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Renat R. Letfullin · Thomas F. George

Computational
Nanomedicine and
Nanotechnology
Lectures with Computer Practicums
Computational Nanomedicine and Nanotechnology
Renat R. Letfullin • Thomas F. George

Computational
Nanomedicine
and Nanotechnology
Lectures with Computer Practicums
Renat R. Letfullin Thomas F. George
Rose-Hulman Institute of Technology University of Missouri-St. Louis
Terre Haute, IN, USA St. Louis, MO, USA

ISBN 978-3-319-43575-6 ISBN 978-3-319-43577-0 (eBook)

DOI 10.1007/978-3-319-43577-0

Library of Congress Control Number: 2016955820

© Springer International Publishing Switzerland 2016

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Preface

The field of nanomedicine as combined with nanotechnology is new and exciting,

with broad applications that are most relevant to our everyday lives and well-being.
This field, which combines multiple disciplines including medicine, biotechnology,
physics, optics/radiology, engineering, and pharmacy, has matured to the extent
that the time is ripe for this current textbook aimed at advanced undergraduate and
graduate students. In addition to its pedagogical nature, it is also of value to
research scientists who want to enter the field or even those who are already in
the field.
The book is organized according to chapters, and within each chapter is a set of
lectures in the form of both text for the student and PowerPoint for use by the
instructor, followed by homework exercises. Selected chapters also contain com-
puter practicums, including Maple codes and worked-out examples.
A special emphasis in the book is on how the combined use of chemistry and
light with nanoparticles can serve as treatments and therapies for cancer. This
includes nanodevices, nanophototherapies, nanodrug design, and laser heating of
nanoparticles and cell organelles.
Nanomedicine is a new science. Because of this, the material of this book is
mostly based on our own original journal papers, in some cases reproducing them in
the text of the chapters. Also, we provide very few references in the textbook. The
detailed list of references and reviews can be found in those original papers listed in
the book.
The first three chapters of the book are general introductory chapters introducing
the basic knowledge required for nanomedicine and nanotechnology study.
Chapter 1 presents the definition of nanomedicine and nanotechnology, introduces
the functions and properties of medical nanodevices, the design and fabrication of
nanorobots and nanoparticles, and discusses current and potential applications of
nanomedicine.
Chapter 2 gives a brief introduction to the structure of cancer cells and their
properties and how cancer cells differ from normal cells. The causes of cancer,

v
vi Preface

types of cancer, techniques for selective targeting of cancer, and gene therapy are
explained in detail in this chapter.
Chapter 3 introduces cancer therapy and detection techniques based on utilizing
the plasmonic nanoparticles. We discuss here the design and methods of activation
of the nanodrugs selectively delivered to the tumor site and the plasmon resonance
detection techniques using fiber optics.
The remaining chapters of the book are devoted to the modeling and computer
simulations of the complex phenomena of electromagnetic radiation interaction
with nanostructures, resulting in various accompanying effects around the
nanoparticles and nanoclusters. The results of these simulations are then discussed
in relation to the effective implementation of nanotherapy treatments. For example,
in Chap. 4 we model the light absorption properties of nanoparticles in the X-ray,
optical, and RF ranges of the spectrum.
In Chap. 5 we introduce a computer software and perform Lorenz-Mie diffrac-
tion simulations of absorption, scattering, and extinction efficiencies of different
types of nanoparticles as a function of particle size and the wavelength of radiation
in different surrounding biological media. Also, we calculate and then use the
differences in optical properties of normal and cancer cell organelles in order to
design new cancer detection and treatment methods.
Chapters 6 and 7 first introduce the thermodynamic model for nanoheat transfer
and then focus on the heating and cooling kinetics of nanoparticles by short and
ultrashort laser pulses in the femtosecond, picosecond, and nanosecond regimes.
Time dynamic simulations are performed for metal nanoparticles in a surrounding
biological medium as well as for healthy and cancerous cell organelles heated by
optical, RF, and X-ray pulses. Chapter 8 is devoted to spatial thermal fields
modeling and 3D simulations within and around a plasmonic nanoparticle and
cell organelles surrounded by a biological medium heated by radiation.
In Chap. 9 we perform optical, thermal, kinetic, and dynamic modeling
to develop and test new ideas and new dynamic modes in selective
nanophotothermolysis, involving nanocluster aggregation in living cells,
nanobubble overlapping around heated intracellular nanoparticles/clusters, and
the laser thermal explosion mode of single nanoparticles—“nano-bombs”—
delivered to the cells.
A goal of plasmonic laser nanosurgery/nanoablation is to deliver extremely
precise heat blasts in programmed patterns to cancer cells, abnormal cell organelles,
or mutated DNA molecules in order to destroy them. In Chap. 10, we perform
modeling of soft and hard biological tissue ablation by plasmonic nanoparticles
heated by short and ultrashort laser pulses. Short and ultrashort laser pulses hold
key interest in precise nanoablation as they can allow for deposition of thermal
energy to the target area by many orders of magnitude faster than the heat diffusion
process that leaks heat to adjacent healthy cells.
This book, written for teachers and students and for research scientists, is on the
cutting edge of a most exciting realm of science and medicine. It should not only
Preface vii

help the reader to become more knowledgeable and versant in nanomedicine and
nanotechnology but also stimulate the reader to be creative and go beyond the
topics and ideas presented here.

Terre Haute, IN Renat R. Letfullin

St. Louis, MO Thomas F. George
Contents

1 Introduction to Nanomedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Lecture 1: Definition of Nanomedicine
and Nanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Lecture 2: Medical Nanodevices, Properties,
and Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.2.1 Medical Nanomachines and Nanorobots . . . . . . . . . . 9
1.2.2 Nanoparticles in Medicine . . . . . . . . . . . . . . . . . . . . 12
1.2.3 Functions and Properties of Medical
Nanodevices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.3 Lecture 3: Design and Fabrication of Medical
Nanodevices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
1.3.1 Design of Medical Nanodevices . . . . . . . . . . . . . . . . 29
1.3.2 Methods of Nanomaterials Fabrication . . . . . . . . . . . 31
1.3.3 Synthesis of Metallic Nanoparticles and
Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
1.3.4 Synthesis of Semiconductor Nanoparticles and
Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
1.3.5 Synthesis of Oxide Nanoparticles and Applications . . 36
1.3.6 Vapor Phase Reactions . . . . . . . . . . . . . . . . . . . . . . . 38
1.3.7 Solid-State Phase Segregation . . . . . . . . . . . . . . . . . . 39
1.3.8 Heterogeneous Nucleation . . . . . . . . . . . . . . . . . . . . 40
1.3.9 Kinetically Confined Synthesis . . . . . . . . . . . . . . . . . 41
1.3.10 Synthesis of Carbon Nanotubes and Applications . . . . 42
1.4 Lecture 4: Applications of Nanomedicine . . . . . . . . . . . . . . . . . 45
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Section 1.1: Definition of Nanomedicine
and Nanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

