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Nanotechnology

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Nanotechnology encompasses the understanding of the fundamental physics, chemistry, biology and technology of nanometre-scale objects.

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Achint Jain et al 2018 Nanotechnology 29 265203

Integrating layered two-dimensional (2D) materials into 3D heterostructures offers opportunities for novel material functionalities and applications in electronics and photonics. In order to build the highest quality heterostructures, it is crucial to preserve the cleanliness and morphology of 2D material surfaces that come in contact with polymers such as PDMS during transfer. Here we report that substantial residues and up to ∼0.22% compressive strain can be present in monolayer MoS 2 transferred using PDMS. We show that a UV-ozone pre-cleaning of the PDMS surface before exfoliation significantly reduces organic residues on transferred MoS 2 flakes. An additional 200 ◦ C vacuum anneal after transfer efficiently removes interfacial bubbles and wrinkles as well as accumulated strain, thereby restoring the surface morphology of transferred flakes to their native state. Our recipe is important for building clean heterostructures of 2D materials and increasing the reproducibility and reliability of devices based on them.

Irene Ayuso-Pérez et al 2024 Nanotechnology 35 325206

Semiconductor nanowires (NWs) are promising candidates for use in electronic and optoelectronic applications, offering numerous advantages over their thin film counterparts. Their performance relies heavily on the quality of the contacts to the NW, which should exhibit ohmic behavior with low resistance and should be formed in a reproducible manner. In the case of heterostructure NWs for high-mobility applications that host a two-dimensional electron gas, ohmic contacts are particularly challenging to implement since the NW core constituting the conduction channel is away from the NW surface. We investigated contact formation to modulation-doped GaAs/(Al,Ga)As core/shell NWs using scanning transmission electron microscopy, energy dispersive x-ray spectroscopy and electron tomography to correlate microstructure, diffusion profile and chemical composition of the NW contact region with the current–voltage ( I–V ) characteristics of the contacted NWs. Our results illustrate how diffusion, alloying and phase formation processes essential to the effective formation of ohmic contacts are more intricate than in planar layers, leading to reproducibility challenges even when the processing conditions are the same. We demonstrate that the NW geometry plays a crucial role in the creation of good contacts. Both ohmic and rectifying contacts were obtained under nominally identical processing conditions. Furthermore, the presence of Ge in the NW core, in the absence of Au and Ni, was found as the key factor leading to ohmic contacts. The analysis contributes to the current understanding of ohmic contact formation to heterostructure core/shell NWs offering pathways to enhance the reproducibility and further optimization of such NW contacts.

Karl Berggren et al 2021 Nanotechnology 32 012002

Recent progress in artificial intelligence is largely attributed to the rapid development of machine learning, especially in the algorithm and neural network models. However, it is the performance of the hardware, in particular the energy efficiency of a computing system that sets the fundamental limit of the capability of machine learning. Data-centric computing requires a revolution in hardware systems, since traditional digital computers based on transistors and the von Neumann architecture were not purposely designed for neuromorphic computing. A hardware platform based on emerging devices and new architecture is the hope for future computing with dramatically improved throughput and energy efficiency. Building such a system, nevertheless, faces a number of challenges, ranging from materials selection, device optimization, circuit fabrication and system integration, to name a few. The aim of this Roadmap is to present a snapshot of emerging hardware technologies that are potentially beneficial for machine learning, providing the Nanotechnology readers with a perspective of challenges and opportunities in this burgeoning field.

Pooja Nag et al 2024 Nanotechnology 35 345602

Rampant pathogenesis induced by communicable microbes has necessitated development of technologies for rapid and sustained disinfection of surfaces. Copper nanoparticles (CuNPs) have been widely reported for their antimicrobial properties. However, nanostructured copper is prone to oxidative dissolution in the oil phase limiting its sustained use on surfaces and coatings. The current study reports a systematic investigation of a simple synthesis protocol using fatty acid stabilizers (particularly essential oils) for synthesis of copper nanoparticles in the oil phase. Of the various formulations synthesized, rosemary oil stabilized copper nanoparticles (RMO CuNPs) were noted to have the best inactivation kinetics and were also most stable. Upon morphological characterization by TEM and EELS, these were found to be monodispersed ( φ 5–8 nm) with copper coexisting in all three oxidation states on the surface of the nanoparticles. The nanoparticles were drop cast on woven fabric of around 500 threads per inch and exposed to gram positive bacteria ( Staphylococcus aureus ), gram negative bacteria ( Escherichia coli and Pseudomonas aeruginosa ), enveloped RNA virus (phi6), non-enveloped RNA virus (MS2) and non-enveloped DNA virus (T4) to encompass the commonly encountered groups of pathogens. It was possible to completely disinfect 10 7 copies of all microorganisms within 40 min of exposure. Further, this formulation was incorporated with polyurethane as thinners and used to coat non-woven fabrics. These also exhibited antimicrobial properties. Sustained disinfection with less than 9% cumulative copper loss for upto 14 washes with soap water was observed while the antioxidant activity was also preserved. Based on the studies conducted, RMO CuNP in oil phase was found to have excellent potential of integration on surface coatings, paints and polymers for rapid and sustained disinfection of microbes on surfaces.

