Everand Logo

Welcome to Everand!

  • Discover millions of ebooks, audiobooks, and so much more with a free trial

    Only $11.99/month after trial. Cancel anytime.

    Micro- and Nanotechnology in Vaccine Development
    Micro- and Nanotechnology in Vaccine Development
    Micro- and Nanotechnology in Vaccine Development
    Ebook1,029 pages10 hours

    Micro- and Nanotechnology in Vaccine Development

    ()

    Read preview

    About this ebook

    This book provides a comprehensive overview of how use of micro- and nanotechnology (MNT) has allowed major new advance in vaccine development research, and the challenges that immunologists face in making further progress.

    MNT allows the creation of particles that exploit the inherent ability of the human immune system to recognize small particles such as viruses and toxins. In combination with minimal protective epitope design, this permits the creation of immunogenic particles that stimulate a response against the targeted pathogen. The finely tuned response of the human immune system to small particles makes it unsurprising that many of the lead adjuvants and vaccine delivery systems currently under investigation are based on nanoparticles.

    • Provides a comprehensive and unparalleled overview of the role of micro- and nanotechnology in vaccine development
    • Allows researchers to quickly familiarize themselves with the broad spectrum of vaccines and how micro- and nanotechnologies are applied to their development
    • Includes a combination of overview chapters setting out general principles, and focused content dealing with specific vaccines, making it useful to readers from a variety of disciplines
    LanguageEnglish
    PublisherElsevier Science
    Release dateSep 20, 2016
    ISBN9780323400299
    Micro- and Nanotechnology in Vaccine Development

    Related to Micro- and Nanotechnology in Vaccine Development

    Titles in the series (97)

    View More
    View More

    Related ebooks

    Chemical Engineering For You

    View More
    View More

    Related podcast episodes

    Related articles

    • Article

      Anatomy Of A Pandemic

      Jul 24, 2020

      Anatomy Of A Pandemic
      19 min read

    • Article

      Researchers Rush To Test Coronavirus Vaccine In People Without Knowing How Well It Works In Animals

      Mar 11, 2020

      Researchers aren’t waiting to see how well an experimental #Covid19 #coronavirus vaccine prevents infection in animals before trying it in people, breaking from the usual protocol.

      6 min read

    • Article

      ‘Physicians Need To Be Aware’

      Mar 16, 2021

      There’s an entire medical textbook, Vaccines and Autoimmunity (Wiley-Blackwell, 2015), in which dozens of researchers and doctors survey the literature linking vaccines to autoimmune diseases from alopecia to ulcerative colitis. It is mostly inconclu

      1 min read

    • Article

      Vatican OKs Receiving COVID-19 Vaccines, Even If Research Involved Fetal Tissue

      Dec 21, 2020

      The Vatican said it's permitted to get COVID-19 vaccines due to the "grave danger" of the pandemic, even if scientists used "cell lines from aborted fetuses in their research and production process."

      1 min read

    • Article

      VACCINES & VARIANTS

      Jul 16, 2021

      VACCINES & VARIANTS
      6 min read

    • Article

      Covid Vaccines Compared: What Are The Differences Between Pfizer, Moderna, Oxford-AstraZeneca And Novavax? - OLD

      Jan 29, 2021

      After almost a year in which the entire world has been paralysed by coronavirus, a way out is finally in sight through the Covid-19 vaccines. The past few months have brought positive news of candidates from Pfizer, Moderna, Oxford University with As

      9 min read

    • Article

      Covid Vaccines Compared: What Are The Differences Between Pfizer, Moderna, Oxford-AstraZeneca And Novavax?

      Apr 13, 2021

      After almost a year in which the entire world has been paralysed by coronavirus, a way out is finally in sight through the Covid-19 vaccines. The past few months have brought positive news of candidates from Pfizer, Moderna, Oxford University with As

      10 min read

    • Article

      Covid Vaccines Compared: What Are The Differences Between Pfizer, Moderna, Oxford-AstraZeneca And Novavax? OLD

      Feb 16, 2021

      After almost a year in which the entire world has been paralysed by coronavirus, a way out is finally in sight through the Covid-19 vaccines. The past few months have brought positive news of candidates from Pfizer, Moderna, Oxford University with As

      10 min read

    • Article

      Covid Vaccines Compared: What Are The Differences Between Pfizer, Moderna, Oxford-AstraZeneca And Novavax? - OLD

      Mar 2, 2021

      After almost a year in which the entire world has been paralysed by coronavirus, a way out is finally in sight through the Covid-19 vaccines. The past few months have brought positive news of candidates from Pfizer, Moderna, Oxford University with As

      10 min read

    • Article

      How Are Covid Vaccines Produced And Why Have There Been Delays?

      Mar 19, 2021

      When the first Covid-19 vaccines were approved in the UK and elsewhere three months ago, many thought the end of the pandemic was almost within reach. Few, however, had anticipated the vast logistical problems involved in mass-producing and deliverin

      3 min read

    • Article

      A Vaccine For Cancer

      Jan 4, 2022

      A Vaccine For Cancer
      7 min read

    • Article

      When Will We Get A Vaccine?

      Sep 11, 2020

      When Will We Get A Vaccine?
      18 min read

    Related categories

    Reviews for Micro- and Nanotechnology in Vaccine Development

    0 ratings

    0 ratings0 reviews

    What did you think?

    Tap to rate

    Review must be at least 10 words

      Book preview

      Micro- and Nanotechnology in Vaccine Development - Mariusz Skwarczynski

      Micro- and Nanotechnology in Vaccine Development

      Edited by

      Mariusz Skwarczynski

      School of Chemistry and Molecular Biosciences

      University of Queensland, St Lucia, QLD, Australia

      Istvan Toth

      School of Chemistry and Molecular Biosciences

      University of Queensland, St Lucia, QLD, Australia

      School of Pharmacy, University of Queensland

      Woolloongabba, QLD, Australia

      Institute for Molecular Biosciences, University of Queensland

      St Lucia, QLD, Australia

      Table of Contents

      Cover

      Title page

      Copyright

      List of Contributors

      Introduction

      Chapter One: The Growing Influence of Nanotechnology in Our Lives

      Abstract

      1.1. Nanomaterials and Fabrication Techniques

      1.2. Nanomaterials in Modern Life

      1.3. Conclusions

      Chapter Two: Nanotechnology in Medical Research

      Abstract

      2.1. Introduction

      2.2. Diagnostic Nanoparticles

      2.3. Therapeutic Nanoparticles

      2.4. Multimodal Nanoparticles

      2.5. In Development

      Chapter Three: Introduction to Vaccines and Vaccination

      Abstract

      3.1. Introduction to Vaccines and Vaccination

      3.2. Challenges

      3.3. Conclusions

      Chapter Four: Overview of the Immune System

      Abstract

      4.1. A Short History of Immunology

      4.2. Immune Responses to Infection

      4.3. Innate Immunity

      4.4. Induced Innate Immune System

      4.5. The Adaptive Immune System

      4.6. Cells of the Adaptive Immune System

      4.7. Immunoglobulin Classes and Function

      4.8. Blurring the Lines Between Innate and Adaptive Immunity

      4.9. Concluding Remarks

      Chapter Five: The Role of Antigen Presentation and Innate Immunity During Immune Induction by Particulate Antigens

      Abstract

      5.1. Introduction to Vaccine Adjuvants

      5.2. The Innate Immune System as a Regulator of Adaptive Immunity

      5.3. Nanoparticle Vaccine Delivery Systems

      5.4. Targeting APCs at the Site of Vaccination and in the Draining Lymph Node

      5.5. Concluding Remarks

      Chapter Six: Inflammatory/Noninflammatory Adjuvants and Nanotechnology—The Secret to Vaccine Design

