Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Acclaimed for its clear, friendly style, excellent illustrations, leading author team, and compelling theme of exploration, Neuroscience: Exploring the Brain, 4e takes a fresh, contemporary approach to the study of neuroscience, emphasizing the biological basis of behavior. The authors' passion for the dynamic field of neuroscience is evident on every page, engaging students and helping them master the material. In just a few years, the field of neuroscience has been transformed by exciting new technologies and an explosion of knowledge about the brain. The human genome has been sequenced, sophisticated new methods have been developed for genetic engineering, and new methods have been introduced to enable visualization and stimulation of specific types of nerve cells and connections in the brain. The new Fourth Edition has been fully updated to reflect these and other rapid advances in the field, while honoring its commitment to be student-friendly with striking new illustrations, additional animations, and an unparalleled array of online resources. <s> BIB001 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Despite the amount of resources that have been invested by national and international academic, government, and commercial sectors to develop affinity-based biosensor products, little obvious success has been realized through commercialization of these devices for specific applications (such as the enzyme biosensors for blood glucose analysis). Nevertheless, the fastest growing area in the biosensors research literature continues to involve advances in affinity-based biosensors and biosensor-related methods. Numerous biosensor techniques have been reported that allow researchers to better study the kinetics, structure, and (solid/liquid) interface phenomena associated with protein-ligand binding interactions. In addition, potential application areas for which affinity-based biosensor techniques show promise include clinical/diagnostics, food processing, military/antiterrorism, and environmental monitoring. The design and structural features of these devices--composed of a biological affinity element interfaced to a signal transducer--primarily determine their operational characteristics. This paper, although not intended as a comprehensive review, will outline the principles of affinity biosensors with respect to potential application areas. <s> BIB002 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Abstract Progress in biosensors has mainly been made by the improvement of the biological components and the implementation of microsystem technologies. Enzymes are still the most appropriate recognition elements because they combine high chemical specificity and inherent biocatalytic signal amplification. A breakthrough has been achieved in the application of membrane-integrated receptor systems for analyte recognition and signal transduction in biosensors. Sensor integration of RNA aptamers has been initiated, and the performance of fully synthetic molecularly imprinted polymers has been improved. <s> BIB003 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Abstract One of the characteristics of biological systems is their ability to produce and sustain spatial and spatio-temporal pattern. Elucidating the underlying mechanisms responsible for this phenomenon has been the goal of much experimental and theoretical research. This paper illustrates this area of research by presenting some of the mathematical models that have been proposed to account for pattern formation in biology and considering their implications. To cite this article: P.K. Maini, C. R. Biologies 327 (2004). <s> BIB004 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The shortening of telomeric repeats as a cell replicates has long been implicated as a determinant of cell viability. However, recent studies have indicated that it is not telomere length, but rather whether telomeres have bound a telomere-related protein, which in mammals is TTAGGG repeat binding factor-2 (TRF2), that determines whether a cell undergoes apoptosis (programmed cell death), enters senescence (a quiescent, non-replicative state), or continues to proliferate. When bound to a telomere, TRF2 allows a cell to recognize the telomere as the point where a chromosome ends rather than a break in DNA. When telomeres are not bound by TRF2, the cell can either immediately trigger senescence or apoptosis via the DNA damage response pathway, or indirectly trigger it by attempting to repair the chromosome, which results in chromosomal end joining. We model the ability of telomeres to bind TRF2 as a function of telomere length and apply the resulting binding probability to a model of cellular replication that assumes a homogeneous cell population. The model fits data from cultured human fibroblasts and human embryonic kidney cells for two free parameters well. We extract values for the percent of telomere loss at which cell proliferation ceases. We show, in agreement with previous experiments, that overexpression of TRF2 allows a cell to delay the senescence setpoint. We explore the effect of oxidative stress, which increases the rate of telomere loss, on cell viability and show that cells in the presence of oxidative stress have reduced lifespans. We also show that the addition of telomerase, an enzyme that maintains telomere length, is sufficient to result in cell immortality. We conclude that the increasing inability of TRF2 to bind telomeres as they shorten is a quantitatively reasonable model for a cause of either cellular apoptosis or senescence. <s> BIB005 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We study the statistical behavior of affinity-based biosensors. The detection uncertainty and noise in such devices originates primarily from probabilistic molecular-level bindings within the sensing regions, and the stochastic mass-transfer processes within the reaction chamber. In this paper, we model the dynamic behavior of these sensory systems by a Markov process, which enables us to estimate the sensor inherent noise power spectral density (PSD) and response time. We also present the methods by which the Markov parameters are extracted from the reaction kinetic rates, diffusion coefficients, and reaction chamber boundary conditions. Using this model, we explain why Poisson shot noise has been reported in such biosensors and additionally predict a Lorentzian profile for the fluctuation PSD. Furthermore, we demonstrate that affinity-based biosensors have a quantum-limited signal-to-noise ratio (SNR). We also show that the SNR decreases as the dimensions are isomorphically scaled down while the biosens... <s> BIB006 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Quantum electrodynamics (resulting from the merger of quantum mechanics and relativity theory) has provided a clear understanding of phenomena ranging from particle physics to cosmology and from astrophysics to quantum chemistry. The ideas underlying quantum electrodynamics also influence the theory of condensed matter, but quantum relativistic effects are usually minute in the known experimental systems that can be described accurately by the non-relativistic Schrödinger equation. Here we report an experimental study of a condensed-matter system (graphene, a single atomic layer of carbon) in which electron transport is essentially governed by Dirac's (relativistic) equation. The charge carriers in graphene mimic relativistic particles with zero rest mass and have an effective 'speed of light' c* approximately 10(6) m s(-1). Our study reveals a variety of unusual phenomena that are characteristic of two-dimensional Dirac fermions. In particular we have observed the following: first, graphene's conductivity never falls below a minimum value corresponding to the quantum unit of conductance, even when concentrations of charge carriers tend to zero; second, the integer quantum Hall effect in graphene is anomalous in that it occurs at half-integer filling factors; and third, the cyclotron mass m(c) of massless carriers in graphene is described by E = m(c)c*2. This two-dimensional system is not only interesting in itself but also allows access to the subtle and rich physics of quantum electrodynamics in a bench-top experiment. <s> BIB007 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Dynamic modeling and simulation of signal transduction pathways is an important topic in systems biology and is obtaining growing attention from researchers with experimental or theoretical background. Here we review attempts to analyze and model specific signaling systems. We review the structure of recurrent building blocks of signaling pathways and their integration into more comprehensive models, which enables the understanding of complex cellular processes. The variety of mechanisms found and modeling techniques used are illustrated with models of different signaling pathways. Focusing on the close interplay between experimental investigation of pathways and the mathematical representations of cellular dynamics, we discuss challenges and perspectives that emerge in studies of signaling systems. <s> BIB008 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Carbon nanotubes (CNT) are well-ordered, high aspect ratio allotropes of carbon. The two main variants, single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT) both possess a high tensile strength, are ultra-light weight, and have excellent chemical and thermal stability. They also possess semi- and metallic-conductive properties. This startling array of features has led to many proposed applications in the biomedical field, including biosensors, drug and vaccine delivery and the preparation of unique biomaterials such as reinforced and/or conductive polymer nanocomposites. Despite an explosion of research into potential devices and applications, it is only recently that information on toxicity and biocompatibility has become available. This review presents a summary of the performance of existing carbon biomaterials and gives an outline of the emerging field of nanotoxicology, before reviewing the available and often conflicting investigations into the cytotoxicity and biocompatibility of CNT. Finally, future areas of investigation and possible solutions to current problems are proposed. <s> BIB009 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Field-effect sensors used to detect and identify biological species have been proposed as alternatives to other methods such as fluorescence deoxyribonucleic acid (DNA) microarrays. Sensors fabricated using commercial complementary metal-oxide-semiconductor technology would enable low-cost and highly integrated biological detection systems. In this paper, the small-signal and noise modeling of biosensors implemented with electrolyte-insulator-semiconductor structures is studied, with emphasis on design guidelines for low-noise performance. In doing so, a modified form of the general charge sheet metal-oxide-semiconductor field-effect transistor model that better fits the electrolyte-insulator-semiconductor structure is used. It is discussed how if the reference electrode and the insulator-electrolyte generate no noise associated with charge transport, then the main noise mechanisms are the resistive losses of the electrolyte and the low-frequency noise of the field-effect transistor. It is also found that... <s> BIB010 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We demonstrate that the electronic gap of a graphene bilayer can be controlled externally by applying a gate bias. From the magnetotransport data (Shubnikov-de Haas measurements of the cyclotron mass), and using a tight-binding model, we extract the value of the gap as a function of the electronic density. We show that the gap can be changed from zero to midinfrared energies by using fields of less, approximately < 1 V/nm, below the electric breakdown of SiO2. The opening of a gap is clearly seen in the quantum Hall regime. <s> BIB011 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The ultimate aim of any detection method is to achieve such a level of sensitivity that individual quanta of a measured entity can be resolved. In the case of chemical sensors, the quantum is one atom or molecule. Such resolution has so far been beyond the reach of any detection technique, including solid-state gas sensors hailed for their exceptional sensitivity1, 2, 3, 4. The fundamental reason limiting the resolution of such sensors is fluctuations due to thermal motion of charges and defects5, which lead to intrinsic noise exceeding the sought-after signal from individual molecules, usually by many orders of magnitude. Here, we show that micrometre-size sensors made from graphene are capable of detecting individual events when a gas molecule attaches to or detaches from graphene's surface. The adsorbed molecules change the local carrier concentration in graphene one by one electron, which leads to step-like changes in resistance. The achieved sensitivity is due to the fact that graphene is an exceptionally low-noise material electronically, which makes it a promising candidate not only for chemical detectors but also for other applications where local probes sensitive to external charge, magnetic field or mechanical strain are required. <s> BIB012 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We investigate single-molecule electrophoretic translocation of A(50), C(50), A(25)C(50), and C(50)A(25) RNA molecules through the alpha-hemolysin transmembrane protein pore. We observe pronounced bilevel current blockages during translocation of A(25)C(50) and C(50)A(25) molecules. The two current levels observed during these bilevel blockages are very similar to the characteristic current levels observed during A(50) and C(50) translocation. From the temporal ordering of the two levels within the bilevel current blockages, we infer whether individual A(25)C(50) and C(50)A(25) molecules pass through the pore in a 3'-->5' or 5'-->3' orientation. Correlation between the level of current obstruction and the inferred A(25)C(50) or C(50)A(25) orientation indicates that 3'-->5' translocation of a poly C segment causes a significantly deeper current obstruction than 5'-->3' translocation. Our analysis also suggests that the 3' ends of C(50) and A(25)C(50) RNA molecules are more likely to initiate translocation than the 5' ends. Orientation dependent differences in a smaller current blockage that immediately precedes many translocation events suggest that this blockage also contains information about RNA orientation during translocation. These findings emphasize that the directionality of polynucleotide molecules is an important factor in translocation and demonstrate how structure within ionic current signals can give new insights into the translocation process. <s> BIB013 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> There is an increasing demand for portable, reliable, and cost effective bioelectronic systems for applications ranging from clinical diagnosis to homeland security. Conventional detection systems involve labeling the probe molecules, large amount of target molecules to enable detection, and elaborate signal transduction methods. Most of them also have to couple with optical detection equipments that are bulky and expensive. One dimensional (1-D) and two dimensional (2-D) structures such as nanowire, nanobelts and films are capable of detecting the molecular interactions in terms of significant change in their electrical properties leading to ultrahigh sensitivity and easy integration. In this paper, we demonstrate ZnO nanowires based bio-sesnors to detect IgG antibodies. Current-voltage (I-V) and Scanning Electron Microscopy (SEM) characterization were used to monitor the change in the conductivity as well as morphology. By comparing with the reference sample, the specific binding event between anti-IgG and IgG antibodies was detected. The data indicated a conductivity change by more than 12% after the protein hybridization. SEM images confirm the morphological change from reference samples to reacted samples. In addition, same experiment protocols are carried out for ZnO thin film devices. Similar change in I-V characteristics and morphologies are observed. Through this work, we have demonstrated to use ZnO nanowires as building blocks to fabricate bio-sensors which can potentially detect any protein. Conductimetric sensing results in a label-free detection system as it detects the protein hybridization events electrically. It is a cost effective process, which can