Gold nanoparticles in analytical chemistry

Advisory Board
Joseph A. Caruso
University of Cincinnati, Cincinnati, OH, USA
Hendrik Emons
Joint Research Centre, Geel, Belgium
Gary Hieftje
Indiana University, Bloomington, IN, USA
Kiyokatsu Jinno
Toyohashi University of Technology, Toyohashi, Japan
Uwe Karst
University of Muănster, Muănster, Germany
Gyroăgy Marko-Varga
AstraZeneca, Lund, Sweden
Janusz Pawliszyn
University of Waterloo, Waterloo, Ont., Canada
Susan Richardson
US Environmental Protection Agency, Athens, GA, USA


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Gold Nanoparticles in
Analytical Chemistry
Comprehensive Analytical Chemistry
Volume 66
Edited by

Miguel Valca´rcel and A´ngela I. Lo´pez-Lorente
Department of Analytical Chemistry
University of Co´rdoba
Co´rdoba, Spain

AMSTERDAM l BOSTON l HEIDELBERG l LONDON l NEW YORK l OXFORD
PARIS l SAN DIEGO l SAN FRANCISCO l SINGAPORE l SYDNEY l TOKYO


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Contributors to Volume 66
Marı´a Jesu´s Almendral Parra, Departamento de Quı´mica Analı´tica, Nutricio´n y
Bromatologı´a, University of Salamanca, Plaza de la Merced s/n, Salamanca, Spain
Vincenzo Amendola, Department of Chemical Sciences, University of Padova,
Padova, Italy
Pedro Baptista, CIGMH, Departamento de Cieˆncias da Vida, Faculdade de Cieˆncias e
Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
Encarnacio´n Caballero-Dı´az, Department of Analytical Chemistry, University of
Co´rdoba, Co´rdoba, Spain
Shaowei Chen, Department of Chemistry and Biochemistry, University of California,
Santa Cruz, CA, USA
Han-Wen Cheng, Department of Chemistry, State University of New York at
Binghamton, Binghamton, NY, USA

Jose´ M. Costa-Ferna´ndez, Department of Physical and Analytical Chemistry,
University of Oviedo, Oviedo, Spain
Patricia Crespo, Instituto de Magnetismo Aplicado and Dpto. Fı´sica de Materiales,
Universidad Complutense de Madrid, Madrid, Spain
Elizabeth R. Crew, Department of Chemistry, State University of New York at
Binghamton, Binghamton, NY, USA
Jorge Ruiz Encinar, Department of Physical and Analytical Chemistry, University of
Oviedo, Oviedo, Spain
Alfredo de la Escosura-Mun˜iz, Institut Catala de Nanociencia i Nanotecnologia
(ICN2), Bellaterra (Barcelona), Spain
Sara Figueiredo, CIGMH, Departamento de Cieˆncias da Vida, Faculdade de Cieˆncias
e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
Ricardo Franco, REQUIMTE, Departamento de Quı´mica, Faculdade de Cieˆncias e
Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
Miguel Angel Garcı´a, Instituto de Magnetismo Aplicado and Dpto. Fı´sica de Materiales, Universidad Complutense de Madrid, Madrid, Spain
Ineˆs Gomes, REQUIMTE, Departamento de Quı´mica e Bioquı´mica, Faculdade de
Cieˆncias, Universidade do Porto, Porto, Portugal; Instituto de Medicina Molecular,
Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
Yan Guo, School of Environmental Science and Engineering, Nanjing University of
Information Science and Technology, Nanjing, Jiangsu, P. R. China; Department of
Chemistry and Biochemistry, University of California, Santa Cruz, CA, USA

xv


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xvi Contributors to Volume 66
Antonio Hernando, Instituto de Magnetismo Aplicado and Dpto. Fı´sica de Materiales,
Universidad Complutense de Madrid, Madrid, Spain
Dominik Huăhn, Fachbereich Physik, Philipps Universitaăt Marburg, Marburg, Germany

Christine Kranz, Institute of Analytical and Bioanalytical Chemistry, University of
Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Bernhard Lendl, Institute of Chemical Technologies and Analytics, Vienna University
of Technology, Vienna, Austria
´ ngela Inmaculada Lo´pez-Lorente, Department of Analytical Chemistry, University
A
of Co´rdoba, Co´rdoba, Spain
Jin Luo, Department of Chemistry, State University of New York at Binghamton,
Binghamton, NY, USA
Moreno Meneghetti, Department of Chemical Sciences, University of Padova, Padova,
Italy
Arben Merkoc¸i, Institut Catala de Nanociencia i Nanotecnologia (ICN2), Bellaterra
(Barcelona), Spain; Institucio Catalana de Recerca i Estudis Avanc¸ats (ICREA),
Barcelona, Spain
Boris Mizaikoff, Institute of Analytical and Bioanalytical Chemistry, University of
Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Sara Sa´nchez Paradinas, Departamento de Quı´mica Analı´tica, Nutricio´n y Bromatologı´a, University of Salamanca, Plaza de la Merced s/n, Salamanca, Spain; Institut
fuăr Physikalische Chemie und Elektrochemie, Leibniz Universitaăt Hannover,
Schneiderberg, Hannover, Germany
Wolfgang J. Parak, Fachbereich Physik, Philipps Universitaăt Marburg, Marburg,
Germany
Lucia Pasquato, Department of Chemical and Pharmaceutical Sciences, University of
Trieste, Trieste, Italy
Miguel Peixoto de Almeida, REQUIMTE, Departamento de Quı´mica e Bioquı´mica,
Faculdade de Cieˆncias, Universidade do Porto, Porto, Portugal
Paolo Pengo, Department of Chemical and Pharmaceutical Sciences, University of
Trieste, Trieste, Italy
Eula´lia Pereira, REQUIMTE, Departamento de Quı´mica e Bioquı´mica, Faculdade de
Cieˆncias, Universidade do Porto, Porto, Portugal
Rosario Pereiro, Department of Physical and Analytical Chemistry, University of

