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Pulmonary protein and DNA delivery
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between the spin of an electron and an electric field. ‘‘We use the Rashba effect to produce a magnetic anisotropy [in an ultra-thin ferromagnetic layer], which leads to our control of magnetism,’’ says Barnes. ‘‘We produce the electric field, in part, by an appropriate choice of the magnetic and non-magnetic elements in our bi-layer and by generating an electric field with a capacitor.’’ The team – Barnes from the University of Miami Coral Gables Florida and colleagues
Materials Today Volume 17, Number 4 May 2014
Jun’ichi Ieda and Sadamichi Maekawa all based at the Advanced Science Research Center, of the Japan Atomic Energy Agency, in Tokai, Ibaraki – explains that thin magnetic films with a controllable perpendicular magnetic anisotropy (PMA) have important applications, not only for MRAM and logic units, but also for electromechanical devices, such as actuators. The researchers’ theoretical work on the phenomena for ferromagnetic/metal and ferromagnetic/oxide insulator interfaces will
now be followed up with experiments to verify the basic principles of the current study. ‘‘The Japanese are working on first principle calculations of the materials,’’ Barnes told Materials Today. ‘‘More important is that there is interest to test the ideas experimentally. We have some suggestions for bi-layer combinations which work more efficiently than existing systems.’’ David Bradley
Trapping and moving 3D objects on the nanoscale Researchers from ICFO – The Institute of Photonic Sciences in Spain have developed a new non-invasive approach to the manipulation of individual nano-objects in three dimensions. The team, led by Romain Quidant, showed for the first time the ability to utilize near-field optical tweezers to trap and manipulate single 50 nm dielectric objects in 3D, which could lead to new techniques for controlling such objects, including heat-sensitive biospecimens. Optical tweezers and using light to manipulate small objects, which was invented in Bell Labs as long ago as the 1980s, has had a fundamental effect on both biological systems and quantum optics. However, the technology has been limited by an inability to directly trap objects smaller than a few hundred nanometers. This has led to an increase in research into nano-tweezers based on plasmonics that could trap nanoscale objects, including proteins and nanoparticles, without overheating and damaging the sample. This new study, published in Nature Nanotechnology [Berthelot, et al., Nat. Nanotechnol. (2014), doi:10.1038/nnano.2014.24], demonstrated the trapping and 3D displacement of specimens as small as tens of nanometers with non-invasive laser intensity. The team had previously found that, by
focusing light on a very small gold nanostructure lying on a glass surface that acted as a nano-lens, it was possible to trap a
specimen near the metal where the light is concentrated. Although this proof of concept demonstrated the mechanism, it did not allow any 3D manipulation necessary for practical applications. The new research went further by implementing the concept of plasmonic nano-tweezers at the extremity of a tapered mobile optical fiber, nano-engineered with a bowtie-like gold aperture. Crucial to the approach was that trapping and monitoring the trapped specimen could be achieved through the optical fiber, thereby manipulating nano-objects in a simple and manageable way outside the lab. The nano-tweezers were completely autonomous and free of bulky optical elements, with the trapping allowing the specimen to be moved over tens of micrometers for several minutes. The innovative approach could lead to a wide range of new research directions that rely on non-invasive manipulation of objects at the single molecule/virus level. This could especially be the case in medicine, where it could provide a better understanding of the biological mechanisms underlying how diseases develop, but could also find value in a range of different fields. The next stage for the team is to apply their nano tool to some practical problems. Laurie Donaldson
research published in Acta Biomaterialia this month [Menon, et al., Acta Biomater. (2014), doi:10.1016/j.actbio.2014.01.033]. Kytai Nguyen of The University of Texas at Arlington, Arlington and the Southwestern
Medical Center at Dallas and colleagues point out that there have been no studies investigating the details of such nanoparticles for the delivery of protein or nucleic acids to the lung. They have now studied
Optical nano-tweezers are able to control 3D objects.