Syed Nabeel Ahmed and Waseem Haider 2018 Nanotechnology 29 342001

There has been a considerable amount of research in the development of sustainable water treatment techniques capable of improving the quality of water. Unavailability of drinkable water is a crucial issue especially in regions where conventional drinking water treatment systems fail to eradicate aquatic pathogens, toxic metal ions and industrial waste. The research and development in this area have given rise to a new class of processes called advanced oxidation processes, particularly in the form of heterogeneous photocatalysis, which converts photon energy into chemical energy. Advances in nanotechnology have improved the ability to develop and specifically tailor the properties of photocatalytic materials used in this area. This paper discusses many of those photocatalytic nanomaterials, both metal-based and metal-free, which have been studied for water and waste water purification and treatment in recent years. It also discusses the design and performance of the recently studied photocatalytic reactors, along with the recent advancements in the visible-light photocatalysis. Additionally, the effects of the fundamental parameters such as temperature, pH, catalyst-loading and reaction time have also been reviewed. Moreover, different techniques that can increase the photocatalytic efficiency as well as recyclability have been systematically presented, followed by a discussion on the photocatalytic treatment of actual wastewater samples and the future challenges associated with it.

Ashna Rajeev et al 2024 Nanotechnology 35 352003

Fabrication and operation on increasingly smaller dimensions have been highly integrated with the development of smart and functional materials, which are key to many technological innovations to meet economic and societal needs. Along with researchers worldwide, the Waterloo Institute for Nanotechnology (WIN) has long realized the synergetic interplays between nanotechnology and functional materials and designated 'Smart & Functional Materials' as one of its four major research themes. Thus far, WIN researchers have utilized the properties of smart polymers, nanoparticles, and nanocomposites to develop active materials, membranes, films, adhesives, coatings, and devices with novel and improved properties and capabilities. In this review article, we aim to highlight some of the recent developments on the subject, including our own research and key research literature, in the context of the UN Sustainability development goals.

Mathijs G C Mientjes et al 2024 Nanotechnology 35 325602

Topological crystalline insulators (TCIs) are interesting for their topological surface states, which hold great promise for scattering-free transport channels and fault-tolerant quantum computing. A promising TCI is SnTe. However, Sn-vacancies form in SnTe, causing a high hole density, hindering topological transport from the surface being measured. This issue could be relieved by using nanowires with a high surface-to-volume ratio. Furthermore, SnTe can be alloyed with Pb reducing the Sn-vacancies while maintaining its topological phase. Here we present the catalyst-free growth of monocrystalline PbSnTe in molecular beam epitaxy. By the addition of a pre-deposition stage before the growth, we have control over the nucleation phase and thereby increase the nanowire yield. This facilitates tuning the nanowire aspect ratio by a factor of four by varying the growth parameters. These results allow us to grow specific morphologies for future transport experiments to probe the topological surface states in a Pb 1– x Sn x Te-based platform.

Guanxuan Lu et al 2024 Nanotechnology 35 352002

The development of 6 G networks has promoted related research based on terahertz communication. As submillimeter radiation, signal transportation via terahertz waves has several superior properties, including non-ionizing and easy penetration of non-metallic materials. This paper provides an overview of different terahertz detectors based on various mechanisms. Additionally, the detailed fabrication process, structural design, and the improvement strategies are summarized. Following that, it is essential and necessary to prevent the practical signal from noise, and methods such as wavelet transform, UM-MIMO and decoding have been introduced. This paper highlights the detection process of the terahertz wave system and signal processing after the collection of signal data.

I I Olaniyan et al 2024 Nanotechnology 35 335301

The realization of perovskite oxide nanostructures with controlled shape and dimensions remains a challenge. Here, we investigate the use of helium and neon focused ion beam (FIB) milling in an ion microscope to fabricate BaTiO 3 nanopillars of sub-500 nm in diameter starting from BaTiO 3 (001) single crystals. Irradiation of BaTiO 3 with He ions induces the formation of nanobubbles inside the material, eventually leading to surface swelling and blistering. Ne-FIB is shown to be suitable for milling without inducing surface swelling. The resulting structures are defect-free single crystal nanopillars, which are enveloped, on the top and lateral sidewalls, by a point defect-rich crystalline region and an outer Ne-rich amorphous layer. The amorphous layer can be selectively etched by dipping in diluted HF. The geometry and beam-induced damage of the milled nanopillars depend strongly on the patterning parameters and can be well controlled. Ne ion milling is shown to be an effective method to rapidly prototype BaTiO 3 crystalline nanostructures.

Latest articles

Gaeun Bae et al 2024 Nanotechnology 35 372001

A new type of 0-dimensional carbon-based materials called graphene quantum dots (GQDs) is gaining significant attention as a non-toxic and eco-friendly nanomaterial. GQDs are nanomaterials composed of sp 2 hybridized carbon domains and functional groups, with their lateral size less than 10 nm. The unique and exceptional physical, chemical, and optical properties arising from the combination of graphene structure and quantum confinement effect due to their nano-size make GQDs more intriguing than other nanomaterials. Particularly, the low toxicity and high solubility derived from the carbon core and abundant edge functional groups offer significant advantages for the application of GQDs in the biomedical field. In this review, we summarize various synthetic methods for preparing GQDs and important factors influencing the physical, chemical, optical, and biological properties of GQDs. Furthermore, the recent application of GQDs in the biomedical field, including biosensor, bioimaging, drug delivery, and therapeutics are discussed. Through this, we provide a brief insight on the tremendous potential of GQDs in biomedical applications and the challenges that need to be overcome in the future.

