Modeling convection-diffusion-reaction systems for microfluidic molecular communications with surface-based receivers in Internet of Bio-Nano Things.

We consider a microfluidic molecular communication (MC) system, where the concentration-encoded molecular messages are transported via fluid flow-induced convection and diffusion, and detected by a surface-based MC receiver with ligand receptors placed at the bottom of the microfluidic channel. The overall system is a convection-diffusion-reaction system that can only be solved by numerical methods, e.g., finite element analysis (FEA). However, analytical models are key for the information and communication technology (ICT), as they enable an optimisation framework to develop advanced communication techniques, such as optimum detection methods and reliable transmission schemes. In this direction, we develop an analytical model to approximate the expected time course of bound receptor concentration, i.e., the received signal used to decode the transmitted messages. The model obviates the need for computationally expensive numerical methods by capturing the nonlinearities caused by laminar flow resulting in parabolic velocity profile, and finite number of ligand receptors leading to receiver saturation. The model also captures the effects of reactive surface depletion layer resulting from the mass transport limitations and moving reaction boundary originated from the passage of finite-duration molecular concentration pulse over the receiver surface. Based on the proposed model, we derive closed form analytical expressions that approximate the received pulse width, pulse delay and pulse amplitude, which can be used to optimize the system from an ICT perspective. We evaluate the accuracy of the proposed model by comparing model-based analytical results to the numerical results obtained by solving the exact system model with COMSOL Multiphysics

Introducing purely hydrodynamic networking mechanisms in microfluidic systems

Microfluidic is a multidisciplinary field with prac- tical applications to the design of systems, called Lab-on-a- Chip (LoC), where tiny volumes of fluids are circulated through channels with millimeter size and driven into structures where precise chemical/physical processes take place. One subcategory of microfluidic is droplet-based microfluidic, which disperse discrete volumes of fluids into a continuous stream of another immiscible fluid, which act as droplet carrier. Droplets can then be moved, merged, split, or processed in many other ways by suitably managing the hydrodynamic parameters of the LoC. A very interesting research challenge consists in developing basic microfluidic structures able to interconnect specialized LoCs by means of a flexible and modular microfluidic network. The aim of this paper is to exploit the properties of droplet- based microfluidics to realize purely hydrodynamic microfluidic elements that provide basic networking functionalities, such as addressing and switching. We define some simple mathematical models that capture the macroscopic behavior of droplets in microfluidic networks and use such models to design and analyze a simple microfluidic network system with bus topology

A comprehensive survey of recent advancements in molecular communication

With much advancement in the field of nanotechnology, bioengineering and synthetic biology over the past decade, microscales and nanoscales devices are becoming a reality. Yet the problem of engineering a reliable communication system between tiny devices is still an open problem. At the same time, despite the prevalence of radio communication, there are still areas where traditional electromagnetic waves find it difficult or expensive to reach. Points of interest in industry, cities, and medical applications often lie in embedded and entrenched areas, accessible only by ventricles at scales too small for conventional radio waves and microwaves, or they are located in such a way that directional high frequency systems are ineffective. Inspired by nature, one solution to these problems is molecular communication (MC), where chemical signals are used to transfer information. Although biologists have studied MC for decades, it has only been researched for roughly 10 year from a communication engineering lens. Significant number of papers have been published to date, but owing to the need for interdisciplinary work, much of the results are preliminary. In this paper, the recent advancements in the field of MC engineering are highlighted. First, the biological, chemical, and physical processes used by an MC system are discussed. This includes different components of the MC transmitter and receiver, as well as the propagation and transport mechanisms. Then, a comprehensive survey of some of the recent works on MC through a communication engineering lens is provided. The paper ends with a technology readiness analysis of MC and future research directions

