Biologists are increasingly interested in the behaviour of individual cells, rather than the one of an entire cell population. A new method developed at Eidgenössische Technische Hochschule (ETH) Zürich could revolutionise single cell analysis. The technology uses the world’s smallest syringe to sample the content of individual cells for molecular analyses. ETH researchers have developed a method using a nanosyringe whose tiny needle is able to penetrate single living cells and extract their content. The technology can be used for cell cultures, for example, in order to investigate the interior of the cells. This allows scientists to identify the differences between individual cells at the molecular level, as well as to identify and analyse rare cell types. “Our method opens up new frontiers in biological research. It is the start of a whole new chapter, so to speak”, says Professor Julia Vorholt from the Department of Biology. The new method has numerous advantages: researchers can sample individual cells of a tissue culture directly in the petri dish. “This means we can study how a cell affects its neighbouring cells”, says Orane Guillaume-Gentil, a postdoc in Professor Vorholt’s research group. This type of investigation is not possible using conventional methods, as molecular analyses generally require the cells to first be physically separated and then destroyed. On top of that, the microscopic needle can be controlled so precisely that scientists are able either to harvest the content of the nucleus or collect the intracellular fluid surrounding the nucleus, the cytosol. Last but not least, the researchers can determine the amount of intracellular material they extract with incredible accuracy, down to one tenth of a pictolitre (one trillionth of a litre). By way of comparison: the volume of a cell is 10 to 100 times bigger.
What's New in Nanotechnology?
The fountain of youth may reside in an embryonic stem cell gene named Nanog. In a series of experiments at the University at Buffalo, the gene kicked into action dormant cellular processes that are key to preventing weak bones, clogged arteries and other telltale signs of growing old. The findings also show promise in counteracting premature aging disorders such as Hutchinson-Gilford progeria syndrome. “Our research into Nanog is helping us to better understand the process of aging and ultimately how to reverse it,” says Stelios T. Andreadis, PhD, professor and chair of the Department of Chemical and Biological Engineering at the UB School of Engineering and Applied Sciences, and the study’s lead author. To battle aging, the human body holds a reservoir of nonspecialized cells that can regenerate organs. These cells are called adult stem cells, and they are located in every tissue of the body and respond rapidly when there is a need. But as people age, fewer adult stem cells perform their job well, a scenario which leads to age-related disorders. Reversing the effects of aging on adult stem cells, essentially rebooting them, can help overcome this problem. In the study, Panagiotis Mistriotis, a graduate student in Andreadis’ lab and first author of the study, introduced Nanog into aged stem cells. He found that Nanog opens two key cellular pathways: Rho-associated protein kinase (ROCK) and Transforming growth factor beta (TGF-β). In turn, this jumpstarts dormant proteins (actin) into building cytoskeletons that adult stem cells need to form muscle cells that contract. Force generated by these cells ultimately helps restore the regenerative properties that adult stem cells lose due to aging.
A team led by University of Washington engineers has developed a new tool that could aid in the quest for better batteries and fuel cells. Although battery technology has come a long way since Alessandro Volta first stacked metal discs in a “voltaic pile” to generate electricity, major improvements are still needed to meet the energy challenges of the future, such as powering electric cars and storing renewable energy cheaply and efficiently. The key likely lies in the nanoscale, said Jiangyu Li, University of Washington professor of mechanical engineering. Li and his colleagues describe a nanoscale probe that offers a new window into this world to help scientists better understand how batteries really work. Research in the last 10 to 15 years has revealed just how much local variations in material properties can affect the performance of batteries and other electrochemical systems, Li said. The complex nanoscale landscape makes it tricky to fully understand what’s going on, but “it may also create new opportunities to engineer material properties so as to achieve quantum leaps in performance,” he said.To get a better understanding of how chemical reactions progress at the level of atoms and molecules, Li and his colleagues developed a nanoscale probe. The method is similar to atomic force microscopies: a tiny cantilever “feels” the material and builds a map of its properties with a resolution of nanometers or smaller. The device identifies the Vegard strain-induced vibrations and can extrapolate the concentration of ions and electronic defects near the probe tip. “By measuring these properties locally on the nanoscale, we can build a much better understanding of how electrochemical systems really work, and thus how to develop new materials with much higher performance,” Li said.
The next generation of nanosubmarines being developed at Rice University has been upgraded with tags that fluoresce longer, which enables the submersibles to be tracked for greater periods while being driven through a solution. The single-molecule vehicles introduced by the Rice lab of chemist James Tour last year may someday be used to deliver drugs or other cargo. The new version was built and tested with collaborators at Tel Aviv University in Israel. The first nanosub, USN-1, could be monitored but not imaged by a technique that would irradiate it with light for very short times. But that did not offer information about the submersible’s trajectory, according to lead author Víctor García-Lopéz, a former Rice graduate student. The latest model, the 334-atom USN-2, can be viewed by single-molecule microscopy for at least 1.5 seconds, long enough for 30 frames of video. “This makes it possible for us to track the trajectory of a single nanosubmersible,” Tour said. “It should lead to a better understanding of how our vehicles move.”