Oviedo, Oviedo, Spain
Josefina Pons, Inorganic Chemistry Unit, Chemistry Department, Science Faculty,
Autonomous University of Barcelona, Barcelona, Spain
Georg Ramer, Institute of Chemical Technologies and Analytics, Vienna University of
Technology, Vienna, Austria
Lourdes Rivas, Institut Catala de Nanociencia i Nanotecnologia (ICN2), Bellaterra
(Barcelona), Spain; Inorganic Chemistry Unit, Chemistry Department, Science
Faculty, Autonomous University of Barcelona, Barcelona, Spain
Alfredo Sanz-Medel, Department of Physical and Analytical Chemistry, University of
Oviedo, Oviedo, Spain


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Contributors to Volume 66 xvii

Shiyao Shan, Department of Chemistry, State University of New York at Binghamton,
Binghamton, NY, USA
Zakiya R. Skeete, Department of Chemistry, State University of New York at Binghamton, Binghamton, NY, USA
Leonor Soares, REQUIMTE, Departamento de Quı´mica e Bioquı´mica, Faculdade de
Cieˆncias, Universidade do Porto, Porto, Portugal; REQUIMTE, Departamento de
Quı´mica, Faculdade de Cieˆncias e Tecnologia, Universidade Nova de Lisboa,
Caparica, Portugal
Mauro Stener, Department of Chemical and Pharmaceutical Sciences, University of
Trieste, Trieste, Italy
Laura Trapiella-Alfonso, Department of Physical and Analytical Chemistry, University of Oviedo, Oviedo, Spain
Marek Trojanowicz, Department of Chemistry, University of Warsaw, Poland and
Laboratory of Nuclear Analytical Methods, Institute of Nuclear Chemistry and
Technology, Warsaw, Poland
Miguel Valca´rcel, Department of Analytical Chemistry, University of Co´rdoba,
Co´rdoba, Spain

Chuan-Jian Zhong, Department of Chemistry, State University of New York at
Binghamton, Binghamton, NY, USA


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Series Editor’s Preface
“Nanotechnology has been defined as the technology of the twenty-first
century, and it is expected that the broad range of nanomaterials together with
their applications on the global market will constantly increase in the coming
years.” This sentence was written two years ago in the preface to Volume 59 of
Comprehensive Analytical Chemistry, Analysis and Risk of Nanomaterials in
Environmental and Food Samples, edited by myself and Dr M. Farre.
It is then obvious that there is a need for the Comprehensive Analytical
Chemistry series to look for new books in the field of nanomaterials. This task
was relatively easy. In one of my regular telephone conversations with Prof.
Miguel Valca´rcel, an old friend and well-known expert in analytical chemistry,
he suggested editing a book on gold nanoparticles. I accepted immediately.
The book that you have in your hands contains 14 chapters. The first five
cover general aspects such as an introduction to analytical nanoscience and
nanotechnology, the synthesis, characterization, and toxicity of gold nanoparticles. In the second part, gold nanoparticles are considered as target analytes, with emphasis on their characterization and determination, including
spectroscopic, mass spectrometric, and separation techniques. Part three
describes the use of gold nanoparticles as analytical tools. They can be
incorporated in electrodes, and used as (bio)chemical sensors as well as lateral
flow biosensors.
With the comprehensive information on this type of nanoparticles, this
multipurpose book with novel applications in biology, the environment, and
food is a useful addition to the series and will be of great benefit to the broad
nanoscience and nanotechnology community.
Finally I would like to thank both editors of this book, Miguel Valca´rcel

´ ngela I. Lo´pez-Lorente, for the amount of work, time, and expertise that
and A
they devoted to it. I would like to acknowledge as well the various well-known
authors for their contributions in compiling such a world-class and timely book
that will be of help to newcomers, PhD students, and those senior researchers
who consider nanotechnology as one of the emerging challenges in the years to
come.
D. Barcelo´
IDAEA-CSIC, Barcelona, and ICRA, Girona
July 10, 2014

xix


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Volume Editor’s Preface
Today we are immersed in a full expansion of Nanoscience and Nanotechnology (N&N). Analytical Science is an integral part of N&N since reliable
information about the nanoworld is crucial in order to make well-founded
scientific and technical decisions in this area. Two key facets of Analytical
Nanoscience and Nanotechnology (AN&N) can be noted: on the one hand, the
consideration of nanoparticles and nanostructured materials as tools for the
innovation and improvement of (bio)chemical measurement processes, and, on
the other hand, their consideration as objects (analytes). The use of nanomaterials as analytical tools is the more developed field, however, the balance
is bound to change over the next few years due to the growing significance of
the characterization of nanomaterials and the development of new instruments
based on nanotechnological approaches.
Among the wide variety of nanoparticles commonly used in AN&N,
namely carbon nanostructures such as carbon nanotubes, carbon dots, graphene, fullerenes, nanodiamonds, etc., semiconductor nanoparticles (quantum
dots), or metallic nanoparticles (i.e., silver, titanium oxide, or magnetic

nanoparticles), this book focuses on nanoparticles of a specific nature: gold. In
this sense, the book is unique as it presents a systematic review on the different
aspects of gold nanoparticles in analytical chemistry. Without doubt, gold
nanoparticles are among the most relevant nanoparticles, having analytical
connotations at a similar level to carbon nanotubes.
The aim of this book is to bring gold nanoparticles closer to the reader
interested in AN&N, providing a comprehensive overview. Although the focus
is on gold nanoparticles, many of the general conclusions can be extrapolated
to other nanoparticles. Those professionals working not only in AN&N but
also in different fields involving the use of gold nanoparticles, such as catalysis, biological and medical applications, can also benefit from the book since
many of the exceptional properties of gold nanoparticles can be applied for
different purposes.
The 14 chapters are classified into three sections. First, basic aspects of
gold nanoparticles such as their synthesis, physicochemical properties, or
derivatization procedures are described in order to envisage their potential.
The second part of the book reviews the techniques employed for both the
characterization and determination of gold nanoparticles. The last part is
devoted to the improvement of analytical processes by using gold nanoparticles as tools in electrochemistry, spectroscopy, or biosensors.
xxi


