A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Abstract ::: This study demonstrates that blastocyst-derived embryonic stem cells (ES cells) can be used as a vehicle for transgenesis. The method is nearly as efficient as other methods, and the introduced neomycin phosphotransferase (neo) gene is stably transmitted through several generations with no apparent loss in G418 resistance. An important factor contributing to the efficiency of this process is the rigorous selection, before blastocyst injection, of genetically transformed cells for in vitro developmental pluripotency. One of the advantages of the ES cell route to transgenesis is that it provides investigators with the opportunity to screen for the desired genetic alterations before reintroducing the ES cells into the animal. <s> BIB001 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Gene therapy is now being applied to the treatment of a wide variety of acquired and inherited diseases. One of the rate-limiting steps for successful gene therapy is the efficiency of gene transfer. A number of different viral systems are being developed for use as vectors for ex vivo and in vivo gene transfer, including retroviruses, adenoviruses, herpes-simplex viruses and adeno-associated viruses. These viral vectors have a number of specific advantages and disadvantages that make them suited to particular gene-therapeutic applications. This review will summarize the current status of the development of viral vectors for gene therapy. <s> BIB002 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> De novo engineering of gene circuits inside cells is extremely difficult, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells. Here we demonstrate that by coupling gene expression to cell survival and death using cell-cell communication, we can programme the dynamics of a population despite variability in the behaviour of individual cells. Specifically, we have built and characterized a 'population control' circuit that autonomously regulates the density of an Escherichia coli population. The cell density is broadcasted and detected by elements from a bacterial quorum-sensing system, which in turn regulate the death rate. As predicted by a simple mathematical model, the circuit can set a stable steady state in terms of cell density and gene expression that is easily tunable by varying the stability of the cell-cell communication signal. This circuit incorporates a mechanism for programmed death in response to changes in the environment, and allows us to probe the design principles of its more complex natural counterparts. <s> BIB003 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> The construction of synthetic cell-cell communication networks can improve our quantitative understanding of naturally occurring signaling pathways and enhance our capabilities to engineer coordinated cellular behavior in cell populations. Towards accomplishing these goals in eukaryotes, we developed and analyzed two artificial cell-cell communication systems in yeast. We integrated Arabidopsis thaliana signal synthesis and receptor components with yeast endogenous protein phosphorylation elements and new response promoters. In the first system, engineered yeast 'sender' cells synthesize the plant hormone cytokinin, which diffuses into the environment and activates a hybrid exogenous/endogenous phosphorylation signaling pathway in nearby engineered yeast 'receiver' cells. For the second system, the sender network was integrated into the receivers under positive-feedback regulation, resulting in population density-dependent gene expression (that is, quorum sensing). The combined experimental work and mathematical modeling of the systems presented here can benefit various biotechnology applications for yeast and higher level eukaryotes, including fermentation processes, biomaterial fabrication and tissue engineering. <s> BIB004 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Pattern formation is a hallmark of coordinated cell behaviour in both single and multicellular organisms. It typically involves cell–cell communication and intracellular signal processing. Here we show a synthetic multicellular system in which genetically engineered ‘receiver’ cells are programmed to form ring-like patterns of differentiation based on chemical gradients of an acyl-homoserine lactone (AHL) signal that is synthesized by ‘sender’ cells. In receiver cells, ‘band-detect’ gene networks respond to user-defined ranges of AHL concentrations. By fusing different fluorescent proteins as outputs of network variants, an initially undifferentiated ‘lawn’ of receivers is engineered to form a bullseye pattern around a sender colony. Other patterns, such as ellipses and clovers, are achieved by placing senders in different configurations. Experimental and theoretical analyses reveal which kinetic parameters most significantly affect ring development over time. Construction and study of such synthetic multicellular systems can improve our quantitative understanding of naturally occurring developmental processes and may foster applications in tissue engineering, biomaterial fabrication and biosensing. <s> BIB005 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Chemical signalling is the main mechanism by which biological function is controlled at all levels, from the single cell to the whole organism. Chemical recognition is the function of receptors, which, in addition to recognising endogenous chemical signals, are also the target of many important experimental and therapeutic drugs. Receptors, therefore, lie at the heart of pharmacology. This article describes the way in which the receptor concept originated early in the 20th century, and evolved through a highly innovative stage of