ix
x Contents

Section 1.2: Medical Nanodevices, Properties

and Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Section 1.3: Design and Fabrication of
Medical Nanodevices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Section 1.4: Applications of Nanomedicine . . . . . . . . . . . . . . . 60
Topics for Presentations and Writing Assignments . . . . . . . . . . . . . . . 61
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
2 Introduction to Cancer Cells and Targeting . . . . . . . . . . . . . . . . . . 63
2.1 Lecture 5: Introduction to Cell Biology . . . . . . . . . . . . . . . . . . 64
2.1.1 Cell Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
2.1.2 Cell Division . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
2.2 Lecture 6: Introduction to Cancer Biology . . . . . . . . . . . . . . . . 76
2.2.1 Some Causes of Cancer . . . . . . . . . . . . . . . . . . . . . . 79
2.2.2 Stages of Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
2.2.3 Categories of Cancer . . . . . . . . . . . . . . . . . . . . . . . . 81
2.2.4 Types of Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
2.2.5 Cancer Formation . . . . . . . . . . . . . . . . . . . . . . . . . . 83
2.2.6 Normal Cells Versus Cancer Cells . . . . . . . . . . . . . . 85
2.2.7 Cancer Cell Structure . . . . . . . . . . . . . . . . . . . . . . . . 88
2.2.8 Properties of Cancer Cells . . . . . . . . . . . . . . . . . . . . 91
2.3 Lecture 7: Selective Targeting of Cancer Cells . . . . . . . . . . . . . 97
2.3.1 Passive Targeting . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
2.3.2 Active Targeting . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
2.3.3 Advances in Drug Delivery . . . . . . . . . . . . . . . . . . . . 110
2.4 Lecture 8: Gene Therapy and Nanomedicine . . . . . . . . . . . . . . 111
2.4.1 Cancer and Gene Therapy . . . . . . . . . . . . . . . . . . . . . 111
2.4.2 Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
2.4.3 Mutations and Cancer . . . . . . . . . . . . . . . . . . . . . . . . 117
2.4.4 Gene Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
2.4.5 Nanomedicine for Gene Therapy . . . . . . . . . . . . . . . . 121
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Section 2.1: Introduction to Cell Biology . . . . . . . . . . . . . . . . . 125
Section 2.2: Introduction to Cancer Biology . . . . . . . . . . . . . . . 126
Section 2.3: Selective Targeting of Cancer Cells . . . . . . . . . . . 127
Section 2.4: Gene Therapy and Nanomedicine . . . . . . . . . . . . . 129
Topics for Presentations and Writing Assignments . . . . . . . . . . . . . . . 130
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
3 Introduction to Cancer Therapy and Detection by Plasmonic
Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
3.1 Lecture 9: Introduction to Nanophototherapies . . . . . . . . . . . . . 134
3.1.1 Conventional Cancer Treatments . . . . . . . . . . . . . . . . 135
3.1.2 Nanophototherapies for Cancer Treatment . . . . . . . . . 139
3.1.3 Selective Nanophotothermolysis of Cancer Cells . . . . 141
Contents xi

3.1.4 New Dynamic Modes in Selective

Nanophotothermolysis . . . . . . . . . . . . . . . . . . . . . . . 146
3.2 Lecture 10: Nanodrug Design and Methods of Activation . . . . . 152
3.2.1 Nanodrug Design . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
3.2.2 Methods of Activation . . . . . . . . . . . . . . . . . . . . . . . 154
3.3 Lecture 11: Surface Plasmon Resonance Detection
Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
3.3.1 Fiber Optics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
3.3.2 Optical Fiber Sensors Based on Surface
Plasmon Resonances (SPRs) . . . . . . . . . . . . . . . . . . . 172
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Topics for Presentations and Writing Assignments . . . . . . . . . . . . . . . 181
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
4 Introduction to Light–Particle Interactions . . . . . . . . . . . . . . . . . . 183
4.1 Lecture 12: Nanoparticle Optics—Lorenz–Mie Solutions . . . . . 184
4.1.1 Introduction to Waves . . . . . . . . . . . . . . . . . . . . . . . 184
4.1.2 Interaction of Light with a Medium . . . . . . . . . . . . . . 188
4.1.3 Maxwell’s Equations . . . . . . . . . . . . . . . . . . . . . . . . 193
4.1.4 Lorenz–Mie Formalism . . . . . . . . . . . . . . . . . . . . . . 196
4.2 Lecture 13: X-ray Optics of Nanoparticles . . . . . . . . . . . . . . . . 200
4.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
4.2.2 Wave Optics vs. X-ray Optics . . . . . . . . . . . . . . . . . . 202
4.2.3 Optical Constants for X-ray Photons . . . . . . . . . . . . . 203
4.2.4 Nanoparticle Optics in the X-ray Range
of the Spectrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
4.2.5 Effective Intensity-Absorption Efficiency . . . . . . . . . 212
4.3 Lecture 14: RF Optics of Nanoparticles . . . . . . . . . . . . . . . . . . 220
4.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
4.3.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
4.3.3 Absorption Efficiency of Nanoparticles in
the RF Range of the Spectrum . . . . . . . . . . . . . . . . . 227
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
Topics for Presentations and Writing Assignments . . . . . . . . . . . . . . . 238
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
5 Modeling Nanoparticle Optics . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
5.1 Computer Practicum 1 (Lecture 15): Lorenz–Mie
Simulations of Nanoparticle Optics . . . . . . . . . . . . . . . . . . . . . 242
5.1.1 Statement of the Research Task . . . . . . . . . . . . . . . . 243
5.1.2 Input Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
5.1.3 Mie Simulations of the Absorption and
Scattering Spectrum of Nanoparticles . . . . . . . . . . . . 249
5.1.4 Practice Example 1: Optical Properties of
Gold Nanoparticles in Low-Absorbing
Biological Media . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
xii Contents

5.2 Computer Practicum 2 (Lecture 16): Simulations of

Optical Properties of Biological Particles . . . . . . . . . . . . . . . . . 272
5.2.1 Statement of the Research Task . . . . . . . . . . . . . . . . 273
5.2.2 Mie Simulations for User-Defined Nanoparticles
and Surrounding Media . . . . . . . . . . . . . . . . . . . . . . 278
5.2.3 Optical Properties of Normal and Cancer Cell
Organelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
5.2.4 Practice Example 2: Simulation of Optical
Properties of Normal and Cancerous
Ribosomes in Cytoplasm . . . . . . . . . . . . . . . . . . . . . 290
5.2.5 Practice Example 3: Simulation of Optical
Properties of Bone Particles . . . . . . . . . . . . . . . . . . . 293
Appendix A: Mie Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
Section 5.1: Lorenz–Mie Simulations of Nanoparticle
Optics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
Section 5.2: Simulations of Optical Properties of
Biological Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6 Thermal Interaction of Particle and Radiation . . . . . . . . . . . . . . . . 307
6.1 Lecture 17: Kinetics of Heating and Cooling
of Nanoparticles: Time-Dynamic Models . . . . . . . . . . . . . . . . . 308
6.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
6.1.2 Thermodynamics of Nanoparticles . . . . . . . . . . . . . . 311
6.1.3 One-Temperature Model . . . . . . . . . . . . . . . . . . . . . . 316
6.1.4 Two-Temperature Model . . . . . . . . . . . . . . . . . . . . . 320
6.2 Lecture 18: Ultrashort Laser Pulse Heating of Nanoparticles
in Femtosecond, Picosecond, and Nanosecond Modes . . . . . . . . 323
6.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
6.2.2 Comparison of Theoretical Approaches . . . . . . . . . . . 327
6.2.3 Femtosecond Pulses . . . . . . . . . . . . . . . . . . . . . . . . . 329
6.2.4 Picosecond Pulses . . . . . . . . . . . . . . . . . . . . . . . . . . 334
6.2.5 Nanosecond Pulses . . . . . . . . . . . . . . . . . . . . . . . . . . 336
6.2.6 Conclusions and Summary . . . . . . . . . . . . . . . . . . . . 343
6.3 Computer Practicum 3 (Lecture 19): Single-Pulse
Heating of Nano/Bioparticles . . . . . . . . . . . . . . . . . . . . . . . . . 345
6.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
6.3.2 Practice Problem 4: Time Dynamics of the
Gold Nanoparticle Temperature in a Single-
Pulse Heating Mode . . . . . . . . . . . . . . . . . . . . . . . . . 358
6.3.3 Practice Problem 5: Thermal Dynamics of
Normal and Cancerous Ribosome in Cytoplasm
Heated by a Single Pulse of Laser Radiation . . . . . . . 366
Contents xiii

