Latest Articles Include:
- The story so far
- Nat Nanotechnol 6(10):603 (2011)
Nature Nanotechnology | Editorial The story so far Journal name:Nature NanotechnologyVolume: 6,Page:603Year published:(2011)DOI:doi:10.1038/nnano.2011.181Published online07 October 2011 Basic research in nanoscience and technology is flourishing, but obstacles to real-world applications remain. Subject terms: * Education and research Article tools * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Five years ago, the editorial in the first issue of Nature Nanotechnology started as follows: "Depending on who you ask, nanotechnology started in 1981, 1974, 1959 or the Bronze Age." That is still true. "And depending on who you believe, and the definitions they use," the article went on, "the world market for nanotechnology products will be worth $2,600 billion in 2014, or $1,000 billion in 2015." This remains to be seen, although there are definitely fewer outlandish predictions about the commercial impact of nanotechnology today than there were back in 2006. The editorial continued by pondering some familiar themes that we will return to below — such as the definition of nanotechnology and the need to know more about impact of nanomaterials on the environment and health — and went on to coin a new word to describe the large amount of funding that was flowing into nanoscale science and technology. This author hoped that this word would enter common usage, ! but half a decade later a Google search returns a meagre three hits for the term 'nanolargesse'. To mark the first five years of Nature Nanotechnology we have prepared a series of web pages that bring together all the papers we have published in four particularly active areas — DNA nanotechnology, graphene, nanopores and nanotoxicology — along with a collection of articles on the public perceptions of nanotechnology1. We could have chosen other areas, but these four seemed to offer the best combination of overall activity and number of relevant papers published in Nature Nanotechnology, and the articles on public perception help place nanotechnology in a wider context. Research into DNA nanotechnology has branched out in recent years, and in addition to a proliferation of DNA-based nanostructures and devices, this famous molecule is also increasingly being used to organize other nanomaterials (such as nanoparticles and quantum dots). RNA nanotechnology2 is also emerging as a growing area. The paper that kick-started the rise of graphene was published in 2004 (ref. 3), but the number of papers grew only slowly at first, and in its early years Nature Nanotechnology received many more manuscripts on carbon nanotubes than its two-dimensional cousin. Indeed authors submitted more than 100 papers about nanotubes in 2006, compared with just three on graphene, and nanotubes featured in four of the seven papers published in the first issue. Following the initial gold rush of novel physics, chemists became interested in the production of graphene, and the list of this material's remarkable properties grew longer and longer. However, there remains much to do: the lack of an intrinsic band gap, for example, is still a major disadvantage for applications in electronics4. The ultimate goal of research into nanopore-based sensors is to be able to sequence the human genome for under $1,000. The main advantage of the nanopore approach to sequencing is that it does not require labels or amplification, and workers in the field are developing sensors based on naturally occurring biological nanopores, solid-state nanopores and hybrids of the two. However, each has its own strengths and weaknesses (for example, at present the DNA molecules pass through solid-state nanopores too fast to be sequenced), and nanopore sensors in general face competition from a range of other technologies5. Of course, nanotechnology products will only be able to enter the market if we know for sure that they do not present a threat to health or the environment, and there has been a series of reports over the past five years bemoaning lack of progress in this area. Addressing this problem requires a combination of research in nanotoxicology (including computational approaches)6 and changes to the regulations governing the use of chemicals and materials7. Despite what many researchers think, nanotechnology does not get a bad press. Moreover, the public does not fear nanotechnology — indeed the majority know little or nothing about it, and the responses of those who are aware of it depend on a wide range of factors, with some applications being viewed more favourably than others. "The number of nanotechnology papers has grown from about 8,000 in 1991 to about 87,000 in 2009." Another noticeable trend over the past five years has been the increase in the number of nanotechnology papers (and journals) published. A recent analysis found that the number of nanotechnology papers has grown from about 8,000 in 1991 to about 87,000 in 2009 (ref. 8). Researchers based in China were the most prolific authors, followed by those in the United States, which is not surprising. However, when countries are ranked according to nanotechnology papers as a percentage of all papers, Singapore emerges at the top of the list (16.41%), followed by China (15.32%) and South Korea (13.30%). Nanotechnology accounts for a noticeably smaller percentage of research activity in Japan (8.45%), the European Union (5.24%) and the United States (4.7%). The complexity of the search query used in this analysis also highlights the difficulties inherent in trying to define nanotechnology. So what has become of the research published in the first issue of Nature Nanotechnology, and the authors of those papers? One now works for Intel, two have made the jump from graduate student to assistant professor, and the rest are all working as postdoctoral researchers (page 607). Of the senior authors, some still have students and postdocs building on the results they published back in 2006, whereas others have moved into new fields, notably energy-related research and the interface between nanoscience and biology. Based on this (admittedly small) sample, it is also clear that the bulk of progress over the past five years has been in understanding the basic science, rather than developing new technology for real-world applications. Will the same still be true five years from now? References * http://www.nature.com/nnano/focus/highlights/index.html * Guo, P.Nature Nanotech.5, 833–842 (2010). * ChemPort * ISI * Article * Novoselov, K.et al. Science306, 666–669 (2004). * ChemPort * ISI * PubMed * Article * Schwierz, F.Nature Nanotech.5, 487–496 (2010). * ChemPort * ISI * Article * Venkatesan, B. M. & Bashir, R.Nature Nanotech.6, 615–624 (2011). * Article * Nature Nanotech.6, 329 (2011). * Article * Maynard, A.Nature475, 31 (2011). * ChemPort * PubMed * Article * Grieneisen, M. & Zhang, M.Smallhttp://dx.doi.org/10.1002/smll.201100387 (2011). Download references Additional data - Democratizing nanotech, then and now
- Nat Nanotechnol 6(10):605-606 (2011)
Nature Nanotechnology | Thesis Democratizing nanotech, then and now * Chris Toumey1Journal name:Nature NanotechnologyVolume: 6,Pages:605–606Year published:(2011)DOI:doi:10.1038/nnano.2011.168Published online07 October 2011 What progress has been made in efforts to engage the public in decisions about nanotechnology over the past five years? asks various experts in the field. Subject terms: * Ethical, legal and other societal issues Article tools * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg In October 2006, in the first issue of this journal, I described the idea of 'democratizing science' — a state of affairs in which non-experts have active and constructive roles in science policy decisions1. At that time, there were expectations that nanotechnology would be a laboratory for experimenting with the idea of democratizing science. From this came an impressive battery of focus groups, citizen juries, consensus conferences, large-scale surveys and other instruments, both in the US and the UK. If democratizing science is going to happen, and especially if it is going to become standard practice in the formulation of science policy, then it needs to navigate a course between two undesirable options. First, we do not want science policy determined by political values that disregard scientific knowledge. In the dreadful case of Lysenkoism, for example, Soviet agricultural policy was based on crazy biological theories modelled on Stalinist ideology, with disastrous results for food production. Second, we want to avoid forcing science policy on a population that resents it, even if the policy is grounded in good scientific knowledge. Some places in the US and elsewhere have laws that require childhood vaccines for the human papilloma virus (HPV) on the grounds that this reduces the likelihood of getting cervical cancer or genital warts. However, in many cases parents can exempt their daughters from the vaccine if it conflicts with the family's religious values. This wa! y, a democratic society makes science policy through democratic processes, but its conscience-based exemptions enable families to disagree with that policy. This is an eye of a needle that is difficult to thread: avoid decisions based on pseudoscience, but also avoid decisions that come from undemocratic processes2. Where are we now, five years later? First observation * First observation * Second observation * Third observation * Fourth observation * Conclusions * References * Author information It has been easier to praise the idea of democratizing science than to achieve it. One of the more robust projects for creating conditions of democratizing science, with a focus on nanotechnology, has been the work on 'anticipatory governance' at the Center for Nanotechnology and Society (CNS) at Arizona State University. David Guston, director of the CNS, defines anticipatory governance as "a broad-based capacity extended throughout society that can act on a variety of inputs to manage emerging knowledge-based technologies while such management is possible". The anticipatory governance project at the CNS is a work in progress. It has evolved from an earlier Arizona State University paradigm known as 'real-time technology assessment'3, and it recognizes the need to experiment with numerous kinds of interactions between non-experts and the scientific community to get the conditions right for democratizing science. Moreover, Guston told me during my research for this article that he and his co-workers are aware that any one experiment in anticipatory governance is subject to multiple independent variables. In addition to the scientific and technical differences between nanotechnology and, say, biotechnology or information technology, the public that engages with nanotechnology can also be different from the public that engages with other areas of science and technology, and the economic or political conditions in which nanotechnology exists can also be different from those in which other sciences or technologies exist. There is no ! easy model for democratizing science. Dietram Scheufele (University of Wisconsin–Madison) argues that the development of reliable methods for learning and deliberation will not, on their own, be enough to democratize nanotechnology. There are also social factors to consider. Science museums, for example, aspire to make science accessible to non-experts, especially in the case of the museums in the US Nanoscale Informal Science Education (NISE) Network, and they hope to enable non-experts to participate in deliberations about science, but they only reach those people who attend science museums in the first place. Moreover, nanotechnology also suffers from the problem that only a small minority of the public is aware of it, even though it has the potential to affect many aspects of our lives. According to Scheufele's argument, this combination of great potential and low awareness makes it very difficult to democratize nanotechnology4. Second observation * First observation * Second observation * Third observation * Fourth observation * Conclusions * References * Author information The UK equivalent of democratizing science is usually called 'upstream public engagement' (or just public engagement). This line of argument has been carefully developed over the past 25 years. Its point of departure is a report that was published by the Royal Society in 1985 titled Public Understanding of Science. This report suggested a simplistic plan in which scientists will talk, non-scientists will listen, and then all will know the value of science. Reactions against the Royal Society report instigated a golden age of theories, critiques and experiments in public engagement. At a conference on Science and the Public at Kingston upon Thames in July 2011, Simon Lock (University College London) said that although policymakers often talk the language of public engagement, policy is still routinely decided without any real public engagement. This makes a mockery of the idea that a democratic society should use democratic processes. At the same conference, Oliver Escobar (University of Edinburgh) provided a concrete example of the difficulties involved in public engagement. Museum staff and academics in Scotland used a number of sophisticated techniques to capture the views of non-experts about various scientific issues, but when they presented their findings to the Scottish Parliament, they were perceived as lobbyists for a special interest group, and their findings were disregarded accordingly. Third observation * First observation * Second observation * Third observation * Fourth observation * Conclusions * References * Author information Nick Pidgeon (Cardiff University) has monitored UK exercises in public engagement, including those related to nanotechnology, ever since he contributed to an influential report on nanotechnology published by the Royal Society and the Royal Academy of Engineering in 2004. He says that the ethos of public engagement has been declining subtly in recent years for two reasons. First, nanotechnology is not as compelling to the public as some other sciences and technologies. Second, the procedures and structures of upstream public deliberation projects are still problematic, even at this late date. If one frames the nanotechnology issues too rigidly in a public engagement exercise by, for example, limiting the possibilities to be deliberated, then this can discourage the contributions of the non-expert participants. But if the discussions of nanotechnology are too open-ended, then public engagement exercises run the risk of being unduly influenced by general ill-defined views about! science and technology, as though nanotechnology has no content of its own. Pidgeon and Scheufele have come to similar conclusions about the UK and US, respectively. Indeed, Pidgeon was one of the co-authors of a paper in this journal5 that compared public perceptions of the risks associated with applications of nanotechnology in two sectors (energy and health) in the UK and US. The similarities between the two countries begin with technical matters, but also touch on broader