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Physics of nano/micro devices and systems

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Recent advancements in nanotechnology have led to a surge of interest in nano and micro devices and systems, such as nanotubes, nano/microstructures, and nanofiber fabrication processes. This progress has ushered in a new era of miniaturized nanodevices. The study of nonlinear vibration and instability represents an exciting frontier in both nanotechnology and nonlinear dynamics, highlighting the importance of controlling instability in the design of nano/micro devices and systems. This Research Topic celebrates the fascinating physical principles that underpin the dynamical properties of these devices and explores the emerging advanced applications in the field. Understanding these principles requires multidisciplinary collaboration, involving fields such as nanotechnology, physics, textile engineering, material science, electro-mechanical engineering, communication science, medical science, and mathematics. Insights into the physical laws governing the operation of nano/micro devices, including energy conservation and nanophysics, are crucial for developing optimal designs and control strategies, thereby promoting advanced applications. This Research Topic encourages exploration in several key areas, including: 1. Mathematical and fractal-fractional models for vibration/instability in nano/micro devices and nanofiber fabrication systems. 2. Optimal control of systems governed by nonlinear vibration equations with fractal or fractional derivatives. 3. Vibration analysis of carbon nanotubes. 4. Investigation into pull-in instability of N/MEMS systems. 5. Study of periodic properties of N/MEMS systems. 6. Nonlinear vibration in electrospinning or bubble electrospinning processes. 7. Vibration analysis of nanofiber-reinforced hierarchical concrete. 8. Vibration and control mechanisms in 3D printing systems. 9. Development of energy harvesting devices and wearable sensors. 10. Application of big data, machine learning, and AI in nonlinear vibration and active control. 11. Advances in analytical and numerical methods for addressing these challenges. This focused collection provides a valuable opportunity for researchers and practitioners to engage with this cutting-edge field of research.

Keywords : Nanotube, N/MEMS system, 3D printing technology, nanofiber fabrication, fractional differential equation, nonlinear vibration, optimal control, fractal vibration, analytical method, numerical method

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Nanotechnology from lab to industry – a look at current trends

First published on 1st August 2022

Nanotechnology holds great promise and is hyped by many as the next industrial evolution. Medicine, food and cosmetics, agriculture and environmental health, and technology industries already profit from nanotechnology innovations and their influence is expected to increase drastically in the near future. However, there are also many challenges that need to be overcome to bring a nanotechnological product or business to the market. In this article we discuss current examples of nanotechnology that have been successfully introduced in the market and their relevance and geographical spread. We then discuss different partners for scientists and their role in the commercialization process. Finally, we review the different steps it takes to bring a nanotechnology to the market, highlight the many difficulties related to these steps, and provide a roadmap for the journey from lab to industry which can be beneficial to researchers.

1. Introduction

2. Nanotechnology developments

All inhabited continents are represented among the top countries involved in scientific publishing; however, only Europe (14 countries), Asia (8 countries), North America (2 countries), and Oceania (1 country) are included among the top 25 countries involved in the patenting of nanotechnology developments. Seventeen countries were common factors among both publishing and patenting discoveries. It is also noteworthy that the two countries that had the highest investments in scientific research (China and The USA) produced highest numbers of publications and patents, respectively. Patents can be used as technological indicators as they provide an insight into the research and development activities that are intended for commercial gain. 12 The transfer of these nanotechnology advancements to commercialized end products is however a major challenge that the scientific community faces. However, it has to be noted here that there are also quite some differences in culture when it comes to patenting. There are differences between countries in how buerocratic the patent process is. Additionally, there are differences in how much is patented at all. In some cultures, it might be more common to keep innovation a secret than to patent. There are also differences in how patents are made. In some places there is a high number of smaller patents while in others there are a few more elaborate ones.

2.1. Nanotechnology industries worldwide

3. The business of ‘lab-to-industry’

3.1. Ideation

These two approaches show how innovation relies on technology seeds and market needs. One might ponder which of the two approaches is better. There are both merits and challenges associated with each approach. While each can lead to innovation, a pairing of the two is recommended. When closely integrated, the potential impact of the innovation increases. This synchronization of the ‘seed’ and ‘need’ approaches is called accelerated innovation. It enables the restructuring of research and development, and innovation processes to make new product development dramatically faster and less costly. 15 Furthermore, it also facilitates functional thinking and exaptation where the latter refers to the discovery of unintended functions for technologies. Altogether creating the ideal conditions for researchers to make radical innovations and bridge the gap between academia and industry.

3.2. Business model

Breakthrough technologies, especially those incorporating the use of nanotechnology, are intended to create value. Value is created via this technology when there is meaningful performance improvement or when the cost of solving problems is significantly reduced. There is however a major challenge for nanotechnology innovations in terms of a business model, and that is, the challenge of taking the product to customers. Several factors can influence this (for example, having limited resources) and for this reason, a go-to-market strategy is critical.

A joint-development partnership is an agreement between two organizations to develop a new product or service. It is a strategic alliance that serves to leverage the assets of each company to create a new offering for commercialization that would be difficult to achieve individually. This type of partnership is commonly used for product development or beta testing. Typically, these agreements are not binding and one party can quit at any time. Profits, access, expenses, and losses are usually shared between the companies. With this type of business partnership, it is important to have a close business relationship with the company before engaging in this agreement. As is the case with licensing arrangements, the most ideal joint-development partnership can be determined with the assistance of an attorney. Matters relating to the ownership and access to intellectual property, responsibilities, disengagement, and termination are some of the issues to be discussed with a suitable attorney before engaging a potential partner.

In partnerships, securing intellectual property early remains crucial. In an innovative nanotechnology business, the science underpinning the technology is critical and must be protected. This can be achieved by engaging an intellectual property counsel. The services of a corporate counsel should also be acquired early to ensure the start-up is properly incorporated. These parties should be appointed at the early stages as they help with structuring the company. The technology transfer process which is discussed in Section 3.3 helps to get these counsels on board.

There are some key players that are needed to guarantee a good business model and these are outlined in Fig. 4 . To assure a diversity of skills that are necessary for success, an often overlooked group of individuals is needed. This is a company board. This can include a board of advisors and a board of directors. The functions of these two bodies bear some similarities and differences. The board of advisors is composed of business professionals who fill skill and expertise gaps and can offer guidance to the management team. This can include matters concerning business performance, market trends, long-term goals of the company, and financing to name a few. While the additional skill set required in a science-based industry might be in business management, it is not unusual for additional technical expertise to be warranted. This can include the skills of fellow scientists who have had prior success in transitioning science to the marketplace. These scientists, when recruited, could form a scientific or technical advisory board. Regardless of the composition of the advisory board, their core function is to provide non-binding strategic advice. Their role is not fiduciary. This means that the team of experts and community leaders has no legal responsibility to the company. Their role however remains critical as they can compensate for some of the weaknesses within the management team and bring different opinions, perspectives, and experiences to the table. The board of advisors is particularly helpful for start-ups. A board of directors, on the other hand, is essentially a panel of people elected or appointed to represent shareholders. They oversee the activities of the company and have a fiduciary responsibility to represent and protect the members' or investors' interests in the company. The management team however reports to the board of directors. Larger companies that will require significant funding need a board of directors. Both the boards of advisors and directors can assist with strategic planning, the development of new ideas, improvement of management structure, improving company image and reputation, reassuring stakeholders and investors, and overall, help to ensure the success of the company.

The management team and the company board can together decide on the most suitable business model for the company. In making this decision, special focus should be placed on the model that will create and deliver great value to customers while simultaneously delivering great margins. The model should also hedge against customer dissatisfaction or dissonance and issues securing adequate funding. While the team is now multifaceted, additional support to make the right decisions that will position the company for success can be sought. This can be achieved using accelerators and incubators (which might be available within the university or municipality), government agencies such as the local chamber of commerce, and small business and technology development centers. Start-ups are generally encouraged to not employ at the early stages and to instead contract personnel for specific functions if necessary.

