Nanobiotechnology Edited by C. M. Niemeyer and C. A. Mirkin

Nanobiotechnology. Edited by Christof Niemeyer, Chad Mirkin Copyright c 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-30658-7

Further Titles of Interest V. Balzani, A. Credi, M. Venturi

Molecular Devices and Machines 2003, ISBN 3-527-30506-8

M. Schliwa (ed.)

Molecular Motors 2002, ISBN 3-527-30594-7

Ch. Zander, J. Enderlein, R. A. Keller (eds.)

Single Molecule Detection in Solution 2002, ISBN 3-527-40310-8

E. Bäuerlein (ed.)

Biomineralization – From Biology to Biotechnology and Medical Application 2000, ISBN 3-527-29987-4

Nanobiotechnology Concepts, Applications and Perspectives Edited by Christof M. Niemeyer and Chad A. Mirkin

Edited by Prof. Dr. Christof M. Niemeyer Universität Dortmund, Fachbereich Chemie Biologisch-Chemische Mikrostrukturtechnik Otto-Hahn-Str. 6 44227 Dortmund Germany [email protected] Prof. Dr. Chad A. Mirkin Department of Chemistry & Institute for Nanotechnology Northwestern University 2145 Sheridan Road Evanston, IL 60208-3113 USA [email protected]

This book was carefully produced. Nevertheless, editors, authors and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data is available in the Internet at http://dnb.ddb.de. c 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Cover illustration Malign (top) and normal cells (bottom) on pillar interfaces which sense cellular forces. In the middle illustration, the molecular distribution of integrin (green) and actin (red) is shown. All micrographs were kindly provided by W. Roos, J. Ulmer, and J.P. Spatz (University of Heidelberg, Germany).

All rights reserved (including those of translation in other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Printed in the Federal Republic of Germany. Printed on acid-free paper. Typesetting Hagedorn Kommunikation, Viernheim Printing betz-druck gmbh, Darmstadt Bookbinding J. Schäffer GmbH & Co. KG, Grünstadt ISBN

3-527-30658-7

Contents

Contents Part I

Interphase Systems

1

Biocompatible Inorganic Devices Thomas Sawitowski Introduction 1 Implant Coatings 1 Stents 2 Seeds 7 Conclusion 10

1.1 1.2 1.2.1 1.2.2 1.3 2

2.1 2.2 2.2.1 2.2.2 2.2.3 2.2.4 2.2.5 2.3 2.3.1 2.3.1.1 2.3.1.2 2.3.1.3 2.3.2 2.3.3 2.3.4 2.3.5 2.3.6 2.4

1

Microfluidics Meets Nano: Lab-on-a-Chip Devices and their Potential for Nanobiotechnology Holger Bartos, Friedrich Götz, and Ralf-Peter Peters Introduction 13 Overview 13 Definition and History 13 Advantages of Microfluidic Devices 14 Concepts for Microfluidic Devices 15 Fluid Transport 17 Stacking and Sealing 18 Methods 19

13

Materials for the Manufacture of Microfluidic Components 19 Silicon 19 Glass 19 Polymers 20 Fluidic Structures 21 Fabrication Methods 23 Surface Modifications 23 Spotting 25 Detection Mechanisms 26 Outlook 26

Nanobiotechnology. Edited by Christof Niemeyer, Chad Mirkin Copyright c 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-30658-7

V

VI

Contents

3

3.1 3.2 3.2.1 3.2.2 3.2.3 3.3 3.3.1 3.3.2 3.3.3 3.4 3.5 3.5.1 3.5.2 3.5.3 3.6 3.6.1 3.6.2 3.6.3 3.6.4 3.6.5 3.6.6 3.7 4