be exploited further by expanding into arrays and integrating with microfluidics. When integrated on the SOP platform, this technology can lead to portable, reliable and cost effective biosensors with applications in many areas. <s> BIB014 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Biosensors based on silicon nanowires (Si-NWs) promise highly sensitive dynamic label-free electrical detection of biomolecules. Despite the tremendous potential and promising experimental results, the fundamental mechanism of electrical sensing of biomolecules and the design considerations of NW sensors remain poorly understood. In this paper, we discuss the prospects and challenges of biomolecule detection using Si-NW biosensors as a function of device parameters, fluidic environment, charge polarity of biomolecules, etc., and refer to experimental results in literature to support the nonintuitive predictions wherever possible. Our results indicate that the design of Si nanobiosensor is nontrivial and as such, only careful optimization supported by numerical simulation would ensure optimal sensor performance. <s> BIB015 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> This article reviews the basic theoretical aspects of graphene, a one-atom-thick allotrope of carbon, with unusual two-dimensional Dirac-like electronic excitations. The Dirac electrons can be controlled by application of external electric and magnetic fields, or by altering sample geometry and/or topology. The Dirac electrons behave in unusual ways in tunneling, confinement, and the integer quantum Hall effect. The electronic properties of graphene stacks are discussed and vary with stacking order and number of layers. Edge (surface) states in graphene depend on the edge termination (zigzag or armchair) and affect the physical properties of nanoribbons. Different types of disorder modify the Dirac equation leading to unusual spectroscopic and transport properties. The effects of electron-electron and electron-phonon interactions in single layer and multilayer graphene are also presented. <s> BIB016 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The electronic structure of nanographene having open edges around its circumference crucially depends on its edge shape. The circumference of an arbitrary shaped nanographene sheet is described in terms of a combination of zigzag and armchair edges. According to theoretical suggestions, nanographene has a non-bonding π-electron state (edge state) localized in zigzag edges. This is reminiscent of the non-bonding π -electron state appearing in non-Kekule-type aromatic molecules. The localized spins of the edge states can give rise to unconventional magnetism in nanographene such as carbon-only ferromagnetism, magnetic switching phenomenon, spin glass state, etc. Nanographene can be prepared by heat-induced conversion of nanodiamond particles. Nanographene ribbons are found by chance around step edges of graphite. The detailed structures of individual nanographene ribbons thus found can be characterized by resonance Raman experiments in which the graphitic G-band is used as a fingerprint. A nanographene shee... <s> BIB017 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Graphene is a rapidly rising star on the horizon of materials science and condensed-matter physics. This strictly two-dimensional material exhibits exceptionally high crystal and electronic quality, and, despite its short history, has already revealed a cornucopia of new physics and potential applications, which are briefly discussed here. Whereas one can be certain of the realness of applications only when commercial products appear, graphene no longer requires any further proof of its importance in terms of fundamental physics. Owing to its unusual electronic spectrum, graphene has led to the emergence of a new paradigm of 'relativistic' condensed-matter physics, where quantum relativistic phenomena, some of which are unobservable in high-energy physics, can now be mimicked and tested in table-top experiments. More generally, graphene represents a conceptually new class of materials that are only one atom thick, and, on this basis, offers new inroads into low-dimensional physics that has never ceased to surprise and continues to provide a fertile ground for applications. <s> BIB018 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> First-generation glucose biosensors relied on the use of the natural oxygen cosubstrate and the production and detection of hydrogen peroxide and were much simpler, especially when miniaturized sensors are concerned. More sophisticated bioelectronic systems for enhancing the electrical response, based on patterned monolayer or multilayer assemblies and organized enzyme networks on solid electrodes, have been developed for contacting GOx with the electrode support. Electrochemical biosensors are well suited for satisfying the needs of personal (home) glucose testing, and the majority of personal blood glucose meters are based on disposable (screen-printed) enzyme electrode test strips, which are mass produced by the thick film (screen-printing) microfabrication technology. In the counter and an additional “baseline” working electrode, various membranes (mesh) are incorporated into the test strips along with surfactants, to provide a uniform sample coverage. Such devices offer considerable promise for obtaining the desired clinical information in a simpler, user-friendly, faster, and cheaper manner compared to traditional assays. Continuous ex-vivo monitoring of blood glucose was proposed in 1974 and the majority of glucose sensors used for in-vivo applications are based on the GOx-catalyzed oxidation of glucose by oxygen. The major factors that play a role in the development of clinically accurate in-vivo glucose sensors include issues related to biocompatibility, miniaturization, long-term stability of the enzyme and transducer, oxygen deficit, short stabilization times, in-vivo calibration, baseline drift, safety, and convenience. <s> BIB019 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Nanowire (NW)-based FETs are promising devices with potential applications ranging from health monitoring to drug discovery. In fact, these devices have demonstrated the ability to detect a variety of analytes such as particular DNA sequences, cancer biomarkers, and larger entities such as viruses. These sensor devices have also been used to monitor enzymatic activities and study the behavior of potential drug molecules. The detection of the analytes occurs with high specificity and sensitivity in reasonably short time. Here, we review the recent literature produced in the field of NW FET biosensors. We elaborate on the parameters that ultimately influence device performance such as methods of NW production, device dimensionality, and active measurement conditions. Significant progress has been made in this field of technology; however, it is often difficult to compare literature reports due to differences in both measurement conditions and data analysis. The standardization of certain active measurement conditions, such as the ionic strength of the analyte solutions, and manipulation of data are proposed to facilitate comparison between different NW biosensors. <s> BIB020 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We demonstrate a reproducible layer engineering technique for multilayer graphene through controllable oxidation via a SiO2 capping layer. The oxidation method is able to reduce the thickness of few layer graphene to a single layer, as determined by a combination of contrast and Raman spectroscopies. We have also studied the electrical transport properties of graphene sheets with different thicknesses by focusing on their minimum conductivity. The average minimum conductivity of single layer graphene was found to be 0.3×4e2∕h, while that of multilayer graphene consisting of n layers is approximately 1.2×4e2∕h for n=2, 2.4×4e2∕h for n=3, and 4ne2∕h for n>3. The results suggest that the substrate plays an important role in determining the transport properties of thin graphene sheets with n<3, while its influence is relatively small in thicker graphene sheets. <s> BIB021 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We have achieved mobilities in excess of 200,000 cm^2/Vs at electron densities of ~2*10^11 cm^-2 by suspending single layer graphene. Suspension ~150 nm above a Si/SiO_2 gate electrode and electrical contacts to the graphene was achieved by a combination of electron beam lithography and etching. The specimens were cleaned in situ by employing current-induced heating, directly resulting in a significant improvement of electrical transport. Concomitant with large mobility enhancement, the widths of the characteristic Dirac peaks are reduced by a factor of 10 compared to traditional, non-suspended devices. This advance should allow for accessing the intrinsic transport properties of graphene. <s> BIB022 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We show that edge stresses introduce intrinsic ripples in freestanding graphene sheets even in the absence of any thermal effects. Compressive edge stresses along zigzag and armchair edges of the sheet cause out-of-plane warping to attain several degenerate mode shapes. Based on elastic plate theory, we identify scaling laws for the amplitude and penetration depth of edge ripples as a function of wavelength. We also demonstrate that edge stresses can lead to twisting and scrolling of nanoribbons as seen in experiments. Our results underscore the importance of accounting for edge stresses in thermal theories and electronic structure calculations for freestanding graphene sheets. <s> BIB023 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Using scanning tunneling microscopy in an ultrahigh vacuum and atomic force microscopy, we investigate the corrugation of graphene flakes deposited by exfoliation on a Si/SiO2 (300 nm) surface. While the corrugation on SiO2 is long range with a correlation length of about 25 nm, some of the graphene monolayers exhibit an additional corrugation with a preferential wavelength of about 15 nm. A detailed analysis shows that the long-range corrugation of the substrate is also visible on graphene, but with a reduced amplitude, leading to the conclusion that the graphene is partly freely suspended between hills of the substrate. Thus, the intrinsic rippling observed previously on artificially suspended graphene can exist as well, if graphene is deposited on SiO2. <s> BIB024 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> A mechanism that induces charge density variations in corrugated graphene is proposed. Here it is shown how the interplay between lattice deformations and exchange interactions can induce charge separation, i.e., puddles of electrons and holes, for realistic deformation values of the graphene sheet. The induced charge density lies in the range of 10 11 –1 0 12 cm �2 , which is compatible with recent measurements. <s> BIB025 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The $1+1$ layer folded graphene sheets that deviate from $AB$ stacking are successfully fabricated and their electronic structures are investigated by Raman spectroscopy. Significant blueshift of the 2D band of folded graphene compared to that of single layer graphene (SLG) is observed. This is attributed to SLG-like electronic structure of folded graphene but with slowing down of Fermi velocity (as much as $\ensuremath{\sim}5.6%$). Different amount of blueshift of 2D band is observed for different folded graphenes, which may correspond to the different twist angle and/or separation between the two layers, resulting in different Fermi velocity of folded graphenes. Electronic structure of $1+1$-folded graphene samples with different stacking order (twist and separation between the two layers, and in-plane shift of the two layers) can be investigated by Raman spectroscopy. <s> BIB026 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> An Engineer's Guide to Genetic Circuits Chemical Reactions Macromolecules Genomes Cells and Their Structure Genetic Circuits Viruses Phage lambda: A Simple Genetic Circuit Learning Models Experimental Methods Experimental Data Cluster Analysis Learning Bayesian Networks Learning Causal Networks Experimental Design Differential Equation Analysis A Classical Chemical Kinetic Model Differential Equation Simulation Qualitative ODE Analysis Spatial Methods Stochastic Analysis A Stochastic Chemical Kinetic Model The Chemical Master Equation Gillespie's Stochastic Simulation Algorithm Gibson/Bruck's Next Reaction Method Tau-Leaping Relationship to Reaction Rate Equations Stochastic Petri-Nets Phage lambda Decision Circuit Example Spatial Gillespie Reaction-Based Abstraction Irrelevant Node Elimination Enzymatic Approximations Operator Site Reduction Statistical Thermodynamical Model Dimerization Reduction Phage lambda Decision Circuit Example Stoichiometry Amplification Logical Abstraction Logical Encoding Piecewise Models Stochastic Finite-State Machines Markov Chain Analysis Qualitative Logical Models Genetic Circuit Design Assembly of Genetic Circuits Combinational Logic Gates PoPS Gates Sequential Logic Circuits Future Challenges Solutions to Selected Problems References Glossary Index Sources and Problems appear at the end of each chapter. <s> BIB027 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> This paper presents a simple and sensitive method for the real-time detection of a prostate cancer marker (PSA-ACT complex) through label-free protein biosensors based on a carbon nanotube field effect transistor (CNT-FET). Herein, the CNT-FET was functionalized with a solution containing various linker-to-spacer ratios, the binding event of the target PSA-ACT complex onto the receptor detected by monitoring the gating effect caused by charges in the target PSA-ACT complex. Since the biosensors were used in a buffer solution, it was crucial to control the distance between the receptors through introduction of linkers and spacers so that the charged target PSA-ACT complex could easily approach the CNT surface within the Debye length to give a large gating effect. The results show that CNT-FET biosensors modified with only linkers could not detect target proteins unless a very high concentration of the PSA-ACT complex solution (approximately 500 ng/ml) was injected, while those modified with a 1:3 ratio of linker-to-spacer could detect 1.0 ng/ml without any pretreatment. Moreover, our linker and spacer-modified CNT-FET could successfully block non-target proteins and selectively detect the target protein in human serum. Significantly, this strategy can be applied to general antibody-based detection schemes and enables production of very simple and sensitive electronic biosensors to detect clinically important biomarkers for disease diagnosis. <s> BIB028 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> This study demonstrates the utility of functionalized GaN nanowires (GaNNWs) for electrochemical detection of nucleic acids, in aqueous solution, using cyclic voltammetry. In order to link probe DNA to the NW surface, we employed an organosulfur compound, 3-mercaptopropyl trimethoxysilane (MPTS), to functionalize the GaNNW surface. Interestingly, the MPTS-modified GaNNWs exhibited a potential window of 4.5 V, the widest reported to date, with very low background current, which provides an advantage for sensing DNA immobilization/hybridization, down to sub-pM concentration, via monitoring adenine and guanine oxidation. The oxidation of guanine was characterized by its peak potential and peak current, where the former serves as a fingerprint for DNA hybridization and the latter as a parameter for the extent of hybridization. Moreover, the GaNNW-based sensor exhibited excellent consistency in hybridization-dehybridization-rehybridization cycles. <s> BIB029 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Label-free detections of biomolecules have attracted great attention in a lot of life science fields such as genomics, clinical diagnosis and practical pharmacy. In this article, we reviewed amperometric and potentiometric biosensors based on carbon nanotubes (CNTs). In amperometric detections, CNT-modified electrodes were used as working electrodes to significantly enhance electroactive surface area. In contrast, the potentiometric biosensors were based on aptamer-modified CNT field-effect transistors (CNTFETs). Since aptamers are artificial oligonucleotides and thus are smaller than the Debye length, proteins can be detected with high sensitivity. In this