Novel Network Paradigms: Microfluidic and M2M Communications

The present thesis focuses on two appealing paradigms that are expected to characterize the next generation of communication systems: microfluidic networking and Machine to Machine (M2M) Communications. Concerning the former topic, we show how it is possible to introduce switching and routing mechanism in microfluidic systems. We define some simple mathematical models that capture the macroscopic behavior of droplets in microfluidic networks. Then, we use them to implement a simulator that is able to reproduce the motion and predict the path of droplets in a generic microfluidic system. We validate the simulator and apply it to design a network with bus topology. Finally, we prove the feasibility of attaining molecular communication in this domain by describing a simple protocol that exploits droplets length/interdistance modulation to send information. The research activity on M2M, instead, is aimed at the investigation of two critical issues that are expected to affect Machine-Type Communication (MTC), i.e. energy efficiency and massive access. Regarding energy efficiency, we address the problem of delivering a fixed data payload over a Rayleigh fading wireless channel with the purpose of minimizing the average total energy cost, given by the sum of the transmit energy and an overhead circuit energy, to complete it. This scenario is well suited for uplink cellular MTC in future 5G Internet of Things (IoT) use cases, where the focus is more on device energy efficiency than on throughput. We describe the optimal transmission policies to be used under various coordinated access scenarios with different levels of channel state information and transmitter/receiver capabilities, and show the corresponding theoretical bounds. In the last part of the work, we study the asymptotic performance of uncoordinated access schemes with Multi Packet Reception (MPR) and Successive Interference Cancellation (SIC) techniques for contention resolution at the receiver. The corresponding results in terms of throughput in a massive access M2M scenario are finally evaluated and discussed

EXPLORING THE ROLE AND IMPACT OF MICROSCALE PHENOMENA ON ELECTRODE, MICRODEVICE, AND CELLULAR FUNCTION

Microfluidic technologies enable the development of portable devices to perform multiple high-resolution unit operations with small sample and reagent volumes, low fabrication cost, facile operation, and quick response times. Microfluidic platforms are expected to effectively interpret both wanted and unwanted phenomena; however, a comprehensive evaluation of the unwanted phenomena has not been appropriately investigated in the literature. This work explored an attenuative evaluation of unwanted phenomena, also called here as secondary phenomena, in a unique approach. Upon electric field utilization within microfluidic devices, electrode miniaturization improves device sensitivity. However, electrodes in contact with medium solution can yield byproducts that can change medium properties such as pH as well as bulk ion concentration and eventually target cell viability. While electrode byproducts are sometimes beneficial; but, this is not always the case. Two strategies were employed to protect cells from the electrode byproducts: (i) coating the electrodes with hafnium oxide (HfO2), and (ii) stabilization of the cell membrane using a low concentration of Triton X-100 surfactant. Our results showed that both strategies are a plausible way to selectively isolate cell and reduce the risk of contamination from electrode byproducts. The design of a medium solution is also critical to minimize unwanted cell-medium interaction. Surfactants are frequently added to cell-medium solutions to improve sensitivity and reproducibility without disrupting protein composition of cell membranes or cell viability. In non-electrokinetic systems, surfactants have been shown to reduce interfacial tensions and prevent analyte sticking. However, the impacts of surfactant interactions with cell membranes have not previously been explored in electrokinetic systems. This work indicated the dynamic surfactant interactions with cell membranes which altered the cell membrane integrity. It is important that the effects of the chemical interactions between cells to be fully explored and to be separately attributed to reported cellular responses to accurate catalog properties and engineer reliable microfluidic electrokinetic devices. Finally, a comprehensive level of understanding led us to utilize dielectrophoresis in its full capacity as a tool to monitor the state and progression of virus infection as well as anti-viral activities of regenerative compound. Glycine was utilized as potential antiviral compounds to reduce porcine parvovirus (PPV) infection in porcine kidney (PK-13) cells. Our results demonstrate that the glycine altered the virus-host interactions during virus assembly. Thus, elucidating the mechanisms of these novel antiviral compounds is crucial to their development as potential therapeutic drugs

Nano/Bio-Receiver Architectures and Detection Methods for Molecular Communications

Internet of Nano Things (IoNT) is an emerging technology, which aims at extending the connectivity into nanoscale and biological environments with collaborative networks of artificial nanomachines and biological entities integrated into the Internet. To enable the IoNT and its groundbreaking applications, such as real-time intrabody health monitoring, it is imperative to devise nanoscale communication techniques with low-complexity transceiver architectures. Bio-inspired molecular communications (MC), which uses molecules to transfer information, is the most promising technique to realise IoNT due to its inherent biocompatibility and reliability in physiologically-relevant environments. Despite the substantial body of work concerning MC, the implications of an interface between MC channel and practical MC transceiver architectures are largely neglected, leading to a major gap between theory and practice. As the first step to remove this discrepancy, in this thesis, I develop a realistic analytical ICT model for microfluidic MC with surface-based receivers as a convection-diffusion-reaction system. In the second part, I focus on biological MC receivers, which can be implemented in living cells using synthetic biology tools. In this direction, I theoretically develop low-complexity and reliable MC detection methods exploiting the various statistics of the stochastic ligand-receptor interactions at the membrane of biological MC receivers. The estimation and detection theoretical analysis of these detection methods demonstrate that even single type of receptors can provide sufficient statistics to overcome the receptor saturation problem, cope with the interference of non-cognate molecules, and simultaneously sense the concentration of multiple types of ligands. I also propose synthetic receptor designs for the transduction of decision statistics into a representation by concentration of intracellular molecules, and design chemical reaction networks performing decoding with intracellular reactions. Finally, I fabricate a micro/nanoscale MC receiver based on graphene field-effect transistor biosensors and perform its ICT characterisation in a custom-designed microfluidic MC system with the information encoded into the concentration of DNAs. This experimental platform is the first practical demonstration of micro/nanoscale MC, and can serve as a testbed for developing realistic MC methods

