From University of New South Wales: “Colour of cells a ‘thermometer’ for molecular imbalance, study finds”

From University of New South Wales

13 May 2020
Sherry Landow
UNSW Media & Content
02 9385 9555
s.landow@unsw.edu.au

Non-invasive colour analysis of cells could one day be used in diagnostics, a proof-of-concept study has shown.

Professor Ewa Goldys and her team used an adapted microscope to capture detailed maps of cells and tissues via a series of photographs. Image: Supplied.

An imbalance of unstable molecular species called ‘free radicals’ will change the colour of cells – and a new imaging technique could one day allow scientists to detect and decode this colour without needing to take samples from the body, a new study by UNSW Sydney researchers has found. The paper was published online yesterday in Redox Biology.

“In our study of cell cultures and tissues in the lab, we found that colour is like a thermometer for oxidative stress,” says UNSW Engineering Professor Ewa Goldys, lead author of the study and Deputy Director of the ARC Centre of Excellence for Nanoscale Biophotonics.

Oxidative stress is caused by an overabundance of free radicals, which can cause damage to cells, DNA and proteins if left unchecked. Poor diet, alcohol consumption and obesity are some factors that can lead to the overproduction of free radicals.

Our body has a natural system for balancing these free radicals with antioxidants, but too many free radicals will make it harder for the body to repair damaged cells. Oxidative stress can cause chronic inflammation and is linked to many diseases, such as heart disease, diabetes and cancer.

“Oxidative stress isn’t disease-specific, but its restoration to healthy levels is an excellent measure of how well a therapeutic approach is working,” says Prof Goldys.

Despite the important role of oxidative stress to our health, it is often overlooked in medical diagnostics. This is largely because it’s difficult to measure on cells ‘in-vivo’ – within the body.

Current methods for testing oxidative stress involve extracting cells from the body and testing their response in a lab. While some cells can be easily removed, such as blood, this method isn’t an option for other parts of the body.

To solve this problem, Prof Goldys and her team adapted a standard fluorescent microscope – a microscope that detects natural fluorescent emissions from cells – to test whether cell and tissue colour is impacted by oxidative stress. They also developed a UV-free version of this technology for instances when UV is too dangerous to use, like in ophthalmology and reproductive health.

The microscopic camera works by emitting bursts of low-level LED light at various wavelengths onto cells and tissues. The light is absorbed by fluorescent molecules, which then emit their own light in response.

This fluorescent light allows the researchers to capture detailed maps of cells and tissues via a series of photographs. The microscope then decodes what the colours mean at a molecular level.

“The microscope has a device that precisely captures the colours in the cells,” explains Prof Goldys.

“We then use a big data approach to digitally ‘unmix’ the colour into its molecular components – red, green and blue, for example.”

The team developed a way to quantify each colour component by assigning it with a value. Once these values are tallied, scientists can measure oxidisation levels without need for cell extraction and analytical procedures.

“Once you have numbers, you can test all sorts of things,” says Prof Goldys, who was awarded a prestigious Eureka Award in 2016 for her discovery that the colours of cells and tissues can be subtle indicators of health and disease.

While their adapted microscope is not yet on the market, Prof Goldys is undertaking steps to begin the clinical trial in two years’ time. First, she will conduct an animal study, then seek TGA approval for the adapted microscope to be used in human studies, before starting a human trial in a selected disease condition.

If these steps are successful, the adapted microscope could become a common tool used in medical practices and scientific research.

In the meantime, Prof Goldys is excited about her next project, which will focus on how this technology can help monitor eye disease – particularly glaucoma.

Alongside researchers including UNSW Scientia Fellow Dr Nicole Carnt, the team are developing a bespoke camera that will photograph the back of the eye via the pupil. This camera will help ophthalmologists measure the oxidative stress of cells and tissues in the retina.

“The findings could change how we monitor and treat eye diseases,” says Prof Goldys.

“Early detection could hopefully help medical staff and patients slow disease progression.”

See the full article here .

