MIT: Researchers Achieve Remote control of Hormone Release Using Magnetic Nanoparticles


Magnetic Nanoparticles 13-researchersa
MIT engineers have developed magnetic nanoparticles (shown in white squares) that can stimulate the adrenal gland to produce stress hormones such as adrenaline and cortisol. Credit: Massachusetts Institute of Technology

Abnormal levels of stress hormones such as adrenaline and cortisol are linked to a variety of mental health disorders, including depression and posttraumatic stress disorder (PTSD). MIT researchers have now devised a way to remotely control the release of these hormones from the adrenal gland, using magnetic nanoparticles.

This approach could help scientists to learn more about how  release influences mental health, and could eventually offer a new way to treat hormone-linked disorders, the researchers say.

“We’re looking how can we study and eventually treat stress disorders by modulating peripheral organ function, rather than doing something highly invasive in the central nervous system,” says Polina Anikeeva, an MIT professor of materials science and engineering and of brain and cognitive sciences.

To achieve control over hormone release, Dekel Rosenfeld, an MIT-Technion postdoc in Anikeeva’s group, has developed specialized  that can be injected into the adrenal gland. When exposed to a weak magnetic field, the particles heat up slightly, activating heat-responsive channels that trigger hormone release. This technique can be used to stimulate an organ deep in the body with minimal invasiveness.

Anikeeva and Alik Widge, an assistant professor of psychiatry at the University of Minnesota and a former research fellow at MIT’s Picower Institute for Learning and Memory, are the senior authors of the study. Rosenfeld is the lead author of the paper, which appears today in Science Advances.

Controlling hormones

Anikeeva’s lab has previously devised several novel magnetic nanomaterials, including particles that can release drugs at precise times in specific locations in the body.

In the new study, the research team wanted to explore the idea of treating disorders of the brain by manipulating organs that are outside the central nervous system but influence it through hormone release. One well-known example is the hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress response in mammals. Hormones secreted by the , including cortisol and adrenaline, play important roles in depression, stress, and anxiety.

“Some disorders that we consider neurological may be treatable from the periphery, if we can learn to modulate those local circuits rather than going back to the global circuits in the ,” says Anikeeva, who is a member of MIT’s Research Laboratory of Electronics and McGovern Institute for Brain Research.

As a target to stimulate hormone release, the researchers decided on  that control the flow of calcium into adrenal cells. Those ion channels can be activated by a variety of stimuli, including heat. When calcium flows through the open channels into adrenal cells, the cells begin pumping out hormones. “If we want to modulate the release of those hormones, we need to be able to essentially modulate the influx of calcium into adrenal cells,” Rosenfeld says.

Unlike previous research in Anikeeva’s group, in this study magnetothermal stimulation was applied to modulate the function of cells without artificially introducing any genes.

To stimulate these heat-sensitive channels, which naturally occur in adrenal cells, the researchers designed nanoparticles made of magnetite, a type of iron oxide that forms tiny magnetic crystals about 1/5000 the thickness of a human hair. In rats, they found these particles could be injected directly into the adrenal glands and remain there for at least six months. When the rats were exposed to a weak magnetic field—about 50 millitesla, 100 times weaker than the fields used for magnetic resonance imaging (MRI)—the particles heated up by about 6 degrees Celsius, enough to trigger the calcium channels to open without damaging any surrounding tissue.

The heat-sensitive  that they targeted, known as TRPV1, is found in many sensory neurons throughout the body, including . TRPV1 channels can be activated by capsaicin, the organic compound that gives chili peppers their heat, as well as by temperature. They are found across mammalian species, and belong to a family of many other channels that are also sensitive to heat.

This stimulation triggered a hormone rush—doubling cortisol production and boosting noradrenaline by about 25 percent. That led to a measurable increase in the animals’ heart rates.

Treating stress and pain

The researchers now plan to use this approach to study how hormone release affects PTSD and other disorders, and they say that eventually it could be adapted for treating such disorders. This method would offer a much less invasive alternative to potential treatments that involve implanting a medical device to electrically stimulate hormone release, which is not feasible in organs such as the adrenal glands that are soft and highly vascularized, the researchers say.

Another area where this strategy could hold promise is in the treatment of pain, because heat-sensitive ion channels are often found in pain receptors.

“Being able to modulate pain receptors with this technique potentially will allow us to study pain, control pain, and have some clinical applications in the future, which hopefully may offer an alternative to medications or implants for chronic pain,” Anikeeva says. With further investigation of the existence of TRPV1 in other organs, the technique can potentially be extended to other peripheral organs such as the digestive system and the pancreas.


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The myth behind adrenal fatigue


More information: Dekel Rosenfeld et al. Transgene-free remote magnetothermal regulation of adrenal hormones, Science Advances (2020). DOI: 10.1126/sciadv.aaz3734

Journal information: Science Advances

Bioprinting techniques advance from shape to function – Revolutionizing the toolkit for Regenerative Medicine


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Possible approaches toward the convergence of bioprinting and self-organization to guide the maturation of bioprinted constructs toward the generation of functional tissues. Inspired by the composition of adult, native tissues, multiple progenitor or differentiated cells can be loaded into bioinks to build tissues or organoids. In this approach, the architecture imposed by the printing process will be templating the cell-driven development of the tissue and its subsequent maturation. Alternatively, specific stem and progenitor cells that possess the ability to autonomously organize into submillimeter to millimeter organoids that exhibit salient tissue features can be used as intermediate building blocks and as bioink components. In both processes, the stimuli provided by the biomaterials, their architecture, and bioactive factors included in the bioinks play key roles for driving the acquisition of native functions. (Reprinted with permission by Wiley-VCH Verlag) (click on image to enlarge)

 

Biofabrication is a revolutionizing toolkit for regenerative medicine that allows cells and other biomaterials to be precisely combined and patterned into three-dimensional (3D) constructs through automated, cell-friendly fabrication methods.

