New nanofiber mesh wraps nerves promoting regeneration

A research team consisting of Mitsuhiro Ebara, MANA associate principal investigator, Mechanobiology Group, NIMS, and Hiroyuki Tanaka, assistant professor, Orthopaedic Surgery, Osaka University Graduate School of Medicine, developed a mesh which can be wrapped around injured peripheral nerves to facilitate their regeneration and restore their functions (Acta Biomaterialia, “Electrospun nanofiber sheets incorporating methylcobalamin promote nerve regeneration and functional recovery in a rat sciatic nerve crush injury model”).

This mesh incorporates vitamin B12—a substance vital to the normal functioning of nervous systems—which is very soft and degrades in the body. When the mesh was applied to injured sciatic nerves in rats, it promoted nerve regeneration and recovery of their motor and sensory functions.

The team is currently considering clinical application of the mesh to treat peripheral nerve disorders such as carpal tunnel syndrome (CTS).


Conceptual diagram showing a nanofiber mesh incorporating vitamin B12 and its application to treat a peripheral nerve injury. (Image: NIMS)

Artificial nerve conduits have been developed in the past to treat peripheral nerve injuries, but they merely form a cross-link to the injury site and do not promote faster nerve regeneration. 

Moreover, their application is limited to relatively few patients suffering from a complete loss of nerve continuity.

Vitamin B12 has been known to facilitate nerve regeneration, but oral administration of it has not proven to be very effective, and no devices capable of delivering vitamin B12 directly to affected sites had been available.

Therefore, it had been hoped to develop such medical devices to actively promote nerve regeneration in the many patients who suffer from nerve injuries but have not lost nerve continuity.

The NIMS-Osaka University joint research team recently developed a special mesh that can be wrapped around an injured nerve which releases vitamin B12 (methylcobalamin) until the injury heals.

By developing very fine mesh fibers (several hundred nanometers in diameter) and reducing the crystallinity of the fibers, the team successfully created a very soft mesh that can be wrapped around a nerve. 
This mesh is made of a biodegradable plastic which, when implanted in animals, is eventually eliminated from the body.

In fact, experiments demonstrated that application of the mesh directly to injured sciatic nerves in rats resulted in regeneration of axons and recovery of motor and sensory functions within six weeks.

The team is currently negotiating with a pharmaceutical company and other organizations to jointly study clinical application of the mesh as a medical device to treat peripheral nerve disorders, such as CTS.

Source: Osaka University

Lithium-ion battery inventor introduces new technology for fast-charging, noncombustible batteries – Is it “Goodenough?”

John Goodenough, professor in the Cockrell School of Engineering at The University of Texas at Austin and co-inventor of the lithium-ion battery, in the battery materials lab he oversees. Credit: Cockrell School of Engineering

A team of engineers led by 94-year-old John Goodenough, professor in the Cockrell School of Engineering at The University of Texas at Austin and co-inventor of the lithium-ion battery, has developed the first all-solid-state battery cells that could lead to safer, faster-charging, longer-lasting rechargeable batteries for handheld mobile devices, electric cars and stationary energy storage.

Goodenough’s latest breakthrough, completed with Cockrell School senior research fellow Maria Helena Braga, is a low-cost all-solid-state battery that is noncombustible and has a long cycle life (battery life) with a high volumetric energy density and fast rates of charge and discharge. The engineers describe their new technology in a recent paper published in the journal Energy & Environmental Science.

“Cost, safety, energy density, rates of charge and discharge and cycle life are critical for battery-driven cars to be more widely adopted. We believe our discovery solves many of the problems that are inherent in today’s batteries,” Goodenough said.

The Basics of the Lithium Ion Battery Principle

Today’s lithium-ion batteries use liquid electrolytes to transport the lithium ions between the anode (the negative side of the battery) and the cathode (the positive side of the battery). If a battery cell is charged too quickly, it can cause dendrites or “metal whiskers” to form and cross through the liquid electrolytes, causing a short circuit that can lead to explosions and fires. Instead of liquid electrolytes, the researchers rely on glass electrolytes that enable the use of an alkali-metal anode without the formation of dendrites.

The researchers demonstrated that their new battery cells have at least three times as much energy density as today’s lithium-ion batteries. A battery cell’s energy density gives an electric vehicle its driving range, so a higher energy density means that a car can drive more miles between charges. The UT Austin battery formulation also allows for a greater number of charging and discharging cycles, which equates to longer-lasting batteries, as well as a faster rate of recharge (minutes rather than hours).