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xxii Volume Editor’s Preface

The editors wish to express their gratitude to those who have helped to
bring this book to completion. We would like to thank to all the authors for
their contributions and the exhaustive revisions they have performed. We also
like to thank the cooperation of Elsevier and, for his technical support, Jose´
Manuel Membrives.
Miguel Valca´rcel

´ ngela I. Lo´pez-Lorente
A
July 2014


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Chapter 1

Analytical Nanoscience
and Nanotechnology
A´ngela Inmaculada Lo´pez-Lorente and Miguel Valca´rcel*
Department of Analytical Chemistry, University of Co´rdoba, Co´rdoba, Spain
*Corresponding author: E-mail:

Chapter Outline
1. Contextualization
1.1 Definitions
1.2 Classifications
1.3 Synthesis of Nanoparticles
1.4 Types of Nanoparticles
1.4.1 Organic
Nanoparticles
1.4.2 Inorganic
Nanoparticles
1.4.3 Hybrid
Nanoparticles
1.5 Properties of
Nanoparticles
2. Introduction to Analytical

Nanoscience
and Nanotechnology
2.1 Facets of Analytical
Nanoscience and
Nanotechnology
2.2 Types of Analytical
Systems
2.2.1 Nanometric
Analytical Systems
2.2.2 Nanotechnological
Analytical Systems
2.2.3 Analytical
Nanosystems

4
4
5
6
7
9
11
12
12

13

13
13
14
15

16

2.3 Evolution and Limit of
Analytical Nanoscience
and Nanotechnology
2.4 Ethical and Social
Implications
3. Use of Nanoparticles as Tools
in Analytical Processes
3.1 Objectives
3.2 Sample Treatment:
Purification and
Preconcentration
of Analytes
3.3 Improvement of
Chromatographic and
Electrophoretic
Separations
3.4 Improvement of Detection
Processes
4. Analysis of Nanoparticles
and Nanostructured Material
4.1 Information from the
Nanoworld
4.2 Determination and
Characterization of
Nanoparticles
4.3 Microscopic Techniques
4.4 Separation Techniques

Gold Nanoparticles in Analytical Chemistry. />Copyright © 2014 Elsevier B.V. All rights reserved.

17
18
19
19

20

22
23
23
23

24
25
26

3


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4 PART j I Generalities
4.5 Spectroscopic Techniques
4.6 Other Techniques
4.7 Nanometrology

27
29
30

5. Final Remarks
Acknowledgments
References

30
31
31

1. CONTEXTUALIZATION
1.1 Definitions
The common characteristic of nanoscience and nanotechnology (N&N) is the
size of the target objects, which are comprised in the so-called “nanometric
scale,” typically between one and 100 nm.
Nanoscience has multiple complementary definitions, such as “the science
of the synthesis, analysis and manipulation of materials at atomic, molecular,
and macromolecular scales where physico-chemical properties may differ
significantly from those at a larger particulate scale,” [1] or, simply: “the
science based on the diverse structures of materials which have dimensions of
a billionth part of the meter” [2].
On the other hand, Nanotechnology “deals with the design, characterization, production and application of structures, devices and systems by controlling the shape and size at the nanometer scale” [1].
A substantial aspect of nanoscience and nanotechnology (N&N) is its
multidisciplinary as well as transversal and convergent character. Physicists,
chemists, and engineers are the scientists and professionals more directly
involved, but their convergence with other areas such as information technology and communication, biotechnology, and materials science, in a first
approach, and medicine, pharmacy, agrifood, and diverse types of industries
such as textile or energetic, in another, has to be pointed out.
Analytical science cannot be left out of N&N [3] and, in fact, it is even present
in many definitions of N&N since reliable information about the nanoworld is
crucial to make well founded scientific and technical decisions in this area.

Words belonging to the analytical discipline such as “analysis” or “characterization” and others shared with other disciplines such as “use” or “employment”
summarize the two key facets of the relationship between analytical chemistry
and nanoscience and nanotechnology, namely, (1) the consideration of nanoparticles and nanostructured materials as objects (analytes) or (2) tools for the
innovation and improvement of the (bio) chemical measurements processes.
The major application areas of nanotechnology can be classified into four
groups [3], namely, (1) nanobiotechnology and nanomedicine, (2) nanomaterials,
(3) nanoelectronics, and (4) nanosensors/nanodevices, nanotechnological
instrumentation, and nanometrology. The last area is directly related to analytical
science, which also plays an essential role in the other three, for example, dealing
with the monitoring of production processes or both the characterization and use
of end products.


