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Nanosensors for Futuristic Smart and Intelligent Healthcare Systems Edited by Suresh Kaushik Department of Chemistry Indian Agricultural Research Institute New Delhi, India Vijay Soni Department of Medicine Weill Cornell Medicine New York, NY, USA Efstathia Skotti Department of Food Science and Technology Ionian University Argostoli, Greece p, p, A SCIENCE PUBLISHERS BOOK A SCIENCE PUBLISHERS BOOK Cover illustration reproduced by permission of Royal Society of Chemistry. Permission given by Copyright Clearance Center. First edition published 2022 by CRC Press 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742 and by CRC Press 4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN © 2022 Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, LLC Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. 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For works that are not available on CCC please contact [email protected] Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging‑in‑Publication Data (applied for) ISBN: 978-0-367-55434-7 (hbk) ISBN: 978-0-367-55436-1 (pbk) ISBN: 978-1-003-09353-4 (ebk) DOI: 10.1201/9781003093534 Typeset in Times New Roman by Radiant Productions Preface Healthcare sector is probably the most benefited from the application of nanotechnology. The concept of nanotechnology was proposed in 1965 by Richard Feynman, a physicist and Nobel Laureate. The main idea behind nanotechnology was to exploit the advantages of miniaturization of materials and explore the future of creating compelling and tinier devices. The standard working range of nanotechnology is 1 to 100 nanometers. The matter changes its behavior as its size reduced to nanoscale due to quantum size effects. One of the early applications of nanotechnology is in the field of nanosensors. A nanosensor is not necessarily a device merely reduced in size to few nanometers, but a device that makes use of the unique properties of nanomaterials and nanoparticles to detect and measure new types of events in the nanoscale. A typical sensor has three main modules: a receptor a transducer and a detector with a digital output. Hence, nanosensors are sensing devices with at least one of their sensing dimensions up to 100 nm. The nanostructure materials used in production of nanosensors include nanoscale wires, carbon nanotubes, thin films, nanoparticles and polymer nanomaterials. In order to provide better-quality healthcare, it is very important that high standards of health care management are achieved by making timely decisions based on rapid diagnostics, smart data analysis and informatics analysis. Smart nanosensors are emerging as efficient and affordable analytical diagnostics tools for early-stage disease detection. Nanosensor can detect analytes or biomarkers in small quantity of samples such as blood, saliva, tears, sweat. A biological marker or biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention. Emerging nanomaterial science and flexible electronics have led to wearable biophysical nanosensors that are capable of monitoring human activities, body motions, and electrophysiological signals such as electrocephalogram and electrocardiogram. Wearable biochemical nanosensors are emerging for noninvasive detection of molecular-level indicators such as electrolytes and metabolites from biofluids. Nanosensors are widely used to detect antibodies, antigens or nucleic acids in crude samples such as saliva, sputum and blood based upon colorimetric, fluorescent or electrochemical detection approaches. Nanobiosensor offers many advantages such as being affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable to end user. Wearable devices such as activity trackers and smart watches can provide unique insights into our health and well-being. During the coronavirus disease 2019 (COVID-19) pandemic, the potential of wearable health devices has become iv Nanosensors for Futuristic Smart and Intelligent Healthcare Systems increasingly apparent. With the advances in point-of-care testing, chip-based and paper-based nanobiosensors have been developed for rapid diagnosis of infectious diseases, ensuring fast detection of analytes near to the patients facilitating a better disease diagnosis, monitoring and management. Hence, nanobiosensors can be a reliable and cost-effective way to detect specific pathogen in point-of-care settings. Wearable nanobiosensors have potential to provide continuous real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluids. Wearable