societal considerations. Nanotechnology is inherently more complex than earlier new technologies, such as information technology, and specific applications of nanotechnology evoke different reactions. Nanotechnology for solving energy problems looks great to most people, whereas the use of nanomaterials in health and medicine generates a sense of unease that advances in this technology will erode our abilities to control our own lives5. Fourth observation * First observation * Second observation * Third observation * Fourth observation * Conclusions * References * Author information Even as we count the imperfections of public engagement with nanotechnology, the world does not stop turning, and there are other areas of science and technology that deserve public engagement. Some people ask what has succeeded with nanotechnology and whether it can be adapted to these other topics. Pidgeon and his Cardiff colleague Adam Corner give the example of large-scale geoengineering to mitigate global climate change. On the horizon are both global proposals (such as placing reflective particles into the stratosphere to deflect solar radiation) and local tools (such as direct carbon sequestration from the air). Each proposal entails difficult social, economic and political choices, and would therefore benefit from reliable procedures for public engagement. This is why policymakers are asking if the lessons learned by public engagement researchers working on nanotechnology can help those working on geoengineering6. "Public engagement with nanotechnology is not nearly as developed as we once expected it to be by the year 2011." Corner and Pidgeon are clear that although public engagement with nanotechnology remains methodologically problematic, global climate change is too immediate to wait until public engagement methods are perfect. Some of the engagement methods developed for nanotechnology should be applied in geoengineering without delay. Like a good French bricoleur, sometimes we have to adapt as we go along because we cannot wait for someone else to deliver an ideal solution. This is interesting: public engagement with nanotechnology is not nearly as developed as we once expected it to be by the year 2011 but, nevertheless, it is distinctly better than sitting on our hands and waiting for perfection to fall into our laps. Conclusions * First observation * Second observation * Third observation * Fourth observation * Conclusions * References * Author information First, it is good for democratic societies to have democratic processes for making decisions about science policy, especially when the citizens of democratic societies recognize the ways that science affects us socially, economically and bodily. Second, it can be extraordinarily difficult to engage citizens in science policy outside of the traditional methods of electing politicians to represent us. But, third, there are numerous ways that non-experts can claim active and constructive roles in science policy decisions. Sometimes these ways are theorized and abetted by academics who care about democratizing science, and other times they arise with no help from them. If a toxic waste repository is going to be built near your home, you will probably protest about it without waiting for philosophers and sociologists to satisfy themselves that various methods of public engagement are everything that they want them to be. Even though public engagement with nanotechnology is less than what we hoped it would be by now, and even though nanotechnology is an extremely difficult test case for democratizing science, it is still one of the best laboratories we have for creating ways for non-experts to have active and constructive roles in science policy decision processes. References * First observation * Second observation * Third observation * Fourth observation * Conclusions * References * Author information * Toumey, C.Nature Nanotech.1, 6–7 (2006). * ChemPort * Article * Toumey, C.Quaderni61, 81–101 (2006). * Article * Guston, D. & Sarewitz, D.Technol. Soc.24, 93–109 (2002). * Article * Corley, E. & Scheufele, D.Scientist24, 22 (2010). * ISI * Pidgeon, N.et al. Nature Nanotech.4, 95–98 (2009). * ChemPort * ISI * Article * Corner, A. & Pidgeon, N.Environment52, 24–37 (2010). * ISI * Article Download references Author information * First observation * Second observation * Third observation * Fourth observation * Conclusions * References * Author information Affiliations * Chris Toumey is at the University of South Carolina NanoCenter Corresponding author Correspondence to: * Chris Toumey Author Details * Chris Toumey Contact Chris Toumey Search for this author in: * NPG journals * PubMed * Google Scholar Additional data - Back to the future
- Nat Nanotechnol 6(10):607-608 (2011)
Nature Nanotechnology | Feature Back to the future * Peter RodgersJournal name:Nature NanotechnologyVolume: 6,Pages:607–608Year published:(2011)DOI:doi:10.1038/nnano.2011.179Published online07 October 2011 The first issue of Nature Nanotechnology, published five years ago, contained seven research papers. We catch up with the authors of those papers and ask how nanotechnology has changed since then. Subject terms: * Education and research Introduction * Introduction * What next * Nanotubes and beyond * When nano meets bio * References Article tools * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg © MISA / MISAPHOTO.COM Peidong Yang of Berkeley (left) and Yang Yang of UCLA (right) are two of a growing number of nanoscientists working on energy-related research. The scanning electron micrograph from Yang's lab at Berkeley shows three solar cells in series on a single nanowire8. Tzahi Cohen-Karni was an MSc student at the Weizmann Institute of Science in Israel when he did the work that resulted in him being the first author on the first paper published in Nature Nanotechnology. Working with Ernesto Joselevich and three other colleagues, he studied how the electronic conductance of a carbon nanotube changed as it was twisted. Five years later he has received a PhD from Harvard for work on nanobioelectronics1 and has just started as a postdoctoral associate in bioengineering at Massachusetts Institute of Technology (MIT). Cohen-Karni was one of seven first authors in that first issue of Nature Nanotechnology, and his story is fairly typical. All seven are still active in science and engineering, with six of them currently based in a university or academic environment: the exception is Ricky Tseng, who has moved from the University of California, Los Angeles (UCLA) — where he worked on novel forms of electronic memory — to become an engineer at Intel. And six of the seven are now based in the United States, compared with four back in 2006. The seven last authors, on the other hand, are all still based in the same institutions as five years ago, although their research interests have evolved since then, and continue to do so. What next * Introduction * What next * Nanotubes and beyond * When nano meets bio * References "Energy, energy, energy," replies Yang Yang, Tseng's PhD supervisor at UCLA, when I ask him what he would like to be working on in five years. "I would like to solve the energy problem, from generation to storage to improved efficiency. There are so many things that need to be done, and there is so little time left." Peidong Yang of Berkeley, last author of a paper on silicon nanowires, is also increasingly interested in applying nanotechnology to energy problems. "I will devote most of my efforts towards artificial photosynthesis," he says, "and the high surface areas available with semiconductor nanowires will play a significant role in this work." The biggest challenge in this area, says Yang, is controlling the transfer of energy and electric charge across interfaces within complex nanostructures. ""Manufacture is the biggest challenge — it is hard to do in a systematic manner."" Yang Yang Another theme to emerge in e-mail interviews with the authors is the need to address the problem of manufacturability. "There seems to be a big gap between research into nanoscale science and technology, and its application in industry," says Tseng, who stresses the need to consider if any proposed device can be produced in high volumes and at low cost. Yang Yang agrees: "Manufacture is the biggest challenge — it is hard to do in a systematic manner." However, Joselevich stresses that a detailed understanding of nanoscale structures and phenomena is needed to underpin applications. "There is a lot of fundamental science yet to be learned about how nanostructures form, how they organize themselves, and how their properties are related to their structure," he says. "I believe that it is investment in fundamental nanoscience that will eventually lead to new technology. There will not be a real technological advance if we only promote applied research." This is particularly true for nanotubes and nanowires, says Joselevich. "These structures are terribly hard to control and manipulate, and this is what is holding back their most promising applications." Nanotubes and beyond * Introduction * What next * Nanotubes and beyond * When nano meets bio * References © WEIZMANN INSTITUTE OF SCIENCE The authors of the first paper to be published in Nature Nanotechnology were based at the Weizmann Institute of Science in Israel. Ernesto Joselevich (sitting with laptop) and Sidney Cohen (right) are still at the Weizmann. Lior Segev (left) is now a physicist at Applied Materials Israel, Onit Srur-Lavi (standing) is a chemist at Tadiran Batteries, and Tzahi Cohen-Karni (on screen) is a postdoc at MIT. 'Welcome to the nanoSQUID', trumpeted the cover of the first issue of Nature Nanotechnology, referring to the carbon nanotube superconducting quantum interference device developed by a group led by Wolfgang Wernsdorfer of the Laboratoire Louis Néel in Grenoble. Wernsdorfer and the first author on the paper, Jean-Pierre Cleuziou, are still working together in Grenoble, where efforts to use the nanoSQUID to study the properties of single-molecule magnets are part of a wider research programme in molecular quantum spintronics2 — a field that combines three rapidly evolving areas of research: molecular electronics, quantum computing and spintronics. "The aim is to manipulate spins and charges in electronic devices containing one or more molecules," says Wernsdorfer. "The weak spin-orbit and hyperfine interactions in organic molecules suggest that spin coherence may be preserved over much longer times and distances than in conventional metals or semiconductors." There is also scope to integrate functions — such as the use of light or electric fields for switching — directly into the molecule. "The main targets for the next five years are in fundamental science," says Wernsdorfer, "but applications in quantum electronics are expected in the long run." Carbon nanotubes featured in four of the seven papers in the first issue, and one of them — about a technique called density gradient ultracentrifugation (DGU) developed at Northwestern University to sort nanotubes by electronic structure — had been cited 566 times at the time of writing, making it the journal's second most-cited paper. (The most cited, 'Processable aqueous dispersions of graphene nanosheets', has received 844 citations since it was published in February 2008). Nanotubes are generally manufactured as a mixture of metallic and semiconducting nanotubes, and finding a reliable method for separating out just the semiconducting nanotubes for applications in electronics had long been a challenge. "Five years ago, I would have said that the isolation of significant quantities of high-quality monodisperse nanomaterials was the primary challenge," says Mark Hersam, who was the last author on the Northwestern paper. "However, I believe that DGU and related separation methods have essentially solved this problem over the past five years. Now the principal challenge is assembly and integration. In the vast majority of applications, nanomaterials will need to be precisely positioned or patterned and interfaced with other materials." Hersam has used monodisperse nanotubes obtained with DGU to make a variety of devices, including transistors and sensors, and is exploring new applications such as batteries, solar cells, drug delivery and biomedical imaging. He has also applied DGU to other materials, including graphene3 and metallic nanoparticles4, and co-founded a company called Nanointegris to commercialize the technology. ""Five years from now, I hope to be publishing on a 20% efficient carbon solar cell."" Mike Arnold Mike Arnold, first author on the DGU paper, is also working on applications of highly pure nanotubes in his new position as an assistant professor at the University of Wisconsin. "My group is especially interested in using purified semiconducting nanotubes as photoabsorbers in photovoltaic and photodetector devices," he says, "because nanotubes are strong optical absorbers with tunable near-infrared bandgaps and excellent chemical stability. Five years from now, I hope to be publishing on a 20% efficient carbon solar cell." When nano meets bio * Introduction * What next * Nanotubes and beyond * When nano meets bio * References Seunghun Hong of Seoul National University was the last author on a paper that reported how conventional microfabrication facilities could be used for the large-scale assembly of devices based on nanotubes or nanowires. Since then Hong and his co-workers have published more than 40 papers on devices and structures assembled with this method, including an artificial nose based on nanotubes5 and surfaces that can control the differentiation of stem cells6. Hong's work at Seoul is now centred on hybrid systems comprised of solid-state devices and organic materials. The biggest challenge in this area, he says, is to develop new methods for the control and measurement of single biomolecules. However, he stresses that there has been significant progress in recent years, citing an approach to real-time DNA sequencing based on photonic nanostructures that has been developed at Pacific Biosciences7. One of Hong's ambitions is to integrate taste receptors with nanotube-based transistors to make an artificial tongue. Another researcher working on biological applications of nanoscale devices is Gang Logan Liu, who was a graduate student at Berkeley when he was first author on a paper that demonstrated that a nanoplasmonic molecule can measure nuclease activity and protein–DNA binding. Now an assistant professor at the University of Illinois in Urbana-Champaign, Liu plans to develop new nanophotonic and nanoelectronic sensors for applications in health care and environmental protection. Back at MIT, Cohen-Karni is also keen to explore the "fascinating" interface between the physical and biological worlds. "Having a background in materials science," he says, "I feel that there is so much that you can do by incorporating nanoscale materials into biological systems, either to create new hybrids of nanomaterials and biological materials such as tissue, or to use nanodevices to investigate biological systems." With so many possibilities, at the bio–nano frontier and elsewhere, the next five years look set to be just as interesting and unpredictable as the past five. References * Introduction * What next * Nanotubes and beyond * When nano meets bio * References * Cohen-Karni, T.et al. Proc. Natl Acad. Sci. USA106, 7309–7313 (2009). * PubMed * Article * Urdampilleta, M.et al. Nature Mater.10, 502–506 (2011). * ChemPort * ISI * Article * Green, A. & Hersam, M. C.Nano Lett.9, 4031–4036 (2009). * ChemPort * ISI * PubMed * Article * Tyler, T. P.et al. J. Phys. Chem. Lett.2, 218–222 (2011). * ChemPort * Article * Kim, T. H.et al. Adv. Mater.21, 91–94 (2009). * ChemPort * ISI * Article * Namgung, S.et al. ACS Nanohttp://dx.doi.org/10.1021/nn2023057 (2011). * Eid, J.et al. Science323, 133–138 (2009). * ChemPort * ISI * PubMed * Article * Tang, J.et al. Nature Nanotech.6, 568–572 (2011). * ChemPort * Article Download references Additional data - Our choice from the recent literature
