#Heart-on-a-Chip Device Holds Promise for Drug-Screening When UC Berkeley bioengineers say they are holding their hearts in the palms of their hands,
they are not talking about emotional vulnerability. The eart-on-a-chipdeveloped at UC Berkeley houses human heart tissue derived from adult stem cells.
The system could one day replace animal models for drug safety screening. Photo by Anurag Mathur, Healy Lab) Instead, the research team led by bioengineering professor Kevin Healy is presenting a network of pulsating cardiac muscle cells housed in an inch-long silicone device that effectively models human heart tissue,
and they have demonstrated the viability of this system as a drug-screening tool by testing it with cardiovascular medications.
This organ-on-a-chip, reported in a study published today (Monday, March 9) in the journal Scientific Reports, represents a major step forward in the development of accurate, faster methods of testing for drug toxicity.
The project is funded through the Tissue Chip for Drug Screening Initiative an interagency collaboration launched by the National institutes of health to develop 3-D human tissue chips that model the structure and function of human organs. ltimately,
these chips could replace the use of animals to screen drugs for safety and efficacy, said Healy.
The study authors noted a high failure rate associated with the use of nonhuman animal models to predict human reactions to new drugs.
Much of this is due to fundamental differences in biology between species, the researchers explained. For instance, the ion channels through which heart cells conduct electrical currents can vary in both number
and type between humans and other animals. any cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans,
said Healy. t takes about $5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase.
Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market.
The heart cells were derived from human-induced pluripotent stem cells, the adult stem cells that can be coaxed to become many different types of tissue.
The researchers designed their cardiac microphysiological system or heart-on-a-chip, so that its 3-D structure would be comparable to the geometry and spacing of connective tissue fiber in a human heart.
They added the differentiated human heart cells into the loading area, a process that Healy likened to passengers boarding a subway train at rush hour.
The system confined geometry helps align the cells in multiple layers and in a single direction.
Microfluidic channels on either side of the cell area serve as models for blood vessels, mimicking the exchange by diffusion of nutrients and drugs with human tissue.
In the future this setup could also allow researchers to monitor the removal of metabolic waste products from the cells. his system is not a simple cell culture where tissue is being bathed in a static bath of liquid,
said study lead author Anurag Mathur, a postdoctoral scholar in Healy lab and a California Institute for Regenerative medicine fellow. e designed this system
so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs.
The heart cells were derived from human-induced pluripotent stem cells, the adult stem cells that can be coaxed to become many different types of tissue.
The researchers designed their cardiac microphysiological system, or heart-on-a-chip, so that its 3-D structure would be comparable to the geometry and spacing of connective tissue fiber in a human heart.
They added the differentiated human heart cells into the loading area, a process that Healy likened to passengers boarding a subway train at rush hour.
The system confined geometry helps align the cells in multiple layers and in a single direction.
a postdoctoral scholar in Healy lab and a California Institute for Regenerative medicine fellow. e designed this system
An EPFL spin-off company, Nanolive, has developed the 3d Cell Explorer first-ever microscope that allows users to see inside living cells without any prior sample preparation,
by using MRI-like technology and proprietary software that uses holographic algorithms. The microscope is called the 3d Cell Explorer.
It combines state-of-the-art hardware with cutting-edge imaging software to record stunning 3d images of entire living cells within seconds and with a higher resolution than any conventional microscope available in the market.
The device works as an MRI SCANNER, taking photographs at different depths across the cells. The photographic"slices"are recombined then using clever holography software that digitally"stains"the cells,
labeling its different parts. The result is a high-resolution 3d image of the cell that can be rotated
The software, called STEVE, is now available for download and can be used to"travel"virtually inside cells.
It allows the user to digitally"paint"any part of a scanned cell. This is possible because it can automatically define all the different parts of a cell based on an optical property called the"refractive index".
"Since different organelles inside the cell have different refractive indices, STEVE can tell them apart
allowing users to explore changes in the cell in real time. Through STEVE, the stains can be modified constantly by the user,
saved and reused for other cells.""Starting from today, scientists, medics and students all around the world will be enabled to travel inside 3d cells in full color by simply downloading STEVE on their laptop"says Nanolive CEO Yann Cotte.