sensors have received much attention since the arrival of smartphones and other mobile devices. Wearable monitoring platforms can lead insights into dynamic biochemical processes in biofluids by enabling continuous, real-time monitoring of biomarkers. Such real-time monitoring can provide information on wellness and health. As the disease can be diagnosed at an early stage, quick medical decision can be taken to start early treatment. Numerous potential point-of-care devices have been developed in recent years which are paving the way to next-generation point-of-care testing. Significant advances in wireless communication and networking technologies have paved the way to envisage and design innovative healthcare services. Various wireless technologies have been used to transmit data within a wearable body area network. Wearable sensor nodes are deployed inside a wearable body area network to monitor physiological signals. The Internet of NanoThing, the interconnection of nanoscale devices to the existing communication networks, has the potential to bring a revolutionizing advancement in the field of real-time monitoring of healthcare services. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. The overall theme of this book is to compile a comprehensive treatise on nanosensors for healthcare system. Specifically, we address the enthusiasm that nanosensors technology including wearable and wireless tools have provided to monitor health status in real-time and diagnosis of infectious disease particularly keeping the in view the current situation of pandemic COVID-19 disease worldwide, which might change the behavior of people in future. With this view, we have designed the book with two Sections-I and II, explaining the fundamentals and applied technologies in nanosensor based-medical devices used in healthcare systems. Under Section-I from Chapters 1 to 9, we have attempted to focus on the basic concept of nanosensor technologies applied in wearable and implantable medical devices used in disease diagnosis and monitoring health status, while sensing paradigms, wireless, array and microfluidics technologies applied in implantable and wearable devices for real-time monitoring health status are discussed under Section-II from Chapters 10 to 17. In Chapter 1, we provided the basics and recent advances of smart nanosensor technology in healthcare sector. Chapter 2 discusses about the development of nanosensor technology in biomarkers detection used for disease diagnosis, while Chapter 3 addresses infectious disease diagnosis including COVID-19 disease using innovative nanosensors. Chapters 4 to 9 are centered on recent advances in wearable and implantable devices providing a glimpse into the world of wearables. In Chapter 4, wearable devices for real-time disease monitoring are covered to Preface v provide insight into the point of care treatment (POCT), specially during pandemic coronavirus disease period. Nanocarbon-based sensor are discussed for wearable health monitoring parameters such as EEG, ECG, EMG in Chapter 5. Chapter 6 provides a basic background of electrochemical wearable sensors for applications in biomedical and healthcare system. Smart textile-based wearables nanosensors are addressed in Chapter 7, while emerging topic of electronic-skin (E-skin) is introduced in Chapter 8. Non-invasive and implantable wearable and dermal nanosystems applied for healthcare are covered in Chapter 9. Chapters 10 and 11 discuss the use of nanogenerator-based self-powered sensors in healthcare system and provide the recent development in this technology. Chapter 12 describes minimally invasive microneedle nanosensors focusing on COVID-19 disease. Wireless nanosensors used in healthcare system for monitoring health status in real-time are described in Chapter 13. Chapter 14 explores the potential role of nanosensors in Internet of Medical Things (IoMT). In Chapter 15, microfluidics chip technology for disease diagnosis is discussed using the dielectrophoresis technique. Chapter 16 provides the recent development in nanosensor array technology for multiplexed sensing in real- time monitoring of health status. The book will not be complete without a discussion on the use of artificial intelligence in healthcare systems (Chapter 17), as these are becoming fundamental to innovative approaches for smart and intelligence medical diagnosis and monitoring health status in real-time in futuristic healthcare sector. We believe that this book will