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. K aA, Weinheim
ISBN 3-527-30658-7
G
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
cmn@chemie.uni-dortmund.de
Prof. Dr. Chad A. Mirkin
Department of Chemistry &
Institute for Nanotechnology
Northwestern University
2145 Sheridan Road
Evanston, IL 60208-3113
USA
camirkin@chem.northwestern.edu
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).
This book was carefully produced. Never-
theless, 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
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 permis-
sion 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
Part I
Interphase Systems
1
Biocompatible Inorganic Devices
1
Thomas Sawitowski
1.1
Introduction
1
1.2
Implant Coatings
1
1.2.1
Stents
2
1.2.2
Seeds
7
1.3
Conclusion
10
2
Microfluidics Meets Nano:
Lab-on-a-Chip Devices and their Potential for Nanobiotechnology
13
Holger Bartos, Friedrich Götz, and Ralf-Peter Peters
2.1
Introduction
13
2.2
Overview
13
2.2.1
Definition and History
13
2.2.2
Advantages of Microfluidic Devices
14
2.2.3
Concepts for Microfluidic Devices
15
2.2.4
Fluid Transport
17
2.2.5
Stacking and Sealing
18
2.3
Methods
19
2.3.1
Materials for the Manufacture of Microfluidic Components
19
2.3.1.1
Silicon
19
2.3.1.2
Glass
19
2.3.1.3
Polymers
20
2.3.2
Fluidic Structures
21
2.3.3
Fabrication Methods
23
2.3.4
Surface Modifications
23
2.3.5
Spotting
25
2.3.6
Detection Mechanisms
26
2.4
Outlook
26
V
Contents
Nanobiotechnology. Edited by Christof Niemeyer, Chad Mirkin
Copyright
c 2004 WILEY-VCH Verlag GmbH & Co. K aA, Weinheim
ISBN 3-527-30658-7
G
3
Microcontact Printing of Proteins
31
Emmanuel Delamarche
3.1
Introduction
31
3.2
Strategies for Printing Proteins on Surfaces
33
3.2.1
Contact Processing with Hydrogel Stamps
33
3.2.2
Microcontact Printing
33
3.2.3
Affinity-Contact Printing
34
3.3
Microcontact Printing Polypeptides and Proteins
34
3.3.1
Printing One Type of Biomolecule
35
3.3.2
Substrates
36
3.3.3
Resolution and Contrast of the Patterns
38
3.4
Activity of Printed Biomolecules
40
3.5
Printing Multiple Types of Proteins
42
3.5.1
Additive and Subtractive Printing
42
3.5.2
Parallel Inking and Printing of Multiple Proteins
44
3.5.3
Affinity-Contact Printing
44
3.6
Methods
45
3.6.1
Molds and Stamps
45
3.6.2
Surface Chemistry of Stamps
47
3.6.3
Inking Methods
47
3.6.4
Treatments of Substrates
48
3.6.5
Printing
48
3.6.6
Characterization of the Printed Patterns
49
3.7
Outlook
49
4
Cell–Nanostructure Interactions
53
Joachim P. Spatz
4.1
Introduction
53
4.2
Methods
56
4.3
Outlook
63
5
Defined Networks of Neuronal Cells in Vitro
66
Andreas Offenhäusser and Angela K. Vogt
5.1
Introduction
66
5.2
Overview: Background and History
67
5.2.1
Physiology of Information Processing within Neuronal Networks
67
5.2.2
Topographical Patterning
67
5.2.3
Chemical Patterning
68
5.3
Methods
69
5.3.1
Topographical Patterning
69
5.3.2
Photolithographic Patterning
70
5.3.3
Photochemical Patterning
70
5.3.4
Microcontact Printing
71
5.4
Outlook
72
VI
Contents
Part II Protein-based Nanostructures
6
S-Layers
77
Uwe B. Sleytr, Eva-Maria Egelseer, Dietmar Pum, and Bernhard Schuster
6.1
Overview
77
Abbreviations
77
6.1.1
Chemistry and Structure
78
6.1.2
Genetics and Secondary Cell-Wall Polymers
80
6.1.3
Assembly
82
6.1.3.1
Self-Assembly in Suspension
82
6.1.3.2
Recrystallization at Solid Supports
83
6.1.3.3
Recrystallization at the Air/Water Interface
and on Langmuir Lipid Films
83
6.2
Methods
84
6.2.1
Diagnostics
84
6.2.2
Lipid Chips
85
6.2.3
S-Layers as Templates for the Formation of
Regularly Arranged Nanoparticles
87
6.3
Outlook
89
7
Engineered Nanopores
93
Hagan Bayley, Orit Braha, Stephen Cheley, and Li-Qun Gu
7.1
Overview
93
7.1.1
What is a Nanopore?