4.1 4.2 4.3 5

5.1 5.2 5.2.1 5.2.2 5.2.3 5.3 5.3.1 5.3.2 5.3.3 5.3.4 5.4

Microcontact Printing of Proteins 31 Emmanuel Delamarche Introduction 31

Strategies for Printing Proteins on Surfaces 33 Contact Processing with Hydrogel Stamps 33 Microcontact Printing 33 Affinity-Contact Printing 34 Microcontact Printing Polypeptides and Proteins 34 Printing One Type of Biomolecule 35 Substrates 36 Resolution and Contrast of the Patterns 38 Activity of Printed Biomolecules 40 Printing Multiple Types of Proteins 42 Additive and Subtractive Printing 42 Parallel Inking and Printing of Multiple Proteins 44 Affinity-Contact Printing 44 Methods 45 Molds and Stamps 45 Surface Chemistry of Stamps 47 Inking Methods 47 Treatments of Substrates 48 Printing 48 Characterization of the Printed Patterns 49 Outlook 49 Cell–Nanostructure Interactions 53 Joachim P. Spatz Introduction 53 Methods 56 Outlook 63 Defined Networks of Neuronal Cells in Vitro 66 Andreas Offenhäusser and Angela K. Vogt Introduction 66 Overview: Background and History 67

Physiology of Information Processing within Neuronal Networks 67 Topographical Patterning 67 Chemical Patterning 68 Methods 69 Topographical Patterning 69 Photolithographic Patterning 70 Photochemical Patterning 70 Microcontact Printing 71 Outlook 72

Contents

Part II Protein-based Nanostructures 6

6.1 6.1.1 6.1.2 6.1.3 6.1.3.1 6.1.3.2 6.1.3.3 6.2 6.2.1 6.2.2 6.2.3 6.3 7

7.1 7.1.1 7.1.2 7.1.3 7.1.4 7.1.5 7.2 7.2.1 7.2.2 7.2.3 7.2.4 7.3 7.3.1 7.3.2 7.3.3 7.3.4 7.3.5 7.3.6 8

8.1 8.2

S-Layers 77 Uwe B. Sleytr, Eva-Maria Egelseer, Dietmar Pum, and Bernhard Schuster Overview 77 Abbreviations 77 Chemistry and Structure 78 Genetics and Secondary Cell-Wall Polymers 80 Assembly 82 Self-Assembly in Suspension 82 Recrystallization at Solid Supports 83

Recrystallization at the Air/Water Interface and on Langmuir Lipid Films 83 Methods 84 Diagnostics 84 Lipid Chips 85 S-Layers as Templates for the Formation of Regularly Arranged Nanoparticles 87 Outlook 89 Engineered Nanopores 93 Hagan Bayley, Orit Braha, Stephen Cheley, and Li-Qun Gu Overview 93 What is a Nanopore? 93 Engineering Nanopores 96 What Can a Nanopore Do? 97

What are the Potential Applications of Nanopores? 100 Keeping Nanopores Happy 103 Methods 104 Protein Production 104 Protein Engineering 104 Electrical Recording 105 Other Systems 105 Outlook 106 Rugged Pores 106 Supported Bilayers 106 Membrane Arrays 106 Alternative Protein Pores 107 Pores with New Attributes and Applications 108 Theory 108 Genetic Approaches to Programmed Assembly 113 Stanley Brown Introduction 113 Order from Chaos 113

VII

VIII

Contents

8.3 8.4 8.5 8.6 8.7 8.8 8.9 8.10 8.11

Monitoring Enrichment 116 Quantification of Binding and Criteria for Specificity 119 Unselected Traits and Control of Crystallization/Reactivity 119 Dominant Traits, Interpretation of Gain-of-Function Mutants 120 Interpretation and Requirement for Consensus Sequences 120 Sizes of Proteins and Peptides 122 Mix and Match, Fusion Proteins, and Context-Dependence 122 Mix and Match, Connecting Structures 122 Outlook 123

9

Microbial Nanoparticle Production 126 Murali Sastry, Absar Ahmad, M. Islam Khan, and Rajiv Kumar Overview 126 Outlook 133

9.1 9.2 10

10.1 10.1.1 10.1.2 10.1.3 10.1.4 10.1.5 10.1.6 10.1.7 10.1.8 10.2 10.3 11

11.1 11.2 11.2.1 11.2.2 11.2.3 11.2.4 11.3 11.3.1 11.3.1.1 11.3.1.2 11.3.1.3 11.3.2 11.3.2.1 11.3.2.2

Magnetosomes: Nanoscale Magnetic Iron Minerals in Bacteria Richard B. Frankel and Dennis A. Bazylinski Introduction 136 Magnetotactic Bacteria 136 Magnetosomes 137 Cellular Magnetic Dipole and Magnetotaxis 138 Magneto-Aerotaxis 139 Magnetite Crystals in Magnetosomes 140 Greigite Crystals in Magnetosomes 141