- Nat Nanotechnol 6(10):609 (2011)
Article preview View full access options Nature Nanotechnology | Research Highlights Our choice from the recent literature Journal name:Nature NanotechnologyVolume: 6,Page:609Year published:(2011)DOI:doi:10.1038/nnano.2011.174Published online07 October 2011 Angew. Chem. Int. Ed.http://dx.doi.org/10.1002/anie.201102882 (2011) © 2011 WILEY The surfaces of metal nanoparticles are often coated with a single layer of thiol molecules in which the sulphur atoms at the head of the molecules bind to the surface and the molecular tails extend out into the surrounding medium. Such monolayers can also be formed using mixtures of thiols, and these mixed monolayers can undergo phase separations to form nanoscale domains on the surface. By controlling the structure of the domains, the properties of the nanoparticles, such as their solubility, can be modified. However, characterizing the domains is difficult. John McLean, David Cliffel and colleagues at Vanderbilt University have now shown that mass spectrometry can be used to observe and measure phase separation in gold nanoparticle monolayers. Article preview Read the full article * Instant access to this article: US$32 Buy now * Subscribe to Nature Nanotechnology for full access: Subscribe * Personal subscribers: Log in Additional access options: * Login via Athens * Login via your Institution * Purchase a site license * Use a document delivery service * British Library Document Supply Centre * Infotrieve * Thompson ISI Document Delivery * You can also request this document from your local library through inter-library loan services. Author information Article tools * Print * Email * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Additional data - Molecular motors: Powered by electrons
- Nat Nanotechnol 6(10):610-611 (2011)
Article preview View full access options Nature Nanotechnology | News and Views Molecular motors: Powered by electrons * Steven De Feyter1Journal name:Nature NanotechnologyVolume: 6,Pages:610–611Year published:(2011)DOI:doi:10.1038/nnano.2011.171Published online07 October 2011 Electrons from the tip of a scanning tunnelling microscope can be used to drive and monitor the directional rotation of a single molecule on a metal surface. Subject terms: * Molecular machines and motors * Surface patterning and imaging Article preview Read the full article * Instant access to this article: US$18 Buy now * Subscribe to Nature Nanotechnology for full access: Subscribe * Personal subscribers: Log in Additional access options: * Login via Athens * Login via your Institution * Purchase a site license * Use a document delivery service * British Library Document Supply Centre * Infotrieve * Thompson ISI Document Delivery * You can also request this document from your local library through inter-library loan services. Author information Article tools * Print * Email * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Affiliations * Steven De Feyter is at the Department of Chemistry, Katholieke Universiteit of Leuven (KULeuven), B-3001 Heverlee, Belgium Corresponding author Correspondence to: * Steven De Feyter Author Details * Steven De Feyter Contact Steven De Feyter Search for this author in: * NPG journals * PubMed * Google Scholar Additional data - Graphene optoelectronics: Plasmons get tuned up
- Nat Nanotechnol 6(10):611-612 (2011)
Article preview View full access options Nature Nanotechnology | News and Views Graphene optoelectronics: Plasmons get tuned up * Farhan Rana1Journal name:Nature NanotechnologyVolume: 6,Pages:611–612Year published:(2011)DOI:doi:10.1038/nnano.2011.170Published online07 October 2011 Plasmons in graphene nanoribbons have widely tunable frequencies and interact strongly with light. Subject terms: * Photonic structures and devices * Synthesis and processing Article preview Read the full article * Instant access to this article: US$18 Buy now * Subscribe to Nature Nanotechnology for full access: Subscribe * Personal subscribers: Log in Additional access options: * Login via Athens * Login via your Institution * Purchase a site license * Use a document delivery service * British Library Document Supply Centre * Infotrieve * Thompson ISI Document Delivery * You can also request this document from your local library through inter-library loan services. Author information Article tools * Print * Email * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Affiliations * Farhan Rana is in the School of Electrical and Computer Engineering, Cornell University, 223 Phillips Hall, Ithaca, New York 14853, USA Corresponding author Correspondence to: * Farhan Rana Author Details * Farhan Rana Contact Farhan Rana Search for this author in: * NPG journals * PubMed * Google Scholar Additional data - Electron spectroscopy: A new window opens
- Nat Nanotechnol 6(10):612-613 (2011)
Article preview View full access options Nature Nanotechnology | News and Views Electron spectroscopy: A new window opens * Dmitry Zemlyanov1Journal name:Nature NanotechnologyVolume: 6,Pages:612–613Year published:(2011)DOI:doi:10.1038/nnano.2011.173Published online07 October 2011 Graphene membranes allow measurements of surface chemistry under realistic conditions. Subject terms: * Nanomaterials * Nanometrology and instrumentation Article preview Read the full article * Instant access to this article: US$18 Buy now * Subscribe to Nature Nanotechnology for full access: Subscribe * Personal subscribers: Log in Additional access options: * Login via Athens * Login via your Institution * Purchase a site license * Use a document delivery service * British Library Document Supply Centre * Infotrieve * Thompson ISI Document Delivery * You can also request this document from your local library through inter-library loan services. Author information Article tools * Print * Email * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Affiliations * Dmitry Zemlyanov is at the Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, USA Corresponding author Correspondence to: * Dmitry Zemlyanov Author Details * Dmitry Zemlyanov Contact Dmitry Zemlyanov Search for this author in: * NPG journals * PubMed * Google Scholar Additional data - Environmental, health and safety issues: Nanoparticles in the real world
- Nat Nanotechnol 6(10):613-614 (2011)
Article preview View full access options Nature Nanotechnology | News and Views Environmental, health and safety issues: Nanoparticles in the real world * Maxine J. McCall1Journal name:Nature NanotechnologyVolume: 6,Pages:613–614Year published:(2011)DOI:doi:10.1038/nnano.2011.169Published online07 October 2011 Risk assessments of products containing nanomaterials require both the materials in the products and the materials emitted during their use to be analysed so that realistic exposures can be determined. Subject terms: * Environmental, health and safety issues Article preview Read the full article * Instant access to this article: US$18 Buy now * Subscribe to Nature Nanotechnology for full access: Subscribe * Personal subscribers: Log in Additional access options: * Login via Athens * Login via your Institution * Purchase a site license * Use a document delivery service * British Library Document Supply Centre * Infotrieve * Thompson ISI Document Delivery * You can also request this document from your local library through inter-library loan services. Author information Article tools * Print * Email * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Affiliations * Maxine J. McCall is in CSIRO Food and Nutritional Sciences, North Ryde, New South Wales, Australia Corresponding author Correspondence to: * Maxine J. McCall Author Details * Maxine J. McCall Contact Maxine J. McCall Search for this author in: * NPG journals * PubMed * Google Scholar Additional data - Nanopore sensors for nucleic acid analysis
- Nat Nanotechnol 6(10):615-624 (2011)
Nature Nanotechnology | Review Nanopore sensors for nucleic acid analysis * Bala Murali Venkatesan1, 2 * Rashid Bashir1, 2, 3 * Affiliations * Corresponding authorJournal name:Nature NanotechnologyVolume: 6,Pages:615–624Year published:(2011)DOI:doi:10.1038/nnano.2011.129Published online18 September 2011 Abstract * Abstract * Author information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Nanopore analysis is an emerging technique that involves using a voltage to drive molecules through a nanoscale pore in a membrane between two electrolytes, and monitoring how the ionic current through the nanopore changes as single molecules pass through it. This approach allows charged polymers (including single-stranded DNA, double-stranded DNA and RNA) to be analysed with subnanometre resolution and without the need for labels or amplification. Recent advances suggest that nanopore-based sensors could be competitive with other third-generation DNA sequencing technologies, and may be able to rapidly and reliably sequence the human genome for under $1,000. In this article we review the use of nanopore technology in DNA sequencing, genetics and medical diagnostics. View full text Subject terms: * Nanobiotechnology * Nanosensors and other devices Figures at a glance * Figure 1: Trends in nanopore analysis of DNA. DNA translocation velocity in nucleotides per millisecond (on a logarithmic scale) versus year for both ssDNA and dsDNA and for both α-haemolysin and solid-state nanopores. Each data point represents a reduction in translocation velocity or an improvement in sensitivity; for each data point the relevant reference(s) are shown in parentheses and the size of the shortest molecule detected is shown in nucleotides (nt), base pairs (bp) or kilobase pairs (kbp). For solid-state nanopore sequencing applications, the translocation velocity should be in the range 1–100 nt ms−1 (pale blue region). Biological nanopores have already reached velocities below this range, and solid-state nanopores are also expected to approach these values around 2015. However, substantial improvements in sensitivity of both biological and solid-state nanopores are also needed, which is why researchers are exploring the new approaches described in Table 1. The reduced velocities (and improved sensitiv! ities) for α-haemolysin have been achieved by a combination of site-specific mutagenesis and one of the following: the incorporation of DNA processing enzymes into the nanopore21, chemical labelling of the nucleotides106 or the covalent attachment of an aminocyclodextrin adapter24. The improvements in the performance of solid-state nanopores have been due to the optimization of solution conditions (temperature, viscosity, pH)109, chemical functionalization110, surface-charge engineering45, varying the thickness and composition of the membranes38, 61, 112, and the use of smaller diameter nanopores58, 61 (thereby enhancing polymer–pore interactions). This figure contains key nanopore developments in terms of translocation velocity and sensitivity, but is by no means exhaustive. * Figure 2: Biological nanopores for DNA sequencing. , Left: structural cross-section of α-haemolysin. The 1.4 nm constriction permits the passage of ssDNA but not dsDNA. Middle: typical plot of residual ionic current through an aminocyclodextrin-modified α-haemolysin nanopore versus time for individual mononucleotides (dAMP, dCMP, dGMP, dTMP). The reduction in the current caused by the passage of individual nucleotides through the nanopore is nucleotide dependent, facilitating identification. Right: histogram of the residual pore current based on measurements like those shown in the middle panel, which demonstrates how the different bases can be distinguished using ionic current alone under optimized conditions. , Left: structural cross-section of MspA. Middle: typical plot of residual ionic current through an MspA nanopore versus time for a duplex interrupted DNA molecule (that contains a dsDNA segment (the duplex) between each ssDNA nucleotide triplet (AAA, TTT, GGG, CCC)). In this approach the duplex temporarily halts th! e passage of the DNA through the nanopore; when the duplex dissociates owing to the high electric field in the nanopore region, translocation starts again. A unique current level is observed for each triplet of nucleotides in a duplex interrupted molecule. Right: histogram showing that the separation efficiency of MspA is better than that of α-haemolysin. Figures reproduced with permission from: , ref. 13, © 2010 Annual Reviews, Inc. (left panel) and ref. 24, © 2009 NPG (middle and right panels); , ref. 27, © 2010 National Academy of Sciences. * Figure 3: Solid-state nanopore architectures for DNA analysis. , Top: TEM images showing the formation (by a focused electron beam) and controlled contraction of nanopores in Al2O3 membranes. It is possible to control the diameter of the nanopore with subnanometre precision. Bottom: scatter plot of event blockage (the percentage of open pore ionic current that is blocked as a molecule passes through the pore) versus event duration (on a logarithmic scale) for the translocation of segments of dsDNA containing 5,000 base pairs through a 5-nm-diameter Al2O3 pore showing a single blockage level (~20% of the open pore current) corresponding to linear, unfolded dsDNA transport. , Top: schematic (left) and TEM image (right) of a nanopore in a suspended graphene film containing just one to two layers of carbon atoms. Bottom: scatter plot of event blockage versus event duration showing that folded DNA (left of inset, deep blockade level) and unfolded DNA (right of inset, shallow blockade level) can be distinguished. The solid line represents a c! onstant event charge deficit (ecd; which is the total area under each current transient resulting from a DNA translocation event). As shown, fast high-amplitude events and slow low-amplitude events can share a constant ecd or constant area, signifying folded and unfolded translocation events respectively. , Top: TEM image of a terraced nanopore formed in a graphene film containing ~10 monolayers of carbon atoms. Scale bar, 1 nm. Bottom left: nanopore in a monolayer of graphene with primarily armchair edges surrounded by multilayered regions. Scale bar, 1 nm. Bottom right: TEM image of a nanopore in multilayer graphene; ripples at the pore edge again show the terraced structure. Figures reproduced with permission from: , ref. 38, © 2009 Wiley