Hrudya Radhakrishnan et al 2024 Nanotechnology 35 375302

We demonstrate template-assisted growth of gallium-based nanoparticle clusters on silicon substrate using a focused ion beam (FIB) nanolithography technique. The nanolithography counterpart of the technique steers a focussed 30 kV accelerated gallium ion beam on the surface of Si to create template patterns of two-dimensional dot arrays. Growth of the nanoparticles is governed by two vital steps namely implantation of gallium into the substrate via gallium beam exposure and formation of the stable nanoparticles on the surface of the substrate by subsequent annealing at elevated temperature in ammonia atmosphere. The growth primarily depends on the dose of implanted gallium which is in the order of 10 7 atoms per spot and it is also critically influenced by the temperature and duration of the post-annealing treatment. By controlling the growth parameters, it is possible to obtain one particle per spot and particle densities as high as 10 9 particles per square centimetre could be achieved in this case. The demonstrated growth process, utilizing the advantages of FIB nanolithography, is categorized under the guided organization approach as it combines both the classical top-down and bottom-up approaches. Patterned growth of the particles could be utilized as templates or nucleation sites for the growth of an organized array of nanostructures or quantum dot structures.

Yoshiaki Hattori et al 2024 Nanotechnology 35 375704

Optical microscopy with white light illumination has been employed when obtaining exfoliated monolayer hexagonal boron nitride (1L hBN) films from a large number of randomly placed films on a substrate. However, real-time observation of 1L hBN using a color camera under white light illumination remains challenging since hBN is transparent in the visible wavelength range. The poor optical constant of 1L hBN films in microphotographs is significantly improved using a Si substrate coated with a SiN x thin-film (SiN x /Si). When observing hBN thin films on SiN x /Si using a color digital camera in an optical microscope under white light illumination, the clarity of the captured color images depends on the thickness of the SiN x film ( d ). For real-time direct observation, the d was optimized based on quantitative chromatic studies tailored to Bayer filters of a color image sensor. Through image simulation, it was determined that the color difference between 1L hBN and the bare substrate is maximized at d = 59 or 70 nm, which was experimentally verified. The SiN x /Si with optimized d values visualized 1L hBN films without requiring significant contrast enhancement via image processing under white light illumination in real-time. Furthermore, the captured color photographs facilitate the reliable determination of the number of layers in few-layer hBN films using the contrast of the green channel of the images.

J Crêpellière et al 2024 Nanotechnology 35 375703

While silver nanowires (Ag NWs) have been demonstrated as a highly efficient transparent conducting material, they suffer from strong light scattering, which is quantified by a large haze factor (HF) in the optical spectrum. Here we investigate the influence of the dielectric environment on the light scattering of Ag NWs by comparing experimental measurements and simulations. In air, two peaks on the HF spectra are observed experimentally at the wavelength of λ I = 350 nm and λ II = 380 nm and are attributed by simulations to the influence of the Ag NWs pentagonal shape on the localized surface plasmon resonance. The relative intensity between the two peaks is found to be dependent on whether the Ag NWs are in contact with the glass substrate or not. The HF behaviour in the near IR region seems to be dominated by Rayleigh scattering following simulations results. Dielectric environments of Ag NWs with various refractive indexes were obtained experimentally by the conformal deposition of different metal oxide coatings using atomic layer deposition, including Al-doped zinc oxide, Al 2 O 3 and SiO 2 coatings. The HF is found to be correlated with the refractive index environment in terms of HF peaks position, intensity and broadening. This trend of HF peaks is supported by a theoretical model to understand the optical mechanism behind this phenomenon.

Xin Liu et al 2024 Nanotechnology 35 375702

We investigate the effects of oxygen vacancies on the ferroelectric behavior of Al:HfO 2 films annealed in O 2 and N 2 atmosphere. X-ray photoelectron spectroscopy results showed that the O/Hf atomic ratio was 1.88 for N 2 -annealed samples and 1.96 for O 2 -annealed samples, implying a neutralization of oxygen vacancies during O 2 atmosphere annealing. The O 2 -annealed films exhibited an increasing remanent polarization from 23 μ C cm −2 to 28 μ C cm −2 after 10 4 cycles, with a negligible leakage current density of ∼2 μ A cm −2 , while the remanent polarization decreased from 29 μ C cm −2 to 20 μ C cm −2 after cycling in the N 2 -annealed films, with its severe leakage current density decreasing from ∼1200 μ A cm −2 to ∼300 μ A cm −2. A phase transition from the metastable tetragonal (t) phase to the low-temperature stable orthorhombic (o) phase and monoclinic (m) phase was observed during annealing. As a result of the fierce· competition between the t-to-o transition and the t-to-m transition, clear grain boundaries of several ruleless atomic layers were formed in the N 2 -annealed samples. On the other hand, the transition from the t-phase to the low-temperature stable phase was found to be hindered by the neutralization of oxygen vacancies, with almost continuous grain boundaries observed. The results elucidate the phase transformation caused by oxygen vacancies in the Al:HfO 2 films, which may be helpful for the preparation of HfO 2 -based films with excellent ferroelectricity.