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Analytical Nanoscience and Nanotechnology Chapter j 1

5

1.2 Classifications
There are several emerging possibilities when introducing nanoscience and
nanotechnology in the analytical scope. Therefore, a multiple classification
based on four complementary criteria has been created, which is shown
schematically in Figure 1 and is described in the following text.
The first criterion (Figure 1(1)) considers the type of material analyzed,
which can be conventional (macro or micro in size) or nanomaterials. In the
first case, nanoparticles can be involved in the analytical process, conferring to
it nanotechnological character. An example is the use of quantum dots functionalized with antibodies, which can be injected in organisms in order to
detect carcinogenic processes [4]. In the second possibility, the target is the
own nanoworld, which coincides with the consideration of nanomaterials as
analytes. For example, the determination of nanomaterials such as gold

nanoparticles [5] or carbon nanotubes [6e8] from environmental and biological matrices [9].
The second criterion (Figure 1(2)) relies on the analytical consideration of
nanoparticles and nanostructured materials as objects (analytes) or tools
involved in the analytical process. The extraction of chemical information

Nanoworld

TARGET OF THE
ANALYSIS

Macroworld
Microworld

1
ANALYTICAL
NANOSCIENCE AND
NANOTECHNOLOGY

2
Nanomaterials as
ANALYTES

Detection/quantification
of nanomaterials

NANOPARTICLES AND
NANOSTRUCTURED
MATERIAL

Nanometric analytical

systems

Nanomaterials as
ANALYTICAL TOOLS

EXPLOITATION OF
SYSTEM SIZE

3

EXPLOITATION OF
NANOMATTER
PROPERTIES

4

Analytical
nanosystems
Characterization of
nanomaterials
Nanotechnological
analytical systems

FIGURE 1 Inherent classifications of analytical nanoscience and nanotechnology take into
account four criteria: (1) target of the analysis; (2) consideration of the nanomatter; (3) exploitation
of the nanosize; and (4) exploitation of the nanomatter properties.


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6 PART j I Generalities

from the structured nanomaterials (composition, chirality, reactivity, etc.) is an
indispensable complement to the physical characterization, which is more
well-known (dimensions, topography, etc.) [10]. On the other hand, nanomaterials can be used as analytical tools in order to develop new analytical
processes or to improve existing ones (i.e., development of optical sensors,
development of stationary and pseudostationary phases in chromatography and
capillary electrophoresis, mechanical sensors, etc.).
Criteria 3 and 4 (Figure 1(3) and (4)) are based on exploitation in the
analytical scope of the exceptional properties of nanomaterials, in
exploiting the nanosize, or both. This leads to the definition of three types
of analytical systems related to nanoscience and nanotechnology: nanotechnological analytical systems, nanometric analytical systems, and
analytical nanosystems [11]. Nanotechnological analytical systems exploit
the exceptional physico-chemical properties of nanomaterials (although
they are in micro/macro analytical systems) accounting for the most current
uses of analytical nanoscience. Nanometric analytical systems, which are
based exclusively on the nanosize of the devices involved, are exemplified
by nanochip liquid chromatography systems [12] exploiting the advantages
of working with flow rates as low as a few nanolitres per minute, a
nanopipette [13], or levitated nanodrops as analytical containers [14].
Finally, analytical nanosystems successfully integrate the previous two
types of systems by exploiting both the nanosize and nanomaterials
properties (e.g., individual carbon nanotubes for use as electrodes [15],
supramolecular systems that selectively recognize an analyte [16], and the
so-called lab-on-a-particle [17]).

1.3 Synthesis of Nanoparticles
Nanomaterials can exist in the environment from a natural source, such as
organic colloids, magnetite, aerosols, iron oxides, etc. The nanotechnological
revolution is posed in a change of paradigm in the fabrication of products. Two
approaches can be used to raise nanosize, namely, (1) “top-down” strategies,

based on methodologies which achieve nanosize materials from macromaterials (nanoparticles are directly generated from bulk materials via the
generation of isolated atoms usually involving physical methods such as
milling or attrition, repeated quenching and photolithography [18]) and (2)
“bottom-up” strategies, based on the creation of complex nanostructures from
atomic or molecular functional elements. They comprise molecular components as starting materials linked with chemical reactions, nucleation, and
growth processes to promote the formation of clusters. Numerous kinds of
nanoparticles have been produced by liquid-phase synthesis, using techniques
such as co-precipitation of sparingly soluble products by addition, exchange,
and reduction reactions, oxidation, hydrolysis [19], solegel processing [20],
microemulsions [21], etc. The latter approach is generally considered to be far


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Analytical Nanoscience and Nanotechnology Chapter j 1

7

TOP-DOWN
1 µm

Macromaterials

100 nm

NANOSCALE
10 nm

1 nm

Molecules,

atoms

0.1 nm

BOTTOM-UP
FIGURE 2 Scheme of the two approaches employed in the fabrication of nanomaterials: “topdown” and “bottom-up.”

more promising due to the higher level of control offered. Figure 2 shows a
scheme of the different strategies (“top-down” and “bottom-up”) used to
achieve the nanoscale.

1.4 Types of Nanoparticles
According to the IUPAC Glossary, a nanoparticle is a microscopic particle
whose size is measured in nanometers, often restricted to so-called nanosized
particles (NPs; < 100 nm in aerodynamic diameter), also called ultrafine
particles [22]. With the expected increase in the applications of nanotechnology, more and more products will be manufactured containing components
which will fit the commonly used definition of the nanoscale, as having a size


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8 PART j I Generalities

Homogeneous

Heterogeneous

HOMOGENEITY

Naturally
occurring

2

1

ORIGIN

Incidental

Engineered

CLASSIFICATION OF
NANOSTRUCTURES

Organic

3

NATURE

Inorganic

Hybrid

4
2

nd

classification

DIMENSIONALITY

1st classification

Number of dimensions above
100 nm

Number of dimensions below
100 nm

0D No dimension

Nanoscale in ZERO dimensions

ID One dimension

Nanoscale in ONE dimension

2D Two dimensions

Nanoscale in TWO dimensions

3D Three dimensions

Nanoscale in THREE dimensions

FIGURE 3 Classification of nanostructures according to their origin (1), homogeneity (2), nature
(3), and dimensionality (4).