review, we discussed on the technology, characteristics and developments for commercialization in label-free CNT-based biosensors. <s> BIB030 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Graphene-based materials are promising candidates for nanoelectronic devices because very high carrier mobilities can be achieved without the use of sophisticated material preparation techniques. However, the carrier mobilities reported for single-layer and bilayer graphene are still less than those reported for graphite crystals at low temperatures, and the optimum number of graphene layers for any given application is currently unclear, because the charge transport properties of samples containing three or more graphene layers have not yet been investigated systematically. Here, we study charge transport through trilayer graphene as a function of carrier density, temperature, and perpendicular electric field. We find that trilayer graphene is a semimetal with a resistivity that decreases with increasing electric field, a behaviour that is markedly different from that of single-layer and bilayer graphene. We show that the phenomenon originates from an overlap between the conduction and valence bands that can be controlled by an electric field, a property that had never previously been observed in any other semimetal. We also determine the effective mass of the charge carriers, and show that it accounts for a large part of the variation in the carrier mobility as the number of layers in the sample is varied. <s> BIB031 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Graphene is a promising material for the next-generation of nanoelectronic devices, but it has been difficult to produce single-layer samples in bulk quantities. A solution-based process for the large-scale production of single-layer, chemically converted graphene has now been demonstrated and used to make field-effect devices with currents that are three orders of magnitude higher than previously reported for chemically produced graphene. <s> BIB032 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We developed a hydrogen arc discharge exfoliation method for the synthesis of graphene sheets (GSs) with excellent electrical conductivity and good thermal stability from graphite oxide (GO), in combination with solution-phase dispersion and centrifugation techniques. It was found that efficient exfoliation and considerable deoxygenation of GO, and defect elimination and healing of exfoliated graphite can be simultaneously achieved during the hydrogen arc discharge exfoliation process. The GSs obtained by hydrogen arc discharge exfoliation exhibit a high electrical conductivity of210 3 S/cm and high thermal stability with oxidization resistance temperature of 601 °C, which are much better than those prepared by argon arc discharge exfoliation (2 10 2 S/cm, 525 °C) and by conventional thermal exfoliation (80 S/cm, 507 °C) with the same startingGO.Theseresultsdemonstratethatthishydrogenarcdischargeexfoliationmethodisagoodapproachfor the preparation of GSs with a good quality. <s> BIB033 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Graphene is a 2D material with many possible applications in material science, nanomechanics and nanoelectronics. While high-yield production methods for grapheme sheets are a current hot research topic, the only practical way to obtain graphene flakes on insulating substrates is micromechanical cleavage. Using this procedure it is relatively easy to obtain high-quality natural graphene flakes with well defined and clean edges oriented along the graphene crystallographic directions. However, nanoelectronic applications can benefit from an additional reduction of dimensionality from 2D flakes to 1D nanoribbons. So far, the only possible procedure to fabricate graphene nanoribbons (GNR) is using some kind lithography technique but it is not obvious that the edges of these ribbons are cut following a crystallographic grapheme direction. <s> BIB034 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Graphene, a single-atom-thick and two-dimensional carbon material, has attracted great attention recently. Because of its unique electrical, physical, and optical properties, graphene has great potential to be a novel alternative to carbon nanotubes in biosensing. We demonstrate the use of large-sized CVD grown graphene films configured as field-effect transistors for real-time biomolecular sensing. Glucose or glutamate molecules were detected by the conductance change of the graphene transistor as the molecules are oxidized by the specific redox enzyme (glucose oxidase or glutamic dehydrogenase) functionalized onto the graphene film. This study indicates that graphene is a promising candidate for the development of real-time nanoelectronic biosensors. <s> BIB035 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> A label-free immunosensor based on an aptamer-modified graphene field-effect transistor (G-FET) is demonstrated. Immunoglobulin E (IgE) aptamers with an approximate height of 3 nm were successfully immobilized on a graphene surface, as confirmed by atomic force microscopy. The aptamer-modified G-FET showed selective electrical detection of IgE protein. From the dependence of the drain current variation on the IgE concentration, the dissociation constant was estimated to be 47 nM, indicating good affinity and the potential for G-FETs to be used in biological sensors. <s> BIB036 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> From diagnosis of life-threatening diseases to detection of biological agents in warfare or terrorist attacks, biosensors are becoming a critical part of modern life. Many recent biosensors have incorporated carbon nanotubes as sensing elements, while a growing body of work has begun to do the same with the emergent nanomaterial graphene, which is effectively an unrolled nanotube. With this widespread use of carbon nanomaterials in biosensors, it is timely to assess how this trend is contributing to the science and applications of biosensors. This Review explores these issues by presenting the latest advances in electrochemical, electrical, and optical biosensors that use carbon nanotubes and graphene, and critically compares the performance of the two carbon allotropes in this application. Ultimately, carbon nanomaterials, although still to meet key challenges in fabrication and handling, have a bright future as biosensors. <s> BIB037 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Molecular communication (MC) will enable the exchange of information among nanoscale devices. In this novel bio-inspired communication paradigm, molecules are employed to encode, transmit and receive information. In the most general case, these molecules are propagated in the medium by means of free diffusion. An information theoretical analysis of diffusion-based MC is required to better understand the potential of this novel communication mechanism. The study and the modeling of the noise sources is of utmost importance for this analysis. The objective of this paper is to provide a mathematical study of the noise at the reception of the molecular information in a diffusion-based MC system when the ligand-binding reception is employed. The reference diffusion-based MC system for this analysis is the physical end-to-end model introduced in a previous work by the same authors, where the reception process is realized through ligand-binding chemical receptors. The reception noise is modeled in this paper by following two different approaches, namely, through the ligand-receptor kinetics and through the stochastic chemical kinetics. The ligand-receptor kinetics allows to simulate the random perturbations in the chemical processes of the reception, while the stochastic chemical kinetics provides the tools to derive a closed-form solution to the modeling of the reception noise. The ligand-receptor kinetics model is expressed through a block scheme, while the stochastic chemical kinetics results in the characterization of the reception noise using stochastic differential equations. Numerical results are provided to demonstrate that the analytical formulation of the reception noise in terms of stochastic chemical kinetics is compliant with the reception noise behavior resulting from the ligand-receptor kinetics simulations. <s> BIB038 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte-sensor interactions on the nanoscale and of stochastic processes in the sensing environment. <s> BIB039 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We herein report the design of a novel semiconducting silicon nanowire field-effect transistor (SiNW-FET) biosensor array for ultrasensitive label-free and real-time detection of nucleic acids. Highly responsive SiNWs with narrow sizes and high surface-to-volume-ratios were "top-down" fabricated with a complementary metal oxide semiconductor compatible anisotropic self-stop etching technique. When SiNWs were covalently modified with DNA probes, the nanosensor showed highly sensitive concentration-dependent conductance change in response to specific target DNA sequences. This SiNW-FET nanosensor revealed ultrahigh sensitivity for rapid and reliable detection of 1 fM of target DNA and high specificity single-nucleotide polymorphism discrimination. As a proof-of-concept for multiplex detection with this small-size and mass producible sensor array, we demonstrated simultaneous selective detection of two pathogenic strain virus DNA sequences (H1N1 and H5N1) of avian influenza. <s> BIB040 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Numerous threats from biological aerosol exposures, such as those from H1N1 influenza, SARS, bird flu, and bioterrorism activities necessitate the development of a real-time bioaerosol sensing system, which however is a long-standing challenge in the field. Here, we developed a real-time monitoring system for airborne influenza H3N2 viruses by integrating electronically addressable silicon nanowire (SiNW) sensor devices, microfluidics and bioaerosol-to-hydrosol air sampling techniques. When airborne influenza H3N2 virus samples were collected and delivered to antibody-modified SiNW devices, discrete nanowire conductance changes were observed within seconds. In contrast, the conductance levels remained relatively unchanged when indoor air or clean air samples were delivered. A 10-fold increase in virus concentration was found to give rise to about 20–30% increase in the sensor response. The selectivity of the sensing device was successfully demonstrated using H1N1 viruses and house dust allergens. From the... <s> BIB041 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Summary Silicon nanowire field-effect transistors (SiNW-FETs) have recently drawn tremendous attention as a promising tool in biosensor design because of their ultrasensitivity, selectivity, and label-free and real-time detection capabilities. Here, we review the recently published literature that describes the device fabrication and biomedical applications of SiNW-FET sensors. For practical uses, SiNW-FETs can be delicately designed to be a reusable device via a reversible surface functionalization method. In the fields of biological research, SiNW-FETs are employed in the detections of proteins, DNA sequences, small molecules, cancer biomarkers, and viruses. The methods by which the SiNW-FET devices were integrated with these representative examples and advanced to virus infection diagnosis or early cancer detection will be discussed. In addition, the utilization of SiNW-FETs in recording the physiological responses from cells or tissues will also be reviewed. Finally, the novel design of a three dimensional (3D) nano-FET probe with kinked SiNWs for recording intracellular signals will be highlighted in this review. <s> BIB042 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Biosensing is paramount for improving the quality of human life. Biosensors and biosensing protocols are able to detect a wide range of compounds, sensitively and selectively, with applications in security, health care for point-of-care analyses of diseases, and environmental safety. Here, we describe biosensors and biosensing systems employing graphene. Graphene is a zero-gap semiconductor material, which is electroactive and transparent. Because of its interesting properties, graphene has found its way into a wide variety of biosensing schemes. It has been used as a transducer in bio-field-effect transistors, electrochemical biosensors, impedance biosensors, electrochemiluminescence, and fluorescence biosensors, as well as biomolecular labels. In our review, we describe the application of graphene for enzymatic biosensing, DNA sensing, and immunosensing. We compare different techniques and present our views on the future development of the field. <s> BIB043 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Monitoring the binding affinities and kinetics of protein interactions is important in clinical diagnostics and drug development because such information is used to identify new therapeutic candidates. Surface plasmon resonance is at present the standard method used for such analysis, but this is limited by low sensitivity and low-throughput analysis. Here, we show that silicon nanowire field-effect transistors can be used as biosensors to measure protein–ligand binding affinities and kinetics with sensitivities down to femtomolar concentrations. Based on this sensing mechanism, we develop an analytical model to calibrate the sensor response and quantify the molecular binding affinities of two representative protein–ligand binding pairs. The rate constant of the association and dissociation of the protein–ligand pair is determined by monitoring the reaction kinetics, demonstrating that silicon nanowire field-effect transistors can be readily used as high-throughput biosensors to quantify protein interactions. <s> BIB044 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Over the past decade, silicon nanowire (SiNW) biosensors have been studied for the detection of biological molecules as highly sensitive, label-free, and electrical tools. Herein we present a comprehensive review about the fabrication of SiNW biosensors and their applications in disease diagnostics. We discuss the detection of important biomarkers related to diseases including cancer, cardiovascular diseases, and infectious diseases. SiNW biosensors hold great promise to realize point-of-care (POC) devices for disease diagnostics with potential for miniaturization and integration. <s> BIB045 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Rapid and precise discrimination of various odorants is vital to fabricating enhanced sensing devices in the fields of disease diagnostics, food safety, and environmental monitoring. Here, we demonstrate an ultrasensitive and flexible field-effect transistor (FET) olfactory system, namely, a bioelectronic nose (B-nose), based on plasma-treated bilayer graphene conjugated with an olfactory receptor. The stable p- and n-type behaviors from modified bilayer graphene (MBLG) took place after controlled oxygen and ammonia plasma treatments. It was integrated with human olfactory receptors 2AG1 (hOR2AG1: OR), leading to the formation of the liquid-ion gated FET-type platform. ORs bind to the particular odorant amyl butyrate (AB), and their interactions are specific and selective. The B-noses behave as flexible and transparent sensing devices and can recognize a target odorant with single-carbon-atom resolution. The B-noses are ultrasensitive and highly selective toward AB. The minimum detection limit (MDL) is as... <s> BIB046 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Molecular Communication (MC) is a bio-inspired paradigm where information is exchanged by the release, the propagation and the reception of molecules. The objective of this paper is to analyze the effects of interference in the most general type of MC system, i.e., the diffusion of molecules in a fluidic medium. The study of the InterSymbol Interference (ISI) and Co-Channel Interference (CCI) is conducted through the analysis of the propagation of signals in a diffusion-based channel. An in-depth analysis of the attenuation and the dispersion of signals due to molecule diffusion allows to derive simple closed-form formulas for both ISI and CCI. In this paper, two different modulation schemes, namely, the baseband modulation and the diffusion wave modulation are considered for the release of molecules in the diffusion-based MC and are compared in terms of interference. It is determined that the diffusion wave