From Rutgers University: “Better Biosensor Technology Created for Stem Cells”

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From Rutgers University

November 10, 2019

Todd Bates
848-932-0550
todd.bates@rutgers.edu

Rutgers innovation may help guide treatment of Alzheimer’s, Parkinson’s diseases.

This unique biosensing platform consists of an array of ultrathin graphene layers and gold nanostructures. The platform, combined with high-tech imaging (Raman spectroscopy), detects genetic material (RNA) and characterizes different kinds of stem cells with greater reliability, selectivity and sensitivity than today’s biosensors. Image: Letao Yang, KiBum Lee, Jin-Ho Lee and Sy-Tsong (Dean) Chueng

The technology, which features a unique graphene and gold-based platform and high-tech imaging, monitors the fate of stem cells by detecting genetic material (RNA) involved in turning such cells into brain cells (neurons), according to a study in the journal Nano Letters.

Stem cells can become many different types of cells. As a result, stem cell therapy shows promise for regenerative treatment of neurological disorders such as Alzheimer’s, Parkinson’s, stroke and spinal cord injury, with diseased cells needing replacement or repair. But characterizing stem cells and controlling their fate must be resolved before they could be used in treatments. The formation of tumors and uncontrolled transformation of stem cells remain key barriers.

“A critical challenge is ensuring high sensitivity and accuracy in detecting biomarkers – indicators such as modified genes or proteins – within the complex stem cell microenvironment,” said senior author KiBum Lee, a professor in the Department of Chemistry and Chemical Biology in the School of Arts and Sciences at Rutgers University–New Brunswick. “Our technology, which took four years to develop, has demonstrated great potential for analyzing a variety of interactions in stem cells.”

The team’s unique biosensing platform consists of an array of ultrathin graphene layers and gold nanostructures. The platform, combined with high-tech imaging (Raman spectroscopy), detects genes and characterizes different kinds of stem cells with greater reliability, selectivity and sensitivity than today’s biosensors.

The team believes the technology can benefit a range of applications. By developing simple, rapid and accurate sensing platforms, Lee’s group aims to facilitate treatment of neurological disorders through stem cell therapy.

Stem cells may become a renewable source of replacement cells and tissues to treat diseases including macular degeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis, according to the National Institutes of Health.

The study’s co-lead authors are Letao Yang and Jin-Ho Lee, postdoctoral researchers in Lee’s group. Rutgers co-authors include doctoral students Christopher Rathnam and Yannan Hou. A scientist at Sogang University in South Korea contributed to the study.

See the full article here .

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Rutgers, The State University of New Jersey, is a leading national research university and the state’s preeminent, comprehensive public institution of higher education. Rutgers is dedicated to teaching that meets the highest standards of excellence; to conducting research that breaks new ground; and to providing services, solutions, and clinical care that help individuals and the local, national, and global communities where they live.

Founded in 1766, Rutgers teaches across the full educational spectrum: preschool to precollege; undergraduate to graduate; postdoctoral fellowships to residencies; and continuing education for professional and personal advancement.

As a ’67 graduate of University college, second in my class, I am proud to be a member of

Alpha Sigma Lamda, National Honor Society of non-tradional students.

From Harvard Gazette: “Why some people are resistant to Alzheimer’s”

Harvard University

From Harvard Gazette

November 4, 2019
MGH News and Public Affairs

Researchers find gene variants that may protect against the disease.

New study provides insights on why some people may be more resistant to Alzheimer’s disease than others. The findings may lead to strategies to delay or prevent the condition.

The study was led by investigators at Harvard-affiliated Massachusetts General Hospital (MGH), in collaboration with the University of Antioquia, Schepens Eye Research Institute of Massachusetts Eye and Ear, and Banner Alzheimer’s Institute.

According to researchers, some people who carry mutations in genes known to cause early onset Alzheimer’s disease do not show signs of the condition until a very old age — much later than expected. Studying these individuals may reveal insights on gene variants that reduce the risk of developing Alzheimer’s disease and other forms of dementia.

In their Nature Medicine study, Yakeel T. Quiroz, a clinical neuropsychologist and neuroimaging researcher at MGH, and her colleagues describe one such patient, from a large extended family with more than 6,000 living members from Colombia, who did not develop mild cognitive impairment until her 70s, nearly three decades after the typical age of onset.

Like her relatives who showed signs of dementia in their 40s, the patient carried the E280A mutation in a gene called Presenilin 1 (PSEN1), which has been shown to cause early onset Alzheimer’s disease. She also had two copies of a gene variation called ChristChurch, named after the New Zealand city where it was first found in the APOE3 gene (APOE3ch). The team was unable to identify any additional family members who had two copies of this variation who also carried the PSEN1 E280A mutation. In an analysis of 117 kindred members, 6 percent had one copy of the APOE3ch mutation, including four PSEN1 E280A mutation carriers who showed signs of mild cognitive impairment at the average age of 45 years.

Imaging tests revealed only minor neurodegeneration in the patient’s brain. Surprisingly, the patient had unusually high brain levels of amyloid beta deposits, a hallmark of Alzheimer’s disease; however, the amount of tau tangles — another hallmark of the disease — was relatively limited.

The investigators suspect that carrying two copies of the APOE3ch variant may postpone the clinical onset of Alzheimer’s disease by limiting tau pathology and neurodegeneration.