136

Biochemistry and Gene Expression in Magnetosome Formation 141 Applications of Magnetosomes 143 Research Methods 143 Conclusion and Future Research Directions 143 Bacteriorhodopsin and its Potential in Technical Applications Norbert Hampp and Dieter Oesterhelt Introduction 146

146

Overview: The Molecular Properties of Bacteriorhodopsin 147 Haloarchaea and their Retinal Proteins 147 Structure and Function of Bacteriorhodopsin 150 Genetic Modification of Bacteriorhodopsin 153 Biotechnological Production of Bacteriorhodopsins 154 Overview: Technical Applications of Bacteriorhodopsin 155 Photoelectric Applications 156 Preparation of Oriented PM Layers 156 Interfacing the Proton-Motive Force 158 Application Examples 158 Photochromic Applications 159 Photochromic Properties of Bacteriorhodopsin 159 Preparation of Bacteriorhodopsin Films 161

Contents

11.3.2.3 11.3.2.4 11.3.3 11.4 11.5

Interfacing the Photochromic Changes 161 Application Examples 161 Applications in Energy Conversion 163 Methods 165 Outlook 165

12

Polymer Nanocontainers 168 Alexandra Graff, Samantha M. Benito, Corinne Verbert, and Wolfgang Meier Introduction 168 Overview 168

12.1 12.2 12.2.1

From Liposomes in Biotechnology to Polymer Nanocontainers in Therapy 168 12.2.2 Dendrimers 169 12.2.3 Layer by Layer (LbL) Deposition 170 12.2.4 Block Copolymer Self-Assembly 172 12.2.4.1 Shell Cross-linked Knedel’s (SCKs) 173 12.2.4.2 Block Copolymer Nanocontainers 174 12.3 Polymer Nanocontainers with Controlled Permeability 175 12.3.1 Block Copolymer Protein Hybrid Systems 175 12.3.2 Stimuli-responsive Nanocapsules 178 12.4 Nanoparticle Films 179 12.5 Biomaterials and Gene Therapy 180 12.6 Outlook 181 13

13.1 13.2 13.2.1 13.2.2 13.2.3 13.2.4 13.3 14

14.1 14.2 14.2.1 14.2.2

Biomolecular Motors Operating in Engineered Environments Stefan Diez, Jonne H. Helenius, and Jonathon Howard Overview 185 Methods 190 General Conditions for Motility Assays 190 Temporal Control 191 Spatial Control 191 Connecting to Cargoes and Surfaces 194 Outlook 195

185

Nanoparticle–Biomaterial Hybrid Systems for Bioelectronic Devices and Circuitry 200 Eugenii Katz and Itamar Willner Introduction 200

Biomaterial–Nanoparticle Systems for Bioelectronic and Biosensing Applications 202 Bioelectronic Systems Based on Nanopaticle–Enzyme Hybrids 202 Bioelectronic Systems for Sensing of Biorecognition Events Based on Nanoparticles 205

IX

X

Contents

14.3 14.3.1 14.3.2 14.4

Biomaterial-based Nanocircuitry 215 Protein-based Nanocircuitry 216 DNA as Functional Template for Nanocircuitry 218 Conclusions and Perspectives 221

Part III DNA-based Nanostructures 15

15.1 15.1.1 15.1.2 15.1.3 15.1.4 15.1.5 15.1.6 15.2 15.2.1 15.2.2 15.2.3 15.2.4 15.3

DNA–Protein Nanostructures Christof M. Niemeyer Overview 227 Introduction 227

227

Oligonucleotide–Enzyme Conjugates 228 DNA Conjugates of Binding Proteins 229 Noncovalent DNA–Streptavidin Conjugates 231 Multifunctional Protein Assemblies 234 DNA–Protein Conjugates in Microarray Technologies 236 Methods 238 Conjugation of Nucleic Acids and Proteins 238 Immuno-PCR 239 Supramolecular Assembly 240 DNA-directed Immobilization 240 Outlook 241

16

DNA-templated Electronics Erez Braun and Uri Sivan

16.1 16.2 16.3 16.4

Introduction and Background 244 DNA-templated Electronics 246 Sequence-specific Molecular Lithography 249 Summary and Perspectives 253