93
7.1.2
Engineering Nanopores
96
7.1.3
What Can a Nanopore Do?
97
7.1.4
What are the Potential Applications of Nanopores?
100
7.1.5
Keeping Nanopores Happy
103
7.2
Methods
104
7.2.1
Protein Production
104
7.2.2
Protein Engineering
104
7.2.3
Electrical Recording
105
7.2.4
Other Systems
105
7.3
Outlook
106
7.3.1
Rugged Pores
106
7.3.2
Supported Bilayers
106
7.3.3
Membrane Arrays
106
7.3.4
Alternative Protein Pores
107
7.3.5
Pores with New Attributes and Applications
108
7.3.6
Theory
108
8
Genetic Approaches to Programmed Assembly
113
Stanley Brown
8.1
Introduction
113
8.2
Order from Chaos
113
VII
Contents
8.3
Monitoring Enrichment
116
8.4
Quantification of Binding and Criteria for Specificity
119
8.5
Unselected Traits and Control of Crystallization/Reactivity
119
8.6
Dominant Traits, Interpretation of Gain-of-Function Mutants
120
8.7
Interpretation and Requirement for Consensus Sequences
120
8.8
Sizes of Proteins and Peptides
122
8.9
Mix and Match, Fusion Proteins, and Context-Dependence
122
8.10
Mix and Match, Connecting Structures
122
8.11
Outlook
123
9
Microbial Nanoparticle Production
126
Murali Sastry, Absar Ahmad, M. Islam Khan, and Rajiv Kumar
9.1
Overview
126
9.2
Outlook
133
10
Magnetosomes: Nanoscale Magnetic Iron Minerals in Bacteria
136
Richard B. Frankel and Dennis A. Bazylinski
10.1
Introduction
136
10.1.1
Magnetotactic Bacteria
136
10.1.2
Magnetosomes
137
10.1.3
Cellular Magnetic Dipole and Magnetotaxis
138
10.1.4
Magneto-Aerotaxis
139
10.1.5
Magnetite Crystals in Magnetosomes
140
10.1.6
Greigite Crystals in Magnetosomes
141
10.1.7
Biochemistry and Gene Expression in Magnetosome Formation
141
10.1.8
Applications of Magnetosomes
143
10.2
Research Methods
143
10.3
Conclusion and Future Research Directions
143
11
Bacteriorhodopsin and its Potential in Technical Applications
146
Norbert Hampp and Dieter Oesterhelt
11.1
Introduction
146
11.2
Overview: The Molecular Properties of Bacteriorhodopsin
147
11.2.1
Haloarchaea and their Retinal Proteins
147
11.2.2
Structure and Function of Bacteriorhodopsin
150
11.2.3
Genetic Modification of Bacteriorhodopsin
153
11.2.4
Biotechnological Production of Bacteriorhodopsins
154
11.3
Overview: Technical Applications of Bacteriorhodopsin
155
11.3.1
Photoelectric Applications
156
11.3.1.1
Preparation of Oriented PM Layers
156
11.3.1.2
Interfacing the Proton-Motive Force
158
11.3.1.3
Application Examples
158
11.3.2
Photochromic Applications
159
11.3.2.1
Photochromic Properties of Bacteriorhodopsin
159
11.3.2.2
Preparation of Bacteriorhodopsin Films
161
VIII
Contents
11.3.2.3
Interfacing the Photochromic Changes
161
11.3.2.4
Application Examples
161
11.3.3
Applications in Energy Conversion
163
11.4
Methods
165
11.5
Outlook
165
12
Polymer Nanocontainers
168
Alexandra Graff, Samantha M. Benito, Corinne Verbert, and Wolfgang Meier
12.1
Introduction
168
12.2
Overview
168
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
Biomolecular Motors Operating in Engineered Environments
185
Stefan Diez, Jonne H. Helenius, and Jonathon Howard
13.1
Overview
185
13.2
Methods
190