Review articles

Zhong Xu et al 2024 Nanotechnology 35 362006

Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.

Yibin Wang and Xiulian Shi 2024 Nanotechnology 35 362005

Exosomes are extracellular vesicles of diverse compositions that are secreted by numerous cell types. Exosomes contain significant bioactive components, including lipids, proteins, mRNA, and miRNA. Exosomes play an important role in regulating cellular signaling and trafficking under both normal physiological and pathological circumstances. A multitude of factors, including thermal stress, ribosomal stress, endoplasmic reticulum stress, and oxidative stress influence the concentrations of exosomal mRNA, miRNA, proteins, and lipids. It has been stated that exosomes derived from stem cells (SCs) modulate a range of stresses by preventing or fostering cell balance. Exosomes derived from SCs facilitate recovery by facilitating cross-cellular communication via the transmission of information in the form of proteins, lipids, and other components. For this reason, exosomes are used as biomarkers to diagnose a wide variety of diseases. The focus of this review is the bioengineering of artificial exosomal cargoes. This process encompasses the control and transportation of particular exosomal cargoes, including but not limited to small molecules, recombinant proteins, immune modulators, and therapeutic medications. Therapeutic approaches of this nature have the potential to deliver therapeutic medications precisely to the intended site for the cure of a variety of disorders. Notably, our attention has been directed towards the therapeutic implementations of exosomes derived from SCs in the cure of cardiovascular ailments, including but not limited to ischemic heart disease, myocardial infarction, sepsis, heart failure, cardiomyopathy, and cardiac fibrosis. In general, researchers employ two methodologies when it comes to exosomal bioengineering. This review aims to explain the function of exosomes derived from SCs in the regulation of stress and present a novel therapeutic approach for cardiovascular disorders.

Bin Wang et al 2024 Nanotechnology 35 362004

Aqueous aluminum-ion batteries have many advantages such as their safety, environmental friendliness, low cost, high reserves and the high theoretical specific capacity of aluminum. So aqueous aluminum-ion batteries are potential substitute for lithium-ion batteries. In this paper, the current research status and development trends of cathode and anode materials and electrolytes for aqueous aluminum-ion batteries are described. Aiming at the problem of passivation, corrosion and hydrogen evolution reaction of aluminum anode and dissolution and irreversible change of cathode after cycling in aqueous aluminum-ion batteries. Solutions of different research routes such as ASEI (artificial solid electrolyte interphase), alloying, amorphization, elemental doping, electrolyte regulation, etc and different transformation mechanisms of anode and cathode materials during cycling have been summarized. Moreover, it looks forward to the possible research directions of aqueous aluminum-ion batteries in the future. We hope that this review can provide some insights and support for the design of more suitable electrode materials and electrolytes for aqueous aluminum-ion batteries.

Srinivasan Raman et al 2024 Nanotechnology 35 362003

Monocrystalline bulk silicon with doped impurities has been the widely preferred piezoresistive material for the last few decades to realize micro-electromechanical system (MEMS) sensors. However, there has been a growing interest among researchers in the recent past to explore other piezoresistive materials with varied advantages in order to realize ultra-miniature high-sensitivity sensors for area-constrained applications. Of the various alternative piezoresistive materials, silicon nanowires (SiNWs) are an attractive choice due to their benefits of nanometre range dimensions, giant piezoresistive coefficients, and compatibility with the integrated circuit fabrication processes. This review article elucidates the fundamentals of piezoresistance and its existence in various materials, including silicon. It comprehends the piezoresistance effect in SiNWs based on two different biasing techniques, viz., (i) ungated and (ii) gated SiNWs. In addition, it presents the application of piezoresistive SiNWs in MEMS-based pressure sensors, acceleration sensors, flow sensors, resonators, and strain gauges.

Accepted manuscripts

Jain et al 

In this research, we report an enhanced sensing response ethanol gas sensing device based on a ternary nanocomposite of molybdenum diselenide-zinc oxide heterojunctions decorated rGO (MoSe2/ZnO/rGO) at room temperature. The sensing performance of the ternary nanocomposite sensing device has been analysed for various concentrations of ethanol gas (1-500 ppm). The gas-sensing results have revealed that for 500 ppm ethanol gas concentration, the sensing device has exhibited an enhanced response value (Rg/Ra) of 50.2. Significantly, the sensing device has displayed a quick response and recovery time of 6.2 s and 12.9 s respectively. In addition to this, the sensing device has shown a great prospect for long-term detection of ethanol gas (45 days). The sensing device has demonstrated the ability to detect ethanol at remarkably low concentrations of 1 ppm. The enhanced sensing performance of the ternary nanocomposite sensing device has highlighted the effective synergistic effect between MoSe2 nanosheets, ZnO nanorods, and rGO nanosheets. This has been attributed to the formation of two heterojunctions in the ternary nanocomposite sensor: a p-n heterojunction between MoSe2 and ZnO and a p-p heterojunction between MoSe2 and rGO. The analysis of the results has suggested that the proposed MoSe2/ZnO/rGO nanocomposite sensing device could be considered a promising candidate for the real-time detection of ethanol gas.