“This single case opens a new door for treatments of Alzheimer’s disease, based more on the resistance to Alzheimer’s pathology rather than on the cause of the disease. In other words, not necessarily focusing on reduction of pathology, as it has been done traditionally in the field, but instead promoting resistance even in the face of significant brain pathology,” said Quiroz.

APOE3 is one form of the APOE gene, the major susceptibility gene for late-onset Alzheimer’s. The APOE gene provides instructions for making a protein called apolipoprotein E, which is involved in the metabolism of fats in the body. Experiments revealed that the APOE3ch variant may reduce the ability of apolipoprotein E to bind to certain sugars called heparan sulphate proteoglycans (HSPG), which have been implicated in processes involving amyloid beta and tau proteins.

“This finding suggests that artificially modulating the binding of APOE to HSPG could have potential benefits for the treatment of Alzheimer’s disease, even in the context of high levels of amyloid pathology,” said co–lead author Joseph F. Arboleda-Velasquez of the Schepens Eye Research Institute.

The investigators suspect that carrying two copies of the APOE3ch variant may postpone the clinical onset of Alzheimer’s disease by limiting tau pathology and neurodegeneration.

“This single case opens a new door for treatments of Alzheimer’s disease, based more on the resistance to Alzheimer’s pathology rather than on the cause of the disease. In other words, not necessarily focusing on reduction of pathology, as it has been done traditionally in the field, but instead promoting resistance even in the face of significant brain pathology,” said Quiroz.

APOE3 is one form of the APOE gene, the major susceptibility gene for late-onset Alzheimer’s. The APOE gene provides instructions for making a protein called apolipoprotein E, which is involved in the metabolism of fats in the body. Experiments revealed that the APOE3ch variant may reduce the ability of apolipoprotein E to bind to certain sugars called heparan sulphate proteoglycans (HSPG), which have been implicated in processes involving amyloid beta and tau proteins.

“This finding suggests that artificially modulating the binding of APOE to HSPG could have potential benefits for the treatment of Alzheimer’s disease, even in the context of high levels of amyloid pathology,” said co–lead author Joseph F. Arboleda-Velasquez of the Schepens Eye Research Institute.

See the full article here .

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Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

From Stanford University – Medicine: “Robots join workforce at the new Stanford Hospital”

From Stanford University – Medicine

11.4.19
Daphne Sashin

In the new Stanford hospital, the human employees will be joined by a fleet of robots programmed to take on some repetitive and mechanical tasks.

The more than 5,500 Stanford Health Care employees who work at the new Stanford Hospital will be joined by a fleet of robots programmed to deliver linens, packages and medical supplies, keep track of the hospital’s medication inventory and count out pills for nurses to administer.

The new hospital opens Nov. 17.

Tug robots will serve as autonomous couriers, hauling heavy loads of supplies between the central loading dock at 300 Pasteur Drive and the new hospital at 500 Pasteur Drive — a half-mile round-trip. Kevin Meynell Photography.

Handing off repetitive and mechanical tasks to machines — 23 delivery robots that will travel on pre-programmed routes throughout the hospital and three pharmacy robots that will store and package medication — will prevent employee injuries, reduce medication errors and free up staff to focus on the more valuable and satisfying work of assisting clinicians and caring for patients, said Gary Fritz, vice president and chief of applications for Stanford Health Care.

“The real value of pharmacists and pharmacy technicians comes when they use their clinical knowledge to care for patients, not to count pills,” Fritz said. “Similarly, in the supply chain, routine activities like pushing a cart 30 minutes in each direction isn’t really job enriching, but what is enriching is if those people can talk to patients or spend time figuring out how to get better supplies.”

Autonomous robots ‘TUG’ supplies

At 4 feet high, the TUGs will serve as autonomous couriers, hauling heavy loads of supplies between the central loading dock at 300 Pasteur Drive and the new hospital at 500 Pasteur Drive — a half-mile round-trip via tunnel. The TUGs move about 2 miles per hour and can pull more than half a ton.

“We’re automating the heavy movement across long distances to protect our employees,” said Shaheed Hickman, supply chain project manager at the hospital.

The robots use lasers and GPS to create a 3D map of their surroundings and determine if they need to stop or move to get around an obstacle. The robots convert that 3D map to a 2D image, so managers and staff can remotely track them in real-time. The TUGs have the capability to open doors wirelessly and stop when they sense movement that may interfere with their path. They can distinguish between stationary or moving obstructions within a 10-foot radius and alter their course accordingly.

Joel Rivera, a pharmacy technician, next to the PillPick robot, which can package 1,000 doses of medicine per hour. The same work would take a technician 10 hours to complete. Kevin Meynell Photography.

While you can’t have a conversation with them, they do speak a few phrases — including “crossing hallway” and “TUG has arrived” — and they stop the moment they are touched. If a fire alarm goes off, the robots pull off to the side of the hallway to get out of the way.

Initially, the TUGs will be used to carry carts full of small packages, bulk food, nonurgent medical supplies and linens to the basement level of the new hospital, where, for now, a staff member will get the items to their final destination. The TUGs also will haul dirty linens, used food trays and garbage from the new hospital and ferry it back to the dock.

In between jobs, the TUGs automatically return to recharge at their docking stations.

Robotic pharmacy

You won’t see many pills in the new hospital pharmacy. That’s because most of them are stored inside three giant robotic machines, which don’t get tired, rushed or make mistakes as they’re filling drug orders for patients.