One of these methods is bioprinting, an additive 3D-printing method where tissue growth and the behavior of cells can be controlled and investigated by embedding them in a delicate 3D framework.3D bioprinting is a highly-advanced manufacturing platform that allows for the printing of tissue, and eventually vital organs, from cells.

This could open a new world of possibilities for the medical field, while directly benefiting patients who need replacement organs.In the early days of bioprinting, around 2013, the lack of printable materials that could serve as cell-laden bioinks, as well as the limitations of printing and assembly methods, presented major constraints for the usefulness of the technique.Things have changed since then.

With rapid advanced in 3D-printing hardware on one hand and bioink materials on the other, biofabrication techniques have gained significant momentum and provide a powerful approach to tackle major hurdles in the generation of engineered living tissues.While 3D bioprinting is still in its early stages, the remarkable leap it has made in recent years points to the eventual reality of lab-grown, functional organs.

Bioprinted structures are being designed and studied for a wide range of biomedical uses. For instance, researchers have demonstrated 3D-bioprinting of living structures with built-in chemical sensors or to create functional liver tissues. Other potential uses are transplantable grafts for tissue restoration; advanced in vitro models to aid the testing of drugs; and potential alternatives to animal experimentation.With regard to building materials in biofabrication processes, two different types of printable inks can generally be distinguished.

One are biomaterial inks used to print cellular structures on which cells are seeded or that can also be used as surgical tools or implants after fabrication. Many different materials, including thermoplasts and metal powders, can be processed that way. The other types are bioinks – printable formulations that contain living cells.

These two different types of inks have different,sometimes opposing printing requirements. The simultaneous need for these opposing requirements led to the conceptualization of the biofabrication window, the range of material properties suitable both for printability with high shape fidelity and for the support of cell function.

In a recent review in Advanced Materials (“From Shape to Function: The Next Step in Bioprinting”), the authors summarize key strategies that have expanded the biofabrication window and that lead to improved control over shape. Building on such advances in material science, their main focus is on the current and future steps toward mimicking salient functionalities of living tissues, through the creation of hierarchically structured constructs, in particular when using bioinks as building blocks for extrusion-based bioprinting.

The review discusses the impact of bioprinted constructs with preformed spatial organization to facilitate tissue morphogenesis. The authors highlight recent and upcoming developments in biofabrication that could influence the next generation of engineered tissues. They point out that the recent progress in hydrogel design together with the development of new bioprinting strategies, have introduced effective solutions to extend the biofabrication window, reducing the need to compromise on the use of materials that display satisfactory structural properties, but provide a nonoptimal environment for cells to thrive.Cell functionality is necessary both for in vitro models and to move forward toward the demonstration of applicability of bioprinted constructs as biomedical devices that can eventually be used as clinical solution to repair damaged tissues, and bring researchers a step closer toward the ambitious goal of functional bioprinting.Despite this remarkable progress, scientists are only beginning to tap into the potential of biofabrication in aiding the reconstruction of fully functional living engineered tissues.

Finally, the authors urge that future strategies embrace biological (developmental) processes and integrate them with bioprinting technologies to yield constructs with biological function toward the ambitious goal of printing functional tissues or even entire organs.

By 

Copyright @Nanowerk

MIT: The coronavirus test that might exempt you from social distancing—if you pass – An Update


MIT COVID 0420 gettyimages-1212775374webA demonstration of a covid-19 blood test developed by Surescreen Diagnostics. C. FURLONG Image

There is a lot of hype around the potential for antibody testing to help get us back outside sooner rather than later. Here’s how it works.

MIT Technology Review: Neel V. Patel

On Monday, President Trump announced that the US had tested over a million patient samples for coronavirus, by far more than any other country in the world. Though the horrendously slow rollout of testing has already set America back in its effort to stop the spread of covid-19, testing is still vital. To beat the virus and stop its spread, says the World Health Organization, we need to identify those who are infected and isolate them, as well as those at risk (who ought to be self-isolating too, whether they are symptomatic or asymptomatic). We also need to figure out which communities can expect to see a rise in coronavirus cases, and where to allocate resources in anticipation of rising hospitalizations.

As reported by MIT Technology Review a few weeks ago, there’s also a serious need for us to find out who has already been infected and is now, presumably, immune to the virus (at least for a while). Since the coronavirus outbreak began, many different groups have ramped up their efforts to develop a serological test that looks for antibodies to the virus—an indication of whether an individual was once infected. Should a test like this ever become available to the public, it could radically shape how we decide who gets to leave home and return to some semblance of normal life.

You can read all our coverage of the coronavirus/Covid-19 outbreak for free, and also sign up for our coronavirus newsletter. But please consider subscribing to support our nonprofit journalism.

Here are the biggest things you should know about the status of antibody testing for covid-19. 

A Berlin Biotech Company Got a Head Start on Coronavirus Tests

Why do we want antibody testing?

Many infected individuals experience only mild or moderate symptoms that clear out fairly quickly. Since there are simply not enough test kits to go around, a lot of people who aren’t showing more severe symptoms are being turned away for testing. Those individuals (myself included) are effectively in limbo, having no way to verify if they were once sick and now potentially immune, or still at risk of being sick and spreading the virus. Moreover, if we’re not able to test everyone, we have no way to really answer questions such as how widespread the infection is, what the true fatality rate is, and what kinds of measures to stop the spread are actually working.