13.2.1
General Conditions for Motility Assays
190
13.2.2
Temporal Control
191
13.2.3
Spatial Control
191
13.2.4
Connecting to Cargoes and Surfaces
194
13.3
Outlook
195
14
Nanoparticle–Biomaterial Hybrid Systems
for Bioelectronic Devices and Circuitry
200
Eugenii Katz and Itamar Willner
14.1
Introduction
200
14.2
Biomaterial–Nanoparticle Systems for Bioelectronic
and Biosensing Applications
202
14.2.1
Bioelectronic Systems Based on Nanopaticle–Enzyme Hybrids
202
14.2.2
Bioelectronic Systems for Sensing of
Biorecognition Events Based on Nanoparticles
205
IX
Contents
14.3
Biomaterial-based Nanocircuitry
215
14.3.1
Protein-based Nanocircuitry
216
14.3.2
DNA as Functional Template for Nanocircuitry
218
14.4
Conclusions and Perspectives
221
Part III DNA-based Nanostructures
15
DNA–Protein Nanostructures
227
Christof M. Niemeyer
15.1
Overview
227
15.1.1
Introduction
227
15.1.2
Oligonucleotide–Enzyme Conjugates
228
15.1.3
DNA Conjugates of Binding Proteins
229
15.1.4
Noncovalent DNA–Streptavidin Conjugates
231
15.1.5
Multifunctional Protein Assemblies
234
15.1.6
DNA–Protein Conjugates in Microarray Technologies
236
15.2
Methods
238
15.2.1
Conjugation of Nucleic Acids and Proteins
238
15.2.2
Immuno-PCR
239
15.2.3
Supramolecular Assembly
240
15.2.4
DNA-directed Immobilization
240
15.3
Outlook
241
16
DNA-templated Electronics
244
Erez Braun and Uri Sivan
16.1
Introduction and Background
244
16.2
DNA-templated Electronics
246
16.3
Sequence-specific Molecular Lithography
249
16.4
Summary and Perspectives
253
17
Biomimetic Fabrication of DNA-based Metallic Nanowires and Networks
256
Michael Mertig and Wolfgang Pompe
17.1
Introduction
256
17.2
Template Design
258
17.2.1
DNA as a Biomolecular Template
258
17.2.2
Integration of DNA into Microelectronic Contact Arrays
258
17.2.3
DNA Branching for Network Formation
261
17.3
Metallization
262
17.3.1
Controlled Cluster Growth on DNA Templates
263
17.3.2
First-Principle Molecular Dynamics Calculations
of DNA Metallization
267
17.4
Conductivity Measurements on Metalized DNA Wires
270
17.5
Conclusions and Outlook
272
X
Contents
17.6
Methods
274
17.6.1
Site-Specific DNA Attachment
274
17.6.2
DNA Junctions
274
17.6.3
DNA Metallization
274
18
Mineralization in Nanostructured Biocompartments:
Biomimetic Ferritins For High-Density Data Storage
278
Eric L. Mayes and Stephen Mann
18.1
Overview
278
18.2
Biomimetic Ferritins
279
18.3
High-Density Magnetic Data Storage
280
18.4
Methods
282
18.5
Results
283
18.6
Outlook
285
19
DNA–Gold-Nanoparticle Conjugates
288
C. Shad Thaxton and Chad A. Mirkin
19.1
Overview
288
19.1.1
Introduction
288
19.1.2
Nanoparticles
289
19.1.3
DNA-functionalized Gold Nanoparticles
291
19.1.4
Nanoparticle Based DNA and RNA Detection Assays
292
19.1.4.1
Homogeneous DNA Detection
292
19.1.4.2
Chip-based (Heterogeneous) DNA Detection Assays
293
19.1.5
DNA-Nanoparticle Detection of Proteins: Biobarcodes
299
19.1.6
Conclusion
300
19.2
The Essentials: Methods and Protocols
301
19.2.1
Nanoparticle Synthesis
301
19.2.2
DNA-functionalized Au-NP Probe Synthesis
301
19.2.3