3.3. Technology transfer process

The efficiency of the transfer of nanotechnology innovations from the lab to the industry is dependent on the efficacy of the technology transfer process. Countries that invest in improving nanotechnology transfer policies and practices have greater nanotechnology outputs. This is evident in the United States where the National Nanotechnology Initiative (NNI) was developed. It is a collaboration of federal departments and agencies with interests in nanotechnology research, development, and commercialization. 17 Within the NNI are agencies such as the Nano manufacturing and Small Business Innovation Research (SBIR) programs, and the NNI's National Nanotechnology Coordination Office (NNCO) that are concerned with the transfer of newly developed nanotechnologies into products for commercial use. In Asia, there has been an increase in expenditure towards nanotechnology research and deliberate efforts to transfer research findings to industries. While the production of nanotechnology publications in China is higher than in other countries ( Fig. 2a ), the transfer of these technologies to industries is not equivalent. 18 The National Steering Committee for Nanoscience and Nanotechnology (NSCNN) was established to oversee and coordinate nanotechnology policies and programs in China. Some key members of this group include the Chinese Academy of Sciences (CAS), the National Natural Science Foundation of China (NSFC), the National Development and Reform Commission (NDRC), and the Chinese Academy of Engineering. These agencies are expected to impact the technology transfer process within the country.

The success of the transfer of technology in The United States reveals that more favorable environments for nanotechnology transfer need to be created globally. This will create a stronger ecosystem for nanotechnology research and innovation, and in turn, result in greater success in the use of intellectual property to facilitate the creation of start-ups formed from the ground up or through partnerships. Some nanotechnology and nano-engineering associations across the world that can be modelled in other countries to positively impact the transfer of technology are outlined in Table 2 . These associations were selected from the Nanotechnology 2020 Market Analysis. 9

3.4. Readiness for commercialization

Technology readiness evaluates the technology itself and seeks to determine if the technology will maintain itself in the market. This is usually determined by performing a technology readiness assessment (TRA). It is recommended that this TRA is done at several points during the ‘life cycle’ of the new technology or system. Possible components of this assessment include an evaluation of the conceptual design, a clear protocol to facilitate a decision from among several competing design options, and similarly, a defined approach to decide when to begin full-scale development. These decisions might be made by the research team or they can be more complex and warrant an external, independent peer-review process. 20 Market readiness assesses how marketable the technology is; that is, how well the technology will be accepted by the target market. This is generally done by examining whether the technology offers meaningful identifiable and quantifiable benefits, has distinct advantages over competing products, has access to a market of a suitable size that is defined and is growing (demand-based), has immediate market uses, and has feasible manufacturing requirements. 21

The commercialization readiness assessment also evaluates the readiness of the technology's business model. This is done to verify the stability and readiness of the foundation upon which the technology will be delivered. Within this component, parameters for assessment include determining whether prospective licensees are identified, if industry contacts are available, and if further development or patenting is possible based on the availability of financial support for the licensee. Additionally, anticipated future royalty revenue of the license, access to venture capital, a profitable investment, and availability of government support for additional development for innovations resulting from universities are also crucial. 22 The last key area is management readiness which assesses the readiness of the management team that is responsible for the technology. It addresses matters such as the ability of the inventor to champion the innovation as a team player, whether the inventor's expectations for success are realistic, if the inventor is recognized and reputable in the field, if commercialization skills such as sales and marketing skills are available, whether management capabilities are available, and also whether the inventor is the patent holder for innovations resulting from government labs. 23

A method of quantifying the judgments made for each criterion of the four areas of the Cloverleaf framework to determine the degree to which each condition is met was suggested. 19 If all components of the criteria list for the four ‘leaves’ assessing readiness are satisfied, then the technology is ready for commercialization. If a partnership agreement is being utilized, some components should be completed before engaging a partner and others should be finalized with the partner. Regardless of the business model, if any area is found lacking, additional preparation is warranted to ensure the success of the venture when it enters the market.

Alternative to the Cloverleaf framework is the Technology Readiness Levels (TRL) model. This was developed by NASA and is a type of measurement system that is used to permit more effective assessment and communication regarding the maturity of new technologies. 20 The different levels of the framework are outlined in Fig. 6 . There are nine technology readiness levels. A project is evaluated against the parameters for each technology level and is then assigned a TRL rating based on its progress. TRL 1 is the lowest level and indicates that a technology requires further research and development, and testing. TRL 9 is the highest level and signifies a mature technology that is proven to work and may be put into use and commercialized.

3.5. Financials

Another type of capital provider is venture capitalists. These private investors provide funds to early-stage companies that are pursuing big opportunities with high growth potential. Venture capital firms exchange capital for equity ownership and can also provide strategic assistance, and an invaluable network. To capture the interest of a venture capitalist, a start-up should have a good “elevator pitch” and a strong investor pitch deck for their innovative product. This should therefore include the strength of the management team and clearly outline the large potential market for the nanotechnology innovation, and a unique product or service with a strong competitive advantage. Another entity that can provide financing and has a similar structure to a venture capital firm is a family office. This is a special investment firm that manages the wealth owned by individuals and families with a high net worth. 26 Family offices make optimal investors and are increasingly entering venture investment as a relatively new capital provider. They are comprised of qualified professionals with extensive experience and tend to offer more patient capital and expect lower returns than traditional investors.

4. The challenge of moving technology from lab to industry

Biological or environmental challenges are other factors that can impede the transfer of nanotechnology from the lab to the industry. Biological challenges include insufficient knowledge involving the interaction of nanomaterials in vitro and in vivo , inadequate information on their bioaccumulation in target organs, tissues, and cells, and also limited information on their biocompatibility. 30,31 Physical properties such as particle size, composition, surface area, surface charge, surface chemistry, and agglomeration state all influence the biocompatibility of nanomaterials and so more information is needed on their safety in vivo . 31 Environmental challenges include nanomaterials entering the environment either directly or indirectly (for example, via landfills). Nanomaterials can have potentially adverse effects on natural systems and can enter the environment at different stages of their life cycle. Three emission scenarios that are generally of relevance are (i) release during the production of various nanotechnology products or nano-enabled products; (ii) release during use; and (iii) release after disposal. 32 While present in the environment, nanomaterials can then undergo many transformations. These include chemical transformations (for example, photo-degradation), physical transformations (such as aggregation), biologically-mediated transformations (for instance, redox reactions in biological systems), and interactions with macromolecules (for example, flocculation). 30 The interplay between these transformations and the transport of the nanomaterial within the ecosystem ultimately determine their fate and ecotoxicity.

Possible biological and environmental impacts of nanotechnology innovations should be determined with in vitro and in vivo models, as well as within aquatic and terrestrial ecosystems. The production process from which the nanomaterial results should also be considered so that any such material emitted during this time or released from nano-enabled devices during their fabrication, use, recycling or disposal can be studied and minimized. Biological and environmental challenges can also be mitigated by providing employers and the extended workforce with information on the potential toxicity of nanomaterials at different stages of their life cycle. With the help of modelling, recent developments have been geared towards predicting the fate, behavior, and concentration of nanomaterials in the environment. 33 While these simulations can be helpful, more efficient and reliable analytical instruments and methods must be developed so that nanomaterials can be satisfactorily characterized and quantified, and the necessary tools developed to detect, monitor and track them in biological media and complex environmental matrixes.