The use of an alkali-metal anode (lithium, sodium or potassium)—which isn’t possible with conventional batteries—increases the energy density of a cathode and delivers a long cycle life. In experiments, the researchers’ cells have demonstrated more than 1,200 cycles with low cell resistance.

Additionally, because the solid-glass electrolytes can operate, or have high conductivity, at -20 degrees Celsius, this type of battery in a car could perform well in subzero degree weather. This is the first all-solid-state battery cell that can operate under 60 degree Celsius.

Braga began developing solid-glass electrolytes with colleagues while she was at the University of Porto in Portugal. About two years ago, she began collaborating with Goodenough and researcher Andrew J. Murchison at UT Austin. Braga said that Goodenough brought an understanding of the composition and properties of the solid-glass electrolytes that resulted in a new version of the electrolytes that is now patented through the UT Austin Office of Technology Commercialization.

The engineers’ glass electrolytes allow them to plate and strip alkali metals on both the cathode and the anode side without dendrites, which simplifies battery cell fabrication.

Another advantage is that the battery cells can be made from earth-friendly materials.

“The glass electrolytes allow for the substitution of low-cost sodium for lithium. Sodium is extracted from seawater that is widely available,” Braga said.

Goodenough and Braga are continuing to advance their battery-related research and are working on several patents. In the short term, they hope to work with battery makers to develop and test their new materials in electric vehicles and energy storage devices.

 

Explore further: Cathode material with high energy density for all-solid lithium-ion batteries

Provided by University of Texas at Austin

Australian National University Claim: Hydro storage can secure 100 percent renewable electricity -What Do You Think?

Pumped hydro storage can be used to help build a secure and cheap Australian electricity grid with 100 per cent renewable energy, a new study from The Australian National University (ANU) has found.

 

Lead researcher Professor Andrew Blakers from ANU said the zero-emissions grid would mainly rely on wind and solar photovoltaic (PV) technology, with support from pumped hydro storage, and would eliminate Australia’s need for coal and gas-fired power.

“With Australia wrestling with how to secure its energy supply, we’ve found we can make the switch to affordable and reliable clean power,” said Professor Blakers from the ANU Research School of Engineering.

Professor Blakers said wind and solar PV electricity provided nearly all new generation capacity in Australia and half the world’s new generation capacity each year. At present, renewable energy accounts for around 15 per cent of Australia’s electricity generation while two thirds comes from coal-fired power stations.

“However, most existing coal and gas stations will retire over the next 15 years, and it will be cheaper to replace them with wind and solar PV,” he said.

The ANU research considers the potential benefits of using hydro power energy storage, where water is pumped uphill and stored to generate electricity on demand.

“Pumped hydro energy storage is 97 per cent of all storage worldwide, and can be used to support high levels of solar PV and wind,” Professor Blakers said.

Map showing South Australia’s extensive array of potential pumped hydro energy storage sites (excluding national parks and other protected areas). In general, larger heads (red areas) lead to lower cost. Credit: Australian National University

Professor Blakers said the cost of a 100 per cent stabilized renewable electricity system would be around AU$75/MWh, which is cheaper than coal and gas-fueled power.

ANU is leading a study to map potential short-term off-river pumped hydro energy storage (STORES) sites that could support a much greater share of renewable energy in the grid.

STORES sites are pairs of reservoirs, typically 10 hectares each, which are separated by an altitude difference of between 300 and 900 metres, in hilly terrain, and joined by a pipe with a pump and turbine. Water is circulated between the upper and lower reservoirs in a closed loop to store and generate power.

Dr Matthew Stocks from the ANU Research School of Engineering said STORES needed much less water than power generated by fossil fuels and had minimal impact on the environment because water was recycled between the small reservoirs.

“This hydro power doesn’t need a river and can go from zero to full power in minutes, providing an effective method to stabilise the grid,” he said.

“The water is pumped up from the low reservoir to the high reservoir when the sun shines and wind blows and electricity is abundant, and then the water can run down through the turbine at night and when electricity is expensive.”

Co-researcher Mr Bin Lu said Australia had hundreds of potential sites for STORES in the extensive hills and mountains close to population centres from North Queensland down the east coast to South Australia and Tasmania.

