Entering the Era of Nanoscience: Time to be so Small
Vuk Uskoković
University of California, San Francisco, CA, USA
Abstract The field of nanoscience has produced more hype than probably any other branch of
materials science and engineering in its history. However, it seems as if the potentials of this new
field are still mostly unrevealed and what we have realized so far with respect to the peculiarity
of physical phenomena on the nano scale is merely a tip of an iceberg. What this brief
perspective article aims at is standing on the constantly expanding seashore of the coast of
nanoscience and nanoengineering and envisioning the parts of the island where the most
significant advances may be expected to occur and where, therefore, most of the attention of
scientist in this field are to be directed. (a) Crossing the gap between life science and materials
science perspectives; (b) Increasing limits in sensitivity; (c) Crisscrossing theoretical and
experimental knowledge; (d) Conjoining top-down and bottom-up synthetic approaches; and (e)
Fulfilling the aesthetic potentials of materials science are in that sense outlined as the main
challenges for this relatively new field of materials science, which shows us once again that
critical boundaries of immense importance lie dormant in small things and details of the reality.
As shown in Fig. 1, humanity has over time produced a gradual increase in the fineness
with which it is able to manipulate with the material substrate of its environment1. As the result,
we have witnessed miniaturization of devices in our everyday surrounding. As of a few decades
ago, materials science has entered the era of controlling physical phenomena at the nanoscale.
Potentials for producing ever greater technological and biomedical applications have
consequently arisen. Yet, as the limits in controllability are stretched more than ever, questions
have been posed: how far would we be able to go from now on? Certainly, advances are not only
possible in the realm of nanoscience, but seem inevitable. In what follows I will briefly outline
some of the provinces within the kingdom of nanoscience where I would expect the most critical
advances to be made in the near future. At the same time, those could be currently seen as the
most exciting frontiers in the research of nanoscale physical processes.
Fig.1. Critical length scales for some of the key inventions from the history of humanity. As one shifts from
prehistoric huts, cutting tools and garments to modern musical instruments, automobiles and mechanical clocks to
computers, nanocopters and nanomotors, the critical lengths shift from millimeter to micrometer to nanometer scale,
respectively.
1)
Crossing the gap between life science and materials science perspectives. This is a vital
challenge for scientists that dwell on any of these two mainstream sides of the contemporary
research. The gap between the two fields is caused by different methods and vocabularies that
biological and materials scientists employ to describe and fundamentally understand the subjects
of their inquiry. Namely, whereas the former mostly tackle highly specific molecular recognition
properties of biomolecules, the latter rely on more robust, math-based and classical physical
concepts. Yet, it is an inescapable transition for the frontiers of materials science, and especially
its nano fields, to adopt synthetic and characterization approaches that are applied in life
sciences. Biomedical contexts of a large extent of the modern materials science research simply
dictate that2,3,4. Many successful biocombinatorial screening techniques, including selective
adsorption using phage display panning techniques, to assess specificity of protein-nanomaterial
interactions have led to important and highly functional organic-inorganic interfaces. However,
although numerous highly specific interactions between polypeptides and inorganic surfaces
were elucidated and applied using this technique, it still does not allow for discerning the aspects
of crystal formation on which the proteins have the most decisive influence: nucleation, diffusion
or surface-controlled crystal growth, aggregation of subunits, morphological evolution during
aging, etc (yet, strictly speaking, all of these aspects are intertwined and affecting one of them is
hardly possible without affecting all the other). Standing on the bridge that links the two fields,
one would also be able to understand better the currently odd and unexpected effects of
nanoparticles on cells and organisms5. Although most commercially applied nanoparticles are
either confined within functional devices or coated, which minimizes their exposure to air and
thus mitigates their possible toxic effects, toxicity evaluations are expected to attract more
funding in future compared to its current levels, especially since it is known that just as material
properties are often subject to dramatic change as the grain sizes are decreased down to nano
scale, the same happens to the biological response thereof. In fact, the field of nanoscience arose
to explain strange effects that nanosized particles exhibited in comparison with their bulk