Pulmonary protein and DNA delivery Polymeric nanoparticles that are easily modified and can carry therapeutic and diagnostic agents deep into the lung can also be made biocompatible and have localized action with few side effects, according to
158
Materials Today Volume 17, Number 4 May 2014
six polymeric NPs: gelatin, chitosan, alginate, poly(lactic-co-glycolic) acid (PLGA), PLGA–chitosan and PLGA–poly(ethylene glycol) (PEG), as carriers for protein or DNA that can be delivered to the patient by inhalation. The researchers tested particle uptake by human alveolar type-1 epithelial cells in vitro as well as inhalation of a nanoparticles bearing DNA encoding for yellow fluorescent-tagged and nanoparticles encapsulating rhodamine-conjugated erythropoietin in laboratory rats. They demonstrated that PLGA-based and natural polymer nanoparticles made from gelatin, for instance, were the most biocompatible with the live cells and gave the best dose-dependent in vitro uptake. They also showed that a single inhalation of the nanoparticles was able to induce widespread distribution of the erythropoietin in the rat lung, which persisted for up to
NEWS
ten days. Similarly, they could see yellow fluorescent protein being expressed continuously by the encapsulated DNA in the rat lung for up to a week. Given that conventional methods of delivering biological agents to the lung are limited by toxicity, low bioavailability and instability issues, the team’s findings suggest that nanotechnology might represent the way forward in this area of research. Moreover, inhalation is a noninvasive delivery route, avoids the issues of oral agents having to pass through the harsh and denaturing environment of the alimentary tract. The size of the optimal nanoparticles – 160 and 187 nanometers for PLGA and gelatin, respectively) are amenable to nebulization while being too small to trigger an attack from white blood cells, phagocytes, in the alveolar pockets of the lung.
The researchers point out that their work highlights an important point in that the results differ between in vitro and in vivo experiments. Although greater cellular uptake of natural polymer-based nanoparticles was observed in vitro, the in vivo tissue distribution profiles following nebulization were relatively similar for both PLGA and gelatin particles. It will, therefore, be necessary for future research not to make assumptions about the properties of a given nanoparticle based solely on in vitro tests. ‘‘Our future work will determine the optimal therapeutic dose and frequency of administration as well as the local and systemic effects of specific encapsulated therapeutic reagents following nanoparticle delivery to facilitate lung regeneration,’’ Nguyen told Materials Today. David Bradley
Turning graphene into a superconductor With superconductors and low-dimensional materials being material classes under intense study, the combination of the two is bound to cause a stir. Now, a study by a team from the University of Vienna, along with international collaborators, has uncovered the potential superconducting coupling mechanism in the muchtouted wonder material, graphene. It is only comparatively recently that reports of superconductivity in graphene have appeared, although its close relatives – such as graphite and fullerenes – can be made superconducting through doping. However, this work, reported in Nature Communications [Fedorov, et al., Nat. Commun. (2014), doi:10.1038/ncomms4257], demonstrated the superconducting pairing mechanism in calcium-doped graphene based on the angle-resolved photoemission spectroscopy (ARPES) technique. In the ARPES method, when a light particle interacts with a material, it can transfer all its energy to an electron inside that material. If the energy of the light is large enough, the electron acquires sufficient energy to escape from the material. The technique helped identify the angle under
Image showing the kink feature of the ARPES data used to extract the electron–photon coupling constant and predict the superconducting transition temperature.