Appendix B: Maple Code for Nanoparticle Heating in a

Single-Pulse Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
Appendix C: Maple Code for Cell Organelle Heating in
a Single-Pulse Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Section 6.1: Kinetics of Heating and Cooling of
Nanoparticles: Time-Dynamic Models . . . . . . . . . . . . . . . . . . . 381
Section 6.2: Ultrashort Laser Pulse Heating of
Nanoparticles in Femtosecond, Picosecond, and
Nanosecond Modes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Section 6.3: Computer Practicum 3: Single-Pulse
Heating of Nano/Bioparticles . . . . . . . . . . . . . . . . . . . . . . . . . 384
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
7 Time Dynamic Modes of Nano/Bioparticle Heating . . . . . . . . . . . . 389
7.1 Lecture 20: Modeling Photothermal Heating in a
Multipulse Radiation Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
7.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
7.1.2 Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
7.1.3 Multipulse Mode of Heating . . . . . . . . . . . . . . . . . . . 394
7.1.4 Multipulse Heating of Healthy and
Cancerous Cell Organelles . . . . . . . . . . . . . . . . . . . . 398
7.1.5 Conclusions and Summary . . . . . . . . . . . . . . . . . . . . 401
7.2 Computer Practicum 4 (Lecture 21): Multipulse
Mode of Heating Healthy and Cancerous Cell Organelles . . . . . 405
7.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
7.2.2 Time Profile of Multipulsed Radiation . . . . . . . . . . . . 407
7.2.3 Practice Problem 6: Thermal Dynamics of
Healthy and Cancerous Lysosomes in Cytoplasm
Media Using Multipulsed Radiation . . . . . . . . . . . . . 410
7.3 Lecture 22: X-Ray and RF Heating of Nanoparticles . . . . . . . . 414
7.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
7.3.2 Nanoparticle-Enhanced X-Ray Therapy of Cancer . . . 416
7.3.3 RF Activation of Nanoparticles in Single-Pulse
and Multipulse Modes of Heating . . . . . . . . . . . . . . . 426
Appendix D: Maple Code for Bioparticle Heating in a
Multipulse Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
Section 7.1: Modeling Photothermal Heating for
Multipulsed Radiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
Section 7.2: Computer Practicum: Multipulse Mode of
Heating Healthy and Cancerous Cell Organelles . . . . . . . . . . . . 441
Section 7.3: X-Ray and RF Heating of Nanoparticles . . . . . . . . 443
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
xiv Contents

8 Spatial Behavior of Temperature Fields at Nanoscale . . . . . . . . . . . 447

8.1 Lecture 23: Modeling Heat Diffusion . . . . . . . . . . . . . . . . . . . . 448
8.1.1 Heat Transfer Model . . . . . . . . . . . . . . . . . . . . . . . . 448
8.1.2 Temperature Fields Around the Nanoparticle . . . . . . . 454
8.1.3 Material Properties and Input Parameters . . . . . . . . . . 454
8.2 Computer Practicum 5 (Lecture 24): Simulating the
Temperature Fields Within and Outside a Nanoparticle . . . . . . . 465
8.2.1 Computer Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
8.2.2 Practice Example 7: Thermal Fields Around
a Gold Nanoparticle in Aqueous Solution . . . . . . . . . 472
8.2.3 Practice Example 8: Thermal Ablation of
Cancerous Cell Nuclei in Cytoplasm . . . . . . . . . . . . . 479
Appendix E: Maple Code for Simulating Heat Diffusion
Around a Nanoparticle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
Appendix F: Maple Code for 3D Simulation of Heat
Diffusion Around the Nanoparticle . . . . . . . . . . . . . . . . . . . . . . . . . . 489
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
Section 8.1: Modeling Heat Diffusion . . . . . . . . . . . . . . . . . . . 494
Section 8.2: Computer Practicum 5: Simulating the
Temperature Fields Within and Outside the Nanoparticle . . . . . 494
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 498
9 New Dynamic Modes in Selective Nanophotothermolysis . . . . . . . . 499
9.1 Lecture 25: Nanocluster Aggregation Mode . . . . . . . . . . . . . . . 500
9.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 500
9.1.2 Self-Assembling of Nanoclusters in
Living Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
9.1.3 Criteria for Interparticle Distance and
Nanocluster Concentration . . . . . . . . . . . . . . . . . . . . 505
9.1.4 Thermal Field Simulations for Nanoclusters . . . . . . . 507
9.2 Computer Practicum 6 (Lecture 26): Simulating
Temperature Fields Around a Nanocluster . . . . . . . . . . . . . . . . 516
9.2.1 Computer Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517
9.2.2 Practice Example 9: RF Heating of Nanoclusters
for Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . . . 520
9.2.3 Practice Example 10: Heating of Silver
Nanoclusters by Laser Radiation . . . . . . . . . . . . . . . . 532
9.3 Lecture 27: Nanobubble Overlapping Mode . . . . . . . . . . . . . . . 539
9.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
9.3.2 Spherical Bubble Dynamics . . . . . . . . . . . . . . . . . . . 541
9.3.3 Nanobubble Overlapping . . . . . . . . . . . . . . . . . . . . . 544
9.3.4 Conditions for Nanoparticle Concentration . . . . . . . . 549
9.3.5 Conditions for Nanoparticle Size . . . . . . . . . . . . . . . . 550
9.3.6 Microbubble Generation Around Nanoparticles
and Nanoclusters . . . . . . . . . . . . . . . . . . . . . . . . . . . 552
Contents xv

9.4 Computer Practicum 7 (Lecture 28): Simulating

Nanobubble Dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
9.4.1 Computer Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
9.4.2 Practice Example 11: Bubble Formation
and Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563
9.4.3 Discussion and Results . . . . . . . . . . . . . . . . . . . . . . . 564
9.4.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 570
9.5 Lecture 29: Laser-Induced Thermal Explosion Mode—
“Nanobombs” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572
9.5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572
9.5.2 Thermal Explosion . . . . . . . . . . . . . . . . . . . . . . . . . . 574
9.5.3 Coulomb Explosion . . . . . . . . . . . . . . . . . . . . . . . . . 576
9.5.4 Time Scale Approximations . . . . . . . . . . . . . . . . . . . 576
9.5.5 Threshold Intensity for Laser-Induced Thermal
Explosion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
9.5.6 Cell Damage Effects . . . . . . . . . . . . . . . . . . . . . . . . 580
9.5.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585
Appendix G: Maple Code for Simulating the Spatial
Distribution of Thermal Fields Around a Nanocluster . . . . . . . . . . . . . 587
Appendix H: Maple Code for Simulating Bubble Growth
Around a Nanoparticle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593
Section 9.1: Nanocluster Aggregation Mode . . . . . . . . . . . . . . . 593
Section 9.2: Computer Practicum 6: Simulating
Temperature Fields Around a Nanocluster . . . . . . . . . . . . . . . . 595
Section 9.3: Nanobubble Overlapping Mode . . . . . . . . . . . . . . 599
Section 9.4: Computer Practicum 7: Simulating
Nanobubble Dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 600
Section 9.5: Laser-Induced Thermal Explosion
Mode—“Nanobombs” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
10 Ablation of Biological Tissues by Plasmonic Nanoparticles . . . . . . . 609
10.1 Lecture 30: Bone Cancer Ablation by Short and
Ultrashort Pulses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 610
10.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 610
10.1.2 Bone Targeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 614
10.1.3 Radiation Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . 620
10.1.4 Plasmonic Nanoparticles . . . . . . . . . . . . . . . . . . . . . . 622
10.1.5 Modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 624
10.1.6 Materials Properties and Input Data . . . . . . . . . . . . . . 628
10.1.7 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . 629
10.1.8 Ablation of Bone Tissue . . . . . . . . . . . . . . . . . . . . . . 644
10.1.9 Future Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . 647
10.1.10 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649
xvi Contents