between approximately one and 100 nm. These wide varieties of nanostructures have been classified in multiple ways in the literature.
Figure 3shows the most relevant types of nanostructures in analytical nanoscience and nanotechnology, classified according to four nonexclusive criteria.
Nanoparticles can be classified as natural, anthropogenic (incidental), or
engineered in origin [9] (Figure 3(1)).
From a practical point of view, it is important to know the homogeneity of
the nanostructured materials both for scientific studies as well as for industrial
applications. Homogeneity can be referred to in terms of chemical composition or dimensionality (Figure 3(2)). Identical nanoparticles are those with the
same chemical composition and dimensions. On the contrary, nanoparticles
with the same chemical composition but different dimensions usually present
different properties.
Concerning the nature or chemical composition of nanostructures, those
can be classified (Figure 3(3)) as inorganic (e.g., noble metal nanoparticles,
quantum dots, etc.), organic (fullerenes, carbon nanotubes, dendrimers,
molecular imprinted polymers, etc.) or mixed (gold nanoparticles modified
with calixarenes, carbon nanotubes functionalized with ferrocene, etc.). In this
context, there is a growing interest in the development of hybrid nanoparticles,
which can be defined as well-organized nanomaterials consisting of two or
more types of individual nanocomponents [23].


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Analytical Nanoscience and Nanotechnology Chapter j 1

9

The last classification of nanomaterials is based on dimensionality criteria
(Figure 3(4)). As shown in the figure, two classifications may be done, taking
into account both the strict dimensions (in the nanoscale) of the nanostructure
that give rise to those exceptional properties and the dimensions of the
material where nanostructures are present.

The Royal Society of Chemistry and the Royal Academy of Engineering
classified nanostructures in function of the number of dimensions in the
nanoscale (below 100 nm) [24], distinguishing three types of nanostructures:
(1) nanoscale in one dimension, such as surfaces with nanometric thickness
(e.g., graphene sheets); (2) nanoscale in two dimensions, such as carbon
nanotubes, inorganic nanotubes, nanowires, etc.; (3) nanoscale in three
dimensions, which includes metallic nanoparticles and their oxides, quantum
dots, fullerenes, and dendrimers. Classification of nanoscale at zero dimension
can also be added, such as materials composed by dispersed nanoparticles.
Other authors [25] have classified nanostructures depending on the number
of dimensions which exceed 100 nm, being above the nanoscale, nanostructures being thus categorized as 0D, 1D, 2D, or 3D. A 0D nanostructure is
a material with all its dimensions comprised in the nanometric scale (e.g.,
metallic nanoparticles, quantum dots, etc.). Carbon nanotubes are an example
of 1D nanostructures, which have one dimension of micro/macrometric size,
such as nanowires or nanorods. 2D nanostructures have two dimensions above
nanoscale while one of them is below 100 nm. That is the case of surface
nanocoatings or thin films of molecular monolayers. Finally, 3D nanostructures are those whose three dimensions escape from the nanoscale, but the
material is comprised by a set of nanoparticles forming a block of micro/
macrometric size (e.g., nanoporous materials, powders).
We will focus on engineered nanoparticles, which can be classified according to their nature as organic, inorganic, or hybrid.

1.4.1 Organic Nanoparticles
1.4.1.1 Carbon Nanomaterials
Graphitic forms include 0D fullerene, 1D CNT, and 3D graphite, and the 2D
case comes to the graphene, a single layer of carbon atoms formed in a
honeycomb lattice.
Graphene is an open, flat, two dimensional structure composed of carbon
atoms organized in a network of hexagons attached to each other. This is
possibly a result of sp2 hybridization of the carbon atoms present in the sheet.
It has a large specific surface area and can be easily modified with functional

groups, especially via graphene oxide. Graphene quantum dots (GQDs), a new
kind of quantum dots, have emerged and ignited tremendous research interest.
GQDs are defined as graphene sheets with lateral dimensions less than 100 nm
in single, double, and few (3 to <10) layers. GQDs show low cytotoxicity,
excellent solubility, chemical inertia, stable photoluminescence, and better


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10 PART j I Generalities

surface grafting. Therefore, they are promising in optoelectronic devices,
sensors, bioimaging, etc. [26].
Another two examples of 0D carbon-based fluorescent nanomaterials are
diamond nanocrystals (DNs) and carbon dots (CDs), which have also drawn
much attention in recent years. In general, DNs consist of about 98% carbon
with residual hydrogen, oxygen, and nitrogen; they possess a sp3 hybridized
core and have small amounts of graphitic carbon on the surface. Luminescent
CDs comprise discrete, quasispherical carbon nanoparticles with sizes below
10 nm.
Fullerenes are closed-cage carbon molecules containing pentagonal and
hexagonal rings. They comprise a wide range of isomers and homologous
series, from the most studied C60 and C70 to the so-called higher fullerenes like
C240, C540, and C720. They possess relatively high electron affinity, hydrophobic surface, and high surface/volume ratio.
Carbon nanotubes have received special attention ever since their discovery
by Iijima in 1991 [27]. They are tubular in shape and consist entirely of
covalently bonded carbon atoms. They can be described as hollow graphitic
nanomaterials comprising one (single-walled carbon nanotubes, SWNTs), two
(double-walled carbon nanotubes, DWNTs) or multiple (multiwalled carbon
nanotubes, MWNTs) layers of graphene sheets. They possess nonpolar bonds
and high aspect ratios, which make them insoluble in water and facilitate their