modulation scheme shows lower interference values than the baseband modulation scheme. Moreover, it is revealed that the higher is the frequency of the modulating diffusion wave, the lower are the effects of the ISI and the CCI on the communication channel. The obtained analytical results are compared and validated by numerical simulation results. <s> BIB047 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <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> BIB048 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In this paper, we perform receiver design for a diffusive molecular communication environment. Our model includes flow in any direction, sources of information molecules in addition to the transmitter, and enzymes in the propagation environment to mitigate intersymbol interference. We characterize the mutual information between receiver observations to show how often independent observations can be made. We derive the maximum likelihood sequence detector to provide a lower bound on the bit error probability. We propose the family of weighted sum detectors for more practical implementation and derive their expected bit error probability. Under certain conditions, the performance of the optimal weighted sum detector is shown to be equivalent to a matched filter. Receiver simulation results show the tradeoff in detector complexity versus achievable bit error probability, and that a slow flow in any direction can improve the performance of a weighted sum detector. <s> BIB049 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <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> BIB050 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In this work, we describe the first modular, and programmable platform capable of transmitting a text message using chemical signalling - a method also known as molecular communication. This form of communication is attractive for applications where conventional wireless systems perform poorly, from nanotechnology to urban health monitoring. Using examples, we demonstrate the use of our platform as a testbed for molecular communication, and illustrate the features of these communication systems using experiments. By providing a simple and inexpensive means of performing experiments, our system fills an important gap in the molecular communication literature, where much current work is done in simulation with simplified system models. A key finding in this paper is that these systems are often nonlinear in practice, whereas current simulations and analysis often assume that the system is linear. However, as we show in this work, despite the nonlinearity, reliable communication is still possible. Furthermore, this work motivates future studies on more realistic modelling, analysis, and design of theoretical models and algorithms for these systems. <s> BIB051 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We present receptor-modified carbon nanotube sensors for the highly selective and sensitive detection of acetylcholine (ACh), one kind of neurotransmitter. Here, we successfully expressed the M1 muscarinic acetylcholine receptor (M1 mAChR), a family of G protein-coupled receptors (GPCRs), in E. coli and coated single-walled carbon nanotube (swCNT)-field effect transistors (FETs) with lipid membrane including the receptor, enabling highly selective and sensitive ACh detection. Using this sensor, we could detect ACh at 100 pM concentration. Moreover, we showed that this sensor could selectively detect ACh among other neurotransmitters. This is the first demonstration of the real-time detection of ACh using specific binding between ACh and M1 mAChR, and it may lead to breakthroughs for various applications such as disease diagnosis and drug screening. <s> BIB052 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The functioning principles of electronic sensors based on organic semiconductor field-effect transistors (OFETs) are presented. The focus is on biological sensors but also chemical ones are reviewed to address general features. The field-induced electronic transport and the chemical and biological interactions for the sensing, each occurring at the relevant functional interface, are separately introduced. Once these key learning points have been acquired, the combined picture for the FET electronic sensing is proposed. The perspective use of such devices in point-of-care is introduced, after some basics on analytical biosensing systems are provided as well. This tutorial review includes also a necessary overview of the OFET sensing structures, but the focus will be on electronic rather than electrochemical detection. The differences among the structures are highlighted along with the implications on the performance level in terms of key analytical figures of merit such as: repeatability, sensitivity and selectivity. <s> BIB053 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> This study presents a review on biosensors with an emphasis on recent developments in the field. A brief history accompanied by a detailed description of the biosensor concepts is followed by rising trends observed in contemporary micro- and nanoscale biosensors. Performance metrics to quantify and compare different detection mechanisms are presented. A comprehensive analysis on various types and subtypes of biosensors are given. The fields of interest within the scope of this review are label-free electrical, mechanical and optical biosensors as well as other emerging and popular technologies. Especially, the latter half of the last decade is reviewed for the types, methods and results of the most prominently researched detection mechanisms. Tables are provided for comparison of various competing technologies in the literature. The conclusion part summarises the noteworthy advantages and disadvantages of all biosensors reviewed in this study. Furthermore, future directions that the micro- and nanoscale biosensing technologies are expected to take are provided along with the immediate outlook. <s> BIB054 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The role of diffusion in the kinetics of reversible ligand binding to receptors on a cell surface or to a macromolecule with multiple binding sites is considered. A formalism is developed that is based on a Markovian master equation for the distribution function of the number of occupied receptors containing rate constants that depend on the ligand diffusivity. The formalism is used to derive (1) a nonlinear rate equation for the mean number of occupied receptors and (2) an analytical expression for the relaxation time that characterizes the decay of equilibrium fluctuations of the occupancy of the receptors. The relaxation time is shown to depend on the ligand diffusivity and concentration, the number of receptors, the cell radius, and intrinsic association/dissociation rate constants. This result is then used to estimate the accuracy of the ligand concentration measurements by the cell, which, according to the Berg-Purcell model, is related to fluctuations in the receptor occupancy, averaged over a finite interval of time. Specifically, a simple expression (which is exact in the framework of our formalism) is derived for the variance in the measured ligand concentration in the limit of long averaging times. <s> BIB055 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Field-effect transistor-based biosensors (bioFETs) have shown great promise in the field of fast, ultra-sensitive, label-free detection of biomolecules. Reliability and accuracy, when trying to measure small concentrations, is of paramount importance for the translation of these research devices into the clinical setting. Our knowledge and experience with these sensors has reached a stage where we are able to identify three main aspects of bioFET sensing that currently limit their applications. By considering the intrinsic device noise as a limitation to the smallest measurable signal, we show how various parameters, processing steps and surface modifications, affect the limit of detection. We also introduce the signal-to-noise ratio of bioFETs as a universal performance metric, which allows us to gain better insight into the design of more sensitive devices. Another aspect that places a limit on the performance of bioFETs is screening by the electrolyte environment, which reduces the signal that could be potentially measured. Alternative functionalization and detection schemes that could enable the use of these charge-based sensors in physiological conditions are highlighted. Finally, the binding kinetics of the receptor-analyte system are considered, both in the context of extracting information about molecular interactions using the bioFET sensor platform and as a fundamental limitation to the number of molecules that bind to the sensor surface at steady-state conditions and to the signal that is generated. Some strategies to overcome these limitations are also proposed. Taken together, these performance-limiting issues, if solved, would bring bioFET sensors closer to clinical applications. <s> BIB056 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Diffusion-based communication refers to the transfer of information using molecules as message carriers whos ep rop- agation is governed by the laws of molecular diffusion. It has been identified that diffusion-based communication is one of the most promising solutions for end-to-end communication between nanoscale devices. In this paper, the design of a diffusion-based communication system considering stochastic signaling, arbitrary orders of channel memory, and noisy receptio ni s proposed. The diffusion in the cases of one, two, and three dimensions are all considered. Three signal processing techniques for the molecular concentration with low computational complexity are proposed. For the detector design, both a low-complexity one-shot optimal detector for mutual information maximization and a near Max- imum Likelihood (ML) sequence detector are proposed. To the best of our knowledge, our paper is thefirst that gives an analytical treatment of the signal processing, estimation, and detection prob- lems for diffusion-based communication in the presence of ISI and reception noise. Numerical results indicate that the proposed signal processing technique followed by the one-shot detector achieves near-optimal throughput without the need of ap riori information in both short-range and long-range diffusion-based communication scenarios, whic hs uggests an ML sequence de- tector is not necessary. Furthermore, the proposed receiver design guarantees diffusion-based communication to operate without failure even in the case of infinite channel memory. A channel capacity of 1 bit per channel utilization can be ultimately achieved by extending the duration of the signaling interval. <s> BIB057 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In this paper, a diffusion-based molecular communication channel between two nano-machines is considered. The effect of the amount of memory on performance is characterized, and a simple memory-limited decoder is proposed and its performance is shown to be close to that of the best possible imaginable decoder (without any restriction on the computational complexity or its functional form), using Genie-aided upper bounds. This effect is specialized for the case of Molecular Concentration Shift Keying; it is shown that a four-bits memory achieved nearly the same performance as infinite memory. Then a general class of threshold decoders is considered and shown not to be optimal for Poisson channel with memory, unless SNR is higher than a value specified in the paper. Another contribution is to show that receiver sampling at a rate higher than the transmission rate, i.e., a multi-read system, can significantly improve the performance. The associated decision rule for this system is shown to be a weighted sum of the samples during each symbol interval. The performance of the system is analyzed using the saddle point approximation. The best performance gains are achieved for an oversampling factor of three. <s> BIB058 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Within the domain of molecular communications, researchers mimic the techniques in nature to come up with alternative communication methods for collaborating nanomachines. This work investigates the channel transfer function for molecular communication via diffusion. In nature, information-carrying molecules are generally absorbed by the target node via receptors. Using the concentration function, without considering the absorption process, as the channel transfer function implicitly assumes that the receiver node does not affect the system. In this letter, we propose a solid analytical formulation and analyze the signal metrics (attenuation and propagation delay) for molecular communication via diffusion channel with an absorbing receiver in a 3-D environment. The proposed model and the formulation match well with the simulations without any normalization. <s> BIB059 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <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> BIB060 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Abstract Recent advances in synthetic biology, in particular towards the engineering of DNA-based circuits, are providing tools to program man-designed functions within biological cells, thus paving the way for the realization of biological nanoscale devices, known as nanomachines. By stemming from the way biological cells communicate in the nature, Molecular Communication (MC), i.e., the exchange of information through the emission, propagation, and reception of molecules, has been identified as the key paradigm to interconnect these biological nanomachines into nanoscale networks, or nanonetwork. The design of MC nanonetworks built upon biological circuits is particularly interesting since cells possess many of the elements required to realize this type of communication, thus enabling the design of cooperative functions in the biological environment. In this paper, a systems-theoretic modeling is realized by analyzing a minimal subset of biological circuit elements necessary to be included in an MC nanonetwork design where the message-bearing molecules are propagated via free diffusion between two cells. The obtained system-theoretic models stem from the biochemical processes underlying cell-to-cell MC, and are analytically characterized by their transfer functions, attenuation and delay experienced by an information signal exchanged by the communicating cells. Numerical results are presented to evaluate the obtained analytical expressions as functions of realistic biological parameters. <s> BIB061 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. <s> BIB062 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Among the variety of transducer concepts pro- posed for label-free detection of biomolecules, the semi- conductor field-effect device (FED) is one of the most at- tractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on bio- markers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologi- cally relevant molecules with high specificity and sensitiv- ity offers very promising prospects for their application in point-of-care and personalized medicine for an early diag- nosis and treatment of diseases. The presented paper re- views recent advances and current trends in research and development of different FEDs for label-free, direct elec- trical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-anti- gen affinity reaction as well as clinically relevant biomole- cules such as cardiac and cancer biomarkers. <s> BIB063 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The sense of taste helps humans to obtain information and form a picture of the world by recognizing chemicals in their environments. Over the past decade, large advances have been made in understanding the mechanisms of taste detection and mimicking its capability using artificial sensor devices. However, the detection capability of previous artificial taste sensors has been far inferior to that of animal tongues, in terms of its sensitivity and selectivity. Herein, we developed a bioelectronic tongue using heterodimeric human sweet taste receptors for the detection and discrimination of sweeteners with human-like performance, where single-walled carbon nanotube field-effect transistors were functionalized with nanovesicles containing human sweet taste receptors and used to detect the binding of sweeteners to the taste receptors. The receptors are heterodimeric G-protein-coupled