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Welcome to UNSW Australia (The University of New South Wales), one of Australia’s leading research and teaching universities. At UNSW, we take pride in the broad range and high quality of our teaching programs. Our teaching gains strength and currency from our research activities, strong industry links and our international nature; UNSW has a strong regional and global engagement.

In developing new ideas and promoting lasting knowledge we are creating an academic environment where outstanding students and scholars from around the world can be inspired to excel in their programs of study and research. Partnerships with both local and global communities allow UNSW to share knowledge, debate and research outcomes. UNSW’s public events include concert performances, open days and public forums on issues such as the environment, healthcare and global politics. We encourage you to explore the UNSW website so you can find out more about what we do.

From University of Washington: “Sleep difficulties in the first year of life linked to altered brain development in infants who later develop autism”

From University of Washington

May 7, 2020
Kim Eckart

An 8-month-old boy wears an EEG cap to measure brain activity during a visit to the UW Autism Center.Kiyomi Taguchi/U. of Washington

Studying baby brains at UW Autism Center

Infants spend most of their first year of life asleep. Those hours are prime time for brain development, when neural connections form and sensory memories are encoded.

But when sleep is disrupted, as occurs more often among children with autism, brain development may be affected, too. New research led by the University of Washington finds that sleep problems in a baby’s first 12 months may not only precede an autism diagnosis, but also may be associated with altered growth trajectory in a key part of the brain, the hippocampus.

In a study published May 7 in the American Journal of Psychiatry, researchers report that in a sample of more than 400 6- to 12-month-old infants, those who were later diagnosed with autism were more likely to have had difficulty falling asleep. This sleep difficulty was associated with altered growth trajectories in the hippocampus.

“The hippocampus is critical for learning and memory, and changes in the size of the hippocampus have been associated with poor sleep in adults and older children. However, this is the first study we are aware of to find an association in infants as young as 6 months of age,” said lead author Kate MacDuffie, a postdoctoral researcher at the UW Autism Center.

As many as 80% of children with autism spectrum disorder have sleep problems, said Annette Estes, director of the UW Autism Center and senior author on the study. But much of the existing research, on infants with siblings who have autism, as well as the interventions designed to improve outcomes for children with autism, focus on behavior and cognition. With sleep such a critical need for children — and their parents — the researchers involved in the multicenter Infant Brain Imaging Study Network, or IBIS Network, believed there was more to be examined.

“In our clinical experience, parents have a lot of concerns about their children’s sleep, and in our work on early autism intervention, we observed that sleep problems were holding children and families back,” said Estes, who is also a UW professor of speech and hearing sciences.

Researchers launched the study, Estes said, because they had questions about how sleep and autism were related. Do sleep problems exacerbate the symptoms of autism? Or is it the other way around — that autism symptoms lead to sleep problems? Or something different altogether?

“It could be that altered sleep is part-and-parcel of autism for some children. One clue is that behavioral interventions to improve sleep don’t work for all children with autism, even when their parents are doing everything just right. This suggests that there may be a biological component to sleep problems for some children with autism,” Estes said.

To consider links among sleep, brain development and autism, researchers at the IBIS Network looked at MRI scans of 432 infants, surveyed parents about sleep patterns, and measured cognitive functioning using a standardized assessment. Researchers at four institutions — the UW, University of North Carolina at Chapel Hill, Washington University in St. Louis and the Children’s Hospital of Philadelphia — evaluated the children at 6, 12 and 24 months of age and surveyed parents about their child’s sleep, all as part of a longer questionnaire covering infant behavior. Sleep-specific questions addressed how long it took for the child to fall asleep or to fall back asleep if awakened in the middle of the night, for example.

At the outset of the study, infants were classified according to their risk for developing autism: Those who were at higher risk of developing autism — about two-thirds of the study sample — had an older sibling who had already been diagnosed. Infant siblings of children with autism have a 20 percent chance of developing autism spectrum disorder — a much higher risk than children in the general population.

A 2017 study by the IBIS Network found that infants who had an autistic older sibling and who also showed expanded cortical surface area at 6 and 12 months of age were more likely to be diagnosed with autism compared with infants without those indicators.