10.2 Lecture 31: Soft-Tissue Ablation by Short and

Ultrashort Pulses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 651
10.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 652
10.2.2 Hepatocellular Carcinoma Ablation . . . . . . . . . . . . . . 655
10.2.3 Ductal Breast Carcinoma Ablation . . . . . . . . . . . . . . 659
10.2.4 Ribosomal Ablation . . . . . . . . . . . . . . . . . . . . . . . . . 662
10.2.5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664
10.3 Computer Practicum 8 (Lecture 32): Simulating
Biological Tissue Ablation . . . . . . . . . . . . . . . . . . . . . . . . . . . 666
10.3.1 Computer Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . 666
10.3.2 Practice Example 12: Cell Ablation
Through Nanoparticle Heating . . . . . . . . . . . . . . . . . 671
Appendix I: Maple Code for Simulating the Ablation of
Biological Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 678
Section 10.1: Bone Cancer Ablation by Short and
Ultrashort Pulses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 678
Section 10.2: Soft-Tissue Ablation by Short and
Ultrashort Pulses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 680
Section 10.3: Simulating Biological Tissue Ablation . . . . . . . . . 681
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 681
Author Bios

Renat R. Letfullin is a faculty member in the

Department of Physics and Optical Engineering
at Rose-Hulman Institute of Technology and
holds an appointment as full Professor of Physics
and Nanotechnology at Radiological Technologies
University. He is also Founder and Director of
the Nanomedicine program at Radiological
Technologies University.
Dr. Letfullin has made seminal contributions to
the fields of wave and quantum optics, lasers,
aerosol physics, and nanoscience, including
nanooptics and nanobiotechnology. He is an
outstanding theoretician and experimentalist in
the fields of optics and kinetics of chemical pulsed lasers and, during the past
decade, has branched out into biophotonics and nanomedicine. He has discovered
new phenomena and scientific effects in these fields, where examples include effect
of diffractive multifocal focusing of plane and spherical waves, effect of giant laser
energy gain, the autowave of a new type—self-supporting photon-branched chain
reaction, and effect of focusing of de Broglie matter waves. He has carried out an
extensive array of studies in nanoscience, including laser heating and evaporation
of nanostructures and optical properties of nanoparticles. He has developed and
designed new self-contained laser systems with multi-mega-joule output energy per
pulse, optical reactor for efficient laser processing of dispersed materials, phase
technique for optical diagnostics of small particles, and new diffractive atom lens.
His latest achievements are in the field of nanophotonics and nanomedicine,
including discoveries of a plasmon explosion of nanoparticles, new dynamics
modes in selective nanophototherapy, and RF and X-ray optics of nanoparticles.
Dr. Letfullin is a world-class physicist and an expert in the areas of optics, laser
physics, nanophotonics, and nanomedicine. He has been recognized nationally and
worldwide, such as being elected as a SPIE (Society of Photo-Optical

xvii
xviii Author Bios

Instrumentation Engineers) Fellow and named an OSA (Optical Society of Amer-

ica) Senior Member for achievements in optics, photonics, laser physics,
nanophotonics, biophotonics, and nanomedicine. A well-respected international
researcher, Dr. Letfullin has authored over 150 papers and conference proceedings,
edited 4 books, and coauthored 12 chapters in 7 different books. His work has
garnered several grants and awards including 4 patents in laser technology and
optical engineering.
Dr. Letfullin has made numerous and important contributions to designing and
teaching physics, optics and biomedical optics courses, and developing a national
first Master of Science degree program in nanomedicine. He has led the develop-
ment of several new research laboratories on biophotonics and nanomedicine,
created innovative teaching tools including online video courses and webinars,
and supervised numerous masters and doctoral students.
Dr. Letfullin actively serves the research community as an editor for the research
journal International Journal of Theoretical Physics, Group Theory and Nonlinear
Optics published by Nova Science. He is an editorial board member and reviewer
for a number of high-ranking scientific journals, and he has chaired numerous
conferences.
Born in Russia, Dr. Letfullin received a Bachelor of Science degree in Physics
and earned a Master of Science degree in Optics and Spectroscopy from Samara
State University. He received a Doctor of Philosophy degree in Laser Physics from
Saratov State University, followed by junior/senior research appointments at P. N.
Lebedev Physics Institute of Russian Academy of Sciences (Samara Branch). He
then served as a visiting faculty at Mississippi State University, and since 2004
joined the faculty at Rose-Hulman Institute of Technology. He also serves as a
faculty member and program director at Radiological Technologies University.
Dr. Letfullin has been married since 1992 to Tatiana Letfullin who is an
accomplished classical pianist. They are proud to have two daughters, Alla and
Mary. Alla is Nanoscience Ph.D. student at Joint School of Nanoscience and
Nanoengineering—a collaborative project of North Carolina A&T State University
and the University of North Carolina. Youngest daughter Mary is a cheerful girl
who enjoys art.
Author Bios xix

Thomas F. George is chancellor and professor of

chemistry and physics at the University of Mis-
souri—St. Louis. As chancellor, he oversees aca-
demic and administrative operations of a university
with 17,000 students, 2500 faculty and staff, 40 aca-
demic buildings, and a $200 million annual operat-
ing budget. In addition, $150 million of new capital
construction, renovation, and landscaping on cam-
pus is taking place during 2014–2016. The annual
amount of philanthropic contributions during his
tenure as chancellor has quadrupled to over $26
million, reaching as high as $31 million in 2014.
Chancellor George is active in the St. Louis community. He has received the
Distinguished Higher Education Award from the Dr. Martin Luther King, Jr.,
Missouri State Celebration Commission, the Outstanding Community Service
Award from the St. Louis County Branch of the National Association for the
Advancement of Colored People, the Lifelong Vision Award from the Lifelong
Vision Foundation of St. Louis, and the Silver Beaver Award and Good Scout
Award from the Greater St. Louis Area Council of the Boy Scouts of America; and
he has been named St. Louis North County Chamber of Commerce Citizen of the
Year. He serves on numerous civic boards and currently is chair of the Higher
Education Consortium of Metropolitan St. Louis, and he served for 4 years as chair
of the Great Lakes Valley Conference (athletics). In addition to his role as campus
and community leader and fund-raiser, Chancellor George contributes at the state
and national levels, such as currently serving as vice chair of the Council on Public
Higher Education in Missouri and president of the Coalition of Metropolitan and
Urban Universities (comprised of 95 institutions across the USA and Canada).
Chancellor George is an active researcher in chemistry and physics, specializ-
ing in chemical/materials/laser physics and nanoscience, including nanomedicine.
His work, supported by a wide variety of federal and international agencies, has
led to 775 papers, 7 authored and 18 edited books, and 225 conference abstracts.
He has been recognized nationally and worldwide, such as being awarded the
Marlow Medal by the Royal Society of Chemistry in Great Britain and named a
fellow in various professional organizations (New York Academy of Sciences,
American Physical Society, Society of Photo-Optical Instrumentation Engineers,
American Association for the Advancement of Science) and foundations (Drey-
fus, Sloan, Guggenheim). He has been elected as a foreign member of the Korean
Academy of Science and Technology, and he has held the title of visiting
professor of physics at Korea University in Seoul. His research has been acknowl-
edged by an honorary doctorate in physics (honoris causa) from the University of
Szeged in Hungary. He also has received an honorary doctorate in education for
locality development from Phranakhon Rajabhat University in Thailand. He has
been awarded the Medal of Honor from Gulf University for Science and
xx Author Bios