Explore further: How South Australia can function reliably while moving to 100% renewable power

More information: 100% renewable electricity in Australia: energy.anu.edu.au/files/100%25%20renewable%20electricity%20in%20Australia.pdf

Provided by: Australian National University

 

U of Illinois: Tiny nanoclusters could solve big problems for lithium-ion batteries

Illustrations show the crystal structure of a superionic conductor. 

Illinois professor Prashant Jain’s research group found that ultrasmall nanoclusters of copper selenide could make superionic solid electrolytes for next-generation lithium-ion batteries. Credit: L. Brian Stauffer

As devices become smaller and more powerful, they require faster, smaller, more stable batteries. University of Illinois chemists have developed a superionic solid that could be the basis of next-generation lithium-ion batteries.

Chemistry professor Prashant Jain and graduate students Sarah White and Progna Banerjee described the material – ultrasmall nanoclusters of copper selenide – in the journal Nature Communications.

“Now that we’re seeing this nanoelectronics boom, we need tiny batteries that can be put on a chip, and that can’t happen with liquid electrolytes,” Jain said. “We are using nanostructured materials to achieve the properties at the heart of lithium-ion technology. They have much more thermal and mechanical stability, there are no leakage issues, and we can make extremely thin electrolyte layers so we can miniaturize batteries.”

Standard lithium-ion and other ionic batteries are filled with a liquid electrolyte that the lithium ions move through. The ions flow one direction when the battery is being used, and the opposite direction when the battery is charged. However, liquid electrolytes have several drawbacks: They require volume, degrade as the battery cycles, leak and are highly flammable, which has led to explosions in phones, laptops and other devices. Though solid electrolytes are considerably more stable, ions move through them much more slowly, making them less efficient for battery applications.

The copper selenide nanocluster electrolyte combines the best of both liquid and solid electrolytes: It has the stability of a solid, but ions easily move through it like a liquid. Copper selenide is known to be superionic at high temperatures, but the tiny nanoclusters are the first demonstration of the material being superionic at room temperature.

The researchers discovered this superionic property by accident while investigating copper selenide’s surface reactivity. They noticed that ultrasmall nanoclusters – about 2 nanometers in diameter – looked very different from larger copper selenide nanoparticles in an electron microscope.

“That was our first hint that they have different structures,” Jain said. “We investigated further, and we realized that these small clusters are actually semiliquid at room temperature.”

The reason for the semiliquid, superionic property is the special structure of the nanoclusters, Jain said. The much larger selenium ions form a crystal lattice, while the smaller copper ions move around them like a liquid. This crystal structure is a result of internal strain in the clusters.

“With around 100 atoms, these nanoclusters are right at the interface of molecules and nanoparticles,” Jain said. “Right now, the big push is to make every nanoparticle in a sample exactly the same size and shape. It turns out with these clusters, every single cluster is exactly the same structure. Somehow, at this size, the electronic structure of the material is so stable that every single cluster has the same arrangement of atoms.”

The researchers are working to incorporate the nanoclusters into a battery, measure the conductivity of lithium ions and compare the performance with existing solid-state electrolytes and liquid electrolytes.

Explore further: Solid electrolytes open doors to solid-state batteries

More information: Sarah L. White et al, Liquid-like cationic sub-lattice in copper selenide clusters, Nature Communications (2017). DOI: 10.1038/ncomms14514

Journal reference: Nature Communications

 

Rice Researchers Build Nano ‘sandwich’ with unique Electronic and Optical Properties

Nanoclusters of magnesium oxide sandwiched between layers of graphene make a compound with unique electronic and optical properties, according to researchers at Rice University who made computer simulations of the material. Credit: Lei Tao/Rice University

Rice University researchers have modeled a nanoscale sandwich, the first in what they hope will become a molecular deli for materials scientists.

Their recipe puts two slices of atom-thick graphene around nanoclusters of magnesium oxide that give the super-strong, conductive material expanded optoelectronic properties.

Rice materials scientist Rouzbeh Shahsavari and his colleagues built computer simulations of the compound and found it would offer features suitable for sensitive molecular sensing, catalysis and bio-imaging. Their work could help researchers design a range of customizable hybrids of two- and three-dimensional structures with encapsulated molecules, Shahsavari said.

The research appears this month in the Royal Society of Chemistry journal Nanoscale.