Antibody testing that’s made available en masse might be able to help answer some of those basic questions. Once we have a better understanding of how immunity works with the coronavirus, it could also give survivors of the infection confirmation that they are now immune, meaning they no longer pose a threat to others and could potentially return to work and public life. This would be especially critical for clinics and hospitals experiencing staffing shortages, or infrastructure and utilities providers who need properly trained workers to keep things like our power grids running.

How does it work?

When the body is introduced to a pathogen, the immune system develops tailor-made antibodies that act against the infection. Antibodies can last a long time—anywhere from a couple of years to a lifetime, depending on the disease. During the period that immunity lasts, your body is prepared to ramp up production of those antibodies to neutralize the threat should it ever appear again.

An antibody test, also known as a serology test, analyzes a patient’s serum—the liquid portion of blood that excludes cells and clotting factors but includes antibodies. Many of these tests are simple and require only a small sample, like a finger prick. In this case, through a technique like ELISA (enzyme-linked immunosorbent assay), clinicians look for antibodies that were made in response to the large protein that sticks out of the coronavirus’s surface. A viral fragment is placed on a plate. If there’s an antibody in the patient sample, it will attach to this “spike” protein. Another antibody, engineered by the clinicians and capable of attaching to the first antibody, is introduced to the solution. When they bind, the new antibody will activate an enzyme that changes the color of the solution, indicating that the patient has the antibodies we’re looking for, and has therefore been exposed to the coronavirus.

How is this different from the testing we already do?

The way we’re testing infections right now is by looking for viral genetic material in patient samples. Using a method called polymerase chain reaction (PCR), clinicians can amplify any coronavirus RNA in a patient’s nasal swab so its presence can be confirmed. Viral DNA or RNA can be found in the body as soon as an infection begins, even if you’re asymptomatic. But it disappears soon after the immune system clears the infection out. So this type of test is useful to find out who is currently infected, but not who once was infected.

Antibodies, on the other hand, aren’t developed until several days after infection has taken hold, so they aren’t a useful indicator of who is currently infected. But because they’re around in the blood in large numbers for many months after infection, they would be extremely useful to identify past cases long after the infection has been beaten.

How much does it cost?

A serological test for coronavirus antibodies is much less costly than a PCR test that looks for coronavirus genetic material. California-based Biomerica, for example, sells a serological test for less than $10. A PCR test for covid-19 can cost up to $51 under Medicare. 

How fast is it?

You can get results from a serological test in just minutes. Many groups are working on versions that can be run at home, with no need to send samples to a lab. A PCR test takes hours to run, and because samples must typically be shipped back and forth from the testing site, patients usually don’t get results for at least several days (although the FDA is fast-tracking a portable point-of-care genetic test for coronavirus that’s supposed to take less than 15 minutes).

Who’s working on this?

Many, many groups. Singapore, China, and other countries have already conducted limited numbers of antibody testing. A group led by virologist Florian Krammer at the Icahn School of Medicine at Mount Sinai in New York City recently developed an ELISA-based antibody test for covid-19. American companies like Biomerica and Chembio Diagnostics (from New York) are selling antibody tests outside the US, with aggressive plans to get these kits up to snuff for FDA approval. BioMedomics of North Carolina, in collaboration with medical tech company BD, just launched a point-of-care test that can be administered at the doctor’s office and give results in 15 minutes. The UK has its own test, developed by Public Health England, and recently ordered 3.5 million kits to be distributed by Amazon and pharmacies around the country in just a matter of days.

What are the limitations?

Since we still don’t know how long covid-19 immunity lasts, the presence of antibodies is not a guarantee a person is totally immune to future reinfection. Similarly, antibodies can’t be used to determine whether someone is still contagious—a follow-up PCR test might be necessary to rule out an ongoing infection. In other words, you’d want to test positive for immunity through an antibody test (even well after the infection is cleared), and negative for the virus through a PCR test.

There is a huge concern about the accuracy of serological tests. PCR testing, for all its drawbacks, is still considered pretty accurate. In an antibody test, however, a patient might test positive for covid-19 because of antibodies against a different coronavirus (like ones that cause the common cold). Two patients might be infected and recover at about the same time, but one’s antibody test might not stay positive as long as the other’s. And again, there is a huge window of uncertainty because it could take up to a week for a body to start generating antibodies against the virus after infection has set in. Taking the test during infection may not deliver a very confident result. An accuracy of, say, 80% still leaves one in five people with a false result. Spain recently recalled more than 8,000 Chinese-made test kits because of worries about inaccurate results. More than a dozen companies that have notified the FDA they are producing antibody tests are allowed to begin distributing the tests to hospitals and doctors’ offices, but they must carry disclaimer statements that read: “This test has not been reviewed by the FDA.” Accuracy and reliability won’t be ensured without validation and experience over time.

And because covid-19 is such a new disease, we don’t know how long immunity will last. Right now the virus seems to be mutating slowly and shouldn’t pose an annual problem like the flu, but we’ve only been studying it for a little over three months. Tony Mazzulli, chief microbiologist with Toronto’s Sinai Health, told the New York Times it’s also unclear whether antibodies would prevent infection from exposure to a large amount of the virus, as in a hospital setting.