counterparts in the context of physics and chemistry, and assessing the same may lead to
evolution of many other natural and social fields of inquiry. Hence, it is this urge to explain
similarly strange effects in the nano domain that will drive the further development of this and
multiple other fields and disciplines. Also, there has been a lot of discussion in the circle of
nanoscientists regarding whether agglomerates of nanosized particles should be considered as
nanosystems or not. It was recently shown that temperature could be used for iron oxide based
polymeric micelle-like particles as a control parameter for achieving controllable
aggregation/redispersion. By knowing that the cellular response oftentimes depends on the
particle size and largely differs for aggregates and for singlets of the same particulate
composition, such new ways of control of aggregation properties of nanoparticles may lead to
novel applications in the field of biomaterials and drug delivery. This is especially so since it is
known that certain nanoparticles, such as those used for hyperthermia and other magnetismbased drug delivery purposes (Fig.2), can be attracted by an external magnetic field and made
bind to the cell membrane only insofar as they are aggregated, but can efficiently play their
intracellular delivery role only as individual entities.
Fig.2. An example of biocompatible magnetic nanoparticles with biomedical application (hyperthermia cancer
therapies). By controlling the stochiometry of the given manganite compound (La 1-xSrxMnO3+δ (0.16 < x < 0.5)), the
Neel point thereof equivalent to the maximal temperature achievable using one such smart material could be varied
and optimized for the given therapy (mild hyperthermic or more intensive thermoblastic ones, e.g.).
2)
Increasing limits in sensitivity. My previous works contained discourses on the limits in
precision with which we will be able to control physical processes as we keep on proceeding
along the line of the constant increase in resolution of human interference with the material
structures6. I emphasized that the first signs in reaching the current limits will be associated
irreproducible experimental outcomes. This could be compared to magnifying any imaginable
signal up to the level when we start discerning merely the noise fluctuations. What may seem as
a meaningful flow of information would be merely a random noise. Yet, an incessant challenge
is to establish methods to convert this apparent randomness into more sophisticated signals.
Dynamic light scattering methods for probing the diffusion and size properties of colloidal
systems were, for example, designed to extract meaningful information from the seemingly
random, Brownian motion, reminding us that everything that appears random could be actually
seen as ordered and governed by certain laws when understood on a sufficiently small scale.
Whether we have the effect of air bubbles in water (which have been used to explain why
studying such a simple but fundamental process such as Mpemba effect has failed), stirring rates,
natural magnetic field, or unavoidable impurities, these minor effects will be increasingly paid
attention to. Typical distilled water contains a few solutes at a level higher than 0.01 mM (a few
ppm), a few dozens of solutes at a level higher than 1 nM, and hundreds of solutes at a level
higher than 10 pM7. The effects of impurities in such minor concentrations will, however, prove
as increasingly important in attaining ideals of sophisticated sensitivity and precise localizations
of ultrafine physicochemical processes. The reaction volume is, for example, now already
established as a crucial parameter of a synthesis procedure. Many attempts to transfer a
preparation procedure from a lab-scale to large-scale fabrication volumes have failed exactly
owing to sensitivity of the given process to the reaction vessel size and oftentimes geometry and
chemical composition of its walls as well. For, not a single reaction system is perfectly isolated
from its environment and quite often it is the interface between the system and its environment
(that is, reaction and its container) that presents an important factor that drives the reaction
towards its desired outcome. An example of the effect of reaction volume comes from the
recently proposed evolutionary tree of the morphology of gold nanorods prepared by hydrolysis
of HAuCl4 in the presence of CTAB at mild to highly acidic pHs8. It was found out that shifting
merely the reaction volume from 0.9 to 45 ml changed the size and aspect ratio of gold
nanoparticles by more than a single order of magnitude. Purity of the reaction systems also
presents a critical parameter of synthesis, and as shown in Fig.3, sometimes introducing
seemingly negligible amount of impurities results in drastic changes in morphologies and other
properties of the material prepared. As the fineness of the chemical reactions and
physicochemical processes is increased and as windows of conditions that lead to desirable
products are narrowed, impurities previously disregarded will have to be taken into account.