      Abstract

      6.1. Current Challenges Facing Vaccine Design

      6.2. Inflammation: Angel or Devil?

      6.3. Adjuvant Selection for Vaccine Design

      6.4. Mechanisms of Conventional Adjuvants

      6.5. Noninflammatory Adjuvants: Introducing Nanoparticles as Vaccine Adjuvants

      Summary

      Chapter Seven: Vaccine Adjuvant Nanotechnologies

      Abstract

      7.1. Introduction

      7.2. Emulsion Adjuvants

      7.3. Microparticulate Polysaccharide Adjuvants

      7.4. Immune Targeting Strategies

      7.5. Innate Immune Receptor Ligands

      7.6. Template-Based Nanoparticle Manufacturing Methods

      7.7. Conclusions

      Chapter Eight: Nanoparticle-Based Peptide Vaccines

      Abstract

      8.1. Introduction

      8.2. Vaccine Components

      8.3. Utility of Synthetic Peptides for Subunit Vaccines

      8.4. Upsizing Peptide Antigens

      8.5. Lipopeptide-Based Nanovaccines

      8.6. Self-Assembling Peptides

      8.7. Concluding Remarks

      Acknowledgments

      Chapter Nine: Microparticles and Nanoparticles for Cancer-Targeting Vaccines

      Abstract

      9.1. Introduction

      9.2. Conclusions

      Chapter Ten: Polymer-Based Nanoparticles as Modern Vaccine Delivery Systems

      Abstract

      10.1. Introduction

      10.2. Immune Defense Mechanisms: From Innate to Adaptive Immunity

      10.3. Design of Polymeric Nanovaccines

      10.4. Polymers Used for Nanovaccine Design

      10.5. Routes of Administrations

      10.6. Polymer-Based Nanoparticles in Clinical Trials

      10.7. Conclusions and Future Perspectives

      Acknowledgments

      Chapter Eleven: Virus-Like Particles

      Abstract

      11.1. Introduction

      11.2. Conclusions

      Chapter Twelve: Liposomes as a Vaccine Delivery System

      Abstract

      12.1. Vaccines and Vaccinations

      12.2. Liposomes: A Brief Introduction

      12.3. Influence of Liposome Size and Surface Charge on Vaccine Responses

      12.4. Types of Liposomes

      12.5. Methods of Liposomal Manufacturing

      12.6. Size Manipulation

      12.7. Factors to Consider for Scaling Up of Vaccine Production

      12.8. Conclusions

      Chapter Thirteen: Nanomaterials Based on Lipids for Vaccine Development

      Abstract

      13.1. The Importance of Particles As Adjuvants

      13.2. Lipid-Covered Particles and Bilayer Fragments As Adjuvants

      13.3. Lipidic Immunostimulants and Solid Lipid Nanoparticles

      13.4. Conclusions

      Acknowledgments

      Chapter Fourteen: Microparticles for Vaccine Delivery

      Abstract

      14.1. Introduction

      14.2. Conclusions

      Chapter Fifteen: Nasal Vaccine Delivery

      Abstract

      15.1. Introduction

      15.2. The Nasal Route

      15.3. Immune Response to Mucosal Infection

      15.4. Nasal Vaccine Delivery Systems

      15.5. Different Dosage Forms of Vaccine Through the Nasal Route

      Summary

      Chapter Sixteen: Toward Mucosal DNA Delivery: Structural Modularity in Vaccine Platform Design

      Abstract

      16.1. Introduction

      16.2. Discovery and Critical Landmarks in HEV Biology

      16.3. HEV Biology and the Capsid Protein

      16.4. Life Cycle of HEV Makes it Amenable to Being Used as an Orally Delivered Drug

      16.5. Virus-like Particles as Drug Delivery Systems/Vaccine Epitope Carriers

      16.6. HEV VLPs are Well Suited as Nanocarriers for Oral Delivery

      Acknowledgments

      Chapter Seventeen: Nano- and Microtechnology in Skin Delivery of Vaccines

      Abstract

      17.1. Introduction

      17.2. Immunization via Skin

      17.3. Nano/Microvaccination Techniques for Skin Delivery

      17.4. Concluding Remarks

      Chapter Eighteen: Nanopatches for Vaccine Delivery

      Abstract

      18.1. The Context of the Mechanical Vaccination Devices

      18.2. Designing a Device to Reach Precise Locations in Skin

      18.3. Immune Responses to and Hypothesized Mechanisms of the Nanopatch

      18.4. Thermostability of Vaccine Coating

      18.5. Clinical/Medical Device Technology Implications

      18.6. Conclusions

      Chapter Nineteen: Rationale for Pulmonary Vaccine Delivery: Formulation and Device Considerations

      Abstract

      19.1. Introduction

      19.2. Anatomy of the Human Lung

      19.3. Pulmonary Mucosal Vaccination

      19.4. Rationale for Pulmonary Delivery of Vaccines

      19.5. Challenges in Delivery of Vaccines via Inhalation

      19.6. Carriers for Lung Vaccine Delivery

      19.7. Dry Powder Vaccines

      19.8. Conclusions

      Chapter Twenty: Nanotoxicology and Nanovaccines

      Abstract

      20.1. Introduction

      20.2. General Toxicological Pathways for Nanoparticles

      20.3. Acute and Chronic Toxicity

      20.4. Toxicology of Nanovaccines

      20.5. Concluding Remarks

      Chapter Twenty One: Regulatory Development of Nanotechnology-Based Vaccines

      Abstract

      21.1. Introduction

      21.2. Current State of Nanomedicine Regulatory Framework

      21.3. Major Aspects for Nanovaccine regulation

      21.4. Nanovaccine Major Features and Related Concerns

      21.5. Current Challenges for the Translation of Nanovaccines to Clinic Use

      21.6. Conclusions and Future Perspectives

      Acknowledgments

      Chapter Twenty Two: Commercial Aspects of Vaccine Development

      Abstract

      22.1. Introduction

      22.2. Challenges in Commercialization of Micro- and Nanotechnology Therapeutics

      22.3. Challenges in Commercialization of Vaccines

      22.4. Conclusions

      Subject Index

      Copyright

      William Andrew is an imprint of Elsevier

      The Boulevard, Langford Lane, Kidlington, Oxford, OX5 1GB, United Kingdom

      50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States

      Copyright © 2017 Elsevier Inc. All rights reserved.

      No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

      This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

      Notices

      Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

      Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

      To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

      Library of Congress Cataloging-in-Publication Data

      A catalog record for this book is available from the Library of Congress

      British Library Cataloguing-in-Publication Data

      A catalogue record for this book is available from the British Library

      ISBN: 978-0-323-39981-4

      For information on all William Andrew publications visit our website at https://www.elsevier.com/

      Publisher: Matthew Deans

      Acquisition Editor: Simon Holt

      Editorial Project Manager: Sabrina Webber

      Production Project Manager: Julie-Ann Stansfield

      Designer: Greg Harris

      Typeset by Thomson Digital

      List of Contributors

      Z. Al-Mansour,     School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, QLD, Australia

      M. Arumugam,     Manufacturing Technology, Shantha biotechnics Pvt Limited (A Sanofi Company), Hyderabad, India

      M.A. Baikoghli,     Department of Molecular and Cellular Biology, University of California, Davis, CA, United States

      T. Barclay,     Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia

      F.M. Buonaguro,     Molecular Biology and Viral Oncology, Department of Experimental Oncology, Istituto Nazionale Tumori Fond Pascale, Naples, Italy

      L. Buonaguro,     Molecular Biology and Viral Oncology, Department of Experimental Oncology, Istituto Nazionale Tumori Fond Pascale, Naples, Italy

      A.M. Carmona-Ribeiro,     Biocolloids Laboratory, Institute of Chemistry, University of São Paulo, São Paulo, Brazil

      S.R. Chakrabarti,     Manufacturing Technology, Shantha biotechnics Pvt Limited (A Sanofi Company), Hyderabad, India

      R.H. Cheng,     Department of Molecular and Cellular Biology, University of California, Davis, CA, United States

      M.A. Cooper,     Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD, Australia

      M.L. Corvo,     Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

      M.L. Crichton

      Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, University of Queensland

      ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Queensland, Brisbane, QLD, Australia

      N. Dang,     Dermatology Research Centre, University of Queensland, Brisbane, QLD, Australia

      T.P. Davis

      ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University

      Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia

      Department of Chemistry, University of Warwick, Coventry, United Kingdom

      M.J. de Veer,     Biotechnology Research Laboratories, Department of Physiology, Monash University, Clayton, VIC, Australia

      A.C.I. Depelsenaire,     Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, Australia

      S. Dubey,     Department of Pharmaceutical Sciences, Drug Delivery Research Laboratory, Dr. H. S. Gour Vishwavidyalaya, Sagar, India