17

Biomimetic Fabrication of DNA-based Metallic Nanowires and Networks Michael Mertig and Wolfgang Pompe Introduction 256 Template Design 258 DNA as a Biomolecular Template 258 Integration of DNA into Microelectronic Contact Arrays 258 DNA Branching for Network Formation 261 Metallization 262 Controlled Cluster Growth on DNA Templates 263

17.1 17.2 17.2.1 17.2.2 17.2.3 17.3 17.3.1 17.3.2 17.4 17.5

244

First-Principle Molecular Dynamics Calculations of DNA Metallization 267 Conductivity Measurements on Metalized DNA Wires 270 Conclusions and Outlook 272

256

Contents

17.6 17.6.1 17.6.2 17.6.3

Methods 274 Site-Specific DNA Attachment 274 DNA Junctions 274 DNA Metallization 274

18

Mineralization in Nanostructured Biocompartments: Biomimetic Ferritins For High-Density Data Storage 278 Eric L. Mayes and Stephen Mann Overview 278 Biomimetic Ferritins 279 High-Density Magnetic Data Storage 280 Methods 282 Results 283 Outlook 285

18.1 18.2 18.3 18.4 18.5 18.6 19

19.1 19.1.1 19.1.2 19.1.3 19.1.4 19.1.4.1 19.1.4.2 19.1.5 19.1.6 19.2 19.2.1 19.2.2 19.2.3 19.2.4 19.3 19.3.1 19.3.2 20

20.1 20.2 20.3 20.4 20.5 20.6

DNA–Gold-Nanoparticle Conjugates 288 C. Shad Thaxton and Chad A. Mirkin Overview 288 Introduction 288 Nanoparticles 289

DNA-functionalized Gold Nanoparticles 291 Nanoparticle Based DNA and RNA Detection Assays 292 Homogeneous DNA Detection 292 Chip-based (Heterogeneous) DNA Detection Assays 293 DNA-Nanoparticle Detection of Proteins: Biobarcodes 299 Conclusion 300 The Essentials: Methods and Protocols 301 Nanoparticle Synthesis 301 DNA-functionalized Au-NP Probe Synthesis 301 Chip Functionalization with DNA Target “Capture” Strands 303 Typical Assay Design 304 Outlook 304 Challenges Ahead 304 Academic and Commercial Applications 305 DNA Nanostructures for Mechanics and Computing: Nonlinear Thinking with Life’s Central Molecule 308 Nadrian C. Seeman Overview 308 Introduction 308 DNA Arrays 311 DNA Nanomechanical Devices 313 DNA-based Computation 315 Summary and Outlook 317

XI

XII

Contents

21

21.1 21.2 21.3 21.3.1 21.3.2 21.3.3 21.3.4 21.3.5 21.3.6 21.4 21.5

Nanoparticles as Non-Viral Transfection Agents 319 M. N. V. Ravi Kumar, Udo Bakowsky, and Claus-Michael Lehr Introduction to Gene Delivery 319 Nanoparticles for Drug and Gene Targeting 321

Nonviral Nanomaterials in Development and Testing 321 Chitosan 321 Liposomes and Solid Lipids 327 Poly-l-Lysine and Polyethylenimines 332 Poly(lactide-co-glycolide) 334 Silica 335 Block Copolymers 336 Setbacks and Strategies to Improve Specific Cell Uptake of Nonviral Systems 338 Prospects for Nonviral Nanomaterials 338

Part IV Nanoanalytics 22

22.1 22.2 22.3 23

23.1 23.2 23.3 23.4 23.4.1 23.4.2 23.4.3 23.5 23.6 23.7 23.8 23.9 23.9.1 23.9.2 23.9.3 23.9.4 23.10 23.11 23.12

Luminescent Quantum Dots for Biological Labeling Xiaohu Gao and Shuming Nie Overview 343 Methods 348 Outlook 349

343

Nanoparticle Molecular Labels 353 James F. Hainfeld, Richard D. Powell, and Gerhard W. Hacker Introduction 353 Immunogold-Silver Staining: A History 354 Combined Fluorescent and Gold Probes 356 Methodology 357 Choice of Gold and AMG Type 357 Iodinization 359 Sensitivity 359