and ref. 45, © 2010 Wiley (inset); , ref. 51, © 2010 NPG; , ref. 55, © 2011 ACS (top and bottom left panels) and ref. 52, © 2010 ACS (bottom right panel). * Figure 4: Other applications of nanopores: miRNA detection and genomic profiling. , Probe-specific hybridization is used to separate and concentrate sequence-specific miRNAs from tissue samples; nanopore-based sensors are then used to measure the level of miRNAs. This technique offers comparable sensitivity to conventional microarray techniques. , Sequences containing single nucleotide polymorphisms (SNPs) have been detected with nanopore-based techniques. Top: protein-bound dsDNA complexes (105 base pairs (bp) long) were electrophoretically driven into a ~2-nm-diameter nanopore and then sheared. Bottom: the shearing occurs when the voltage across the nanopore exceeds a threshold (purple line), thereby dislodging the protein and allowing the electrophoretic transport of the 105 bp fragment through the nanopore. Cog refers to the cognate protein binding sequence. Note: the y axis here represents the number of copies of 105 bp DNA that have translocated through the nanopore as a result of protein shearing (and measured by quantitative PCR). Changing just on! e nucleotide in the protein binding sequence caused the threshold voltage to drop (green line), thus allowing SNPs to be detected. The inset shows a TEM image of the nanopore. , Genomic profiling. Top: Schematic showing translocation of PNA-tagged DNA molecules through a solid-state nanopore. Middle: PNA-tagged dsDNA complexes produced unique current transients in nanopore measurements. Bottom: the number of PNA tags per molecule can be quantified, facilitating rapid electrical profiling of DNA molecules. Figures reproduced with permission from: , ref. 61, © 2010 NPG; , ref. 68, © 2007 ACS; , ref. 69, © 2010 ACS. * Figure 5: Hybrid biological–solid-state nanopores. , A SiO2 nanopore functionalized with hairpin DNA (top) can distinguish between ssDNA that is perfectly complementary (PC DNA) to the hairpin sequence (bottom, red data points) and ssDNA that differs by a single base (bottom, blue data points; 1MM, one base mismatch), thereby allowing for the detection of SNPs. , A SiN nanopore coated with a fluid lipid bilayer containing mobile ligands attached to the surface (top) can detect and differentiate various protein analytes because they lead to different current blockage distributions as shown in the histograms (bottom). , α-haemolysin can be inserted into a SiN nanopore by attaching a dsDNA tail that can be pulled through the nanopore by electrophoresis (top left). The formation of the hybrid nanopore occurs in three stages (top right), each of which is associated with a characteristic conductance (bottom). When the α-haemolysin has been inserted into the SiN nanopore (stage III), the conductance is consistent with values meas! ured for α-haemolysin in a lipid bilayer. Figures reproduced from: , ref. 70, © 2007 NPG; , ref. 74, © 2011 NPG; , ref. 75, © 2010 NPG. * Figure 6: Possible novel nanopore architectures for sequencing. , Schematic cross-section showing ssDNA passing through a solid-state nanopore with an embedded tunnelling detector92. The detector consists of two electrodes spaced ~1 nm apart on opposite sides of the nanopore. Changes in the tunnelling current as ssDNA passes through the nanopore (and between the electrodes) could be used to identify the sequence of bases in the DNA. Inset: top view showing a nucleotide positioned in the nanogap between the electrodes of the tunnelling detector. Figure reproduced from ref. 92, © 2010 NPG. , Schematic showing ssDNA passing through a solid-state nanopore with an embedded graphene gate and a graphene nanoribbon on the membrane containing the nanopore; both the gate and the nanoribbon contain circular openings for the DNA to pass through. The graphene gate could be used to induce either p-type or n-type behaviour in the nanoribbon and to electrostatically slow down ssDNA. Changes in the transverse conductance of the nanoribbon as ssDNA passe! s through the nanopore could be used to identify the sequence of bases in the DNA84. Functionalization of the edges of the circular opening in the nanoribbon could further enhance nucleotide-specific interactions. Author information * Abstract * Author information Affiliations * Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61820, USA * Bala Murali Venkatesan & * Rashid Bashir * Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61820, USA * Bala Murali Venkatesan & * Rashid Bashir * Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61820, USA * Rashid Bashir Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Rashid Bashir Author Details * Bala Murali Venkatesan Search for this author in: * NPG journals * PubMed * Google Scholar * Rashid Bashir Contact Rashid Bashir Search for this author in: * NPG journals * PubMed * Google Scholar Additional data - Experimental demonstration of a single-molecule electric motor
- Nat Nanotechnol 6(10):625-629 (2011)
Nature Nanotechnology | Letter Experimental demonstration of a single-molecule electric motor * Heather L. Tierney1 * Colin J. Murphy1 * April D. Jewell1 * Ashleigh E. Baber1 * Erin V. Iski1 * Harout Y. Khodaverdian1 * Allister F. McGuire1 * Nikolai Klebanov1 * E. Charles H. Sykes1 * Affiliations * Contributions * Corresponding authorJournal name:Nature NanotechnologyVolume: 6,Pages:625–629Year published:(2011)DOI:doi:10.1038/nnano.2011.142Received23 May 2011Accepted26 July 2011Published online04 September 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg For molecules to be used as components in molecular machines, methods that couple individual molecules to external energy sources and that selectively excite motion in a given direction are required1, 2, 3, 4, 5, 6. Significant progress has been made in the construction of molecular motors powered by light1, 2, 7 and by chemical reactions3, 4, 5, 8, but electrically driven motors have not yet been built, despite several theoretical proposals for such motors9, 10, 11, 12, 13. Here we report that a butyl methyl sulphide molecule adsorbed on a copper surface can be operated as a single-molecule electric motor. Electrons from a scanning tunnelling microscope are used to drive the directional motion of the molecule in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. The direction and rate of the rotation are related to the chiralities of both the molecule and the t! ip of the microscope (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices14. View full text Subject terms: * Molecular machines and motors * Surface patterning and imaging Figures at a glance * Figure 1: Single-molecule rotors. A STM image of the two enantiomeric forms of BuSMe, R and S, adsorbed on a Cu(111) surface. The pinwheel appearance of the molecule arises from the rotation of the alkyl groups (the butyl and methyl groups) around the central sulphur atom. BuSMe is achiral in the gas phase, but becomes chiral when bound to a surface. The molecules in the main panel rotate because of the high tunnelling current used to form the image. The inset shows a static BuSMe rotor imaged under non-perturbative conditions. Scale bars, 1 nm. (Imaging conditions. Main panel: I = 300 pA, Vtip = 0.1 V, T = 7 K; inset: I = 5 pA, Vtip = 0.07 V, T = 5 K.) * Figure 2: Exciting and measuring molecular rotation. Current versus time spectra, such as the I versus t spectrum on the left, provide a way of measuring both the rotational rate (events/time) and the direction of rotation of the BuSMe molecule by following its progression between six equivalent orientations on the Cu(111) surface. The top right of the figure shows these six orientations; the bottom right shows a model of the BuSMe molecule (to scale) on the Cu(111) surface, with the sulphur atom shown in blue, and the representation used in the schematic. Rotation of the BuSMe molecule can be excited by placing the STM tip at the position marked 'x' because this leads to inequivalent tunnelling current levels for each orientation. (Experimental conditions used to measure the I versus t spectrum: I = 5 pA, Vtip = 0.38 V, T = 5 K.) * Figure 3: Mechanism of directional rotation. , Schematic of the S chirality (left) and R chirality (right) of the BuSMe molecular rotor electrically excited with a chiral STM tip. The rotors can rotate in either the clockwise or anticlockwise direction in multiples (or 'hops') of 60°. , Histograms showing the experimentally measured distributions of hop angles for the two chiralities of the rotor. The S chirality of the rotor is more directional than the R chirality, and is more likely to hop by ±60° and least likely to hop by ±180° (left); the R chirality of the rotor makes hops of all angles (±60°, ±120° and ±180°) with almost equal probability. , Proposed fluctuating-temperature-like ratchet mechanism in which electrical excitation of a C–H stretch in the rotor arm acts in a way that is equivalent to a periodic temperature modulation (thick black arrow)26, 27. Energy redistribution leading mostly to single (±60°) or double (±120°) hops (red arrows) yields measurable directional motion across the! asymmetric molecule–surface potential landscape (left); roughly equal excitation of hops of all sizes (blue arrows) leads to no net measured directionality (right). See main text for further details. Author information * Abstract * Author information * Supplementary information Affiliations * Department of Chemistry, Tufts University, Medford, Massachusetts 02155-5813, USA * Heather L. Tierney, * Colin J. Murphy, * April D. Jewell, * Ashleigh E. Baber, * Erin V. Iski, * Harout Y. Khodaverdian, * Allister F. McGuire, * Nikolai Klebanov & * E. Charles H. Sykes Contributions H.L.T., C.J.M., A.D.J., A.E.B. and E.V.I. performed the experiments. Data analysis was performed by H.L.T., C.J.M., H.Y.K., A.F.M., N.K. and E.C.H.S. The paper was written by H.L.T., C.J.M. and E.C.H.S. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * E. Charles H. Sykes Author Details * Heather L. Tierney Search for this author in: * NPG journals * PubMed * Google Scholar * Colin J. Murphy Search for this author in: * NPG journals * PubMed * Google Scholar * April D. Jewell Search for this author in: * NPG journals * PubMed * Google Scholar * Ashleigh E. Baber Search for this author in: * NPG journals * PubMed * Google Scholar * Erin V. Iski Search for this author in: * NPG journals * PubMed * Google Scholar * Harout Y. Khodaverdian Search for this author in: * NPG journals * PubMed * Google Scholar * Allister F. McGuire Search for this author in: * NPG journals * PubMed * Google Scholar * Nikolai Klebanov Search for this author in: * NPG journals * PubMed * Google Scholar * E. Charles H. Sykes Contact E. Charles H. Sykes Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (762 KB) Supplementary information Movies * Supplementary information (7,177 KB) Supplementary movie Additional data - Graphene plasmonics for tunable terahertz metamaterials
- Nat Nanotechnol 6(10):630-634 (2011)
Nature Nanotechnology | Letter Graphene plasmonics for tunable terahertz metamaterials * Long Ju1 * Baisong Geng1, 6 * Jason Horng1 * Caglar Girit1 * Michael Martin2 * Zhao Hao2, 3 * Hans A. Bechtel2 * Xiaogan Liang4 * Alex Zettl1, 5 * Y. Ron Shen1, 5 * Feng Wang1, 5 * Affiliations * Contributions * Corresponding authorJournal name:Nature NanotechnologyVolume: 6,Pages:630–634Year published:(2011)DOI:doi:10.1038/nnano.2011.146Received27 April 2011Accepted27 July 2011Published online04 September 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Plasmons describe collective oscillations of electrons. They have a fundamental role in the dynamic responses of electron systems and form the basis of research into optical metamaterials1, 2, 3. Plasmons of two-dimensional massless electrons, as present in graphene, show unusual behaviour4, 5, 6, 7 that enables new tunable plasmonic metamaterials8, 9, 10 and, potentially, optoelectronic applications in the terahertz frequency range8, 9, 11, 12. Here we explore plasmon excitations in engineered graphene micro-ribbon arrays. We demonstrate that graphene plasmon resonances can be tuned over a broad terahertz frequency range by changing micro-ribbon width and in situ electrostatic doping. The ribbon width and carrier doping dependences of graphene plasmon frequency demonstrate power-law behaviour characteristic of two-dimensional massless Dirac electrons4, 5, 6. The plasmon resonances have remarkably large oscillator strengths, resulting in prominent room-temperature optical ab! sorption peaks. In comparison, plasmon absorption in a conventional two-dimensional electron gas was observed only at 4.2 K (refs 13, 14). The results represent a first look at light–plasmon coupling in graphene and point to potential graphene-based terahertz metamaterials. View full text Subject terms: * Electronic properties and devices * Nanomaterials * Photonic structures and devices * Synthesis and processing Figures at a glance * Figure 1: Plasmon resonance in gated graphene micro-ribbon arrays. , Top-view illustration of a typical graphene micro-ribbon array. The array was fabricated on transferred large-area CVD graphene using optical lithography and plasma etching. , Side view of a typical device incorporating the graphene micro-ribbon array on a Si/SiO2 substrate. The carrier concentration in graphene is controlled using the ion-gel top gate. , AFM image of a graphene micro-ribbon array sample with a ribbon width of 4 µm and a ribbon and gap width ratio of 1:1. , Gate-dependent electrical resistance of this graphene micro-ribbon array. The resistance has a maximum at charge neutral point VCNP = 0.2 V. ,, Gate-induced change of transmission spectra, −(T − TCNP)/TCNP (red solid line), with incident light polarized parallel () and perpendicular () to the ribbon length, respectively. The gate voltage was set at Vg = −2 V. For parallel polarization in , the response originates from free carrier oscillation and can be well reproduced by a Drude fit (black dashe! d line). For perpendicular polarization in , the spectrum shows a prominent absorption peak at 3 THz (1 THz = 33.3 cm−1) because of plasmon excitation. Plasmon resonance is characterized by a Lorentzian lineshape (blue dashed line). A small free carrier contribution described by Drude absorption (magenta dashed line) is also present as a result of graphene absorption outside the fabricated micro-ribbon array area. The plasmon absorption of over 13% is remarkably strong, and its integrated oscillator strength is more than an order of magnitude larger than that achieved in 2DEGs in conventional semiconductors. * Figure 2: Control of plasmon resonance through electrical gating and micro-ribbon width. , Mid-infrared transmission spectra, T/TCNP, of the graphene ribbon array in Fig. 1 as gate voltage Vg − VCNP varies from −0.3 to −2.2 V. The voltages corresponding to the unlabelled lines, starting with the red line and alternating downwards, are: −2.0 V, −1.6 V, −1.2 V, −0.7 V and −0.3 V. On electrical gating, optical transmission is increased up to a threshold energy of 2|EF| as a result of blocked interband optical transitions. This threshold energy