The nanotechnology industry plays a major role in economic development; however, several economic challenges can hinder the transfer of innovations from the lab to the industry. Generally, these include limited investment in relevant research and development activities and a lack of appropriate mechanisms to secure these investments, lack of laboratory equipment and appropriate infrastructure to facilitate research and its commercialization, and insufficient funding opportunities to engage in research that has the potential for commercialization. Constraints imposed on the activities needed to commercialize nanotechnology outputs are also impacted by the socio-economic dynamics of innovation. While many believe the rapid growth in nanotechnology will have significant economic benefits, some advocate to reduce or halt its development. The backlash against nanotechnology by this group is based on the belief that it will exacerbate problems concerning existing socio-economic inequity and power imbalance caused by inequality. This, they suggest, will cause a nano-divide which refers to differing access to nanotechnology between low-, middle-, and high-income countries. 34,35 The ethical criticism is mainly concerned with inequity based on where knowledge is developed and retained and a country's capacity to engage in these processes. 35 An attempt to combat these challenges is outlined in the European Union's Framework Programs through the Responsible Research and Innovation (RRI) approach. This approach ‘anticipates and assesses potential implications and societal expectations concerning research and innovation, intending to foster the design of inclusive and sustainable research and innovation’ (https://ec.europa.eu). These measures which are intended to facilitate broader access to nano-technology and its innovations globally are critical in addressing a nano-divide.

The final category of challenges that can significantly impact the transfer of nanotechnology from the lab to the industry is regulatory challenges. These are concerned with a lack of clear regulatory guidelines for nanotechnology and nanotechnology-enabled products. Some regulatory challenges include inadequate policies to foster the development and operation of nanotechnology businesses or insufficient strategies implemented by governments to attract nanotechnology business initiatives. Additionally, a lack of technology transfer protocols, or requisites for regulatory approvals to facilitate the movement of innovation from the lab to commercial products are problematic. 36 The multidisciplinary nature of nanotechnology also presents regulatory challenges. With its cross-industry applications, policing and enforcement nanotechnology patents have proven to be prohibitively expensive (WIPO, 2011). New intellectual property practices and protocols are therefore required to simplify the pathway from lab to industry thereby reducing time and expense.

The technical, biological, environmental, economic, and regulatory challenges of nanotechnology need to be addressed urgently. Policies governing all aspects of nanotechnology research and subsequent commercialization must balance its potential benefits with its current challenges. Combatting these challenges will require considerable efforts to prevent any possible harmful effects of nanotechnology while also facilitating the awareness of its benefits to society. 37 The involvement of scientific, governmental, industry, and labor force representatives is therefore critical in decision making so the challenges associated with the commercialization of nanotechnology can be controlled, minimized or mitigated.

5. Conclusions

The necessary risk assessment to understand the potentially harmful effects of products resulting from nanotechnology have however not kept pace with their proliferation; and researchers are racing to address this knowledge gap. 38 Companies resulting from the transfer of nanotechnology innovations from the lab to the marketplace must therefore have rigorous risk management protocols where risks are identified, control measures are planned and implemented, and risks communication. 37 Identified regulatory impediments should also be addressed and technology transfer policies and practices implemented. Entrepreneurial education and training, and the establishment of business incubators should also be supported within the necessary departments or research institutes. Improvement in the understanding of nanotechnology within society would also help commercialization efforts. Overall, societal actors such as researchers, policymakers, investors, citizens etc. must work together during the research and commercialization stages so that the many benefits of nanotechnology outputs can be aligned with the needs and expectations of society.

Conflicts of interest

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Selected Topics in Nanoscience and Nanotechnology

• Edited by: 
• Andrew T S Wee ( NUS, Singapore )
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• Description
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Selected Topics in Nanoscience and Nanotechnology contains a collection of papers in the subfields of scanning probe microscopy, nanofabrication, functional nanoparticles and nanomaterials, molecular engineering and bionanotechnology. Written by experts in their respective fields, it is intended for a general scientific readership who may be non-specialists in these subjects, but who want a reasonably comprehensive introduction to them. This volume is also suitable as resource material for a senior undergraduate or introductory graduate course in nanoscience and nanotechnology.

The review articles have been published in journal COSMOS Vol 3 & 4.

Sample Chapter(s) Chapter 1: Scanning Probe Microscopy Based Nanoscale Patterning and Fabrication (861 KB)

• Scanning Probe Microscopy Based Nanoscale Patterning and Fabrication (X N Xie et al.)
• Nanoscale Characterization by Scanning Tunneling Microscopy (H Xu et al.)
• EUV Lithography for Semiconductor Manufacturing and Nanofabrication (H Kinoshita et al.)
• Synchrotron-Radiation-Supported High-Aspect-Ratio Nanofabrication (A Chen et al.)
• Chemical Interactions at Noble Metal Nanoparticle Surfaces — Catalysis, Sensors and Devices (A S Nair et al.)
• Diamond-Like Carbon: A New Material Base for Nanoarchitectures (X Li & D H C Chua)
• Hotplate Technique for Nanomaterials (Y Zhu & C H Sow)
• π- d Interaction Based Molecular Conducting Magnets: How to Increase the Effects of the π- d Interaction (A Miyazaki & T Enoki)
• Recent Developments on Porphyrin Assemblies (R Charveta et al.)
• Nanostructures from Designer Peptides (B T Ong et al.)
• Nanotechnology and Human Diseases (G Y H Lee & C T Lim)
• Nanomedicine: Nanoparticles of Biodegradable Polymers for Cancer Diagnosis and Treatment (S S Feng)

FRONT MATTER

• Andrew T. S. Wee
• Pages: i–viii

https://doi.org/10.1142/9789812839565_fmatter

Scanning Probe Techniques

Scanning probe microscopy based nanoscale patterning and fabrication.

• XIAN NING XIE ,
• HONG JING CHUNG , and 
• ANDREW THYE SHEN WEE
• Pages: 3–23

https://doi.org/10.1142/9789812839565_0001

Nanotechnology is vital to the fabrication of integrated circuits, memory devices, display units, biochips and biosensors. Scanning probe microscope (SPM) has emerged to be a unique tool for materials structuring and patterning with atomic and molecular resolution. SPM includes scanning tunneling microscopy (STM) and atomic force microscopy (AFM). In this chapter, we selectively discuss the atomic and molecular manipulation capabilities of STM nanolithography. As for AFM nanolithography, we focus on those nanopatterning techniques involving water and/or air when operated in ambient. The typical methods, mechanisms and applications of selected SPM nanolithographic techniques in nanoscale structuring and fabrication are reviewed.

NANOSCALE CHARACTERIZATION BY SCANNING TUNNELING MICROSCOPY

• M. A. K. ZILANI ,
• WEI CHEN , and 
• Pages: 25–52

https://doi.org/10.1142/9789812839565_0002

Nanoscale characterization is a key field in nanoscience and technology as it provides fundamental understanding of the properties and functionalities of materials down to the atomic and molecular scale. In this article, we review the development and application of scanning tunneling microscope (STM) techniques in nanoscale characterization. We will discuss the working principle, experimental setup, operational modes, and tip preparation methods of scanning tunneling microscope. Selected examples are provided to illustrate the application of STM in the nanocharacterization of semiconductors. In addition, new developments in STM techniques including spin-polarized STM (SP-STM) and multiprobe STM (MP-STM) are discussed in comparison with conventional non-magnetic and single tip STM methods.

Nanofabrication

Euv lithography for semiconductor manufacturing and nanofabrication.

• HIROO KINOSHITA
• Pages: 55–81

https://doi.org/10.1142/9789812839565_0003

EUV lithography is the exposure technology in which even 15 nm node which is the limit of Si device can be achieved. Unlike the conventional optical lithography, this technology serves as a reflection type optical system, and a multilayer coated mirror is used. Development of manufacturing equipment is accelerated to aim at the utilization starting from 2011. The critical issues of development are the EUV light source which has the power over 115 W and resist with high sensitivity and low line edge roughness (LER).