Chip Functionalization with DNA Target “Capture” Strands
303
19.2.4
Typical Assay Design
304
19.3
Outlook
304
19.3.1
Challenges Ahead
304
19.3.2
Academic and Commercial Applications
305
20
DNA Nanostructures for Mechanics and Computing:
Nonlinear Thinking with Life’s Central Molecule
308
Nadrian C. Seeman
20.1
Overview
308
20.2
Introduction
308
20.3
DNA Arrays
311
20.4
DNA Nanomechanical Devices
313
20.5
DNA-based Computation
315
20.6
Summary and Outlook
317
XI
Contents
21
Nanoparticles as Non-Viral Transfection Agents
319
M. N. V. Ravi Kumar, Udo Bakowsky, and Claus-Michael Lehr
21.1
Introduction to Gene Delivery
319
21.2
Nanoparticles for Drug and Gene Targeting
321
21.3
Nonviral Nanomaterials in Development and Testing
321
21.3.1
Chitosan
321
21.3.2
Liposomes and Solid Lipids
327
21.3.3
Poly-l-Lysine and Polyethylenimines
332
21.3.4
Poly(lactide-co-glycolide)
334
21.3.5
Silica
335
21.3.6
Block Copolymers
336
21.4
Setbacks and Strategies to Improve Specific Cell Uptake
of Nonviral Systems
338
21.5
Prospects for Nonviral Nanomaterials
338
Part IV Nanoanalytics
22
Luminescent Quantum Dots for Biological Labeling
343
Xiaohu Gao and Shuming Nie
22.1
Overview
343
22.2
Methods
348
22.3
Outlook
349
23
Nanoparticle Molecular Labels
353
James F. Hainfeld, Richard D. Powell, and Gerhard W. Hacker
23.1
Introduction
353
23.2
Immunogold-Silver Staining: A History
354
23.3
Combined Fluorescent and Gold Probes
356
23.4
Methodology
357
23.4.1
Choice of Gold and AMG Type
357
23.4.2
Iodinization
359
23.4.3
Sensitivity
359
23.5
Applications for the Microscopical Detection of Antigens
359
23.6
Detection of Nucleic Acid Sequences
360
23.7
Applications for Microscopical Detection of Nucleic Acids
361
23.8
Technical Guidelines and Laboratory Protocols
362
23.9
Gold Derivatives of Other Biomolecules
362
23.9.1
Protein Labeling
363
23.9.2
Gold Cluster-labeled Peptides
364
23.9.3
Gold Cluster Conjugates of Other Small Molecules
364
23.9.4
Gold–Lipids: Metallosomes
365
23.10
Larger Covalent Particle Labels
366
23.11
Gold Targeted to His Tags
367
23.12
Enzyme Metallography
368
XII
Contents
23.13
Gold Cluster Nanocrystals
369
23.14
Gold Cluster–Oligonucleotide Conjugates:
Nanotechnology Applications
369
23.14.1
DNA Nanowires
370
23.14.2
3-D Nanostructured Mineralized Biomaterials
370
23.14.3
Gold-quenched Molecular Beacons
372
23.15
Other Metal Cluster Labels
372
23.15.1
Platinum and Palladium
373
23.15.2
Tungstates
374
23.15.3
Iridium
375
24
Surface Biology: Analysis of Biomolecular Structure
by Atomic Force Microscopy and Molecular Pulling
387
Emin Oroudjev, Signe Danielsen and Helen G. Hansma
24.1
Introduction
387
24.2
Recent Results
388
24.2.1
DNA
388
24.2.1.1
DNA Condensation
388
24.2.1.2
DNA Sequences Recognized by Mica
390
24.2.1.3
Drug-binding to Single ds-DNA Molecules
390
24.2.2
Proteins
390
24.2.2.1
Prion Proteins
391
24.2.2.2
Membrane Proteins
393
24.2.2.3
Spider Silk
394
24.2.3
Fossils
394
24.2.4
Science and Nature
394
24.3
Methodology
395
24.3.1
The Probe
396
24.3.2
The Sample
397
24.4
The Future
398
24.4.1
Unity or Diversity?