Molecular Communication: From Theory to Practice

Always-on, always-available digital communication has changed the world – allowing us to collaborate and share information in ways unimaginable not long ago. Yet many of the physical principles used in everyday digital communication break down as the size of the devices approach micro- or nano-scale dimensions. As a result, tiny devices, with dimensions of microns or less, need to do something different in order to communicate. Moreover, at meter scales there are areas where use of radio signals is not possible or desirable. An emerging biomimetic technique called molecular communication, which relies on chemical signaling is a promising solution to these problems. Although biologists have studied molecular communication extensively, it is very poorly understood from a telecommunication engineering perspective. Engineering molecular communication systems is important since micro- and nano-scale systems are the key to unlocking a realm of futuristic possibilities such as: self-repairing machines, micro- and nano-scale robotics, synthetic biological devices, nanomedicine, and artificial immune systems that detect and kill cancer cells and pathogens. All these transformative applications have one feature in common: they involve not just single devices working independently, but swarms of devices working in concert. Besides solving the communication problem at small scales, use of molecular communication in areas such as robotics, and infrastructure monitoring can unlock new applications in smart cities and disaster search and rescue. In this dissertation, after providing a comprehensive survey of the field, two areas of study with high potential impact are identified: on-chip molecular communication, and experimental platforms for molecular communication. First, on-chip molecular communication is investigated towards the goal of networking components within lab-on-chip devices and point-of-care diagnostic devices. This has numerous applications in medicine, environmental monitoring systems, and the food industry. Then in the second part of the dissertation, a tabletop demonstrator for molecular communication is designed and built that could be used for research and experimentation. In particular, no macroscale or microscale molecular communication platform capable of reliably transporting sequential data had existed in the past, and this platform is used to send the world's first text message ("O Canada") using chemical signals

Error control in bacterial quorum communications

Quorum sensing (QS) is used to describe the communication between bacterial cells, whereby a coordinated population response is controlled through the synthesis, accumulation and subsequent sensing of specific diffusible chemical signals called autoinducers, enabling a cluster of bacteria to regulate gene expression and behavior collectively and synchronously, and assess their own population. As a promising method of molecular communication (MC), bacterial populations can be programmed as bio-transceivers to establish information transmission using molecules. In this work, to investigate the key features for MC, a bacterial QS system is introduced, which contains two clusters of bacteria, specifically Vibrio fischeri, as the transmitter node and receiver node, and the diffusive channel. The transmitted information is represented by the concentration of autoinducers with on-off keying (OOK) modulation. In addition, to achieve better reliability and energy efficiency, different error control techniques, including forward error correction (FEC) and Automatic Repeat reQuest (ARQ) are taken into consideration. For FEC, this work presents a comparison of the performance of traditional Hamming codes, Minimum Energy Codes (MEC) and Luby Transform (LT) codes over the channel. In addition, it applied several ARQ protocols, namely Stop-N-Wait (SW-ARQ), Go-Back-N (GBN-ARQ), and Selective-Repeat (SR-ARQ) combined with error detection codes to achieve better reliability. Results show that both the FEC and ARQ techniques can enhance the channel reliability, and that ARQ can resolve the issue of out-of-sequence and duplicate packet delivery. Moreover, this work further addresses the question of optimal frame size for data communication in this channel capacity and energy constrained bacterial quorum communication system. A novel energy model which is constructed using the experimental validated synthetic logic gates has been proposed to help with the optimization process. The optimal fixed frame length is determined for a set of channel parameters by maximizing the throughput and energy efficiency matrix