Typical distilled water contains a few solutes at a level higher than 0.01 mM (a few ppm), a few
dozens of solutes at a level higher than 1 nM, and hundreds of solutes at a level higher than 10
pM, whereby water under atmospheric conditions contains approximately 5 mM of dissolved
gas, which adds up to a single gas molecule per each 3 nm (note that oils contain ten times more
than that). These fine impurities could be expected to exert critical influences on the given
reaction pathways, as many reactions are now known to be catalyzed by the dissolved gas, as
well as that its presence can be comparable to defects in a solid body9. Then, as biomolecules
will become increasingly utilized in production of fine material structures, sensitivity of their
folding and assembly into proper configurations will introduce uncontrollable energy landscapes
into the game. For example, it is known that single post-translational modifications can
drastically change the protein functionality, as well as that recombinant proteins may
occasionally exhibit completely different properties compared to their native counterparts,
despite having identical primary structures as them, which is often caused by different folding10.
Fig.3. Cholesterol particles prepared using 2-propanol of laboratory grade (left) and technical grade (right) as the
solvent.
3)
Crisscrossing theoretical and experimental knowledge. These two are quite often
separated and most materials scientists are equipped with either the theoretical or experimental
knowledge. Although the term “tunable” has been extensively used to describe size-dependent
material properties, it cannot be strictly speaking linked with “designable” since the connections
between lab notebook blueprints and the final experimental outcomes in terms of desirable
material properties are not that easily established, and although it has ever since been the dream
of materials scientists to establish a perfectly precise algorithm that connects synthesis
parameters, material structure and properties, and its function and performance, it is still
permeated with numerous missing links. For example, although quantum dots do exhibit sizedependent optoelectronic properties, Fermi levels of quantum dots can still not be designed prior
to depositing them. Only after the material is prepared and characterized for properties of
interest, one would select the experimental conditions which would be correlated with specific
properties. The same observation applies for the field of drug discovery, where despite the
extensive initial screening steps, the final candidates for the drug undergo randomized, trial-anderror studies in vitro, on animals and then on humans, eventually unexplainably failing or living
up to their promises. Reinforcing links between the theory and the experiment, in all contexts of
nanoscience, from particle syntheses to drug discovery, would bring the ideal of predicting
experimental outcomes with a greater certainty closer.
4) Conjoining top-down and bottom-up synthetic approaches. Many subfields of materials
science have traditionally relied on classical, top-down ways of synthesizing new materials. Most
of those, however, currently undergo the trend of adoption of soft and more elegant, colloidal
chemistry approaches, as opposed to the robust top-down methods11. However, whereas the
former may be said to exhibit drawbacks associated with the lack of facileness to process the
self-assembled systems into technologically functional units, the main downside of the latter is
the lack of ability to simultaneously organize a multitude of entities12. Still, by applying these
two mainstream synthetic approaches in parallel, so that they complement each other’s strengths
and weaknesses, there is a chance that more superior bases for fabrication of new materials will
be established. In the past, I also hypothesized that each self-assembly process should be, strictly
speaking, considered as a co-assembly since the spontaneous reorganization of a system may
take place only in parallel with a well coordinated reorganization of its immediate environment13.
Such a perspective where qualities of a system are inextricably related to the state of its
environment has been established in agreement with the previously proposed co-creational thesis
and its cognitive and epistemological connotations14,15. The idea of co-assembly was supported
by studies on reverse micelles16 where it was noticed that these molecular aggregates do not act
as passive templates for the formation of nanocrystals within their cores, but undergo mutual
transformations with the nucleating phase17. Fig.4 thus demonstrates how different compounds
may be synthesized by following the same preparation procedure, depending on whether reverse
micelles are present in the reaction system or not. They also play an active role in catalyzing the
transformations between intermediaries which may have crucial effect on the final products of
precipitation reactions and other phase transitions that take place in their presence18.