Nanolive SA was founded in November 2013 at the EPFL Innovation Park (Lausanne) by Yann Cotte (CEO) and Fatih Toy (scientific advisor),
#Real-time Nanoscale Images of Lithium Dendrite Structures That Degrade Batteries Scientists at the Department of energy Oak ridge National Laboratory have captured the first real-time nanoscale images of lithium dendrite structures known to degrade lithium
-ion batteries. The ORNL team electron microscopy could help researchers address longstanding issues related to battery performance and safety.
ORNL electron microscopy captured the first real-time nanoscale images of the nucleation and growth of lithium dendrite structures known to degrade lithium-ion batteries.
CREDIT: ORNL Dendrites form when metallic lithium takes root on a battery anode and begins growing haphazardly.
If the dendrites grow too large, they can puncture the divider between the electrodes and short-circuit the cell,
resulting in catastrophic battery failure. The researchers studied dendrite formation by using a miniature electrochemical cell that mimics the liquid conditions inside a lithium-ion battery.
Placing the liquid cell in a scanning transmission electron microscope and applying voltage to the cell allowed the researchers to watch as lithium depositshich start as a nanometer-size seedrew into dendritic structures. t gives us a nanoscopic view of how dendrites nucleate and grow,
said ORNL Raymond Unocic, in situ microscopy team leader. e can visualize the whole process on a glassy carbon microelectrode
and observe where the dendrites prefer to nucleate and also track morphological changes during growth.
Watch a video of the dendrite growth here: https://www. youtube. com/watch? v=rpputm u pm.
In addition to imaging the structures at high-resolution, the team microscopy technique gathered precise measurements of the cell electrochemical performance. his technique allows us to follow subtle nano-sized structural
and chemical changes that occur and more importantly, correlate that to the measured performance of a battery,
said Robert Sacci, ORNL postdoctoral researcher and lead author of the Nano Letters study. This real-time analysis in a liquid environment sets the ORNL team approach apart from other characterization methods. sually
when you run a battery over many charge-discharge cycles, you typically wait until things start failing
and at that point you perform a root-cause failure analysis, Unocic said. hen you see there a dendriteut so what?
and nanoscopic level to look at the structural and chemical evolution that happening in the cellshen you can truly address those issues that come up.
The study is published as anoscale Imaging of Fundamental Li Battery Chemistry: Solid electrolyte Interphase Formation and Preferential Growth of Lithium Metal Nanoclusters.
Coauthors are Robert Sacci, Jennifer Black, Nina Balke, Nancy Dudney, Karren More and Raymond Unocic.
an Energy Frontier Research center funded by DOE Office of Science. The study also used resources at Center for Nanophase Materials sciences, a DOE Office of Science User Facility at ORNL.
UT-Battelle manages ORNL for the Department of energy Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United states
For more information, please visit http://science. energy. gov/a
#N1 Technologies Seeks Patent for Non-Petroleum Nano Organic Motor oil The directors and management of N1 Technologies Inc. have filed a patent for a bio-based non-petroleum motor oil.
The company has taken renewable plant oils and added Tungsten and Carbon nanotubes to the oil blend.
"Tests conducted on older high mileage vehicles have yielded tremendous results, one 200,000 mile engine still runs like new,"states N1 Technologies CEO Steve Lovern.
The nanotechnology engineered into the organic oil blend is the key to its ability to transfer heat,
The Organic Bio-Based Motor oil patent describes the assembly process for blending Nanotubes and various highly viscous all natural plant oils to form Nanosave N1-Organic.
Plans are in the works to seek a Green Seal Certificate in the near future.
and now sells Nanosave N1-Organic from their website and it is available directly from Amazon.
It has proven to be one of the best selling oil products in the Nanosave N1 lineup. http://www. amazon com/nanosave Video Link:
http//www. nanosave. blogspot. com N1 Technologies Inc. is a Global leader in Nanotechnology research and Development.
