unimodal densities with zero mode, the FA detector is equivalent to the ML detector, and significantly outperforms the linear detector. Moreover, even for densities with positive mode, the diversity gain achieved by the FA detector is very close to that achieved by the ML detector and much higher than the gain achieved by the linear detector. <s> BIB014 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Modulation Techniques for MC <s> We study diversity in one-shot communication over molecular timing channels. We consider a channel model where the transmitter simultaneously releases a large number of information particles, while the information is encoded in the time of release. The receiver decodes the information based on the random time of arrival of the information particles. The random propagation is characterized by the general class of right-sided unimodal densities. We characterize the asymptotic exponential decrease rate of the probability of error as a function of the number of released particles, and denote this quantity as the system diversity gain. Four types of detectors are considered: the maximum-likelihood (ML) detector, a linear detector, a detector that is based on the first arrival (FA) among all the transmitted particles, and a detector based on the last arrival (LA). When the density characterizing the random propagation is supported over a large interval, we show that the simple FA detector achieves a diversity gain very close to that of the ML detector. On the other hand, when the density characterizing the random propagation is supported over a small interval, we show that the simple LA detector achieves a diversity gain very close to that of the ML detector. <s> BIB015
In MC, several modulation schemes have been proposed to encode information into concentration, molecule type, and molecule release time as in Table I . The first and simplest modulation method that was proposed for MC is on-off keying (OOK), in which certain number of molecules are released for high logic and no molecule is released to represent low logic BIB002 . In a similar manner by using a single molecule, concentration shift keying (CSK) that is analogous to amplitude shift keying (ASK) in traditional wireless channels is introduced in order to increase the number of symbols in the modulation scheme by encoding information into concentration levels BIB007 . In BIB005 , a similar modulation scheme based on the concentration levels is proposed and named as pulse amplitude modulation (PAM), which uses pulses of continuous IM release instead of instantaneous release as in CSK. The number of concentration levels that can be exploited significantly depends on molecule type and channel characteristics as ISI at MC-Rx can be a limiting factor. Hitherto, we have discussed modulation techniques that use single type of molecules. However, information can be encoded by using multiple molecules such that each molecule represents different symbol, and k information symbols can be represented with 2 k different types of molecules in molecule shift keying (MoSK) BIB006 . That is, 1-bit MoSK requires two molecules to encode bit-0 with molecule A and bit-1 with molecule B. The modulation of each molecule in MoSK is based on other modulation techniques such as OOK. MoSK can achieve higher capacity, but the main limiting factor for this modulation type is the number of molecules that can be selectively received. The authors of BIB010 further improve MoSK by representing low logic with no molecule release and enabling simultaneous release of different type of molecules such that 2 k symbols can be represented with k molecules, which is named as depleted MoSK (D-MoSK). That is, 1-bit D-MoSK is equivalent to OOK. 2-bit D-MoSK requires only two molecules, and four distinct symbols can be encoded with these molecules (molecule A and molecule B), such as N (00), A (01), B (10), and AB (11) , where N represents no molecule release. Furthermore, the authors of BIB009 propose the utilization of isomers, i.e., the molecules having the same atoms in a different orientation, and a new modulation scheme, named as isomer-based ratio shift keying (IRSK), in which information is encoded into the ratio of isomers, i.e., molecule ratio-keying. The release time of molecules can be also used to encode information. In BIB005 , the authors propose pulse position modulation in which signaling period is divided into two blocks such that a pulse in the first block means high logic and a pulse in the second block means low logic. More complex modulation schemes-based on release timing, i.e., release time shift keying (RTSK), where information is encoded into the time interval between molecule release has been investigated in BIB003 , BIB015 , BIB011 , BIB014 . The channel characteristics in case of RTSK is significantly different than other modulation schemes as additive noise is distributed with inverse Gaussian distribution in the presence of flow in the channel BIB003 , and Levy distribution without any flow BIB011 . In MC, ISI is an important performance degrading factor during detection due to random motion of particles in the diffusive channels. The effects of ISI can be compensated by considering ISI-robust modulation schemes. In BIB012 , an adaptive modulation technique exploiting memory of the channel is utilized to encode information into emission rate of IMs, and this approach makes the channel more robust against ISI by adaptive control of the number of released molecules. In addition, the order of molecules can be also used for information encoding as in molecular array-based communication (MARCO) BIB008 . In this approach, different types of molecules are released consecutively to transmit symbols, and by assuming perfect molecular selectivity at the transmitter, the effects of ISI can be reduced. The modulation schemes based on concentration, molecule type/ratio/order, and molecule release time offer limited number of symbols. Therefore, MC suffers from low data rates by considering limited number of symbols and slow diffusive propagation. To tackle this problem, large amount of information can be encoded into the base sequences of DNAs, i.e., Nucleotide Shift-Keying (NSK). For this purpose, information can be encoded directly using nucleotides with an error coding algorithm such as Reed Solomon (RS) block codes BIB013 , or an alphabet can be generated out of DNA sequences (100-150bp per letter) to encode information. The latter approach can yield higher performance in terms of BER considering the complexity and size of MC-Tx and MC-Rx architectures. Although identification of base pairs with nanopores can be performed with relatively low costs and high speeds BIB001 , BIB004 , there is yet no practical system to write DNA sequences with a microscale device. Therefore, future technological advancements towards low-cost and practical synthesis/sequencing of DNA are imperative for MC communications with high data rates, e.g., on the order of Mbps.