      H. Florindo,     Faculty of Pharmacy, Drug Research Institute (iMed.ULisboa), Universidade de Lisboa, Lisbon, Portugal

      H.F. Florindo,     Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

      Y. Fujita,     Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan

      R. Gaspar,     Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

      S.M. Geary,     Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, United States

      K.A. Ghaffar,     School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia

      J. Halliday,     UniQuest Pty Ltd, University of Queensland, Brisbane, QLD, Australia

      P. Holla,     Department of Molecular and Cellular Biology, University of California, Davis, CA, United States

      K.S. Jaganathan,     Manufacturing Technology, Shantha biotechnics Pvt Limited (A Sanofi Company), Hyderabad, India

      M. Kavallaris

      Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Australia

      ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, UNSW Australia

      Australian Centre for NanoMedicine, UNSW Australia, Sydney, NSW, Australia

      S. Kellie

      School of Chemistry and Molecular Biosciences, University of Queensland

      Australian Infectious Diseases Research Centre, University of Queensland

      Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD, Australia

      M.A.F. Kendall

      Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, University of Queensland

      ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Queensland, Brisbane

      Faculty of Medicine and Biomedical Sciences, Royal Brisbane and Women’s Hospital, University of Queensland, Herston, QLD, Australia

      L. Lambricht,     Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium

      T.Y. Liu,     Dermatology Research Centre, University of Queensland, Brisbane, QLD, Australia

      J. Lopes,     Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

      F.M. Mansfeld

      Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Australia

      ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, UNSW Australia

      Australian Centre for NanoMedicine, UNSW Australia, Sydney, NSW, Australia

      ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University

      Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia

      N. Marasini,     School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia

      M.B. Martins,     Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

      R.F. Minchin,     School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia

      N. Mody,     Department of Pharmaceutical Sciences, Drug Delivery Research Laboratory, Dr. H. S. Gour Vishwavidyalaya, Sagar, India

      A.S. Morris,     Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, United States

      G.M. Mortimer,     School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia

      D.A. Muller

      Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, University of Queensland

      Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia

      M.R. Neeland,     Biotechnology Research Laboratories, Department of Physiology, Monash University, Clayton, VIC, Australia

      C. Peres,     Faculty of Pharmacy, Drug Research Institute (iMed.ULisboa), Universidade de Lisboa, Lisbon, Portugal

      K. Petkar,     Department of Pharmaceutics, School of Pharmacy, University College London, London, United Kingdom

      N. Petrovsky

      Department of Endocrinology and Diabetes, Flinders University

      Vaxine Pty Ltd, Adelaide, SA, Australia

      M. Plebanski,     Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia

      V. Préat,     Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium

      T.W. Prow,     Dermatology Research Centre, University of Queensland, Brisbane, QLD, Australia

      M. Ramvikas,     Manufacturing Technology, Shantha biotechnics Pvt Limited (A Sanofi Company), Hyderabad, India

      A. Ranzoni,     Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD, Australia

      I. Saleem,     School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom

      A.K. Salem,     Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, United States

      J.-P.Y. Scheerlinck,     Centre for Animal Biotechnology, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC, Australia

      R. Sharma,     Department of Pharmaceutical Sciences, Drug Delivery Research Laboratory, Dr. H. S. Gour Vishwavidyalaya, Sagar, India

      L.C. Silva,     Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

      M. Skwarczynski,     School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia

      S. Somavarapu,     Department of Pharmaceutics, School of Pharmacy, University College London, London, United Kingdom

      P. Soonsawad

      Department of Molecular and Cellular Biology, University of California, Davis, CA, United States

      Department of Anatomy, Faculty of Dentistry, Mahidol University, Bangkok, Thailand

      M. Tagliamonte,     Molecular Biology and Viral Oncology, Department of Experimental Oncology, Istituto Nazionale Tumori Fond Pascale, Naples, Italy

      H. Taguchi,     Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan

      M.L. Tornesello,     Molecular Biology and Viral Oncology, Department of Experimental Oncology, Istituto Nazionale Tumori Fond Pascale, Naples, Italy

      I. Toth

      School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia

      School of Pharmacy, University of Queensland, Woolloongabba

      Institute for Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia

      G. Vandermeulen,     Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Brussels, Belgium

      S.P. Vyas,     Department of Pharmaceutical Sciences, Drug Delivery Research Laboratory, Dr. H. S. Gour Vishwavidyalaya, Sagar, India

      K.L. Wilson,     Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia

      A. Wongrakpanich,     Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand

      S.D. Xiang,     Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia

      P.R. Young

      Australian Infectious Diseases Research Centre, University of Queensland

      School of Chemical and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia

      Introduction

      We are constantly surrounded by nanoscopic and microscopic enemies that are trying to invade our bodies and feed on us. Unsurprisingly, our bodies have developed a sophisticated defense (immune) system to survive in such a hostile environment. However, the immune system does not perform perfectly in all cases; the protection is often impaired or does not arrive quickly enough. On the bright side, our survival is made possible by a defense system that is clever and can learn rapidly. This ability for learning has allowed us to develop vaccines to teach the immune system about dangerous pathogens by mimicking infection.

      Classical vaccination is based on presenting the immune system with a weakened or killed version of the pathogen that is dangerous enough to provoke a response, but does not cause serious infections. Unfortunately, vaccines based on whole microorganisms are becoming less popular because of the potential risk of side effects, instability of the vaccine material, and difficulties with mass production. Furthermore, traditional vaccines are often less effective for pathogens that have high interstrain variability or complex life cycles.

      Subunit vaccines based on small pathogen-derived components are becoming the most popular design for modern vaccines. However, the small subunit components usually lack the native danger signal that is critical for stimulating an immune response. Thus, an equivalent signal must be included to produce an effective subunit vaccine. The particle size component of vaccine formulation has been recognized as a crucial factor that affects vaccine performance. Many recent vaccine development approaches aim to mimic the size of the native pathogen in their preparation. Truthfully, the vast majority of vaccines exploit size-related immune responses even though they were not specifically designed to form particles. Furthermore, most vaccine adjuvants (immunostimulants) are particles, emulsions, and other nano- or microscopic agents.

      This book aims to provide an overview of recent trends in vaccine design and delivery with a special focus on the application of micro- and nanotechnology. Beginning by introducing modern nanotechnology, this book takes its readers through a general overview of immunology and vaccination to present more detailed sections about antigen and adjuvant design, common antigen carriers and delivery pathways, and the toxicological considerations of using particles in vaccination, before discussing regulatory and commercial perspectives on vaccine development. The core of this book describes nano- and microsized vaccine delivery systems (eg, polymer nanoparticles, liposomes, virus-like particles, emulsions, nanopatches, etc.) and delivery pathways (eg, dermal, nasal, and pulmonary). The twenty-two chapters (especially the first six chapters) of this book are designed to provide enough background information for researchers and students entering the field while simultaneously presenting detailed insights into the field of vaccination to satisfy the curiosity of researchers.

      We hope that you find this book pleasant and rewarding to read.

      Mariusz Skwarczynski

      Istvan Toth

           Editors

      Chapter One

      The Growing Influence of Nanotechnology in Our Lives

      A. Ranzoni

      M.A. Cooper    Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD, Australia

      Abstract

      The semantic umbrella term nanotechnology covers every branch of science pursuing controlled manipulation of matter at the nanoscale, at which point a discrete set of atoms constitute a functional object. At these scales, proximal surface effects, such as, quantum coherence completely redefine the physical properties of nanostructures. Insulating polymeric materials, if properly engineered, are transformed into electrical conductors resulting in the flexible light-emitting materials such as organic LEDs or OLEDs now found in modern consumer electronics. Such novel material classes have been accompanied by major technological advances in high-throughput manufacture, measurement, and characterization. We now are able to engineer complex systems based on nanostructured materials that interact at the molecular scale. The ability to interrogate single molecules with techniques, such as, scanning tunneling microscopy (STM) and atomic force microscopy (AFM), has opened a whole new chapter in life sciences, where biomolecules could be manipulated and analyzed directly, paving the way for nanobiotechnology and personalized nanomedicine. This chapter details the major classes of nanomaterials and highlights their translation into modern technologies and products that now affect our daily life.