Technology in Kuwait and the Diploma of Honour from Seinäjoki University of

Applied Sciences in Finland.
An accomplished jazz pianist, Dr. George has studied with faculty at the
Berklee College of Music in Boston and the Eastman School of Music in
Rochester, New York. He has performed extensively in public, including recent
performances at various venues in Missouri and Illinois, the University of
Arkansas, Gettysburg College in Pennsylvania, Nanjing University and North-
western Polytechnical University in China, city of Szeged in Hungary, West
University of Timisoara in Romania, Gulf University for Science and Technol-
ogy in Kuwait, University of Sarajevo in Bosnia, and University of Dubrovnik in
Croatia, and the Cultural Club in Muscat, Oman. He has also performed in
Russian Siberia.
Born in Philadelphia, Chancellor George became an Eagle Scout (with bronze,
gold, and silver palms) and received his high school diploma from Friends’ Central
School, where he earned varsity letters in soccer and wrestling. He received a
Bachelor of Arts degree (Phi Beta Kappa) with a double major in chemistry and
mathematics from Gettysburg College in Pennsylvania. He earned a Master of
Science degree and Doctor of Philosophy degree in theoretical chemistry from
Yale University at age 23, followed by postdoctoral appointments at MIT and UC
Berkeley. Joining the faculty at the University of Rochester, he was promoted by
age 29 to full professor of chemistry. He then served as dean of natural sciences and
mathematics at SUNY—Buffalo, provost at Washington State University, chancel-
lor at the University of Wisconsin—Stevens Point, and since 2003 as chancellor at
the University of Missouri—St. Louis.
Dr. George has been married since 1970 to Dr. Barbara Harbach, Curators’
Professor of Music, director of the School of Fine and Performing Arts, and director
of Women in the Arts at the University of Missouri St. Louis. They are the proud
owners (actually, servants) of four cats—two tortoise females (Luna and Stella) and
two younger, mischievous males (Jeremiah and Jarrett).
Chapter 1
Introduction to Nanomedicine

Contents
1.1 Lecture 1: Definition of Nanomedicine and Nanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Lecture 2: Medical Nanodevices, Properties, and Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.2.1 Medical Nanomachines and Nanorobots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.2.2 Nanoparticles in Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.2.3 Functions and Properties of Medical Nanodevices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.3 Lecture 3: Design and Fabrication of Medical Nanodevices . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
1.3.1 Design of Medical Nanodevices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
1.3.2 Methods of Nanomaterials Fabrication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
1.3.3 Synthesis of Metallic Nanoparticles and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . 35
1.3.4 Synthesis of Semiconductor Nanoparticles and Applications . . . . . . . . . . . . . . . . . . 36
1.3.5 Synthesis of Oxide Nanoparticles and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
1.3.6 Vapor Phase Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
1.3.7 Solid-State Phase Segregation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
1.3.8 Heterogeneous Nucleation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
1.3.9 Kinetically Confined Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
1.3.10 Synthesis of Carbon Nanotubes and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
1.4 Lecture 4: Applications of Nanomedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Homework Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Section 1.1: Definition of Nanomedicine and Nanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Section 1.2: Medical Nanodevices, Properties and Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Section 1.3: Design and Fabrication of Medical Nanodevices . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Section 1.4: Applications of Nanomedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Topics for Presentations and Writing Assignments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

Abstract This chapter presents the definition of nanomedicine and nanotechnology,

describes the relation of nanomedicine to the basic sciences, introduces the
functions and properties of medical nanodevices, the design and fabrication of
nanorobots and nanoparticles, and discusses the current and potential applications
of nanomedicine.

Electronic supplementary material: The online version of this chapter (doi:10.1007/978-3-319-

43577-0_1) contains supplementary material, which is available to authorized users.

© Springer International Publishing Switzerland 2016 1

R.R. Letfullin, T.F. George, Computational Nanomedicine and Nanotechnology,
DOI 10.1007/978-3-319-43577-0_1
2 1 Introduction to Nanomedicine

1.1 Lecture 1: Definition of Nanomedicine

and Nanotechnology (Slide 1.1)

• New Technological Frontiers in Twenty-First Century

• Relation of Nanomedicine to the Basic Sciences
• Definition of Nanomedicine
• Definition of Nanotechnology
• Imaging and Treatment Modalities: Advantages and Disadvantages
• Conclusions
The last century was a renaissance time for many sciences as shown on Slide 1.2.
In physics, the twentieth century began with the discovery of quantum mechanics
and theory of relativity, breakthroughs in atomic and nuclear physics, and the
invention of superconductivity and lasers. Microelectronics brought fast computers
and high-speed communication, information technologies, and the invention of the
Internet. Transportation also changed a lot during the twentieth century. But where
is science and technology going today in the current century?
In the natural sciences, there are three main science and technological frontiers in
the twenty-first century: nanotechnology, biology and information technology as
shown on Slide 1.2. Nanomedicine is a new science which combines two new
technological frontiers—nano and bio, i.e., applying nanotechnology to biology
with medical applications. Nanotechnology is revolutionizing medicine, giving
unprecedented opportunities to treat the human body at the atomic and molecular
levels like we are recrafting conventional machines today.
What is nanomedicine? An efficient way to define this is to find its place among
the established sciences. Slide 1.3 shows the interdisciplinary relation of
nanomedicine to basic sciences and engineering. Biophysics itself is a

LECTURE 1:
DEFINITION OF NANOMEDICINE AND
NANOTECHNOLOGY

Contents:
• New Technological Frontiers in the 21st Century
• Relation of Nanomedicine to the Basic Sciences
• Definition of Nanomedicine
• Definition of Nanotechnology
• Imaging and Treatment Modalities:
Advantages and Disadvantages
• Conclusions

Slide 1.1 Contents of Lecture 1

1.1 Lecture 1: Definition of Nanomedicine and Nanotechnology 3

New Technological Frontiers

• 20th Century:
- Physics,
- Microelectronics,
- High-Speed Communications
- Transportation

• 21st Century:
- Nanotechnology
- Biology
- Information
- but also Energy, Environment, and Sustainability

Slide 1.2 New technological frontiers

Nanomedicine Relation to Basic Sciences

Biophysics Engineering:
Interdisciplinary study • Optical technology
combines • Laser technology
Physics: • Nanotechnology
Biology:
• and so on
• Cellbiology • Optics
• Cytology • Thermodynamics
• Microbiology • Kinetics New Technology
• and so on • and so on
Diagnosis and Treatment of
Diseases
Fundamental Knowledge for

Medical Physics
Imaging Radiation Oncology Photodynamic Therapy Nanomedicine

Slide 1.3 Relation of nanomedicine to the basic sciences

multidisciplinary science, combining biology and physics. From biology,

nanomedicine involves disciplines like cell biology, microbiology, cytology etc.
Physics provides nanomedicine with basic knowledge in optics, thermodynamics,
kinetics, so on. The chemistry is needed for nanomedicine, for example, to target
the cancer cells by nanodrugs, and to understand the chemical bonding between
protein molecules of antibodies and the cell to the surface atoms of nanoparticles.
4 1 Introduction to Nanomedicine

What is Nanomedicine?