#Fluid-Based Gating Mechanism for Controlling Passage of Materials through Micropores Just as they help control the transport of materials through pores,
these systems often get clogged during use due to accumulation of materials and fouling, and are also not energy efficient over long periods of use.
a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard university and the Amy Smith Berylson Professor of Materials science at Harvard School of engineering and Applied sciences (SEAS), has developed an entirely new,
highly versatile mechanism for controlling passage of materials through micropores, using fluid to modulate their opening and closing.
Aizenberg, who is also Professor of Chemistry and Chemical Biology in Harvard's Faculty of arts and Sciences and Co-Director of the Kavli Institute for Bionano Science and Technology
"The work is reported in the March 5 issue of Nature.""The ability to selectively transport or extract materials is valuable for uses such as separating components of oil, gas and wastewater,
and is extraordinarily precise due to the fact that the fluid-filled gate adjusts to accommodate filtration of each substance it encounters,
"The fluid used in the gate is repellent and prevents any material from sticking to it
operators of the system simply need to adjust the pressure to influence what substances will be allowed to flow through the fluid-filled gates."
leading to high costs and risk of gas accidentally escaping into the environment. Additionally, the tunable pressurization and antifouling properties could result in more than 50-percent energy savings compared to current methods."
"Fundamentally, it's an elegant concept. While conventional membrane technology uses all kinds of specialized materials and engineered micropores to achieve selectivity,
who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical school and Boston Children's Hospital and Professor of Bioengineering at Harvard SEAS."
"This advance offers an entirely new approach with which to confront a broad range of problems in fields ranging from energy to medicine."
#Researchers Determine Molecular Structure of Nanobody-P Domain Complex for Norovirus Infection with highly contagious noroviruses,
while not usually fatal, can lead to a slew of unpleasant symptoms such as excessive vomiting and diarrhea.
This makes the development of an effective vaccine to protect against infection, as well as antiviral therapy to combat already-existing infections,
particularly challenging",says Dr. Grant Hansman, a virologist who leads the CHS Research Group on Noroviruses at the German Cancer Research center (Deutsches Krebsforschungszentrum, DKFZ) and Heidelberg University.
Hansman's research team recently discovered that a"nanobody"called Nano-85 was able to bind to intact norovirus-like particles (VLPS) in culture.
Nanobodies are very similar to antibodies, which recognize and bind to antigens.""However, nanobodies are much smaller, more stable, easier to produce,
and cost-effective than traditional monoclonal antibodies, "says Hansman. Interestingly, Nano-85 was able to recognize the VLPS from a variety of different norovirus strains.
"Using a technique called X-ray crystallography, the researchers were able to determine the shape and molecular components of the Nano-85/P domain complex,
as well as specific sites where Nano-85 and the P domain formed bonds. According to Hansman,"this is,
"Interestingly, the investigators found that the site where Nano-85 bound to the P domain was hidden actually under the viral particle's surface."
"From the virus's point of view, this could be a strategy to keep potentially vulnerable sites protected from attack,
This led them to believe that Nano-85 itself was actually causing the VLPS to break apart.
this could be a very promising lead in developing norovirus antiviral therapy. This could be especially beneficial to immunosuppressed individuals such as cancer patients.
Administering a vaccine to protect against infection would overwhelm the patient's immune system. However, if he or she has the option of receiving an antiviral to eliminate the infection,
the norovirus becomes much less dangerous.""Source: http://www. dkfz. d d
#Canatu Announce Multitouch, Button-Free Automotive Panels with Carbon nanobud Films Canatu, a leading manufacturer of transparent conductive films, has in partnership with Schuster Group
and Display Solution AG, showcased a pioneering 3d encapsulated touch sensor for the automotive industry. The partnership is delivering the first ever,
button free, 3d shaped true multitouch panel for automotives, being the first to bring much anticipated touch applications to dashboards and paneling.
The demonstrator provides an example of multifunctional display with 5 finger touch realized in IML technology.