Phage capsid against influenza: Perfectly fitting inhibitor prevents viral infection


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Phage shell docks on and inhibits the influenza virus. Credit: Barth van Rossum / FMP

A new approach brings the hope of new therapeutic options for suppressing seasonal influenza and avian flu. On the basis of an empty and therefore non-infectious shell of a phage virus, researchers from Berlin have developed a chemically modified phage capsid that stifles influenza viruses.

Perfectly fitting binding sites cause influenza viruses to be enveloped by the phage capsids in such a way that it is practically impossible for them to infect . This phenomenon has been proven in preclinical trials using human lung tissue. Researchers from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Freie Universität Berlin, Technische Universität Berlin (TU), Humboldt-Universität (HU), the Robert Koch Institute (RKI) and Charité-Universitätsmedizin Berlin report that the results are also being used for the immediate investigation of the coronavirus. The findings have now been published in Nature Nanotechnology.

Influenza viruses are still highly dangerous. The World Health Organization (WHO) estimates that flu is responsible for up to 650,000 deaths per year worldwide. Current antiviral drugs are only partially effective because they attack the  after lung cells have been infected. It would be desirable—and much more effective—to prevent infection in the first place.

This is exactly what the new approach from Berlin promises. The phage capsid, developed by a multidisciplinary team of researchers, envelops flu viruses so perfectly that they can no longer infect cells. “Pre-clinical trials show that we are able to render harmless both  viruses and avian flu viruses with our chemically modified phage shell,” explained Professor Dr. Christian Hackenberger, Head of the Department Chemical Biology at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and Leibniz Humboldt Professor for Chemical Biology at HU Berlin. “It is a major success that offers entirely new perspectives for the development of innovative antiviral drugs.”

Multiple bonds fit like Velcro

The new inhibitor makes use of trivalent receptors on the surface of the influenza virus, referred to as hemagglutinin protein, that attach to sugar molecules (sialic acids) on the cell surfaces of lung tissue. In the case of infection, viruses hook into their victim—in this case, lung cells—like a hook-and-loop fastener. The core principle is that these interactions occur due to multiple bonds, rather than single bonds.

It was the surface structure of flu viruses that inspired the researchers to ask the following initial question more than six years ago: Would it not be possible to develop an inhibitor that binds to trivalent receptors with a perfect fit, simulating the surface of lung tissue cells?

They found that this is indeed possible with the help of a harmless intestinal inhabitant: The Q-beta phage has the ideal surface properties and is excellently suited to equip it with ligands—in this case, sugar molecules—as “bait.” An empty phage shell does the job perfectly. “Our multivalent scaffold molecule is not infectious, and comprises 180 identical proteins that are spaced out exactly as the trivalent receptors of the hemagglutinin on the surface of the virus,” explained Dr. Daniel Lauster, a former Ph.D. student in the Group of Molecular Biophysics (HU) and now a postdoc at Freie Universität Berlin. “It therefore has the ideal starting conditions to deceive the influenza virus—or, to be more precise, to attach to it with a perfect spatial fit. In other words, we use a phage virus to disable the influenza virus!”

To enable the Q-beta scaffold to fulfill the desired function, it must first be chemically modified. Produced from E. coli bacteria at TU Berlin, Professor Hackenberger’s research group at FMP and HU Berlin use synthetic chemistry to attach sugar molecules to the defined positions of the virus shell.

Virus is deceived and enveloped

Several studies using animal models and  have proven that the suitably modified spherical structure possesses considerable bond strength and inhibiting potential. The study also enabled the Robert Koch Institute to examine the antiviral potential of phage capsids against many current influenza virus strains, and even against  viruses. Its therapeutic potential has even been proven on human lung tissue, as fellow researchers from the Medical Department, Division of Infectiology and Pneumology, of Charité were able to show: When tissue infected with flu viruses was treated with the phage capsid, the influenza viruses were practically no longer able to reproduce.

The results are supported by structural proof by FU scientists from the Research Center of Electron Microscopy (FZEM): High-resolution cryo-electron microscopy and cryo-electron microscopy show directly and spatially that the inhibitor completely encapsulates the virus. In addition, mathematical-physical models were used to simulate the interaction between  and the phage capsid on the computer. “Our computer-assisted calculations show that the rationally designed inhibitor does indeed attach to the hemagglutinin, and completely envelops the influenza virus,” confirmed Dr. Susanne Liese from the AG Netz of Freie Universität Berlin. “It was therefore also possible to describe and explain the high bond strength mathematically.”

Therapeutic potential requires further research

These findings must now be followed up by more preclinical studies. It is not yet known, for example, whether the phage capsid provokes an  in mammals. Ideally, this response could even enhance the effect of the inhibitor. However, it could also be the case that an immune response reduces the efficacy of  capsids in the case of repeated-dose exposure, or that flu viruses develop resistances. And, of course, it has yet to be proven that the inhibitor is also effective in humans.

Nonetheless, the alliance of Berlin researchers is certain that the approach has great potential. “Our rationally developed, three-dimensional, multivalent inhibitor points to a new direction in the development of structurally adaptable   binders. This is the first achievement of its kind in multivalency research,” emphasized Professor Hackenberger. The chemist believes that this approach, which is biodegradable, non-toxic and non-immunogenic in cell culture studies, can in principle also be applied to other viruses, and possibly also to bacteria. It is evident that the authors regard the application of their approach to the current coronavirus as one of their new challenges. The idea is to develop a drug that prevents coronaviruses from binding to host cells located in the throat and subsequent airways, thus preventing infection.


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NREL – Meet Three Women Making Waves in Marine Energy Research


March 30, 2020

To offer some light in a tough time, the National Renewable Energy Laboratory (NREL) celebrates Women’s History Month and highlights the innovation and leadership of women in marine energy research.