Singh et al 

With the increasing demand for sensing platforms operating across UV, visible, and near-infrared wavelengths, nanoporous gold has emerged as an ideal substrate for rapid, quantitative detection of analytes with excellent specificity and high sensitivity. This study investigates thickness-mediated compositional changes and their impact on scattering characteristics of thin nanoporous gold films fabricated using selective chemical etching. Specifically, we observe thickness-induced morphological and structural changes across different fabricated samples from 25-100nm in thickness. Upon their optical characterization across UV-VIS-NIR spectral regime, we notice that the constitutional differences among samples manifest distinctively \& deterministically in their total optical scattering response. In order to gain insights into these observed scattering responses and to fathom the subtle connections between structural properties of NPG films and their optical response, a hybrid theoretical model comprising Maxwell-Garnett \& Bruggeman effective medium approximations has been adopted. Our approach not only allows to appropriately account for the inhomogeneous nature of these films, but also corroborates well with the atomic force microscopy characterizations of the fabricated samples. Furthermore, tracing such a theoretical model is important as it helps in systematically ascertaining additional loss terms emerging in the complex dielectric function of films due to their nanoscale porosity \& roughness, permitting a good reproduction of measured optical spectra. We believe, our approach will not only facilitate accurate regulation of losses in NPG thin films but will also aid in deriving customized optical performance from them, thereby advancing their potential applications in sensing and beyond.

Sardari et al 

Tissue engineering is a multidisciplinary field that merges engineering, material science, and medical biology in order to develop biological alternatives for repairing, replacing, maintaining, or boosting the functionality of tissues and organs. The ultimate goal of tissue engineering is to create biological alternatives for repairing, replacing, maintaining, or enhancing the functionality of tissues and organs. However, the current landscape of tissue engineering techniques presents several challenges, including a lack of suitable biomaterials, inadequate cell proliferation, limited methodologies for replicating desired physiological structures, and the unstable and insufficient production of growth factors, which are essential for facilitating cell communication and the appropriate cellular responses. Despite these challenges, there has been significant progress made in tissue engineering techniques in recent years. Nanoparticles hold a major role within the realm of nanotechnology due to their unique qualities that change with size. These particles, which provide potential solutions to the issues that are met in tissue engineering, have helped propel nanotechnology to its current state of prominence. Despite substantial breakthroughs in the utilization of nanoparticles over the past two decades, the full range of their potential in addressing the difficulties within tissue engineering remains largely untapped. This is due to the fact that these advancements have occurred in relatively isolated pockets. In the realm of tissue engineering, the purpose of this research is to conduct an in-depth investigation of the several ways in which various types of nanoparticles might be put to use. In addition to this, it sheds light on the challenges that need to be conquered in order to unlock the maximum potential of nanotechnology in this area.

Qin et al 

Memristors have recently received substantial attention because of its promising and unique application scenes emerging in neuromorphic computing which can achieve gains in computation speed by mimicking the topology of brains in electronic circuits. Traditional memristors made of bulk MoO3 and HfO2, etc. suffer from low switching ratio, short durability and poor stability. In this work, a floating-gate memristor is developed based on a mixed-dimensional heterostructure which is comprised of two-dimensional (2D) molybdenum disulfide (MoS2) and 0-dimensional (0D) Au nanoparticles (AuNPs) separated by an insulating hexagonal boron nitride (h-BN) layer, hereafter, MoS2/h-BN/AuNPs. We find that under the modulation of back-gate voltages, the MoS2/h-BN/AuNPs device operates reliably between a high resistance state (HRS) and a low resistance state (LRS) and that it shows multiple stable LRS states, demonstrating high potential of our memristor in application of multibit storage. The modulation effect can be attributed to the electron quantum tunneling between the AuNPs charge-trapping layer and MoS2 channel. Our memristor exhibits excellent durability and stability: the HRS and LRS remain more than 104 s without obvious degradation and the on/off ratio retains > 104 after more than 3000 switching cycles. We also demonstrate frequency-dependent memory properties upon electrical and optical pulse stimuli.

Xiao et al 

Lu doped Hf0.5Zr0.5O2 (HZO) ferroelectric films were prepared on Pt/TiN/SiO2/Si substrate by chemical solution deposition (CSD) method, and an interfacial engineering strategy for improving the ferroelectric property was explored by capping the Lu doped HZO films with a cerium oxide layer. Compared with the Lu doped HZO film without the CeOx coating layer, the Lu doped HZO film with the CeOx coating layer has a larger remanent polarization (2Pr=34.72 µC/cm2) and presents weaker wake-up behavior, which result from the higher orthogonal phase ratio and the lower oxygen vacancy of the CeOx coated Lu doped HZO film. In addition, the CeOx coating can remarkably improve the fatigue resistance and retention performance of the Lu doped HZO films. It is hoped that the results can provide an effective approach for the realization of high-performance and highly reliable hafnium oxide based ferroelectric thin films.