• Nanomedicine is an interdisciplinary field of science

which involves physics, engineering biology, chemistry,
medicine and other sciences for diagnosis and treatment
of diseases by means of nanotechnology.
• The ultimate goal of nanomedicine is to treat the human
body at the atomic and molecular levels, and to repair a
body like we repair conventional machines today.
Slide 1.4 Definition of nanomedicine

Nanomedicine has strong application components as well, and it uses engineering

tools like nanotechnology, laser technology, nanophotonics, etc. Thus, biophysics
and chemistry provide the fundamental knowledge for nanomedicine, and engi-
neering supplies new technologies and tools for nanomedicine. All this is needed
and designed for diagnosis and treatment of different diseases.
The diagnosis and treatment of diseases by means of physics and engineering
tools falls under the large area called medical physics, which has many branches
like radiography, brachytherapy, nuclear imaging, fluoroscopy, etc. Photodynamic
therapy and nanomedicine are parts of medical physics, where nanomedicine
utilizes the established disciplines of biophysics, chemistry and engineering for
the diagnosis and treatment of diseases.
Now we are ready to give a definition of nanomedicine (Slide 1.4):
Nanomedicine is an interdisciplinary science which involves physics, biology,
chemistry, optics, medicine, and engineering for diagnosis and treatment of dis-
eases by means of nanotechnology.
The ultimate goal of nanomedicine is to treat the human body at the atomic and
molecular levels and repair the body like we are repairing the conventional
machines today.
A key point in the definition of nanomedicine is nanotechnology (Slide 1.5).
What is nanotechnology? The word “nano” comes from the Greek language and
means “dwarf”, i.e., something very small. When we say “nano,” specifically we
mean “one billionth” of something. For example, one nanometer is one billionth of
a meter, i.e., 10 9 m. “Any research and development at the atomic, molecular, or
macromolecular levels, on the length scale of approximately 1–100 nm range, is
called nanoscience [1]”.
The behavior and the properties of matter at this size range is quite different from
the behavior and properties of bulk material. Nanotechnology creates and designs
structures, devices and systems that have novel properties and functions because
of their small and/or intermediate size [1]. Nanotechnology involves purposeful
imaging, measuring, modeling, and manipulating matter at this length scale [1].
1.1 Lecture 1: Definition of Nanomedicine and Nanotechnology 5

Nanotechnology Defined
Video 1
• Nano = Greek for “Dwarf”
• Nano = “1 billionth”

• Research and development at the atomic, molecular or

macromolecular levels, on the length scale of approximately 1-
100 nanometer range . . .
• . . . to create and use structures, devices and systems that have
novel properties and functions because of their small and/or
intermediate size

• Nanotechnology involves purposeful imaging, measuring,

modeling, and manipulating matter at this length scale
Source: National Nanotechnology Initiative 5

Slide 1.5 Definition of nanotechnology

Dr. Richard Feynman started a nanotechnology discussion in his lecture “There’s

Plenty of Room at the Bottom” in 1959 at a meeting of the American Physical
Society. He stated that (1) it should be possible to build machines small enough to
fabricate objects with atomic precision; (2) if information could be written on an
atomic scale, the entire 24 volumes of the Encyclopedia Britannica could be placed
on a pinhead; (3) an electron microscope could be made to see individual atoms;
and (4) microcomputers could be built. There are many short videos available on
YouTube presenting Feynman’s vision of the small world.
How can the nanoworld actually help conventional medicine today? Current clinics
already have many imaging and treatment modalities as listed on the Slide 1.6, like
radiography, fluoroscopy, mammography, computed tomography, nuclear medicine,
positron emission tomography, magnetic resonance imaging, chemotherapy, mag-
netic field treatment, microwave and RF treatments. Definitely they have some
benefits as shown on the Slide 1.7. For example, conventional clinical modalities
allow deep penetration into the body, with slice scans at specific regions, and with the
fast scanning speeds, the entire body scan takes less than an hour. They provide
accurate information on the position, density, structure and boundaries of internal
organs. And most importantly, these modalities extend patients’ lives.
However, besides the benefits, there are disadvantages of conventional imaging
and treatment modalities listed on Slide 1.8. Today’s clinical modalities are unable
to detect and treat diseases at the single cell or DNA levels. But cancer, for
example, is a DNA mutation disease. Missing the mutations of DNA results in
late diagnosis and treatments leading to metastasis with the disease around the
body. The spatial resolution of most modalities is about 1 mm, and a 1 mm tumor
already contains thousands of cancer cells since a single cell has a size range of
6 1 Introduction to Nanomedicine

Traditional Imaging and Treatment

Modalities

• Radiography
• Fluoroscopy
• Mammography
• Computed tomography
• Nuclear medicine
• Positron emission tomography
• Magnetic resonance imaging
• Chemotherapy
• Magnetic field treatment
• Microwave and RF treatment
Slide 1.6 Traditional imaging and treatment modalities

Benefits of Conventional Clinical

Modalities

• Deep penetration into the body

• Whole body scan
• Slice scan
• Fast scan
• Position accuracy
• Density information
• Organs structure and boundaries
• Extend patient life
Slide 1.7 Benefits of the conventional clinical modalities

10–20 μm. Those cells metastasize throughout the body via blood circulation.
Because of the resolution limit, the today’s imaging modalities can detect only
tumors larger than 1 mm.
Finally, when we see a tumor, we have three main treatment methods available
today: chemotherapy, radiation therapy and surgery. All of them are unselective,
damaging healthy tissue and organs with many side effects. For example, X-ray
radiation treatments at therapeutic doses can cause secondary cancer. Today’s
1.1 Lecture 1: Definition of Nanomedicine and Nanotechnology 7

Disadvantages of Conventional Clinical Modalities

• Unable to detect and treat at the single cell level

• Unable to detect and treat at the DNA level
• Late diagnosis and treatment
• Unable to detect and treat metastasis in time
• Unable to carry out selective treatment on only
cancer cells
• Healthy tissue damage Nanomedicine
• X-rays treatment could cause a secondary cancer is a future
• Unable to treat effectively bone cancer and medicine
marrow
• Unable to complete cancer cure
• Recurrence occurs after the treatment
• Patients eventually die
• Expensive treatment

Slide 1.8 Disadvantages of the conventional clinical modalities

modalities are unable to treat effectively bone cancer and marrow. But marrow is
responsible for the body’s immune system to produce blood cells fighting any
disease. For instance, when a cancer reaches the marrow the only treatment option
we have today is marrow transplantation by shutting down an immune system of the
patient first, i.e., sterilizing a patient’s marrow by radiation. This procedure puts the
patient at very high risk to be killed by any germs like a flu. Today’s clinical
modalities are unable to completely cure cancer, where recurrences can occur after
the treatment, and many patients eventually die from the cancer. One more disad-
vantage is that chemotherapy, radiation therapy and surgery are very expensive
with often unpredictable results.
The nanomedicine is able to resolve the abovementioned deficiencies of imaging
and treatment modalities we have in clinics today. Nanomedicine can operate at the
single cell and gene levels of detection, which provides early diagnosis and
treatment of diseases, solving the metastasis problem. The nanomedicine is a
selective treatment, with no side effects, and has capability for effective treatment
of bone cancer and marrow.
In conclusion, nanomedicine is a smart medicine, and it is an exciting future
medicine (Slide 1.9). It will provide fast and painless selective treatment
without a side effects. We believe that via 3–5 year immunization cycle with
nanodrugs, nanomedicine will defeat cancer for good and give life for cancer
patients.
8 1 Introduction to Nanomedicine

Conclusions: Nanomedicine is a Smart Medicine

• Nanomedicine is a future medicine.