The scientists were inspired by experiments elsewhere in which various molecules were encapsulated using van der Waals forces to draw components together. The Rice-led study was the first to take a theoretical approach to defining the electronic and optical properties of one of those “made” samples, two-dimensional magnesium oxide in bilayer graphene, Shahsavari said.

“We knew if there was an experiment already performed, we would have a great reference point that would make it easier to verify our computations, thus allowing more reliable expansion of our computational results to identify performance trends beyond the reach of experiments,” Shahsavari said.

Graphene on its own has no band gap – the characteristic that makes a material a semiconductor. But the hybrid does, and this band gap could be tunable, depending on the components, Shahsavari said. The enhanced optical properties are also tunable and useful, he said.

“We saw that while this single flake of magnesium oxide absorbed one kind of light emission, when it was trapped between two layers of graphene, it absorbed a wide spectrum. That could be an important mechanism for sensors,” he said.

Shahsavari said his group’s theory should be applicable to other two-dimensional materials, like hexagonal boron-nitride, and molecular fillings. “There is no single material that can solve all the technical problems of the world,” he said. “It always comes down to making hybrid materials to synergize the best features of multiple components to do a specific job. My group is working on these hybrid materials by tweaking their components and structures to meet new challenges.”

Explore further: Nano-hybrid materials create magnetic effect

More information: Farzaneh Shayeganfar et al, Electro- and Opto-Mutable Properties of MgO Nanoclusters Adsorbed on Mono- and Double-Layer Graphene, Nanoscale (2017). DOI: 10.1039/C6NR08586E

Journal reference: Nanoscale

Provided by: Rice University

 

Two New Technologies that could charge your phone in seconds, Power the ioT (Internet of Things) and Power a New Generation of EF Drones (extended flight) and EL Marine Batteries (extended life)

   Image: UCF

Technology I: University of Central Florida

Leaving your phone plugged in for hours could become a thing of the past, thanks to a new type of battery technology that charges in seconds and lasts for over a week.

Watch the Video

While it probably won’t be commercially available for a years, the researchers said it has the potential to be used in phones, wearables and electric vehicles.

“If they were to replace the batteries with these supercapacitors, you could charge your mobile phone in a few seconds and you wouldn’t need to charge it again for over a week,” said Nitin Choudhary, a UCF postdoctoral associate, who conducted much of the research, published in the academic journal ACS Nano.

How does it work?

Unlike conventional batteries, supercapacitors store electricity statically on their surface which means they can charge and deliver energy rapidly. But supercapacitors have a major shortcoming: they need large surface areas in order to hold lots of energy.

To overcome the problem, the researchers developed supercapacitors built with millions of nano-wires and shells made from two-dimensional materials only a few atoms thick, which allows for super-fast charging. Their prototype is only about the size of a fingernail.

“For small electronic devices, our materials are surpassing the conventional ones worldwide in terms of energy density, power density and cyclic stability,” Choudhary said.

Cyclic stability refers to how many times a battery can be charged, drained and recharged before it starts to degrade. For lithium-ion batteries, this is typically fewer than 1,500 times.

Supercapacitors with two-dimensional materials can be recharged a few thousand times. But the researchers say their prototype still works like new even after being recharged 30,000 times.

 

Those that use the new materials could be used in phones, tablets and other electronic devices, as well as electric vehicles. And because they’re flexible, it could mean a significant development for wearables.

 

 

 

Technology II: Rice University

A new company has been formed (with exclusive licensing rights) to exploit and commercialize the Next Generation Super-Capacitors and Batteries. The opportunity is based on Nanoporous-Nickel Flexible Thin-form, Scalable Super Capacitors and Si-Nanowire Battery Technologies, developed by Rice University and Dr. James M. Tour, PhD – named “One of the Fifty (50) most influential scientists in the World today” is the inventor, patent holder and early stage developer. 

Identified Key Markets and Commercial Applications 

• Medical Devices and Wearable Electronics
• Drone/Marine Batteries and Power Banks
• Powered Smart Cards and Motor Cycle/ EV Batteries
• Sensors & Power Units for the iOT (Internet of Things) [Flexible Form, Energy Dense]  

 

The Coming Power Needs of the iOT

• The IoT is populated with billions of tiny devices.
• They’re smart.
• They’re cheap.
• They’re mobile.
• They need to communicate.
• Their numbers growing at 20%-30%/Year.

The iOT is Hungry for POWER! All this demands supercapacitors that can pack a lot of affordable power in very small volumes …Ten times more than today’s best supercapacitors can provide.