receptors (GPCRs) composed of human taste receptor type 1 member 2 (hTAS1R2) and human taste receptor type 1 member 3 (hTAS1R3), which have multiple binding sites and allow a human tongue-like broad selectivity for the detection of sweeteners. This nanovesicle-based bioelectronic tongue can be a powerful tool for the detection of sweeteners as an alternative to labor-intensive and time-consuming cell-based assays and the sensory evaluation panels used in the food and beverage industry. Furthermore, this study also allows the artificial sensor to exam the functional activity of dimeric GPCRs. <s> BIB064 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Biosensors based on field-effect transistors (FETs) have attracted much attention, as they offer rapid, inexpensive, and label-free detection. While the low sensitivity of FET biosensors based on bulk 3D structures has been overcome by using 1D structures (nanotubes/nanowires), the latter face severe fabrication challenges, impairing their practical applications. In this paper, we introduce and demonstrate FET biosensors based on molybdenum disulfide (MoS2), which provides extremely high sensitivity and at the same time offers easy patternability and device fabrication, due to its 2D atomically layered structure. A MoS2-based pH sensor achieving sensitivity as high as 713 for a pH change by 1 unit along with efficient operation over a wide pH range (3–9) is demonstrated. Ultrasensitive and specific protein sensing is also achieved with a sensitivity of 196 even at 100 femtomolar concentration. While graphene is also a 2D material, we show here that it cannot compete with a MoS2-based FET biosensor, which ... <s> BIB065 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> For on-site clinical diagnosis of biomolecules, the detection performances of most point-of-care (POC) biosensor devices are limited by undesired cross-detection of other non-analyte proteins in patient serum samples and other complex samples. To conquer this obstacle, this work presents a fully integrated bottom-gate poly-silcion nanowire (polySi NW) biosensor system-on-chip (SoC) to enhance the detection performance of cardiac-specific troponin-I (cTnI) concentration levels in serum samples. By applying proper electrical potential at the bottom gate under polySi NW biosensor, the biosensor response to cTnI biomarker can be improved by at least 16 fold in 50% phantom serum samples. The experimental result shows its detection range is from 3.2 × 10(-13)M(mol l(-1)) to 3.2 × 10(-10)M. This enhancement can be attributed to the electrostatic interactions between target biomolecules and voltage-applied bottom gate electrodes. This is the first time that a polySi NW CMOS biosensor chip has shown feasibilities to detect specific biomarkers in serum samples. Therefore, the developed technology paves the way toward on-field applications of CMOS compatible SiNW biosensing technologies and it can be employed for future biomolecular analysis in on-site serum diagnosis applications. <s> BIB066 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Graphene, because of its excellent mechanical, electrical, chemical, physical properties, sparked great interest to develop and extend its applications. Particularly, graphene based field-effect transistors (GFETs) present exciting and bright prospects for sensing applications due to their greatly higher sensitivity and stronger selectivity. This Review highlights a selection of important topics pertinent to GFETs and their application in electronic sensors. This article begins with a description of the fabrications and characterizations of GFETs, and then introduces the new developments in physical, chemical, and biological electronic detection using GFETs. Finally, several perspective and current challenges of GFETs development are presented, and some proposals are suggested for further development and exploration. <s> BIB067 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Molecular nanonetworks stand at the intersection of nanotechnology, biotechnology, and network engineering. The research on molecular nanonetworks proposes the interconnection of nanomachines through molecule exchange. Amongst different solutions for the transport of molecules between nanomachines, the most general is based on free diffusion. The objective of this paper is to provide a statistical–physical modeling of the interference when multiple transmitting nanomachines emit molecules simultaneously. This modeling stems from the same assumptions used in interference study for radio communications, namely, a spatial Poisson distribution of transmitters having independent and identically distributed emissions, while the specific molecule emissions model is in agreement with a chemical description of the transmitters. As a result of the property of the received molecular signal of being a stationary Gaussian Process (GP), the statistical–physical modeling is operated on its Power Spectral Density (PSD), for which it is possible to obtain an analytical expression of the log-characteristic function. This expression leads to the estimation of the received PSD probability distribution, which provides a complete model of the interference in diffusion-based molecular nanonetworks. Numerical results in terms of received PSD probability distribution and probability of interference are presented to compare the proposed statistical–physical model with the outcomes of simulations. <s> BIB068 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> DNA nanotechnology has enabled the construction of DNA origami nanopores; synthetic nanopores that present improved capabilities for the area of single molecule detection. Their extraordinary versatility makes them a new and powerful tool in nanobiotechnology for a wide range of important applications beyond molecular sensing. In this review, we briefly present the recent developments in this emerging field of research. We discuss the current challenges and possible solutions that would enhance the sensing capabilities of DNA origami nanopores. Finally, we anticipate novel avenues for future research and highlight a range of exciting ideas and applications that could be explored in the near future. <s> BIB069 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In this paper, we consider the bacterial point-to-point and multiple-access molecular communications with ligand-receptors. For the point-to-point communication, we investigate common signaling methods, namely the Level Scenario (LS), which uses one type of a molecule with different concentration levels, and the Type Scenario (TS), which employs multiple types of molecules with a single concentration level. We investigate the trade-offs between the two scenarios from the capacity point of view. We derive an upper bound on the capacity using a Binomial Channel (BIC) model and the symmetrized Kullback-Leibler (KL) divergence. A lower bound is also derived when the environment noise is negligible. For the TS, we also consider the effect of blocking of a receptor by a different molecule type. Then, we consider multiple-access communications, for which we investigate three scenarios based on molecule and receptor types, i.e., same types of molecules with Different Labeling and Same types of Receptors (DLSR), Different types of Molecules and Receptors (DMDR), and Same types of Molecules and Receptors (SMSR). We investigate the trade-offs among the three scenarios from the total capacity point of view. We derive some inner bounds on the capacity region of these scenarios when the environment noise is negligible. <s> BIB070 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In this paper, we present an analytical model for the diffusive molecular communication (MC) system with a reversible adsorption receiver in a fluid environment. The widely used concentration shift keying (CSK) is considered for modulation. The time-varying spatial distribution of the information molecules under the reversible adsorption and desorption reaction at the surface of a receiver is analytically characterized. Based on the spatial distribution, we derive the net number of newly-adsorbed information molecules expected in any time duration. We further derive the number of newly-adsorbed molecules expected at the steady state to demonstrate the equilibrium concentration. Given the number of newly-adsorbed information molecules, the bit error probability of the proposed MC system is analytically approximated. Importantly, we present a simulation framework for the proposed model that accounts for the diffusion and reversible reaction. Simulation results show the accuracy of our derived expressions, and demonstrate the positive effect of the adsorption rate and the negative effect of the desorption rate on the error probability of reversible adsorption receiver with last transmit bit-1. Moreover, our analytical results simplify to the special cases of a full adsorption receiver and a partial adsorption receiver, both of which do not include desorption. <s> BIB071 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Molecular Communication (MC) is a nano-scale communication paradigm where the information is carried by molecular signals. To establish information transmission using molecules, biological nanomachines can be utilized as transmitters and receivers. A bacteria can be programmed as a biotransceiver by modifying their genetic code to implement biological circuits. In this paper, genetically engineered bacteria-based biotransceivers are investigated for MC, where bacteria can generate and respond to the molecular signals. A biochemical model of biological circuits is presented, and both analog and digital signaling are studied. The challenges in connecting basic biological circuits to build these blocks are revealed. A biotransceiver architecture is introduced that combines sensing, transmitting, receiving and processing blocks. Furthermore, biological circuit design framework is proposed for transmission of signals with M-ary pulse amplitude modulation. The biological circuits designed for biotransceiver are elaborated via numerical results based on biochemical parameters of the genetically engineered bacteria. The provided results show that using biological circuits, bacteria can function as a transmitter and receiver node for MC. Our work stands as a basis for future biotransceiver design for MC. <s> BIB072 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <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> BIB073 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Molecular communication (MC) is a bio-inspired communication method based on the exchange of molecules for information transfer among nanoscale devices. MC has been extensively studied from various aspects in the literature; however, the physical design of MC transceiving units is largely neglected with the assumption that network nodes are entirely biological devices, e.g., engineered bacteria, which are intrinsically capable of receiving and transmitting molecular messages. However, the low information processing capacity of biological devices and the challenge to interface them with macroscale networks hinder the true application potential of nanonetworks. To overcome this limitation, recently, we proposed a nanobioelectronic MC receiver architecture exploiting the nanoscale field-effect transistor-based biosensor (bioFET) technology, which provides noninvasive and sensitive molecular detection while producing electrical signals as the output. In this paper, we introduce a comprehensive model for silicon nanowire FET-based MC receivers by integrating the underlying processes in MC and bioFET to provide a unified analysis framework. We derive closed-form expressions for the noise statistics, the signal-to-noise ratio (SNR) at the receiver output, and the symbol error probability (SEP). Performance evaluation in terms of SNR and SEP reveals the effects of individual system parameters on the detection performance of the proposed MC receiver. <s> BIB074 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Chronic diseases are becoming more prevalent, and the complexities of managing patients continue to escalate, since their care must be balanced between the home and clinical settings. Diabetes is the most advanced example, where self-monitoring has been shown to be necessary. Glucometers are point-of-care (POC) devices that have become standard platforms at home and clinical settings. Similarly, many other POC biosensors have also been developed. Enzymes are often used in these sensors because of their specificity and the reaction products can be electrochemically transduced for the measurement. When enzymes are immobilized to an electronically active substrate, enzymatic reactions can be transduced by direct electron transport. This paper describes an approach for the development of graphene-based POC devices. This includes modifying enzymes for improved performance, developing methods to bind them to the graphene surface, incorporation of the functionalized graphene on a field-effect transistor (FET), and integration into a microfluidic device suitable for home use. This paper describes an approach for the development of a graphene-based POC biosensor platform using glucose as an example of target molecule. <s> BIB075 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In this paper, we propose an end-to-end channel model for molecular communication systems with metal-oxide sensors. In particular, we focus on the recently developed table top molecular communication platform. The system is separated into two parts: the propagation and the sensor detection. There is derived, based on this, a more realistic end-to-end channel model. However, since some of the coefficients in the derived models are unknown, we collect a great deal of experimental data to estimate these coefficients and evaluate how they change with respect to the different system parameters. Finally, a noise model is derived for the system to complete an end-to-end system model for the tabletop platform. <s> BIB076 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Solid-state nanopores are single-molecule sensors that measure changes in ionic current as charged polymers such as DNA pass through. Here, we present comprehensive experiments on the length, voltage, and salt dependence of the frequency of double-stranded DNA translocations through conical quartz nanopores with mean opening diameter 15 nm. We observe an entropic barrier-limited, length-dependent translocation frequency at 4M LiCl salt concentration and a drift-dominated, length-independent translocation frequency at 1M KCl salt concentration. These observations are described by a unifying convection-diffusion equation, which includes the contribution of an entropic barrier for polymer entry. <s> BIB077 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Within an hour, as little as one disseminated tumor cell (DTC) per lymph node can be quantitatively detected using an intraoperative biosensing platform based on silicon nanowire field-effect transistors (SiNW FET). It is also demonstrated that the integrated biosensing platform is able to detect the presence of circulating tumor cells (CTCs) in the blood of colorectal cancer patients. The presence of DTCs in lymph nodes and CTCs in peripheral blood is highly significant as it is strongly associated with poor patient prognosis. The SiNW FET sensing platform out-performed in both sensitivity and rapidity not only the current standard method based on pathological examination of tissue sections but also the emerging clinical gold standard based on molecular assays. The possibility to achieve accurate and highly sensitive analysis of the presence of DTCs in the lymphatics within the surgery time frame has the potential to spare cancer patients from an unnecessary secondary surgery, leading to reduced patient ... <s> BIB078 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Scalable production of all-electronic DNA biosensors with high sensitivity and selectivity is a critical enabling step for research and applications associated with detection of DNA hybridization. We have developed a scalable and very reproducible (>90% yield) fabrication process for label-free DNA biosensors based upon graphene field effect transistors (GFETs) functionalized with single-stranded probe DNA. The shift of the GFET sensor Dirac point voltage varied systematically with the concentration of target DNA. The biosensors demonstrated a broad analytical range and limit of detection