Articles from May 2014

Mimic Nature To Build Man-made Molecular Systems

Using molecules of DNA like an architectural scaffold, Arizona State University (ASU) scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway, a major breakthrough for future biomedical and energy applications.

Remaking an artificial enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology. To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes. In the middle of the DNA scaffold, a research team led by ASU professor Hao Yan affixed a single strand of DNA, with the molecule called NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes to carry out a chemical reaction

We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level,” Yan said, who holds the Milton Glick Chair in the ASU Department of Chemistry and Biochemistry.
An even loftier and more valuable goal is to engineer highly programmed cascading enzyme pathways on DNA nanostructure platforms with control of input and output sequences. Achieving this goal would not only allow researchers to mimic the elegant enzyme cascades found in nature and attempt to understand their underlying mechanisms of action, but would facilitate the construction of artificial cascades that do not exist in nature,” said Yan.
The findings were published in the journal Nature Nanotechnology.

Nanoflowers Deliver Drugs To Cancer Cells

Biomedical engineering researchers have developed daisy-shaped, nanoscale structures that are made predominantly of anti-cancer drugs and are capable of introducing a “cocktail” of multiple drugs into cancer cells. The researchers are all part the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill.
To make the “nanodaisies,” the researchers begin with a solution that contains a polymer called polyethylene glycol (PEG). The PEG forms long strands that have much shorter strands branching off to either side. Researchers directly link the anti-cancer drug camptothecin (CPT) onto the shorter strands and introduce the anti-cancer drug doxorubicin (Dox) into the solution. Once injected, the nanodaisies float through the bloodstream until they are absorbed by cancer cells. Once in a cancer cell, the drugs are released.

Early tests of the “nanodaisy” drug delivery technique show promise against a number of cancers
We found that this technique was much better than conventional drug-delivery techniques at inhibiting the growth of lung cancer tumors in mice,” says Dr. Zhen Gu, senior author of the paper. “And based on in vitro tests in nine different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian and brain cancers.”

How To Directly Control The Nano-World In Motion

Researchers have announced the first ever method for controlling the growth of metal-crystals from single atoms. Professor Peter Sadler from the University of Warwick, – United Kingdom – Department of Chemistry, commented that “The breakthrough with Nanocrystallometry is that it actually allows us to observe and directly control the nano-world in motion“. Using a doped-graphene matrix to slow down and then trap atoms of the precious metal osmium the researchers were able to control and quantify the growth of metal-crystals. When the trapped atoms come into contact with further osmium atoms they bind together, eventually growing into 3D metal-crystals.

Tailoring nanoscopic objects is of enormous importance for the production of the materials of the future“, says Dr Barry from the University’s Department of Chemistry. “Until now the formation of metal nanocrystals, which are essential to those future materials, could not be controlled with precision at the level of individual atoms, under mild and accessible conditions.”
Prof. Sadler says: Nanocrystallometry‘s significance is that it has made it possible to grow with precision metal-crystals which can be as small as only 0.00000015cm, or 15 ångström, wide. If a nanodevice requires a million osmium atoms then from 1 gram of osmium we can make about 400 thousand devices for every person on this earth. Compared to existing methods of crystal growth Nanocrystallometry offers a significant improvement in the economic and efficient manufacture of precision nanoscopic objects.”

Published in the journal Nature Communications and developed at the University of Warwick, the method, called Nanocrystallometry, allows for the creation of precise components for use in nanotechnology.

How To Map Your Blood System

A new method allows calcified and constricted blood vessels to be visualized with micrometer (one thousandth of a millimeter) precision, and can be used to design containers for targeted drug delivery. Within the project “NO-stress”, materials scientists from the Medical Faculty of the University of Basel combined cutting-edge-imaging techniques to visualize and quantify the constrictions caused by atherosclerosis. Cardiovascular diseases, including atherosclerosis, are associated with plaque formation and the most prevalent cause of death worldwide. Unlike vessels and other soft tissues, the plaque formed provides strong contrast in X-rays, as known from bone. So far, it has therefore been difficult or even impossible to identify soft tissues in the direct neighborhood of calcifications using X-rays.

A team of researchers from laboratories in three European countries, led by Bert Müller (Biomaterials Science Center at University of Basel), has developed a protocol that is based on the combination of hard X-ray tomography and established histology methods, to visualize the vessels constricted by atherosclerosis.

The data about the morphology of the constricted vessels is used to simulate blood flow and determine related shear stresses. The shear stress is significantly enhanced at the constrictions and forms the basis for the development of specialized nano-containers for the targeted and local delivery of vasodilation drugs


Cancer Detection In Its Earliest Stages

An international team of researchers led by Professor Romain Quidant from The Institute of Photonic Sciences (ICFO ) -Spain -, report on the successful development of a “lab-on-a-chip” platform capable of detecting protein cancer markers in the blood using the very latest advances in plasmonics, nano-fabrication, microfluids and surface chemistry. The device is able to detect very low concentrations of protein cancer markers, enabling diagnoses of the disease in its earliest stages. This cancer-tracking nano-device shows great promise as a tool for future cancer treatments, not only because of its reliability, sensitivity and potential low cost, but also because of its easy carry-on portable properties, which is foreseen to facilitate effective diagnosis and suitable treatment procedures in remote places with difficult access to hospitals or medical clinics.