• Fast painless treatment.
• Early diagnostics at the single cell or DNA levels.
• Metastasis treatment at the cellular level.
• Bone cancer treatment.
• Defeat cancer for good and give full life for
cancer patients.
Slide 1.9 Conclusions

1.2 Lecture 2: Medical Nanodevices, Properties,

and Functions (Slide 2.1)

• Medical Nanomachines and Nanorobots

• Nanoparticles in Medicine
• Functions and Properties of Medical Nanodevices
• Removing Used Nanorobots
• Conclusion
In recent years, there has been a tremendous increase in research at the nanoscale
for materials. Nanomedicine utilizes several varieties of nanostructured materials
and nanodevices currently being developed: nanorobots, nanoparticles, nanochips,
quantum dots, nanovalves, etc. Nanorobots are defined as nanomachines capable of
operating with nanosized objects and with nanoscale precision. Nanorobots are also
known as nanobots, nanoids, nanites, nanomachines or nanomites. Nanoparticles
are tiny particles of matter made of any material (metal, semiconductor, glass,
polymer, organic, liquid or combinations of different materials) of any shape
(nanosphere, nanoshell, nanorod, nanotube, fullerene) and structure (solid, porous,
bubble, bilayer) in size range 1–100 nm designed to perform varies functions and
manipulation of matter at this length scale. A quantum dot is a tiny piece of
semiconductor material where the charge carriers are confined in all three dimen-
sions. This lecture briefly describes medical nanodevices, nanoparticles, and their
properties and functions.
1.2 Lecture 2: Medical Nanodevices, Properties, and Functions 9

Contents:
• Medical Nanomachines and Nanorobots
• Nanoparticles in Medicine
• Functions and Properties of Medical
Nanodevices
• Removing Used Nanorobots
• Conclusion
Slide 2.1 Contents of Lecture 2

Medical Nanomachines and Nanorobots

• Nanorobots are defined as nanomachines capable of

operating with nanosized objects and with nanoscale
precision.
• Nanorobots are also known as nanobots, nanoids,
nanites, nanomachines or nanomites.
• Medical nanomachines are designed to perform
single or repetitive tasks in biological cells with
nanoscale resolution.
Slide 2.2 Medical Nanomachines and nanorobots

1.2.1 Medical Nanomachines and Nanorobots

Nanorobotics represent a new molecular technology field that has grown over the
years, creating robots or machines made up of parts that are at or close to the scale
of nanometers (Slide 2.2). Having evolved through several developmental stages,
this field is still under research and development. Nanodevices have opened a new
world of discoveries and feasibilities in many fields, such as space exploration,
military defense, medicine, industry and energy. Applications of nanorobots in
medicine are briefly discussed in Lecture 3.
10 1 Introduction to Nanomedicine

Main Components of a Typical Nanorobot

• Payload – A vacant portion in a nanorobot design that reserves a

small dose of drug/medicine for onward delivering to an
infection/injury site as it moves in the blood.
• A power source – Supplier of energy for nanodevice operation and
functions. Two types of energy sources are available for
nanomachines: external and internal power sources.
• Swimming tail – Needed for traversing through the body.
• Motor and manipulator arms/mechanical legs – Structures used
for different types of movements of nanomachines.
• Signal receiver and transmitter – A nanorobot must have the
ability to communicate that allows a human to physically guide the
robot as it transverses the body.

Slide 2.3 Main components of atypical nanorobot

Medical nanomachines are designed to perform single or repetitive tasks in

biological cells with nanoscale resolution. Nanorobots could be designed as self-
replicating machines. The main components of the typical nanorobot could include
(Slide 2.3):
• Payload—This is a vacant portion in nanorobot design that reserves a small dose
of drug/medicine for onward delivering to an infection/injury site as it moves in
the blood.
• Power source—This supplies the energy for the nanodevice operation and
functions. Two types of energy sources are available for nanomachines: external
and internal power sources described below.
• Swimming tail—This is needed for traversing through the body.
• Motor and manipulator arms/mechanical legs—These are structures used for
different types of movements of nanomachines.
• Signal receiver and transmitter—Nanorobots must have the ability to
communicate, allowing humans to physically guide the robot as it transverses
the body.
Currently built medical nanodevices include (Slide 2.4) three-dimensional DNA
crystals, nanovalves for drug delivery, molecular propellers, nanochips, DNA
nanorobots, nanorobots treating hepatitis C, etc.
A three dimensional DNA crystal is an assembly of synthetic DNA molecules
forming 3D crystal structures capable of hosting guest structures (Slide 2.4). These
porous crystals can be used as molecular containers to build biochips, nanorobots,
biodegradable solid-state catalysts and biosensors, or for delivery of enzymes in
enzyme replacement therapies.
Another random document with
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 [7] This is an instrument through which we can see things much
clearer and larger than we could with the naked eye.
 LESSON VI.
DESCRIPTION OF THE EARTH’S SURFACE.—DIVISION OF IT INTO ZONES.—
TORRID, TEMPERATE AND ARCTIC ZONES.—THE FIVE GREAT
CONTINENTS.—RELATIVE DIMENSIONS OF AMERICA, EUROPE, ASIA,
AFRICA AND AUSTRALIA.
§ 32. Having learned the relation of our Earth to the Sun and the
Planets, it will be well to acquaint ourselves with the principal objects
on its surfaces.—What the Interior of our Earth consists of, we have
as yet no idea, because we have not yet been able to penetrate
deeper than a few hundred feet; and this is, in proportion to the
Earth’s Diameter, little more than nothing. But as regards her
surface, we know that it consists partly of land and partly of water.
Little more than one fourth of the Earth’s surface is covered with
land; all the rest is water.—The great lands are called Continents;
the great waters are called Oceans. Smaller portions of land
surrounded on all sides by water, are called Islands. Smaller bodies
of water surrounded by land are called Lakes.
§ 33. The land on our Earth is divided into Five Continents:
America, Europe, Asia, Africa and Australia.—These, however, are
not all of the same extent. Europe is the smallest of them. America
and Asia are the greatest.
The adjoining Plate No. XI, will give you an idea of the proportion of
land and water on our Earth, and of the relative extent of the Five
Continents.
Fig. I represents the surface of the Earth divided into land and
water. Were all land on our Earth put together in a circle, and the
water placed round it, then the land would only fill the inner circle, the
water occupying the surrounding ring, a space nearly four times as
large as the circle. Fig. II, III, IV, V and VI represent the comparative
surfaces of America, Europe, Asia, Africa and Australia. Fig. VII
represents the comparative surface of the Moon.
Upon close inspection of these figures you will perceive;
 1. That the extent of America and Asia are nearly equal; but that
each of these Continents is several times larger than either Europe
or Australia.
2. That the next greatest portion of our Globe is Africa, which is
more than three times larger than Europe.
3. That Europe is the smallest Continent of our globe.
4. That the whole surface of the Moon would not be more than
enough to cover either America or Asia.
 No. XI.
Fig. 1.
THE OCEAN
THE LAND

Fig. 2.
EUROPE

Fig. 3.
ASIA

Fig. 4.
AFRICA

Fig. 5.
AMERICA

Fig. 6.
AUSTRALIA
Fig 7.
THE MOON’S
SURFACE

Geographical Miles.
 No. XII.
Fig. 1.
THE WHOLE TORRID ZONE

Comparative Extent
of the
TWO TEMPERATE
ZONES

Comparative
EXTENT
of the
TWO ARCTIC
ZONES

Fig. 2.

Comparative Extent
of one of the
WHOLE TORRID
ZONE

Fig. 3.

Comparative Extent
of one of the
TWO TEMPERATE
ZONES

Fig. 4.

ONE
of the
ARCTIC
ZONES

Fig. 5.

Comparative Extent
of the
WHOLE LAND
on our
GLOBE
No. XIII.
 No. XIV.
Square contents
of the Two
TEMPERATE
ZONES.

Square contents
of the
WHOLE TORRID
ZONE.

Square contents
of the Two
ARCTIC ZONES.

The whole surface

of the five
GREAT CONTINENTS
on our
GLOBE
Compared to one of the two
TEMPERATE ZONES.

