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

Frequency-Domain Detection for Molecular Communication with Cross-Reactive Receptors

Molecular Communications (MC) is a bio-inspired communication paradigm that uses molecules as information carriers, requiring unconventional transceivers and modulation/detection techniques. Practical MC receivers (MC-Rxs) can be implemented using field-effect transistor biosensor (bioFET) architectures, where surface receptors reversibly react with ligands. The time-varying concentration of ligand-bound receptors is translated into electrical signals via field effect, which is used to decode the transmitted information. However, ligand-receptor interactions do not provide an ideal molecular selectivity, as similar ligand types, i.e., interferers, co-existing in the MC channel, can interact with the same type of receptors. Overcoming this molecular cross-talk in the time domain can be challenging, especially when Rx has no knowledge of the interferer statistics or operates near saturation. Therefore, we propose a frequency-domain detection (FDD) technique for bioFET-based MC-Rxs that exploits the difference in binding reaction rates of different ligand types reflected in the power spectrum of the ligand-receptor binding noise. We derive the bit error probability (BEP) of the FDD technique and demonstrate its effectiveness in decoding transmitted concentration signals under stochastic molecular interference compared to a widely used time-domain detection (TDD) technique. We then verified the analytical performance bounds of the FDD through a particle-based spatial stochastic simulator simulating reactions on the MC-Rx in microfluidic channels.Comment: Submitted to the IEEE for possible publication. arXiv admin note: text overlap with arXiv:2301.0104

Frequency-Domain Model of Microfluidic Molecular Communication Channels with Graphene BioFET-based Receivers

Molecular Communication (MC) is a bio-inspired communication paradigm utilizing molecules for information transfer. Research on this unconventional communication technique has recently started to transition from theoretical investigations to practical testbed implementations, primarily harnessing microfluidics and sensor technologies. Developing accurate models for input-output relationships on these platforms, which mirror real-world scenarios, is crucial for assessing modulation and detection techniques, devising optimized MC methods, and understanding the impact of physical parameters on performance. In this study, we consider a practical microfluidic MC system equipped with a graphene field effect transistor biosensor (bioFET)-based MC receiver as the model system, and develop an analytical end-to-end frequency-domain model. The model provides practical insights into the dispersion and distortion of received signals, thus potentially informing the design of new frequency-domain MC techniques, such as modulation and detection methods. The accuracy of the developed model is verified through particle-based spatial stochastic simulations of pulse transmission in microfluidic channels and ligand-receptor binding reactions on the receiver surface

Affinity-Division Multiplexing for Molecular Communications with Promiscuous Ligand Receptors

A key challenge in Molecular Communications (MC) is low data transmission rates, which can be addressed by channel multiplexing techniques. One way to achieve channel multiplexing in MC is to leverage the diversity of different molecule types with respect to their receptor binding characteristics, such as affinity and kinetic binding/unbinding rates. In this study, we propose a practical multiplexing scheme for MC, which is based on the diversity of ligand-receptor binding affinities. This method requires only a single type of promiscuous receptor on the receiver side, capable of interacting with multiple ligand types. We analytically derive the mean Bit Error Probability (BEP) over all multiplexed MC channels as a function of similarity among ligands in terms of their receptor affinities, the number of receptors, the number of multiplexed channels, and the ratio of concentrations encoding bit-1 and bit-0. We investigate the impact of each design parameter on the performance of multiplexed MC system

Fabrication and microfluidic analysis of graphene-based molecular communication receiver for Internet of Nano Things (IoNT).

Bio-inspired molecular communications (MC), where molecules are used to transfer information, is the most promising technique to realise the Internet of Nano Things (IoNT), thanks to its inherent biocompatibility, energy-efficiency, and reliability in physiologically-relevant environments. Despite a substantial body of theoretical work concerning MC, the lack of practical micro/nanoscale MC devices and MC testbeds has led researchers to make overly simplifying assumptions about the implications of the channel conditions and the physical architectures of the practical transceivers in developing theoretical models and devising communication methods for MC. On the other hand, MC imposes unique challenges resulting from the highly complex, nonlinear, time-varying channel properties that cannot be always tackled by conventional information and communication tools and technologies (ICT). As a result, the reliability of the existing MC methods, which are mostly adopted from electromagnetic communications and not validated with practical testbeds, is highly questionable. As the first step to remove this discrepancy, in this study, we report on the fabrication of a nanoscale MC receiver based on graphene field-effect transistor biosensors. We perform its ICT characterisation in a custom-designed microfluidic MC system with the information encoded into the concentration of single-stranded DNA molecules. This experimental platform is the first practical implementation of a micro/nanoscale MC system with nanoscale MC receivers, and can serve as a testbed for developing realistic MC methods and IoNT applications.Tis work was supported in part by the ERC (Project MINERVA, ERC-2013-CoG #616922) and by the AXA Research Fund (AXA Chair for Internet of Everything at Koc University)

Development and characterization of a potent free fatty acid receptor 1 (FFA1) fluorescent tracer

The free fatty acid receptor 1 (FFA1/GPR40) is a potential target for treatment of type 2 diabetes. Although several potent agonists have been described, there remains a strong need for suitable tracers to interrogate ligand binding to this receptor. We address this by exploring fluorophore-tethering to known potent FFA1 agonists. This led to the development of 4, a high affinity FFA1 tracer with favorable and polarity-dependent fluorescent properties. A close to ideal overlap between the emission spectrum of the NanoLuciferase receptor tag and the excitation spectrum of 4 enabled the establishment of a homogenous BRET-based binding assay suitable for both detailed kinetic studies and high throughput competition binding studies. Using 4 as a tracer demonstrated that the compound acts fully competitively with selected synthetic agonists but not with lauric acid and allowed for the characterization of binding affinities of a diverse selection of known FFA1 agonists, indicating that 4 will be a valuable tool for future studies at FFA1