Monday, June 9, 2014

Researchers use living systems as a guide to develop advanced technologies

Biologically driven design leads to the development of novel multi-functional materials, miniaturized electromechanical systems, and reliable living tissues as a more sustainable solution to pressing technological problems facing the human race.
Credit: Edited by: Esmaiel Jabbari (University of South Carolina, USA), Deok-Ho Kim (University of Washington, USA), Luke P Lee (University of California, Berkeley, USA), Amir Ghaemmaghami (University of Nottingham, UK), Ali Khademhosseini (Harvard University, USA & Massachusetts Institute of Technology, USA)


How should we respond to technologies around us that are inefficient, wasteful, pollute our environment, and overburden our health care system?

In their latest three three volume "Handbook of Biomimetics and Bioinspiration" published with World Scientific, renowned researcher Dr Jabbari and his co-editors provide answers to this question.

Nature has evolved over millions of years to create structures with amazing complexity. Nowhere this complexity is more apparent than in plants and animals: mimicking non-sticking of lotus leaves to produce self-cleaning devices, stickiness of gecko's feet for space walking, water strider's walking on water to build aquatic reconnaissance microrobots, mimicking laminated structure of the skin to generate advanced membranes for water purification, anti-reflectivity of cicada's wings to build improve medical imaging systems, mimicking self-healing of earthworms to make tires that repair themselves, desert beetle's water collecting ability to design water storage systems in dry and hot climates, and mimicking uneven wetting of butterfly wings to trigger motion in a particular direction.

Nature-driven design that mimics the hierarchical complexity of biological systems leads to the development of more reliable miniaturized and compact devices that perform multiple tasks. These include muscle mimetic actuators and robots, algae mimetic photoreception devices, sea star mimetic light sensing, ocellus mimetic optical devices, cell membrane mimetic nanochannels, nerve tissue mimetic sensory systems, olfactory mimetic odor sensing systems, cochlea mimetic acoustic resonators, cilia mimetic microfluidic systems, pyrophilous insect mimetic infrared sensing devices, cricket mimetic flow sensing devices, locust mimetic micro air vehicles, insect mimetic motion sensing, cochlea mimetic hearing aid devices, pigeon mimetic geometric perception, and rat mimetic silent flight systems.

As our ability to observe living systems has expanded from macro to micro and nano scale, our understanding of complex biological systems at different length scales has increased dramatically leading to the development of engineered tissues to improve human health. These include models for bone regeneration, models of muscle tissue that enable the study of cardiac infarction and myopathy, models for differentiation of embryonic stem cells, bioreactors for cultivation of mammalian cells, human lung, liver and heart tissue models, biomimetics constructs for regeneration of soft tissues, and engineered constructs for the regeneration of musculoskeletal and corneal tissues.

"Nature is by far the world's greatest engineer and materials scientist. We can learn from this great source novel technology to develop new materials and devices with a diverse range of applications and to repair and replace human tissue, bone, and organs", said Joel R. Fried from Florida A&M University.


The co-editors of the handbook include DeokHo Kim from University of Washington, Luke P. Lee from University of California Berkeley, Amir Ghaem-Maghami from University of Nottingham, and Ali Khademhosseini from Harvard-MIT.

Source: http://www.worldscientific.com/worldscibooks/10.1142/8169.