aggregation.
Carbon nano-onions (CNOs) are nanoparticles with a diameter between 20
and 100 nm composed of several layers of concentric fullerenes and constitute
the spherical version of MWNTs. They were described by Ugarte [28] in 1992,
although few applications have been reported.
Moreover, carbon nanofibers (CNFs) are solid carbon fibers with lengths in
the order of a few microns and diameters below 100 nm. CNFs differ from
CNTs in the absence of a hollow cavity, and the diameters of CNFs are
generally higher than those of the corresponding CNTs [29].
Finally, carbon nanocones were first synthesized by vapor condensation of
carbon atoms on a graphite substrate [30]. The disclination of each structure
corresponds to the presence of a given number of pentagons in the seed from
which it grew: disks (no pentagons), five types of cones (one to five pentagons), and open tubes (six pentagons). The unique electronic distribution,
which is provided by these pentagonal rings to the carbon nanocones, results in
enhanced local density at the cone apex. One major class of cone structures are
single-walled carbon nanohorns (SWNHs) with the narrowest opening angle
with five pentagonal rings in their apex (Figure 4).
1.4.1.2 Other Organic Nanomaterials
Organic polymeric nanoparticles are prepared from polymers and considered
potential drug delivery devices. Dendrimers are one kind of polymeric nanoparticles constructed by the successive addition of layers of branching groups.


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FIGURE 4 Main types of carbon-based nanomaterials. Adapted with permission from Ref. [29].

Molecularly imprinted polymers (MIPs) are a specific class of selective

sorbents that have built-in functionality to achieve the complementary
recognition of a given chemical compound [31]. Although MIP particles can
be nanometric in size, they usually fall in the micrometric range.
In addition, an increasing number of diverse nanomaterials are emerging
for biopharmaceutical applications, such as liposomes, nanomicelles, nanovesicles. nanoemulsions, etc. [32].

1.4.2 Inorganic Nanoparticles
Inorganic nanoparticles cover a broad range of substances including elemental
metals, metal oxides, and metal salts. Silver nanoparticles (AgNPs) are used
in many products as a bactericide, whereas gold nanoparticles (AuNPs) are
explored for many possible applications because of their catalytic activity.
Both silver and gold nanoparticles possess the so-called surface plasmon as a
result of the collective oscillation of the electrons, which gives them excellent
optical properties and a large enhancement of the electric field on their
surface.
Quantum dots (QDs) are semiconductor nanocrystals with all three
dimensions falling in the 1e10 nm size range. In many respects, these luminescent nanocrystals constitute a transitional stage between bulk semiconductors and single atoms. The QD core is made up of elements from the
IIeVI (e.g., CdSe, CdTe, CdS, and ZnSe), IIIeV (e.g., InP and InAs), or
IVeVI (e.g., PbSe) group [33]. They have aroused widespread interest by
virtue of their exceptional optical, electronic, electrochemical, photophysical,
redox, and catalytic properties.
Nanoparticulate metal oxides are widely used, such as TiO2, Al2O3,
ZrO2, MnO and CeO2, as well as nanoparticles of iron oxides (FeOx).
Attention should be paid to the increasingly used magnetic nanoparticles,
which have been synthesized with a number of different compositions and
phases, including iron oxides, such as Fe3O4 and g-Fe2O3, pure metals, such
as Fe and Co, and spinel-type ferromagnets, as well as alloys [34]. Moreover, silica nanoparticles (SiO2) are characterized by presenting high surface
areas and exhibit intrinsic surface reactivity, which allows chemical modifications [10].

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12 PART j I Generalities
FIGURE 5 Transmission electron microscopy
images of model inorganic nanoparticles, namely,
Ag, Au, TiO2, Fe3O4, CeO2, and NPs. Adapted with
permission from Ref. [36].

Nano-size zeolite, clays, and ceramics are other nanoparticles that have
been proposed for various applications [35] (Figure 5).

1.4.3 Hybrid Nanoparticles
Hybrid nanoparticles can be defined as well-organized nanomaterials consisting of two or more types of individual nanocomponents [23]. Those
nanocompounds can be bound via organic/inorganic molecular bridges or
directly attached to one another. Apart from the special type of bonding between the nanocompounds, the exceptional properties of hybrid nanoparticles
are due to the highly organized arrangement of the nanoconstituents.
Nanoparticles possess excellent properties that can be boosted or supplemented by combining two or more types of materials into a hybrid nanocomposite. In general, hybrid nanoparticles can be classified into two different
types according to the combined properties [23], namely, (1) properties of the
isolated nanoparticles are different but complementary, and (2) properties of
the isolated nanoparticles are of the same nature, but their combination
produces important synergistic effects.

1.5 Properties of Nanoparticles
The “nanoscale” has introduced a new scenario where impressive changes in
physico-chemical principles, laws, and properties are observed as regards
macro- and micro-materials.
Two especially significant differences have been described: the surface/
volume ratios and chemical reactivities of nanostructured matter in comparison to macro- and micro-scale matter. In addition, quantum effects are
enhanced by effect of the configuration of molecular orbitals (similar to that of
atomic orbitals) and, as a consequence, chemical, optical, electrical, thermal,
and magnetic characteristics are unique on the nanoscale. Such changes have

shaped the impact of nanotechnology in a number of scientific, technical, and
industrial fields.