Applications for the Microscopical Detection of Antigens 359 Detection of Nucleic Acid Sequences 360 Applications for Microscopical Detection of Nucleic Acids 361 Technical Guidelines and Laboratory Protocols 362 Gold Derivatives of Other Biomolecules 362 Protein Labeling 363 Gold Cluster-labeled Peptides 364 Gold Cluster Conjugates of Other Small Molecules 364 Gold–Lipids: Metallosomes 365 Larger Covalent Particle Labels 366 Gold Targeted to His Tags 367 Enzyme Metallography 368

Contents

23.13 23.14 23.14.1 23.14.2 23.14.3 23.15 23.15.1 23.15.2 23.15.3 24

24.1 24.2 24.2.1 24.2.1.1 24.2.1.2 24.2.1.3 24.2.2 24.2.2.1 24.2.2.2 24.2.2.3 24.2.3 24.2.4 24.3 24.3.1 24.3.2 24.4 24.4.1 24.4.2 25

25.1 25.1.1 25.1.2 25.1.3 25.1.4 25.1.5 25.1.6 25.1.7 25.1.8 25.2

Gold Cluster Nanocrystals 369 Gold Cluster–Oligonucleotide Conjugates: Nanotechnology Applications 369 DNA Nanowires 370 3-D Nanostructured Mineralized Biomaterials 370 Gold-quenched Molecular Beacons 372 Other Metal Cluster Labels 372 Platinum and Palladium 373 Tungstates 374 Iridium 375 Surface Biology: Analysis of Biomolecular Structure by Atomic Force Microscopy and Molecular Pulling 387 Emin Oroudjev, Signe Danielsen and Helen G. Hansma Introduction 387 Recent Results 388 DNA 388 DNA Condensation 388 DNA Sequences Recognized by Mica 390 Drug-binding to Single ds-DNA Molecules 390 Proteins 390 Prion Proteins 391 Membrane Proteins 393 Spider Silk 394 Fossils 394 Science and Nature 394 Methodology 395 The Probe 396 The Sample 397 The Future 398 Unity or Diversity? 398 World-wide Research 399 Force Spectroscopy Markus Seitz Overview 404

404

Dynamic Force Spectroscopy of Specific Biomolecular Bonds 405 Force Spectroscopy and Force Microscopy of Cell Membranes 409 Protein (Un-)folding 409 Elasticity of Individual Polymer Molecules 412 DNA Mechanics 414 DNA–Protein Interactions 416 Molecular Motors 417 Synthetic Functional Polymers 418 Methods 419

XIII

XIV

Contents

25.2.1 25.2.2 25.2.3 25.2.4 25.2.5 25.3

AFM Cantilevers 419 Microneedles 421 Optical Tweezers 421 Magnetic Tweezers 422 Biomembrane Force Probe 423 Outlook 424

26

Biofunctionalized Nanoparticles for Surface-Enhanced Raman Scattering and Surface Plasmon Resonance 429 Mahnaz El-Kouedi and Christine D. Keating Overview 429 Introduction 429 Applications in SPR 430 Nanoparticle Substrates 430 Planar Substrates 431 Applications in SERS 434 Proteins 434 Nucleic Acids 437 Methods 439 Planar SPR Substrate Preparation 439 Metal Nanoparticles 439 Bioconjugates 439 General Comments 440 Future Outlook 440

26.1 26.1.1 26.1.2 26.1.2.1 26.1.2.2 26.1.3 26.1.3.1 26.1.3.2 26.2 26.2.1 26.2.2 26.2.3 26.2.4 26.3 27

27.1 27.2 27.2.1 27.2.2 27.2.2.1 27.2.2.2 27.2.3 27.2.3.1 27.2.3.2 27.2.3.3 27.2.3.4 27.2.4 27.2.4.1 27.2.4.2 27.2.4.3 27.3

Bioconjugated Silica Nanoparticles for Bioanalytical Applications Timothy J. Drake, Xiaojun Julia Zhao, and Weihong Tan Overview 444 Methods 445 Fabrication 445 Particle Probes 447 Dye-doped Silica Nanoparticles 447 Magnetic Silica Nanoparticles 449 Biofunctionalization of Silica Nanoparticles 449 Amino-Group Cross-Linkage 450 Avidin–Biotin Linking Bridge 451 Disulfide-coupling Chemical Binding 451 Cyanogen Bromide Modification 451 Bioanlytical Applications for Silica Nanoparticles 452 Cellular Labeling/Detection 452 DNA Analysis 453 Ultrasensitive DNA Detection 453 Outlook 454 Index 458