provides direct determination of Fermi energy EF and carrier concentration n = (|EF|/vF)2/π in gated graphene. , Control of terahertz resonance of plasmon excitations through electrical gating. Terahertz radiation was polarized perpendicular to the graphene ribbons. The plasmon resonance shifts to higher energy and gains oscillator strength with increased carrier concentration. For comparison, the inset shows corresponding spectra due to free carrier absorption for terahertz radiation polarized parallel to th! e ribbons. For this polarization, absorption strength increases with carrier concentration, but spectral shape remains the same. , AFM images of samples with micro-ribbon widths (w) of 1, 2 and 4 µm. , Change of transmission spectra with different graphene micro-ribbon widths for the same doping concentration of 1.5 × 1013 cm−2. The Drude background contributed by unpatterned graphene around the arrays (as in Fig. 1f) was subtracted, and all spectra were normalized by their respective peak values for convenience of comparison. Plasmon resonance frequency ωp shifts from 3 to 6 THz when micro-ribbon width decreases from 4 to 1 µm. * Figure 3: Scaling laws of graphene plasmon resonance frequency. , Plasmon resonance frequency ωp as a function of |EF| (or equivalently |n|1/2 in the top label) for micro-ribbon arrays of different widths. , Plasmon excitation ωp was normalized by 1/√w for micro-ribbon arrays of different widths, which fits all data points (symbols) into a universal curve (solid line). This w−1/2 scaling of ωp is characteristic of 2D electron systems. The universal doping dependence of plasmon resonances is described by a scaling law of ωp ∝ |EF|1/2 ∝ n1/4. This n1/4 scaling law is a signature of massless Dirac fermions. In comparison, ωp scales as n1/2 (dashed line) in conventional semiconductors. * Figure 4: Simulation of plasmon excitations. , Transmission change spectrum −ΔT/TCNP simulated by finite element analysis (dashed line) for the sample in Fig. 1 at carrier concentration of 1.5 × 1013 cm−2. It reproduces well the experimentally observed spectrum (solid line) when the effective environment dielectric constant κ was set as 5, and corresponds to an electron–electron interaction strength of e2/κvF ≈ 0.4. –, Simulation results for current density amplitude (upper panel) and phase (lower panel) of the device at frequencies below resonance (1 THz, ), at resonance (3 THz, ) and above resonance (5 THz, ). The charge carriers oscillate perpendicular to the graphene ribbons on terahertz irradiation. The oscillating current is highest at the plasmon resonance frequency. The relative phase of the oscillating current with reference to the incident electrical field also varies quickly and changes sign at the resonance frequency. Both are characteristics of a resonant excitation. Author information * Abstract * Author information * Supplementary information Affiliations * Department of Physics, University of California at Berkeley, Berkeley, California 94720, USA * Long Ju, * Baisong Geng, * Jason Horng, * Caglar Girit, * Alex Zettl, * Y. Ron Shen & * Feng Wang * Advanced Light Source Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA * Michael Martin, * Zhao Hao & * Hans A. Bechtel * Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA * Zhao Hao * Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA * Xiaogan Liang * Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA * Alex Zettl, * Y. Ron Shen & * Feng Wang * School of Physical Science and Technology, Lanzhou University, Lanzhou 730000, China * Baisong Geng Contributions F.W. and L.J. conceived the experiment. L.J. carried out optical measurements, B.G., J.H., X.L. and C.G. contributed to sample growth and fabrication, and L.J. and F.W. performed theoretical analysis. All authors discussed the results and wrote the paper. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Feng Wang Author Details * Long Ju Search for this author in: * NPG journals * PubMed * Google Scholar * Baisong Geng Search for this author in: * NPG journals * PubMed * Google Scholar * Jason Horng Search for this author in: * NPG journals * PubMed * Google Scholar * Caglar Girit Search for this author in: * NPG journals * PubMed * Google Scholar * Michael Martin Search for this author in: * NPG journals * PubMed * Google Scholar * Zhao Hao Search for this author in: * NPG journals * PubMed * Google Scholar * Hans A. Bechtel Search for this author in: * NPG journals * PubMed * Google Scholar * Xiaogan Liang Search for this author in: * NPG journals * PubMed * Google Scholar * Alex Zettl Search for this author in: * NPG journals * PubMed * Google Scholar * Y. Ron Shen Search for this author in: * NPG journals * PubMed * Google Scholar * Feng Wang Contact Feng Wang Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (720 KB) Supplementary information Additional data - Direct observation of a propagating spin wave induced by spin-transfer torque
- Nat Nanotechnol 6(10):635-638 (2011)
Nature Nanotechnology | Letter Direct observation of a propagating spin wave induced by spin-transfer torque * M. Madami1, 10 * S. Bonetti2, 10 * G. Consolo3, 4 * S. Tacchi1 * G. Carlotti1, 5 * G. Gubbiotti1, 6 * F. B. Mancoff7 * M. A. Yar8 * J. Åkerman2, 9 * Affiliations * Contributions * Corresponding authorsJournal name:Nature NanotechnologyVolume: 6,Pages:635–638Year published:(2011)DOI:doi:10.1038/nnano.2011.140Received20 June 2011Accepted22 July 2011Published online28 August 2011 Abstract * Abstract * Author information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Spin torque oscillators with nanoscale electrical contacts1, 2, 3, 4 are able to produce coherent spin waves in extended magnetic films, and offer an attractive combination of electrical and magnetic field control, broadband operation5, 6, fast spin-wave frequency modulation7, 8, 9, and the possibility of synchronizing multiple spin-wave injection sites10, 11. However, many potential applications rely on propagating (as opposed to localized) spin waves, and direct evidence for propagation has been lacking. Here, we directly observe a propagating spin wave launched from a spin torque oscillator with a nanoscale electrical contact into an extended Permalloy (nickel iron) film through the spin transfer torque effect. The data, obtained by wave-vector-resolved micro-focused Brillouin light scattering, show that spin waves with tunable frequencies can propagate for several micrometres. Micromagnetic simulations provide the theoretical support to quantitatively reproduce the resul! ts. View full text Subject terms: * Electronic properties and devices * Nanomagnetism and spintronics * Nanometrology and instrumentation Figures at a glance * Figure 1: Schematic sample layout. Cross-section of the sample, revealing the layers of the spin valve mesa and the active area of the STO device. An aluminium coplanar waveguide is deposited onto the spin valve mesa, and an optical window is etched into the central conductor of the waveguide close to the nanocontact. * Figure 2: Characterization of the optical window. , Scanning electron microscope image of a processed device, showing the optical window in the central conductor of the aluminium waveguide, the nanocontact approximate position and the line (dotted arrow) across which the μ-BLS laser spot was scanned. , EDS data acquired in regions outside and inside the etched window (indicated by dashed and solid squares in , respectively). Inset: experimental μ-BLS spectra (Stokes side), measured outside and inside the etched optical window in the absence of any injected current and within an applied perpendicular field of 2.0 kOe, revealing the presence of thermal spin waves. * Figure 3: Spin-wave frequencies as a function of the injected d.c. intensity. Measured (filled symbols) and simulated (open symbols) spin-wave frequency dependence on d.c. intensity for two different values of the magnetic field. Dashed lines represent the calculated FMR frequency. Inset: μ-BLS spectra (Stokes side) recorded at μ0Hext = 0.6 T and for different signs of the current |I| = 70 mA. * Figure 4: Proof of spin-wave propagation. , Schematic of the experimental procedure used to prove the propagating character of the detected spin wave. L and SW represent the wave vectors of the incoming light and of the emitted spin wave, respectively. , Measured μ-BLS spectra (I = 70 mA and μ0H = 0.6 T) corresponding to the case of fully opened (bottom spectrum) and partially closed (upper spectra) collected beam. * Figure 5: Spin-wave attenuation as a function of distance from the STO. Integrated intensity (symbols) of the spin-wave excitations detected using μ-BLS as a function of distance from the centre of the point contact (r). Analytical calculation (line) of the decay obtained using the function described in the text. Inset: simulated spin-wave wavelength as a function of applied d.c. intensity. Author information * Abstract * Author information Primary authors * These authors contributed equally to this work * M. Madami & * S. Bonetti Affiliations * CNISM, Unità di Perugia and Dipartimento di Fisica, Università di Perugia, Via A. Pascoli, I-06123 Perugia, Italy * M. Madami, * S. Tacchi, * G. Carlotti & * G. Gubbiotti * Materials Physics, School of Information Communication Technology, KTH – Royal Institute of Technology, Electrum 229, 164 40, Kista, Sweden * S. Bonetti & * J. Åkerman * Dipartimento di Scienze per l'Ingegneria e l'Architettura, Università di Messina C.da di Dio, I-98166 Messina, Italy * G. Consolo * CNISM, Unità di Ferrara, Via G. Saragat 1, I-44100 Ferrara, Italy * G. Consolo * Centro S3, CNR-Istituto di Nanoscienze, Via Campi 213A, I-41125 Modena, Italy * G. Carlotti * Istituto Officina dei Materiali del CNR (CNR-IOM), Unità di Perugia, c/o Dipartimento di Fisica, Via A. Pascoli, I-06123 Perugia, Italy * G. Gubbiotti * Everspin Technologies, Inc., 1347 N. Alma School Road, Suite 220, Chandler, Arizona 85224, USA * F. B. Mancoff * Functional Materials Division, School of Information Communication Technology, KTH – Royal Institute of Technology, Electrum 229, 164 40, Kista, Sweden * M. A. Yar * Department of Physics, University of Gothenburg, 412 96 Gothenburg, Sweden * J. Åkerman Contributions M.M., G.G., S.T. and G.Ca. performed μ-BLS measurements. S.B., M.A.Y. and J.Å. realized the procedure to open the optical access to the sample and performed EDS measurements. F.B.M. fabricated the original samples. G.Co. performed numerical simulations. All authors co-wrote the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * M. Madami or * S. Bonetti Author Details * M. Madami Contact M. Madami Search for this author in: * NPG journals * PubMed * Google Scholar * S. Bonetti Contact S. Bonetti Search for this author in: * NPG journals * PubMed * Google Scholar * G. Consolo Search for this author in: * NPG journals * PubMed * Google Scholar * S. Tacchi Search for this author in: * NPG journals * PubMed * Google Scholar * G. Carlotti Search for this author in: * NPG journals * PubMed * Google Scholar * G. Gubbiotti Search for this author in: * NPG journals * PubMed * Google Scholar * F. B. Mancoff Search for this author in: * NPG journals * PubMed * Google Scholar * M. A. Yar Search for this author in: * NPG journals * PubMed * Google Scholar * J. Åkerman Search for this author in: * NPG journals * PubMed * Google Scholar Additional data - Gold nanoparticles for high-throughput genotyping of long-range haplotypes
- Nat Nanotechnol 6(10):639-644 (2011)
Nature Nanotechnology | Letter Gold nanoparticles for high-throughput genotyping of long-range haplotypes * Peng Chen1, 7 * Dun Pan2, 7 * Chunhai Fan1, 2 * Jianhua Chen1 * Ke Huang1 * Dongfang Wang2 * Honglu Zhang2 * You Li1 * Guoyin Feng1 * Peiji Liang3 * Lin He1, 4, 5 * Yongyong Shi1, 6 * Affiliations * Contributions * Corresponding authorsJournal name:Nature NanotechnologyVolume: 6,Pages:639–644Year published:(2011)DOI:doi:10.1038/nnano.2011.141Received18 April 2011Accepted26 July 2011Published online04 September 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Completion of the Human Genome Project1 and the HapMap Project2 has led to increasing demands for mapping complex traits in humans to understand the aetiology of diseases3. Identifying variations in the DNA sequence, which affect how we develop disease and respond to pathogens and drugs, is important for this purpose, but it is difficult to identify these variations in large sample sets3, 4, 5. Here we show that through a combination of capillary sequencing and polymerase chain reaction assisted by gold nanoparticles, it is possible to identify several DNA variations that are associated with age-related macular degeneration6, 7, 8 and psoriasis9 on significant regions of human genomic DNA. Our method is accurate and promising for large-scale and high-throughput genetic analysis of susceptibility towards disease and drug resistance10, 11, 12. View full text Subject terms: * Nanoparticles * Nanomedicine Figures at a glance * Figure 1: Schematic showing the AuNPs-enhanced allele-specific sequencing (AuNAS) strategy. A heterozyous sample with two SNPs is amplified with AS-PCR in the presence and absence of AuNPs. , The complementary (blue line) and mismatched (red line) template strands are annealed with the allele-specific primers (short purple line). For simplicity, the other strand of the template and the corresponding primer are omitted. Small polygons with four different colours represent four types of bases (A, yellow; T, green; C, orange; G, red). The two SNP sites are marked with red arrows (SNP1 and SNP2). Yellow oval, polymerase; red circle, AuNPs. ,, In the presence of polymerase, the templates direct primer extension following the typical Watson–Crick base pairing. Complementary primer–template pairs are extended normally (top panel of and ). Because conventional AS-PCR (without AuNPs) has poor specificity for distinguishing single-base mismatches, primer extension for the mismatched primer–template pair passes the SNP1 site (bottom panel in ). In AuNPs-enhanced AS-PCR,! primer extension is effectively terminated at the SNP1 site (bottom panel in ). Dashed black arrows represent the direction of primer extension. Dotted brown ovals represent areas intended for subsequent capillary sequencing shown in and . ,, Sequencing gel maps for highlighted areas (SNP2 sites are underlined) of the heterozygous sample using conventional AS-PCR () and AuNPs-enhanced AS-PCR (). Each peak is differentially coloured to represent four types of bases (A, green; T, red; C, blue; G, black). The presence of non-specific amplification in results in two peaks at the SNP2 site, which makes it difficult to identify this base (marked with a red '?'). In contrast, only one peak appears at this site in , leading to unambiguous haplotyping of this heterozygous sample. * Figure 2: Real-time amplification curves and Ct values of AS-PCR and AuNPs-enhanced AS-PCR using 5 nm AuNPs. ,, Real-time PCR amplification curves for mismatched primer–template (A/G) () and complementary primer–template (A/T) () on lambda DNA in the presence of 0 (black), 0.5 (red) and 1 nM (blue) AuNPs. Increased Ct values in the presence of AuNPs suggest that