Fig.4. X-ray diffractograms of the powders synthesized by the same precipitation procedure, with (upper) and
without (lower) reverse-micelle microemulsion. The peaks denoted with an S are spinel-ferrite-derived, whereas the
peaks denoted with a D are -FeOOH-derived.
5) Fulfilling the aesthetic potentials of materials science. Scientists should more widely be
spurred to write and recognize the metaphoric meanings of relationships and imagery that is
present in their sciences19. This would help interrelate their scientific thinking with real-life
observations all until a feedback between the two is established so that the real-life insights can
inspire one’s scientific quests and vice versa. Fig.5 thus gives an example of an aesthetic image
which possesses a scientific meaning too. In Fig.5a, one could see a penguin-shaped deposit of
amelogenin on the surface of fluoroapatite/silica glass-ceramic, showing mineral formation
associated with its “heart”. Aside from an aesthetic appeal of the image, it possesses an intricate
scientific message too by demonstrating that the nucleation and crystal growth of apatite in the
presence of amelogenin, the main protein of the developing enamel matrix, starts from the
amelogenin layers deposited on top of apatite surface, thus handing us vital insights into the
mechanism by which amelogenesis in vivo may proceed. The same parallel scientific and artistic
meaningfulness could be ascribed to the TEM images in Fig.5b-c, where one could see an
amelogenin cloud surrounding a few apatite particles akin to a supermodel doing a catwalk
(Fig.5b) and a cheerful hailer (Fig.5c). Aside from its aesthetic appeal, it demonstrates the
thorough binding of amelogenin to apatite particles. Also, Fig.6 demonstrates high levels of
semblance between the pattern adopted by self-assembled collagen monolayers (Fig.6a) and that
drawn by the Dutch master, Vincent Van Gogh, in his renowned masterpiece, The Starry Night
(Fig.6b). There are hopes that scientific tools and imagery will be increasingly utilized in future
in attempts to enrich and improve the fineness of artistic expression in numerous artistic genre
and schools.
Needless to add, by explicating the importance of creative qualities forged through
appreciation of human arts for productive and innovative scientific conduct, as well as by
enhancing the impressiveness of artistic expressions by utilizing scientific eye to the world,
many benefits for both sciences and arts could be reached. In such a way, lights on the
importance of bridges that extend between more aesthetic fields of human inquiry about the
nature of reality, including theology20 and arts21, and empirical sciences, traditionally dominated
by the merits of analytical reasoning, would be shed.
Fig.5. SEM image of calcium phosphate nucleating from within an amelogenin layer deposited on top of an
FAP/glass substrate (a), and a 100 x 100 nm TEM images of hydroxyapatite particles suspended inside of an
amelogenin matrix (b, c).
Fig.6. SEM image of monolayers of assemblies of collagen fibers on glass (a), resembling the pattern of the sky on
the legendary Van Gogh’s painting, Starry Night (b).
Acknowledgment
TEM images were obtained during the author’s work performed at NCEM, which is supported
by the Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy
under Contract No. DE-AC02-05CH11231 (#1375).
References:
Vuk Uskoković – “Nanomaterials and Nanotechnologies: Approaching the Crest of this Big Wave”, Current
Nanoscience 4, 119 – 129 (2008).
2
Vuk Uskoković, Aljoša Košak, Miha Drofenik – “Preparation of Silica-Coated Lanthanum-Strontium Manganite
Particles with Designable Curie Point, for Application in Hyperthermia Treatments”, International Journal of
Applied Ceramic Technology 3 (2) 134 – 143 (2006).