 

 

Highly Scalable – Energy Dense – Flexible Form – Rapid Charge

 Problem 1: Current capacitors and batteries being supplied to the relevant markets lack the sustainable power density, discharge and recharge cycle, warranty life combined with a ‘flexible form factor’ to scale and satisfy the identified industry need for commercial viability & performance.

Solution I: (Minimal Value Product) Tenka is currently providing full, functional Super Capacitor prototypes to an initial customer in the Digital Powered Smart Card industry and has received two (2) phased Contingent Purchase Orders during the First Year Operating Cycle for 120,000 Units and 1,200,000 Units respectively.

Solution II: For Drone/ Marine Batteries – Power Banks & Medical Devices

• Double the current ‘Time Aloft’ (1 hour+)
• Reduces operating costs
• Marine batteries – Less weight, longer life, flex form
• Provides Fast Recharging,  Extended Life Warranty.
• Full -battery prototypes being developed

Small batteries will be produced first for Powered Digital Smart Cards (In addition to the MVP Super Caps) solving packaging before scaling up drone battery operations. Technical risks are mainly associated with packaging and scaling.

The Operational Plan is to take full advantage of the gained ‘know how’ (Trade Secrets and Processes) of scaling and packaging solutions developed for the Powered Digital Smart Card and the iOT, to facilitate the roll-out of these additional Application Opportunities. Leveraging gained knowledge from operations is projected to significantly increase margins and profitability. We will begin where the Economies of Scale and Entry Point make sense (cents)!

“We are building and Energy Storage Company starting Small & Growing Big!”

Watch the YouTube Video

 

It’s ALL in Our Heads ~ Studying the Consciousness to Better Understand …

The physical brain and the conceptual mind are linked in ways that we don’t fully understand. A new collaboration is getting us closer.

How does the brain give rise to the mind? This question lies at the interface between philosophy and biology. Researchers are starting to zero in on how brain activity translates into consciousness and how we experience the world around us. The results have broad implications for cognition, brain health, human nature, and artificial intelligence.

The Azrieli Program in Brain, Mind & Consciousness is a collaboration started by the Canadian Institute for Advanced Research, bringing together a team of neuroscientists to answer these big questions.

Watch the Video

 

 

But how is it possible to probe something like consciousness? Professors Adrian Owen, Melvyn Goodale, and Lisa Saksida are all fellows of the Azrieli Program working at Western University, and they look at brain activity at the boundaries between health and dysfunction.

Owen studies patients who are losing consciousness. Communicating with patients who will soon be in a vegetative state, Owen takes functional magnetic resonance imaging (fMRI) scans to observe transitions in the brain as they lose awareness, allowing a better understanding what types of brain activity are preserved or lost.

Along similar lines, Goodale looks at how brain damage impacts cognition, memory, sensory processing, and motor control. These insights illuminate how the brain solves problems and controls complex movement, which have implications not only in health, but also in computer science and artificial intelligence, says Goodale.

Saksida wants to understand how brain circuits are altered in Alzheimer’s Disease. Drug treatment for Alzheimer’s only treats symptoms. There is still no proven therapy that stops or reverses progression of Alzheimer’s. Saksida believes the key to effective treatments is to better understand the brain circuits involved so that they can be targeted to improve cognition.

While the mind remains a bit of a mystery, these studies are working to fill in the gaps. This understanding allows researchers to better understand how the mind emerges, how it can be damaged, and perhaps one day, how it can be imitated or repaired.

NASA & MIT Collaborate to develop space-based quantum-dot spectrometer ~ Quantum Dots in Space “simplifying instrument integration.”

A NASA technologist has teamed with the inventor of a new nanotechnology that could transform the way space scientists build spectrometers, the all-important device used by virtually all scientific disciplines to measure the properties of light emanating from astronomical objects, including Earth itself.

Mahmooda Sultana, a research engineer at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, now is collaborating with Moungi Bawendi, a chemistry professor at the Cambridge-based Massachusetts Institute of Technology, or MIT, to develop a prototype imaging spectrometer based on the emerging quantum-dot technology that Bawendi’s group pioneered. NASA’s Center Innovation Fund, which supports potentially trailblazing, high-risk technologies, is funding the effort.