More Accepted manuscripts

Open access

İlkgül Akmayan et al 2024 Nanotechnology

Safe and effective vaccine candidates are needed to address the limitations of existing vaccines against Brucellosis, a disease responsible for substantial economic losses in livestock. The present study aimed to encapsulate Omp25 and EipB proteins, knowledged antigen properties, into PLGA nanoparticles, characterize synthesized nanoparticles with different methods, and assessed their in vitro/in vivo immunostimulatory activities to develop new vaccine candidates. The rOmp25 and EipB proteins produced with recombinant DNA technology were encapsulated into PLGA nanoparticles by double emulsion solvent evaporation technique. The nanoparticles were characterized using SEM, Zeta-sizer, and FTIR instruments to determine size, morphology, zeta potentials, and polydispersity index values, as well as to analyze functional groups chemically. Additionally, the release profiles and encapsulation efficiencies were assessed using UV–Vis spectroscopy. After loading with recombinant proteins, O-NPs reached sizes of 221.2±5.21 nm, while E-NPs reached sizes of 274.4±9.51 nm. The cumulative release rates of the antigens, monitored until the end of day 14, were determined to be 90.39% for O-NPs and 56.1% for E-NPs. Following the assessment of the in vitro cytotoxicity and immunostimulatory effects of both proteins and nanoparticles on the J774 murine macrophage cells, in vivo immunization experiments were conducted using concentrations of 16 µg/ml for each protein. Both free antigens and antigen-containing nanoparticles excessively induced humoral immunity by increasing produced Brucella-specific IgG antibody levels for 3 times in contrast to control. Furthermore, it was also demonstrated that vaccine candidates stimulated Th1-mediated cellular immunity as well since they significantly raised IFN-gamma and IL-12 cytokine levels in murine splenocytes rather than IL-4 following to immunization. Additionally, the vaccine candidates conferred higher than 90% protection from the infection according to challenge results. Our findings reveal that PLGA nanoparticles constructed with the encapsulation of recombinant Omp25 or EipB proteins possess great potential to trigger Brucella-specific humoral and cellular immune response.

Jingxuan Kang et al 2024 Nanotechnology 35 375301

The dewetting of thin Pt films on different surfaces is investigated as a means to provide the patterning for the top-down fabrication of GaN nanowire ensembles. The transformation from a thin film to an ensemble of nanoislands upon annealing proceeds in good agreement with the void growth model. With increasing annealing duration, the size and shape uniformity of the nanoislands improves. This improvement speeds up for higher annealing temperature. After an optimum annealing duration, the size uniformity deteriorates due to the coalescence of neighboring islands. By changing the Pt film thickness, the nanoisland diameter and density can be quantitatively controlled in a way predicted by a simple thermodynamic model. We demonstrate the uniformity of the nanoisland ensembles for an area larger than 1 cm 2 . GaN nanowires are fabricated by a sequence of dry and wet etching steps, and these nanowires inherit the diameters and density of the Pt nanoisland ensemble used as a mask. Our study achieves advancements in size uniformity and range of obtainable diameters compared to previous works. This simple, economical, and scalable approach to the top-down fabrication of nanowires is useful for applications requiring large and uniform nanowire ensembles with controllable dimensions.

Stanislav Musikhin et al 2024 Nanotechnology

A direct current (DC) arc discharge is a widely used method for large-scale production of metal nanoparticles, core-shell particles, and carbon nanotubes. Here, the growth of iron nanoparticles is explored in a modified DC arc discharge. Iron particles are produced by the evaporation of an anode, made from low-carbon steel. Methane admixture into argon gas serves as a carbon source. Electron microscopy and elemental analysis suggest that methane and/or products of its decomposition adhere to iron clusters forming a carbon shell, which inhibits iron particle growth until its full encapsulation, at which point the iron core growth is ceased. Experimental observations are explained using an aerosol growth model. The results demonstrate the path to manipulate metal particle size in a hydrocarbon arc environment.

Hayk Minassian et al 2024 Nanotechnology

The electromagnetic field enhancement mechanisms leading to surface-enhanced Raman scattering
(SERS) of R6G molecules near Ti3C2Tx MXene flakes of different shapes and sizes are analyzed theoretically. In COMSOL simulations for the enhancement factor (EF) of SERS, the dye molecule is modeled
as a small sphere with polarizability spectrum based on experimental data. It is demonstrated for the
first time, that in the wavelength range 500 nm − 1000 nm the enhancement of Raman signal is largely
conditioned by quadrupole surface plasmon (QSP) oscillations that induce strong polarization of MXene substrate. We show that in 
vis-NIR spectral range quadrupole SP resonances, strengthened due to
interband transitions (IBT) provide EF values of the order of 10 5 - 10 7 in agreement with experimental
data. The weak sensitivity of the EF to the shape and size of MXene nanoparticles (NPs) is interpreted
as a consequence of the low dependence of the absorption cross-section of QSP oscillations and IBT
on the geometry of the flakes. This reveals a new feature - the independence of EF on the geometry of
MXene substrates, allowing to avoid the monitoring of the shape and size of flakes during their synthe-
sis. Thus, MXene flakes can be advantageous for easy manufacturing of universal substrates for SERS
applications. The electromagnetic SERS enhancement is determined by the "lightning rod" and "hot-spot" effects due to partial overlapping of absorption spectrum of the R6G molecule with these MXene resonances.