The integration of touch applications to dashboards and other paneling in cars has long been desired by automotive designers
but a suitable technology was not available. Finally the technology is now here. Canatu CNB#(Carbon nanobud) In-Mold Film with its unique stretch properties provides a clear path to the eventual replacement of mechanical controls with 3d touch sensors.
The touch application was made using an existing mass manufacturing tool and industry standard processes. New possibilities for design Specifically designed for automobile center consoles and dashboards, household machines, wearable devices, industrial user interfaces, commercial applications and consumer devices,
CNB#In-Mold Films can be formed easily into shape. The film is patterned first to the required touch functionality, then formed,
then back-molded by injection molding, resulting in a unique 3d shape with multitouch functionality.
With a bending radius of 1mm CNB#In-Mold Films can bring touch to almost any surface imaginable.
A natural partnership Schuster Group has a long history in manufacturing customized paneling for the automotive industry.
Schuster Group is keen to utilize Canatu proprietary CNB#(Carbon nanobuds) In-Mold Film in their latest next generation product design.
#Touch-Sensitive Flexible Silicone Stickers Worn on the Skin Can Help Control Mobile devices Someone wearing a smartwatch can look at a calendar
A method currently being developed by a team of computer scientists from Saarbrücken in collaboration with researchers from Carnegie mellon University in the USA may provide a solution to this problem.
They have developed touch-sensitive stickers made from flexible silicone and electrically conducting sensors that can be worn on the skin.
The stickers can act as an input space that receives and executes commands and thus controls mobile devices.
Depending on the type of skin sticker used, applying pressure to the sticker could, for example, answer an incoming call or adjust the volume of a music player.'
'The stickers allow us to enlarge the input space accessible to the user as they can be attached practically anywhere on the body,
a Phd student in the team led by Jürgen Steimle at the Cluster of Excellence at Saarland University.
Users can also design their iskin patches on a computer beforehand to suit their individual tastes.'
The silicone used to fabricate the sensor patches makes them flexible and stretchable.''This makes them easier to use in an everyday environment.
The music player can simply be rolled up and put in a pocket, 'explains Jürgen Steimle, who heads the'Embodied Interaction Group'in
as they are attached to the skin with a biocompatible, medical-grade adhesive. Users can therefore decide where they want to position the sensor patch
and how long they want to wear it.''In addition to controlling music or phone calls, the iskin technology could be used for many other applications.
For example, a keyboard sticker could be used to type and send messages. Currently the sensor stickers are connected via cable to a computer system.
According to Steimle, inbuilt microchips may in future allow the skin-worn sensor patches to communicate wirelessly with other mobile devices.
The publication about'iskin'won the'Best Paper Award'at the SIGCHI conference, which ranks among the most important conferences within the research area of human computer interaction.
The researchers will present their project at the SIGCHI conference in April in Seoul Korea, and beforehand at the computer expo Cebit,
which takes place from the 16th until the 20th of March in Hannover (hall 9, booth E13) E
#Lab on a Chip Acoustofluidic Sputum Liquefaction Device for Safe Asthma and Tuberculosis Diagnostics A device to mix liquids utilizing ultrasonics is the first and most difficult component in a miniaturized system for low-cost analysis
of sputum from patients with pulmonary diseases such as tuberculosis and asthma. The device, developed by engineers at Penn State in collaboration with researchers at the National Heart, Lung,
and Blood Institute (NHLBI), part of the National institutes of health, and the Washington University School of medicine, will benefit patients in the U s.,where 12 percent of the population,
or around 19 million people, have asthma, and in undeveloped regions where TB is still a widespread
and often deadly contagion. o develop more accurate diagnosis and treatment approaches for patients with pulmonary diseases,
we have to analyze sample cells directly from the lungs rather than by drawing blood,
said Tony Jun Huang, professor of engineering science and mechanics at Penn State and the inventor, with his group, of this and other acoustofluidic devices based on ultrasonic waves. or instance,
different drugs are used to treat different types of asthma patients. If you know what a person immunophenotype is
you can provide personalized medicine for their particular disease. There are several issues with the current standard method for sputum analysis. The first is that human specimens can be contagious,
and sputum analysis requires handling of specimens in several discrete machines. With a lab on a chip device, all biospecimens are contained safely in a single disposable component.