Introducing Quantum Dots

Quantum dots are a type of semiconductor nanocrystal discovered in the early 1980s. Invisible to the naked eye, the dots have proven in testing to absorb different wavelengths of light depending on their size, shape, and chemical composition. The technology is promising to applications that rely on the analysis of light, including smartphone cameras, medical devices, and environmental-testing equipment.

“This is as novel as it gets,” Sultana said, referring to the technology that she believes could miniaturize and potentially revolutionize space-based spectrometers, particularly those used on uninhabited aerial vehicles and small satellites. “It really could simplify instrument integration.”

Absorption spectrometers, as their name implies, measure the absorption of light as a function of frequency or wavelength due to its interaction with a sample, such as atmospheric gases.

After passing through or interacting with the sample, the light reaches the spectrometer. Traditional spectrometers use gratings, prisms, or interference filters to split the light into its component wavelengths, which their detector pixels then detect to produce spectra. The more intense the absorption in the spectra, the greater the presence of a specific chemical.

While space-based spectrometers are getting smaller due to miniaturization, they still are relatively large, Sultana said. “Higher-spectral resolution requires long optical paths for instruments that use gratings and prisms. This often results in large instruments. Whereas here, with quantum dots that act like filters that absorb different wavelengths depending on their size and shape, we can make an ultra-compact instrument. In other words, you could eliminate optical parts, like gratings, prisms, and interference filters.”

Just as important, the technology allows the instrument developer to generate nearly an unlimited number of different dots. As their size decreases, the wavelength of the light that the quantum dots will absorb decreases. “This makes it possible to produce a continuously tunable, yet distinct, set of absorptive filters where each pixel is made of a quantum dot of a specific size, shape, or composition. We would have precise control over what each dot absorbs. We could literally customize the instrument to observe many different bands with high-spectral resolution.”

Prototype Instrument Under Development

With her NASA technology-development support, Sultana is working to develop, qualify through thermal vacuum and vibration tests, and demonstrate a 20-by-20 quantum-dot array sensitive to visible wavelengths needed to image the sun and the aurora. However, the technology easily can be expanded to cover a broader range of wavelengths, from ultraviolet to mid-infrared, which may find many potential space applications in Earth science, heliophysics, and planetary science, she said.

Under the collaboration, Sultana is developing an instrument concept particularly for a CubeSat application and MIT doctoral student Jason Yoo is investigating techniques for synthesizing different precursor chemicals to create the dots and then printing them onto a suitable substrate. “Ultimately, we would want to print the dots directly onto the detector pixels,” she said.

“This is a very innovative technology,” Sultana added, conceding that it is very early in its development. “But we’re trying to raise its technology-readiness level very quickly. Several space-science opportunities that could benefit are in the pipeline.”

NASA

UC Berkeley: Magnetic nano-particle imaging Research May Lead to Early Cancer Detection

Tracer dynamics in a group of rats

 

Magnetic particle imaging is a new, up-and-coming, safe and highly sensitive tracer imaging technique that works by detecting super-para-magnetic iron oxide nano-particles with high image contrast (that is, no background tissue signal). The technique, which does not use any ionizing radiation, can be used to image anywhere inside the body, which means that it could be promising for detecting and monitoring tumors. Researchers in the US are now the first to have used MPI to passively detect cancer by basically exploiting the abnormal leakiness of tumor blood vessels – a finding that bodes well for the early detection of cancers like breast cancer in patients at risk for the disease.

Biomedical imaging is important at every stage of diagnosing and treating cancer, beginning with initial screening, through to diagnosis, treatment planning and monitoring. The biggest challenge here is to be able to reliably distinguish tumour tissue from healthy tissue, something that is not as easy as it sounds.

“Conventional anatomical techniques, such as X-ray, X-ray computed tomography (CT), ultrasound and magnetic resonance imaging (MRI), are very useful for detecting the tissue architecture changes that generally accompany cancer, but the native contrast of tumours may not differ sufficiently from healthy tissue for a confident diagnosis, especially for metastatic or so-called diffuse tumours” explains lead author of the study Elaine Yu, who is completing her Bioengineering PhD in Steven Conolly’s lab at the University of California at Berkeley (UCB). “This is why exogenous contrast agents, such as iodine (for X-ray and CT) and gadolinium (for MRI) are often administered to highlight crucial vascular differences between normal and cancerous tissue for more precise screening.”