Mohammad Razzakul Islam et al 2024 Nanotechnology 35 365401

Thermal rectifiers are essential in optimizing heat dissipation in solid-state devices to enhance energy efficiency, reliability, and overall performance. In this study, we experimentally investigate the thermal rectification phenomenon in suspended asymmetric graphene ribbons (GRs). The asymmetry within the graphene is introduced by incorporating periodic parallel nanoribbons on one side of the GR while maintaining the other side in a pristine form. Our findings reveal a substantial thermal rectification effect in these asymmetric graphene devices, reaching up to 45% at room temperature and increasing further at lower environmental temperatures. This effect is attributed to a significant thermal conductivity contrast between pristine graphene and nanoribbon graphene within the asymmetric structure. We observe that the incorporation of nanoribbons leads to a notable reduction in thermal conductivity, primarily due to phonon scattering and bottleneck effects near the nanoribbon edges. These findings suggest that graphene structures exhibiting asymmetry, facilitated by parallel nanoribbons, hold promise for effective heat management at the nanoscale level and the development of practical phononic devices.

Edward Fratto et al 2024 Nanotechnology 35 355604

The field of nanotechnology continues to grow with the ongoing discovery and characterization of novel nanomaterials with unconventional size-dependent properties; however, the ability to apply modern manufacturing strategies for practical device design of these nanoscale structures is significantly limited by their small size. Although interconnection has been previously demonstrated between nanoscale components, such approaches often require the use of expensive oxidation-resistant noble metal materials and time-consuming or untargeted strategies for welded interconnection such as laser ablation or plasmonic resonance across randomly oriented component networks. In this work, a three-segment gold–nickel–gold nanowire structure is synthesized using templated electrodeposition and modified via monolayer-directed aqueous chemical reduction of tin solder selectively on the gold segments. This core/shell nanowire structure is capable of directed magnetic assembly tip-to-tip and along substrate pads in network orientation. Upon infrared heating in a flux vapor atmosphere, the solder payload melts and establishes robust and highly conductive wire–wire joints. The targeted solder deposition strategy has been applied to various other multi-segment gold/nickel nanowire configurations and other metallic systems to demonstrate the capability of the approach. This core/shell technique of pre-loading magnetically active nanowires with solder material simplifies the associated challenges of size-dependent component orientation in the manufacture of nanoscale electronic devices.

Robin Schürmann et al 2024 Nanotechnology

Biomedical analytical applications, as well as the industrial production of high-quality nano- and submicrometre
particles, require accurate methods to quantify the absolute number concentration of
particles. In this context, small angle X-ray scattering (SAXS) is a powerful tool to determine the
particle size and concentration traceable to the Système international d'unités (SI). Therefore,
absolute measurements of the scattering cross-section must be performed, which require precise
knowledge of all experimental parameters, such as the electron density of solvent and particles,
whereas the latter is often unknown. Within the present study, novel SAXS-based approaches to
determine the size distribution, density and number concentrations of sub-micron spherical silica
particles with narrow size distributions and mean diameterss between 160 nm and 430 nm are
presented. For the first-time traceable density and number concentration measurements of silica
particles are presented and current challenges in SAXS measurements such as beam-smearing,
poorly known electron densities and moderately polydisperse samples are addressed. In addition,
and for comparison purpose, atomic force microscopy has been used for traceable measurements of
the size distribution and single particle inductively coupled plasma mass spectrometry with the
dynamic mass flow approach for the accurate quantification of the number concentrations of silica
particles. The possibilities and limitations of the current approaches are critically discussed in this
study.

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• 1990-present Nanotechnology doi: 10.1088/issn.0957-4484 Online ISSN: 1361-6528 Print ISSN: 0957-4484

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June 24, 2024

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New research uncovers hidden phenomena in ultra-clean quantum materials

by Forschungsverbund Berlin e.V. (FVB)

In a paper published today in Nature Communications , researchers unveiled previously unobserved phenomena in an ultra-clean sample of the correlated metal SrVO 3 . The study offers experimental insights that challenge the prevailing theoretical models of these unusual metals.

The international research team—from the Paul Drude Institute of Solid State Electronics (PDI), Germany; Oak Ridge National Laboratory (ORNL); Pennsylvania State University; University of Pittsburgh; the Pittsburgh Quantum Institute; and University of Minnesota—believes their findings will prompt a re-evaluation of current theories on electron correlation effects, shedding light on the origins of valuable phenomena in these systems, including magnetic properties , high-temperature superconductivity , and the unique characteristics of highly unusual transparent metals.

The perovskite oxide material SrVO 3 is classified as a Fermi liquid—a state describing a system of interacting electrons in a metal at sufficiently low temperatures.

In conventional metals, electrons that conduct electricity move independently, commonly referred to as a Fermi gas. In contrast, Fermi liquids feature significant mutual interactions between electrons, meaning the motion of one electron strongly influences the others. This collective behavior can lead to unique electronic properties with profound technological applications, providing insights into the interactions between electrons in correlated metals.

SrVO 3 serves as an ideal model system for studying electron correlation phenomena due to its crystalline and electronic simplicity. This simplicity is crucial for understanding complex phenomena such as magnetic order or superconductivity, which can complicate theoretical and experimental studies.