Although very compact (only a few cm2), the lab-on-a-chip hosts various sensing sites distributed across a network of fluidic micro-channels that enables it to conduct multiple analyses. Gold nano-particles lie on the surface of the chip and are chemically programed with an antibody receptor in such a way that they are capable of specifically attracting the protein markers circulating in blood. When a drop of blood is injected into the chip, it circulates through the micro-channels and if cancer markers are present in the blood, they will stick to the nano-particles located on the micro-channels as they pass by, setting off changes in what is known as the “plasmonic resonance”. The device monitors these changes, the magnitude of which are directly related to the concentration/number of markers in the patient blood thus providing a direct assessment of the risk for the patient to develop a cancer.


Car Waste Heat Transformed Into Electricity

Thermoelectric materials can turn a temperature difference into an electric voltage. Among their uses in a variety of specialized applications: generating power on space probes and cooling seats in fancy cars.

University of Miami physicist Joshua Cohn and his collaborators report new surprising properties of a metal named lithium purple-bronze (LiPB) that may impact the search for materials useful in power generation, refrigeration, or energy detection.

If current efficiencies of thermoelectric materials were doubled, thermoelectric coolers might replace the conventional gas refrigerators in your home,” said Cohn, professor and chairman of the UM Department of Physics in the College of Arts and Sciences and lead author of the study. “Converting waste heat into electric power, for example, using vehicle exhaust, is a near-termgreen’ application of such materials.”
The findings are published in the journal Physical Review Letters.


World’s Smallest, Fastest Nanomotor

Researchers at the Cockrell School of Engineering at The University of Texas at Austin have built the smallest, fastest and longest-running tiny synthetic motor to date. The team’s nanomotor is an important step toward developing miniature machines that could one day move through the body to administer insulin for diabetics when needed, or target and treat cancer cells without harming good cells.

With the goal of powering these yet-to-be invented devices, UT Austin engineers focused on building a reliable, ultra-high-speed nanomotor that can convert electrical energy into mechanical motion on a scale 500 times smaller than a grain of salt.

Mechanical engineering assistant professor Donglei “Emma” Fan led a team of researchers in the successful design, assembly and testing of a high-performing nanomotor in a nonbiological setting. The team’s three-part nanomotor can rapidly mix and pump biochemicals and move through liquids, which is important for future applications. One amazing arena of application for this nanomotor is the field of nanoelectromechanical systems (NEMS), where such a machine will be able to push forward the frontiers of cheaper and more energy efficient systems.
The team’s study was published in the April issue of Nature Communications.


Bionic Particles To Turn Sunlight Into Fuel

Inspired by fictional cyborgs like Terminator, a team of researchers at the University of Michigan and the University of Pittsburgh has made the first bionic particles from semiconductors and proteins. These particles recreate the heart of the process that allows plants to turn sunlight into fuel.

Human endeavors to transform the energy of sunlight into biofuels using either artificial materials or whole organisms have low efficiency,” said Nicholas Kotov, the Florence B. Cejka Professor of Engineering at the University of Michigan, who led the experiment. A bionic approach could change that. The bionic particles blend the strengths of inorganic materials, which can readily convert light energy to electron energy, with biological molecules whose chemical functions have been highly developed through evolution. The team first designed the particles to combine cadmium telluride, a semiconductor commonly used in solar cells, with cytochrome C, a protein used by plants to transport electrons in photosynthesis. With this combination, the semiconductor can turn a ray from the sun into an electron, and the cytochrome C can pull that electron away for use in chemical reactions that could clean up pollution or produce fuel, for instance. U-M‘s Sharon Glotzer, the Stuart W. Churchill Professor of Chemical Engineering, who led the simulations, compares the self-assembly to the way that the surfaces of living cells form, using attractive forces that are strong at small scales but weaken as the structure grows. Kotov’s group confirmed that the semiconductor particles and proteins naturally assemble into larger particles, roughly 100 nanometers (0.0001 millimeters) in diameter.

We merged biological and inorganic in a way that leverages the attributes of both to get something better than either alone,” Glotzer said. Powered by electrons from the cytochrome C, the enzyme could remove oxygen from nitrate molecules. Like the structures that accomplish photosynthesis in plants, the bionic particles took a beating from handling the energy. Nature constantly renews these working parts in plants, and through self-assembly, the particles may also be able to renew themselves.