SYNCHROTRON-RADIATION-SUPPORTED HIGH-ASPECT-RATIO NANOFABRICATION

• L. K. JIAN , and 
• HERBERT O. MOSER
• Pages: 83–92

https://doi.org/10.1142/9789812839565_0004

X-ray lithography with synchrotron radiation is an important nanolithographic tool which has unique advantages in the production of high aspect ratio nanostructures. The optimum synchrotron radiation spectrum for nanometer scale X-ray lithography is normally in the range of 500 eV to 2 keV. In this paper, we present the main methods, equipment, process parameters and preliminary results of nanofabrication by proximity X-ray lithography within the nanomanufacturing program pursued by Singapore Synchrotron Light Source (SSLS). Nanostructures with feature sizes down to 200 nm and an aspect ratio up to 10 have been successfully achieved by this approach.

Functional Nanomaterials

Chemical interactions at noble metal nanoparticle surfaces — catalysis, sensors and devices.

• A. SREEKUMARAN NAIR ,
• RENJIS T. TOM ,
• V. R. RAJEEV KUMAR ,
• C. SUBRAMANIAM , and 
• Pages: 95–116

https://doi.org/10.1142/9789812839565_0005

In this paper, a summary of some of the recent research efforts in our laboratory on chemical interactions at noble metal nanoparticle surfaces is presented. The article is divided into five sections, detailing with (i) interactions of simple halocarbons with gold and silver nanoparticle surfaces at room temperature by a new chemistry and the exploitation of this chemistry in the extraction of pesticides from drinking water, (ii) interaction of biologically important proteins such as Cyt c , hemoglobin and myoglobin as well as a model system, hemin with gold and silver nanoparticles and nanorods forming nano–bio conjugates and their surface binding chemistry, (iii) formation of polymer–nano composites with tunable optical properties and temperature sensing characteristics by single and multi-step methodologies, (iv) nanomaterials-based flow sensors and (v) composites of noble metal nanoparticles and metallic carbon nanotubes showing visible fluorescence induced by metal–semiconductor transition.

DIAMOND-LIKE CARBON: A NEW MATERIAL BASE FOR NANO-ARCHITECTURES

• XIJUN LI  and 
• DANIEL H. C. CHUA
• Pages: 117–148

https://doi.org/10.1142/9789812839565_0006

Diamond-like carbon (DLC) is a form of amorphous carbon which has high fraction of sp 3 hybridization. Due to its nature of sp 3 bonding, diamond-like carbon has been shown to have excellent properties similar to that of diamond. This includes high hardness, excellent wear-resistance, large modulus and chemically inert. Traditional applications include wear resistant coatings and protective film. This article intends to review the synthesis and material properties of diamond-like carbon as well as its potential as a novel material for applications in nano-architecture and nano-mechanical devices. An introduction into metal-dopants in diamond-like carbon film will be briefly mentioned as well as techniques on the design and fabrication of this material.

HOTPLATE TECHNIQUE FOR NANOMATERIALS

• YANWU ZHU  and 
• CHORNG HAUR SOW
• Pages: 149–169

https://doi.org/10.1142/9789812839565_0007

As an efficient and cost-effective method to synthesize nanomaterials, the hotplate technique has been reviewed in this article. Systematic studies have been carried out on the characterizations of the materials synthesized. In addition to the direct preparation of nanomaterials on metals, this method has been extended to the substrate-friendly and plasma-assisted hotplate synthesis. Apart from chemically pure nanostructures, a few nanohybrids were synthesized, further demonstrating the flexibility of this technique. The investigations on their applications indicate that they are promising material systems with potential applications in field emission devices, gas sensors, Li-ion batteries and ultrafast optical devices.

Molecular Engineering

Π–d interaction based molecular conducting magnets: how to increase the effects of the π–d interaction.

• AKIRA MIYAZAKI  and 
• TOSHIAKI ENOKI
• Pages: 173–182

https://doi.org/10.1142/9789812839565_0008

The crystal structures and electronic and magnetic properties of conducting molecular magnets developed by our group are reviewed from the viewpoints of our two current strategies for increasing the efficiency of the π–d interaction. (EDTDM) 2 FeBr 4 is composed of quasi-one-dimensional donor sheets sandwiched between magnetic anion sheets. The ground state of the donor layer changes from the insulator state to the metallic state by the application of pressure. When it is near to the insulator-metal phase boundary pressure, the magnetic order of the anion spins considerably affects the transport properties of the donor layer. The crystal structure of (EDO–TTFBr 2 ) 2 FeX 4 (X = Cl, Br) is characterized by strong intermolecular halogen-halogen contacts between the organic donor and FeX 4 anion molecules. The presence of the magnetic order of the Fe 3+ spins and relatively high magnetic order transition temperature proves the role of the halogen-halogen contacts as exchange interaction paths.

RECENT DEVELOPMENTS ON PORPHYRIN ASSEMBLIES

• RICHARD CHARVET ,
• JONATHAN P. HILL ,
• YONGSHU XIE ,
• YUTAKA WAKAYAMA , and 
• KATSUHIKO ARIGA
• Pages: 183–213

https://doi.org/10.1142/9789812839565_0009

The porphyrin macrocycle is one of the most frequently investigated functional molecular entities and can be incorporated into advanced functional nanomaterials upon formation of organized nanostructures. Thus, study of the science and technology of porphyrin assemblies has attracted many organic, biological and supramolecular chemists. A wide variety of nanostructures can be obtained by supramolecular self-assembly because the porphyrin moiety is amenable to chemical modifications through thoughtful synthetic design and moderate preparative effort. Some recent developments in porphyrin assembly, obtained through various supramolecular approaches, are briefly summarized. Topics described in this review are classified into four categories: (i) non-specific assemblies; (ii) specific assemblies; (iii) assemblies in organized films; (iv) molecular-level arrangement. We present examples in the order of structural precision of assemblies.

Bionanotechnology and Nanomedicine

Nanostructures from designer peptides.

• BOON TEE ONG ,
• PARAYIL KUMARAN AJIKUMAR , and 
• SURESH VALIYAVEETTIL
• Pages: 217–227

https://doi.org/10.1142/9789812839565_0010

The present article reviews the self-assembly of oligopeptides to form nanostructures, both in solution and in solid state. The solution structures of the peptides were examined using circular dichroism and dynamic light scattering. The solid state assembly was examined by adsorbing the peptides onto a mica surface and analyzing it using atomic force microscopy. The role of pH and salt concentration on the peptide self-assembly was also examined. Nanostructures within a size range of 3–10 nm were obtained under different conditions.

NANOTECHNOLOGY AND HUMAN DISEASES

• GABRIEL YEW HOE LEE  and 
• CHWEE TECK LIM
• Pages: 229–241

https://doi.org/10.1142/9789812839565_0011

Tissues, cells and biomolecules can experience changes in their structural and mechanical properties during the occurrence of certain diseases. Recent advances in the fields of nanotechnology, biomechanics and cell and molecular biology have led to the development of state-of-the-art and novel biophysical and nanotechnological tools to probe the mechanical properties of individual living cells and biomolecules. Here we will review the basic principles and application of some of these nanotechnological tools used to relate changes in the elastic and viscoelastic properties of cells to alterations in the cellular and molecular structures induced by diseases such as malaria and cancer. Knowing the ways and the extent to which mechanical properties of living cells are altered with the onset of disease progression will be crucial for us to gain vital insights into the pathogenesis and pathophysiology of malaria and cancer, and potentially offers the opportunity to develop new and better methods of detection, diagnosis and treatment.