Two of them, the BoxPickers, aren’t what you imagine when you think of a robot. They are more like giant cabinets with a computer interface on the outside. Inside, there are stacks of drawers containing boxes of medications and a mechanical arm, or picker, that moves up and down the aisles. The BoxPickers currently store nearly $5 million worth of medications — about 80 percent of what’s stored in the patient care unit’s medication dispensing cabinets, located in the medication areas on the hospital floors.

Each day, when it’s time to restock the dispensers with medications, the technician checks the BoxPicker’s computer to determine which are needed and in what quantities. On the other side of the cabinet, the arm locates the box containing that specific medication and moves it into a drawer that unlocks for the technician.

Besides the time-savings afforded by the pharmacy robots, the machines reduce the chance of pill-selection errors, said Douglas Del Paggio, PharmD, assistant director of pharmacy.

“Instead of me going over to a bin and pulling a drug and looking at it — and if I’m in a rush, I may accidentally pull the wrong one, or the wrong drug is in the wrong bin — in these robots, it is all bar-code scanned and checked, so it’s very accurate — like 99.9 percent,” Del Paggio said.

The BoxPickers also keep a running inventory and automatically generate new orders for the drug wholesaler on a daily basis.

“You have more seamless control of inventory, because you’re not just eyeballing and saying, ‘I think I need more of that,’ which is how we’ve been doing it for decades,” Del Paggio said.

Across the room, a third robot — a suction-powered machine called the PillPick — counts out bulk medications and slides them into individual, bar-coded packets.

When a physician puts a patient’s order into the electronic health record system for one of these drugs, the only human work required is for a pharmacist to verify the order. Then the robot goes to work, whirring and hissing. Within seconds, a day’s worth of medicine slides down a conveyor belt, organized on a plastic ring.

The PillPick can package 1,000 doses per hour — the same amount that it would take a pharmacy technician about 10 hours to pack by hand.

“This allows our pharmacists and technicians to instead spend more of their time with physicians, nurses, and most importantly,” Del Paggio said, “directly with patients and family members.”

See the full article here .

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Stanford Medicine integrates research, medical education and health care at its three institutions – Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children’s Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.

Stanford University campus. No image credit

Stanford University

Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members

From Rensselaer Polytechnic Institute: “Living Skin Can Now be 3D-Printed With Blood Vessels Included”

From Rensselaer Polytechnic Institute

Development is significant step toward skin grafts that can be integrated into patient’s skin.

Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published online today in Tissue Engineering Part A, is a significant step toward creating grafts that are more like the skin our bodies produce naturally.

“Right now, whatever is available as a clinical product is more like a fancy Band-Aid,” said Pankaj Karande, an associate professor of chemical and biological engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), who led this research at Rensselaer. “It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells.”

A significant barrier to that integration has been the absence of a functioning vascular system in the skin grafts.

Karande has been working on this challenge for several years, previously publishing one of the first papers [Tissue Engineering Part C: Methods] showing that researchers could take two types of living human cells, make them into “bio-inks,” and print them into a skin-like structure. Since then, he and his team have been working with researchers from Yale School of Medicine to incorporate vasculature.

In this paper, the researchers show that if they add key elements — including human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells — with animal collagen and other structural cells typically found in a skin graft, the cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks.

Watch Karande explain this development:

“As engineers working to recreate biology, we’ve always appreciated and been aware of the fact that biology is far more complex than the simple systems we make in the lab,” Karande said. “We were pleasantly surprised to find that, once we start approaching that complexity, biology takes over and starts getting closer and closer to what exists in nature.”

Once the Yale team grafted it onto a special type of mouse, the vessels from the skin printed by the Rensselaer team began to communicate and connect with the mouse’s own vessels.

“That’s extremely important, because we know there is actually a transfer of blood and nutrients to the graft which is keeping the graft alive,” Karande said.

In order to make this usable at a clinical level, researchers need to be able to edit the donor cells using something like the CRISPR technology, so that the vessels can integrate and be accepted by the patient’s body.

“We are still not at that step, but we are one step closer,” Karande said.

“This significant development highlights the vast potential of 3D bioprinting in precision medicine, where solutions can be tailored to specific situations and eventually to individuals,” said Deepak Vashishth, the director CBIS. “This is a perfect example of how engineers at Rensselaer are solving challenges related to human health.”

Karande said more work will need to be done to address the challenges associated with burn patients, which include the loss of nerve and vascular endings. But the grafts his team has created bring researchers closer to helping people with more discrete issues, like diabetic or pressure ulcers.

“For those patients, these would be perfect, because ulcers usually appear at distinct locations on the body and can be addressed with smaller pieces of skin,” Karande said. “Wound healing typically takes longer in diabetic patients, and this could also help to accelerate that process.”

At Rensselaer, Karande’s team also includes Carolina Catarino, doctoral student in chemical and biological engineering. The Yale team includes Tania Baltazar, a postdoctoral researcher who previously worked on this project at Rensselaer; Dr. Jordan Pober, a professor of immunobiology; and Mark Saltzman, a professor of biomedical engineering.

This work was supported by a grant from the National Institutes of Health.

See the full article here .

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With 7,900 students and more than 100,000 living alumni, Rensselaer is addressing the global challenges facing the 21st century—to change lives, to advance society, and to change the world.