In the current study, 127 of the 432 infants were identified as “low risk” at the time the MRI scans were taken because they had no family history of autism. They later evaluated all the participants at 24 months of age to determine whether they had developed autism. Of the roughly 300 children originally considered “high familial risk,” 71 were diagnosed with autism spectrum disorder at that age.

Those results allowed researchers to re-examine previously collected longitudinal brain scans and behavioral data and identify some patterns. Problems with sleep were more common among the infants later diagnosed with autism spectrum disorder, as were larger hippocampi. No other subcortical brain structures were affected, including the amygdala, which is responsible for certain emotions and aspects of memory, or the thalamus, a signal transmitter from the spinal cord to the cerebral cortex.

The UW-led sleep study is the first to show links between hippocampal growth and sleep problems in infants who are later diagnosed with autism.

Other studies have found that “overgrowth” in different brain structures among infants who go on to develop those larger structures has been associated, at different stages of development, with social, language and behavioral aspects of autism.

While the UW sleep study found a pattern of larger hippocampal volume, and more frequent sleep problems, among infants who went on to be diagnosed with autism, what isn’t yet known is whether there is a causal relationship. Studying a broader range of sleep patterns in this population or of the hippocampus in particular may help determine why sleep difficulties are so prevalent and how they impact early development in children with autism spectrum disorder.

“Our findings are just the beginning — they place a spotlight on a certain period of development and a particular brain structure but leave many open questions to be explored in future research,” MacDuffie said.

A focus on early assessment and diagnosis prompted the UW Autism Center to establish an infant clinic in 2017. The clinic provides evaluations for infants and toddlers, along with psychologists and behavior analysts to create a treatment plan with clinic- and home-based activities — just as would happen with older children.

The UW Autism Center has evaluated sleep issues as part of both long-term research studies and in the clinical setting, as part of behavioral intervention.

“If kids aren’t sleeping, parents aren’t sleeping, and that means sleep problems are an important focus for research and treatment,” said MacDuffie.

The authors note that while parents reported more sleep difficulties among infants who developed autism compared to those who did not, the differences were very subtle and only observed when looking at group averages across hundreds of infants. Sleep patterns in the first years of life change rapidly as infants transition from sleeping around the clock to a more adult-like sleep/wake cycle. Until further research is completed, Estes said, it is not possible to interpret challenges with sleep as an early sign of increased risk for autism.

The study was funded by the National Institutes of Health, Autism Speaks and the Simons Foundation. Dr. Stephen Dager, professor of radiology at the UW School of Medicine and Tanya St. John, research scientist at the UW Autism Center, were co-authors. Additional co-authors, all at IBIS Network institutions, were Mark Shen, Martin Styner, Sun Hyung Kim and Dr. Joseph Piven at the University of North Carolina at Chapel Hill; Sarah Paterson, now at the James S. McDonnell Foundation; Juhi Pandey at the Children’s Hospital of Philadelphia; Jed Elison and Jason Wolff at the University of Minnesota; Meghan Swanson at the University of Texas at Dallas; Kelly Botteron at Washington University in St. Louis; and Dr. Lonnie Zwaigenbaum at the University of Alberta.

See the full article here .

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The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

From Purdue University: “New imaging technology allows visualization of nanoscale structures inside whole cells and tissues”

From Purdue University

This image shows a 3D super-resolution reconstruction of dendrites in primary visual cortex. (Image provided)

Since Robert Hooke’s first description of a cell in Micrographia 350 years ago, microscopy has played an important role in understanding the rules of life.

However, the smallest resolvable feature, the resolution, is restricted by the wave nature of light. This century-old barrier has restricted understanding of cellular functions, interactions and dynamics, particularly at the sub-micron to nanometer scale.

Super-resolution fluorescence microscopy overcomes this fundamental limit, offering up to tenfold improvement in resolution, and allows scientists to visualize the inner workings of cells and biomolecules at unprecedented spatial resolution.