      Keywords

      nanotechnology

      nanomaterials

      nanoparticles

      nanowires

      nanofilms

      nanostructures

      Contents

      1.1 Nanomaterials and Fabrication Techniques

      1.1.1 Nanoparticles

      1.1.2 Nanowires

      1.1.3 Nanofilms

      1.2 Nanomaterials in Modern Life

      1.2.1 Zero-dimensional nanostructures

      1.2.2 One-dimensional nanostructures

      1.2.3 Two-dimensional nanostructures

      1.3 Conclusions

      References

      Nanotechnology has its roots in precision engineering. Manipulation of individual atoms was first postulated by Richard Feynman in 1959 in his famous lecture There is plenty of room at the bottom.¹ Decades before nanotechnologies were even conceived, his lecture highlighted the importance of miniaturization: objects composed of just a few atoms are small enough for quantum mechanics to influence their physical properties. The temporal evolution of the state of any object, macroscopic or nanoscopic, is described by a complex wave function, dependent on how the Hamiltonian satisfies the Schrödinger equation given a set of external stimuli and boundary conditions. Boundary conditions can differ between bulk volume and a surface, and certain physical states are therefore unique to surfaces (eg, transition from bulk Bloch waves to Shockley or Tamm states in the outermost atomic layers due to symmetry breaking at the surface). In addition, since nanoscale objects accommodate the vast majority of their atoms at the surface, they are characterized by a wide catalytic interface for interaction with other systems. The unique surface states and high surface-to-volume ratio of nanomaterials render them remarkably different from their macroscopic counterparts. For macroscopic objects, phase information is lost when coupling with the surrounding environment induces decoherence and subsequent collapse of the wave function onto the classical limit. However, the wave function of nanoscale objects can superimpose and interfere, thus conferring unique physical properties to these novel classes of materials. Nanomaterials can be classified based on their dimensionality in the nanoscale: nanoparticles are objects where all spatial dimensions are nanometric, nanowires are objects elongating into the mesoscale in one spatial direction but with nanometric cross-section and thin surfaces, such as coatings or films, are surfaces constituted by a few atomic layers in thickness (Fig. 1.1).

      Figure 1.1   A summary of representative classes of nanomaterials classified by their dimensionality in the nanoscale and the nanofabrication technologies.

      Macroscopic materials with atomic arrangement varying at the nanoscale throughout the bulk, such as zeolites and heterogeneous assembly of nanometer-sized crystallites, are referred to as nanostructured materials.²,³ Due to their diversity in terms of nanofabrication and applications, this class of nanomaterials won’t be discussed in this chapter. Polymeric nanomaterials are becoming progressively integrated into life sciences thanks to their biomimetic properties (eg, polypeptide lipid-like vesicles⁴), their ability to deliver drugs⁵ or biosensing.⁶ This important class of nanomaterials is addressed in detail in subsequent chapters.

      1.1. Nanomaterials and Fabrication Techniques

      The following sections describe the most distinctive features of nanoparticles, nanowires, and thin film as well as provide a general overview of the technologies that enable large-scale manufacturing of these nanomaterials.

      1.1.1. Nanoparticles

      Nanoparticles are ultrafine aggregates of matter ranging from few to hundreds of nanometers. They can be amorphous or crystalline with conductive or insulating properties depending on their composition (Fig. 1.1). Typical materials include metals (eg, gold, silver, platinum) or metal oxides (eg, titanium oxide, iron oxide), semiconductors (eg, quantum dots), or polymers (eg, latex). The atomic arrangement is defined by minimization of their surface energy, sometimes resulting in different crystal structures compared with bulk arrangement. With up to 90% of the total atoms constituting the surface, almost the entire nanoparticle can participate in physical or chemical reactions, which accounts for their fast reaction kinetics.⁷

      Nanoparticles can be manufactured with a wide variety of technologies. Although top-down approaches based on mechanical grinding have been demonstrated, bottom-up technologies are probably the most widely used.⁸ In such approaches, educts are dispersed in either liquid of gaseous phases (eg, by introducing heat to the system by laser pyrolysis or by exposing to plasmas⁹,¹⁰) prior to a phase transition to a condensed solid phase. Due to the high energy of the system, molecules are highly reactive and tend to aggregate, or nucleate, into islands. This spontaneous process is a first-order polymorphic phase transition, and it is therefore critical to carefully tune the conditions of the nucleation process to control the properties (eg, size distribution) of the formed islands.¹¹ Rapid nucleation results in simultaneous formation of multiple islands, depleting the solution and, consequently, lowering the supersaturation of the discrete molecular phase. The decrease in Gibbs energy associated with reduced supersaturation balances the cost of introducing a new interface, the surface of the islands, and eventually results in arresting of the nucleation process. Since the balance between two opposing thermodynamic potentials regulates the nucleation process, only islands larger than a minimum critical size can continue their growth process, and smaller islands are unstable and tend to dissolve.¹⁰ The nucleation process is rather homogeneous provided the system is in a state of sufficient supersaturation and enables synthesis of nanoparticles with well-controlled demographics.

      1.1.2. Nanowires

      Nanowires are semiconducting, insulating, or metallic nanostructures characterized by two quantum-confined spatial dimensions leading to a unique distribution of their electronic states. The highly anisotropic geometry of the wires can dictate their crystal structure, thus defining their optical, electrical, and magnetic properties.¹²

      Compared to nanoparticles, the major distinctive feature is the exquisite control in nanofabrication technologies.¹³ Bottom-up strategies include vapor–liquid–solid (VLS) chemical vapor deposition, solution–liquid–solid¹⁴ (SLS) processes and template-assisted synthesis, whereas top-down approaches encompass optical and electron beam lithography.¹³ VLS deposition uses seed catalysts into a supersaturated vapor, where the material desired for the growth of the nanowire is dissolved at concentrations higher than the solubility limit. Typically, a metallic seed (eg, Au) is deposited onto a substrate and heated above the eutectic point to generate alloy droplets. The droplets adsorb vapor containing the precursor elements for assembly of the nanowire, thus becoming supersaturated. Atomic rearrangement within the droplet leads to precipitation of the vapor components in order to minimize the free energy of the alloy. As the vapor continues feeding the alloy droplet, further contributing to its supersaturated state, a one-dimensional growth mechanism occurs and can be sustained as long as the vapor is supplied, thus achieving macroscopic lengths of the nanowires. SLS growth occurs based on similar principles of VLS where the liquid droplets are not located onto a substrate but, as the name suggests, in solution. The precursors are dissolved in the liquid phase and induce supersaturation of the liquid droplets and subsequent growth. This technique complements VLS as it operates at lower temperatures, thus enabling the use of low-melting-point metals or polymers, and is more suitable for upscaling. Template-assisted synthesis consists of the preparation of a porous substrate with one-dimensional nanochannels, subsequently filled with the desired composition of the nanowires,¹⁵ either in liquid form or by means of electrodeposition.

      Top-down approaches exploit optical lithography to etch a resist substrate and manufacture nanometer-sized features. This nanotechnology is diffraction-limited, and Rayleigh criterion dictates that the wavelength used for etching defines the minimum feature size that can be accurately resolved by lithography. Accordingly, the past decades sought to reduce the wavelength, and the current standard is based on excimer lasers (ArF emits at 193 nm). Next-generation lithography attempts further reduction of the wavelength by using extreme ultraviolet radiation (λ = 13.5 nm) or even the X-ray region of the spectrum (λ < 1 nm). Both technologies pose hard technical challenges. The energy of a photon is inversely proportional to its wavelength; therefore extremely high energy (tens of eV) is required before extreme ultraviolet radiation can be emitted. Accordingly, atoms need to be ionized in a plasma, which strongly absorbs photons at such short wavelengths, and operation in a vacuum is required, with the subsequent drawbacks of lower throughput and constraints in compatible materials that can be used as resists. X-ray coherent sources require synchrotron radiation, which could impose an insurmountable cost barrier to the spreading of the technology for mass production. Massive particles, such as electrons, have a DeBroglie wavelength much shorter than photons of identical energy and have been used for demonstrating lithography with features well below 10 nm.¹⁶,¹⁷ Even though the electron beam can resolve nanometer features, electron scattering, proximity effects, and generation of secondary electrons contribute to limiting the actual resolution. Super-resolution techniques¹⁸,¹⁹ have been devised to overcome these limitations, for example, with interference lithography where multiple overlapping coherent beams generate an interference pattern whose features are subwavelength.²⁰ Due to the high symmetry of the interference patterns, this approach is mostly used for manufacturing of gratings. Alternative approaches to improve resolution focus on controlling the other parameters defining the Rayleigh resolution limit, namely the numerical aperture of the focusing lens by using immersion lenses in media with refractive index higher than air (eg, water n = 1.43).