quantitative theory based on chemical kinetics, to the point where receptors were first isolated and later cloned, until we now have a virtually complete catalogue of all the receptors present in the genome. Studies on signal transduction are revealing great complexity in the events linking ligand binding to the physiological or therapeutic response. Though some simple quantitative rules of ‘receptor theory' are still useful, the current emphasis is on unravelling the pathways that link receptors to responses, and it will be some time before we know enough about them to embark on the next phase of ‘receptor theory'. <s> BIB006 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Miniaturizing in chip technology, optics, micro mechanics, medicine, gene and biotechnology requires highly precise positioning techniques. The motivation for the new manipulation technology is the desire to enter the micro- and nanoworld not only by viewing but also acting, altering micro- and nanosized objects. A new era on medicine are expected to happen in the coming years. Due to the advances in the field of nanotechnology, nanodevice manufacturing has been growing gradually. From such achievements in nanotechnology and recent results in biotechnology and genetics, the first operating biological nanorobots are expected to appear in the coming 5 years and more complex diamondoid based nanorobots will become available in about 10 years. In terms of time, it means a very near better future with significant improvements in medicine. <s> BIB007 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Biological systems display a functional diversity, density and efficiency that make them a paradigm for synthetic systems. In natural systems, the cell is the elemental unit and efforts to emulate cells, their components, and organization have relied primarily on the use of bioorganic materials. Impressive advances have been made towards assembling simple genetic systems within cellular scale containers. These biological system assembly efforts are particularly instructive, as we gain command over the directed synthesis and assembly of synthetic nanoscale structures. Advances in nanoscale fabrication, assembly, and characterization are providing the tools and materials for characterizing and emulating the smallest scale features of biology. Further, they are revealing unique physical properties that emerge at the nanoscale. Realizing these properties in useful ways will require attention to the assembly of these nanoscale components. Attention to systems biology principles can lead to the practical development of nanoscale technologies with possible realization of synthetic systems with cell-like complexity. In turn, useful tools for interpreting biological complexity and for interfacing to biological processes will result. <s> BIB008 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Receptors constitute the interface of cells to their external environment. These molecules bind specific ligands involved in multiple processes, such as signal transduction and nutrient transport. Although a variety of cell surface receptors undergo endocytosis, the systems-level design principles that govern the evolution of receptor trafficking dynamics are far from fully understood. We have constructed a generalized mathematical model of receptor–ligand binding and internalization to understand how receptor internalization dynamics encodes receptor function and regulation. A given signaling or transport receptor system represents a particular implementation of this module with a specific set of kinetic parameters. Parametric analysis of the response of receptor systems to ligand inputs reveals that receptor systems can be characterized as being: i) avidity-controlled where the response control depends primarily on the extracellular ligand capture efficiency, ii) consumption-controlled where the ability to internalize surface-bound ligand is the primary control parameter, and iii) dual-sensitivity where both the avidity and consumption parameters are important. We show that the transferrin and low-density lipoprotein receptors are avidity-controlled, the vitellogenin receptor is consumption-controlled, and the epidermal growth factor receptor is a dual-sensitivity receptor. Significantly, we show that ligand-induced endocytosis is a mechanism to enhance the accuracy of signaling receptors rather than merely serving to attenuate signaling. Our analysis reveals that the location of a receptor system in the avidity-consumption parameter space can be used to understand both its function and its regulation. <s> BIB009 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Designs and simulation results are given for two small, special-purpose nanoelectronic circuits. The area of special-purpose nanoelectronics has not been given much consideration previously, though much effort has been devoted to the development of general-purpose nanoelectronic systems, i.e., nanocomputers. This paper demonstrates via simulation that the nanodevices and nanofabrication techniques developed recently for general-purpose nanocomputers also might be applied with substantial benefit to implement less complex nanocircuits targeted at specific applications. Nanocircuits considered here are a digital controller for the leg motion on an autonomous millimeter-scale robot and an analog nanocircuit for amplification of signals in a tiny optoelectronic sensor or receiver. Simulations of both nanocircuit designs show significant improvement over microelectronic designs in metrics such as footprint area and power consumption. These improvements are obtained from designs employing nanodevices and nanofabrication techniques that already have been demonstrated experimentally. Thus, the results