NANOMEDICINE: NANOPARTICLES OF BIODEGRADABLE POLYMERS FOR CANCER DIAGNOSIS AND TREATMENT

• Pages: 243–259

https://doi.org/10.1142/9789812839565_0012

Nanomedicine is to apply and further develop nanotechnology to solve problems in medicine, i.e. to diagnose, treat and prevent diseases at the cellular and molecular level. This article demonstrates through a full spectrum of proof-of-concept research, from nanoparticle preparation and characterization, in vitro drug release and cytotoxicity, to in vivo pharmacokinetics and xenograft model, how nanoparticles of biodegradable polymers could provide an ideal solution for the problems encountered in the current regimen of chemotherapy. A system of vitamin E TPGS coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles is used as an example for paclitaxel formulation as a model drug. In vitro HT-29 cancer cell viability experiment demonstrated that the paclitaxel formulated in the nanoparticles could be 5.64 times more effective than Taxol ® after 24 hr of treatment. In vivo pharmacokinetics showed that the drug formulated in the nanoparticles could achieve 3.9 times higher therapeutic effects judged by area-under-the curve (AUC). One shot can realize sustainable chemotherapy of 168 hr compared with 22 hr for Taxol ® at a single 10mg/kg dose. Xenograft tumor model further confirmed the advantages of the nanoparticle formulation versus Taxol ® .

Sample Chapter(s) Chapter 1: Scanning Probe Microscopy Based Nanoscale Patterning and Fabrication (861k)

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Research Area/ Research Interest: Nanotechnology

Research Paper Topics for:  Masters and PhD Thesis and publication

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Economics JIW - Tips for Choosing a Topic: Home

Choosing a topic.

Choosing a topic that can answer an economic research question is challenging.  Some tips:

•  Ripped from the headlines rarely makes a good economic paper.  You will be using data to determine causation or correlation.  Sometimes a similar event can be used.  Topics such as artificial intelligence may make a good policy paper but not a good economic one due to lack of data.
• Literature Review: Your JIW should use primarily scholarly sources.  Start with Econlit (the database of the American Economic Association).  Econlit indexes major journals, working papers, conference proceedings, dissertations, and chapters in critical books. It takes a long time for scholarly literature to appear.   Preprints are called working papers in economics and major ones are indexed in Econlit.  Y ou are your own research team and have limited time.  Many articles are written over a couple of years and involve many people gathering and cleaning the data. Some starting places: see https://libguides.princeton.edu/econliterature/gettingstarted
• Outside of finance and some macroeconomic data, most data will not have many points in time.  Data determines the methods used .   While a linear regression can be great for time series data, it is likely not what you will use for survey data.
• Longitudinal or panel study :  same group of individuals is interviewed at intervals over a period of time.  This can be very useful to observe changes over time. Keep in mind when using a long running longitudinal dataset that the panel generally is not adding new participants so may not reflect today’s demographics.
• Cross-sectional study :  data from particular subjects are obtained only once.  While you are studying different individuals each time, you are looking at individuals with similar demographic characteristics.  Demography is typically rebalanced to reflect the population.
• Summary statistics : aggregated counts of survey or administrative data.
• Typically around a 2 year time lag from the time the survey data is collected to the time of release.  The Economic Census and Census of Agriculture take about 4 years for all data to be released.  Many surveys never release the microdata.
• Very little subnational data is available and is often restricted when available.   State level macro data for the United States is more prevalent.  City level data is often a case study or only available for very large cities.
• Many micro-level datasets are restricted. It is not uncommon to wait a year before getting permission or denial to use the data.  Each organization has its own rules.
• Historical data in electronic format prior to 1950 is rare. Most governmental links provide current data only.
• What is measured changes over time .  Do not assume modern concepts were tracked in the past.  Definitions of indicators often change over time.
• Data cannot be made more frequent.  Many items are collected annually or even once a decade.  Major macroeconomic indicators such as GDP tend to be quarterly but some countries may only estimate annually. 
• What exists for one country may not exist for another country. Data is generally inconsistent across borders .
• Documentation is typically in the native language .
• Always look at the methodology. The methodology section is one of the most important parts of the paper. Someone should be able to replicate your work. Describe the dataset and its population. Describe how the data was subset, any filters used, and any adjustment methods. While you are likely not trying to publish in American Economic Review  or Journal of Finance , these are the gold standards.  See how they layout the articles and in particular the methodology and data sections.
• The basic question to ask when looking for economic data is " who cares about what i am studying ?"  Unfortunately, the answer may be no one. Ideally, look for an organization that is concerned with your research as part of its mission. Examples include the International Labor Organization or the Bureau of Labor Statistics focusing on labor research; the International Monetary Fund or the Board of Governors of the Federal Reserve System focusing on monetary and fiscal concerns; the World Bank focusing on development; and the World Health Organization focusing on health. This does not mean these organizations collect data on all topics related to that field.
• Find a topic for which there is literature and data but allows room to add a contribution.  Topics such as sports and music are popular due to personal interests but may not make good research topics due to lack of data and overuse.

   More tips:

• Data is typically not adjusted for inflation.  It is usually presented in current (nominal) currency.  This means the numbers as they originally appeared.  When data has been adjusted for inflation (constant or real), a base year such as 2020 or 1990 will be shown.  If a base year is not provided, then data is current and therefore not adjusted for inflation.  If given a choice, choose current dollars.  Data is often derived from different datasets and many will use different base years.  Adjust everything at the end.  It is easier than doing reverse math!
• While most datasets are consistent within the dataset for currency used such as all in US Dollars or Euro or Japanese Yen or each item in local currency, some will mix and match.  LCU is a common abbreviation meaning local currency units. Consider looking at percent changes rather than actual values.  If adjusting use the exchange rate for each period of time, not the latest one.
• Economic indicators may be either seasonally adjusted or not seasonally adjusted.  This is very common for employment and retail sales.   Unless something says it is seasonally adjusted, it is not.  Be consistent and note in methodology.

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Nanotechnology Research: Applications in Nutritional Sciences 1 , 2

Pothur r. srinivas.

3 Atherothrombosis and Coronary Artery Diseases Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, 4 Division of Nutrition Research Coordination, 5 Office of Science Policy Analysis, Office of Science Policy, Office of the Director, 6 Office of Dietary Supplements, Office of the Director, and; 7 Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, MD 20892; 8 University of Michigan School of Public Health, Ann Arbor, MI 48109; 9 Oregon Health and Sciences University, Portland, OR 97239; 10 Rutgers University, New Brunswick, NJ 08901; 11 University of Illinois Urbana-Champaign Urbana, IL 61801; 12 National Institute for Food and Agriculture, USDA, Washington, DC 20024; 13 Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD 21702; and 14 Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

Martin Philbert

Tania q. vu, qingrong huang, josef l. kokini, hongda chen, charles m. peterson, karl e. friedl, crystal mcdade-ngutter, van hubbard, pamela starke-reed, nancy miller, joseph m. betz, johanna dwyer, john milner, sharon a. ross.

The tantalizing potential of nanotechnology is to fabricate and combine nanoscale approaches and building blocks to make useful tools and, ultimately, interventions for medical science, including nutritional science, at the scale of ∼1–100 nm. In the past few years, tools and techniques that facilitate studies and interventions in the nanoscale range have become widely available and have drawn widespread attention. Recently, investigators in the food and nutrition sciences have been applying the tools of nanotechnology in their research. The Experimental Biology 2009 symposium entitled “Nanotechnology Research: Applications in Nutritional Sciences” was organized to highlight emerging applications of nanotechnology to the food and nutrition sciences, as well as to suggest ways for further integration of these emerging technologies into nutrition research. Speakers focused on topics that included the problems and possibilities of introducing nanoparticles in clinical or nutrition settings, nanotechnology applications for increasing bioavailability of bioactive food components in new food products, nanotechnology opportunities in food science, as well as emerging safety and regulatory issues in this area, and the basic research applications such as the use of quantum dots to visualize cellular processes and protein-protein interactions. The session highlighted several emerging areas of potential utility in nutrition research. Nutrition scientists are encouraged to leverage ongoing efforts in nanomedicine through collaborations. These efforts could facilitate exploration of previously inaccessible cellular compartments and intracellular pathways and thus uncover strategies for new prevention and therapeutic modalities.