From renewable energy to cybersecurity, from biotechnology to materials science, from big data to nanotechnology, the world needs problem solvers—exactly the kind of talent Rensselaer produces—to address the urgent issues of today and the emerging issues of tomorrow.

From MIT News: “Double-sided tape for tissues could replace surgical sutures”

From MIT News

October 30, 2019
Anne Trafton

MIT engineers have devised a double-sided adhesive that can be used to seal tissues together. Image: Felice Frankel, Christine Daniloff, MIT.

MIT graduate student Hyunwoo Yuk displays the double-sided tissue adhesive. Image: Tony Pulsone

New adhesive that binds wet surfaces within seconds could be used to heal wounds or implant medical devices.

Inspired by a sticky substance that spiders use to catch their prey, MIT engineers have designed a double-sided tape that can rapidly seal tissues together.

In tests in rats and pig tissues, the researchers showed that their new tape can tightly bind tissues such as the lungs and intestines within just five seconds. They hope that this tape could eventually be used in place of surgical sutures, which don’t work well in all tissues and can cause complications in some patients.

“There are over 230 million major surgeries all around the world per year, and many of them require sutures to close the wound, which can actually cause stress on the tissues and can cause infections, pain, and scars. We are proposing a fundamentally different approach to sealing tissue,” says Xuanhe Zhao, an associate professor of mechanical engineering and of civil and environmental engineering at MIT and the senior author of the study.

The double-sided tape can also be used to attach implantable medical devices to tissues, including the heart, the researchers showed. In addition, it works much faster than tissue glues, which usually take several minutes to bind tightly and can drip onto other parts of the body.

Graduate students Hyunwoo Yuk and Claudia Varela are the lead authors of the study, which appears today in Nature. Other authors are MIT graduate student Xinyu Mao, MIT assistant professor of mechanical engineering Ellen Roche, Mayo Clinic critical care physician Christoph Nabzdyk, and Brigham and Women’s Hospital pathologist Robert Padera.

A tight seal

Forming a tight seal between tissues is considered to be very difficult because water on the surface of the tissues interferes with adhesion. Existing tissue glues diffuse adhesive molecules through the water between two tissue surfaces to bind them together, but this process can take several minutes or even longer.

The MIT team wanted to come up with something that would work much faster. Zhao’s group had previously developed other novel adhesives, including a hydrogel superglue that provides tougher adhesion than the sticky materials that occur in nature, such as those that mussels and barnacles use to cling to ships and rocks.

To create a double-sided tape that could rapidly join two wet surfaces together, the team drew inspiration from the natural world — specifically, the sticky material that spiders use to capture their prey in wet conditions. This spider glue includes charged polysaccharides that can absorb water from the surface of an insect almost instantaneously, clearing off a small dry patch that the glue can adhere to.

To mimic this with an engineered adhesive, the researchers designed a material that first absorbs water from wet tissues and then rapidly binds two tissues together. For water absorption, they used polyacrylic acid, a very absorbent material that is used in diapers. As soon as the tape is applied, it sucks up water, allowing the polyacrylic acid to quickly form weak hydrogen bonds with both tissues.

These hydrogen bonds and other weak interactions temporarily hold the tape and tissues in place while chemical groups called NHS esters, which the researchers embedded in the polyacrylic acid, form much stronger bonds, called covalent bonds, with proteins in the tissue. This takes about five seconds.

To make their tape tough enough to last inside the body, the researchers incorporated either gelatin or chitosan (a hard polysaccharide found in insect shells). These polymers allow the adhesive to hold its shape for long periods of time. Depending on the application that the tape is being used for, the researchers can control how fast it breaks down inside the body by varying the ingredients that go into it. Gelatin tends to break down within a few days or weeks in the human body, while chitosan can last longer (a month or even up to a year).

“Combining two innovative concepts, the research team succeeded in adhering quickly and effectively to the wet and soft surface of a tissue, and in maintaining good adhesion and mechanical properties for several days without causing too much inflammatory response,” says Costantino Creton, a research director at ESPCI Paris, who was not involved in the research.

Rapid healing

This type of adhesive could have a major impact on surgeons’ ability to seal incisions and heal wounds, Yuk says. To explore possible applications for the new double-sided tape, the researchers tested it in a few different types of pig tissue, including skin, small intestine, stomach, and liver. They also performed tests in pig lungs and trachea, showing that they could rapidly repair damage to those organs.

“It’s very challenging to suture soft or fragile tissues such as the lung and trachea, but with our double-sided tape, within five seconds we can easily seal them,” Yuk says.

The tape also worked well to seal damage to the gastrointestinal tract, which could be very useful in preventing leakage that sometimes occurs following surgery. This leakage can cause sepsis and other potentially fatal complications.

“I anticipate tremendous translational potential of this elegant approach into various clinical practices, as well as basic engineering applications, in particular in situations where surgical operations, such as suturing, are not straightforward,” says Yu Shrike Zhang, an assistant professor of medicine at Harvard Medical School, who was not involved in the research.

Implanting medical devices within the body is another application the MIT team is exploring. Working with Roche’s lab, the researchers showed that the tape could be used to firmly attach a small polyurethane patch to the hearts of living rats, which are about the size of a thumbnail. Normally this kind of procedure is extremely complicated and requires an experienced surgeon to perform, but the research team was able to simply stick the patch on with their tape by pressing for a few seconds, and it stayed in place for several days.

In addition to the polyurethane heart patch, the researchers found that the tape could successfully attach materials such as silicone rubber, titanium, and hydrogels to tissues.