which the electrons escape from the material, allowing useful information to be gleaned about its electronic properties and interactions. In this case, ARPES was used to identify an electron donor for monolayer graphene capable of inducing strong electron–phonon coupling and superconductivity, investigating the common electron dopant atoms. It was found that calcium was the most promising candidate for realizing
superconductivity in graphene with a critical temperature of about 1.5K. On examining the strength of the kink in the spectral function in the two crystallographic main directions to estimate the superconducting critical temperature, they found an unexpected low-energy peak for all dopants with an energy and intensity dependent on the dopant atom, demonstrating this peak resulted from dopantrelated vibration. As researcher Alexander ¨ neis points out, the work does ‘‘yield a Gru quantity called the spectral function that is related to the electron energy band structure of a material and the many-body effects. The spectral function allows us to probe the coupling mechanism that in turn allows us to predict superconductivity.’’ As the properties of graphene are so easily altered, the study could improve our understanding of superconducting coupling mechanisms, especially that of carbon materials. The team now intend to further explore the stacking of graphene layers to research the transition between 2D and 3D superconductivity, as well as looking at how many layers are needed to achieve superconductivity. Laurie Donaldson
159
between the spin of an electron and an electric field. ‘‘We use the Rashba effect to produce a magnetic anisotropy [in an ultra-thin ferromagnetic layer], which leads to our control of magnetism,’’ says Barnes. ‘‘We produce the electric field, in part, by an appropriate choice of the magnetic and non-magnetic elements in our bi-layer and by generating an electric field with a capacitor.’’ The team – Barnes from the University of Miami Coral Gables Florida and colleagues
Materials Today Volume 17, Number 4 May 2014
Jun’ichi Ieda and Sadamichi Maekawa all based at the Advanced Science Research Center, of the Japan Atomic Energy Agency, in Tokai, Ibaraki – explains that thin magnetic films with a controllable perpendicular magnetic anisotropy (PMA) have important applications, not only for MRAM and logic units, but also for electromechanical devices, such as actuators. The researchers’ theoretical work on the phenomena for ferromagnetic/metal and ferromagnetic/oxide insulator interfaces will
now be followed up with experiments to verify the basic principles of the current study. ‘‘The Japanese are working on first principle calculations of the materials,’’ Barnes told Materials Today. ‘‘More important is that there is interest to test the ideas experimentally. We have some suggestions for bi-layer combinations which work more efficiently than existing systems.’’ David Bradley
Trapping and moving 3D objects on the nanoscale Researchers from ICFO – The Institute of Photonic Sciences in Spain have developed a new non-invasive approach to the manipulation of individual nano-objects in three dimensions. The team, led by Romain Quidant, showed for the first time the ability to utilize near-field optical tweezers to trap and manipulate single 50 nm dielectric objects in 3D, which could lead to new techniques for controlling such objects, including heat-sensitive biospecimens. Optical tweezers and using light to manipulate small objects, which was invented in Bell Labs as long ago as the 1980s, has had a fundamental effect on both biological systems and quantum optics. However, the technology has been limited by an inability to directly trap objects smaller than a few hundred nanometers. This has led to an increase in research into nano-tweezers based on plasmonics that could trap nanoscale objects, including proteins and nanoparticles, without overheating and damaging the sample. This new study, published in Nature Nanotechnology [Berthelot, et al., Nat. Nanotechnol. (2014), doi:10.1038/nnano.2014.24], demonstrated the trapping and 3D displacement of specimens as small as tens of nanometers with non-invasive laser intensity. The team had previously found that, by
focusing light on a very small gold nanostructure lying on a glass surface that acted as a nano-lens, it was possible to trap a
specimen near the metal where the light is concentrated. Although this proof of concept demonstrated the mechanism, it did not allow any 3D manipulation necessary for practical applications. The new research went further by implementing the concept of plasmonic nano-tweezers at the extremity of a tapered mobile optical fiber, nano-engineered with a bowtie-like gold aperture. Crucial to the approach was that trapping and monitoring the trapped specimen could be achieved through the optical fiber, thereby manipulating nano-objects in a simple and manageable way outside the lab. The nano-tweezers were completely autonomous and free of bulky optical elements, with the trapping allowing the specimen to be moved over tens of micrometers for several minutes. The innovative approach could lead to a wide range of new research directions that rely on non-invasive manipulation of objects at the single molecule/virus level. This could especially be the case in medicine, where it could provide a better understanding of the biological mechanisms underlying how diseases develop, but could also find value in a range of different fields. The next stage for the team is to apply their nano tool to some practical problems. Laurie Donaldson
research published in Acta Biomaterialia this month [Menon, et al., Acta Biomater. (2014), doi:10.1016/j.actbio.2014.01.033]. Kytai Nguyen of The University of Texas at Arlington, Arlington and the Southwestern
Medical Center at Dallas and colleagues point out that there have been no studies investigating the details of such nanoparticles for the delivery of protein or nucleic acids to the lung. They have now studied
Optical nano-tweezers are able to control 3D objects.