be very useful and valuable to researchers, scientists, engineers, technocrats working in development of nanosensors for smart healthcare systems. Fast, portable, new, and easy-to-use devices that involves nanosensors can be modified according to the information presented in this book. The completion of this book could not have been possible without help, inspiration, and encouragement from many people including our families. Finally, we would like to express our sincere gratitude to the leading authors, who accepted our invitation to join us and dedicated their valuable time and efforts to guarantee the success of the book. Suresh Kaushik Vijay Soni Efstathia Skotti Contents Preface iii List of Abbreviations ix Section I: Sensing Paradigms of Wearables and Implantable Devices for Medical Diagnostics 1. Smart Nanosensors in Healthcare: Recent Developments 3 and Applications Sneh Lata Gupta and Srijani Basu 2. Nanosensor Technology in Biomarker Detection 19 Priyanka Mishra and Shashi Kant Tiwari 3. Innovative Nanobiosensors for Infectious Disease Diagnosis 41 Amitesh Anand and Deependra Kumar Ban 4. Wearable Devices for Real-time Disease Monitoring in Healthcare 54 Pramila Jakhar, Pandey Rajagopalan, Mayoorika Shukla and Vipul Singh 5. Nanocarbon-Based Sensor for Wearable Health Monitoring 80 Md. Milon Hossain, Abbas Ahmed and Maliha Marzana 6. Electrochemical Wearable Sensor for Biomedical and 99 Healthcare Applications Yugender Goud Kotagiri, Shekher Kummari, Roger Narayan, Vinay Sharma and Rupesh Kumar Mishra 7. Smart Textile-Based Interactive, Stretchable and Wearable 112 Sensors for Healthcare Abbas Ahmed, Bapan Adak and Samrat Mukhopadhyay 8. E-Skin for Futuristic Nanosensor Technology for the 133 Healthcare System Venkateswaran Vivekananthan, Gaurav Khandelwal, Nagamalleswara Rao Alluri and Sang‑Jae Kim viii Nanosensors for Futuristic Smart and Intelligent Healthcare Systems 9. Implantable and Non-Invasive Wearable and Dermal 158 Nanosensors for Healthcare Applications Joseph Sonia, Kannan Sapna, Ashaiba Asiamma, Kodiadka Ayshathil Bushra, Ananthapadmanabha Bhagwath Arun and Kariate Sudhakara Prasad Section II: Multiplexed Sensing and Wireless Tools for Monitoring Real-time Health Status 10. Monitoring Human Health in Real-Time using Nanogenerator-Based 181 Self-Powered Sensors Ammu Anna Mathew, Charanya Sukumaran, S. Vivekanandan and Arunkumar Chandrasekhar 11. Nanogenerator Based Self-Powered Sensors for Healthcare 197 Applications Gaurav Khandelwal, Pandey Rajagopalan, Nirmal Prashanth Maria Joseph Raj, Xiaozhi Wang and Sang‑Jae Kim 1 2. Minimally Invasive Microneedle Sensors: Developments in Wearable 216 Healthcare Devices Akshay Krishnakumar, Ganesh Kumar Mani, Raghavv Raghavender Suresh, Arockia Jayalatha Kulandaisamy, Kazuyoshi Tsuchiya and John Bosco Balaguru Rayappan 1 3. Smart Wireless Nanosensor Systems for Human Healthcare 265 Rajesh Ahirwar and Nabab Khan 1 4. Nanosensors and their Potential Role in Internet of Medical Things 293 Priya Rani 1 5. Microfluidic-Chip Technology for Disease Diagnostic Applications via 318 Dielectrophoresis Soumya K. Srivastava and Anthony T. Giduthuri 1 6. Nanosensor Arrays: Innovative Approaches for Medical Diagnosis 350 Naumih M. Noah and Peter M. Ndangili 1 7. Smart Nanosensors for Healthcare Monitoring and Disease Detection 387 using AIoT Framework Kunwar Shahbaaz Singh Sahi and Suresh Kaushik Index 401 List of Abbreviations HRS : Hyper-Rayleigh scattering QDNB : Quantum dot-nanobeads HIV : Human Immunodeficiency Virus BBB : blood-brain barrier FRET : Fluorescence resonance energy transfer CNT : Carbon nanotube QD : Quantum dot FITC : Fluorescein isothiocyanate CNTs : Carbon nanotubes SWCNTs : single-wall carbon nanotubes MWCN : multi-wall carbon nanotubes GO : graphene oxide MNs : Magnetic nanoparticles DMR : diagnostic magnetic resonance CLIO : Cross-linked Iron Oxide Nanoparticles, SQUID : Superconducting quantum interference devices ELISA : Enzyme-linked immunosorbent assay EIA : enzyme immunoassay MRI : Magnetic resonance imaging PET : Positron emission tomography CT : Computed tomography AgNPs : Silver nanoparticles AuNPs : Gold nanoparticles SPR : surface plasmon resonance POCT : Point-of-care technology FDA : Food and Drug Administration t-TENG : textile tri-boelectric nanogenerators PPG : Photoplethysmogram e-skin : electronic skin R2R : roll-to-roll NPs : nanoparticles CNT : carbon nanotubes NW : Nanowires PEDOT : polyethylenedioxythiophene PPy : polypyrrole PDES : polymerizable deep eutectic solvent