Exploiting the EPR effect

Contrast agents are all injected intravenously, but the way they highlight tumours differs considerably. Nanosized agents are better than conventional low molecular weight agents in one respect because they are not immediately excreted by the kidneys if designed to be large enough. They are thus able to circulate in the blood for extended periods of time. The naturally leaky vasculature of some tumours also allows nanosized particles to preferentially end up in tumour tissue, where they can be held. This is known as the enhanced permeability and retention (EPR) effect.

“Our work is the first to exploit the EPR effect with the high sensitivity and contrast afforded by magnetic particle imaging (MPI),” says Yu. “We have succeeded in imaging tumours in rats with vivid tumour-to-background contrast. “Thanks to its high sensitivity and good signal throughout the entire body, we were able to clearly capture the nanoparticle dynamics in the tumour: so-called rim enhancement, peak particle uptake at six hours after administration and eventual clearance beyond 48 hours.”

Synthesizing the SPIOs

The MPI-tailored superparamagnetic iron oxide nanoparticle (SPIO) tracers were synthesized by team members at LodeSpin Labs and by Kannan Krishnan’s lab at the University of Washington (UW), and were designed for optimal imaging resolution and long blood circulation time. “The iron oxide nanoparticles were made by thermolysis of iron III oleate in 1-octadcene, with subsequent oxidation to achieve the desired magnetic behaviour and coated with the biocompatible coating MPAO-PEG,” explains Yu.

The researchers injected the nanoparticles into the tail veins of rats and then performed a series of MPI scans as the nanoparticles travelled through the circulation. Thanks to the EPR effect, the particles preferentially accumulated in tumours and were retained there for up to six days.

Imaging the SPIO electronic moment

MPI was first developed by Philips Research in 2005 and is a tracer imaging technique that directly measures the location and concentration of SPIO nanoparticles in vivo. It images the SPIO electronic moment, which is 22 million times more intense than nuclear MRI moments. When a time-varying exciting field is applied, it causes the moments of the SPIOs to instantaneously “flip”, thereby inducing a signal in a receiver coil.

“The advantages of MPI are its superb contrast and sensitivity, which could very soon rival the dose-limited sensitivity of nuclear medicine techniques,” Conolly tells nanotechweb.org. “This is very exciting, since MPI does not rely on ionizing radiation. The scanner and iron oxide tracer are also thought to be safe for humans. Indeed, some SPIO agents are already FDA or EU safety approved for human use in other clinical applications.”

MPI tracers are excreted through the liver

Importantly, the MPI tracers are excreted through the liver, rather than through the kidneys, and there is evidence that SPIOs could be safer than iodine and gadolinium for patients with chronic kidney disease. “Given all these advantages, we are very hopeful that MPI could play an important role in early-stage cancer detection. Indeed, we are particularly focusing on early-stage breast cancer detection in the subpopulation of women with radiologically dense breast tissue and who are at high risk for cancer (because of, for example, BRCA1 or BRCA2 defects, or family history of the disease).”

Conolly says that he and his colleagues are now working hard to improve MPI in terms of resolution and sensitivity. “We are also studying MPI for stem-cell tracking, detecting pulmonary embolism, brain perfusion to detect and monitor strokes or traumatic brain injuries, and T-cell immunotherapy studies in collaboration with researchers at Berkeley, the University of California at San Francisco, UW, Case Western, Harvard and Stanford. We would also like to follow up on several promising demonstrations of MPI-guided magnetic fluid hyperthermia exploiting the unique ‘focusing’ capabilities of MPI to selectively heat tumours or to release chemotherapeutic agents specifically into a tumour. We are doing this work with University of Florida collaborators.”

The new MPI cancer imaging study is described in Nano Letters DOI: 10.1021/acs.nanolett.6b04865.

“Your Heart (Organ) on-a-chip” ~ mimics heart’s biomechanical properties (w/video)

Posted: Feb 23, 2017

The human heart beats more than 2.5 billion times in an average lifetime. Now scientists at Vanderbilt University have created a three-dimensional organ-on-a-chip that can mimic the heart’s amazing biomechanical properties.

“We created the I-Wire Heart-on-a-Chip so that we can understand why cardiac cells behave the way they do by asking the cells questions, instead of just watching them,” said Gordon A. Cain University Professor John Wikswo, who heads up the project. 

“We believe it could prove invaluable in studying cardiac diseases, drug screening and drug development, and, in the future, in personalized medicine by identifying the cells taken from patients that can be used to patch damaged hearts effectively.”