444

Preface

Preface Nanobiotechnology is a young and rapidly evolving field of research at the crossroads of biotechnology and nanoscience, two interdisciplinary areas each of which combines advances in science and engineering. Although often considered one of the key technologies of the 21st century, nanobiotechnology is still in a fairly embryonic state. Topical areas of research are still being defined, and the entire scope of technological applications cannot be imagined. At present, nanobiotechnology is a field that concerns the utilization of biological systems optimized through evolution, such as cells, cellular components, nucleic acids, and proteins, to fabricate functional nanostructured and mesoscopic architectures comprised of organic and inorganic materials. Nanobiotechnology also concerns the refinement and application of instruments, originally designed to generate and manipulate nanostructured materials, to basic and applied studies of fundamental biological processes. This book is intended to provide the first systematic and comprehensive framework of specific research topics in nanobiotechnology. To this end, the current state-of-the-art has been accumulated in 27 chapters, all of them written by experts in their fields. Each of the chapters consists of three sections, (i) an overview which gives a brief but comprehensive survey on the topic, (ii) a methods section which orients the reader to the most important techniques relevant for the specific topic discussed, and (iii) an outlook discussing academic and commercial applications as well as experimental challenges to be solved. Nanobiotechnology: Concepts, Applications and Perspectives combines contributions from analytical, bioorganic, and bioinorganic chemistry, physics, molecular and cell biology, and materials science in an attempt to give the reader a feel for the full scope of current and potential future developments. The articles in this volume clearly emphasize the high degree of interdisciplinary research that forms the backbone of this joint-venture of biotechnology and nanoscience. The book is divided into four main sections. The first concerns interphase systems pertaining to biocompatible inorganic devices for medical implants, microfluidic systems for handling biological components in analytical lab-on-a-chip applications, and microelectronic silicon substrates for the investigation and manipulation of neuronal cells. Moreover, two chapters describe methodologies regarding the microcontact printing of proteins and the use of nanostructured substrates to study basic principles of cell adhesion. Nanobiotechnology. Edited by Christof Niemeyer, Chad Mirkin Copyright c 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-30658-7

XV

XVI

Preface

The second section is devoted to protein-based nanostructures. Individual chapters concern the use of specific proteins, such as S-layers to be used as building blocks and templates for generating functional nanostructures, bacteriorhodopsin for photochromic applications, protein nanopores as nanoscopic cavities for analytical and synthetic tasks, and biomolecular motors for the translocation of cargo in synthetic environments. The use of a variety of functional proteins as transducers and amplifiers of biomolecular recognition events is described in the chapters on nanobioelectronic devices and polymer nanocontainers. Contributions concerning the microbial production of inorganic nanoparticles and magnetosomes as well as the discussion of genetic approaches to generate proteins for the specific organization of particles provide insight into the body of classical biotechnology, implemented in nanobiotechnology. In the third section, DNA-based nanostructures are described, beginning with semisynthetic conjugates of DNA and proteins, which link the advantages of nucleic acids to the unlimited functionality of proteins. Three contributions concern the use of the topographic and electrostatic properties of DNA and proteins for the templated growth of inorganic materials. Hybrid conjugates of gold nanoparticles and DNA oligomers are described with a focus on their applications in the high sensitivity analyses of nucleic acids. Finally, the use of pure DNA molecules for applications in nanomechanics and computing is discussed. The fourth section deals with the area of nanoanalytics, which currently includes the majority of commercial products in nanobiotechnology. In particular, four chapters describe the use of metal or semiconductor nanoparticles, supplemented with nucleic acid- and protein-based recognition groups, for biolabeling, histochemical applications and for signal enhancement in optical detection methods. Nanoparticles are also employed as carriers for genetic material in the non-viral transfection of cells. To exemplify the use of modern nano-instrumentation for the study of biological systems, two chapters describe the use of the scanning probe microscope, the key instrument in nanotechnologies, for investigating biomolecular structure, conformation and reactivity. The purpose of Nanobiotechnology: Concepts, Applications and Perspectives is to provide both a broad survey of the field and also instruction and inspiration to all levels of scientists, from novices to those intimately engaged in this new and exciting field of research. Although the collection of articles addresses numerous scientific and technical challenges ahead, the future of nanobiotechnology is bright and appears to be limited, at present, only by imagination. Dortmund, November 2003 Evanston, November 2003