of 1 fM for 60-mer DNA oligonucleotide. In control experiments with mismatched DNA oligomers, the impact of the mismatch position on the DNA hybridization strength was confirmed. This class of highly sensitive DNA biosensors offers the prospect of detection of DNA hybridization and sequencing in a rapid, inexpensive, and accurate way. <s> BIB079 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Nanomaterial-based field-effect transistor (FET) sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although direct measurements in high–ionic-strength physiological solutions remain challenging due to the Debye screening effect. Recently, we demonstrated a general strategy to overcome this challenge by incorporating a biomolecule-permeable polymer layer on the surface of silicon nanowire FET sensors. The permeable polymer layer can increase the effective screening length immediately adjacent to the device surface and thereby enable real-time detection of biomolecules in high–ionic-strength solutions. Here, we describe studies demonstrating both the generality of this concept and application to specific protein detection using graphene FET sensors. Concentration-dependent measurements made with polyethylene glycol (PEG)-modified graphene devices exhibited real-time reversible detection of prostate specific antigen (PSA) from 1 to 1,000 nM in 100 mM phosphate buffer. In addition, comodification of graphene devices with PEG and DNA aptamers yielded specific irreversible binding and detection of PSA in pH 7.4 1x PBS solutions, whereas control experiments with proteins that do not bind to the aptamer showed smaller reversible signals. In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under physiological conditions. The current work presents an important concept toward the application of nanomaterial-based FET sensors for biochemical sensing in physiological environments and thus could lead to powerful tools for basic research and healthcare. <s> BIB080 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In diffusion-based molecular communication, information transport is governed by diffusion through a fluid medium. The achievable data rates for these channels are very low compared to the radio-based communication system, since diffusion can be a slow process. To improve the data rate, a novel multiple-input multiple-output (MIMO) design for molecular communication is proposed that utilizes multiple molecular emitters at the transmitter and multiple molecular detectors at the receiver (in RF communication these all correspond to antennas). Using particle-based simulators, the channel’s impulse response is obtained and mathematically modeled. These models are then used to determine interlink interference (ILI) and intersymbol interference (ISI). It is assumed that when the receiver has incomplete information regarding the system and the channel state, low complexity symbol detection methods are preferred since the receiver is small and simple. Thus, four detection algorithms are proposed—adaptive thresholding, practical zero forcing with channel models excluding/including the ILI and ISI, and Genie-aided zero forcing. The proposed algorithms are evaluated extensively using numerical and analytical evaluations. <s> BIB081 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Multiplexed sensing of single molecules can be achieved with solid-state nanopores by using digitally encoded DNA nanostructures, allowing four different antibodies to be simultaneously detected at nanomolar concentrations. <s> BIB082 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The threading of a polymer chain through a small pore is a classic problem in polymer dynamics and underlies nanopore sensing technology. However important experimental aspects of the polymer motion in a solid-state nanopore, such as an accurate measurement of the velocity variation during translocation, have remained elusive. In this work we analysed the translocation through conical quartz nanopores of a 7 kbp DNA double-strand labelled with six markers equally spaced along its contour. These markers, constructed from DNA hairpins, give direct experimental access to the translocation dynamics. On average we measure a 5% reduction in velocity during the translocation. We also find a striking correlation in velocity fluctuations with a decay constant of 100s of {\mu}s. These results shed light on hitherto unresolved problems in the dynamics of DNA translocation and provide guidance for experiments seeking to determine positional information along a DNA strand. <s> BIB083 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> This paper introduces the equivalent discrete-time channel model (EDTCM) to the area of diffusion-based molecular communication (DBMC). Emphasis is on an absorbing receiver, which is based on the so-called first passage time concept. In the wireless communications community the EDTCM is well known. Therefore, it is anticipated that the EDTCM improves the accessibility of DBMC and supports the adaptation of classical wireless communication algorithms to the area of DBMC. Furthermore, the EDTCM has the capability to provide a remarkable reduction of computational complexity compared to random walk based DBMC simulators. Besides the exact EDTCM, three approximations thereof based on binomial, Gaussian, and Poisson approximation are proposed and analyzed in order to further reduce computational complexity. In addition, the Bahl-Cocke-Jelinek-Raviv (BCJR) algorithm is adapted to all four channel models. Numerical results show the performance of the exact EDTCM, illustrate the performance of the adapted BCJR algorithm, and demonstrate the accuracy of the approximations. <s> BIB084 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In nano-bio networks, multiple transmitter–receiver pairs will operate in the same medium. Both inter-symbol interference and multi-user interference can cause saturation at the receiver side, and this effect may cause an outage. Thus, we propose a tractable framework to calculate the theoretical operating points for fully absorbing receiver. <s> BIB085 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> This work presents a new multi-chemical experimental platform for molecular communication where the transmitter can release different chemicals. This platform is designed to be inexpensive and accessible, and it can be expanded to simulate different environments including the cardiovascular system and complex network of pipes in industrial complexes and city infrastructures. To demonstrate the capabilities of the platform, we implement a time-slotted binary communication system where a bit-0 is represented by an acid pulse, a bit-1 by a base pulse, and information is carried via pH signals. The channel model for this system, which is nonlinear and has long memories, is unknown. Therefore, we devise novel detection algorithms that use techniques from machine learning and deep learning to train a maximum-likelihood detector. Using these algorithms the bit error rate improves by an order of magnitude relative to the approach used in previous works. Moreover, our system achieves a data rate that is an order of magnitude higher than any of the previous molecular communication platforms. <s> BIB086 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array. <s> BIB087 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Odorant-binding proteins (OBPs) have attracted considerable attention as sensing substrates for the development of olfactory biosensors. The Drosophila LUSH protein is an OBP and is known to bind to various alcohols. Technology that uses the LUSH protein has great potential to provide crucial information through odorant detection. In this work, the LUSH protein was used as a sensing substrate to detect the ethanol concentration. Furthermore, we fused the LUSH protein with a silicon-on-insulator (SOI)-based ion-sensitive field-effect transistor (ISFET) to measure the electrical signals that arise from molecular interactions between the LUSH and ethanol. A dual-gate sensing system for self-amplification of the signal resulting from the molecular interaction between the LUSH and ethanol was then used to achieve a much higher sensitivity than a conventional ISFET. In the end, we successfully detected ethanol at concentrations ranging between 0.001 and 1% using the LUSH OBP-fused ISFET olfactory sensor. The OB... <s> BIB088 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Food allergy has increased rapidly in recent years affecting millions of people worldwide. With the increased consumption of packed food nowadays, a sensitive, accurate and rapid screening method for potential food allergens has become an urgent need in order to protect the sensitive consumers from life-threatening reactions. The current detection methods for food allergens are mostly based on immunoassays which are costly and times-consuming. In this work, we developed an aptamer/graphene-based electrochemical biosensor for on-step, sensitive and low cost detection of β-lactoglobulin (β-LG) milk protein, one of the most common food allergens specially in infants. The selection of DNA aptamers against the two β-LG variants A and B was successfully realised using systemic evolution of ligands by exponential enrichment (SELEX) method. Among the selected aptamers, BLG14 aptamer sequence has shown high affinity and specificity to both β-LG A and B with dissociation constants (Kds) of 82 and 80nM, respectively as calculated using fluorescence binding assays. The aptamer was then integrated in a voltammetric biosensor utilizing graphene-modified screen printed carbon electrodes. The binding is monitored by following the change in the square wave voltammetry (SWV) reduction peak signal of ferrocyanide/ferricyanide redox couple due to the removal of the negatively charged aptamers from the surface upon protein binding. This one-step "signal on" biosensor takes 20min for the sensitive and selective detection of β-LG without using any labelling or sophisticated designs. The method was also tested in spiked food sample extract achieving good recovery percentage. The integration of the novel aptamer in the graphene biosensor allows a promising way for cost-effective, rapid and sensitive on-site detection of milk allergen in food stuff. <s> BIB089 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Remarkable advances have been achieved in modern material technology, especially in device fabrication, and these have facilitated the use of diverse materials in various applications. Carbon nanotubes (CNTs) are being successfully implemented in drug delivery, sensing, water purification, composite materials, and bone scaffolds. Thus, CNTs must meet a wide range of criteria such as surface modification, high aspect ratio, desired conductivity, high porosity and loading, non-toxicity, specificity, and selectivity, and compatibility for device fabrication. The main focus of this review is to explore the maximum applications of CNTs for human health, and we particularly focus on nanocarrier and biomedical applications. The scope of this review initially covers the basic aspects of CNTs and is also extended further to describe their synthesis strategies as well as various challenges encountered in their functionalization, dispersion, and toxicity. Our discussion also emphasizes future directions for these emerging fields of research. <s> BIB090 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> This study reports biosensing using graphene field-effect transistors with the aid of pyrene-tagged DNA aptamers, which exhibit excellent selectivity, affinity, and stability for Escherichia coli (E. coli) detection. The aptamer is employed as the sensing probe due to its advantages such as high stability and high affinity toward small molecules and even whole cells. The change of the carrier density in the probe-modified graphene due to the attachment of E. coli is discussed theoretically for the first time and also verified experimentally. The conformational change of the aptamer due to the binding of E. coli brings the negatively charged E. coli close to the graphene surface, increasing the hole carrier density efficiently in graphene and achieving electrical detection. The binding of negatively charged E. coli induces holes in graphene, which are pumped into the graphene channel from the contact electrodes. The carrier mobility, which correlates the gate voltage to the electrical signal of the APG-FETs, is analyzed and optimized here. The excellent sensing performance such as low detection limit, high sensitivity, outstanding selectivity and stability of the graphene biosensor for E. coli detection paves the way to develop graphene biosensors for bacterial detection. <s> BIB091 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Nanopore sensors show great potential for rapid, single-molecule determination of DNA sequence information. Here, we develop an ionic current-based method for determining the positions of short sequence motifs in double-stranded DNA molecules with solid-state nanopores. Using the DNA-methyltransferase M.TaqI and a biotinylated S-adenosyl-l-methionine cofactor analogue we create covalently attached biotin labels at 5'-TCGA-3' sequence motifs. Monovalent streptavidin is then added to bind to the biotinylated sites giving rise to additional current blockade signals when the DNA passes through a conical quartz nanopore. We determine the relationship between translocation time and position along the DNA contour and find a minimum resolvable distance between two labeled sites of ∼200 bp. We then characterize a variety of DNA molecules by determining the positions of bound streptavidin and show that two short genomes can be simultaneously detected in a mixture. Our method provides a simple, generic single-molecule detection platform enabling DNA characterization in an electrical format suited for portable devices for potential diagnostic applications. <s> BIB092 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Synthetic biology, through genetic circuit engineering in biological cells, is paving the way toward the realization of programmable man-made living devices, able to naturally operate within normally less accessible domains, i.e. , the biological and the nanoscale. The control of the information processing and exchange between these engineered-cell devices, based on molecules and biochemical reactions, i.e. , molecular communication (MC), will be enabling technologies for the emerging paradigm of the Internet of Bio-Nano Things, with applications ranging from tissue engineering to bioremediation. In this paper, the design of genetic circuits to enable MC links between engineered cells is proposed by stemming from techniques for information coding and inspired by recent studies favoring the efficiency of analog computation over digital in biological cells. In particular, the design of a joint encoder-modulator for the transmission of binary-modulated molecule concentration is coupled with a decoder that computes the a-posteriori log-likelihood ratio of the information bits from the propagated concentration. These functionalities are implemented entirely in the biochemical domain through activation and repression of genes, and biochemical reactions, rather than classical electrical circuits. Biochemical simulations are used to evaluate the proposed design against a theoretical encoder/decoder implementation taking into account impairments introduced by diffusion noise. <s> BIB093 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Biological cells naturally exchange information for adapting to the environment, or even influencing other cells. One of the latest frontiers of synthetic biology stands in engineering cells to harness these natural communication processes for tissue engineering and cancer treatment, amongst others. Although experimental success has been achieved in this direction, approaches to characterize these systems in terms of communication performance and their dependence on design parameters are currently limited. In contrast to more classical communication systems, information in biological cells is propagated through molecules and biochemical reactions, which in general result in nonlinear input-output behaviors with system-evolution-dependent stochastic effects that are not amenable to analytical closed-form characterization. In this paper, a computational approach is proposed to characterize the information exchange in these systems, based on stochastic simulation of biochemical reactions and the