3
Vuk Uskoković, Egon Matijević – “Uniform Particles of Pure and Silica Coated Cholesterol”, Journal of Colloid
and Interface Science 315 (2) 500 – 511 (2007).
4
Vuk Uskoković, Min-Kyeong Kim, Wu Li, Stefan Habelitz – “Enzymatic Processing of Amelogenin during
Continuous Crystallization of Apatite”, Journal of Materials Research 32, 3184 – 3195 (2008).
5
Vuk Uskoković – “Nanotechnologies: What We Do Not Know”, Technology in Society 29 (1) 43 – 61 (2007).
6
Vuk Uskoković – “Challenges for the Modern Science in its Descend towards Nano Scale”, Current Nanoscience
5 (3) 372 – 389 (2009).
7
M. Kosmulski – Surface charging and points of zero charge”, Surfactant Science Series 145, CRC Press, Francis &
Taylor, Boca Raton, FL (2009).
8
K. Sohn, F. Kim, K. C. Pradel, J. Wu, Y. Peng, F. Zhou, J. Huang – “Construction of Evolutionary Tree for
Morphological Engineering of Nanoparticles”, ACS Nano 3 (8) 2191 – 2198 (2009).
9
Ninham, B. Self-Assembly – Some Thoughts. In: Self-Assembly, edited by B. H. Robinson, IOS Press: Amsterdam,
2003.
10
A. A. Sahasrabuddhe, S. M. Gaikwad, M. V. Krishnasastry, M. I. Khan – “Studies on recombinant single chain
Jacalin lectin reveal reduced affinity for saccharides despite normal folding like native Jacalin”, Protein Science 13
(12) 3264 – 3273 (2004).
11
Vuk Uskoković, Luiz Eduardo Bertassoni – “Nanotechnology in Dental Sciences: Moving towards a Finer Way of
Doing Dentistry”, Materials 3 (3) 1674 – 1691 (2010).
12
Vuk Uskoković – “Theoretical and Practical Aspects of Colloid Science and Self-Assembly Phenomena
Revisited”, Reviews in Chemical Engineering 23 (5) 301 - 372 (2007).
13
Vuk Uskoković – “Isn't Self-Assembly a Misnomer? Multi-Disciplinary Arguments in Favor of Co-Assembly”,
Advances in Colloid and Interface Science 141 (1-2) 37 - 47 (2008).
14
Vuk Uskoković – “On the Relational Character of Mind and Nature”, Res Cogitans: Journal of Philosophy 6 (1)
286 – 400 (2009).
15
Vuk Uskoković – “On the Light Doves and Learning on Mistakes”, Axiomathes: An International Journal in
Ontology and Cognitive Systems 19, 17 - 50 (2009).
16
Vuk Uskoković, Miha Drofenik – “Synthesis of Materials within Reverse Micelles”, Surface Review and Letters
12 (2) 239 – 277 (2005).
17
Vuk Uskoković, Miha Drofenik – “Reverse Micelles: Inert Nano-Reactors or Physico-Chemically Active Guides
of the Capped Reactions”, Advances in Colloid and Interface Science 133 (1) 23 – 34 (2007).
18
Vuk Uskoković, Miha Drofenik – “A Mechanism for the Formation of Nanostructured NiZn Ferrites via a
Microemulsion-Assisted Precipitation Method”, Colloids and Surfaces A: Physicochemical and Engineering Aspects
266, 168 – 174 (2005).
19
Vuk Uskoković – “On Science of Metaphors and the Nature of Systemic Reasoning”, World Futures: Journal of
General Evolution 65, 241 – 269 (2009).
20
Vuk Uskoković – “The Metaphorical Model: The Bridge between Science and Religion”, Journal for
Interdisciplinary Research on Religion and Science 6, 11 – 34 (2010).
21
Vuk Uskoković – “A Collection of Micrographs: Where Science and Art Meet”, Technoetic Arts: A Journal of
Speculative Research 7 (3) 231 – 248 (2010).
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