presented here suggest that such improvements might be realized in the near term for important, special-purpose applications. <s> BIB010 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Molecular communication is a bio-inspired communication paradigm using molecules as information carriers. The molecular communication system includes propagation of information carrier molecules between a molecular sender and a molecular receiver and followed by amplification of the information at the receiver. In this article, we built an example molecular communication system using a gemini peptide lipid as a molecular switch. The molecular switch embedded in the lipid bilayer membranes exhibited photoresponsive recognition behaviour towards metal ions, such as Cu2+ and Zn2+, to control propagation of molecular capsules formed by small liposomes to a giant liposomal receiver. In addition, the molecular switch acted as an artificial receptor in the receiver, receiving a photonic signal to communicate with an enzyme as a signal amplifier by using Cu2+ ion as a mediator between the receptor and the amplifier. <s> BIB011 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Brings the latest advances in nanotechnology and biology to computing This pioneering book demonstrates how nanotechnology can create even faster, denser computing architectures and algorithms. Furthermore, it draws from the latest advances in biology with a focus on bio-inspired computing at the nanoscale, bringing to light several new and innovative applications such as nanoscale implantable biomedical devices and neural networks. Bio-Inspired and Nanoscale Integrated Computing features an expert team of interdisciplinary authors who offer readers the benefit of their own breakthroughs in integrated computing as well as a thorough investigation and analyses of the literature. Carefully edited, the book begins with an introductory chapter providing a general overview of the field. It ends with a chapter setting forth the common themes that tie the chapters together as well as a forecast of emerging avenues of research. Among the important topics addressed in the book are modeling of nano devices, quantum computing, quantum dot cellular automata, dielectrophoretic reconfigurable nano architectures, multilevel and three-dimensional nanomagnetic recording, spin-wave architectures and algorithms, fault-tolerant nanocomputing, molecular computing, self-assembly of supramolecular nanostructures, DNA nanotechnology and computing, nanoscale DNA sequence matching, medical nanorobotics, heterogeneous nanostructures for biomedical diagnostics, biomimetic cortical nanocircuits, bio-applications of carbon nanotubes, and nanoscale image processing. Readers in electrical engineering, computer science, and computational biology will gain new insights into how bio-inspired and nanoscale devices can be used to design the next generation of enhanced integrated circuits. <s> BIB012 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> By exploiting recent advances in both our understanding of pheromone biosynthesis pathways and the detection of molecules in the insect nervous system, we are developing a novel communication system based on functional equivalents of the cellular, sub-cellular and molecular biological machinery. This will form the basis of a new branch of information technology employing infochemical ligands for communication over space and time. In order to achieve this objective, both chemical signal generation and reception are replicated by taking a systematic approach that implements reaction steps as biosynthetic modules, which are then hierarchically integrated as a technological solution towards realising ‘infochemical communication’. <s> BIB013 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Recent studies have shown that many cell-signaling networks contain interactions and feedback loops that give rise to complex dynamics. Synthetic biology has allowed researchers to construct and analyze well-defined signaling circuits exhibiting behavior that can be predicted and quantitatively understood. Combining these approaches—wiring natural network components together with engineered interactions—has the potential to precisely modulate the dynamics of endogenous signaling processes and control the cell decisions they influence. Here, we focus on the p53 signaling pathway as a template for constructing a tunable oscillator comprised of both natural and synthetic components in mammalian cells. We find that a reduced p53 circuit implementing a single feedback loop preserves some features of the full network's dynamics, exhibiting pulses of p53 with tightly controlled timing. However, in contrast to the full natural p53 network, these pulses are damped in individual cells, with amplitude that depends on the input strength. Guided by a computational model of the reduced circuit, we constructed and analyzed circuit variants supplemented with synthetic positive and negative feedback loops and subjected to chemical perturbation. Our work demonstrates that three important features of oscillator dynamics—amplitude, period, and the rate of damping—can be controlled by manipulating stimulus level, interaction strength, and feedback topology. The approaches taken here may be useful for the rational design of synthetic networks with defined dynamics, and for identifying perturbations that control dynamics in natural biological circuits for research or therapeutic purposes. <s> BIB014 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> or keywords. 