Christof M. Niemeyer Chad A. Mirkin

Contributors

Contributors Absar Ahmad Biochemical Sciences Divison National Chemical Laboratory 411 008 Pune India Udo Bakowsky Department of Biopharmaceutics and Pharmaceutical Technology Saarland University Im Stadtwald 66123 Saarbrücken Germany Holger Bartos STEAG microParts GmbH Hauert 7 44227 Dortmund Germany Hagan Bayley Department of Chemistry University of Oxford Mansfield Road Oxford, OX1 3TA UK Dennis A. Bazylinski Department of Physics California Polytechnic State University San Luis Obispo, CA 93407 USA

Samantha M. Benito Department of Chemistry University of Basel Klingelbergstrasse 80 4056 Basel Switzerland Orit Braha Department of Chemistry University of Oxford Mansfield Road Oxford, OX1 3TA UK Erez Braun Department of Physics Solid State Institute Technion-Israel Institute of Technology 32000 Haifa Israel Stanley Brown Department of Molecular Cell Biology University of Copenhagen Øster Farimagsgade 2A 1353 Copenhagen K Denmark

Nanobiotechnology. Edited by Christof Niemeyer, Chad Mirkin Copyright c 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-30658-7

XVII

XVIII

Contributors

Stephen Cheley Texas A&M University Health Science Center Medical Biochemistry and Genetics 440 Reynolds Medical Building College Station, TX 77843-1114 USA Signe Danielsen Norwegian University of Science and Technology Department of Physics Høgskoleringen 5 7491 Trondheim Norway Emmanuel Delamarche IBM Research Zürich Research Laboratory Säumerstrasse 4 8803 Rüschlikon Switzerland Stefan Diez Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstrasse 108 01307 Dresden Germany Timothy J. Drake Center for Research at the Bio-nano Interface Department of Chemistry, McKnight Brain Institute, University of Florida, Gainesville, FL 32611 USA

Eva-Maria Egelseer Center for Ultrastructure Research and Ludwig Boltzmann Institute for Molecular Nanotechnology University of Natural Resources and Applied Life Sciences Gregor-Mendel-Straße 33 1180 Wien Austria Mahnaz El-Kouedi Department of Chemistry, The Pennsylvania State University University Park, PA 16802 USA Richard B. Frankel Department of Physics California Polytechnic State University San Luis Obispo, CA 93407 USA Xiaohu Gao Department of Biomedical Engineering Emory University School of Medicine 1639 Pierce Drive Atlanta, GA 30322 USA Friedrich Götz Gelsenkirchen University of Applied Sciences Neidenburger Str. 43 45877 Gelsenkirchen Germany Alexandra Graff Department of Chemistry University of Basel Klingelbergstrasse 80 4056 Basel Switzerland

Contributors

Li-Qun Gu Texas A&M University Health Science Center Medical Biochemistry and Genetics 440 Reynolds Medical Building College Station, TX 77843-1114 USA Gerhard W. Hacker Research Institute for Frontier Questions of Medicine and Biotechnology St. Johanns-Hospital Landeskliniken Salzburg Muellner Hauptstr. 48 5020 Salzburg Austria James F. Hainfeld Brookhaven National Laboratory Department of Biology Upton, NY 11973 USA Norbert Hampp Fachbereich Chemie Philipps-Universität Marburg Hans-Meerwein-Straße, Geb. H 35032 Marburg Germany Helen G. Hansma Physics Department University of California Santa Barbara, CA 93106 USA John H. Helenius Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstrasse 108 01307 Dresden Germany

Jonathon Howard Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstrasse 108 01307 Dresden Germany Eugenii Katz Department of Organic Chemistry Hebrew University Givat Ram 91904 Jerusalem Israel Christine D. Keating Department of Chemistry, The Pennsylvania State University University Park, PA 16802 USA M. Islam Khan Biochemical Sciences Divison National Chemical Laboratory 411 008 Pune India Rajiv Kumar Catalysis Divison National Chemical Laboratory 411 008 Pune India M. N. V. Ravi Kumar Department of Pharmaceutics NIPER SAS Nagar, Sector 67 160 062 Mohali India