“This provides a more elegant, more straightforward, and more universally applicable way of introducing an implantable monitor or drug delivery device, because we can adhere to many different sites without causing damage or secondary complications from puncturing tissue to affix the devices,” Yuk says.

The researchers are now working with doctors to identify additional applications for this kind of adhesive and to perform more tests in animal models.

The research was funded by the National Science Foundation and the Office of Naval Research.

See the full article here .

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Please help promote STEM in your local schools.

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The mission of MIT is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of the MIT community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

From UC Riverside: “Crimped or straight? Lung fiber shape influences elasticity”

From UC Riverside

October 28, 2019
Holly Ober

Students in Mona Eskandari’s bMECH lab at UC Riverside performing lung experiments.

The shape and architecture of collagen and elastin fibers can improve our understanding of lung diseases, including the one associated with vaping.

Take a deep breath. Now exhale. Congratulations! You’ve just done something completely ordinary, yet so mysterious that scientists still don’t know everything about it.

How oxygen and carbon dioxide enter and leave the bloodstream is well known, but scientists are just beginning to understand what happens to respiratory tissues as they expand and contract with every breath. The answers they find could help identify better ways to diagnose and treat lung diseases, including the deadly illnesses associated with vaping, cigarettes, and/or air pollution exposure.

Stiff collagen and stretchy elastin, tissue fibers packed together in rows, enable lungs and other parts of the respiratory system to stretch and snap back into shape. Damage to these fibers from environmental contaminants such as air pollution contributes to diseases like chronic obstructive pulmonary disease, or COPD, and asthma. Scientists had previously thought these fibers govern the mechanics of the airways due to their composition.

New research [Acta Biomaterialia] published by University of California, Riverside BREATHE Center collaborators Mona Eskandari, an assistant professor of mechanical engineering and Tara Nordgren, an assistant professor of biomedical sciences; and Grace O’Connell, an associate professor of mechanical engineering at UC Berkeley, has instead observed differences in the shape and form of the tissue fibers from proximal to distal airways, influencing respiratory elasticity.

Mona Eskandari

Tara Nordgren

Grace O’Connell

The researchers, led by Eskandari, stretched the airways of pig lungs obtained from a slaughterhouse and observed the tissue stress response. In addition to measuring the biochemical composition of the tissue, they also made detailed microscopic observations. In some parts of the respiratory tract, such as the trachea — the “windpipe” that transports air from the nasal passages to the lungs — collagen and elastin fibers were seen to have a crimped, “Z” shape, while in smaller airways they were straight.

Overall, the experiments correlated with mathematical models accounting for fiber structural reinforcement, the first predictions of tissue behavior throughout the bronchial tree.

One surprising result stood out.

“We were shocked to not find definitive trends between our models and fiber content but rather in microstructural shape, suggesting the mechanics to be governed by morphology,” Eskandari said. “Similar to having a wavy versus straight spring, the former exhibits more flexibility. We think this explains why our previous experiments on smaller airways were found to be stiffer.”

The results show the importance of linking mathematical models with the real tissue structure in order to understand how lungs function in health and illness, and suggest that changes to the shape of the fibers might contribute to lung disease.

The researchers are now conducting extensive studies to measure the waviness of these fibers. These findings have broad implications. They will help scientists better understand a variety of lung diseases, from chronic lung diseases such as COPD — a leading cause of death in the U.S. — to the strange lung ailment associated with vaping that has so far affected nearly 1,500 people and killed 33.

“The chemical compounds inhaled during vaping, as well as in other environmental exposures, can cause direct and indirect damage to the lungs,” said Nordgren. “This damage, especially if not appropriately repaired, can lead to alterations in the lungs including the collagen and elastin components that alter the lung’s functional capacity.”

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

The University of California, Riverside is one of 10 universities within the prestigious University of California system, and the only UC located in Inland Southern California.

Widely recognized as one of the most ethnically diverse research universities in the nation, UCR’s current enrollment is more than 21,000 students, with a goal of 25,000 students by 2020. The campus is in the midst of a tremendous growth spurt with new and remodeled facilities coming on-line on a regular basis.

We are located approximately 50 miles east of downtown Los Angeles. UCR is also within easy driving distance of dozens of major cultural and recreational sites, as well as desert, mountain and coastal destinations.

From École Polytechnique Fédérale de Lausanne: “A high-precision instrument for ophthalmologists”

From École Polytechnique Fédérale de Lausanne

29.10.19
Nathalie Jollien

The high-precision miniaturized medical device, SPOT-RVC © Instant-Lab

EPFL scientists have helped develop a microscopic glass device that doctors could use to inject medicine into retinal veins with unprecedented accuracy. Their instrument meets an important need in eye surgery, delivering exceptional stability and precision.

A team of researchers presented a breakthrough device for eye surgery at EPFL Neuchâtel’s Research Day on 11 September. The device – called SPOT-RVC, which is short for Safe Puncture Optimized Tool for Retinal Vein Cannulation – was developed through an Innosuisse sponsored R&D project involving two EPFL Neuchâtel labs (Instant-Lab and Galatea), the Jules-Gonin Hospital of Ophthalmology in Lausanne and Ticino-based FEMTOprint as implementation partner. The team’s findings has been the subject of several publications, including one recently in the Journal of Medical Devices.

