A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> Multicellular organisms create complex patterned structures from identical, unreliable components. Learning how to engineer such robust behavior is important to both an improved understanding of computer science and to a better understanding of the natural developmental process. Earlier work by our colleagues and ourselves on amorphous computing demonstrates in simulation how one might build complex patterned behavior in this way. This work reports on our first efforts to engineer microbial cells to exhibit this kind of multicellular pattern directed behavior. We describe a specific natural system, the Lux operon of Vibrio fischeri, which exhibits density dependent behavior using a well characterized set of genetic components. We have isolated, sequenced, and used these components to engineer intercellular communication mechanisms between living bacterial cells. In combination with digitally controlled intracellular genetic circuits, we believe this work allows us to begin the more difficult process of using these communication mechanisms to perform directed engineering of multicellular structures, using techniques such as chemical diffusion dependent behavior. These same techniques form an essential part of our toolkit for engineering with life, and are widely applicable in the field of microbial robotics, with potential applications in medicine, environmental monitoring and control, engineered crop cultivation, and molecular scale fabrication. <s> BIB001 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <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> BIB002 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> Nanostructured metal oxides (NMOs) have recently become important as materials that provide an eff ective surface for biomolecule immobilization with desired orientation, better conformation and high biological activity resulting in enhanced sensing characteristics. Nanostructured metal oxides with unique optical, electrical and molecular properties along with desired functionalities and surface charge properties provide interesting platforms for interfacing biorecognition elements with transducers for signal amplifi cation. In this review, we discuss the various approaches that have been adopted for improving the performance of NMO-based biosensors for clinical and non-clinical applications. The performance of an NMO-based biosensor can be improved by tailoring the properties of the metal oxide–biomolecule interface through engineering of morphology, particle size, eff ective surface area, functionality, adsorption capability and electron-transfer properties. These interesting NMOs are expected to fi nd applications in a new generation of miniaturized, smart biosensing devices. <s> BIB003 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> For synthetic biologists' creativity to be unleashed, basic circuits must become truly interchangeable, that is, modular and scalable. This study, one of two linked papers, has harnessed bacterial 'quorum sensing' to achieve complex computation through communication between individual cells performing simple logic functions. Such extracellular 'chemical wiring' is one promising way to get around intracellular noise when building more complex genetic circuitry. <s> BIB004 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> BackgroundEvolution has selected for organisms that benefit from genetically encoded cell-cell communication. Engineers have begun to repurpose elements of natural communication systems to realize programmed pattern formation and coordinate other population-level behaviors. However, existing engineered systems rely on system-specific small molecules to send molecular messages among cells. Thus, the information transmission capacity of current engineered biological communication systems is physically limited by specific biomolecules that are capable of sending only a single message, typically “regulate transcription.”ResultsWe have engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. We demonstrate the decoupling of messages from a common communication channel via the autonomous transmission of various arbitrary genetic messages. Further, we increase the range of engineered DNA messaging across semisolid media by linking message transmission or receipt to active cellular chemotaxis.ConclusionsWe demonstrate decoupling of a communication channel from message transmission within engineered biological systems via the autonomous targeted transduction of user-specified heterologous DNA messages. We also demonstrate that bacteriophage M13 particle production and message transduction occurs among chemotactic bacteria. We use chemotaxis to improve the range of DNA messaging, increasing both transmission distance and communication bit rates relative to existing small molecule-based communication systems. We postulate that integration of different engineered cell-cell communication platforms will allow for more complex spatial programming of dynamic cellular consortia. <s> BIB005 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <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> BIB006 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> The introduction of synthetic devices that provide precise fine-tuning of transgene expression has revolutionized the field of biology. The design and construction of sophisticated and reliable genetic control circuits have increased dramatically in complexity in recent years. The norm when creating such circuits is to program the whole network in a single cell. Although this has been greatly successful, the time will soon come when the capacity of a single cell is no longer adequate. Therefore, synthetic biology-inspired research has started to shift towards a multicellular approach in which specialized cells are constructed and then interconnected, enabling the creation of higher-order networks that do not face the same limitations as single cells. This approach is conceptually appealing in many respects. The fact that overall workload can be easily divided between cells eliminates the problem of limited program capacity of a single cell. Furthermore, engineering of specialized cells will enable a plug-and-play approach in which cells are combined into multicellular consortia depending on the requested task. Recent advances in synthetic biology to implement intercellular communication and multicellular consortia have demonstrated an impressive arsenal of new devices with novel functions that are unprecedented even in engineered single cells. Engineering of such devices have been achieved in bacteria, yeast and mammalian cells, all of which is covered in this review. The introduction of synthetic intercellular communication into the cell engineering toolbox will open up new frontiers and will greatly contribute to the future success of synthetic biology and its clinical applications. <s> BIB007 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> This demonstration will present the world's first macroscale molecular communication link to reliably transmit a continuous data stream. The system modulates alcohol molecules, which are then diffused via ambient and induced air currents to carry information to a receiver. The communication distance is several meters and the propagation channel we will demonstrate consists of both free space and tunnel environments. The goal is to show that molecules can be used as an alternative to electromagnetic (EM) waves in challenging environments where EM waves do not perform well. <s> BIB008 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> In this paper, we consider a molecular diffusion based communications link that can reliably transport data over-the-air. We show that the system can also reliably transport data across confined structural environments, especially in cases where conventional electromagnetic (EM) wave based systems