398
24.4.2
World-wide Research
399
25
Force Spectroscopy
404
Markus Seitz
25.1
Overview
404
25.1.1
Dynamic Force Spectroscopy of Specific Biomolecular Bonds
405
25.1.2
Force Spectroscopy and Force Microscopy of Cell Membranes
409
25.1.3
Protein (Un-)folding
409
25.1.4
Elasticity of Individual Polymer Molecules
412
25.1.5
DNA Mechanics
414
25.1.6
DNA–Protein Interactions
416
25.1.7
Molecular Motors
417
25.1.8
Synthetic Functional Polymers
418
25.2
Methods
419
XIII
Contents
25.2.1
AFM Cantilevers
419
25.2.2
Microneedles
421
25.2.3
Optical Tweezers
421
25.2.4
Magnetic Tweezers
422
25.2.5
Biomembrane Force Probe
423
25.3
Outlook
424
26
Biofunctionalized Nanoparticles for Surface-Enhanced
Raman Scattering and Surface Plasmon Resonance
429
Mahnaz El-Kouedi and Christine D. Keating
26.1
Overview
429
26.1.1
Introduction
429
26.1.2
Applications in SPR
430
26.1.2.1
Nanoparticle Substrates
430
26.1.2.2
Planar Substrates
431
26.1.3
Applications in SERS
434
26.1.3.1
Proteins
434
26.1.3.2
Nucleic Acids
437
26.2
Methods
439
26.2.1
Planar SPR Substrate Preparation
439
26.2.2
Metal Nanoparticles
439
26.2.3
Bioconjugates
439
26.2.4
General Comments
440
26.3
Future Outlook
440
27
Bioconjugated Silica Nanoparticles for Bioanalytical Applications
444
Timothy J. Drake, Xiaojun Julia Zhao, and Weihong Tan
27.1
Overview
444
27.2
Methods
445
27.2.1
Fabrication
445
27.2.2
Particle Probes
447
27.2.2.1
Dye-doped Silica Nanoparticles
447
27.2.2.2
Magnetic Silica Nanoparticles
449
27.2.3
Biofunctionalization of Silica Nanoparticles
449
27.2.3.1
Amino-Group Cross-Linkage
450
27.2.3.2
Avidin–Biotin Linking Bridge
451
27.2.3.3
Disulfide-coupling Chemical Binding
451
27.2.3.4
Cyanogen Bromide Modification
451
27.2.4
Bioanlytical Applications for Silica Nanoparticles
452
27.2.4.1
Cellular Labeling/Detection
452
27.2.4.2
DNA Analysis
453
27.2.4.3
Ultrasensitive DNA Detection
453
27.3
Outlook
454
Index
458
XIV
Contents
Preface
Nanobiotechnology is a young and rapidly evolving field of research at the cross-
roads 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 21
st
century, nanobiotechnology is still in a fairly embryo-
nic 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 func-
tional nanostructured and mesoscopic architectures comprised of organic and inor-
ganic materials. Nanobiotechnology also concerns the refinement and application of
instruments, originally designed to generate and manipulate nanostructured mate-
rials, to basic and applied studies of fundamental biological processes.
This book is intended to provide the first systematic and comprehensive frame-
work 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 back-
bone of this joint-venture of biotechnology and nanoscience.
The book is divided into four main sections. The first concerns interphase sys-
tems pertaining to biocompatible inorganic devices for medical implants, micro-
fluidic systems for handling biological components in analytical lab-on-a-chip ap-
plications, and microelectronic silicon substrates for the investigation and manip-
ulation 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.
XV
Preface
Nanobiotechnology. Edited by Christof Niemeyer, Chad Mirkin
Copyright
c 2004 WILEY-VCH Verlag GmbH & Co. K aA, Weinheim
ISBN 3-527-30658-7
G
The second section is devoted to protein-based nanostructures. Individual chap-
ters 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 analy-
tical 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 organiza-
tion of particles provide insight into the body of classical biotechnology, implemen-
ted in nanobiotechnology.
In the third section, DNA-based nanostructures are described, beginning with
semisynthetic conjugates of DNA and proteins, which link the advantages of nu-
cleic 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 ap-
plications 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, histo-
chemical 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 bio-
molecular structure, conformation and reactivity.
The purpose of Nanobiotechnology: Concepts, Applications and Perspectives is to pro-
vide both a broad survey of the field and also instruction and inspiration to all le-
vels 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 ap-
pears to be limited, at present, only by imagination.
Dortmund, November 2003
Christof M. Niemeyer
Evanston, November 2003
Chad A. Mirkin
XVI
Preface
Contributors
XVII
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. K aA, Weinheim
ISBN 3-527-30658-7
G
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
XIX
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
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
XXI
Contributors
Wolfgang Pompe
Technische Universität Dresden
Institut für Werkstoffwissenschaft
01062 Dresden
Germany
Richard D. Powell
Nanoprobes, Incorporated
95 Horseblock Road
Yaphank, NY 11980-9710
USA
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
Nadrian C. Seeman
Department of Chemistry
New York University
New York, NY 10003
USA
Markus Seitz
Department of Applied Physics
Ludwig-Maximilians-Universität
Amalienstrasse 54
80799 München
Germany
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
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
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