Another crucial factor in understanding experimental results that guide theoretical models for electron correlation effects is the presence or absence of defects in the material itself. Dr. Roman Engel-Herbert, study lead and Director of PDI in Berlin, said, "If you want to get to the bottom of one of the best-kept secrets in condensed matter physics, then you must study it in its purest form; in the absence of any extrinsic disturbance. High-quality materials that are virtually defect-free are essential. You need to synthesize ultra-clean materials."

Achieving a defect-free sample of SrVO 3 has been a seemingly insurmountable challenge until now. By employing an innovative thin film growth technique that combines the advantages of molecular beam epitaxy and chemical vapor deposition , the team achieved an unprecedented level of material purity.

Dr. Matt Brahlek, first author of the study, quantifies the improvement: "A simple measure of material purity is the ratio of how easily electricity flows at room temperature compared to low temperature, called the residual resistivity ratio, RRR value. If the metal contains many defects, RRR values are low, typically around 2–5.

"We have been able to synthesize SrVO 3 films with RRR nearly 100 times larger, 200, opening the door to study the true properties of the correlated metal SrVO 3 . In particular, the high material quality allowed accessing special regime at high magnetic fields for the first time, where surprises were found."

The interdisciplinary team of scientists was surprised to discover a series of peculiar transport phenomena that were in sharp contrast to the transport properties measured previously on highly defective samples. Their findings challenge the long-standing scientific consensus regarding SrVO 3 as a simple Fermi liquid.

Engel-Herbert explains, "This situation was very exciting but also puzzling. While we reproduced previously reported transport behavior of SrVO 3 in our highly defective samples, identical measurements in ultraclean samples with high RRR values differed."

Results from defective samples allowed a straight-forward interpretation of the results that matched theoretical expectation. These results were used as experimental evidence that the theoretical understanding correctly captured the electron correlation effects in SrVO 3 . However, the team found that measurements on the ultraclean samples could not be explained so easily.

Brahlek added, "An observation that stands out is the expectation that the number of electrons that carry electricity in a metal is independent of temperature and magnetic field. This is of course true, but the interpretation of the measured quantity is not a direct measure of the carrier concentration.

"Rather, this quantity is mixed up with other aspects of the material properties, such as how defects and temperature impact the flow of electricity. We had to delve deeper into the physics to understand what we saw. That is what makes it so important and exciting."

The researchers believe their discovery can serve as a basis to refine theoretical models and prompt a re-examination of established views and interpretations of materials exhibiting a sizeable electron correlation.

Engel-Herbert says, "Our job as experimental physicists is to push beyond the boundaries of the current understanding of nature. This is where discoveries can be made, where we advance science. As condensed matter physicists, it is key to keep perfecting our object of study by challenging ourselves to push the limits of perfecting materials.

"This can potentially give new insights into the true behavior of this class of materials and enables a comprehensive explanation of the phenomena measured and observed. It takes an interdisciplinary team of experts to do this.

"While the job is not yet completed, our results are an opportunity for the community to recalibrate their theories; re-examining materials we believed were well-understood and re-evaluate their potential for applications."

Journal information: Nature Communications

Provided by Forschungsverbund Berlin e.V. (FVB)

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Hot technology and technical evolution of polypeptide nanotechnology in medical application field based on patent data analysis

• Published: 27 June 2024
• Volume 26 , article number  142 , ( 2024 )

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• Kai Zhao 1 ,
• Tong Wu 1 ,
• Donglin Wei 1 &
• Hongmei Yuan 1  

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The design of nanostructures based on peptides has attracted wide attention, especially the design of new nanomaterials with higher levels of multifunctional ability is gradually needed. Patent layout allows to identification of related technologies and trends. To reveal the development of global polypeptide nanotechnology in the field of medical application, this paper uses the text mining technology based on patent semantic content to extract the contained knowledge from the patent data set from 1978 to 2023 retrieved from incoPat database and combines the knowledge network with the theme evolution. The hot topics were obtained, and the main technical topics of improving the function of nanomaterials modified by polypeptide were analyzed: the nanointelligent delivery system modified by polypeptide improved the response to stimuli, the transfection rate of gene therapy was improved, the targeting and cell penetration of tumor therapy were improved, the diagnostic sensitivity and biocompatibility were improved, and the detection time of sensors was improved. The research shows that most nanotechnology based on polypeptide is used in medicine to optimize the effect of chemotherapy for tumor treatment. The development of gene therapy is developing rapidly, and technologies such as diagnosis and sensors are emerging, which seems to be very promising. They may hide great potential and represent the field of opportunity research. Most importantly, the technologies related to polypeptide-modified nanostructures are still rapidly developing, and this trend is expected to continue in the next few years.

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This study was supported by the Shanghai Center for Drug Evaluation and Inspection under the project “Control Strategy and Regulatory Consideration of Pharmaceutical and Pharmaceutical Combination Products Based on Patent Technology Trajectory” (No. 2222430097).

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Zhao, K., Wu, T., Wei, D. et al. Hot technology and technical evolution of polypeptide nanotechnology in medical application field based on patent data analysis. J Nanopart Res 26 , 142 (2024). https://doi.org/10.1007/s11051-024-06055-7

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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.

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