The lab attached cyclooctatetraene (COT) to the molecule’s body and motor to keep them from bleaching, which quenches fluorescence. The light-driven motor developed by scientists in the Netherlands is a tail-like ligand that spins about a million times per second. The new subs, like the originals, are capable of moving 15 meters per second over nanoscale distances, based on the thrust provided by each turn of the rotating motor. Between the frequent collisions that stop their forward motion, Tour said, they are “the fastest-moving molecules ever seen in solution.” The nanosubmarines still can’t be steered in the traditional sense, Tour said. The team is satisfied for the moment with achieving “enhanced diffusion” that lets them figure out how to move a one-molecule vehicle in a solution of similarly sized molecules. “The next step is to track these nanosubmarines in solution and see if we can use them to deliver cargo or interact with cells,” Tour said.
Scientists are working diligently to prepare for the expected increase in global population — and therefore an increased need for food production— in the coming decades. A team of engineers at Washington University in St. Louis has found a sustainable way to boost the growth of a protein-rich bean by improving the way it absorbs much-needed nutrients.Ramesh Raliya, a research scientist, and Pratim Biswas, the Lucy & Stanley Lopata Professor and chair of the Department of Energy, Environmental & Chemical Engineering, both in the School of Engineering & Applied Science, discovered a way to reduce the use of fertilizer made from rock phosphorus and still see improvements in the growth of food crops by using zinc oxide nanoparticles. Raliya said this is the first study to show how to mobilize native phosphorus in the soil using zinc oxide nanoparticles over the life cycle of the plant, from seed to harvest. Food crops need phosphorus to grow, and farmers are using more and more phosphorus-based fertilizer as they increase crops to feed a growing world population. However, the plants can only use about 42 percent of the phosphorus applied to the soil, so the rest runs off into the water streams, where it grows algae that pollutes our water sources. In addition, nearly 82 percent of the world’s phosphorus is used as fertilizer, but it is a limited supply, Raliya says. Raliya and his collaborators, including Jagadish Chandra Tarafdar at the Central Arid Zone Research Institute in Jodhpur, India, created zinc oxide nanoparticles from a fungus around the plant’s root that helps the plant mobilize and take up the nutrients in the soil. Zinc also is an essential nutrient for plants because it interacts with three enzymes that mobilize the complex form of phosphorus in the soil into a form that plants can absorb. When Raliya and the team applied the zinc nanoparticles to the leaves of the mung bean plant, it increased the uptake of the phosphorus by nearly 11 percent and the activity of the three enzymes by 84 percent to 108 percent. That leads to a lesser need to add phosphorus on the soil, Raliya said.
Rice University researchers who developed the first nanocars and colleagues at North Carolina State University found in recent tests that driving their vehicles in ambient conditions – exposed to open air, rather than a vacuum – got dicey after a time because the hydrophobic single-molecule cars stuck to the “road” and created what amounted to large speed bumps. The work by Rice chemist James Tour, NC State analytical chemist Gufeng Wang and their colleagues came as Rice prepares to take part in the first NanoCar Race in Toulouse, France, in October. Rice researchers are members of one of five international teams that plan to enter the competition. Just like in the macro world, driving conditions are important for moving nanocars. Though the race will be run in an ultra-cold vacuum, the Rice researchers thought it wise to study how their latest model of nanocars would fare in a more natural setting. “Our long-term goal is to make nanomachines that operate in ambient environments,” Tour said. “That’s when they will show potential to become useful tools for medicine and bottom-up manufacturing.” The newest generation of Rice nanocars features adamantane wheels that are slightly hydrophobic (water-repellent). Tour said some hydrophobicity is important to help keep the nanocars attached to a surface, but if the tires are too hydrophobic, the cars could become permanently immobilized. That is because hydrophobic things tend to stick together to minimize the amount of surface area that is in contact with water. Things that are hydrophilic, or water-liking, are more amenable to floating freely in water, Tour said. In the latest Rice tests with the new tires, the nanocars were placed on surfaces that were either clean glass or glass coated with the polymer polyethylene glycol (PEG). Glass is the most frequently used substrate in nanocar research. Tour said the PEG-coated glass slides were used for their anti-fouling – nonsticky – properties, while the clean glass slides were treated with hydrogen peroxide so the hydrophobic wheels wouldn’t stick. He said the cars weren’t so much being driven as undergoing “directed diffusion” in the tests. The point, he said, was to establish the kinetics of nanocar movement and understand the potential energy surface interaction between the car and surface over time.