Such resolving capability is impeded, however, when observing inside whole-cell or tissue specimens, such as the ones often analyzed during the studies of the cancer or the brain. Light signals, emitted from molecules inside a specimen, travel through different parts of cell or tissue structures at different speeds and result in aberrations, which will deteriorate the image.

Now, Purdue University researchers have developed a new technology to overcome this challenge.

“Our technology allows us to measure wavefront distortions induced by the specimen, either a cell or a tissue, directly from the signals generated by single molecules – tiny light sources attached to the cellular structures of interest,” said Fang Huang, an assistant professor of biomedical engineering in Purdue’s College of Engineering. “By knowing the distortion induced, we can pinpoint the positions of individual molecules at high precision and accuracy. We obtain thousands to millions of coordinates of individual molecules within a cell or tissue volume and use these coordinates to reveal the nanoscale architectures of specimen constituents.”

The Purdue team’s technology is recently published in Nature Methods. A video showing an animated 3D super-resolution is available at https://youtu.be/c9j621vUFBM. This tool from Purdue researchers allows visualization of nanoscale structures inside whole cells and tissues. It could allow for better understanding for diseases affecting the brain and regenerative therapies.

“During three-dimensional super-resolution imaging, we record thousands to millions of emission patterns of single fluorescent molecules,” said Fan Xu, a postdoctoral associate in Huang’s lab and a co-first author of the publication. “These emission patterns can be regarded as random observations at various axial positions sampled from the underlying 3D point-spread function describing the shapes of these emission patterns at different depths, which we aim to retrieve. Our technology uses two steps: assignment and update, to iteratively retrieve the wavefront distortion and the 3D responses from the recorded single molecule dataset containing emission patterns of molecules at arbitrary locations.”

The Purdue technology allows finding the positions of biomolecules with a precision down to a few nanometers inside whole cells and tissues and therefore, resolving cellular and tissue architectures with high resolution and fidelity.

“This advancement expands the routine applicability of super-resolution microscopy from selected cellular targets near coverslips to intra- and extra-cellular targets deep inside tissues,” said Donghan Ma, a postdoctoral researcher in Huang’s lab and a co-first author of the publication. “This newfound capacity of visualization could allow for better understanding for neurodegenerative diseases such as Alzheimer’s, and many other diseases affecting the brain and various parts inside the body.”

The National Institutes of Health provided major support for the research.

Other members of the research team include Gary Landreth, a professor from Indiana University’s School of Medicine; Sarah Calve, an associate professor of biomedical engineering in Purdue’s College of Engineering (currently an associate professor of mechanical engineering at the University of Colorado Boulder); Peng Yin, a professor from Harvard Medical School; and Alexander Chubykin, an assistant professor of biological sciences at Purdue. The complete list of authors can be found in Nature Methods.

“This technical advancement is startling and will fundamentally change the precision with which we evaluate the pathological features of Alzheimer’s disease,” Landreth said. “We are able to see smaller and smaller objects and their interactions with each other, which helps reveal structure complexities we have not appreciated before.”

Calve said the technology is a step forward in regenerative therapies to help promote repair within the body.

“This development is critical for understanding tissue biology and being able to visualize structural changes,” Calve said.

Chubykin, whose lab focuses on autism and diseases affecting the brain, said the high-resolution imaging technology provides a new method for understanding impairments in the brain.

“This is a tremendous breakthrough in terms of functional and structural analyses,” Chubykin said. “We can see a much more detailed view of the brain and even mark specific neurons with genetic tools for further study.”

The team worked with the Purdue Research Foundation Office of Technology Commercialization to patent the technology. The office recently moved into the Convergence Center for Innovation and Collaboration in Discovery Park District, adjacent to the Purdue campus.

The inventors are looking for partners to commercialize their technology. For more information on licensing this innovation, contact Dipak Narula of OTC at dnarula@prf.org.

See the full article here .

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Purdue University is a public research university in West Lafayette, Indiana, and the flagship campus of the Purdue University system. The university was founded in 1869 after Lafayette businessman John Purdue donated land and money to establish a college of science, technology, and agriculture in his name. The first classes were held on September 16, 1874, with six instructors and 39 students.