Tuesday, June 3, 2014

‘Quadrapeutics’ works in preclinical study of hard-to-treat tumors

Animal tests show Rice-developed technology effective against aggressive cancer

The first preclinical study of a new Rice University-developed anti-cancer technology found that a novel combination of existing clinical treatments can instantaneously detect and kill only cancer cells — often by blowing them apart — without harming surrounding normal organs. The research, which is available online this week Nature Medicine, reports that Rice’s “quadrapeutics” technology was 17 times more efficient than conventional chemoradiation therapy against aggressive, drug-resistant head and neck tumors.
The work was conducted by researchers from Rice, the University of Texas MD Anderson Cancer Center and Northeastern University.
“We address aggressive cancers that cannot be efficiently and safely treated today,” said Rice scientist Dmitri Lapotko, the study’s lead investigator. “Surgeons often cannot fully remove tumors that are intertwined with important organs. Chemotherapy and radiation are commonly used to treat the residual portions of these tumors, but some tumors become resistant to chemoradiation. Quadrapeutics steps up when standard treatments fail. At the same time, quadrapeutics complements current approaches instead of replacing them.”
quadrapeutics diagram
The first preclinical study of the anti-cancer technology "quadrapeutics" found it to be 17 times more efficient than conventional chemoradiation therapy against aggressive, drug-resistant head and neck tumors. Credit: D. Lapotko and E. Lukianova-Hleb/Rice University
Lapotko said quadrapeutics differs from other developmental cancer treatments in that it radically amplifies the intracellular effect of drugs and radiation only in cancer cells. The quadrapeutic effects are achieved by mechanical events — tiny, remotely triggered nano-explosions called “plasmonic nanobubbles.” Plasmonic nanobubbles are non-stationary vapors that expand and burst inside cancer cells in nanoseconds in response to a short, low-energy laser pulse. Plasmonic nanobubbles act as a “mechanical drug” against cancer cells that cannot be surgically removed and are otherwise resistant to radiation and chemotherapy.
In prior studies, Lapotko showed he could use plasmonic nanobubbles alone to literally blow cells apart. In quadrapeutics, his team is using them to detect and kill cancer cells in three ways. In cancer cells that survive the initial explosions, the bursting nanobubbles greatly magnify the local doses of both chemotherapy drugs and radiation. All three effects — mechanical cell destruction, intracellular drug ejection and radiation amplification — occur only in cancer cells and do not harm vital healthy cells nearby.
To administer quadrapeutics, the team uses four clinically approved components: chemotherapy drugs, radiation, near-infrared laser pulses of low energy and colloidal gold.
Dmitri Lapotko
Dmitri Lapotko
“Quadrapeutics shifts the therapeutic paradigm for cancer from materials — drugs or nanoparticles — to mechanical events that are triggered on demand only inside cancer cells,” Lapotko said. “Another strategic innovation is in complementing current macrotherapies with microtreatment. We literally bring surgery, chemotherapies and radiation therapies inside cancer cells.”
The first component of quadrapeutics is a low dose of a clinically validated chemotherapy drug. The team tested two: doxorubicin and paclitaxel. In each case, the scientists used encapsulated versions of the drug that were tagged with antibodies designed to target cancer cells. Thanks to the magnifying effect of the plasmonic nanobubbles, the intracellular dose — the amount of the drug that is active inside cancer cells — is very high even when the patient receives only a few percent of the typical clinical dose.
The second component is an injectable solution of nontoxic gold colloids, tiny spheres of gold that are thousands of times smaller than a living cell. Quadrapeutics represents a new use of colloidal gold, which has been used for decades in the clinical treatment of arthritis. In quadrapeutics, the gold colloids are tagged with cancer-specific clinically approved antibodies that cause them to accumulate and cluster together inside cancer cells. These gold “nanoclusters” do nothing until activated by a laser pulse or radiation.
Ekaterina Lukianova-Hleb
Ekaterina Lukianova-Hleb
The third quadrapeutic component is a short near-infrared laser pulse that uses 1 million times less energy that a typical surgical laser. A standard endoscope delivers the laser pulse to the tumor, where the gold nanoclusters convert the laser energy into plasmonic nanobubbles.
The fourth component is a single, low dose of radiation. The gold nanoclusters amplify the deadly effects of radiation only inside cancer cells, even when the overall dose to the patient is just a few percent of the typical clinical dose.
“What kills the most-resistant cancer cells is the intracellular synergy of these components and the events we trigger in cells,” Lapotko said. “This synergy showed a 100-fold amplification of the therapeutic strength of standard chemoradiation in experiments on cancer cell cultures.”
In the Nature Medicine study, the team tested quadrapeutics against head and neck squamous cell carcinoma (HNSCC), an aggressive and lethal form of cancer that had grown resistant to both chemotherapy drugs and radiation. Quadrapeutics proved so deadly against HNSCC tumors that a single treatment using just 3 percent of the typical drug dose and 6 percent of the typical radiation dose effectively eliminated tumors in mice within one week of the administration of quadrapeutics.
Lapotko, a faculty fellow in biochemistry and cell biology and in physics and astronomy, said he is working with colleagues at MD Anderson and Northeastern to move as rapidly as possible toward prototyping and a human clinical trial. In clinical applications, quadrapeutics will be applied as either a stand-alone or intra-operative procedure using standard endoscopes and other clinical equipment and encapsulated drugs such as Doxil or Lipoplatin. Though the current study focused on head and neck tumors, Lapotko said quadrapeutics is a universal technology that can be applied for local treatment of various solid tumors, including other hard-to-treat types of brain, lung and prostate cancer. He said it might also prove especially useful for treating children due to its safety.
“The combination of aggressiveness and drug and radiation resistance is particularly problematic in tumors that cannot be fully resected, and new efficient solutions are needed,” said Dr. Ehab Hanna, a surgeon and vice chair of the Department of Head and Neck Surgery at MD Anderson, who was not involved with the testing or development of quadrapeutics. “Technologies that can merge and amplify the effects of surgery, drugs and radiation at the cellular level are ideal, and the preclinical results for quadrapeutics make it a promising candidate for clinical translation.”
Study co-authors included Rice research scientist Ekaterina Lukianova-Hleb, MD Anderson researchers Xiangwei Wu and Xiaoyang Ren and Northeastern researchers Vladimir Torchilin and Rupa Sawant.
The research was supported by the National Institutes of Health, the National Science Foundation and the Virginia and L.E. Simmons Family Foundation.
Source: http://news.rice.edu/2014/06/01/quadrapeutics-works-in-preclinical-study-of-hard-to-treat-tumors-2/#sthash.5grfIIMZ.dpuf