Another issue is the sample size required for analysis in the current system, which is often larger than a person can easily produce.
With the lab on a chip system a nurse can operate the device with a touch of a few buttons
In addition, the disposable portion of the device should cost less than a dollar to manufacture. Po-Hsun Huang, a graduate student in the Huang group and the first author on the recent paper describing the device in the Royal Society of Chemistry journal Lab on a Chip,
said his will offer quick analysis of samples without having to send them out to a centralized lab
This is the first on-chip sputum liquefier anyone has developed. Stewart J. Levine, a Senior Investigator and Chief of the Laboratory of Asthma and Lung Inflammation in the Division of Intramural Research at NHLBI, said his on-chip sputum liquefier is a significant advance regarding our goal
of developing a point-of-care diagnostic device that will determine the type of inflammation present in the lungs of asthmatics.
This will allow health care providers to individualize asthma treatments for each patient and advance the goal of bringing precision medicine into clinical practice.
This research was supported by the American Asthma Foundation Scholar Award the National Science Foundation, and the NHLBI Division of Intramural Research.
Portions of this work were carried out in the Penn State Nanofabrication Facility, a node of the NSF-funded National Nanotechnology Infrastructure Network s
California, has developed a miniaturized sensor based on Raman spectroscopy that can quickly and accurately detect or diagnose substances at a molecular level. ur system can do chemistry, biology, biochemistry, molecular biology, clinical diagnosis,
and chemical analysis, said company president and cofounder Fanqing Frank Chen. nd our system can be implemented very cheaply,
without much human intervention. he technology is enhanced based on surface Raman spectroscopy, a technique for molecular fingerprinting.
what they called anoplasmonic resonators, which measures the interaction of photons with an activated surface using nanostructures
in order to do chemical and biological sensing. The method produces measurements much more reliably. t Optokey wee able to mass produce this nanoplasmonic resonator on a wafer scale,
Chen said. e took something from the R&d realm and turned it into something industrial-strength. he miniaturized sensors use a microfluidic control system for ab on a chipautomated liquid sampling.
The company is taking a page from the semiconductor industry in making its chip. ee leveraging knowledge acquired from high-tech semiconductor manufacturing methods to get the cost
the volume, and the accuracy in the chip, said VP of Manufacturing Robert Chebi, a veteran of the microelectronic industry who previously worked at Lam research
and Applied materials. ee also leveraging all the knowledge in lasers and optics for this specific Raman-based method. hebi calls Optokey product a iochemical nose,
or an advanced nanophotonic automated system, with sensitivity to the level of a single molecule, far superior to sensors on the market today. oday detection and diagnosis methods are far from perfectetection limits are in PPM (parts
per million) and PPB (parts per billion), he said. lso, our system can provide information in minutes,
including food safety, environmental monitoring (of both liquids and gases), medical diagnosis, and chemical analysis. Optokey customers include a major European company interested in food safety,
a Chinese petrochemical company interested in detecting impurities in its products, and a German company interested in point-of-care diagnosis. think wee at the cusp of a really major transition in the field,
Chen said. he product wee envisioning is something that is compact and automated but also connected, and it can go into schools, restaurants, factories, hospitals, ambulances, airports,
and even battlefields. he next market Chen is targeting is the smart home, where a nanophotonic sensor could be built to scan for pollutants not just in food but also in air and water.
Trained at Los alamos National Laboratory and Mount sinai Hospital at NYU, Chen started out as a biochemist working on biomedical devices.
After he joined Berkeley Lab around 2000, he learned about quantum dots, which are nanocrystals with peculiar properties,
and began exploring their use in biology. That led to further investigations into nanomaterials. One accomplishment was a so-called molecular ruler made of gold nanoparticles tethered to DNA strands,
which, using plasmon resonance, was capable of measuring protein-DNA interactions. Ultimately Chen and his group developed about 20 patents involving hybrid bionanomaterials.