Introduction

“Nanotechnology” is the creation of functional materials, devices, and systems through the manipulation of matter at a length scale of ∼1–100 nm. At such a scale, novel properties and functions occur because of size ( 1 ). This emerging field is becoming important in enabling breakthroughs of new and effective tools in the medical sciences (e.g. nanomedicine), because it offers the possibility of examining biological processes in ways that were not previously possible. The medical use of nanotechnology includes the development of nanoparticles for diagnostic and screening purposes (i.e. early detection of cancer), development of artificial cellular proteins such as receptors, DNA and protein sequencing using nanopores and nanosprays, the manufacture of unique drug (and nutrient) delivery systems, as well as gene therapy and tissue engineering applications ( 2 ). Nanotechnology offers a range of tools capable of monitoring individual cells at the level of individual molecules. It enables researchers to investigate and monitor cellular and molecular function and to alter systems that are deregulated in disease. It is conceivable that nanomachines with the ability to circulate through the bloodstream, kill microbes, supply oxygen to hypoxic organs, or undo tissue damage could one day be delivered to the human body through medicines or even foods. There are challenges with the emergence of nanomedicine that include issues related to toxicity and the environmental impact of nanoscale materials. The social, ethical, legal, and cultural implications of nanotechnology must also be considered.

In nutrition research, nanotechnology applications may assist with obtaining accurate spatial information about the location of a nutrient or bioactive food component in a tissue, cell, or cellular component. Ultrasensitive detection of nutrients and metabolites, as well as increasing an understanding of nutrient and biomolecular interactions in specific tissues, has become possible. In theory, such new technologies have the potential to improve nutritional assessment and measures of bioavailability. They may help to identify and characterize molecular targets of nutrient activity and biomarkers of effect, exposure, and susceptibility and therefore may also inform “personalized” nutrition. Specific applications of nanotechnology to date in food and nutrition include: modifying taste, color, and texture of foods; detection of food pathogens and spoilage microorganisms; enhancing nutrition quality of foods; and novel vehicles for nutrient delivery, as well as serving as a tool to enable further elucidation of nutrient metabolism and physiology ( 3 – 5 ). For example, one food technology application involves creating coatings for foods and food packaging that serve as barriers to bacteria or that contain additional nutrients ( 6 ).

Nutritional products claiming to use nanotechnology are currently available in the market. It is important to recognize that the potential toxicity of nutrients can be affected by a change in particle size [see ( 7 ) for current updates]. Furthermore, little is known about the absorption and excretion of nanoparticles by experimental animals or in humans. Thus, there are challenges with the application of nanoscale compared with microscale materials. These include higher exposure per unit mass; small size:large surface area ratio; different routes of exposure due to smaller size (i.e. dermal penetration); different distribution to tissues by virtue of their different size or surface coating, chemistry, or particle charge; and novel properties of a nanoscale material that may alter absorption, digestion, metabolism, or excretion in the body.

To highlight nanotechnology applications and challenges for nutrition research and to encourage collaboration between various disciplines with the aim of advancing food and nutrition research, a symposium was convened at Experimental Biology 2009 on the topic “Nanotechnology Research: Applications in Nutritional Sciences.” This session presented various nanotechnology approaches for use in food and nutrition research. It also identified several safety/regulatory issues in nanotechnology, foods, and health. Experts focused on topics that included “Nanotechnology approaches for medical and nutrition research,” presented by Martin A. Philbert, University of Michigan School of Public Health. He provided an overview to set the stage about the application of nanotechnology in research, particularly focusing on how nanotechnology will be used to guide new prevention and therapeutic strategies for nutrition scientists. “Quantum dot technologies for visualizing live cell dynamic signaling and ultra-sensitive protein detection” was presented by Tania Q. Vu, Oregon Health and Sciences University. She discussed the use of quantum dots (QD) 15 to visualize cellular processes. The 3rd presentation, focused on nanotechnology applications for increasing bioavailability of bioactive food components in new food products, was presented by Dr. Qingrong Huang, Rutgers University (entitled “Bioavailability and delivery of dietary factors using nanotechnology”). “Food, nutrition and nanotechnology research: challenges and promises” was presented by Jozef Kokini, University of Illinois. He provided a compendium of nanotechnology opportunities for food science as well as safety and regulatory issues. A panel comprised of individuals from various federal agencies discussed and emphasized research opportunities and challenges in nanotechnology, foods, and health. The sections that follow provide a synopsis of each of these topics as well as recommendations for future applications of nanotechnology research in the nutritional sciences.

Nanotechnology approaches for medical and nutrition research

Dr. Martin Philbert discussed the challenges and opportunities of nanotechnology applications in clinical and nutrition settings. The very properties of nanostructured materials that make them so attractive could potentially lead to unforeseen health or environmental hazards ( 8 ). Some of these properties include high aspect ratio, bio-persistence, reactive surfaces and points that are capable of producing reactive oxygen species, composition and solubility. Coating the nanoparticle with biocompatible materials, however, has been shown to significantly reduce toxicity in some applications. Dr. Philbert also encouraged the design of products and processes in nanotechnology that reduce or eliminate the use and generation of hazardous substances. The translation of much of the current research in nanotechnology into clinical practice will rely on solving challenges that relate to the toxicity of nanoparticles.

Examples from this presentation highlight both the promises/possibilities and problems of nanomedicine. Probes encapsulated by biologically localized embedding (PEBBLE) 15 are sub-micron optical sensors that have been designed for minimally invasive analyte monitoring in viable, single cells ( 8 ). PEBBLE nanosensors are composed of matrices of cross-linked polyacrylamide, cross-linked poly(decyl methacrylate), or sol-gel silica, which have been fabricated as sensors for H + , Ca 2+ , K + , Na + , Mg 2+ , Zn 2+ , Cu 2+ , Cl − , and some nonionic species ( 9 ). A number of techniques have been used to deliver PEBBLE nanosensors into mouse oocytes, rat alveolar macrophages, rat C6-glioma, and human neuroblastoma cells ( 9 ). Using gene gun injection as a delivery method, a sol gel-based PEBBLE nanosensor for reliable, real-time measurement of subcellular molecular oxygen was inserted into rat C6 glioma cells. The cells responded to differing oxygen concentrations and provided real-time intracellular oxygen analysis. The PEBBLE contained an oxygen-sensitive fluorescent indicator, Ru(II)-Tris(4,7-diphenyl-1,10-phenanthroline) chloride ([Ru(dpp) 3 ] 2+ ), and an oxygen-insensitive fluorescent dye, Oregon Green 488-dextran, as a reference for the purpose of ratiometric intensity measurements ( 10 ). The small size and inert matrix of these sensors allow them to be inserted into living cells with minimal physical and chemical perturbations to their biological functions. Compared with using free dyes for intracellular measurements, the PEBBLE matrix protects the fluorescent dyes from interference by proteins in cells, enabling reliable in vivo chemical analysis. The matrix significantly reduces the toxicity of the indicator and reference dyes to the cells so that a wide variety of dyes can be used in optimal fashion. Hence, the sol gel-based PEBBLE sensors are extremely useful for real-time intracellular measurements such as oxygen levels. It is conceivable that PEBBLE technology can be utilized to monitor nutrient metabolism, the effects of reactive oxygen species generation, and ion distributions.