SPOT-RVC is a high-precision, miniaturized medical device made entirely of glass. It’s just 6 cm long and 1 mm thick, and it contains a tiny fluidic channel no wider than a strand of hair as well as a sophisticated mechanism of flexible blades. Doctors can use the device to inject medicine directly into a patient’s retinal veins – something that has never before been possible.

The high-precision miniaturized medical device, SPOT-RVC © Instant-Lab

“We wanted to develop a surgical method for treating retinal vein occlusion, which occurs when the main vein carrying blood away from the eye is blocked. There is currently no way to treat this condition – we can only treat the resulting complications,” says Professor Thomas J. Wolfensberger, the chief physician at Jules-Gonin Hospital. And those complications can be severe. When the retinal vein is blocked by a blood clot, this reduces the amount of oxygen carried to the retina and can trigger sudden vision loss. Over 16 million people around the world suffer from this condition, which mostly afflicts the elderly.

Combining microengineering and microfluid mechanics

Thanks to SPOT-RVC, doctors will be able to inject blood-clot-dissolving compounds directly into patients’ retinal veins safely, without damaging the surrounding tissue. “One of the biggest problems we faced is that because veins are so small and their walls so thin, it’s hard to get the needle into the vein without overpuncturing. It’s like if you want to drill a hole into a plank of wood but don’t want the hole to go all the way through,” says Dr. Charles Baur, a senior scientist at Instant-Lab who imagined this novel concept of surgical instruments.

The researchers therefore drew on Instant-Lab’s expertise in flexible microstructures and multistable systems to engineer a microscopic device (< 1 mm in diameter) that can transition from one stable state to another very quickly – in around a millisecond – and in a controlled manner. “With this dynamic perforation mechanism that controls both the penetration force and direction of the needle, retinal veins don’t have time to deform. In addition, the penetration force is independent of the force exerted by the surgeon’s hand, which limits the risk of overpuncturing,” says Dr. Baur.

Another innovative feature of SPOT-RVC is its microscopic, flexible channel that extends all the way down to the needle tip, enabling doctors to inject the medicine. The channel was developed using an innovative process developed by scientists at Galatea, that allows for fabricating, arbitrarily long and shaped, sealed cavities.

And finally, the device is made of a single piece of fused silica (SiO2), thanks to the unique expertise of FEMTOprint for integrating multiple functions in a same substrate. “Since it’s monolithic, there’s no assembly required – a step that would be nearly impossible and would make it very difficult to sterilize the instrument,” says Dr. Baur. To achieve this complex monolithic integration with the required levels of precision, FEMTOprint uses ultrafast lasers 3D printing and proprietary post-processing techniques. In this context, the Galatea lab provides expertise in the understanding of ultrafast laser-matter interactions and its use for making complex micro-devices, such as optofluidics and optomechanical devices.

Winner of the Swiss high-precision industry award

FEMTOprint presented SPOT-RVC at the Swiss high-precision industry convention (EPHJ), which was held this past June in Geneva. The device won the 2019 Exhibitors’ Grand Prix – an encouraging start.

For now the device is still in the prototyping stage. “We got good results from our in vitro and in vivo tests,” says Dr. Baur. “Now it is necessary to conduct preclinical trials and obtain the necessary certifications. Then we’ll move on to the production stage, which will require a fairly large investment from the industrial partner. We genuinely hope that one day the device will become a useful tool for eye surgeons.”

Discover the mechanism in video on https://youtu.be/1ZNGuvkzNsE.

See the full article here .

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EPFL campus

EPFL is Europe’s most cosmopolitan technical university. It receives students, professors and staff from over 120 nationalities. With both a Swiss and international calling, it is therefore guided by a constant wish to open up; its missions of teaching, research and partnership impact various circles: universities and engineering schools, developing and emerging countries, secondary schools and gymnasiums, industry and economy, political circles and the general public.

From Michigan Technical University: “Be Brief: Glow”

From Michigan Technical University

October 24, 2019
Allison Mills

MTU. Fluorescent dyes help chemists see the inner workings of disease.

Dysfunctional mitochondria have been linked to neurological and cardiovascular diseases, such as Alzheimer’s and Parkinson’s disease, and even to some types of cancer. To keep these powerhouses working efficiently, cells remove damaged mitochrondria. This process, called mitophagy, is like a cell taking out the trash. In diseased cells, the garbage piles up and the cell’s pH changes.

To watch the mitophagy process closely, chemist Haiying Liu collaborated with biologists to make a glowing dye that shines brighter under certain pH conditions that mimic changes caused by disease. The team uses a rhodol-based dye, which is sensitive, permeates cells well and shows low cell toxicity.

“It is important to track the mitophagy process and we need a tool to track it,” Liu said, explaining that mitophagy is not readily visible to the naked eye or even under a microscope.

In order to track and visualize the mitophagy process, two different mitochondria- and lysosome-targeting fluorescent probes with different emission wavelengths would be needed to detect the dramatic pH changes during mitophagy: a slightly basic pH of 8.0 in the mitochondria and an acidic pH of 4.5 in the autolysosomes.

The rhodol dyes emit in both visible and the near-infrared regions with self-calibration capability and can effectively track the mitophagy. Liu hopes they will one day work in near-infrared spectra to take advantage of near-infrared imaging such as deep-tissue penetration, the smallest water Raman peak, very little background fluorescence and minimal photo damage to cells and tissues. The end goal: “We hope to make a tool that is easy for industry to prepare and use.”