Flexible Nanogenerator

Nanogenerators are innovative self-powered energy harvesters that convert kinetic energy created from vibrational and mechanical sources into electrical power, removing the need of external circuits or batteries for electronic devices. This innovation is vital in realizing sustainable energy generation in isolated, inaccessible, or indoor environments and even in the human body. Nanogenerators, a flexible and lightweight energy harvester on a plastic substrate, can scavenge energy from the extremely tiny movements of natural resources and human body such as wind, water flow, heartbeats, and diaphragm and respiration activities to generate electrical signals. The generators are not only self-powered, flexible devices but also can provide permanent power sources to implantable biomedical devices, including cardiac pacemakers and deep brain stimulators.

However, poor energy efficiency and a complex fabrication process have posed challenges to the commercialization of nanogenerators. Keon Jae Lee, Associate Professor of Materials Science and Engineering at KAIST – Korea -, and his colleagues have recently proposed a solution by developing a robust technique to transfer a high-quality piezoelectric thin film from bulk sapphire substrates to plastic substrates using laser lift-off (LLO). Applying the inorganic-based laser lift-off (LLO) process, the research team produced a large-area PZT thin film nanogenerators on flexible substrates (2cm x 2cm).

Flexible PZT thin film nanogenerator using inorganic-based laser lift-off process

We were able to convert a high-output performance of ~250 V from the slight mechanical deformation of a single thin plastic substrate. Such output power is just enough to turn on 100 LED lights,” Keon Jae Lee explained.


Lithium-Ion Batteries That Last 3 Times Longer

Using a material found in Silly Putty and surgical tubing, a group of researchers at the University of California, Riverside Bourns College of Engineering have developed a new way to make lithium-ion batteries that will last three times longer between charges compared to the current industry standard.
The team created silicon dioxide (SiO2) nanotube anodes for lithium-ion batteries and found they had over three times as much energy storage capacity as the carbon-based anodes currently being used. This has significant implications for industries including electronics and electric vehicles, which are always trying to squeeze longer discharges out of batteries.

We are taking the same material used in kids’ toys and medical devices and even fast food and using it to create next generation battery materials,” said Zachary Favors, the lead author of a just-published paper online in the journal Nature Scientific Reports.


Massive Injection Of Measles Killed Stacy’s Cancer

A massive injection of the measles virus received by a 50-year-old woman in the United States shrank her tumours and eventually made them disappear.
The trial at the Mayo Clinic in Rochester, Minnesota was carried out on Stacy Erholtz, who was declared free of the disease. She was one of two patients to participate in the trial which did not prove successful with the other volunteer.
The next step will be a similar trial involving a larger group of patients, which is expected to take place in September.
Ms Erholtz of Pequot Lakes, Minnesota has for years suffered from myeloma, a blood cancer that affects bone marrow.
Two stem cell transplants and chemotherapy had proved unsuccessful and her body was riddled with cancer with one tumour growing on her forehead.
Previous trials had shown that a virus can kill cancer in mice, but this was the first time the technique had been used on a human being.
The Mayo experiment was described as a “proof of concept” that a single massive overdose of a virus can overcome a cancer’s natural defences.
In this case it entailed injecting Ms Erholtz with 100 billion units of the measles virus – enough to provide inoculations for 10 million people. However the virus had to be “engineered” before using the therapy.
Within five minutes she was suffering a splitting headache and then as her temperature soared to 105 degrees (40,5 degrees Celsius) she started shaking and vomiting.
But 36 hours later the tumour on her forehead began to shrink, in the weeks that followed it disappeared along with others in her body.

We have a virus that can do that selectively to a tumor without at the same time causing damage to normal tissues in the body,” said Stephen Russell, professor of molecular medicine, who carried out the experiment, and described the successful trial as a landmark..
We’ve known for a long time that we can give a virus intravenously and destroy metastatic cancer in mice. Nobody’s shown that you can do that in people before.”


RNA Silences Genes, Treats Cancer

RNA interference (RNAi), a technique that can turn off specific genes inside living cells, holds great potential for treating many diseases caused by malfunctioning genes. RNA, a nanoparticle, transfers information from DNA to protein-forming system of the cell. However, it has been difficult for scientists to find safe and effective ways to deliver gene-blocking RNA to the correct targets.
Up to this point, researchers have gotten the best results with RNAi targeted to diseases of the liver, in part because it is a natural destination for nanoparticles. But now, in a study appearing in the May 11 issue of Nature Nanotechnology, an MIT-led team reports achieving the most potent RNAi gene silencing to date in nonliver tissues.
Using nanoparticles designed and screened for endothelial delivery of short strands of RNA called siRNA, the researchers were able to target RNAi to endothelial cells, which form the linings of most organs. This raises the possibility of using RNAi to treat many types of disease, including cancer and cardiovascular disease, the researchers say.

MIT engineers designed RNA-carrying nanoparticles (red) that can be taken up
There’s been a growing amount of excitement about delivery to the liver in particular, but in order to achieve the broad potential of RNAi therapeutics, it’s important that we be able to reach other parts of the body as well,” says Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and one of the paper’s senior authors.
The paper’s other senior author is Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute. Lead authors are MIT graduate student James Dahlman and Carmen Barnes of Alnylam Pharmaceuticals.