Representing two national laboratories, NREL and Pacific Northwest National Laboratory (PNNL), as well as the Department of Energy (DOE), the three women featured here direct departments to advance marine energy research and technology, conduct research themselves, and manage projects. These researchers demonstrate the impact women have in the water power industry and exemplify the variety of marine energy careers.

Jennifer Daw

Headshot of Jennifer Daw.

As a senior researcher and group manager in NREL’s Integrated Application Center (IAC), Jennifer Daw focuses her work on integrated strategies for energy, water, and land/food systems, with an emphasis on the water systems, including water utilities, wastewater, hydropower, and marine energy.

Daw began working at NREL nearly a decade ago, and her work to leverage the energy-water-food nexus to develop sustainable solutions has become increasingly relevant over the years. When addressing complex, global issues caused by population growth, extreme weather events, obsolete infrastructure, and other factors, Daw believes that a comprehensive, cross-sectoral approach is key to creating balance that supports the environment, communities, and the economy. See how Daw’s background in water systems sustainability supports the IAC’s systems-based approach.

Carrie Schmaus

A woman, Carrie Schmaus, stands in front of a body of water with arms raised.

Carrie Schmaus is an Oak Ridge Institute for Science and Education Science, Technology, and Policy Fellow in DOE’s Water Power Technologies Office (WPTO). She has a background in marine science and policy and joined WPTO as a Sea Grant Knauss Fellow.

For Schmaus, her work at DOE is driven by her passion for marine energy research and the impact it has on communities, the environment, aspiring marine scientists, and “the greater good.” Read why Schmaus encourages diversity in science and technology and her tips on how to get involved in the renewable energy sector.

Genevra Harker-Klimeš

A woman, Genevra Harker-Klimeš, smiles at camera in front of a blurred blue background.

Genevra Harker-Klimeš leads PNNL’s Coastal Sciences Division. An expert in oceanography with a background in the physical aspects of the ocean, Harker-Klimeš develops marine renewable energy devices at PNNL as part of a DOE initiative.

Working in the male-dominated world of oil rigs and boats, she quickly learned that her knowledge and perseverance were useful to advancing in the marine energy field. Harker-Klimeš appreciates that her work at PNNL promotes a cross-section of knowledge, where industry experts collaborate to address the country’s leading energy issues. Learn how Harker-Klimeš’ love for travel, outdoor spaces, and the ocean led her to working in marine energy.

The marine energy industry has the potential to provide consistent, predictable clean power and support global energy demands. Follow in the footsteps of Daw, Schmaus, and Harker-Klimeš and see how other women in water power are paving the way for a more diverse representation in the water power industry through both hydropower and marine energy research.

Heart Attack on a Chip: Scientists Model Conditions of Ischemia on a Microfluidic Device


heartattacko
The microfluidic device containing HL-1 cardiac cells is capable of modeling conditions observed during a heart attack, including a reduction in levels of oxygen. Credit: Tufts University

Researchers led by biomedical engineers at Tufts University invented a microfluidic chip containing cardiac cells that is capable of mimicking hypoxic conditions following a heart attack—specifically when an artery is blocked in the heart and then unblocked after treatment.

The chip contains multiplexed arrays of electronic sensors placed outside and inside the cells that can detect the rise and fall of voltage across individual cell membranes, as well as voltage waves moving across the cell layer, which cause the cells to beat in unison in the chip, just as they do in the heart. After reducing levels of oxygen in the fluid within the device, the sensors detect an initial period of tachycardia (accelerated beat rate), followed by a reduction in beat rate and eventually arrhythmia which mimics cardiac arrest.

The research, published in Nano Letters, is a significant advance toward understanding the electrophysiological responses at the cellular level to ischemic heart attacks, and could be applied to future drug development. The paper was selected by the American Chemical Society as Editors’ Choice, and is available with open access.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, with most patients suffering from cardiac ischemia—which occurs when an artery supplying blood to the heart is partially or fully blocked. If ischemia occurs over an extended period, the heart tissue is starved of oxygen (a condition called “hypoxia”), and can lead to tissue death, or myocardial infarction. The changes in cardiac  and tissues induced by hypoxia include changes in voltage potentials across the cell membrane, release of neurotransmitters, shifts in gene expression, altered metabolic functions, and activation or deactivation of ion channels.

The  used in the microfluidic chip combines multi-electrode arrays that can provide extracellular readouts of voltage patterns, with nanopillar probes that enter the membrane to take readouts of voltage levels (action potentials) within each cell. Tiny channels in the chip allow the researchers to continuously and precisely adjust the fluid flowing over the cells, lowering the levels of oxygen to about 1-4 percent to mimic hypoxia or raising oxygen to 21 percent to model normal conditions. The changing conditions are meant to model what happens to cells in the heart when an artery is blocked, and then re-opened by treatment.

“Heart-on-a-chip models are a powerful tool to model diseases, but current tools to study electrophysiology in those systems are somewhat lacking, as they are either difficult to multiplex or eventually cause damage to the cells,” said Brian Timko, assistant professor of biomedical engineering at Tufts University School of Engineering, and corresponding author of the study. “Signaling pathways between molecules and ultimately electrophysiology occur rapidly during hypoxia, and our device can capture a lot of this information simultaneously in real time for a large ensemble of cells.”

When tested, the extracellular electrode arrays provided a two-dimensional map of voltage waves passing over the layer of , and revealed a predictable wave pattern under normal (21 percent) oxygen levels. In contrast, the researchers observed erratic and slower wave patterns when the oxygen was reduced to 1 percent.