Those potential uses include assessing drug treatments, drug interactions, a better understanding of cellular function and disease monitoring. The team examined how well the dye worked in live cells and fruit fly larvae. The next steps include modification of rhodol dyes to develop water-soluble, near-infrared theranostic prodrugs to precisely target cancer cells, deliver therapeutic drugs to tumors, improve the therapeutic efficacy, and significantly reduce toxicity to normal cells through real-time fluorescence monitoring of drug delivery process.

In order to track and visualize the mitophagy process, two different mitochondria- and lysosome-targeting fluorescent probes with different emission wavelengths would be needed to detect the dramatic pH changes during mitophagy: a slightly basic pH of 8.0 in the mitochondria and an acidic pH of 4.5 in the autolysosomes.

See the full article here .

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Michigan Technological University (http://www.mtu.edu) is a leading public research university developing new technologies and preparing students to create the future for a prosperous and sustainable world. Michigan Tech offers more than 130 undergraduate and graduate degree programs in engineering; forest resources; computing; technology; business; economics; natural, physical and environmental sciences; arts; humanities; and social sciences.
The College of Sciences and Arts (CSA) fills one of the most important roles on the Michigan Tech campus. We play a part in the education of every student who comes through our doors. We take pride in offering essential foundational courses in the natural sciences and mathematics, as well as the social sciences and humanities—courses that underpin every major on campus. With twelve departments, 28 majors, 30-or-so specializations, and more than 50 minors, CSA has carefully developed programs to suit many interests and skill sets. From sound design and audio technology to actuarial science, applied cognitive science and human factors to rhetoric and technical communication, the college offers many unique programs.

From UC Riverside: “Small magnets reveal big secrets”

From UC Riverside

October 24, 2019
Iqbal Pittalwala

Work by international research team could have wide-ranging impact on information technology applications.

An international research team led by a physicist at the University of California, Riverside, has identified a microscopic process of electron spin dynamics in nanoparticles that could impact the design of applications in medicine, quantum computation, and spintronics.

Magnetic nanoparticles and nanodevices have several applications in medicine — such as drug delivery and MRI — and information technology. Controlling spin dynamics — the movement of electron spins — is key to improving the performance of such nanomagnet-based applications.

“This work advances our understanding of spin dynamics in nanomagnets,” said Igor Barsukov, an assistant professor in the Department of Physics and Astronomy and lead author of the study that appears today in Science Advances.

Physicist Igor Barsukov is an assistant professor at UC Riverside. (UCR/Barsukov lab)

Electron spins, which precess like spinning tops, are linked to each other. When one spin begins to precess, the precession propagates to neighboring spins, which sets a wave going. Spin waves, which are thus collective excitations of spins, behave differently in nanoscale magnets than they do in large or extended magnets. In nanomagnets, the spin waves are confined by the size of the magnet, typically around 50 nanometers, and therefore present unusual phenomena.

In particular, one spin wave can transform into another through a process called “three magnon scattering,” a magnon being a quantum unit of a spin wave. In nanomagnets, this process is resonantly enhanced, meaning it is amplified for specific magnetic fields.

In collaboration with researchers at UC Irvine and Western Digital in San Jose, as well as theory colleagues in Ukraine and Chile, Barsukov demonstrated how three magnon scattering, and thus the dimensions of nanomagnets, determines how these magnets respond to spin currents. This development could lead to paradigm-shifting advancements.

“Spintronics is leading the way for faster and energy-efficient information technology,” Barsukov said. “For such technology, nanomagnets are the building blocks, which need to be controlled by spin currents.”

Barsukov explained that despite its technological importance, a fundamental understanding of energy dissipation in nanomagnets has been elusive. The research team’s work provides insights into the principles of energy dissipation in nanomagnets and could enable engineers who work on spintronics and information technology to build better devices.

“Microscopic processes explored in our study may also be of significance in the context of quantum computation where researchers currently are attempting to address individual magnons,” Barsukov said. “Our work can potentially impact multiple areas of research.”

Barsukov was joined in the research by H. K. Lee, A. A. Jara, Y.-J. Chen, A. M. Gonçalves, C. Sha, and I. N. Krivorotov of UC Irvine; J. A. Katine of Western Digital in San Jose; R. E. Arias of the University of Chile in Santiago; and B. A. Ivanov of the National Academy of Sciences of Ukraine and the National University of Science and Technology in Russia.

The collaborative study was primarily funded by the U.S. Army Research Office, Defense Threat Reduction Agency, and National Science Foundation, or NSF, as well as by agencies in Chile, Brazil, Ukraine, and Russia. Barsukov was funded by the NSF.

See the full article here .

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The University of California, Riverside is one of 10 universities within the prestigious University of California system, and the only UC located in Inland Southern California.

Widely recognized as one of the most ethnically diverse research universities in the nation, UCR’s current enrollment is more than 21,000 students, with a goal of 25,000 students by 2020. The campus is in the midst of a tremendous growth spurt with new and remodeled facilities coming on-line on a regular basis.

We are located approximately 50 miles east of downtown Los Angeles. UCR is also within easy driving distance of dozens of major cultural and recreational sites, as well as desert, mountain and coastal destinations.