Pulmonary protein and DNA delivery Polymeric nanoparticles that are easily modified and can carry therapeutic and diagnostic agents deep into the lung can also be made biocompatible and have localized action with few side effects, according to
158
Materials Today Volume 17, Number 4 May 2014
six polymeric NPs: gelatin, chitosan, alginate, poly(lactic-co-glycolic) acid (PLGA), PLGA–chitosan and PLGA–poly(ethylene glycol) (PEG), as carriers for protein or DNA that can be delivered to the patient by inhalation. The researchers tested particle uptake by human alveolar type-1 epithelial cells in vitro as well as inhalation of a nanoparticles bearing DNA encoding for yellow fluorescent-tagged and nanoparticles encapsulating rhodamine-conjugated erythropoietin in laboratory rats. They demonstrated that PLGA-based and natural polymer nanoparticles made from gelatin, for instance, were the most biocompatible with the live cells and gave the best dose-dependent in vitro uptake. They also showed that a single inhalation of the nanoparticles was able to induce widespread distribution of the erythropoietin in the rat lung, which persisted for up to
NEWS
ten days. Similarly, they could see yellow fluorescent protein being expressed continuously by the encapsulated DNA in the rat lung for up to a week. Given that conventional methods of delivering biological agents to the lung are limited by toxicity, low bioavailability and instability issues, the team’s findings suggest that nanotechnology might represent the way forward in this area of research. Moreover, inhalation is a noninvasive delivery route, avoids the issues of oral agents having to pass through the harsh and denaturing environment of the alimentary tract. The size of the optimal nanoparticles – 160 and 187 nanometers for PLGA and gelatin, respectively) are amenable to nebulization while being too small to trigger an attack from white blood cells, phagocytes, in the alveolar pockets of the lung.
The researchers point out that their work highlights an important point in that the results differ between in vitro and in vivo experiments. Although greater cellular uptake of natural polymer-based nanoparticles was observed in vitro, the in vivo tissue distribution profiles following nebulization were relatively similar for both PLGA and gelatin particles. It will, therefore, be necessary for future research not to make assumptions about the properties of a given nanoparticle based solely on in vitro tests. ‘‘Our future work will determine the optimal therapeutic dose and frequency of administration as well as the local and systemic effects of specific encapsulated therapeutic reagents following nanoparticle delivery to facilitate lung regeneration,’’ Nguyen told Materials Today. David Bradley
Turning graphene into a superconductor With superconductors and low-dimensional materials being material classes under intense study, the combination of the two is bound to cause a stir. Now, a study by a team from the University of Vienna, along with international collaborators, has uncovered the potential superconducting coupling mechanism in the muchtouted wonder material, graphene. It is only comparatively recently that reports of superconductivity in graphene have appeared, although its close relatives – such as graphite and fullerenes – can be made superconducting through doping. However, this work, reported in Nature Communications [Fedorov, et al., Nat. Commun. (2014), doi:10.1038/ncomms4257], demonstrated the superconducting pairing mechanism in calcium-doped graphene based on the angle-resolved photoemission spectroscopy (ARPES) technique. In the ARPES method, when a light particle interacts with a material, it can transfer all its energy to an electron inside that material. If the energy of the light is large enough, the electron acquires sufficient energy to escape from the material. The technique helped identify the angle under
Image showing the kink feature of the ARPES data used to extract the electron–photon coupling constant and predict the superconducting transition temperature.
which the electrons escape from the material, allowing useful information to be gleaned about its electronic properties and interactions. In this case, ARPES was used to identify an electron donor for monolayer graphene capable of inducing strong electron–phonon coupling and superconductivity, investigating the common electron dopant atoms. It was found that calcium was the most promising candidate for realizing
superconductivity in graphene with a critical temperature of about 1.5K. On examining the strength of the kink in the spectral function in the two crystallographic main directions to estimate the superconducting critical temperature, they found an unexpected low-energy peak for all dopants with an energy and intensity dependent on the dopant atom, demonstrating this peak resulted from dopantrelated vibration. As researcher Alexander ¨ neis points out, the work does ‘‘yield a Gru quantity called the spectral function that is related to the electron energy band structure of a material and the many-body effects. The spectral function allows us to probe the coupling mechanism that in turn allows us to predict superconductivity.’’ As the properties of graphene are so easily altered, the study could improve our understanding of superconducting coupling mechanisms, especially that of carbon materials. The team now intend to further explore the stacking of graphene layers to research the transition between 2D and 3D superconductivity, as well as looking at how many layers are needed to achieve superconductivity. Laurie Donaldson
159