      1.1.3. Nanofilms

      Nanofilms are thin layers of material spanning from a fraction of a nanometer to several micrometers in thickness. They represent an atomic-thick frontier with the surrounding environment, where the vast majority of physicochemical processes occur. Accordingly, having a thin layer of a certain material can influence its behavior and provide leverage for decoupling bulk and surface engineering. Assembly of multiple layers of opposite charge is probably the largest class of nanofilms, where the density of states is confined to a two-dimensional arrangement and quantum coupling between multiple layers regulates the properties of the multilayer. Layer-by-layer deposition is the prevalent method for deposition of functional thin films. There are a variety of approaches to deposit individual layers: immersion, spin coating, spraying, electromagnetic deposition, and fluidic assembly.²¹

      Immersion is the gold standard for benchmarking other approaches and consists of wetting a substrate by immersion into a solution and subsequent washing of the unbound material. The process is intrinsically very simple and versatile and can be applied to colloids, polymers, and nanoparticles that can be deposited in complex geometries (eg, nonplanar). The process is diffusion-limited and can require several minutes per layer, depending on the material being deposited. Subsequent immersions are interspersed by thorough washing steps to remove excess material. Several groups focused on attempts for enhancing throughput by either automating¹⁴ the process or by resorting to de-wetting,²² where rapid evaporation of organic solvents, rather than diffusion, drives mass transport and controls the deposition rate. Relatively low throughput and nonuniform or fuzzy deposition²³ of the layers triggered investigation of alternative technologies for generation of multilayer structures.

      Deposition of the layer precursors onto a spinning substrate reduces the deposition time from minutes to tens of seconds²⁴–²⁶ and, importantly, results in stratified deposition without interpenetrating layers.²⁵,²⁷–²⁹ The homogeneity of the layers derives from two simultaneously occurring phenomena: elimination of excess fluid by centrifugal force and evaporation of the solvent. The radial outflow is controlled by rheological properties such as viscosity of the fluid, duration, and speed of spinning, and results in film thinning. When the rate of thinning equals the evaporation rate, mass transfer dominates the thinning process and defines the final film thickness.³⁰ Weakly bound material needs to be removed by washing steps with pure solvent to minimize surface roughness. When the material being deposited bears a charge, for example, in the case of polyelectrolytes, electrostatic interactions also contribute to the final quality and homogeneity of the film²⁹; therefore key parameters of the spin-coating process are pH and ionic strength of the solvents.

      Spray coating is an alternative to immersion deposition, which delivers rapid (<30 s) and uniform layer formation by accelerating a flux of coating material in vapor state onto a substrate, which can have complex three-dimensional geometry. The vapor accumulates at the substrate, forming a liquid interface where convection-driven diffusion leads to capture of the molecules by the substrate through electrostatic interactions. As electrostatic recognition by the substrate occurs on a much faster timescale, mass transport to and through the liquid layer until the material reaches the capture volume (defined by Debye length) limits the speed of the deposition process. Accordingly, key parameters which control the deposition are the flow rate, the concentration of the spray droplets, and the total deposition time.³¹

      Immersion, spin coating, and spray deposition are the most widespread technologies for film deposition in industrial settings, thanks to their versatility, rapidity, and ease of automation and scale-up. Electromagnetic deposition, where external electric or magnetic fields induce mass transport onto the substrate, and fluidic assembly, where pressure gradients induce fluid transport of the material onto the substrate, are more specialized alternatives for layer-by-layer deposition. In electromagnetic deposition local changes on the electrode surface (eg, pH or redox potential) control the properties of film assembly; however, the process requires specialized equipment and several minutes per layer.³²,³³ Fluid assembly enables coating of microfluidic channels, especially when complex three-dimensional geometries are involved. Even though passive perfusion of the channels can be achieved by capillary action, active manipulation enables handling of larger volume and parallel deposition of multiple channels and selective wetting of a portion of the fluidic channel for local deposition.

      1.2. Nanomaterials in Modern Life

      Nanomaterials are ubiquitous. The enhanced catalytic effects and their unique quantum properties enabled deployment into several applications in electronics, magnetics, mechanics, photonics, fluidics, and biology. The ability to manipulate nanomaterials into shaped nanodevices and combine multiple nanodevices into complex nanosystems has led to consumer products that are now commonly encountered in daily life. The next section will review the major classes of nanoparticles, nanowires, and nanofilms and their utilization in modern technologies.

      1.2.1. Zero-dimensional nanostructures

      Noble metal nanoparticles, in particular gold and silver, can be synthesized in a wide variety of shapes and sizes by multiple physical/chemical routes. Their properties are dependent on their size³⁴: for example, when used as catalysts, the shape, crystal structure, and size dictate the reaction rate.³⁵ Noble metal nanoparticles are biocompatible and have large extinction cross-section in the so-called blood window, where biological tissue have minimal absorption of radiation, thus representing ideal candidates for biomedical applications, for example diagnostics,³⁶ imaging, and therapeutics.³⁷,³⁸ The plasmonic effects of gold/silver nanoparticles combined with the ease of coating/functionalization led to rapid detection or imaging of biomarkers,³⁹,⁴⁰ cells,⁴¹–⁴⁴ and nucleic acids,⁴⁵–⁴⁷ even at the single molecule level.⁴⁸ Anisotropic particles, nanocages, nanoshells, and nanostars with high absorption cross section have proven powerful contrast agents in vivo tumor tomography.⁴⁹ When irradiated with high-frequency laser pulses, the high absorption cross-section resulted in nonradiative decay of the absorbed photons into phonons, thus enabling photothermal therapy for targeted destruction of tumor cells.⁵⁰–⁵²

      Purification of drinking water however remains the most important application of noble metal nanoparticles⁵³ as they enable degradation, removal, or detection of pesticides⁵⁴,⁵⁵ and heavy metals.⁵⁶–⁵⁸ Silver nanoparticles, well known for their antibacterial properties, represent a remarkable case of daily use of nanotechnology. Even though their actual mode of action is still under investigation, it has been demonstrated that the cellular membrane of bacteria suffers structural damage leading to accumulation of silver nanoparticles in the cytoplasm. Separate studies also indicate that their potency depends on the size of the silver core,⁵⁹ probably related to size constraints of diffusing through a lipid membrane. Nanometer-sized silver nanoparticles are commercially available as additives for disinfection of drinking water and in toothpaste.⁵⁹

      Recently several groups have discussed a transition in physicochemical properties of noble metal nanoclusters of diameter below 1 nm.⁶⁰ At such short scales, the nanoparticles have a mean diameter much shorter than the wavelength of probing electromagnetic fields, resulting in highly polarizable discrete electronic states with high fluorescence emission. The emission occurs in a narrow range of wavelengths and is dependent on the size of the nanoparticles with quantum yields as high as 25%.⁶¹ Thanks to their biocompatibility, they have been deployed in biotechnology⁶² for imaging⁶³–⁶⁷ and fluorescent detection of metal ions,⁶⁸–⁷⁰ small molecules,⁷¹,⁷² nucleic acids,⁷³–⁷⁵ and protein biomarkers.⁷⁶,⁷⁷