Monday, June 2, 2014

Rensselaer Researchers Predict the Electrical Response of Metals to Extreme Pressures


Findings Published in the Proceedings of the National Academy of Sciences Could Have Applications in Computer Chip Design

Research published today in the Proceedings of the National Academy of Sciences makes it possible to predict how subjecting metals to severe pressure can lower their electrical resistance, a finding that could have applications in computer chips and other materials that could benefit from specific electrical resistance. 

The semiconductor industry has long manipulated materials like silicon through the use of pressure, a strategy known as “strain engineering,” to improve the performance of transistors. But as the speed of transistors has increased, the limited speed of interconnects – the metal wiring between transistors – has become a barrier to increased computer chip speed. The published research paper, “Pressure Enabled Phonon Engineering in Metals,” opens the door to a new variant of strain engineering that can be applied to the metal interconnects, and other materials used to conduct or insulate electricity. “We looked at a fundamental physical property, the resistivity of a metal, and show that if you pressurize these metals, resistivity decreases. And not only that, we show that the decrease is specific to different materials – aluminum will show one decrease, but copper shows another decrease,” said Nicholas Lanzillo, a doctoral candidate at Rensselaer Polytechnic Institute and lead author on the study. 

“This paper explains why different materials see different decreases in these fundamental properties under pressure.” The research involved theoretical predictions, use of a supercomputer, and experimentation with equipment capable of exerting pressures up to 40,000 atmospheres (nearly 600,000 pounds per square inch). It was made possible through a collaboration between three Rensselaer professors – Saroj Nayak, a professor of physics, applied physics, and astronomy; Morris Washington, associate director of the Center for Materials, Devices, and Integrated Systems and professor of practice of physics, applied physics, and astronomy; and E. Bruce Watson, Institute Professor of Science, and professor of earth and environmental sciences and of materials science and engineering – with a diverse mix of disciplinary backgrounds and skill sets. Jay Thomas, a senior research scientist in Watson’s lab, was primarily responsible for designing the complex experiments detailed in the paper. When an electrical current is applied to metal, electrons travel through a lattice structure formed by the individual metal atoms, carrying the current along the wiring. But as an electron travels, it is impeded by the normal collective vibration of atoms in the lattice, which is one of the factors that leads to electrical resistance. In physics, the vibration is called phonon, and the resistance it creates by coupling with electrons is known as electron-phonon coupling, a quantum mechanical feature that amplifies strongly at the atomic scale. 