The intracellular nanoprobe sensors provided a remarkably accurate picture of action potentials within each cell. These sensors were arranged as an array of tiny platinum tipped needles upon which the cells rest, like a bed of nails. When stimulated with an electric field, the needles puncture through the cell membrane, where they can begin taking measurements at single cell resolution. Both types of devices were created using photolithography—the technology used to create integrated circuits—which allowed researchers to achieve device arrays with highly reproducible properties.

The extracellular and intracellular sensors together provide information of the eletro-physiological effects of a modeled ischemic attack, including a “time lapse” of cells as they become dysfunctional and then respond to treatment. As such, the  could form the basis of a high throughput platform in drug discovery, identifying therapeutics which help cells and tissues recover normal function more rapidly.

“In the future, we can look beyond the effects of hypoxia and consider other factors contributing to acute heart disease, such as acidosis, nutrient deprivation and waste accumulation, simply by modifying the composition and flow of the medium,” said Timko. “We could also incorporate different types of sensors to detect specific molecules expressed in response to stresses.”


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Study reveals how low oxygen levels in the heart predispose people to cardiac arrhythmias


More information: Haitao Liu et al, Heart-on-a-Chip Model with Integrated Extra- and Intracellular Bioelectronics for Monitoring Cardiac Electrophysiology under Acute Hypoxia, Nano Letters (2020). DOI: 10.1021/acs.nanolett.0c00076

Journal information: Nano Letters

MIT: An Experimental Peptide could Block Covid-19


MIT-Covid19-Drug-01_0

MIT chemists are testing a protein fragment that may inhibit coronaviruses’ ability to enter human lung cells.

The research described in this article has been published on a preprint server but has not yet been peer-reviewed by scientific or medical experts.

In hopes of developing a possible treatment for Covid-19, a team of MIT chemists has designed a drug candidate that they believe may block coronaviruses’ ability to enter human cells. The potential drug is a short protein fragment, or peptide, that mimics a protein found on the surface of human cells.

The researchers have shown that their new peptide can bind to the viral protein that coronaviruses use to enter human cells, potentially disarming it.

“We have a lead compound that we really want to explore, because it does, in fact, interact with a viral protein in the way that we predicted it to interact, so it has a chance of inhibiting viral entry into a host cell,” says Brad Pentelute, an MIT associate professor of chemistry, who is leading the research team.

The MIT team reported its initial findings in a preprint posted on bioRxiv, an online preprint server, on March 20. They have sent samples of the peptide to collaborators who plan to carry out tests in human cells.

Molecular targeting

Pentelute’s lab began working on this project in early March, after the Cryo-EM structure of the coronavirus spike protein, along with the human cell receptor that it binds to, was published by a research group in China. Coronaviruses, including SARS-CoV-2, which is causing the current Covid-19 outbreak, have many protein spikes protruding from their viral envelope.

Studies of SARS-CoV-2 have also shown that a specific region of the spike protein, known as the receptor binding domain, binds to a receptor called angiotensin-converting enzyme 2 (ACE2). This receptor is found on the surface of many human cells, including those in the lungs. The ACE2 receptor is also the entry point used by the coronavirus that caused the 2002-03 SARS outbreak.

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What Does COVID Mean>

In hopes of developing drugs that could block viral entry, Genwei Zhang, a postdoc in Pentelute’s lab, performed computational simulations of the interactions between the ACE2 receptor and the receptor binding domain of the coronavirus spike protein. These simulations revealed the location where the receptor binding domain attaches to the ACE2 receptor — a stretch of the ACE2 protein that forms a structure called an alpha helix.

“This kind of simulation can give us views of how atoms and biomolecules interact with each other, and which parts are essential for this interaction,” Zhang says. “Molecular dynamics helps us narrow down particular regions that we want to focus on to develop therapeutics.”

The MIT team then used peptide synthesis technology that Pentelute’s lab has previously developed, to rapidly generate a 23-amino acid peptide with the same sequence as the alpha helix of the ACE2 receptor. Their benchtop flow-based peptide synthesis machine can form linkages between amino acids, the buildings blocks of proteins, in about 37 seconds, and it takes less than an hour to generate complete peptide molecules containing up to 50 amino acids.

“We’ve built these platforms for really rapid turnaround, so I think that’s why we’re at this point right now,” Pentelute says. “It’s because we have these tools we’ve built up at MIT over the years.”

They also synthesized a shorter sequence of only 12 amino acids found in the alpha helix, and then tested both of the peptides using equipment at MIT’s Biophysical Instrumentation Facility that can measure how strongly two molecules bind together. They found that the longer peptide showed strong binding to the receptor binding domain of the Covid-19 spike protein, while the shorter one showed negligible binding.

Many variants

Although MIT has been scaling back on-campus research since mid-March, Pentelute’s lab was granted special permission allowing a small group of researchers to continue to work on this project. They are now developing about 100 different variants of the peptide in hopes of increasing its binding strength and making it more stable in the body.

“We have confidence that we know exactly where this molecule is interacting, and we can use that information to further guide refinement, so that we can hopefully get a higher affinity and more potency to block viral entry in cells,” Pentelute says.

In the meantime, the researchers have already sent their original 23-amino acid peptide to a research lab at the Icahn School of Medicine at Mount Sinai for testing in human cells and potentially in animal models of Covid-19 infection.