PCR amplification of the mismatched primer–template was hampered. , Effect of AuNPs on the Ct values for four primer–template pairs (A/A, A/G, A/C and A/T) on human genomic DNA. Increased Ct values confirm that amplification for mismatched pairs (A/A, A/G and A/C) was inhibited in the presence of AuNPs. ,, Real-time amplification curves of AS-PCR () and AuNPs-enhanced AS-PCR () for SNP rs7758706 with genotype A/A (allele A or G). The black line represents complementary primer for allele A and the red line represents mismatched primer for allele G. The curves suggest that the presence of AuNPs increased the selectivity of amplification. , Gel electrophoresis of PCR products from AS-PCR (lanes 1, 2) and AuNPs-enhanced! AS-PCR (lanes 3, 4) using complementary primers containing T at the 3′-end (lanes 1, 3) and mismatched primers containing C at the 3′-end (lanes 2, 4) further confirms the ability of AuNPs to selectively inhibit amplification of base mismatches. Lane M is a DNA marker (DL2000). * Figure 3: Chromosome separation using AuNPs-enhanced AS-PCR. , Schematic showing AS-PCR of a homozygous locus (blue horizontal line). Two allele-specific primers (complementary and mismatched) were used in separate reactions. Red hexagons represent two alleles at the locus. , Gel electrophoresis shows that the 7-kb PCR product (arrow) decreases with increasing AuNP concentration for both complementary and mismatched primer–template pairs, suggesting that AuNPs can increase the selectivity of long-range PCR amplification. Lane M: lambda DNA/HindIII marker; lanes 0–3 are for amplification with 0, 0.67, 1.33 and 2 nM AuNPs, respectively. –, Sequencing gel maps showing the amplification products of the heterozygous sample, rs2223089 (bearing two alleles, G or C), obtained by AS-PCR (,) and AuNPs-enhanced AS-PCR (,) at two annealing temperatures, 57 °C (,) and 55 °C (,). Site 'G' is highlighted as the allele. Different peak colours represent four types of bases (red, T; blue, C; green, A; black, G). Peaks for the highlighted �! �G' are marked with a blue ellipse, and the black and blue peaks represent complementary and mismatched pairs, respectively. Two sequencing peaks appeared for AS-PCR, suggesting the presence of non-specific amplification. In the presence of AuNPs, the mismatched peaks were greatly suppressed at a suboptimal annealing temperature of 55 °C and completely disappeared when the temperature was increased to 57 °C. * Figure 4: Reconstruction of the whole haplotype for wet AMD using AuNPs-enhanced allele-specific sequencing. , Relative location of SNPs and fragments for the 34-kb region (thick horizontal line) of wet AMD. Open and filled circles represent two different alleles at a locus. Left-pointing arrows represent distances from one SNP to the first SNP (rs6585829). Among these SNPs, rs10490924 and rs11200638 (marked in red) are strongly associated with AMD (rs-numbers represent reference SNP IDs in the Single Nucleotide Polymorphism Database, or dbSNP, http://www.ncbi.nlm.nih.gov/projects/SNP/). , Splitting of the 34-kb region relevant to wet AMD into 12 PCR fragments (frag1–frag12) as represented by arrows. To establish the joint loci, one AuNPs-enhanced long-range AS-PCR reaction was started from one locus of one fragment of a heterozygous sample and ended on the shared locus of the adjacent fragment. As an example, sample AMDC157 was reconstructed by frag3, frag10 and frag4 through the joint loci. The primer sequences are shown in Supplementary Table S12. Author information * Abstract * Author information * Supplementary information Primary authors * These authors contributed equally to this work * Peng Chen & * Dun Pan Affiliations * Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China * Peng Chen, * Chunhai Fan, * Jianhua Chen, * Ke Huang, * You Li, * Guoyin Feng, * Lin He & * Yongyong Shi * Laboratory of Physical Biology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China * Dun Pan, * Chunhai Fan, * Dongfang Wang & * Honglu Zhang * School of Life Science and Technology, Shanghai Jiao Tong University, Shanghai 200030, China * Peiji Liang * Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China * Lin He * Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China * Lin He * Changning Mental Health Center, Shanghai 200042, China * Yongyong Shi Contributions Y.S. and C.F. conceived and designed the experiments. P.C., D.P., J.C., D.W. and H.Z. performed the experiments. J.C. and P.C. analysed the data. K.H., Y.L., P.L. and L.H. contributed materials/analysis tools. Y.S. and G.F. collected DNA samples. P.C., D.P., C.F. and Y.S. co-wrote the paper. P.C. and D.P. contributed equally to this work. All authors discussed the results and commented on the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * Yongyong Shi or * Chunhai Fan Author Details * Peng Chen Search for this author in: * NPG journals * PubMed * Google Scholar * Dun Pan Search for this author in: * NPG journals * PubMed * Google Scholar * Chunhai Fan Contact Chunhai Fan Search for this author in: * NPG journals * PubMed * Google Scholar * Jianhua Chen Search for this author in: * NPG journals * PubMed * Google Scholar * Ke Huang Search for this author in: * NPG journals * PubMed * Google Scholar * Dongfang Wang Search for this author in: * NPG journals * PubMed * Google Scholar * Honglu Zhang Search for this author in: * NPG journals * PubMed * Google Scholar * You Li Search for this author in: * NPG journals * PubMed * Google Scholar * Guoyin Feng Search for this author in: * NPG journals * PubMed * Google Scholar * Peiji Liang Search for this author in: * NPG journals * PubMed * Google Scholar * Lin He Search for this author in: * NPG journals * PubMed * Google Scholar * Yongyong Shi Contact Yongyong Shi Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (706 KB) Supplementary information Additional data - Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response
- Nat Nanotechnol 6(10):645-650 (2011)
Nature Nanotechnology | Letter Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response * Haiyan Li1 * Yuhuan Li2 * Jun Jiao1 * Hong-Ming Hu2 * Affiliations * Contributions * Corresponding authorsJournal name:Nature NanotechnologyVolume: 6,Pages:645–650Year published:(2011)DOI:doi:10.1038/nnano.2011.153Received15 April 2011Accepted17 August 2011Published online18 September 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Therapeutic cancer vaccination is an attractive strategy because it induces T cells of the immune system to recognize and kill tumour cells in cancer patients. However, it remains difficult to generate large numbers of T cells that can recognize the antigens on cancer cells using conventional vaccine carrier systems1, 2. Here we show that α-Al2O3 nanoparticles can act as an antigen carrier to reduce the amount of antigen required to activate T cells in vitro and in vivo. We found that α-Al2O3 nanoparticles delivered antigens to autophagosomes in dendritic cells, which then presented the antigens to T cells through autophagy. Immunization of mice with α-Al2O3 nanoparticles that are conjugated to either a model tumour antigen or autophagosomes derived from tumour cells resulted in tumour regression. These results suggest that α-Al2O3 nanoparticles may be a promising adjuvant in the development of therapeutic cancer vaccines. View full text Subject terms: * Nanoparticles * Nanomedicine Figures at a glance * Figure 1: Conjugation of OVA to α-Al2O3 nanoparticles resulted in efficient cross-presentation of the OVA antigen in vitro. , Schematic showing the structure of the α-Al2O3–OVA conjugate. ,, TEM images of α-Al2O3 nanoparticles (60 nm) before () and after () conjugation with OVA protein. Inset in : high-resolution TEM image of an α-Al2O3 nanoparticle. , Representative bright-field (left), fluorescence (middle) and overlaid (right) images of DCs after incubation with FITC-labelled α-Al2O3 (60 nm)–OVA for 0.5 h (upper) and 24 h (lower). , Surface expression of major histocompatibility complex class I peptide complexes (Kb -SIINFEKL) on DCs without antigen (shadow) and the DCs pulsed with 10 µg ml−1 OVA (red), or α-Al2O3 (60 nm)–OVA containing 0.1 µg ml−1 OVA (green). * Figure 2: DCs pulsed with α-Al2O3–OVA efficiently cross-presented OVA antigen to naive OT-I T cells in vitro and in vivo. –, Flow cytometric analysis showing that DCs loaded with α-Al2O3–OVA induced the proliferation () and secretion of IFN-γ and IL-2 (,) by OT-I CD8+ T cell more efficiently than DCs loaded with either TiO2–OVA or α-Fe2O3–OVA. , DCs loaded with α-Al2O3–OVA were more effective at stimulating naive OT-I T cells in vitro than DCs loaded with OVA immunocomplexes or OVA plus TLR4 agonist. , Subcutaneous injection of α-Al2O3–OVA activated OT-I CD8+ T cells more efficiently than OVA, anatase TiO2–OVA, α-Fe2O3–OVA or the mixture of OVA/alum in vivo. *P < 0.05. Error bars show standard error of the mean. * Figure 3: Autophagy is required for α-Al2O3 nanoparticle-mediated cross-presentation of OVA to naive T cells. , Confocal images of untreated DCs, and DCs loaded with α-Al2O3–OVA and stained with antibody against LC3 (red) (upper panels). Lower panels show DCs expressing tdtomato-LC3 or tdtomato-p62 fusion proteins (red) after loading with FITC-labelled α-Al2O3–OVA. , TEM analysis showing that internalized α-Al2O3–OVA were mainly inside endosomes/phagosomes, autophagosomes and autolysosomes of DCs. –, Flow cytometric analysis showing that cross-presentation of α-Al2O3–OVA by DCs, but not OVA, was blocked by treatment with 3-MA or wortmannin () and by knockdown of the autophagy initiation genes, Beclin 1 or Atg 12 (), and was reduced by Brefeldin A treatment (). Results confirmed by western blot analysis (). Ammonium chloride treatment enhanced cross-presentation of OVA by DCs, but not α-Al2O3–OVA (). * Figure 4: α-Al2O3 nanoparticles increased the efficiency of cross-presentation and antitumour response of cancer vaccines. ,, Vaccination with α-Al2O3–OVA induced a high frequency of OVA-specific IFN-γ producing CD8+ T cells in spleens of mice () and eliminated the established B16-OVA tumours (). , Scanning electron microscopy images of isolated autophagosomes derived from 3LL tumour cells () and of α-Al2O3–autophagosome conjugates (). Inset in : TEM image of an autophagosome. , Flow cytometry profiles showing that DCs loaded with α-Al2O3–autophagosomes (bottom) more efficiently cross-primed naive OT-I T cells than DCs loaded with naked autophagosomes (top) in vitro. , With assistance of the anti-OX40 antibody, α-Al2O3–autophagosome demonstrated high therapeutic efficacy in mice bearing 3LL lung tumours. *P < 0.05. Author information * Abstract * Author information * Supplementary information Affiliations * Department of Physics, Portland State University, Portland, Oregon, USA * Haiyan Li & * Jun Jiao * Laboratory of Cancer Immunobiology, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA * Yuhuan Li & * Hong-Ming Hu Contributions H.L. performed the experiments and wrote the manuscript. Y.L. performed some experiments. J.J. and H-M.H. directed this work and wrote the manuscript. Competing financial interests H.L., J.J. and H-M.H. have filed a patent application titled 'Alumina nanoparticle bioconjugates and methods of stimulating immune response using said bioconjugates'. Y.L. has no competing financial interests. Corresponding authors Correspondence to: * Jun Jiao or * Hong-Ming Hu Author Details * Haiyan Li Search for this author in: * NPG journals * PubMed * Google Scholar * Yuhuan Li Search for this author in: * NPG journals * PubMed * Google Scholar * Jun Jiao Contact Jun Jiao Search for this author in: * NPG journals * PubMed * Google Scholar * Hong-Ming Hu Contact Hong-Ming Hu Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (1,986 KB) Supplementary information Additional data - Graphene oxide windows for in situ environmental cell photoelectron spectroscopy
- Nat Nanotechnol 6(10):651-657 (2011)
Nature Nanotechnology | Article Graphene oxide windows for in situ environmental cell photoelectron spectroscopy * Andrei Kolmakov1 * Dmitriy A. Dikin2 * Laura J. Cote2 * Jiaxing Huang2 * Majid Kazemian Abyaneh3 * Matteo Amati3 * Luca Gregoratti3 * Sebastian Günther4 * Maya Kiskinova3 * Affiliations * Contributions * Corresponding authorJournal name:Nature NanotechnologyVolume: 6,Pages:651–657Year published:(2011)DOI:doi:10.1038/nnano.2011.130Received21 April 2011Accepted14 July 2011Published online28 August 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg The performance of new materials and devices often depends on processes taking place at the interface between an active solid element and the environment (such as air, water or other fluids). Understanding and controlling such interfacial processes require surface-specific spectroscopic information acquired under real-world operating conditions, which can be challenging because standard approaches such as X-ray photoelectron spectroscopy generally require high-vacuum conditions. The state-of-the-art approach to this problem relies on unique and expensive apparatus including electron analysers coupled with sophisticated differentially pumped lenses. Here, we develop a simple environmental cell with graphene oxide windows that are transparent to low-energy electrons (down to 400 eV), and demonstrate the feasibility of X-ray photoelectron spectroscopy measurements on model samples such as gold nanoparticles and aqueous salt solution placed on the back side of a window. These pr! oof-of-principle results show the potential of using graphene oxide, graphene and other emerging ultrathin membrane windows for the fabrication of low-cost, single-use environmental cells compatible with commercial X-ray and Auger microprobes as well as scanning or transmission electron microscopes. View full text Subject terms: * Nanomaterials * Nanometrology and instrumentation Figures at a glance * Figure 1: Design of ambient-pressure XPS systems. , Combination of differential pumping stages and advanced transfer electron optics. For details see the recent review in ref. 16. , An alternative design uses an E-cell with a membrane that is transparent to electrons, but cannot be penetrated by molecules. , Dependence of inelastic mean free path (IMFP) for electrons in carbon on their kinetic energy, calculated using the NIST SRD-71 database38. The shaded light-yellow area corresponds to the kinetic energy of photoelectrons capable of escaping 1-nm-thick membranes (analogous to GO single-layer membranes). * Figure 2: Fabrication of GO windows for E-cells. , Ion-beam milling of the microhole in the primary Si3N4 (or SiO2) membrane. , Deposition of the GO suspended secondary membrane over the ion-milled hole using the Langmuir–Blodgett approach. , SEM image of the resultant deposit (scale bar, 20 µm). , Deposition of the metal colloid nanoparticles on the back side of the membrane. , SEM image and EDX of gold nanoparticle aggregates made through the GO membrane (scale bar, 3 µm). , Enclosed E-cell with ultraviolet-curable sealant placed along the perimeter of the silicon wafer containing the primary Si3N4 and secondary GO membrane. , Magnified (×50) optical image of the front membrane sealing the E-cell filled with