§ 34. The Earth’s surface is not throughout equally illumined or

heated by the Sun; because the Sun’s rays strike some portions of
the Earth more perpendicular than others. Our Earth, therefore, is
divided into Climates or Zones, which you will understand better from
Plate XII.
You will see from it that the Sun’s rays are perpendicular to the
central part of the Earth’s surface; but that toward the extremities of
the Earth’s Diameter these rays strike us more and more obliquely.
The greatest heat, therefore, must be felt by the people living
between the two circles EF and IK. The circle GH, which is exposed
to the perpendicular rays, is termed the Equator; and the two circles
EF and IK, which are at equal distance from the Equator, are called
Tropic Circles. The whole surface included by these two circles is
called the torrid Zone. The space between either of the circles CD
and EF, or IK and LM, is called a temperate Zone; because the Sun’s
rays striking these portions neither perpendicular nor very obliquely,
their inhabitants suffer neither great heat nor cold. In one of these
Zones are situated the United States of America and the greater
portion of Europe. Beyond them, toward the extremities of the
Diameter AB, are the two icy or arctic zones. The Sun’s rays strike
them very obliquely; which is the cause of their being almost
continually covered with ice or snow.
The two circles, CD and LM, are called Polar circles; and the two
extremities, A and B, of the Earth’s Diameter, situated in those
regions, are called the Poles. A is called the North-Pole and B the
South-Pole of the Earth.
§ 35. The different zones of which we have just spoken, are not
equal to one another. Plate XIII, will show their relative extent.
Fig. I represents the surface of the Earth divided proportionally into
its three zones: the torrid, the temperate and the arctic. The inner
circle represents both the arctic zones; the yellow ring b, which
 surrounds it, represents the united extent of the two temperate zones;
and the outmost red ring, the whole of the two torrid zones.
Fig. II represents separately the whole torrid zone;—Fig. III one of
the temperate zones;—Fig. IV one of the arctic zones; and Fig. V the
whole extent of land on our globe.
The next Plate, No. XIV, represents the comparative surfaces of
these zones, drawn separately in form of squares; and the last figure
on that Plate, shows the extent of the five continents, compared to
one of the temperate zones.

No. XV.
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
 You will observe from a close inspection of these figures, that the
whole extent of land on our globe is nearly equal to that of a
temperate zone; and that if it were possible to unite America,
Europe, Asia, Africa and Australia into one, their united extent would
not yet fill one of the temperate zones! You will also perceive that the
two temperate zones occupy together the greatest portion of the
Earth’s surface, and that the arctic zones occupy comparatively the
smallest.

RECAPITULATION OF LESSON VI.

QUESTIONS.
[§ 32.] Do we know anything about the Interior of our Earth? Why
not? What does the surface of our Earth consist of? What proportion
does the land bear to the water? What are the great lands called?
What, the great waters? What are smaller portions of land,
surrounded by water, called? What, small portions of water,
surrounded by land?
[§ 33.] Into how many continents is all the land of our Globe
divided? What are they? Are all the continents of our globe of the
same extent? Which is the smallest of them? Which are the largest?
Explain Plate, No. XI.
What proportion does the extent of America bear to that of Asia?
What relation do these continents bear to Europe or Australia? What
is the next greatest portion on our globe? Which continent is the
smallest? What relation does the surface of the Moon bear to
America or Asia?
[§ 34.] Is the whole Earth equally illumined or heated by the Sun?
Why not? What is, therefore, the surface of our Earth divided into?
Upon what portion of our Earth do the Sun’s rays fall perpendicular?
What portion do they strike more obliquely? What people, therefore,
will experience the greatest heat?
[The pupil ought now to explain Plate XII. The elder pupils ought to
draw a sphere with the Equator, the tropic and arctic circles. They
 ought also to draw the Diameter of the Earth, and indicate the North
and South Pole.]
[§ 35.] If you compare the whole extent of land on our globe to the
Contents of one of the temperate zones, what proportion do you find
them to bear to each other? If it were possible to unite the five great
continents, America, Europe, Asia, Africa and Australia, what zone
would they nearly fill? What two zones occupy the largest portion of
the Earth’s surface? What two, the smallest?
 APPENDIX
CONTAINING THE COMPARATIVE POPULATION OF THE DIFFERENT
QUARTERS OF OUR GLOBE.
[The numbers are given in Table III.]

§ 36. The Five principal parts of our globe, America, Europe, Asia,
Africa and Australia are not equally thickly settled. Europe and Asia
have, in proportion to their extent, the greatest population; America
and Australia the least.—The following Plate, No. XV, shows the
comparative population of these continents.
Fig. I represents the whole surface of land on our globe, inhabited
by nearly One Thousand Millions (One Billion) human beings. If
these were to live throughout as close together as in Europe, then
they would only occupy a surface of land as large in proportion, as
the inner circle marked a. But the two rings, b and c, occupy each as
much surface as the circle a; hence there is yet room for twice as
many human beings; before each quarter of the world is as thickly
settled as Europe.
Fig. II represents Asia and its population. If this quarter were
settled as thickly as Europe is, then its inhabitants would only fill the
inner circle marked b; the ring a, therefore, is still left for settlement.
Fig. III exhibits the population of Africa. If the inhabitants of this
continent lived as close together as those of Europe, they would only
fill the inner circle, marked c, and the surrounding ring might yet be
inhabited.
Fig. IV shows the comparative population of America. Its
inhabitants, crowded together as the inhabitants of Europe, would
only occupy the small circle e; the whole broad ring f, therefore, is
still left for settlement!!
 Fig. V represents Australia. Its inhabitants, settled as in Europe,
would only fill the circle a.
Fig. VI represents the population of Europe filling the whole of that
Quarter.
The whole of these Six figures may represent to the pupil the
comparative extents of the five great continents of our globe; but the
inner circles of these figures, and the whole of the sixth figure, show
their comparative populations. From a close inspection of this plate
the pupil may learn:
1. That the population of Asia is yet greater than that of all the rest
of the world. (The circle b in figure II being yet larger than the inner
circles of all the other figures, and figure VI taken together.)
2. That the population of Europe is as yet larger than that of
America, Africa and Australia, taken together.
3. That the population of Africa is larger than the joint populations
of America and Australia.
4. That America if once settled as Europe is, will have more than
Six times her population.
[The teacher, if he think proper to ask the pupils some questions in
reference to the Appendix, will find no difficulty in adapting them to the
capacity of his pupils.]

TABLE I.
Showing the Diameter, Surface, and Cubic Contents of the Sun and
the Planets.
Diameter in Surface in Cubic Contents in
Names. Geographical Geographical Square Geographical Cubic
Miles. Miles. Miles.
Sun, 194,000 118,093,000,000 3,825,903,253,970,000
Mercury, 608 1,161,314 117,659,099
Venus, 1678 8,844,063 2,473,469,743
Earth, 1719 9,282,066 2,659,159,061
Mars, 1006 3,178,805 532,996,317
Vesta, 74 15,000 2,121,347
Juno, 309 282,690 2,355,750
Ceres, 352 389,182 22,832,034
Pallas, 465 650,266 52,886,472
Jupiter, 19566 1,202,280,406 23,533,143,597,631
Saturn, 17263 936,530,620 2,757,547,946,775
Herschel, 7564 173,696,911 1,359,227,438,858
Moon, 480 723,686 51,561,578

TABLE II.
Showing the exact Duration of the Revolutions of the different
Planets round the Sun.
Duration of the Moon’s
Planets. Years. Days. Hours. Min. Sec.
revolution round the Earth.
27 days, 7 hours, 43 minutes,
Mercury, — 87 23 15 44
and 12 seconds.
Venus, — 224 16 49 10
Earth, 1 — 6 9 8
Mars, 1 321 22 18 31
Vesta, 3 225 — — —
Juno, 4 131 10 30 —
Ceres, 4 220 13 4 —
Pallas, 4 221 15 35 —
Jupiter, 11 314 20 39 —
Saturn, 29 166 2 — —
Herschel, 83 266 9 — —

TABLE III.
Showing the Extent and Population of the five great Continents.
Names of the Continents. Extent in Sq. Miles. Population.
America, 14,868,000 40,000,000
Europe, 3,292,000 198,000,000
Asia, 15,000,000 500,000,000
Africa, 11,267,900 150,000,000
Australia, 3,823,200 1,500,000
The United States, 1,781,926 13,000,000
 POPULAR
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