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2. INTRODUCTION TO ANALYTICAL NANOSCIENCE
AND NANOTECHNOLOGY
2.1 Facets of Analytical Nanoscience and Nanotechnology
Generally, nanomaterials in the analytical nanoscience and nanotechnology
(AN&N) scope are considered as analytical objects or analytical tools.
Analytical nanoscience and nanotechnology currently provide one of the most
promising avenues for developments in analytical science, derived from their
two main fields of action, namely the analysis of nanostructured materials and
their use as tangible tools [37]. The use of nanotechnological tools in
analytical methods can improve the analytical properties and enables the
development of new types of analysis. On the other hand, analysis of the
nanoworld is an issue of analytical chemistry.
A third classification, as an interface between the two previous, can be
introduced, which is the use of nanomaterials in analytical processes for the
characterization and/or determination of other nanomaterials, see Figure 6.
Examples of this facet are, for instance, the use of silver or gold nanoparticles
as SERS substrates for the determination of other nanomaterials (e.g., carbon
nanotubes [6]), or the use of membranes composed by multiwalled carbon
nanotubes for the preconcentration and determination of single-walled
carbon nanotubes [7].

2.2 Types of Analytical Systems
The use of nanomaterials as analytical tools is one of the facets of analytical
nanoscience and nanotechnology. Nanotechnology-based analytical processes

AN&N
1

3

Nanomatter as
analytical objects

2
Nanomatter as
analytical tools in
analytical processes

Use of nanomaterials in
analytical processes of
characterization and
determination of nanoparticles

FIGURE 6 Different facets of nanoparticles in analytical nanoscience and nanotechnology
(AN&N) scope.


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14 PART j I Generalities

can exploit both the nano size and exceptional properties of structured nanomatter. In this sense, as it was previously introduced (see Figure 1 and related

text), analytical systems based on nanoscience and nanotechnology can be
classified into three types [11]:
1. Nanometric analytical systems are based on nanosize and/or nanofluidics,
for example, nanochip liquid chromatography. However, some authors
have placed them outside the scope of nanotechnology.
2. Nanotechnological analytical systems exploit the exceptional physicochemical properties of nanomaterials.
3. Analytical nanosystems integrate the previous two systems, for example,
individual carbon nanotubes for use as electrodes (Figure 7).

2.2.1 Nanometric Analytical Systems
As previously defined, nanometric analytical systems are analytical systems
that take advantage of the fact that some technical characteristics or elements
of the analytical process have nanometric size of flow. Thus, their foundation
is not based on the new physico-chemical scenario imposed by nanomaterials
and their exceptional physical and chemical properties. They can be considered as a trend of miniaturization.
They cannot be completely considered inside the scope of nanotechnology,
although because of the undoubted advantages they offer, many authors
include them. Some representative examples of this kind of systems are
reported as follows.
Some nanometric analytical systems are based on nanometric volumes
employed. Such is the case of the use of levitated nanodrops [14]. This strategy
has been employed for online monitoring of chemical reactions in

Nanotechnology

Nanoscience
… MiniaturizaƟon

CharacterisƟcs
exploited in the

analyƟcal context

Nanometric
size

ExcepƟonal
properƟes of
nanomaterials

NANOMETRIC
ANALYTICAL
SYSTEMS

NANOTECHNOLOGICAL
ANALYTICAL SYSTEMS

ANALYTICAL
NANOSYSTEMS
(ideals)

Interfaces

FIGURE 7 Difference between the three general types of analytical systems related with
nanoscience and nanotechnology.


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ultrasonically levitated, nanoliter-size droplets by Raman spectroscopy. A
flow-through microdispenser connected to an automated flow injection system
was used to dose picoliter droplets into the node of an ultrasonic trap. A
sequence of reagents can be injected via the microdispenser into the levitated
droplet. Thus, chemical reactions can be carried out and monitored online. The
droplet suspended in the air enables the removal of interferences from the
recipient and a rapid evaporation of the solvent. This has eased the direct
analysis with Raman microscopy [14] as well as the development of interfaces
in direct couplings in which sample solvent is a problem, such as in matrixassisted laser desorption/ionization time of fight mass spectrometry
(MALDI-TOF-MS) [38].
The chromatographic systems called “Nano-LC” are based on the use of
liquid mobile phases with a flow rate of a few nanolitres per minute [39], in
contrast with conventional ones in the range of microliters per minute. That
implies a new design for the chromatography instrument, but it offers advantages such as ease of use, both the delay time for the gradient to arrive at
the head of the column and the dead volume between the separation column
and the ESI tip are minimized, resulting in a shorter running time and reduced
band broadening.
The so-called “nanopipettes” [13] are integrated, carbon-based pipettes
with nanoscale dimensions that can probe cells with minimal intrusion, inject
fluids into the cells, and concurrently carry out electrical measurements. They
allow the direct transference of nanovolumes in the range of nano/picoliters
between micro/nanometric compartments. This transference is based on the
electro-osmotic phenomena. Their applications in the field of biotechnology
are very promising, as well as in high-throughput analysis, key in the field of
the pharmacological industry to perform multisynthetic experiments in the
development of new drugs.

2.2.2 Nanotechnological Analytical Systems
Nanotechnological analytical systems exploit the exceptional properties of the

nanometric materials (nanoparticles and nanostructured materials) with
analytical purposes. They posses micrometric dimensions, but once their
dimensions can be reduced into the nanoscale, they could be called “analytical
nanosystems.”
In these systems, there is a micro-element which acts as a bridge between
the nanocomponents and the signal transduction system through a simple
physical bond. The active nanocomponent is responsible for the interaction
and produces the analytical signal.
One illustrative example is micro-electromechanical systems (“nanocantilevers”) [40,41], which are based on the immobilization of a biochemical
receptor in a probe of nanometric dimensions in a micromechanical silicon
system that is sensitive to the environment, including chemical compounds and