While dozens of research groups around the world are using a variety of approaches to seek new treatments for Covid-19, Pentelute believes his lab is one of a few currently working on peptide drugs for this purpose. One advantage of such drugs is that they are relatively easy to manufacture in large quantities. They also have a larger surface area than small-molecule drugs.

“Peptides are larger molecules, so they can really grip onto the coronavirus and inhibit entry into cells, whereas if you used a small molecule, it’s difficult to block that entire area that the virus is using,” Pentelute says. “Antibodies also have a large surface area, so those might also prove useful. Those just take longer to manufacture and discover.”

One drawback of peptide drugs is that they typically can’t be taken orally, so they would have to be either administered intravenously or injected under the skin. They would also need to be modified so that they can stay in the bloodstream long enough to be effective, which Pentelute’s lab is also working on.

“It’s hard to project how long it will take to have something we can test in patients, but my aim is to have something within a matter of weeks. If it turns out to be more challenging, it may take months,” he says.

In addition to Pentelute and Zhang, other researchers listed as authors on the preprint are postdoc Sebastian Pomplun, grad student Alexander Loftis, and research scientist Andrei Loas.

New Catalyst Recycles Greenhouse Gases into Fuel and Hydrogen Gas: KAIST and Rice University


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       The Korea Advanced Institute of Science and Technology (KAIST

Scientists have taken a major step toward a circular carbon economy by developing a long-lasting, economical catalyst that recycles greenhouse gases into ingredients that can be used in fuel, hydrogen gas, and other chemicals. The results could be revolutionary in the effort to reverse global warming, according to the researchers. The study was published on February 14 in Science.

“We set out to develop an effective catalyst that can convert large amounts of the greenhouse gases carbon dioxide and methane without failure,” said Cafer T. Yavuz, paper author and associate professor of chemical and biomolecular engineering and of chemistry at KAIST.

The catalyst, made from inexpensive and abundant nickel, magnesium, and molybdenum, initiates and speeds up the rate of reaction that converts carbon dioxide and methane into hydrogen gas. It can work efficiently for more than a month.

This conversion is called ‘dry reforming’, where harmful gases, such as carbon dioxide, are processed to produce more useful chemicals that could be refined for use in fuel, plastics, or even pharmaceuticals. It is an effective process, but it previously required rare and expensive metals such as platinum and rhodium to induce a brief and inefficient chemical reaction.

Other researchers had previously proposed nickel as a more economical solution, but carbon byproducts would build up and the surface nanoparticles would bind together on the cheaper metal, fundamentally changing the composition and geometry of the catalyst and rendering it useless.

“The difficulty arises from the lack of control on scores of active sites over the bulky catalysts surfaces because any refinement procedures attempted also change the nature of the catalyst itself,” Yavuz said.

The researchers produced nickel-molybdenum nanoparticles under a reductive environment in the presence of a single crystalline magnesium oxide. As the ingredients were heated under reactive gas, the nanoparticles moved on the pristine crystal surface seeking anchoring points. The resulting activated catalyst sealed its own high-energy active sites and permanently fixed the location of the nanoparticles — meaning that the nickel-based catalyst will not have a carbon build up, nor will the surface particles bind to one another. (Article continues below **)

Read More from Rice University: Rice reactor turns greenhouse gas into pure liquid fuel

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This schematic shows the electrolyzer developed at Rice to reduce carbon dioxide, a greenhouse gas, to valuable fuels. At left is a catalyst that selects for carbon dioxide and reduces it to a negatively charged formate, which is pulled through a gas diffusion layer (GDL) and the anion exchange membrane (AEM) into the central electrolyte. At the right, an oxygen evolution reaction (OER) catalyst generates positive protons from water and sends them through the cation exchange membrane (CEM). The ions recombine into formic acid or other products that are carried out of the system by deionized (DI) water and gas. Illustration by Chuan Xia and Demin Liu

 

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(** New catalyst recycles greenhouse gases into fuel and hydrogen gas continues)

“It took us almost a year to understand the underlying mechanism,” said first author Youngdong Song, a graduate student in the Department of Chemical and Biomolecular Engineering at KAIST. “Once we studied all the chemical events in detail, we were shocked.”

The researchers dubbed the catalyst Nanocatalysts on Single Crystal Edges (NOSCE). The magnesium-oxide nanopowder comes from a finely structured form of magnesium oxide, where the molecules bind continuously to the edge. There are no breaks or defects in the surface, allowing for uniform and predictable reactions.

“Our study solves a number of challenges the catalyst community faces,” Yavuz said. “We believe the NOSCE mechanism will improve other inefficient catalytic reactions and provide even further savings of greenhouse gas emissions.”

This work was supported, in part, by the Saudi-Aramco-KAIST CO2 Management Center and the National Research Foundation of Korea.

Other contributors include Ercan Ozdemir, Sreerangappa Ramesh, Aldiar Adishev, and Saravanan Subramanian, all of whom are affiliated with the Graduate School of Energy, Environment, Water and Sustainability at KAIST; Aadesh Harale, Mohammed Albuali, Bandar Abdullah Fadhel, and Aqil Jamal, all of whom are with the Research and Development Center in Saudi Arabia; and Dohyun Moon and Sun Hee Choi, both of whom are with the Pohang Accelerator Laboratory in Korea. Ozdemir is also affiliated with the Institute of Nanotechnology at the Gebze Technical University in Turkey; Fadhel and Jamal are also affiliated with the Saudi-Armco-KAIST CO2 Management Center in Korea.


Story Source:

Materials provided by The Korea Advanced Institute of Science and Technology (KAIST)Note: Content may be edited for style and length.


