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

Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design with Modulation, Coding, and Detection Techniques

Inspired by nature, molecular communications (MC), i.e., the use of molecules to encode, transmit, and receive information, stands as the most promising communication paradigm to realize the nanonetworks. Even though there has been extensive theoretical research toward nanoscale MC, there are no examples of implemented nanoscale MC networks. The main reason for this lies in the peculiarities of nanoscale physics, challenges in nanoscale fabrication, and highly stochastic nature of the biochemical domain of envisioned nanonetwork applications. This mandates developing novel device architectures and communication methods compatible with MC constraints. To that end, various transmitter and receiver designs for MC have been proposed in the literature together with numerable modulation, coding, and detection techniques. However, these works fall into domains of a very wide spectrum of disciplines, including, but not limited to, information and communication theory, quantum physics, materials science, nanofabrication, physiology, and synthetic biology. Therefore, we believe it is imperative for the progress of the field that an organized exposition of cumulative knowledge on the subject matter can be compiled. Thus, to fill this gap, in this comprehensive survey, we review the existing literature on transmitter and receiver architectures toward realizing MC among nanomaterial-based nanomachines and/or biological entities and provide a complete overview of modulation, coding, and detection techniques employed for MC. Moreover, we identify the most significant shortcomings and challenges in all these research areas and propose potential solutions to overcome some of them.This work was supported in part by the European Research Council (ERC) Projects MINERVA under Grant ERC-2013-CoG #616922 and MINERGRACE under Grant ERC-2017-PoC #780645

Integrated impedance spectroscopy biosensors

textAffinity-based biosensors, or in short biosensors, are extremely powerful and versatile analytical tools which are used for the detection of a wide variety of bio-molecules. In recent times, there has been a need for developing low-cost and portable affinity-based biosensor platforms. Such systems need to have a high density of detection sites (i.e biosensing elements) in order to simultaneously detect multiple analytes in a single sample. This has led to the creation of integrated biosensors, which make use of integrated circuits (ICs) for bio-molecular detection. In such systems, it has been demonstrated that by taking advantage of the capabilities of semiconductor and very large scale integrated (VLSI) circuit fabrication processes, it is possible to build compact miniaturized biosensors, which can be used in wide variety of applications such as in molecular diagnostics and for environmental monitoring. Among the various detection modalities for biosensors, Electrochemical Impedance Spectroscopy (EIS) permits real-time detection and has label-free detection capabilities. EIS is fully electronic in nature. Hence, it can be implemented using standard IC technologies. The versatility and ease of integration of EIS makes it a promising candidate for developing integrated biosensor platforms. In this thesis, we first examine the underlying principles of EIS method of biosensing. By analyzing an immunosensor assay as an example, we show that EIS based biosensing is a highly sensitive detection method, which can be used for the detection of a wide variety of analytes. Since EIS relies on small impedance changes in order to perform detection, it requires highly accurate models for the electrode-electrolyte systems. Hence, we also introduce a compact modeling technique for the distributed electrode-electrolyte systems with non-uniform electric fields, which is capable of modelling noise and other non-idealities in EIS. In the second part of this thesis, we describe the design and implementation of an integrated EIS biosensor array, built using a standard complementary metal-oxide-semiconductor (CMOS) process. The chip is capable of measuring admittance values as small as 10nS and has a wide dynamic range (90dB) over a wide range of frequencies (10Hz-50MHz). We also report the results obtained from the DNA and protein detection experiments performed using this chip.Electrical and Computer Engineerin

in vitro Characterisation of the Complement Cascade for Predicting Patient Outcome Post-operatively

The identification of surgical patients at higher risk of infection enables targeted allocation of critical care resources to improve patient mortality. The Complement cascade of the innate immune system is known to increase risk of infection if compromised and can be tested in vitro as a potential method for stratification of high-risk patients. Existing assays of Complement function are laboratory bound and require trained personnel to operate and interpret. This thesis describes the development of novel immunoassays for C3, C5a, TCC and TNFα, based on a multiplex biosensor platform with a duty cycle of 0.05) from the serum data of 22 volunteers. The model and cohort data provide an initial estimate of effect size for future clinical studies investigating the ability of these Complement activation phenotypes to identify high-risk surgical patients or identify the onset of infection

Particle-modified Surface Plasmon Resonance Biosensor

Surface plasmon resonance (SPR) biosensors have attracted great attention in scientific research in the past three decades. Extensive studies on the immobilisation of biorecognition elements have been conducted in pursuit of higher sensitivity, but trialled formats have focussed on a thin layer modification next to the plasmon film, which usually requires in situ derivatization. This thesis investigates an ‘off-chip’ immobilisation strategy for SPR biosensing using silica particles and considers the implications of a particle-modified evanescent field on the signal amplitude and kinetics, for an exemplar affinity binding between immobilised IgG and its anti-IgG complement. Submicron silica particles were synthesized as carriers for the bio-recognition elements. They were then immobilised to form a sub-monolayer on the gold film of an SPR biosensor using two methods: thiolsilane coupling and physical adsorption aided by mechanical pressure. The bio-sensitivity towards an antigen/antibody interaction was lower than an SPR biosensor with an alkanethiolate SAM due to the difference in ligand capacity and position in the evanescent field. The binding kinetics of antigen/antibody pair was found to follow the Langmuir model closely in a continuous flow configuration but was heavily limited by the mass transport from the bulk to the sensor surface in a stop-flow configuration. A packed channel configuration was designed with larger gel particles as ligand carriers, packed on top of a gold film to create a column-modified SPR biosensor. This sensor has comparable bio-sensitivity to the previous sub-monolayer particle-modified systems, but the binding and dissociation of the analyte was heavily dependent on mass transport and binding equilibria across the column. A bi-directional diffusion mechanism was proposed based on a two-compartment mass transport model and the expanded model fitted well with the experimental data. The column-modified sensor was also studied by SPR imaging and analyte band formation was observed and analysed. Using the lateral resolution, a multiplexing particle column configuration was explored, and its potential in distinguishing a multicomponent analyte.Agency for Science Technology and Research, Singapor