A nanoimaging example highlights the current challenge of brain tumor surgery to achieve complete resection without damaging normal structures near the tumor. Achieving maximal resection currently relies on the neurosurgeon's ability to judge the presence of residual tumor during surgery ( 11 ). The use of fluorescent and visible dyes has been proposed as a means of visualizing tumor margins intraoperatively. Such investigations have been hampered by difficulties in achieving tumor specificity, achieving adequate visual contrast, and identifying a dye useful for a wide range of tumors. Dye-loaded nanoparticles may be able to meet these challenges ( 11 ). Nanoparticle-based magnetic resonance contrast agents have been demonstrated to be useful to visualize portions of tumor in the brain that would be unclear with conventional imaging techniques. Nanoparticle-based contrast agents with a core of iron oxide crystals with or without a shell of organic material, such as polyethylene glycol, have been designed for such purposes ( 11 ).

Challenges related to nanoparticle clearance and toxicity need to be overcome before nanoparticles can be used clinically. Also, a greater understanding of the relationship between toxicity and particle size, geometry, pharmacokinetics, and surface coating is required before nanoparticles should be used in clinical practice.

QD technologies for visualizing live cell dynamic signaling and ultra-sensitive protein detection

Dr. Tania Vu demonstrated how nanotechnology can offer new capabilities that allow investigators to probe the function of key molecules using multiple modalities at the scale of single molecules in live cells. QD allow investigators to examine activities that cannot normally be resolved under a microscope with conventional dyes and florescent labels. When excited by laser light, the QD nano crystals emit photons and shine more brightly and longer in duration than any conventional label. Dr. Vu presented 2 main QD-based technologies that her laboratory has developed to investigate cellular function: 1 ) QD imaging probes for imaging protein trafficking and endocytic events in live cells; and 2 ) ultrasensitive QD assays for studying protein expression and specific protein-protein interactions in limited cell samples. Dr. Vu described tracking a protein within rat cells that regulates the growth of nerve tissue with the use the peptide ligand β nerve growth factor (NGF) conjugated to QD surfaces ( 12 ). The βNGF-QD were found to retain bioactivity, activate tyrosine kinase A (TrkA) receptors, and initiated downstream cellular signaling cascades to promote neuronal differentiation in PC12 cells. This example of receptor-initiated activity of QD-immobilized ligands has wide-ranging implications for the development of molecular tools and therapeutics targeted at understanding and regulating cell function. It is possible that QD may soon be used to visualize drugs or nutrients as they move in cells and cellular compartments in living systems.

QD hybrid gel blotting, which allows the purification and analysis of the action of QD bioconjugate-protein complexes in live cells, was also discussed. This is an alternative approach to PAGE-based Western blotting and immunoprecipitation ( 13 ). Interestingly, the protein interactions that are identified can also be correlated with spatial location in cells. Dr. Vu initially employed this technique to investigate the association of ligand NGF with the TrkA receptor in PC12 cells ( 14 ). It was found that NGF-QD could be retrieved and separated from a mixture of cellular lysate, NGF-QD were colocalized with an anti-TrkA receptor antibody, indicating TrkA −NGF-QD ligation, and discrete NGF-QD were bound to TrkA receptor puncta on the cell membrane surface. This novel nano-based technique has several advantages as a method for: 1 ) identifying specific QD-protein interactions in cells; 2 ) correlating QD-protein interactions with their spatial location in live cells; 3 ) studying the size and composition of QD bioconjugate probes/complexes; and 4 ) directly isolating and visualizing proteins from complex mixtures, offering an improvement over traditional bead-based immunoprecipitation methods ( 13 ).

These QD-based technologies offer investigators a means to probe specific inter-molecular interactions with significantly improved sensitivity and to relate these interactions with high-resolution in real time in live cells at the scale of single molecules. Nutrition researchers can adopt these QD-based technologies to examine questions of interest in nutrient metabolism and physiology.

Bioavailability and delivery of dietary factors using nanotechnology

Dr. Qingrong Huang described how the disease prevention properties of dietary supplements such as polyphenols have attracted much attention in recent years. Their biological effects include antioxidative, anticancer, and other properties that may prevent chronic disease as suggested by evidence from in vitro, animal, and human studies. Sales of the dietary supplements are high and growing annually. Thus, the development of high quality, stable dietary supplements with good bioavailability could become important. Although the use of dietary supplements in capsules and tablets is abundant, their effect is frequently diminished or even lost, because many of these compounds present solubility challenges. The major challenges of dietary polyphenols include their poor water solubility and oral bioavailability. Thus, novel delivery systems are needed to address these problems.

Dr. Huang presented a series of experiments integrating food processing, formulation, and in vivo/in vitro test development for the design of novel polyphenol nanocapsules, specifically for the water insoluble compounds curcumin, extracted from the turmeric plant ( Curcuma longa ), and dibenzoylmethane, a β -diketone analogue of curcumin. For example, high-speed and high-pressure homogenized oil-in-water emulsions using medium-chain triacylglycerols as oil and Tween 20 as emulsifier, were successfully prepared to encapsulate curcumin ( 15 ). These curcumin nanoemulsions were evaluated for antiinflammatory activity using a mouse ear inflammation model. An enhanced antiinflammatory activity was demonstrated (43 and 85% inhibition effect of 12- O -tetradecanoylphorbol-13-acetate-induced edema of mouse ear for 618.6 and 79.5 nm 1% curcumin oil-in-water emulsions, respectively), but a negligible effect was found for 1% curcumin in 10% Tween 20 water solution ( 15 ). Dr. Huang highlighted other recent in vivo biological and pharmacological experiments, which included a skin carcinogenesis model, measures of a series of proinflammatory biomarkers, and products that have demonstrated greatly improved antiinflammation activity and oral bioavailability of nanoencapsulated curcumin and dibenzoylmethane.

A wide variety of encapsulation platforms, including nanostructured emulsions, water-in-oil-in-water or oil-in-water-in-oil double emulsions, solid lipid or biopolymer-based nanoparticles, and direct conjugation of phytochemicals to biopolymer side chains have been developed to encapsulate food constituents for enhanced delivery and bioavailability ( 6 , 16 ). With the aid of nanoencapsulation, in vivo absorption and circulation of bioactive food components appear to increase, which should assist in achieving the desired concentration and biological activity of these compounds. Although an increase in nutrient intake from an enhanced food supply may be beneficial, food and nutrition professionals may need to monitor overconsumption and potential signs of toxicity more closely. Additionally, micronutrient imbalances may become more prevalent and drug-nutrient interactions will also require careful observation ( 5 ). Thus, a greater understanding of the metabolic consequences of nutrients in novel food systems are required as nanotechnology applications expand in the food sciences.

Food, nutrition, and nanotechnology research: challenges and promises

Dr. Josef Kokini described the opportunities for nanotechnology applications to foods and agriculture, including nanomaterials in food packaging, food protein-based nanotubes to bind vitamins or enzymes, and rapid sampling of biological and chemical contaminants using nanocantilevers as detection tools for water and food safety. Nanotechnology has the potential to transform the entire food industry by changing the way food is produced, processed, packaged, transported, and consumed. Applications in food packaging are very promising, because they can improve the safety and quality of food products ( 17 ). The use of bionanocomposites for food packaging not only has the potential to protect the food and increase its shelf life but can also be considered more environmentally friendly, because such composites would reduce the requirement to use plastics as packaging materials, thus decreasing environmental pollution in addition to consuming less fossil fuel for their production ( 17 ). Zein, a prolamin and the major protein found in corn, has been an important material in science and industry because of its distinctive properties and molecular structure. Novel approaches are expected to yield new applications for zein in the foods and biodegradable plastics industry. After solvent treatment, zein can form a tubular structure meshwork that is inert and resistant to microbes ( 17 ). Zein nanoparticles have been synthesized and examined as edible carriers of flavor compounds, for nanoencapsulation of dietary supplements, as well as to improve the strength of plastic and bioactive food packaging. Importantly, controlling the uniformity and organization of zein films at the nanolevel is critical for its mechanical and tensile properties. Dr. Kokini et al. ( 18 ) tested different solvents and found that zein films that were generated in acetic acid were smoother and structurally more homogeneous than those produced using ethanol. Other investigators are examining the use of silicates to strengthen zein films.