40 Sensitivity, Selectivity, and Stability of Gas-Sensitive Metal-Oxide Nanostructures й Sb S i Sr T j O 2 3% 3 % 3% 3o / o W o 3 <s> BIB015 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Background: The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry. Methodology/Principal Findings: To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes (*50%) and latency of the optimized engineered gene networks. Conclusions/Significance: Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems. <s> BIB016 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Biological clocks are self-sustained oscillators that adjust their phase to the daily environmental cycles in a process known as entrainment. Molecular dissection and mathematical modeling of biological oscillators have progressed quite far, but quantitative insights on the entrainment of clocks are relatively sparse. We simultaneously tracked the phases of hundreds of synthetic genetic oscillators relative to a common external stimulus to map the entrainment regions predicted by a detailed model of the clock. Synthetic oscillators were frequency-locked in wide intervals of the external period and showed higher-order resonance. Computational simulations indicated that natural oscillators may contain a positive-feedback loop to robustly adapt to environmental cycles. <s> BIB017 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> The creation of orthogonal ‘AND’ logic gates by combining DNA-binding proteins into complex, layered circuits opens the way to the design of programmable integrated circuits in synthetic biology. <s> BIB018 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Receptor-mediated endocytosis is a highly efficient mechanism for cellular uptake of membrane-impermeant ligands. Cells use this process to acquire nutrients, initiate signal transduction, promote development, regulate neurotransmission, and maintain homeostasis. Natural receptors that participate in receptor-mediated endocytosis are structurally diverse, ranging from large transmembrane proteins to small glycolipids embedded in the outer leaflet of cellular plasma membranes. Despite their vast structural differences, these receptors share common features of binding to extracellular ligands, clustering in dynamic membrane regions that pinch off to yield intracellular vesicles, and accumulation of receptor-ligand complexes in membrane-sealed endosomes. Receptors typically dissociate from ligands in endosomes and cycle back to the cell surface, whereas internalized ligands are usually delivered into lysosomes, where they are degraded, but some can escape and penetrate into the cytosol. Here, we review efforts to develop synthetic cell surface receptors, defined as nonnatural compounds, exemplified by mimics of cholesterol, that insert into plasma membranes, bind extracellular ligands including therapeutics, probes, and endogenous proteins, and engage endocytic membrane trafficking pathways. By mimicking natural mechanisms of receptor-mediated endocytosis, synthetic cell surface receptors have the potential to function as prosthetic molecules capable of seamlessly augmenting the endocytic uptake machinery of living mammalian cells. <s> BIB019 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Infochemical production, release and detection of (Z,E)-9,11-tetradecadienyl acetate, the major component of the pheromone of the moth Spodoptera littoralis, is achieved in a novel microfluidic system designed to mimic the final step of the pheromone biosynthesis by immobilized recombinant alcohol acetyl transferase. The microfluidic system is part of an “artificial gland”, i.e., a chemoemitter that comprises a microreactor connected to a microevaporator and is able to produce and release a pre-defined amount of the major component of the pheromone from the corresponding (Z,E)-9,11-tetradecadienol. Performance of the entire chemoemitter has been assessed in electrophysiological and behavioral experiments. Electroantennographic depolarizations of the pheromone produced by the chemoemitter were ca. 40% relative to that evoked by the synthetic pheromone. In a wind tunnel, the pheromone released from the evaporator elicited on males a similar attraction behavior as 3 virgin females in most of the parameters considered. <s> BIB020 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications. <s> BIB021 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> C. Transmitter/Receiver Mechanisms and Components <s> Communication via diffusion is an effective and energy efficient method for transmitting information in nanonetworks. However, the histogram of the molecules hitting at the receiver has a long tail. The molecules constituting this long tail significantly decrease the data rate since the selection of a high symbol duration becomes mandatory to have acceptable bit error rates. In this paper, a novel signal shaping technique for nanonetworking is proposed. This technique aims to decrease the variance of the hitting times via special so-called “destroyer molecules”. This system is inspired by the neuromuscular junction in biology, in which Acetylcholinesterase molecules are used to clean the channel for further transmissions. We consider a molecular communication channel where a tunnel composed of destroyer molecules exist between the communicating pair. Simulation results show that the inclusion of such destroyer molecules decrease both the mean and the variance of the hitting time distribution, allowing better time-responsiveness and higher data rate for the communication via diffusion system. <s> BIB022