estimation of information-theoretic parameters from sample distributions. In particular, this approach focuses on engineered cell-to-cell communications with a single transmitter and receiver, and it is applied to characterize the performance of a realistic system. Numerical results confirm the feasibility of this approach to be at the basis of future forward engineering practices for these communication systems. <s> BIB094 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Simple and easy to implement testbeds are needed to further advance molecular communication research. To this end, this paper presents an in-vessel molecular communication testbed using magnetic nanoparticles dispersed in an aqueous suspension as they are also used for drug targeting in biotechnology. The transmitter is realized by an electronic pump for injection via a Y-connector. A second pump provides a background flow for signal propagation. For signal reception, we employ a susceptometer, an electronic device including a coil, where the magnetic particles move through and generate an electrical signal. We present experimental results for the transmission of a binary sequence and the system response following a single injection. For this flow-driven particle transport, we propose a simple parameterized mathematical model for evaluating the system response. <s> BIB095 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> In recent years, molybdenum disulfide (MoS2) based field-effect transistors (FETs) have attracted much attention because of the unique properties of MoS2 nano-materials as an ideal channel material. Using a MoS2 FET as a glucose solution biosensor has the advantages of high sensitivity and rapid response. This paper is concerned with the fabrication of a bilayer MoS2-based FET and the study of its application in the high sensitivity detection of an extremely low concentration glucose solution. It was found that the source-drain current (Ids) increases as the concentration of the glucose solution increases at the same gate voltage (Vgs) and drain voltage (Vds). The sensitivity of the biosensor as high as 260.75 mA mM−1 has been calculated and the detection limit of 300 nM was measured. The unknown concentration of a glucose solution was also detected using data based on the relationship between Ids and glucose solution concentration. In addition, many significant advantages of the biosensor were observed, such as short response time (<1 s), good stability, wide linear detection range (300 nM to 30 mM) and the micro-detection of glucose solutions. These unique properties make the bilayer MoS2-based FET a great potential candidate for next generation biosensors. <s> BIB096 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Owing to their two-dimensional confinements, silicon nanowires display remarkable optical, magnetic, and electronic properties. Of special interest has been the development of advanced biosensing approaches based on the field effect associated with silicon nanowires (SiNWs). Recent advancements in top-down fabrication technologies have paved the way to large scale production of high density and quality arrays of SiNW field effect transistor (FETs), a critical step towards their integration in real-life biosensing applications. A key requirement toward the fulfilment of SiNW FETs’ promises in the bioanalytical field is their efficient integration within functional devices. Aiming to provide a comprehensive roadmap for the development of SiNW FET based sensing platforms, we critically review and discuss the key design and fabrication aspects relevant to their development and integration within complementary metal-oxide-semiconductor (CMOS) technology. <s> BIB097 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Liquid-gated Si nanowire field-effect transistor (FET) biosensors are fabricated using a complementary metal-oxide-semiconductor-compatible top-down approach. The transport and noise properties of the devices reflect the high performance of the FET structures, which allows label-free detection of cardiac troponin I (cTnI) molecules. Moreover, after removing the troponin antigens the structures demonstrate the same characteristics as before cTnI detection, indicating the reusable operation of biosensors. Our results show that the additional noise is related to the troponin molecules and has characteristics which considerably differ from those usually recorded for conventional FETs without target molecules. We describe the origin of the noise and suggest that noise spectroscopy represents a powerful tool for understanding molecular dynamic processes in nanoscale FET-based biosensors. <s> BIB098 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> Aerosol Transmission is one of the major spread mechanism for diseases and is responsible for transmission of virus over long distances. The advancement in nanotechnology has resulted in sensors and systems that allow us to deal with nanosized biological entities such as virus and bacteria. In this work, the idea of viewing virus transmission through aerosols and their transport as a molecular communication problem is introduced. In such problems one has little or no control over transmission, however, a robust receiver can be designed using nano-biosensors for information extraction. Thus, the objective of this work is to treat viral aerosol spread as a blind communication problem and present a mathematical model for it. Specifically, we study the virus transmission from an engineering perspective and derive an end-to-end mathematical model for virus transmission in the atmosphere. The receiver architecture composed of air sampler and Silicon Nanowire field effect transistor is also discussed. Furthermore, a detection problem is formulated and simulation results are reported that justify the feasibility of such setups in bio-monitoring applications. <s> BIB099 </s> Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding and Detection Techniques <s> C. Physical Design of MC Receiver <s> The possibility to guide and control magnetic nanoparticles in a non-invasive manner has spawned various applications in biotechnology, such as targeted drug delivery and sensing of biological substances. These applications are facilitated by the engineering of the size, selective chemical reactivity, and general chemical composition of the employed particles. Motivated by their widespread use and favorable properties, in this paper, we provide a theoretical study of the potential benefits of magnetic nanoparticles for the design of molecular communication systems. In particular, we consider a magnetic nanoparticle-based communication in a microfluidic channel where an external magnetic field is employed to attract the information-carrying particles to the receiver. We show that the particle transport affected by the Brownian motion, fluid flow, and an external magnetic field can be mathematically modeled as diffusion with drift. Thereby, we reveal that the key parameters determining the magnetic force are the particle size and the magnetic field gradient. Moreover, we derive an analytical expression for the channel impulse response, which is used to evaluate the potential gain in the expected number of observed nanoparticles due to the magnetic field. Furthermore, adopting the symbol error rate as performance metric, we show that using magnetic nanoparticles can enable a reliable communication in the presence of disruptive fluid flow. The numerical results obtained by the particle-based simulation validate the accuracy of the derived analytical expressions. <s> BIB100
Most of existing studies on the performance of MC ignore the physical design of the receiver and assume that the receiver can perfectly count the number of molecules that (i) enter a reception space with transparent boundaries BIB048 , BIB057 BIB049 BIB058 , (ii) hit a 3-D sphere that absorbs molecules BIB059 BIB084 BIB085 , or (iii) bind to receptors located on its surface BIB038 BIB070 BIB071 . However, the processes involved in the molecular-to-electrical transduction affect the performance of the receiver, thus, the comprehensive communication theoretical modeling of these processes are required. Available approaches in physical design of MC-Rxs can be categorized into two main groups as follows. 1) Biological MC-Rx Architectures: Synthetic biology, the engineering of biological networks inside living cells, has seen remarkable advancements in the last decade, such that it becomes possible to device engineered cells, e.g., bacteria, for use as biological machines, e.g., sensors and actuators, for various applications. Synthetic biology also stands as a promising means of devising nanoscale biotransceivers for IoNT applications, by implementing transmission and reception functionalities within living cells by modifying the natural gene circuits or creating new synthetic ones BIB072 . The technology is already mature enough to allow performing complex digital computations, e.g., with networks of genetic NAND and NOR gates, as well as analog computations, such as logarithmically linear addition, ratiometric and power-law computations, in synthetic cells BIB050 . Synthetic gene networks integrating computation and memory is also proven feasible BIB060 . More importantly in this context, the technology enables implementing bio-nanomachines capable of observing individual receptors, as naturally done by living cells; thus, stands as a suitable domain for practically implementing more information-efficient MC detectors based on the binding state history of individual receptors, as discussed in Section III-D. In DNAs, gene expression is the process that produces a functional gene product, such as a protein. The rate of this expression can be controlled by binding of another protein to the regulatory sequence of the gene. In biological circuits, activation and repression mechanisms, that regulate the gene expressions, are used to connect DNA genes together, i.e., the gene expression of a DNA generates a protein which can then bind to the regulatory sequence of next DNA to control its expression BIB027 . In  , polymerases per second (PoPS) is defined as the unit of input and output of a biological cell, i.e., the circuit processes a PoPS signal as input and generates another PoPS signal at its output using the aforementioned connections among DNAs. The literature in applying synthetic biology tools to design bacteria-based MC-Rxs is scarce. An MC biotransceiver architecture integrating molecular sensing, transmitting, receiving and processing functions through genetic circuits is introduced in BIB072 . However, the analysis is based on the assumption of linearity and time-invariance of the gene translation networks, and does not provide any insight into the associated noise sources. The necessary biological elements for an MC-Rx are shown in Fig. 7 [168] . The process of receiving information is initiated by Receptor Activation Expression, which gets a PoPS auxiliary signal as its input and generates receptor proteins, denoted by R, at its output. The incoming signal molecules from molecular channel, i.e., S Rx , then bind to these receptors in Ligand-Receptor Binding unit and form activator complexes, called RS. Finally, the concentration of RS initiates the Output Transcription Activation, in which RNA polymerase proteins, RN AP , bind to to the promoter sequence, P Rx and produce the PoPS output signal, P oP S Out . Assuming that the intracellular receiver environment is chemically homogeneous, the transfer function of aforementioned biological circuit is derived in BIB061 to provide a system theoretic model for the MC-Rx. Genetic circuits are shown to provide higher efficiency for analog computation compared to digital computations BIB062 . Thus, analog computing functionalities of genetic circuits are utilized in BIB093 to derive an analog parity-check decoder circuit. The major challenge in use of genetic circuits for implementing MC-Rx arises from the fact that information transmission in biological cells is through molecules and biochemical reactions. This results in nonlinear input-output behaviors with system-evolution-dependent stochastic effects that are needed to be comprehensively studied to evaluate the performance of the device. In BIB005 BIB004 BIB008 , initiative studies on mathematical modeling of cellular signaling are provided. However, it is shown in BIB094 that the characterization of the communication performance of these systems is not analytically tractable. Additionally, a computational approach is proposed to characterize the information exchange in a bio-circuit-based receiver using the experimental data published in  . The results in BIB094 reveal that the rate of information transfer through biocircuit based systems is extremely limited by the existing noises in these systems. Thus, comprehensive studies are needed to characterize these noises and derive methods to mitigate them. Additionally, existing studies have only focused on the single transmitter-receiver systems, thus, the connection among biological elements for MC with multiple receiver cells remains as an open issue. 2) Nanomaterial-based Artificial MC-Rx Architectures: Similar to MC-Rxs, biosensors are also designed to detect the concentration of an analyte in a solution BIB003 . Thus, existing literature on MC-Rx design are focused on analyzing the suitability and performance of available biosensing options for receiving the information in MC paradigm BIB073 , BIB051 , BIB074 BIB086 BIB095 . In this direction, researchers must consider the fundamental differences between a biosensor and a MC-Rx, arising from their different application areas, as stated below. • Biosensors are designed to perform typically in equilibrium condition. However, MC-Rxs must continuously observe the environment and detect the information encoded into a physical property related to the molecules, such as concentration, type/ratio/order, or arrival time. • Biosensors are mostly designed for laboratory applications with macroscale readout devices and human observers to compensate the lack of an integrated processor, which is not applicable for an MC-Rx. Thus, while the biosensing literature provides insights for MCRx design, ICT requirements of the device and its performance in an MC paradigm must be considered to reach appropriate solutions. Among existing biosensing options, the electrical biosensors are mainly under the focus of MC-Rx design BIB073 . The remaining options, i.e., optical and mechanical sensing, need macroscale excitation and detection units  [182] BIB039 making them inappropriate for an MC-Rx that requires in situ operation. Biocatalytic BIB019 and affinity-based BIB002 sensors are two types of electrical biosensors with different molecular recognition methods. Biocatalytic recognition is based on two steps. First, an enzyme, immobilized on the device, binds with the target molecule producing an electroactive specie, such as hydrogen ion. Arrival of this specie near the working electrode of the transducer is then being sensed as it modulates one of electrical characteristics of the device. Glucose and glutamate sensors are examples of the biocatalytic electrical sensors BIB019 , BIB035 . Alternatively, binding of receptor-ligand pairs on the recognition layer of the sensor is the foundation of affinity-based sensing BIB002 . Affinity-based sensing, which is feasible for a a wider range of target molecules, such as receptor proteins, and aptamer/DNAs BIB002 , BIB063 , provides a less complicated sensing scheme compared to biocatalytic-based sensing. For example, in the biocatalytic-based sensing, the impact of the additional products of the reaction between target molecule and enzyme in biocatalytic-based sensing on the performance of the device and the application environment must be analyzed thoroughly. Hence, affinity-based recognition is more appropriate for the design of a general MC system. However, this recognition method is not possible for non-electroactive informationcarrying molecules, such as glutamate and acetylcholine, which are highly important neurotransmitters in the mammalian central nervous system BIB001 . Thus, it is essential to study the design of biocatalytic-based electrical biosensors as MC-Rx when these types of information carriers are dictated by the application, e.g., communication with neurons. Recent advances in nanotechnology led to the design of field effect transistor (FET)-based biosensors (bioFETs) providing both affinity-based and biocatalytic-based electrical sensing