      Semiconductor nanoparticles, or quantum dots, have attracted considerable interest in view of their optical properties and have been extensively studied in the past decades.⁷⁸–⁸⁰ A shell of semiconducting material is normally grown onto a core of a different semiconductor material, generating so-called core-shell nanostructures that enable decoupling of surface engineering and optimization of photostability as well as emission wavelengths across the visible and infrared spectral range. Light emission is due to radiative decay of excitons, whose energy is regulated by the quantized electronic states within the valence and conduction bands. Quantum confinement regulates the nanoparticle emission wavelength, which therefore becomes dependent on the size and geometry of the material. The ability to engineer the energy gap has been vital for deployment of semiconductor nanoparticles for energy production. For example, in solar cells the incoming photons from solar radiation generate excitons in semiconducting material that are subsequently separated by means of external electric fields, resulting in a net charge transport. The broad spectrum of the incoming radiation could not be fully harvested by early generation cells as they were responsive only to photons with energy matching the characteristic band gap of the material.⁸¹ Since approximately half of solar radiation emits in the near-infrared and infrared,⁸² semiconductor nanoparticles with tunable gap size enable access of this spectral region⁸³ with high efficiency.⁸⁴,⁸⁵ Nonlinear optical effects in semiconductor nanoparticles can increase the efficiency of solar cells by acting as spectral converters.⁸¹ Absorption of high-energy photons can be followed by either rapid nonradiative or radiative relaxation into lower energy levels. In the first instance, emission of one photon of lower energy (downshifting) occurs, whereas the second scenario results in emission of two photons of lower energy (quantum cutting). The opposite mechanism, where low-energy photons promote electrons into high energy states, leads to subsequent radiative decay with emission of high-energy photons. The emitted photons contribute to exciton creation and therefore to current generation. Another quantum phenomenon associated with semiconductor nanoparticles is the creation of multiple excitons by a single photon of high energy⁸⁶ for enhanced solar cell efficiency.⁸⁷ Semiconductor nanoparticles are extensively used to harvest photons from the incoming solar radiation either simply acting as adsorbing agents, for example, as UV blockers in consumer products such as sun creams⁸⁸,⁸⁹ or acting as photocatalysts to promote the production of hydrogen as an alternative, sustainable energy source.⁷⁵ The incoming photons generate excitons that travel to the surface of the nanoparticle prior to relaxing into lower energy states. Once on the surface, the electrons can promote reductive or oxidative reactions, thus releasing hydrogen.⁹⁰,⁹¹ The superior photophysical properties of semiconductor quantum dots have been highly praised as next-generation fluorescent labels for cell imaging, diagnostics, and multiplexed immunostaining⁹²,⁹³; however, concerns regarding their toxicity prevented widespread usage in vivo.⁹⁴ In an attempt to circumvent concerns about their toxicity, several groups have investigated the use of carbon quantum dots for biomedical applications, as they are free of heavy metals and intrinsically aqueous soluble and, to date, no obvious toxicity in in vitro and in vivo studies was reported.⁷⁹,⁹⁵,⁹⁶ Concerns about the toxicity of several nanomaterials are actually imparting momentum to the investigation of green technologies as well as having deep regulatory implications because nanoparticles are nowadays present in products of daily usage such as cosmetics or shampoos while potential long-term effects on human health or on the environment are still under debate.⁹⁷

      1.2.2. One-dimensional nanostructures

      Nanowires can be mass-produced by either top-down or bottom-up technologies, and the constituting materials can be doped with impurities to modulate their conductivity, thus paving the way to their deployment into high-performance electronics. Devices with basic functionality (eg, bistable resistors,⁹⁸ transistors,⁹⁹–¹⁰¹ diodes¹⁰²–¹⁰⁴) or more complex circuits (eg, logic gates¹⁰⁵) based on doped nanowires have been demonstrated on both rigid and flexible substrates. The use of nanowires for assembly of electronic components is accompanied by miniaturization of the final device, which is desirable not only for reducing the cost but also for the lower amount of incorporated defects that result in more robust and resilient nanowires.¹⁰⁶ The unique optical and mechanical properties of nanowires led to their extensive use as sensing devices. The chemical composition of the nanowire can be engineered to fine-tune the band gap of the electronic states: metal oxides are characterized by large band gaps (3–10 eV), metal chalcogenides (eg, ZnSe), and semiconducting alloys (eg, In2Te3), respectively, exhibit an intermediate band gap (1.5–3 eV) or a narrow band gap (<1.5 eV). Tunable band gaps led to the assembly of photodetector nanodevices, absorbing across the ultraviolet, visible, and infrared portion of the spectrum. Photodetectors formed by individual nanowires are the simplest sensing architecture and can be fabricated by optical lithography;¹⁰⁷ however, the generated current can be modest (tens of nA). Arrays of nanowires have been assembled to circumvent this issue, and photocurrents several orders of magnitude higher than the dark current have been demonstrated.¹⁰⁸,¹⁰⁹ The electronic states defining the band gaps are affected by the interatomic spacing, resulting in piezoresistive behavior that has been exploited to build stress sensors. Giant piezoresistivity compared to bulk has been reported for silicon nanowires with <111> or <100> growth directions, where the orientation of a crystal plane is defined by its intersection with the main crystallographic axes in Miller’s indices notation, and the improved charge mobility could lead to next-generation silicon transistors.¹¹⁰ An interesting application of nanowires as stress sensors is artificial skin, where independently driven nanowire arrays constitute an active matrix of sensing pixels capable of emulating tact by generating pressure-dependent voltage on flexible and robust substrates. Rapid and sensitive arrays have been demonstrated,¹¹¹,¹¹² and current efforts aim to enable real-time interpretation of the voltage signals by the end user¹¹³ and to increase resolution.¹¹⁴ Electrical currents can be used to stimulate nanowires and promote electrons into the conduction band of semiconducting nanowires followed by radiative decay and emission of photons, and multicolor-emitting LEDs based on nanowires have been demonstrated.¹¹⁵ Nanowires are also being investigated for energy storage, conversion, and generation. Rechargeable lithium batteries exploit nanowires to enhance the energy storage capacity of anode and cathode¹¹⁶ or confer mechanical flexibility to the battery.¹¹⁷ In solar cells, nanowires have shorter and faster electron transport paths, high absorption coefficients, and low reflective losses compared to planar semiconductors. In an attempt to increase the surface area and therefore the light trapping capability, branched nanowires, often picturesquely referred as nano-forests, with tunable three-dimensional morphology have been investigated as exciton cells for solar energy production and storage (super capacitors, lithium batteries).¹¹⁸

      Carbon nanotubes, as the name suggests, are hollow nanowires of cylindrical shape obtained by folding a planar honeycomb lattice of carbon atoms (graphene, see Section 1.2.3) into a tube. By folding an individual lattice of carbon, one obtains single-wall carbon nanotubes of nanometric cross section (0.8–2 nm), high aspect ratios (>10⁸), and macroscopic lengths of up to 180 mm.¹¹⁹ Multiple coaxial tubes can be layered concentrically to generate multiwall carbon nanotubes whose diameter ranges between 5 and 20 nm. Carbon nanowires raised considerable interest in the past two decades thanks to their unique capability of bridging the mesoscale and propagating quantum properties to the macroscale. The high symmetry of the planar carbon precursor results in hybridization of the s and p orbitals to sp², where three of the valence electrons are delocalized within planar orbitals arranged at 120 degrees and the remaining electron is delocalized in an orbital orthogonal to the plane. This unique configuration enables interaction with neighboring atoms and results in overlap of sp² orbitals and formation of three very strong σ bonds. The remaining electron forms a weak out-of-plane π bond where the nodal plane coincides with the planar arrangement of the carbon atoms. The spatial arrangement of the electronic states defines the mechanical, thermal, and electrical properties of the nanotubes. In an individual carbon nanotube, the mean free path of an electron can be as high as 1 μm at room temperature¹²⁰ (compared with 0.04 μm in copper¹²¹), corresponding to resistances as low as 10−6 Ω cm−1, and the tensile module can be as high as 1 TPa, far exceeding the specific mechanical properties of steel. The high electron mobility in the axial direction leads to thermal conductivity as high as 3000–3500 W m−1 K−1 for single- and multiwall carbon nanotubes. It is, however, very challenging to devise technologies capable of mass-producing organized nanotube architectures (eg, yarns, forests, and sheets) free of defects with preserved chirality and uniformity. Hence current applications can only partially harvest the superior properties of nanotubes. The first commercial applications based on nanotubes have been composite materials, where dispersions of nanotubes enabled improved electrical conductivity and load bearing in plastics and resins.¹²² Patterned arrays of several thousands of nanotubes can compensate for individual defects, thus minimizing variations between different microelectronic devices.¹²³ Transistors based on carbon nanotubes can be deposited at relatively low temperatures, making them particularly attractive for driving OLEDs,¹²⁴ and feasibility of large-scale manufacturing of low-resistance interconnects capable of carrying large currents has been demonstrated.¹²⁴ Doping of lithium ion batteries with a small number of multiwalled carbon nanotubes leads to increases in battery lifetime by augmenting the electrical connectivity.¹²²,¹²⁵ Carbon nanotubes are also particularly sensitive to environmental changes and have been extensively used as biosensors, where the interaction with a target biomolecule generates a change in either the electrical impedance, mechanical, or optical properties.¹²⁶–¹³⁰ Deployment in vivo enables drug delivery, targeted cancer therapy, or imaging; however, the toxicology profile of carbon nano-allotropes is still being investigated, and early studies indicate that geometry and surface functionalization could enable engineering of biocompatibility.¹²²,¹³¹ In the next decade, understanding potential health hazards of nanotubes and technological advances in large-scale manufacturing will be the key to enable larger spreading of this nanotechnology in future commercial products.