A team of Stanford University engineers has obtained a first look inside phase-changing nanoparticles, elucidating how their shape and crystallinity – the arrangement of atoms within the crystal – can have dramatic effects on their performance. The work has immediate applications in the design of energy storage materials, but could eventually find its way into data storage, electronic switches and any device in which the phase transformation of a material regulates its performance. For instance, in a lithium ion battery, the ability of the battery to store and release energy repeatedly relies on the electrode’s ability to sustain large deformations over several charge and discharge cycles without degrading. Recently, scientists have improved the efficiency of this process by nanosizing the electrodes. The nanoparticles allow for faster charging, increased energy storage and an extended lifetime, but it is unknown which nanoparticle shapes, sizes and crystallinities produce the best performance. Jennifer Dionne, an assistant professor of materials science and engineering, and her group have been studying the behavior of individual particles to establish a stronger link between structure and function that can direct the design of next-generation energy storage materials. Dionne’s group examined how varying the shapes and crystallinity of palladium nanoparticles affected their ability to absorb and release hydrogen atoms – an analog to a lithium-ion battery discharging and charging. They prepared cubic, pyramidal and icosahedral nanoparticles and developed novel imaging techniques to look inside nanoparticles at various hydrogen pressures, determining where the hydrogen was located. The researchers found that nanoparticle structure significantly influences performance. The icosahedral structures, for instance, show reduced energy storage capacity and more gradual hydrogen absorption than the single crystalline cubes and pyramids. High-resolution maps of the particles demonstrate that hydrogen is excluded from the center of the particle, thus lowering the overall capacity to incorporate hydrogen. Structural characterization shows that the gradual absorption of hydrogen occurs because different regions of the particle absorb hydrogen at different pressures, unlike what is observed in single crystals.
Firefighters entering burning buildings, athletes competing in the broiling sun and workers in foundries may eventually be able to carry their own, lightweight cooling units with them, thanks to a nanowire array that cools, according to Penn State materials researchers. "Most electrocaloric ceramic materials contain lead," said Qing Wang, professor of materials science and engineering. "We try not to use lead. Conventional cooling systems use coolants that can be environmentally problematic as well. Our nanowire array can cool without these problems." Electrocaloric materials are nanostructured materials that show a reversible temperature change under an applied electric field. Previously available electrocaloric materials were single crystals, bulk ceramics or ceramic thin films that could cool, but are limited because they are rigid, fragile and have poor processability. Ferroelectric polymers also can cool, but the electric field needed to induce cooling is above the safety limit for humans. Wang and his team looked at creating a nanowire material that was flexible, easily manufactured and environmentally friendly and could cool with an electric field safe for human use. Such a material might one day be incorporated into firefighting gear, athletic uniforms or other wearables.
A simple filtration process helped Rice University researchers create flexible, wafer-scale films of highly aligned and closely packed carbon nanotubes. Scientists at Rice, with support from Los Alamos National Laboratory, have made inch-wide films of densely packed, chirality-enriched single-walled carbon nanotubes. In the right solution of nanotubes and under the right conditions, the tubes assemble themselves by the millions into long rows that are aligned better than once thought possible, the researchers reported. The thin films offer possibilities for making flexible electronic and photonic (light-manipulating) devices, said Rice physicist Junichiro Kono, whose lab led the study. Think of a bendable computer chip, rather than a brittle silicon one, and the potential becomes clear, he said. The Rice lab is closing in, Kono said, but the films reported in the current paper are “chirality-enriched” rather than single-chirality. A carbon nanotube is a cylinder of graphene, with its atoms arranged in hexagons. How the hexagons are turned sets the tube’s chirality, and that determines its electronic properties. Some are semiconducting like silicon, and others are metallic conductors. A film of perfectly aligned, single-chirality nanotubes would have specific electronic properties. Controlling the chirality would allow for tunable films, Kono said, but nanotubes grow in batches of random types.
Engineers at Washington University in St. Louis found a way to keep a cancerous tumor from growing by using nanoparticles of the main ingredient in common antacid tablets. The research team, led by Avik Som, an MD/PhD student, and Samuel Achilefu, PhD, professor of radiology and of biochemistry & molecular biophysics in the School of Medicine and of biomedical engineering in the School of Engineering & Applied Science, in collaboration with two labs in the School of Engineering & Applied Science, used two novel methods to create nanoparticles from calcium carbonate that were injected intravenously into a mouse model to treat solid tumors. The compound changed the pH of the tumor environment, from acidic to more alkaline, and kept the cancer from growing. With this work, researchers showed for the first time that they can modulate pH in solid tumors using intentionally designed nanoparticles. “Cancer kills because of metastasis,” said Som, who is working on a doctorate in biomedical engineering in addition to a medical degree. “The pH of a tumor has been heavily correlated with metastasis. For a cancer cell to get out of the extracellular matrix, or the cells around it, one of the methods it uses is a decreased pH.”