water solution. , Magnified (×1,000) optical image showing the GO membrane sealing the window in the filled E-cell. , TEM image (before sealing) of the same GO membrane as in and . Areas with increased numbers of GO sheets can be seen as darker patches (scale bar, 1 µm). * Figure 3: Experimental setup and GO overlayer characterization. , Sketch of the experimental setup for photoelectron imaging and electron attenuation experiments. , Non-contact AFM topology image of GO deposit on the gold/silicon substrate. Scale bar, 2.5 µm. , Z-height histogram taken for the square area in . , 3D Au 4f map of the gold sample, where discrete colour (Au 4f signal intensity) changes correspond to different local GO thicknesses. * Figure 4: Principle of effective attenuation length measurements of GO sheets. , 2D Au 4f map of the gold sample, with the grey scale contrast (Au 4f signal intensity) changes corresponding to different local GO thicknesses. , Microspot Au 4f spectra taken at different locations depicted as white circles in . The spot corresponding to 9-ML-thick GO is beyond the perimeter of . , Log plot of Au 4f intensity attenuation as a function of the number of GO overlayers. Data point sets were taken from different areas of independently prepared samples, and the slope of the fitting line defines –(λEAL·cosθ)−1. * Figure 5: Suspended GO membranes as windows for an E-cell. , SEM image of the suspended membrane before gold deposition. ,, TEM/HRTEM images after deposition of a few nanometres of gold on the membrane back side. The SAED pattern in shows a typical diffraction pattern from gold deposit, characteristic for randomly oriented fcc gold nanoparticles. ,, Au 4f7/2 and C 1s chemical maps of the GO membrane with percolating gold nanoparticles on the back side. , Survey (bottom right), C 1s (bottom left) and Au 4f (top) photoelectron spectra taken at locations A, B and C in . * Figure 6: XPS on wet samples. Top inset: 40 × 50 µm2 SPEM image of the GO membrane with 3 M NaI aqueous solution on the back side taken with Au 4f7/2 photoelectrons. The bottom inset is an enlarged 12 × 12 µm2 area around the membrane. Point A is at the centre of the GO membrane, and point B is ~30 µm away. Top and bottom spectra were taken at points B and A, respectively. In addition to the common O 1s spectrum from the dry area, the spectrum from the membrane contains H2O vapour and liquid contributions from the enclosed cell compartment. The red dots indicate the raw data points of the O 1s spectra, and the small dark spots represent the interpolated spectrum used for peak deconvolution analysis. The green curve depicts a sum of the fitted peaks. The fitting details can be found in the Methods. Author information * Abstract * Author information * Supplementary information Affiliations * Southern Illinois University, Carbondale, Illinois 62901, USA * Andrei Kolmakov * Northwestern University, Evanston, Illinois 60208, USA * Dmitriy A. Dikin, * Laura J. Cote & * Jiaxing Huang * Sincrotrone Trieste 34012 Trieste, Italy * Majid Kazemian Abyaneh, * Matteo Amati, * Luca Gregoratti & * Maya Kiskinova * TU München, Chemie Department, Lichtenbergstr. 4, D-85748 Garching, Germany * Sebastian Günther Contributions A.K. conceived the project, designed and tested the E-cell prototypes, and assembled the manuscript, with contributions from all co-authors. D.D., L.C. and J.H. developed the methods of GO synthesis, processing and Langmuir–Blodgett deposition onto SiO2/Si3N4 membrane samples. D.D. performed all micromachining and carried out SEM, TEM and HRTEM characterization of the GO overlayers and suspended membranes. M.K.A., M.A., L.G., S.G. and M.K conducted the SPEM experiments and the corresponding data analysis of the photoelectron images and spectra. A.K. and S.G. participated in spectromicroscopy tests as users of the ELETTRA ESCA microscopy beamline. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Andrei Kolmakov Author Details * Andrei Kolmakov Contact Andrei Kolmakov Search for this author in: * NPG journals * PubMed * Google Scholar * Dmitriy A. Dikin Search for this author in: * NPG journals * PubMed * Google Scholar * Laura J. Cote Search for this author in: * NPG journals * PubMed * Google Scholar * Jiaxing Huang Search for this author in: * NPG journals * PubMed * Google Scholar * Majid Kazemian Abyaneh Search for this author in: * NPG journals * PubMed * Google Scholar * Matteo Amati Search for this author in: * NPG journals * PubMed * Google Scholar * Luca Gregoratti Search for this author in: * NPG journals * PubMed * Google Scholar * Sebastian Günther Search for this author in: * NPG journals * PubMed * Google Scholar * Maya Kiskinova Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (1,133 KB) Supplementary information Additional data - Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics
- Nat Nanotechnol 6(10):658-667 (2011)
Nature Nanotechnology | Article Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics * Dan Shu1, 3 * Yi Shu1, 3 * Farzin Haque1, 3 * Sherine Abdelmawla2 * Peixuan Guo1 * Affiliations * Contributions * Corresponding authorJournal name:Nature NanotechnologyVolume: 6,Pages:658–667Year published:(2011)DOI:doi:10.1038/nnano.2011.105Received01 April 2011Accepted08 June 2011Published online11 September 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg RNA nanoparticles have applications in the treatment of cancers and viral infection; however, the instability of RNA nanoparticles has hindered their development for therapeutic applications. The lack of covalent linkage or crosslinking in nanoparticles causes dissociation in vivo. Here we show that the packaging RNA of bacteriophage phi29 DNA packaging motor can be assembled from 3–6 pieces of RNA oligomers without the use of metal salts. Each RNA oligomer contains a functional module that can be a receptor-binding ligand, aptamer, short interfering RNA or ribozyme. When mixed together, they self-assemble into thermodynamically stable tri-star nanoparticles with a three-way junction core. These nanoparticles are resistant to 8 M urea denaturation, are stable in serum and remain intact at extremely low concentrations. The modules remain functional in vitro and in vivo, suggesting that the three-way junction core can be used as a platform for building a variety of multifunc! tional nanoparticles. We studied 25 different three-way junction motifs in biological RNA and found only one other motif that shares characteristics similar to the three-way junction of phi29 pRNA. View full text Subject terms: * Nanobiotechnology * Nanomedicine Figures at a glance * Figure 1: Sequence and secondary structure of phi29 DNA-packaging RNA. , Illustration of the phi29 packaging motor geared by six pRNAs (cyan, purple, green, pink, blue and orange structures). , Schematic showing a pRNA hexamer assembled through hand-in-hand interactions of six pRNA monomers. , Sequence of pRNA monomer Ab′ (ref. 3). Green box: central 3WJ domain. In pRNA Ab′, A and b′ represent right- and left-hand loops, respectively. , 3WJ domain composed of three RNA oligomers in black, red and blue. Helical segments are represented as H1, H2, H3. ,, A trivalent RNA nanoparticle consisting of three pRNA molecules bound at the 3WJ-pRNA core sequence (black, red and blue) () and its accompanying AFM images (). Ab′ indicates non-complementary loops35. * Figure 2: Assembly and stability studies of 3WJ-pRNA. In the tables, '+' indicates the presence of the strand in samples of the corresponding lanes. , 15% native PAGE showing the assembly of the 3WJ core, stained by ethidium bromide (upper) and SYBR Green II (lower). , Tm melting curves for the assembly of the 3WJ core. Melting curves for the individual strands (brown, green, silver), the two-strand combinations (blue, cyan, pink) and the three-strand combination (red) are shown. , Oligo sequences of 3WJ-pRNA cores and mutants. 'del U', deletion of U bulge; 'del UUU', deletion of UUU bulge; 'del 4-nt', deletion of two nucleotides at the 3′ and 5′ ends, respectively. , Length requirements for the assembly of 3WJ cores and stability assays by urea denaturation. , Comparison of DNA and RNA 3WJ core in native and urea gel. * Figure 3: Competition and dissociation assays of 3WJ-pRNA. , Temperature effects on the stability of the 3WJ-pRNA core, denoted as [ab*c]3WJ, evaluated by 16% native gel. A fixed concentration of Cy3-labelled [ab*c]3WJ was incubated with varying concentrations of unlabelled b3WJ at 25, 37 and 55 °C. , Urea denaturing effects on the stability of [ab*c]3WJ evaluated by 16% native gel. A fixed concentration of labelled [ab*c]3WJ was incubated with unlabelled b3WJ at ratios of 1:1 and 1:5 in the presence of 0–6 M urea at 25 °C. , Dissociation assay for the [32P]-3WJ-pRNA complex harbouring three monomeric pRNAs by twofold serial dilution (lanes 1–9). The monomer unit is shown on the left. * Figure 4: Construction of multi-module RNA nanoparticles harbouring siRNA, ribozyme and aptamer. , Assembly of RNA nanoparticles with functionalities using 3WJ-pRNA and 3WJ-5S rRNA as scaffolds. –, Illustration (), 8% native (upper) and denaturing (lower) PAGE gel () and AFM images () of 3WJ-pRNA-siSur-Rz-FA nanoparticles. ,, Assessing the catalytic activity of the HBV ribozyme incorporated into the 3WJ-pRNA () and 3WJ-5S rRNA () cores, evaluated in 10% 8 M urea PAGE. The cleaved RNA product is boxed. Positive control: pRNA/HBV-Rz; negative control: 3WJ-RNA/siSur-MG-FA. ,, Functional assay of the MG aptamer incorporated in RNA nanoparticles using the 3WJ-pRNA () and 3WJ-5S rRNA () cores. MG fluorescence was measured using excitation wavelengths of 475 and 615 nm. * Figure 5: In vitro and in vivo binding and entry of 3WJ-pRNA nanoparticles into targeted cells. , Flow cytometry revealed the binding and specific entry of fluorescent-[3WJ-pRNA-siSur-Rz-FA] nanoparticles into folate-receptor-positive (FA+) cells. Positive and negative controls were Cy3-FA-DNA and Cy3-[3WJ-pRNA-siSur-Rz-NH2] (without FA), respectively. , Confocal images showed targeting of FA+-KB cells by co-localization (overlap, 4) of cytoplasm (green, 1) and RNA nanoparticles (red, 2) (magnified, bottom panel). Blue–nuclei, 3. ,, Target gene knock-down effects shown by () qRT–PCR with GADPH as endogenous control and by () western blot assay with β-actin as endogenous control. , 3WJ-pRNA nanoparticles target FA+ tumour xenografts on systemic administration in nude mice. Upper panel: whole body; lower panel: organ imaging (Lv, liver; K, kidney; H, heart; L, lung; S, spleen; I, intestine; M, muscle; T, tumour). * Figure 6: Comparison of different 3WJ-RNA cores. , Assembly and stability of 11 3WJ-RNA core motifs assayed in 16% native (upper) and 16% 8 M urea (lower) PAGE gel. , Melting curves for each of the 11 RNA 3WJ core motifs assembled from three oligos for each 3WJ motif under physiological buffer TMS. Refer to Table 1 for the respective Tm values. Author information * Abstract * Author information * Supplementary information Primary authors * These authors contributed equally to this work * Dan Shu, * Yi Shu & * Farzin Haque Affiliations * Nanobiomedical Center, University of Cincinnati, Cincinnati, Ohio 45267, USA * Dan Shu, * Yi Shu, * Farzin Haque & * Peixuan Guo * Kylin Therapeutics, West Lafayette, Indiana 47906, USA * Sherine Abdelmawla Contributions P.G. conceived, designed and led the project. D.S., Y.S. and F.H. designed and conducted the in vitro experiments. S.A. performed animal imaging experiments. P.G., D.S., Y.S. and F.H. analysed the data and co-wrote the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Peixuan Guo Author Details * Dan Shu Search for this author in: * NPG journals * PubMed * Google Scholar * Yi Shu Search for this author in: * NPG journals * PubMed * Google Scholar * Farzin Haque Search for this author in: * NPG journals * PubMed * Google Scholar * Sherine Abdelmawla Search for this author in: * NPG journals * PubMed * Google Scholar * Peixuan Guo Contact Peixuan Guo Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (1,902 KB) Supplementary information Additional data - Nanopore-based detection of circulating microRNAs in lung cancer patients
- Nat Nanotechnol 6(10):668-674 (2011)
Nature Nanotechnology | Article Nanopore-based detection of circulating microRNAs in lung cancer patients * Yong Wang1, 3 * Dali Zheng2, 3 * Qiulin Tan1 * Michael X. Wang2 * Li-Qun Gu1 * Affiliations * Contributions * Corresponding authorsJournal name:Nature NanotechnologyVolume: 6,Pages:668–674Year published:(2011)DOI:doi:10.1038/nnano.2011.147Received26 April 2011Accepted29 July 2011Published online04 September 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg MicroRNAs are short RNA molecules that regulate gene expression, and have been investigated as potential biomarkers because their expression levels are correlated with various diseases. However, detecting microRNAs in the bloodstream remains difficult because current methods are not sufficiently selective or sensitive. Here, we show that a nanopore sensor based on the α-haemolysin protein can selectively detect microRNAs at the single molecular level in plasma samples from lung cancer patients without the need for labels or amplification of the microRNA. The sensor, which uses a programmable oligonucleotide probe to generate a target-specific signature signal, can quantify subpicomolar levels of cancer-associated microRNAs and can distinguish single-nucleotide differences between microRNA family members. This approach is potentially useful for quantitative microRNA detection, the discovery of disease markers and non-invasive early diagnosis of cancer. View full text Subject terms: * Nanomedicine * Nanosensors and other devices Figures at a glance * Figure 1: Capturing single microRNA molecules in the nanopore. , Molecular diagram of a microRNA (red) bound to a probe (green) bearing signal tags on each end. , Sequence of nanopore current blocks in the presence of 100 nM miR-155 and 100 nM P155 in the cis solution. Traces were recorded at +100 mV in solutions containing 1 M KCl buffered with 10 mM Tris (pH 8.0). Red boxes represent the multi-level current pattern. , A typical multi-level long block (from ) at +100 mV generated by the miR-155·P155 hybrid. Right panel: diagram showing the molecular mechanism of hybrid dissociation and translocation. Level 1: trapping of the microRNA·probe hybrid in the pore, unzipping of the microRNA from the probe and translocation of the probe through the pore. Level 2: unzipped microRNA residing in the pore cavity. Level 3: translocation of the unzipped microRNA through the pore. Lower panel: multi-level blocks at +150 and +180 mV. Increasing the voltage reduced the duration of Levels 1 and 3, which supports the above mechanistic model. , miR-155! levels detected by qRT-PCR in trans solutions. Before detection, the pore current was monitored in 0.5 M/3 M (cis/trans) KCl at +180 mV in the presence of 1 µM P155 and 0.5, 1 or 10 nM of miR-155 in the cis solution. A much higher probe concentration than microRNA was used to enhance their hybridization in the cis solution (see Supplementary Information S1). , A single-level block (from ) generated by a trapped miR-155·P155 hybrid that exited