      1.2.3. Two-dimensional nanostructures

      Thin film optical filters are widely used to control the transmissivity of a surface by layer-by-layer deposition of multiple materials with different refractive indices.¹³² Maxwell’s equations describe how optical radiation is partially transmitted and reflected at the interface of two different media. Accordingly, the incident light is reflected at both the upper and lower surface of a thin film, and if the thickness of the film is suitably controlled, the resulting phase shift induces either constructive or destructive interference. Multipass circulation within the optical cavities obtained by stacking multiple layers can lead to theoretically arbitrary transmittance profiles, thus resulting in antireflective coatings, dichroic filters, and band-pass filters. The technology for manufacturing such optical components is well established, and thin film coatings are rather ubiquitous in modern consumer electronics. Eyewear makes use of coatings to prevent reflection, microlenses embedded into the cameras of mobile phones exploit optical filters to ensure image quality, and, thanks to the scaling capability of the technology for deposition over large areas, solar cells with antireflective coatings are routinely built to minimize optical losses.¹³³ Recent research focuses on expanding the applicability of the technology, for example, by using highly absorbing media to constitute the layers,¹³⁴ a method traditionally not accessible due to the strong attenuation of the propagating light that destroys interference, or by developing optical elements applicable to ultrahigh frequencies (THz).¹³⁵

      Graphene is probably the best-known example of two-dimensional films with atomic thickness. As with nanotubes, the distribution of the electronic states in a σ and π band is at the basis of the fascinating properties of graphene. Intrinsic graphene is a zero gap semiconductor where conduction and valence bands meet at the Dirac points in the reciprocal space. At the Dirac points the density of electronic states assumes conical profile and electrons, for low energy excitations have negligible effective mass and can therefore be described as chiral Dirac fermions with nonzero constant velocity.¹³⁶ A full quantum electrodynamic treatment is necessary to explain the unusual behavior of electrons in external fields, which accounts for some exotic properties such as the anomalous integer quantum Hall effect (that is, quantization of Hall voltage at room temperature)¹³⁷ and Klein paradox¹³⁸ of unitary tunneling probability through high and wide potential barriers.¹³⁹,¹⁴⁰ This unique electronic structure accounts for high Young modulus (as high as 1 TPa in defect-free graphene) and constant optical transmittance across visible and infrared regions of the spectrum (>97%).¹⁴¹ The low density of states near the Dirac points dictates that the electronic contribution to thermal conductivity is negligible and heat transport is dominated by phonons¹⁴¹ (thermal conductivity 5000–6000 W m−1 K−1).¹⁴²,¹⁴³ The unique band structure leads to the charge carriers being bipolar,¹⁴⁴ with electrons that can be continuously turned into holes by tuning the driving voltage.¹⁴¹ Such effects have been exploited for field-effect transistors (FET) in microelectronics; however, the finite nonnegligible conductance at zero gate voltage prevents complete switching off of transistors made of pristine graphene, which are therefore unsuited for logic applications. A band gap can be artificially generated by applying stress to graphene (eg, by disturbing the symmetry of the lattice¹⁴¹) or by folding a graphene sheet into a nanoribbon.¹⁴⁵,¹⁴⁶ The high electron mobility paired with almost complete transparency renders graphene suitable for fabrication of flexible,¹⁴⁷ transparent¹⁴⁸ electrodes. Chemical functionalization of graphene is mostly used to modulate the hydrophilicity of graphene so that it can be stably dispersed in different solvents that enable further downstream modifications.¹⁴⁹ The possibility of dispersing graphene sheets into aqueous environments enabled their use for biosensing of bacteria,¹⁵⁰,¹⁵¹ protein biomarkers,¹⁵²–¹⁵⁵ small molecules,¹⁵⁶ and nucleic acids.¹⁵⁷ Graphene is also capable of long-range quenching of fluorophores and quantum dots, and it has been extensively used for the development of novel fluorescence-based biosensing paradigms.¹⁵⁸,¹⁵⁹

      Inorganic nanofilms have been the object of recent investigation for potential use as insulators or semiconductors. The microelectronic industry is in dire need of high- permittivity dielectrics as a replacement for SiO2 as gate insulators: the progressive downscaling over the past decades is now approaching a fundamental physical limit where quantum tunneling of electrons can occur with nonnegligible probability. High permittivity enables to match the gate capacitance of SiO2 but with thicker layers, thus minimizing quantum leakage currents.¹⁶⁰ One of the major classes of dielectric nanofilms is based on nonpolar metal oxides of moderate permittivity (<100) and titania (Ti0.87O2) is probably the most interesting example. Bulk rutile TiO2 is an insulator (band gap of approximately 3 eV);¹⁶¹ however, oxygen vacancies, introduced accidentally during manufacturing, dramatically affect its high permittivity. Titania films are not prone to this phenomenon thanks to their Ti vacancies in the crystal structure,¹⁶² thus resulting in 25% higher permittivity compared to TiO2. Moreover, the net negative charge on the nanofilms imparts colloidal stability in aqueous solutions and subsequent layer-by-layer assembly of uniform layers with low surface roughness (<0.5 nm). Highly organized lamellar structures with high permittivity (>200) and of quality comparable to films manufactured by advanced vacuum deposition technologies have been demonstrated.¹⁶³

      Transition metal dichalcogenides (TMDC) are formed by a metal from either group IV, group V, or group VI reacted with two chalcogen (S, Se, Te) atoms, resulting in either hexagonal or rhombohedral crystal symmetry.¹⁶⁴ Their band structure is of interest as the gap transition evolves from indirect for three-dimensional crystals to direct for two-dimensional nanofilms. Such transition is accompanied by an increase in photoconductivity, absorption, and emission quantum yield.¹⁶⁴ Most TMDC semiconducting materials exhibit an energy gap comparable to the one of silicon, thus rendering them suitable for fabrication of microelectronic components. In particular, the sizeable band gap (1.1–1.9 eV) circumvents the issue of high dark currents observed in graphene nanofilms and renders these materials suited for logic switches as high ratios in ON/OFF currents can be achieved.¹⁶⁵ Charge mobility within the TMCD nanofilms is limited by Coulomb scattering against charged impurities and can be improved severalfold when an inorganic layer (eg, titania) is used as gate material in transistors,¹⁶⁶ thus rivaling silicon transistors. Moreover, the exceptional mechanical properties of TMCDs¹⁶⁷ render them suited for flexible optoelectronics and photovoltaics.

      Another interesting class of nanofilms is based on deposition of other nanomaterials as they can expose collective behavior resulting in unexpected material properties. Deposition of randomly distributed carbon nanotubes results in a semiconductor-metal transition of the film that is thickness dependent.¹⁶⁸ Thin films (<10 nm) exhibit a semiconductor behavior that can be harvested for fabrication of novel microelectronic components,¹⁶⁹,¹⁷⁰ whereas thicker films (10–100 nm) are highly conductive and optically transparent¹⁷¹–¹⁷³ and have been used for OLED displays, solar cells, and energy storage.¹⁶⁸ Future direction is likely to encompass deployment for biosensing: sensors based on individual carbon nanotubes are exquisitely sensitive; however, they pose cost constraints that are far too demanding for large-scale reproducible manufacturing. Networks of nanotubes polydispersed in properties are likely to relax such constraints while retaining the potential for high sensitivity.¹⁶⁸ Deposition of metal ions complexed with organic ligands, so-called metal-organic frameworks, is a recent technological development of particular interest for the generation of thin nanoporous films whose major applications are quartz microbalance¹⁷⁴,¹⁷⁵; stress, plasmoni, or chemical sensors¹⁷⁴,¹⁷⁵; wearable flexible electronics¹⁷⁶,¹⁷⁷; and membranes for size filtration.¹⁷⁴,¹⁷⁵

      1.3. Conclusions

      This high-level overview on emerging nanotechnologies offers a glimpse of the broad spectrum of applications that would be unfeasible without the special properties of quantum materials. Over the past three decades the majority of researchers have aimed to unravel the fundamental physics unlocked by nanomaterials and to develop manufacturing technologies for synthesis of a wider portfolio of materials. Today the challenges ahead require us to bridge the gap to high-quality mass production. As most nanomaterials exhibit size-dependent properties and are highly sensitive to structural defects, manufacturing technology must ensure exquisite reproducibility at yielded output costs low enough for economic viability. This also needs to be accompanied by compliance with recent regulatory concerns that have attempted to formalize the classification of a nanomaterial¹⁷⁸ in order to promote a shift toward safe green technologies not hazardous to humans or the environment.