The key discovery that led to the formation of Optokey was the development of the nanoplasmonic resonators to dramatically improve the signal and reliability of Raman spectroscopy.
The method was used initially in the research lab to quickly and accurately detect a biomarker for prostate cancer,
which has a high rate of false positives using conventional diagnostic tools. Optokey is held a privately company with about 10 employees.
Besides Chen, the other cofounder is Richard Mathies, a UC Berkeley chemistry professor and world-renowned expert on Raman spectroscopy.
The company was formed in 2010, and operations were launched in 2013. here was 10 years of research that went into this,
funded by NIH, DARPA, the federal government, private foundations, said Chen. erkeley Lab has a really good culture of multidisciplinary research, excellent engineering,
and very strong basic science. Plus it has strong support for startups. n
#Packaging Cancer drug into Nanoparticles Double Tumor Destroying Efficacy Researchers have packaged a widely used cancer drug into nanoparticles,
more than doubling its effectiveness at destroying tumors. The drug paclitaxel has been used for decades to fight breast, ovarian, lung and other cancers.
But its effectiveness has been limited by its small molecular size and insolubility in water--properties that allow the body to clear the drug too quickly,
reducing its accumulation in tumors. Many molecular packaging systems have been developed to deliver the drug while counteracting these effects, with a protein-bound version of the drug called Abraxane currently the leading therapy.
But Ashutosh Chilkoti professor and chair of the Department of Biomedical engineering at Duke university, thought his team could do better.
By surrounding molecules of paclitaxel with self-assembling spheres composed of amino acids, the Duke team doubled tumor exposure to the drug compared to Abraxane
while simultaneously reducing its effects on healthy tissue. This kept mice with tumors alive significantly longer and, in some cases, completely eradicated the tumors.
The results were published online in Nature Communications on August 4, 2015. The big difference between Abraxane and the Duke approach is the types of molecular bonds that are formed.
In Abraxane the paclitaxel is surrounded physically by albumin, a common blood protein. In the new packaging system, multiple copies of the drug are bonded chemically to an amino acid polypeptide,
forming a water-soluble nanoparticle with the drug hidden in its core. These nanoparticles are highly soluble in blood
and are the perfect size to penetrate and accumulate in tumors where they take advantage of a tumor's acidic environment."
"The chemical bonds holding the polypeptide cage together are stable in blood, but dissolve in a tumor's lower ph levels,"said Jayanta Bhattacharyya, senior researcher in Chilkoti's lab and first author on the paper."
"This delivers the drug directly to the tumor and helps prevent it from randomly absorbing into healthy tissue, reducing side effects."
"To test their system, Chilkoti, Bhattacharyya and their colleagues used two groups of mice. The first group had human breast cancer growing in their own mammary glands.
While none of the mice treated with Abraxane survived past 85 days, most of the mice treated with the new packaging system survived past 100 days.
A second group of mice had human prostate tumors growing under their skin. Similarly, while they did not survive past 60 days
when treated with Abraxane, every single mouse treated with the new packaging system survived past 70 days,
with some experiencing a complete cure. As the mortality rates suggest the Duke technology showed a higher concentration of paclitaxel in the tumors with more staying power than Abraxane,
while simultaneously showing much lower levels throughout the rest of the mice's bodies.""Clearly in the animal model there is a night and day difference,
and if that translates to people it will be transformative for patients, "said Neil Spector, an oncologist at Duke Medicine familiar with the work."
"But it's not just the increase in clinical efficacy and outcomes that are exciting,
it's also the improvement in targeting and reduction in toxicity, which is just icing on the cake.
And since this platform could potentially be used for such a broad array of drugs, it could be a game-changer for cancer therapy."
"In future work, Chilkoti and coworkers will begin applying the packaging system to other cancer drugs with the goal of developing a"one size fits all"technology to improve the effectiveness of many other cancer drugs s
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