the pore from the cis entrance without unzipping and translocation. , A spike-like short block generated by the translocation of unhybridized miR-155 or P155 from the cis solution. * Figure 2: Optimizing the probe sequence for enhanced detection sensitivity. , Left panel: current traces showing the frequencies of signature events for miR-155 hybridized to the probes P5′-C30 (top), P3′-C30 (middle) and P155 (bottom), monitored at +100 mV in 1 M KCl. Right panel: occurrence rate constant of signature events for miR-155 detection with different probes (see Supplementary Table S3 for details). , Left panel: [miR-155]—f155 correlation for target concentration ranges between 10 and 100 nM in 1 M KCl. Right panel: [miR-155]—f155 correlation measured in 0.2 M/3 M (cis/trans) KCl with much lower target concentrations (between 0.1 and 100 pM). Data in both panels were measured at +100 mV. The results between any two miR-155 concentrations were statistically significant (P < 0.01). * Figure 3: Differentiation of let-7 microRNAs that contain one or two different nucleotides. The sequences of let-7a, let-7b and let-7c are provided in Supplementary Table S1. , Detection of let-7a and let-7b using the probe Pa or Pb at +120 mV. Left: current traces. Right: duration of signature events. , Detection of let-7a and let-7c using the probe Pa or Pc at +100 mV. Left: current traces. Right: duration of signature events. See Supplementary Fig. S4 for a representative histogram and Supplementary Table S4 for raw data. , ROC curves for the discrimination of events for fully matched microRNA·probe hybrids (defined as positive events) and microRNA·probe hybrids containing mismatched base pairs (defined as negative events). Open squares: let-7a·Pa/let-7c·Pa; open circles: let-7c·Pc/let-7a·Pc ; filled squares: let-7a·Pa/let-7b·Pa; filled circles: let-7b·Pb/let-7a·Pb. , Correlations between AUCs and the ratio of event duration for fully matched hybrids to those with mismatched base pairs. Filled circles: AUCs measured from the ROC curves in (Supplement! ary Table S5); open circles: AUCs calculated from ROC analyses based on simulated data sets (Supplementary Fig. S5 and Table S6). The computer-generated event duration followed an exponential distribution. The ratios of event duration for ROC analysis were 1, 2, 3, 4, 5 and 10. * Figure 4: Detection of miR-155 in the plasma of lung cancer patients. –, Current traces for total plasma RNAs from healthy volunteers (normal sample) and lung cancer patients without (,) and with (,) the P155 probe. Traces were recorded in 1 M KCl at +100 mV. Red arrows are signature events. Signature events were seen only in the presence of the 100 nM probe for both healthy volunteers () and lung cancer patients (). , Frequencies of miR-155 signature events (f155) from six healthy individuals (1–6) and six patients with lung cancer (7–12) in the presence of spiked-in synthetic miR-39. , Frequencies of miR-39 signature events detected using P39 (sequence in Supplementary Table S1) from all the samples that were used in . Each sample was measured n times (n ≥ 4) using independent nanopores. Data are mean ± s.d. Conditions of patients: 7, metastatic squamous lung carcinoma; 8, recurrent small-cell cancer; 9, early-stage small-cell carcinoma, status post-chemotherapy and radiation; 10, early-stage small-cell cancer, status post-chemother! apy; 11, late-stage non-small-cell carcinoma, status post-resection and post-chemotherapy; 12, late-stage adenocarcinoma, status post-chemotherapy. , f155/f39 calculated from panels and . , Box and whisker plots of the relative miR-155 levels in healthy and lung cancer groups measured with the nanopore sensor and qRT-PCR. Boxes mark the intervals between the 25th and 75th percentiles. Black lines inside the boxes denote medians. Whiskers denote the intervals between the 5th and 95th percentiles. Filled circles indicate data points outside the 5th and 95th percentiles (see Supplementary Table S7 for raw data). Author information * Abstract * Author information * Supplementary information Primary authors * These authors contributed equally to this work * Yong Wang & * Dali Zheng Affiliations * Department of Biological Engineering and Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211 * Yong Wang, * Qiulin Tan & * Li-Qun Gu * Ellis Fischel Cancer Center and Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65211, USA * Dali Zheng & * Michael X. Wang Contributions Y.W. designed and performed the nanopore experiments, collected and analysed the nanopore data, and co-wrote the manuscript. D.Z. designed and performed the qRT-PCR experiments, analysed the qRT-PCR data and co-wrote the manuscript. Q.T. performed molecular biology experiments, including protein synthesis. M.X.W. conceived the qRT-PCR experiments, provided the patients' samples and co-wrote the manuscript. L-Q.G. conceived the principal idea, designed the nanopore experiments and wrote the manuscript. All the authors discussed the results and commented on the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * Li-Qun Gu or * Michael X. Wang Author Details * Yong Wang Search for this author in: * NPG journals * PubMed * Google Scholar * Dali Zheng Search for this author in: * NPG journals * PubMed * Google Scholar * Qiulin Tan Search for this author in: * NPG journals * PubMed * Google Scholar * Michael X. Wang Contact Michael X. Wang Search for this author in: * NPG journals * PubMed * Google Scholar * Li-Qun Gu Contact Li-Qun Gu Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (692 KB) Supplementary information Additional data - A multifunctional core–shell nanoparticle for dendritic cell-based cancer immunotherapy
- Nat Nanotechnol 6(10):675-682 (2011)
Nature Nanotechnology | Article A multifunctional core–shell nanoparticle for dendritic cell-based cancer immunotherapy * Nam-Hyuk Cho1, 2, 3, 8 * Taek-Chin Cheong1, 2, 4, 8 * Ji Hyun Min5, 6, 8 * Jun Hua Wu6, 8 * Sang Jin Lee4 * Daehong Kim4 * Jae-Seong Yang7 * Sanguk Kim7 * Young Keun Kim5, 6 * Seung-Yong Seong1, 2, 6 * Affiliations * Contributions * Corresponding authorsJournal name:Nature NanotechnologyVolume: 6,Pages:675–682Year published:(2011)DOI:doi:10.1038/nnano.2011.149Received03 May 2011Accepted04 August 2011Published online11 September 2011 Abstract * Abstract * Author information * Supplementary information Article tools * Full text * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Dendritic cell-based cancer immunotherapy requires tumour antigens to be delivered efficiently into dendritic cells and their migration to be monitored in vivo. Nanoparticles have been explored as carriers for antigen delivery, but applications have been limited by the toxicity of the solvents used to make nanoparticles, and by the need to use transfection agents to deliver nanoparticles into cells. Here we show that an iron oxide–zinc oxide core–shell nanoparticle can deliver carcinoembryonic antigen into dendritic cells while simultaneously acting as an imaging agent. The nanoparticle–antigen complex is efficiently taken up by dendritic cells within one hour and can be detected in vitro by confocal microscopy and in vivo by magnetic resonance imaging. Mice immunized with dendritic cells containing the nanoparticle–antigen complex showed enhanced tumour antigen specific T-cell responses, delayed tumour growth and better survival than controls. View full text Subject terms: * Nanomedicine Figures at a glance * Figure 1: Characterization of the Fe3O4–ZnO core–shell nanoparticle. , Left: diagram of the core–shell nanoparticle. Right: TEM image of the monodispersed spherical particles. , Point-probe analysis using TEM equipped with EDX, showing that the single nanoparticle consists of both Fe and Zn. , Photographs showing the homogeneous dispersion of nanoparticles (brown) in phosphate-buffered saline (top) and clear transparent solution after collecting the nanoparticles by applying an external magnet (bottom). , Magnetic hysteresis curves of the Fe3O4 core part (red) and the Fe3O4–ZnO nanoparticles (blue). Inset: details of the hysteresis curves around zero field. , Photoluminescence spectrum of the peptide-linked nanoparticles showing both UV and visible emissions. * Figure 2: Immobilization of polypeptide on the nanoparticle. , Graphical sequence logo representation of ZnO-binding motifs. The conserved sequence pattern was generated using WebLogo3 (http://weblogo.berkeley.edu/). Bits represent the relative frequency of amino acids. ,, Detection of the interaction of ZnO-binding peptide (ZBP) with the nanoparticle by isothermal titration calorimetry (ITC). Binding affinity was measured by ITC of 1 × ZBP () or 3 × ZBP () (0.25 mM each) with a solution of nanoparticle (4 µM). The ITC raw data (top) and the integrated heat data (bottom), corrected for dilution, are shown. , Gel electrophoresis data showing nanoparticle-bound CEA after incubation with nanoparticles (50 µg) and the indicated amounts of CEA with or without 3 × ZBP fusion. Bound CEA was resolved by sodium dodecyl sulphate polyacrylamide gel electrophoresis after extensive washing of nanoparticles. * Figure 3: Intracellular delivery of the nanoparticles into DCs. , Intracellular nanoparticles visualized by DAB-enhanced Prussian blue staining of DCs labelled with 100 µg ml−1 of Fe3O4 nanoparticles or Fe3O4–ZnO nanoparticles after incubation for the indicated time. , Optical intensities of 100 randomly selected cells from each sample in . Error bars, standard error of the mean. , Fluorescence images of DCs loaded without (top) or with (bottom) nanoparticles (green). Nuclei (blue) were stained with ToPro-3. DIC, differential interference contrast. , Fluorescence images of DCs incubated with nanoparticle–3 × ZBP complexes. Intracellular 3 × ZBP (green) was stained together with EEA1 (endosomes) or LAMP2 (lysosomes). , Flow cytometric analysis of DCs incubated with nanoparticle-recombinant CEA complexes. The mean fluorescence intensities of intracellular CEA (line) were shown within the histograms. Grey histogram, isotype control. * Figure 4: In vitro and in vivo MRI of nanoparticle-labelled DCs. , In vitro MRI image (top) of DCs labelled with different amounts of Fe3O4–ZnO nanoparticles for 1 h and T2 relaxation time plot (bottom). , In vitro MRI images (top) and T2 relaxation time plot (bottom) of DCs incubated with 40 µg ml−1 Fe3O4–ZnO or Fe3O4 nanoparticles for the indicated time. , In vivo MRI images of draining lymph nodes of a mouse (left) injected with DCs labelled with Fe3O4–ZnO (red arrow) or ZnO nanoparticles (yellow arrow) into the ipsilateral footpads. Right shows a draining lymph node (green arrow) of cell-free Fe3O4–ZnO nanoparticle-injected mouse. , Representative immunohistochemistry of draining lymph node after injection with Fe3O4–ZnO nanoparticle-labelled DCs (dark brown dots). T, T-cell zone (Thy1.2+), B, B-cell follicle (B220+). * Figure 5: Induction of CEA-specific immunity. , In vitro proliferation of lymphocytes from immunized mice after CEA stimulation. Mice were immunized with DCs loaded with nanoparticle/3 × ZBP–CEA (open red squares), nanoparticle/CEA (filled red squares), 3 × ZBP–CEA (open blue triangles), CEA (filled blue triangles), nanoparticle (open black circles) or DC only (filled black circles). Error bars, standard error of three independent experiments. , CEA-specific cytotoxic activity of splenocytes from immunized mice. MC38 cells with (MC38/CEA) or without (MC38) CEA expression were used as targets. Symbols as in . , CEA-specific, IFN-γ+ CD8+ T-cell responses of mice immunized with DCs as in . IFN-γ+ CTLs in splenocytes were detected in the presence (+) or absence (–) of CEA. Left panel: representative dot plots. Right panel: average percentiles of the CTL from three independent experiments. *P < 0.05 by Student's t-test. * Figure 6: Tumour growth and survival of immunized mice. , Tumour volume (left) and survival rate (right) of mice (5 mice/group) injected with MC38/CEA cells. Mice were immunized with DCs, loaded with nanoparticle/3 × ZBP–CEA (open red squares), nanoparticle/CEA (filled red squares), 3 × ZBP–CEA (open blue triangles), CEA (filled blue triangles), nanoparticle (open black circles) or DC only (filled black circles), four times at weekly intervals starting one week after tumour injection. , Tumour growth in human CEA-transgenic mice (5 mice/group) inoculated with MC38/CEA cells. Mice were immunized with DCs three times at weekly intervals and the symbols are the same as in . Error bars, standard error of the mean. *P < 0.05 by Student's t-test for tumour volumes and P < 0.01 using the Kaplan–Meier method (log-rank test). Author information * Abstract * Author information * Supplementary information Primary authors * These authors contributed equally to this work * Nam-Hyuk Cho, * Taek-Chin Cheong, * Ji Hyun Min & * Jun Hua Wu Affiliations * Department of Microbiology and Immunology, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea * Nam-Hyuk Cho, * Taek-Chin Cheong & * Seung-Yong Seong * Department of Biomedical Sciences, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea * Nam-Hyuk Cho, * Taek-Chin Cheong & * Seung-Yong Seong * Bundang Hospital, Seoul, Republic of Korea * Nam-Hyuk Cho * Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea * Taek-Chin Cheong, * Sang Jin Lee & * Daehong Kim * Department of Materials Science and Engineering, Korea University, Seoul, Republic of Korea * Ji Hyun Min & * Young Keun Kim * Pioneer Research Center for Biomedical Nanocrystals, Korea University, Seoul, Republic of Korea * Ji Hyun Min, * Jun Hua Wu, * Young Keun Kim & * Seung-Yong Seong * Department of Life Science and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyungbuk, Republic of Korea * Jae-Seong Yang & * Sanguk Kim Contributions N-H.C., S-Y.S. and Y.K.K. conceived and designed the experiments. T-C.C., J.H.M., J.H.W., S.J.L., D.H.K., J-S.Y. and S.K. performed the experiments. N-H.C., S-Y.S. and Y.K.K. analysed the data and wrote the paper. All authors discussed the results and commented on the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * Seung-Yong Seong or * Young Keun Kim Author Details * Nam-Hyuk Cho Search for this author in: * NPG journals * PubMed * Google Scholar * Taek-Chin Cheong Search for this author in: * NPG journals * PubMed * Google Scholar * Ji Hyun Min Search for this author in: * NPG journals * PubMed * Google Scholar * Jun Hua Wu Search for this author in: * NPG journals * PubMed * Google Scholar * Sang Jin Lee Search for this author in: * NPG journals * PubMed * Google Scholar * Daehong Kim Search for this author in: * NPG journals * PubMed * Google Scholar * Jae-Seong Yang Search for this author in: * NPG journals * PubMed * Google Scholar * Sanguk Kim Search for this author in: * NPG journals * PubMed * Google Scholar * Young Keun Kim Contact Young Keun Kim Search for this author in: * NPG journals * PubMed * Google Scholar * Seung-Yong Seong Contact Seung-Yong Seong Search for this author in: * NPG journals * PubMed * Google Scholar Supplementary information * Abstract * Author information * Supplementary information PDF files * Supplementary information (881 KB) Supplementary information Additional data
No comments:
Post a Comment