      References

      1. Feynman RP. There’s plenty of room at the bottom. Eng Sci. 1960;23:22–36.

      2. Gleiter H. Nanostructured materials: basic concepts and microstructure. Acta Materialia. 2000;48:1–29.

      3. Davis ME, Lobo RF. Zeolite and molecular-sieve synthesis. Chem Mater. 1992;4:756–768.

      4. Bellomo EG, Wyrsta MD, Pakstis L, Pochan DJ, Deming TJ. Stimuli-responsive polypeptide vesicles by conformation-specific assembly. Nat Mater. 2004;3:244–248.

      5. Hubbell JA, Chilkoti A. Nanomaterials for drug delivery. Science. 2012;337:303–305.

      6. Holzinger M, Le Goff A, Cosnier S. Nanomaterials for biosensing applications: a review. Front Chem. 2014;2:63.

      7. Lynch I, Cedervall T, Lundqvist M, Cabaleiro-Lago C, Linse S, Dawson KA. The nanoparticle - protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century. Adv Colloid Interface Sci. 2007;134–135:167–174.

      8. Kruis FE, Fissan H, Peled A. Synthesis of nanoparticles in the gas phase for electronic, optical and magnetic applications—a review. J Aerosol Sci. 1998;29:511–535.

      9. Mueller R, Madler L, Pratsinis SE. Nanoparticle synthesis at high production rates by flame spray pyrolysis. Chem Eng Sci. 2003;58:1969–1976.

      10. Swihart MT. Vapor-phase synthesis of nanoparticles. Curr Opin Colloid Interface Sci. 2003;8:127–133.

      11. Vekilov PG. Nucleation. Crystal Growth Des. 2010;10:5007–5019.

      12. Lieber CM, Wang ZL. Functional nanowires. MRS Bulletin. 2007;32:99–108.

      13. Hobbs RG, Petkov N, Holmes JD. Semiconductor nanowire fabrication by bottom-up and top-down paradigms. Chem Mater. 2012;24:1975–1991.

      14. Wang F, Dong A, Sun J, Tang R, Yu H, Buhro WE. Solution-liquid-solid growth of semiconductor nanowires. Inorg Chem. 2006;45:7511–7521.

      15. Almawlawi D, Coombs N, Moskovits M. Magnetic-properties of Fe deposited into anodic aluminum-oxide pores as a function of particle-size. J Appl Phys. 1991;70:4421–4425.

      16. Hu SF, Weng WC, Wan YM. Fabrication of silicon nanowire structures based on proximity effects of electron-beam lithography. Solid State Commun. 2004;130:111–114.

      17. Jeon KJ, Lee JM, Lee E, Lee W. Individual Pd nanowire hydrogen sensors fabricated by electron-beam lithography. Nanotechnology. 2009;20:135502.

      18. Choi YK, Zhu J, Grunes J, Bokor J, Somorjai GA. Fabrication of sub-10-nm silicon nanowire arrays by size reduction lithography. J Phys Chem B. 2003;107:3340–3343.

      19. Martensson T, Carlberg P, Borgstrom M, Montelius L, Seifert W, Samuelson L. Nanowire arrays defined by nanoimprint lithography. Nano Lett. 2004;4:699–702.

      20. Kim DS, Ji R, Fan HJ, Bertram F, Scholz R, Dadgar A, Nielsch K, Krost A, Christen J, Goesele U, Zacharias M. Laser-interference lithography tailored for highly symmetrically arranged ZnO nanowire arrays. Small. 2007;3:76–80.

      21. Richardson JJ, Björnmalm M, Caruso F. Technology-driven layer-by-layer assembly of nanofilms. Science. 2015;348:6233.

      22. Shim BS, Podsiadlo P, Lilly DG, Agarwal A, Leet J, Tang Z, Ho S, Ingle P, Paterson D, Lu W, Kotov NA. Nanostructured thin films made by diewetting method of layer-by-layer assembly. Nano Lett. 2007;7:3266–3273.

      23. Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science. 1997;277:1232–1237.

      24. Jiang CY, Markutsya S, Tsukruk VV. Collective and individual plasmon resonances in nanoparticle films obtained by spin-assisted layer-by-layer assembly. Langmuir. 2004;20:882–890.

      25. Kharlampieva E, Kozlovskaya V, Chan J, Ankner JF, Tsukruk VV. Spin-Assisted Layer-by-Layer Assembly: Variation of Stratification as Studied with Neutron Reflectivity. Langmuir. 2009;25:14017–14024.

      26. Chiarelli PA, Johal MS, Casson JL, Roberts JB, Robinson JM, Wang HL. Controlled fabrication of polyelectrolyte multilayer thin films using spin-assembly. Adv Mater. 2001;13:1167–1171.

      27. Li XY, Wu YQ, Gu DD, Gan FX. Optical characterization and blu-ray recording properties of metal(II) azo barbituric acid complex films. Mater Sci Eng B. 2009;158:53–57.

      28. Schreiber M, Lutz T, Keeley GP, Kumar S, Boese M, Krishnamurthy S, Duesberg GS. Transparent ultrathin conducting carbon films. Appl Surf Sci. 2010;256:6186–6190.

      29. Cho J, Char K, Hong JD, Lee KB. Fabrication of highly ordered multilayer films using a spin self-assembly method. Adv Mater. 2001;13:1076–1078.

      30. Hall DB, Underhill P, Torkelson JM. Spin coating of thin and ultrathin polymer films. Polym Eng Sci. 1998;38:2039–2045.

      31. Mulhearn WD, Kim DD, Gu Y, Lee D. Facilitated transport enhances spray layer-by-layer assembly of oppositely charged nanoparticles. Soft Matter. 2012;8:10419–10427.

      32. Zhao N, Shi F, Wang ZQ, Zhang X. Combining layer-by-layer assembly with electrodeposition of silver aggregates for fabricating superhydrophobic surfaces. Langmuir. 2005;21:4713–4716.

      33. Wang Y, Liu Y, Cheng Y, Kim E, Rubloff GW, Bentley WE, Payne GF. Coupling Electrodeposition with Layer-by-Layer Assembly to Address Proteins within Microfluidic Channels. Adv Mater. 2011;23:5817–5821.

      34. Pradeep T, Theruvakkattil S. Noble metal nanoparticles. Berlin, Heidelberg: Springer; 2013.

      35. Wang P, Huang B, Dai Y, Whangbo M-H. Plasmonic photocatalysts: harvesting visible light with noble metal nanoparticles. Phys Chem Chem Phys. 2012;14:9813–9825.

      36. Perfezou M, Turner A, Merkoci A. Cancer detection using nanoparticle-based sensors. Chem Soc Rev. 2012;41:2606–2622.

      37. Mieszawska AJ, Mulder WJM, Fayad ZA, Cormode DP. Multifunctional gold nanoparticles for diagnosis and therapy of disease. Mol Pharm. 2013;10:831–847.

      38. Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev. 2009;38:1759–1782.

      39. Brolo AG. Plasmonics for future biosensors. Nat Photonics. 2012;6:709–713.

      40. Cetin AE, Coskun AF, Galarreta BC, Huang M, Herman D, Ozcan A, Altug H. Handheld high-throughput plasmonic biosensor using computational on-chip imaging. Light Sci Appl. 2014;3:e122.

      41. Zhang J, Atay T, Nurmikko AV. Optical detection of brain cell activity using plasmonic gold nanoparticles. Nano Lett. 2009;9:519–524.

      42. Bhattacharyya K, Goldschmidt BS, Hannink M, Alexander S, Jurkevic A, Viator

      Enjoying the preview?
      Page 1 of 1