The transmitter and the receiver of microscale molecular communication can be any machine in the micro-to nano-scale dimensions. For example, the transmitter and the receiver can be generated by genetically modifying cells BIB003 - BIB004 , or by creating artificial cells BIB008 - BIB011 . Regardless of the method used, the transmitter requires at least the three components mentioned in the previous section: a unit for generation or storing information particles, a unit for controlling the release of information particles, and a central processing unit. Similarly, the receiver needs at least two components: a detection unit for sensing the information particles, and a processing unit for decoding and deciphering the intended message from the detection unit's measurements. Physically, the central processing unit of the transmitter and the receiver may be implemented by synthesizing logic gates and memory in to cells as shown in BIB018 , BIB021 . The information particles can be generated by modifying a metabolic pathway of a biological cell, which then synthesizes and releases specific signal molecules BIB005 , BIB004 . Transfection, transfer via viral vectors, direct injection to germ line, transfer via embryonic stem cells are the methods for gene transfer for modifying a metabolic pathway  - BIB001 . Among these methods, viral vectors method is a commonly used tool by molecular biologists to deliver genetic material into cells. This process is used for manipulating a living cell to engineer regulatory networks that can be used for communication. For example, in BIB016 a platform for biological system designers to express desired system functions via high-level programming language is introduced. After forming the genetic regulatory network code, living cells are manipulated via viral vectors. This process can be performed inside a living organism or in cell culture. Viruses efficiently transport their genomes inside the cells they infect for desired function. Main types of viral vectors are retroviruses, lentiviruses, adenoviruses, adeno-associated viruses, and nanoengineered substances BIB002 . To control the release timing, a synthetic oscillator can be introduced into a cell BIB014 , BIB017 which with the help of the central processing unit acts as the release control module. Therefore, it is possible to have all the components of a transmitter synthesized into cells. Similarly, it is possible to synthesize receptors for a specific type of molecules into cells BIB019 , BIB009 . Therefore, it is possible to have all the components required for the receiver inside a synthetic cell. More sophisticated processing units can also be designed as shown in BIB012 , using novel materials and spin waves (spin waves are propagating disturbances in the ordering of magnetic materials). It is also possible to shrink the current electronic technology to nano scales to create nanoscale processing units BIB010 . In nature, signals are received via protein structures called receptors.Therefore, these protein structures can be seen as receiver antennas. Receptors are the special protein structures that can bind to specific ligand structures. The binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and van der Waals forces. The docking (association) is usually reversible (dissociation). Ligand binding to a receptor (receptor protein) alters receptor's chemical conformation and the tendency of binding is called affinity. The conformational state of a receptor determines its functional state  . Almost all the ligand structures, in nature, contribute to the signal only once at the receptor site  . This can be achieved by removing the information molecules from the propagation environment once they arrive at the receiver or destroying the molecules after dissociation (e.g., acetylcholinesterase breaks down the molecules in neuromuscular junctions) BIB022 ,  . Most of the works in receptor theory focus on ligandgated ion channels and G-protein coupled receptors BIB006 . Ligand-gated ion channels are a group of transmembrane ion channel proteins which open to allow ions such as Na + , K + , or Ca 2+ to pass through the membrane in response to the binding of a chemical messenger (i.e., a ligand). These proteins are typically composed of a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an allosteric binding site). G-protein coupled receptors constitute a large protein family of receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. Cells can also be created artificially by using liposome vesicles as the membrane encapsulating different functional proteins that together carry the task of the central processing unit, the particle generation and storage unit, receptors, and the particle release control unit for the transmitter and the receiver. Finally, it is possible to develop the transmitter and the receivers by synthesizing novel materials BIB007 . At macroscales, the transmitter and the receiver require the same set of components depicted in Figure 3 at the beginning of this section. For the transmitter, a storage container is required for holding the information particles. It is also possible to generate the information particles using different processes. A mechanism must be set in place for controlled release of chemicals. For example, sprays could be used for controlling the release of information particles. In  , BIB020 , a technique for releasing complex blends of compounds in specific ratios, which mimics insect pheromones, is developed. For detection at the receiver, chemical sensors could be used to detect the information particles. For example, metaloxide gas sensors BIB015 are typically inexpensive sensors, that are capable of detecting the concentration of various types of volatile chemicals and gases. It is also possible to create more sophisticated sensors for detecting mixture of chemicals as shown in BIB013 . The processing unit at macroscales can be a computer or a microcontroller, depending on the application. The power source could be electrical, solar, or any other source. At macroscales, power sources and processing unit have already been well studied and developed.