Lanzillo and Nayak, his doctoral adviser, said earlier research using the Center for Computational Innovations – the Rensselaer supercomputer – showed that electron phonon coupling varies depending on the scale of the wiring: nanoscale wire has typically higher resistance than ordinary size, or “bulk,” wiring. “Our goal was to understand what limits the resistivity, what accounts for the different resistance at the atomic scale,” said Nayak. “Our earlier findings showed that sometimes the resistance of the same metal in bulk and at the atomic scale could change by a factor of 10. That’s a big number in terms of resistivity.” The researchers wanted to conduct experiments to confirm their findings, but doing so would have required making atomic-scale wires, and measuring the electron-phonon coupling as a current passed through the wire, both difficult tasks. Then they saw an alternative, based on the observation that atoms were closer together in the atomic scale lattice than in bulk lattice. “We theorized that if we compress the bulk wire, we might be able to create a condition where the atoms are closer to each other, to mimic the conditions at the atomic scale,” said Nayak. They approached Watson and Washington to execute an experiment to test their finding. 

Washington and Nayak have long collaborated through the New York State Interconnect Focus Center at Rensselaer, which researches new material systems for the next generation of interconnects in semiconductor integrated circuits with a strong interest in interconnects at dimensions of less than 20 nanometers. Existing experimental data indicated that the resistivity of copper – the current preferred interconnect material – increases as the wiring size dips below 50 nanometers. One goal of the center is to suggest materials and structures for integrated circuit interconnects smaller than 20 nanometers, which often involves fabricating and characterizing experimental thin film structures with the resources of the Rensselaer Micro and Nano Fabrication Clean Room. With this background, Washington was critical to coordinating the experimental research. 

To pressurize the metals, the group turned to Watson, a geochemist who routinely subjects materials to enormous pressures to simulate conditions in the depths of the Earth. Watson had never experimented with the electrical properties of metal wires under pressure – a process that posed a number of technical challenges. Nevertheless, he was intrigued by the theoretical findings, and he and Thomas worked together to design the high-pressure experiments that provided information on the electrical resistivity of aluminum and copper at pressures up to 20,000 atmospheres. Working together, the team was able to demonstrate that the theoretical calculations were correct. “The experimental results were vital to the study because they confirmed that Saroj and Nick’s quantum mechanical calculations are accurate – their theory of electron-phonon coupling was validated,” said Watson. “And I think we would all argue that theory backed up by experimental confirmation makes the best science.” The authors said the research offers a new and exciting capability to predict the response of the resistivity to pressure through computer simulations. The research demonstrates that changes in resistivity can be achieved in thin film nanowires by using strain in combination with existing semiconductor wafer fabrication techniques and material. 

Because of this work, the physical properties and performance of a large number of metals can be further explored in a computer, saving time and expense of wafer fabrication runs. Lanzillo said the results are a complete package. “We can make this prediction with a computer simulation but it’s much more salient if we can get experimental confirmation,” said Lanzillo. “If we can go to a lab and actually take a block of aluminum and a block of copper and pressurize them and measure the resistivity. And that’s what we did. We made the theoretical prediction, and then our friends and colleagues in experiment are able to verify it in the lab and get quantitatively accurate results in both.” Funding for the research was partially supported by the National Science Foundation Integrative Graduate Education in Research and Traineeship (IGERT) Fellowship, Grant No. 0333314, as well as the Interconnect Focus Center (MARCO program) of New York state. Computing resources provided by the Center for Computational Innovations at Rensselaer, partly funded by the state of New York.

Source: http://news.rpi.edu/content/2014/06/02/rensselaer-researchers-predict-electrical-response-metals-extreme-pressures