From MIT News: “New process could make hydrogen peroxide available in remote places”

From MIT News

October 23, 2019
David L. Chandler

In a new method to produce hydrogen peroxide portably, an electrolyzer (left) splits water into hydrogen and oxygen. The hydrogen atoms initially form in an electrolyte material (green), which transfers them to a mediator material (red), which then carries them to a separate unit where the mediator comes in contact with oxygen-rich water (blue), where the hydrogen combines with it to form hydrogen peroxide. The mediator then returns to begin the cycle again. Image courtesy of the researchers.

MIT-developed method may lead to portable devices for making the disinfectant on-site where it’s needed.

Hydrogen peroxide, a useful all-purpose disinfectant, is found in most medicine cabinets in the developed world. But in remote villages in developing countries, where it could play an important role in health and sanitation, it can be hard to come by.

Now, a process developed at MIT could lead to a simple, inexpensive, portable device that could produce hydrogen peroxide continuously from just air, water, and electricity, providing a way to sterilize wounds, food-preparation surfaces, and even water supplies.

The new method is described this week in the journal Joule in a paper by MIT students Alexander Murray, Sahag Voskian, and Marcel Schreier and MIT professors T. Alan Hatton and Yogesh Surendranath.

Even at low concentrations, hydrogen peroxide is an effective antibacterial agent, and after carrying out its sterilizing function it breaks down into plain water, in contrast to other agents such as chlorine that can leave unwanted byproducts from its production and use.

Hydrogen peroxide is just water with an extra oxygen atom tacked on — it’s H2O2, instead of H2O. That extra oxygen is relatively loosely bound, making it a highly reactive chemical eager to oxidize any other molecules around it. It’s so reactive that in high concentrations it can be used as rocket fuel, and even concentrations of 35 percent require very special handling and shipping procedures. The kind used as a household disinfectant is typically only 3 percent hydrogen peroxide and 97 percent water.

Because high concentrations are hard to transport, and low concentrations, being mostly water, are uneconomical to ship, the material is often hard to get in places where it could be especially useful, such as remote communities with untreated water. (Bacteria in water supplies can be effectively controlled by adding hydrogen peroxide.) As a result, many research groups around the world have been pursuing approaches to developing some form of portable hydrogen peroxide production equipment.

Most of the hydrogen peroxide produced in the industrialized world is made in large chemical plants, where methane, or natural gas, is used to provide a source of hydrogen, which is then reacted with oxygen in a catalytic process under high heat. This process is energy-intensive and not easily scalable, requiring large equipment and a steady supply of methane, so it does not lend itself to smaller units or remote locations.

“There’s a growing community interested in portable hydrogen peroxide,” Surendranath says, “because of the appreciation that it would really meet a lot of needs, both on the industrial side as well as in terms of human health and sanitation.”

Other processes developed so far for potentially portable systems have key limitations. For example, most catalysts that promote the formation of hydrogen peroxide from hydrogen and oxygen also make a lot of water, leading to low concentrations of the desired product. Also, processes that involve electrolysis, as this new process does, often have a hard time separating the produced hydrogen peroxide from the electrolyte material used in the process, again leading to low efficiency.

Surendranath and the rest of the team solved the problem by breaking the process down into two separate steps. First, electricity (ideally from solar cells or windmills) is used to break down water into hydrogen and oxygen, and the hydrogen then reacts with a “carrier” molecule. This molecule — a compound called anthroquinone, in these initial experiments — is then introduced into a separate reaction chamber where it meets with oxygen taken from the outside air, and a pair of hydrogen atoms binds to an oxygen molecule (O2) to form the hydrogen peroxide. In the process, the carrier molecule is restored to its original state and returns to carry out the cycle all over again, so none of this material is consumed.

The process could address numerous challenges, Surendranath says, by making clean water, first-aid care for wounds, and sterile food preparation surfaces more available in places where they are presently scarce or unavailable.

“Even at fairly low concentrations, you can use it to disinfect water of microbial contaminants and other pathogens,” Surendranath says. And, he adds, “at higher concentrations, it can be used even to do what’s called advanced oxidation,” where in combination with UV light it can be used to decontaminate water of even strong industrial wastes, for example from mining operations or hydraulic fracking.

So, for example, a portable hydrogen peroxide plant might be set up adjacent to a fracking or mining site and used to clean up its effluent, then moved to another location once operations cease at the original site.

In this initial proof-of-concept unit, the concentration of hydrogen peroxide produced is still low, but further engineering of the system should lead to being able to produce more concentrated output, Surendranath says. “One of the ways to do that is to just increase the concentration of the mediator, and fortunately, our mediator has already been used in flow batteries at really high concentrations, so we think there’s a route toward being able to increase those concentrations,” he says.

“It’s kind of an amazing process,” he says, “because you take abundant things, water, air and electricity, that you can source locally, and you use it to make this important chemical that you can use to actually clean up the environment and for sanitation and water quality.”

“The ability to create a hydrogen peroxide solution in water without electrolytes, salt, base, etc., all of which are intrinsic to other electrochemical processes, is noteworthy,” says Shannon Stahl, a professor of chemistry at the University of Wisconsin, who was not involved in this work. Stahl adds that “Access to salt-free aqueous solutions of H2O2 has broad implications for practical applications.”

Stahl says that “This work represents an innovative application of ‘mediated electrolysis.’ Mediated electrochemistry provides a means to merge conventional chemical processes with electrochemistry, and this is a particularly compelling demonstration of this concept. … There are many potential applications of this concept.”

See the full article here .

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The mission of MIT is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of the MIT community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.