Novel nanosensors are being tested to detect food pathogens. Array techniques with thousands of nanoparticles on a platform have been designed to fluoresce in different colors on contact with food pathogens. Furthermore, intelligent packaging with nanosensors is being considered that has the ability to react to the environment and perhaps interact with the food product with specific applications. One application might be to detect food spoilage.

The challenges for the application of nanotechnology in food and food science were also described. Because of their increased surface area, nanomaterials might have toxic effects in the body that are not apparent in bulk materials. Extensive use of nanoparticles in foods as additives is less likely in the near future because of possible safety concerns. Although nanomaterials from food packaging would not ordinarily be ingested or inhaled, the potential exists for unforeseen risk, such as release of airborne nanoparticles that might aggravate lung function or inadvertent consumption due to leakage of packaging materials into foods. The U.S. FDA requires that manufacturers demonstrate that food ingredients and food products are not harmful to health, but specific regulations about nanoparticles do not exist. Although there is a lack of regulation and knowledge of risk, still there are a number of food and nutrition products that claim to contain nanoscale additives, including iron in nutritional drink mixes, micelles that carry vitamins, minerals and phytochemicals in oil, and zinc oxide in breakfast cereals ( 17 , 19 ). Although more research is needed on the health consequences of nanoparticles, it is unclear what the full range of concerns are, because measurement of exposure to nanomaterials is neither well developed nor characterized. Therefore, an emerging challenge to benefiting from nanotechnology is having the foresight to develop and use it wisely. To this end, governmental agencies (via the National Nanotechnology Initiative) are working together to proactively research and evaluate the benefits and harms of nanotechnology.

Research opportunities and challenges in nanotechnology, foods, and health

A panel discussion entitled “Research Opportunities and Challenges in Nanotechnology, Foods and Health” followed the presentations and included federal government representatives from the Division of Nutrition Research Coordination, NIH (Dr. Crystal McDade-Ngutter), Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command (Dr. Charles Peterson), and the National Institute for Food and Agriculture (NIFA; formerly Cooperative State Research, Education, and Extension Service), USDA (Dr. Etta Saltos). Each panelist provided information about research opportunities in nanotechnology from their agencies that would be of interest to nutrition scientists as well as a perspective on the challenges of nanotechnology, foods, and health. The NIH has supported many initiatives on the topic of nanotechnology, such as the NIH Nanomedicine Roadmap Initiative ( 20 ) and the NCI Alliance for Nanotechnology in Cancer ( 21 ), but none that have been specifically targeted for nutrition research. More opportunities for nutrition scientists to interact and collaborate with nanotechnology experts were emphasized as a way forward for such NIH applications. Similarly, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command supports a Nanotechnology and Biomaterials Portfolio that is focused on identifying novel developments in materials science and biomaterials that can improve drugs and devices for diagnosis and therapy of a broad range of medical conditions ( 22 ). NIFA, USDA in collaboration with food and agricultural scientists from land grant universities and the National Nanotechnology Initiative agencies developed the first strategic roadmap titled “Nanoscale Science and Engineering for Agriculture and Food Systems” ( 23 ). The resulting NIFA, USDA initiative “Nanoscale Science and Engineering for Agriculture and Food Systems” has been offered every other year with next cycle of new applications to be announced in fiscal year 2010 ( 24 ). The goal of this program is to provide knowledge, expertise, and highly qualified research and development in nanotechnology for food and agricultural systems. Examples of 2008 priorities included novel nanoscale processes, materials and systems with improved delivery efficacy, controlled release, modification of sensory attributes, and protection of micronutrients and functional ingredients suitable for food matrices as well as the assessment and analysis of perceptions and acceptance of nanotechnology and nano-based products by the general public, agriculture, and food stakeholders using appropriate social science tools.

During the discussion, several research areas in the nutritional sciences that would benefit from nanotechnology applications were highlighted (summarized in Table 1 ). Nutrition scientists may wish to leverage ongoing efforts and collaborate with experts in nanotechnology so that novel approaches can be developed to tackle many of these research questions. The panel discussion provided insight into the research opportunities and challenges concerning applications for nanotechnology so that nutrition and food scientists can be more informed and productive in their research endeavors.

Examples of research areas in nutrition with nanotech enhancement potential

Recent advances in biomedical and agricultural technology will likely assist in advancing our understanding of health and disease processes. The symposium “Nanotechnology Research: Applications in Nutritional Sciences” highlighted new and emerging technologies that are currently, or soon to be, available for nutritional sciences. Examples discussed included: 1 ) nanoscale optical sensors, such as PEBBLE, for intracellular chemical sensing; 2 ) QD technologies to visualize and quantify cellular protein interactions; 3 ) nanoencapsulation of bioactive food components to improve their bioavailability; and 4 ) intelligent food packaging that acts as a biosensor to monitor and detect spoilage or infection ( Fig. 1 ).

Examples of nanotechnology applications and their associated discipline highlighted during the symposium.

Nutrition and food science research areas that might benefit from applying or understanding nanotechnology include research that aims to: 1 ) identify sites of action (molecular targets) for bioactive food components; 2 ) characterize biomarkers that reflect exposure, response, and susceptibility to foods and their components; 3 ) identify new target delivery systems for optimizing health; and 4 ) improve food composition. Because there is little information about the potential health risks of nanoparticles, more research on the toxicology of nanoparticles, both on a case-by-case basis and for general applicability, is also warranted. Nanotechnology has the potential to advance the science of nutrition by assisting in the discovery, development, and delivery of several intervention strategies to improve health and reduce the risk and complications of several diseases. This symposium was designed to enhance knowledge and understanding about technologies that may be utilized or are currently being employed and or/modified for nutrition and food science research. It is hoped that by highlighting these technologies the potential benefit of nanomaterials to revolutionize food and nutrition research is recognized.

Acknowledgments

P.R.S. and S.A.R. wrote the paper and had primary responsibility for final content; M.P., T.Q.V., Q.H., J.L.K., E.S., H.C., C.M.P., K.E.F., C.M-N., V.H., P.S-R., N.M., J.M.B., J.D., and J.M. provided essential materials and information for the creation and revisions of the manuscript. All authors read and approved the final manuscript.

1 Published as a supplement to The Journal of Nutrition . Presented as part of the symposium entitled “Nanotechnology Research: Applications in Nutritional Sciences” given at the Experimental Biology 2009 meeting, April 21, 2009, in New Orleans, LA. This symposium was sponsored the Division of Nutrition Research Coordination, NIH; the Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH; the Office of Science Policy, Office of the Director, NIH; Office of Dietary Supplements, Office of the Director, NIH; the Atherothrombosis and Coronary Artery Diseases Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH; and the Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command. This symposium was supported by the Division of Nutrition Research Coordination, NIH; the Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH; and the Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command. The symposium was chaired by Pothur R. Srinivas and Sharon A. Ross. Guest Editor for this symposium publication was Sharon M. Nickols-Richardson. Guest Editor disclosure: Sharon M. Nickols-Richardson had no conflicts to disclose.

2 Author disclosures: P. R. Srinivas, M. Philbert, T. Q. Vu, Q. Huang, J. L. Kokini, E. Saos, H. Chen, C. M. Peterson, K. E. Friedl, C. McDade-Ngutter, V. Hubbard, P. Starke-Reed, N. Miller, J. M. Betz, J. Dwyer, J. Milner, and S. A. Ross, no conflicts of interest.

15 Abbreviations used: NGF, nerve growth factor; NIFA, National Institute for Food and Agriculture; PEBBLE, probes encapsulated by biologically localized embedding; QD, quantum dot; TrkA, tyrosine kinase A.