with use of nanowires, nanotubes, organic polymers, and graphene as the transducer unit BIB035 , BIB096 BIB087  BIB014  BIB028 BIB052 . Detection of target molecules by bioFETs is based on the modulation of transducer conductivity as a result of either affinity-based or biocatalytic-based sensing. Simple operation principles together with the extensive literature on FETs established through many years, electrical controllability of the main device parameters, high-level integrability, and plethora of optimization options for varying applications make FET-based biosensing technology also a quite promising approach for electrical MC-Rx. Moreover, these sensors promise label-free, continuous and in situ operation in nanoscale dimensions. Thus, the design of an MC-Rx based on the principles of affinity-based bioFETs is the main approach considered in the literature BIB073 , BIB074 , which will be overviewed in the rest of this section. a) Nanoscale bioFET-based MC-Rx Architectures: As shown in Fig. 8 , a bioFET consists of source and drain electrodes and a transducer channel, which is functionalized by ligand receptors in affinity-based sensors BIB063 . In this type of sensors, the binding of target molecules or analytes to the ligand receptors leads to accumulation or depletion of the carriers on the semiconductor channel. This modulates the transducer conductivity, which, in turn, alters the flow of current between source and drain. Thus, by fixing the source-to-drain potential, the current flow becomes a function of the analyte density and the amount of analyte charges. Since the ligand receptors are being selected according to the target molecule, i.e., ligands, bioFETs do not require any complicated post-processing such as labeling of molecules. Moreover, the measurement of source-drain current does not need any macroscale readout unit. Thus, bioFETs can be used for direct, label-free, continuous and in situ sensing of the molecules in an environment as a standalone device. One of significant advantages of bioFETs over other electrical sensors is their wide range of design parameters. A list of FET-based biosensors and their applications in sensing different type of molecules is provided in Table III . In the following, we further describe these vast design options. Type of bioreceptors: First important design parameter arises from the type of receptors used in the Biorecognition Unit, which causes the selectivity of receiver for a certain type of molecules that will be used as information carrier in MC paradigm. Among possible receptor types for affinity-based bioFETs, natural receptor proteins and aptamer/DNAs are appropriate ones for an MC-Rx, since their binding to the target molecule is reversible and their size is small enough to be used in a nanomachine BIB002 , BIB063 . As an example, the FET transducer channel is functionalized with natural receptors, e.g., neuroreceptors, to detect taste in bioelectronic tongues BIB064 and odorant in olfactory biosensors BIB088 . An advantage of these type of receptors is their biocompatibility that makes them suitable for in vivo applications. In addition, use of aptamers, i.e., artificial single-stranded DNAs and RNAs, in the recognition unit of bioFETs provides detectors for a wide range of targets, such as small molecules, proteins, ions, aminoacids and other oligonucleotides BIB087 , BIB036 , BIB089 . Since an immense number of aptamer-ligand combinations with different affinities exist, it provides a powerful design option to control the selectivity of the MC-Rx. The appropriate aptamer for a target ligand can be find using SELEX process, i.e., searching a large library of DNAs and RNAs to determine a convenient nucleic acid sequence  . Material used for transducer channel: One of the most important bioFET design parameters is the material used as the transducer channel between source and drain electrodes, which determines the receiver geometry and affects the electrical noise characteristics of the device. Nanowires (NWs)  , BIB029 , single walled carbon nanotubes (SWCNTs), graphene BIB037 , molybdenum disulfide (MoS2) BIB065 , and organic materials like conducting polymers BIB053 are some examples of nanomaterials suitable for use in a bioFET channel. In the first generation of bioFETs, one dimensional materials such as SWCNT and NW were used as the channel in a bulk form. However, use in the form of single material or aligned arrays outperformed the bulk channels in terms of sensitivity and reduced noise BIB020 . Among possible NW materials, such as SnO 2 , ZnO and In 2 O 3 BIB054 , silicon NW (SiNW) bioFETs have shown high sensitivity, high integration density, high speed sampling and low power consumption BIB078 BIB044 BIB040 BIB041 BIB066 BIB042 . However, their reliable and cost-effective fabrication is still an important open challenge BIB087 , BIB067 . Comprehensive reviews exist on the performance of SiNW bioFETs, their functionality in biomedical applications such as disease diagnostic, their top-down and bottom-up fabrication paradigms and integration within complementary metaloxide-semiconductor (CMOS) technology BIB020 , BIB042 , BIB045  BIB097 . It is concluded that SiNW bioFETs must be designed according to the requirements arose by applications since defining an ideal characteristic for these devices is difficult. Additionally, both theoretical and experimental studies are needed to find the impact of structure parameters on their functionality. Moreover, fine balancing of important structural factors, such as number of NWs, their doping concentration and length, in SiNW bioFETs design and fabrication remains a challenge, which affects the sensitivity, reliability and stability of the device. SWCNT-based bioFETs offer higher detection sensitivity due to their electrical characteristic, however, these devices also face fabrication challenges, such that their defect free fabrication is the most challenging among all candidates BIB030 . Note that existence of defects can adversely affect the performance of SWCNT bioFETs in an MC-Rx. Moreover, for in vivo applications, the biocompatibility of CNTs and biodurability of functionalized SWCNTs are still under doubt BIB009 BIB090  . While both NWs and CNTs have onedimensional structure, use of two-dimensional materials as the transducer channel leads to higher sensitivity, since a planar structure provides higher spatial coverage, more bioreceptors can be functionalized to its surface and all of its surface atoms can closely interact with the bond molecules. Thus, graphene, with its extraordinary electrical, mechanical and chemical characteristics, is a promising alternative for the transducer channel of bioFETs BIB067 , BIB046 . Intrinsic flexibility of graphene provides higher chance of integration into devices with non-planar surfaces which can be more suitable for the design of nanomachines in an MC application BIB037 . There is currently tremendous amount of interest in building different configurations of graphene bioFETs, e.g., back-gated BIB079 or solution-gated BIB046 , with research showing its superior sensing performance for various analytes, e.g., antigens BIB080 , DNA  , bacteria BIB091 , odorant compounds BIB046 , and glucose BIB075 . General block diagram of a bioFET-based MC-Rx is shown in Fig. 9 . The biorecognition Unit is the interface between communication channel and the receiver, thus, it models sensing of the concentration of ligands. The random motion of ligands near the surface of the receiver, which is governed by Brownian motion, leads to fluctuations in the number of bound receptors. This fluctuation can be modeled as a binding noise, which depends on the transmitted signal and can adversely affect the detection of the ligands concentration BIB006 . The communication theoretical models of binding noise are presented in BIB038 , BIB055 . Background noise, also called biological interference BIB073 , is resulted from binding of molecules different from targeted ligands that might exist in the communication channel and show similar affinity for the receptors BIB006 . Note that this is different from intersymbol interference and co-channel interference studied in BIB068 , BIB047 . Stochastic binding of ligands to the receptors modulated the conductance of the FET channel, which is modeled by Transducer unit in Fig. 9 . This conductance changes is then reflected into the current flowing between source and drain electrodes of FET by Output Unit. The surface potential of the FET channel, thus its source-to-drain current, can be affected by undesirable ionic adsorptions in application with ionic solutions BIB073 . Hence, a reference electrode can be used in the solution to stabilize the surface potential BIB015 . Finally, the transducing noise shown in Fig. 9 covers the impact of noise added to the received signal during transducing operation including thermal noise, caused by thermal fluctuations of charge carriers on the bound ligands, and 1/f (flicker) noise, resulted from traps and defects in the FET channel BIB010 . Flicker noise can be the dominant noise source in low frequencies as it increases with decreasing the frequency BIB073 . Detailed information on the impact of the aforementioned noise processes on the performance of bioFETs can be found in BIB010 , BIB056 . Moreover, experimental studies are provided in BIB098 on the noise resulted from ion dynamic processes related to ligand-receptor binding events of a liquid-gated SiNW array FET by measuring the noise spectra of device before and after binding of target molecules. While the existing biosensing literature can provide insight for the MC-Rx design, there is a need for investigation of design options according to the communication theoretical requirements of an MC-Rx. Few studies have focused on evaluating the performance of bioFETs in an MC paradigm. A SiNW bioFET-based MC-Rx is modeled in BIB073 based on equilibrium assumption for the receptor-ligand reaction at the receiver surface. The study provides a circuit model for the transducer unit of the receiver. This work is further extended in BIB074 , where the spatial and temporal correlation effects resulting from finite-rate transport of ligands to the stochastic ligand-receptor binding process are considered to derive the receiver model and its noise statistics. In BIB099 , an MC-Rx consisting of an aerosol sampler, a SiNW bioFET functionalized with antibodies and a detection stage is designed for virus detection. The performance of the receiver is studied by considering the system in steady state. While the receiver model in BIB099 takes into account the flicker noise and thermal noise, it neglects the interference noise by assuming that the MC-Rx performs in a perfectly sanitized room. Moreover, the models used in all of these studies assume the ligandreceptor binding process in thermal equilibrium and they do not capture well the correlations resulting from the timevarying ligand concentration occurring in the case of molecular communications. More importantly, these studies only cover SiNW bioFET-receivers, and do not provide much insight into the performance of other nanomaterials as the transducer channel, such as graphene that promises to provide higher detection sensitivity due to its two-dimensional structure. Thus, the literature misses stochastic models for nanomaterial-based MC nanoreceiver architectures, which are needed to study the performance of the receiver in MC scenarios, i.e., when the device is exposed to time-varying concentration signals of different types and amplitudes. These models must capture the impacts of receiver geometry, its operation voltage characteristics and all fundamental processes involved in sensing of molecular concentration, such as molecular transport, ligand-receptor binding kinetics, molecular-to-electrical transduction by changes in the conductance of the channel. To provide such a model for graphene-based bioFETs, the major factors that influence the graphene properties must be taken into account. The number of layers is the most dominant factor since electronic band structure, which has a direct impact on the electrical properties of the device, is more complex for graphene with more number of layers BIB043 BIB007 BIB011 BIB031  . Next important parameter is the substrate used in graphene-based bioFET, specially when the number of layers is less than three  , BIB021 . The carrier mobility in graphene sheet is reported to be reduced by more than an order of magnitude on SiO 2 substrate due to charged impurities in the substrate and remote interfacial phonon scattering  . On the other hand, it is shown that impacts of substrate can be reduced in suspended single-layer graphene sheet, resulting in higher carrier mobility BIB022 . Moreover, as a result of graphene's large surface area, the impact of impurities on its performance can be substantial BIB021 . The atomic type, amounts and functional groups on the edges of graphene, which are hard to measure and control, are also among the properties that can result in trial to trial variations in the performance of the fabricated device BIB016 BIB017 BIB023 . Additionally, inherent rippling in graphene sheet, defects and size of sheet also affect the properties of the device BIB021 , BIB018 BIB024 BIB025 BIB032 BIB033 BIB026 BIB034 BIB012 . b) Other MC-Rx Architectures: Few studies exist on the practical MC systems taking into account the physical design of the receiver. In BIB051 , the isopropyl alcohol (rubbing alcohol) is used as information carrier and commercially available metal oxide semiconductor alcohol sensors are used as MCRx. This study provides a test-bed for MC with macroscale dimensions, which is later on utilized in BIB076 to estimate its combined channel and receiver model. This test-bed is extended to a molecular multiple-input multiple-output (MIMO) system in BIB081 to improve the achievable data rate. In BIB086 , the information is encoded in pH level of the transmitted fluid and a pH probe sensor is used as the MC-Rx. Since use of acids and bases for information transmission can adversely affect the other processes in the application environment, such as in the body, magnetic nanoparticles (MNs) are used as information-carrying molecules in microfluidic channels in BIB095 . In this study, a bulky susceptometer is used to detect the concentration of MNs and decode the transmitted messages. In addition, performance of MN-based MC where an external magnetic field is employed to attract the MNs to a passive receiver is analyzed in BIB100 . However, the focus of the aforementioned studies is using macroscale and commercially available sensors as receiver. Thus, these studies do not contribute to the design of a nanoscale MC-Rx. As discussed in Section II-B1, recent advancements in DNA/RNA sequencing and synthesis techniques have enabled DNA/RNA-encoded MC BIB082 , BIB092 . For information transmission, communication symbols can be realized with DNA/RNA strands having different properties, i.e., length BIB077 , dumbbell hairpins BIB082 , BIB083 , and short sequence motifs/labels BIB092 . For information detection, solidstate BIB092 and DNA-origami BIB069 based nanopores can be utilized to distinguish information symbols, i.e., the properties of DNA/RNA strands by examining the current characteristics while DNA/RNA strands pass through the nanopores. As presented in Fig. 3 , MC-Rx contains receptor nanopores through which these negatively charged DNA strands pass thanks to the applied potential, and as they do, they obstruct ionic currents that normally flow through. The duration of the current obstruction is proportional to the length of the DNA strand that passes through, which is utilized for selective sensing. The use of nanopores for DNA/RNA symbol detection also enables the miniaturization of MC capable devices towards the realization of IoNT. According to BIB082 , 3-bit barcode-coded DNA strands with dumbbell hairpins can be detected through nanopores with 94% accuracy. In BIB013 , four different RNA molecules having different orientations are translocated with more than 90% accuracy while passing through transmembrane protein nanopores. The time of the translocation event depends on the voltage, concentration and length of the DNA symbols, and the translocation of symbols can take up to a few ms up to hundred ms time frames BIB082 , BIB083 . Considering the slow diffusion channel in MC, transmission/detection of DNA/RNA-encoded symbols do not introduce a bottleneck and multiple detections can be performed during each symbol transmission.