may fail. In particular, this paper compares the performance of our proprietary molecular communication test-bed with Zigbee wireless sensors in a metal pipe network that does not act as a radio wave-guide. The paper first shows that a molecular-based communication link's performance is determined primarily by the delay time spread of the pulse response. The paper go on to show that molecular-based systems can transmit more reliably in complex and confined structural environments than conventional EM-based systems. The paper then utilizes empirical data to find relationships between the received radio signal strength, the molecular pulse spread, data rate (0.1 bits/s) and the structural propagation environment. <s> BIB009 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> In this paper, we propose a realistic channel model for a table-top molecular communication platform that is capable for transmitting short text messages across a room. The observed system response for this experimental platform does not match the theoretical results in the literature. This is because many simplifying assumptions regarding the flow, the sensor, and environmental conditions, which were used in derivations of previous theoretical models do not hold in practice. Therefore, in this paper, based on experimental observations, theoretical models are modified to create more realistic channel models. <s> BIB010 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> Recently, a tabletop molecular communication platform has been developed for transmitting short text messages across a room. The end-to-end system impulse response for this platform does not follow previously published theoretical works because of imperfect receiver, transmitter, and turbulent flows. Moreover, it is observed that this platform resembles a nonlinear system, which makes the rich body of theoretical work that has been developed by communication engineers not applicable to this platform. In this work, we first introduce corrections to the previous theoretical models of the end-to-end system impulse response based on the observed data from experimentation. Using the corrected impulse response models, we then formulate the nonlinearity of the system as noise and show that through simplifying assumptions it can be represented as Gaussian noise. Through formulating the system's nonlinearity as the output a linear system corrupted by noise, the rich toolbox of mathematical models of communication systems, most of which are based on linearity assumption, can be applied to this platform. <s> BIB011 </s> A Comprehensive Survey of Recent Advancements in Molecular Communication <s> VI. PRACTICAL AND EXPERIMENTAL SYSTEMS <s> Previous efforts to control cellular behaviour have largely relied upon various forms of genetic engineering. Once the genetic content of a living cell is modified, the behaviour of that cell typically changes as well. However, other methods of cellular control are possible. All cells sense and respond to their environment. Therefore, artificial, non-living cellular mimics could be engineered to activate or repress already existing natural sensory pathways of living cells through chemical communication. Here we describe the construction of such a system. The artificial cells expand the senses of Escherichia coli by translating a chemical message that E. coli cannot sense on its own to a molecule that activates a natural cellular response. This methodology could open new opportunities in engineering cellular behaviour without exploiting genetically modified organisms. <s> BIB012
As it was demonstrated in the previous sections, there has been many advancements in theoretical molecular communication over the past couple of years. All these advancements, however, have not translated into practical and experimental systems. Perhaps, one of the culprits is the multidisciplinary nature of molecular communication that requires a strong collaboration between telecommunication engineers, mechanical engineers, chemical engineers and biological engineers. Another possible hurdle is the cost associated with running wet labs. This lab is typically very expensive to run, which makes progress slower. Despite all these issues, however, there have been a number of works that explore the practicality of molecular communication in an experimental setting. In BIB006 the first molecular communication system capable of transmitting short text messages over free air was developed. The macroscale platform used an alcohol metal-oxide sensor BIB002 as the detector at the receiver, and an electronically controlled spray mechanize as the transmitter. Open platform Arduino microcontrollers were used to control the transmitter and the receiver. In this platform, text messages were converted into binary sequence, and the information was transmitted in a time-slotted fashion using on-off-keying, where a one was represented by spray of alcohol and a zero by no spray. The released alcohol particles propagated the environment through flow assisted propagation, which was induced using a tabletop fan. This system was also demonstrated in the IEEE International Conference on Computer Communications (INFOCOM) BIB008 . Figure 12 shows this inexpensive platform. On the left there is the transmitter with the spray, the fan and Arduino for controlling the sprays. On the right is the receiver board with the sensor and the Arduino connected to a laptop. Although this system demonstrates the feasibility of molecular communication at macroscales, it can be shrunk to microscales. For example, metal-oxide sensors can be shrunk to nano-scales [243], BIB003 to detect various biological compounds, and a microfluidics environment could be used as the propagation channel. In BIB009 , the use of molecular communication in infrastructure monitoring was considered. In particular, the performance of molecular communication system developed in BIB006 was compared with Zigbee wireless sensor nodes. It was shown that in confined metallic environments resembling the air duct system in buildings, wireless radio based systems fail as the number of bends in the ducts increase. However, it was shown that it is still possible to send limited information using the platform developed in BIB006 . In BIB010 it was shown that the channel response of the platform developed in BIB006 , did not match the theoretical results in previous works. The authors attempted to add correction factors to the previously developed theoretical models and find the best fit to the observed channel responses. In BIB011 , it was shown that this experimental platform tend to be nonlinear, which was in contrast to the previously derived and used models in the molecular communication literature. The authors demonstrated that the nonlinearity may be modelled as additive Gaussian noise in certain cases. One of the first works on engineering an experimental demonstration of molecular communication at microscales is BIB001 . With the prevalence of synthetic biology and applications such as biological computation, simple intercellular communication has been used for multicellular computation BIB004 . In BIB012 , artificial cells are used as relays (translates) to send a message to E. Coli cells. In this scheme, the intended message is first detected and decoded by the artificial cells, and then relayed to the E. Coli cells. A short survey on cell-to-cell communication in synthetic biology is presented in BIB007 . Most work in synthetic cell-to-cell communication consider sending a single message from a transmitter to a receiver. However, recently in BIB005 it was demonstrated that a message sequence encoded in DNA can be transmitted between cells by packaging the DNA massage inside a bacteriophage. We believe that through more collaborative work between communication theorist and biomedical engineers working on synthetic biology, more advanced systems could be developed in the future.