XIX

XX

Contributors

Claus-Michael Lehr Department of Biopharmaceutics and Pharmaceutical Technology Saarland University Im Stadtwald 66123 Saarbrücken Germany Stephen Mann School of Chemistry University of Bristol Bristol BS8 1TS UK Eric Mayes NanoMagnetics Ltd. 108 Longmead Road Bristol BS16 7FG UK Wolfgang Meier Department of Chemistry University of Basel Klingelbergstrasse 80 4056 Basel Switzerland Michael Mertig Technische Universität Dresden Institut für Werkstoffwissenschaft 01062 Dresden Germany Chad A. Mirkin Department of Chemistry & Institute for Nanotechnology Northwestern University 2145 Sheridan Road Evanston, IL 60208-3113 USA

Shuming Nie Department of Biomedical Engineering Emory University School of Medicine 1639 Pierce Drive Atlanta, GA 30322 USA Christof M. Niemeyer Universität Dortmund Fachbereich Chemie Biologisch-Chemische Mikrostrukturtechnik Otto-Hahn-Str. 6 44227 Dortmund Germany Dieter Oesterhelt Max-Planck Institute for Biochemistry Am Klopferspitz 18A 82152 Planegg-Martinsried Germany Andreas Offenhäusser Institute for Thin Films and Interfaces, Bio- and Chemosensors Research Centre Jülich 52425 Jülich Germany Emin Oroudjev Department of Physics University of California Santa Barbara, CA 93106 USA Ralf-Peter Peters STEAG microParts GmbH Hauert 7 44227 Dortmund Germany

Contributors

Wolfgang Pompe Technische Universität Dresden Institut für Werkstoffwissenschaft 01062 Dresden Germany

Nadrian C. Seeman Department of Chemistry New York University New York, NY 10003 USA

Richard D. Powell Nanoprobes, Incorporated 95 Horseblock Road Yaphank, NY 11980-9710 USA

Markus Seitz Department of Applied Physics Ludwig-Maximilians-Universität Amalienstrasse 54 80799 München Germany

Dietmar Pum Center for Ultrastructure Research and Ludwig Boltzmann Institute for Molecular Nanotechnology University of Natural Resources and Applied Life Sciences Gregor-Mendel-Straße 33 1180 Wien Austria Murali Sastry Materials Chemistry Divison National Chemical Laboratory 411 008 Pune India Thomas Sawitowski Institut für Anorganische Chemie Universität GH Essen Universitätsstr. 5-7 45117 Essen Germany Bernhard Schuster Center for Ultrastructure Research and Ludwig Boltzmann Institute for Molecular Nanotechnology University of Natural Resources and Applied Life Sciences Gregor-Mendel-Straße 33 1180 Wien Austria

Uri Sivan Department of Physics Solid State Institute Technion-Israel Institute of Technology 32000 Haifa Israel Uwe B. Sleytr Center for Ultrastructure Research and Ludwig Boltzmann Institute for Molecular Nanotechnology University of Natural Resources and Applied Life Sciences Gregor-Mendel-Straße 33 1180 Wien Austria Joachim P. Spatz Institut für Physikalische Chemie Universität Heidelberg INF 253 69120 Heidelberg Germany Weihong Tan Center for Research at the Bio-nano Interface Department of Chemistry McKnight Brain Institute University of Florida Gainesville, FL 32611 USA

XXI

XXII

Contributors

C. Shad Thaxton Northwestern University 2145 Sheridan Road Evanston, IL 60208 USA Corinne Verbert Department of Chemistry University of Basel Klingelbergstrasse 80 4056 Basel Switzerland Angela K. Vogt Max-Planck Institute for Polymer Research Ackermannweg 10 55228 Mainz Germany

Itamar Willner Department of Organic Chemistry Hebrew University Givat Ram 91904 Jerusalem Israel Xiaojun Julia Zhao Center for Research at the Bio-nano Interface Department of Chemistry, McKnight Brain Institute, University of Florida, Gainesville, FL 32611 USA