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biological entities which affect their mechanical characteristics in such a
manner that the change can be measured in terms of electrical or optical
properties [5]. Although a micro-electromechanical system is micrometric in
size, its sharp tip, which allows interaction forces at the atomic scale to be
sensed, is a nanometric device. Their most remarkable advantages are their
reduced dimensions, portability (in some cases), and their high levels of
sensitivity and selectivity for the determination of a wide variety of analytes.
Their scope is defined by the biochemical interaction analyte-receptor.
Other examples of nanotechnological analytical systems are the field effect
transistors (FETs), which have been revitalized by the introduction of nanostructured materials [41]. Such is the case of the use of semiconducting carbon
nanotubes or a network of nanotubes placed between two electrodes of
micrometric dimensions. Carbon nanotubes are derivatized in order to achieve
a more specific interaction with the analyte. When it is retained, a change in
the electronic properties of the carbon nanotubes is originated, which leads to

a variation in the potential between the electrodes, used as an analytical signal.
Semiconducting carbon nanotubes have been employed for the determination
of a wide variety of gaseous analytes, such as NH3, CO, and CO2 among
others because they exhibit larges changes in electric conductivity in their
presence [42].
Finally, another example of this type of system is a nano-electrode, consisting of a single multiwalled carbon nanotube (2e3 mm in length and 30 nm
of diameter) bonded to the end of an etched tungsten tip [15], which acts as a
bridge. This is a real nano-electrode since it has nanometric dimensions and
exploits the exceptional properties of nanomatter, although it is coupled to a
micrometric device, the tungsten tip. The carbon nanotube surface can be
functionalized with a wide variety of (bio) chemical compounds in order to
improve the selectivity and the field of application. It offers the advantage of
compatibility with micro/nano-size samples (e.g., cells). This nano-electrode
has been used to determine dopamine and glutamate (immobilizing glutamate oxidase enzyme in CNT surface) in a physiological medium with a
quantification limit of 100 mm.

2.2.3 Analytical Nanosystems
These systems can be defined as instruments or devices that have a nanometric
size and are controlled by the physico-chemical laws of Nanoscience. In
addition to the nanometric size, the exceptional properties of nanomatter are
also exploited. This is an ideal situation, since microcomponents are needed to
connect the nanoworld with the macroworld [3].
A nanochemical approach to a real analytical nanosystem is the so-called
“lab-on-a-particle” [17], which aims to emulate the micrometric scale developments (“lab-on-a-chip”). This nanosystem consists on a supramolecular
nanoarchitecture that incorporates chemical entities that can be employed as a
“gate” to allow controlled access to a specific site on the supramolecular


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complex. An example is mesoporous silica nanoparticles functionalized with
switchable molecules, whose inner pores can be used to entrap chemical
species. The gate will open upon the application of physico-chemical external
impulses, such as photochemical or electrochemical, and can release confined
guests or allow molecular species of the solution to be incorporated.

2.3 Evolution and Limit of Analytical Nanoscience
and Nanotechnology
Nanoscience and nanotechnology unarguably have promising prospects.
A report of the US National Science Foundation [43] predicted that a new
revolution based on the bio-nano-info triangle will shortly surpass the present
evolution of the computer-info binomial.
The scientific and industrial impact of nanoscience and nanotechnology
has grown dramatically in recent years. The exponential growth of the number
of papers on this topic published in the last 10 years in the SciFinder and the
vast amount of economic resources invested in industrial technological
developments each year [44] constitute the best support for the brilliant present
and promising future of nanoscience and nanotechnology. It should be pointed
out that there are more than one million scientific papers published on this
topic (Figure 8).
The impact of nanotechnology leaves no shadow of doubt. Hassan [45]
emphasized that the most crucial aspect in this respect is the small things-big
changes binomial. Analytical chemistry should play a major role in the coming
advances in N&N, particularly in these aspects: (1) the environmental and
toxicological impacts of nanotechnology, (2) the need for homogeneous, pure,

FIGURE 8 Scientific and industrial evolution of nanoscience and nanotechnology: (left) number

of publications per year, (right) millions of euros involved in European nanotechnological industry.


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FIGURE 9 Present situation and trends in the two facets of analytical nanoscience and nanotechnology: nanomaterials as analytical tools and analysis of the nanoworld.

well-characterized nanoparticles, (3) the need to address nanometrology, and
(4) nanomedicine, in the development of biomeasurement nanosystems and
the characterization and monitoring of nanostructured pharmaceuticals [3].
Regarding analytical nanoscience and nanotechnology, the use of nanomaterials as analytical tools is the most developed field. Although more than
one half of reported applications relate to the use of nanoparticles, the balance
is bound to change over the next few years due to the growing significance of
the characterization of nanomaterials and the development of new instruments
based on nanotechnological approaches (Figure 9).
Nowadays, the prefix “nano” is opening many doors, which leads to many
authors misusing it to their advantage. The prefix “nano” should be used in
connection to nanomaterials, nanostructures, and nanodevices that exploit not
only the size but also the exceptional properties of the nanoworld. The same
happened in the past with other overexploited keywords such as “sensor.”
Fortunately, this terminological abuse has vanished over time.

2.4 Ethical and Social Implications
Nanotechnology has been deemed as a key emerging technology for fulfilling
the “grand challenges of our time” (Lund Declaration [46]) in areas such as
health care, energy production, environmental protection, and potable water
procurement. However, it shows two contradictory connotations, namely, (1)
the production of new materials with outstanding mechanical, optical, electric,
and magnetic properties for a wide variety of uses, which is highly positive,

and (2) its uncertain effects on human health and the environment, which is
highly negative [47].
There are two major deficiencies regarding the impact of nanotechnology.
One is that the risks and ethical implications of nanotechnology in the production and industrial domains have not been considered. The other is that,
although the potential hazards of nanotechnological products has been