The device and the results of initial experiments demonstrating that it faithfully reproduces the response of cardiac cells to two different drugs that affect heart function in humans are described in an article published last month in the journal Acta Biomaterialia ~

(“I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology”). 

A companion article in the same issue presents a biomechanical analysis of the I-Wire platform that can be used for characterizing biomaterials for cardiac regenerative medicine.

I-Wire device with cardiac fiber shown in magnification window. (Image: VIIBRE / Vanderbilt)

The unique aspect of the new device, which represents about two millionths of a human heart, is that it controls the mechanical force applied to cardiac cells. 

This allows the researchers to reproduce the mechanical conditions of the living heart, which is continually stretching and contracting, in addition to its electrical and biochemical environment.

“Heart tissue, along with muscle, skeletal and vascular tissue, represents a special class of mechanically active biomaterials,” said Wikswo. “Mechanical activity is an intrinsic property of these tissues so you can’t fully understand how they function and how they fail without taking this factor into account.”

“Currently, we don’t have many models for studying how the heart responds to stress. Without them, it is very difficult to develop new drugs that specifically address what goes wrong in these conditions,” commented Charles Hong, associate professor of cardiovascular medicine at Vanderbilt’s School of Medicine, who didn’t participate in the research but is familiar with it. 

“This provides us with a really amazing model for studying how hearts fail.”

The I-Wire device consists of a thin thread of human cardiac cells 0.014 inches thick (about the size of 20-pound monofilament fishing line) stretched between two perpendicular wire anchors. 

The amount of tension on the fiber can be varied by moving the anchors in and out, and the tension is measured with a flexible probe that pushes against the side of the fiber.

The fiber is supported by wires and a frame in an optically clear well that is filled with liquid medium like that which surrounds cardiac cells in the body. The apparatus is mounted on the stage of a powerful optical microscope that records the fiber’s physical changes. 
The microscope also acts as a spectroscope that can provide information about the chemical changes taking place in the fiber. 
A floating microelectrode also measures the cells’ electrical activity.

According to the researchers, the I-Wire system can be used to characterize how cardiac cells respond to electrical stimulation and mechanical loads and can be implemented at low cost, small size and low fluid volumes, which make it suitable for screening drugs and toxins. Because of its potential applications, Vanderbilt University has patented the device.

Video taken through a microscope shows I-Wire heart fiber. left, beating at different frequencies. The black circle, right, is the flexible cantilever that measures the force of the fiber’s contractions. (Veniamin Sidorov / VIIBRE /Vanderbilt)

Unlike other heart-on-a-chip designs, I-Wire allows the researchers to grow cardiac cells under controlled, time-varying tension similar to what they experience in living hearts. 

As a consequence, the heart cells in the fiber align themselves in alternating dark and light bands, called sarcomeres, which are characteristic of human muscle tissue. The cardiac cells in most other heart-on-a-chip designs do not exhibit this natural organization.

In addition, the researchers have determined that their heart-on-a-chip obeys the Frank-Starling law of the heart. The law, which was discovered by two physiologists in 1918, describes the relationship between the volume of blood filling the heart and the force with which cardiac cells contract. The I-Wire is one of the first heart-on-a-chip devices to do so.

To demonstrate the I-Wire’s value in determining the effects that different drugs have on the heart, the scientists tested its response with two drugs known to affect heart function in humans: isoproterenol and blebbistatin. Isoproterenol is a medication used to treat bradycardia (slow heart rate) and heart block (obstruction of the heart’s natural pacemaker). Blebbistatin inhibits contractions in all types of muscle tissue, including the heart.

According to Veniamin Sidorov, the research assistant professor at the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) who led its development, the device faithfully reproduces the response of cardiac cells in a living heart.

“Cardiac tissue has two basic elements: an active, contractile element and a passive, elastic element,” said Sidorov. “By separating these two elements with blebbistatin, we successfully characterized the elasticity of the artificial tissue. By exposing it to isoproterenol, we tested its response to adrenergic stimulation, which is one of the main systems responsible for regulation of heart contractions. 
We found that the relationship between these two elements in the cardiac fiber is consistent with that seen in natural tissue. 

This confirms that our heart-on-a-chip model provides us with a new way to study the elastic response of cardiac muscle, which is extremely complicated and is implicated in heart failure, hypertension, cardiac hypertrophy and cardiomyopathy.”

Source: Vanderbilt University