Journal Reference:

  1. Youngdong Song, Ercan Ozdemir, Sreerangappa Ramesh, Aldiar Adishev, Saravanan Subramanian, Aadesh Harale, Mohammed Albuali, Bandar Abdullah Fadhel, Aqil Jamal, Dohyun Moon, Sun Hee Choi, Cafer T. Yavuz. Dry reforming of methane by stable Ni–Mo nanocatalysts on single-crystalline MgOScience, 2020; 367 (6479): 777 DOI: 10.1126/science.aav2412

A Nanoscale Device to Generate High-Power Terahertz Waves – Penetrating paper, clothing, wood and walls, detecting air pollution … THz sources could revolutionize Security and Medical Imaging Systems


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The nanoscale terahertz wave generator can be implemented on flexible substrates. Credit: EPFL / POWERlab

Terahertz (THz) waves fall between microwave and infrared radiation in the electromagnetic spectrum, oscillating at frequencies of between 100 billion and 30 trillion cycles per second. These waves are prized for their distinctive properties: they can penetrate paper, clothing, wood and walls, as well as detect air pollution. THz sources could revolutionize security and medical imaging systems. What’s more, their ability to carry vast quantities of data could hold the key to faster wireless communications.

THz waves are a type of non-ionizing radiation, meaning they pose no risk to human health. The technology is already used in some airports to scan passengers and detect dangerous objects and substances.

Despite holding great promise, THz waves are not widely used because they are costly and cumbersome to generate. But new technology developed by researchers at EPFL could change all that. The team at the Power and Wide-band-gap Electronics Research Laboratory (POWERlab), led by Prof. Elison Matioli, built a nanodevice that can generate extremely high-power signals in just a few picoseconds, or one trillionth of a second, which produces high-power THz waves.

The technology, which can be mounted on a chip or a flexible medium, could one day be installed in smartphones and other hand-held devices. The work first-authored by Mohammad Samizadeh Nikoo, a Ph.D. student at the POWERlab, has been published in the journal Nature.

How it works

The compact, inexpensive, fully electric nanodevice generates high-intensity waves from a tiny source in next to no time. It works by producing a powerful “spark,” with the voltage spiking from 10 V (or lower) to 100 V in the range of a picosecond. The device is capable of generating this spark almost continuously, meaning it can emit up to 50 million signals every second. When hooked up to antennas, the system can produce and radiate high-power THz waves.

The device consists of two metal plates situated very close together, down to 20 nanometers apart. When a voltage is applied, electrons surge towards one of the plates, where they form a nanoplasma. Once the voltage reaches a certain threshold, the electrons are emitted almost instantly to the second plate. This rapid movement enabled by such fast switches creates a high-intensity pulse that produces high-frequency waves.

Conventional electronic devices are only capable of switching at speeds of up to one volt per picosecond—too slow to produce high-power THz waves.

The new nanodevice, which can be more than ten times faster, can generate both high-energy and high-frequency pulses. “Normally, it’s impossible to achieve high values for both variables,” says Matioli. “High-frequency semiconductor devices are nanoscale in size. They can only cope with a few volts before breaking out. High-power devices, meanwhile, are too big and slow to generate terahertz waves. Our solution was to revisit the old field of plasma with state-of-the-art nanoscale fabrication techniques to propose a new device to get around those constraints.”

According to Matioli, the new  pushes all the variables to the extreme: “High-frequency, high-power and nanoscale aren’t terms you’d normally hear in the same sentence.”

“These nanodevices, on one side, bring an extremely high level of simplicity and low-cost, and on the other side, show an excellent performance. In addition, they can be integrated with other electronic devices such as transistors. Considering these , nanoplasma can shape a different future for the area of ultra-fast electronics,” says Samizadeh.

The technology could have wide-ranging applications beyond generating THz waves. “We’re pretty sure there’ll be more innovative applications to come,” adds Matioli.


Explore further

Record-breaking terahertz laser beam

A Conversation with a ‘Nano – Entrepreneur’ – Advanced Materials Company Veelo Technologies: National Nanotechnology Initiative


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*** Genesis Nanotechnology, Inc. is embarking on a series Interviews and Articles featuring ‘Nano Entrepreneurs’ and University Innovators – their journeys and their stories. To that end we thought to first introduce to our readers the Nanotechnology Entrepreneurship Network (NEN) as resource. You can also Follow Us On Twitter for Updates Twitter Icon 042616.jpg

 

NNI (National Nanotechnology Initiative) is pleased to launch a new community of interest to support entrepreneurs interested in commercializing nanotechnologies. The Nanotechnology Entrepreneurship Network (NEN) brings new and seasoned entrepreneurs together with the people and resources available to support them.

This emerging network will create a forum for sharing best practices for advancing nanotechnology commercialization and the lessons learned along the technology development pathway. Activities are likely to include a monthly podcast series, webinars, workshops, and town hall discussions.

To kick things off, the inaugural podcast in this series features a conversation between NNCO Director Lisa Friedersdorf and Joe Sprengard, CEO and Founder of Veelo Technologies. Joe talks about his journey as an entrepreneur and shares the advice he received when he was getting started. Check back here for more information, and contact nen@nnco.nano.gov if you would like to join the conversation!

We hope you enjoy watching the Video Below:

More About Veelo Technologies: General Nano manufactures Veelo™, a new-class of lightweight, conductive, multifunctional materials that improve the Size, Weight and Power (SWaP) of next generation air vehicles, including aircraft, rotorcraft, unmanned aerial vehicles (UAV), satellites, and missiles.

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