The main campus in West Lafayette offers more than 200 majors for undergraduates, over 69 masters and doctoral programs, and professional degrees in pharmacy and veterinary medicine. In addition, Purdue has 18 intercollegiate sports teams and more than 900 student organizations. Purdue is a member of the Big Ten Conference and enrolls the second largest student body of any university in Indiana, as well as the fourth largest foreign student population of any university in the United States.

From MIT News: “MIT initiates mass manufacture of disposable face shields for Covid-19 response”

From MIT News

March 31, 2020
Mary Beth Gallagher | Department of Mechanical Engineering

Robyn Goodner, who serves as a maker technical specialist for Project Manus, models the face shield design in the Metropolis Makerspace. Image: Project Manus

Elazer Edelman, the Edward J. Poitras Professor in Medical Engineering and Science at MIT, wears a face shield developed through a collaborative effort involving groups across MIT, while holding an electronic, Bluetooth-enabled stethoscope. In this photo, Edelman is wearing the shield in the snapped up position health care workers also have the option to use. Image: Elazer Edelman

A team from MIT has designed disposable face shields that can be mass produced quickly to address hospitals’ needs nationwide.

The shortage of personal protective equipment (PPE) available to health care professionals has become increasingly problematic as Covid-19 cases continue to surge. The sheer volume of PPE needed to keep doctors, nurses, and their patients safe in this crisis is daunting — for example, tens of millions of disposable face shields will be needed nationwide each month. This week, a team from MIT launched mass manufacturing of a new technique to meet the high demand for disposable face shields.

The single piece face shield design will be made using a process known as die cutting. Machines will cut the design from thousands of flat sheets per hour. Once boxes of these flat sheets arrive at hospitals, health care professionals can quickly fold them into three-dimensional face shields before adjusting for their faces.

“These face shields have to be made rapidly and at low cost because they need to be disposable,” explains Martin Culpepper, professor of mechanical engineering, director of Project Manus, and a member of MIT’s governance team on manufacturing opportunities for Covid-19. “Our technique combines low-cost materials with a high-rate manufacturing that has the potential of meeting the need for face shields nationwide.”

Culpepper and his team at Project Manus spearheaded the development of the technique in collaboration with a number of partners from MIT, local-area hospitals, and industry. The team has been working closely with the MIT Medical Outreach team and the Crisis Management Unit established by Vice President for Research Maria Zuber and directed by Elazer R. Edelman, the Edward J. Poitras Professor in Medical Engineering and Science at MIT.

Extending the life of face masks

When used correctly, face masks should be changed every time a doctor or nurse treats a new patient. However, over the past month, many health care professionals have been asked to wear one face mask per day. That one mask could carry virus particles — potentially contributing to the spread of Covid-19 within hospitals and endangering health care professionals.

“The lack of adequate protective equipment or the idea of reusing potentially contaminated equipment is especially frightening to health care workers who are putting their lives, and by extension the lives and well-being of their families, on the line every day,” explains Edelman, who is also the director of MIT’s Institute for Medical Engineering and Science (IMES) and leader of MIT’s PPE task force.

Face shields can address this problem by providing another layer of protection that covers masks and entire faces while extending the life of PPE. The shields are made of clear materials and have a shape similar to a welder’s mask. They protect the health care professional and their face mask from coming in direct contact with virus particles spread through coughing or sneezing.

“If we can slow down the rate at which health care professionals use face masks with a disposable face shield, we can make a real difference in protecting their health and safety,” explains Culpepper.

Culpepper and his team at Project Manus set out to design a face shield that could be rapidly produced at a scale large enough to meet the growing demand. They landed on a flat design that people could quickly fold into a three dimensional structure when the shield was ready for use. Their design also includes extra protection with flaps that fold under the neck and over the forehead.

As much of MIT’s campus came to a halt in light of social distancing measures being put in place, Culpepper started prototyping using a laser cutter he had in his house. Along with some design input from his children, he tested different materials and made the first 10 prototypes at home.

“When you’re thinking of materials, you have to keep supply chains in mind. You can’t choose a material that could evaporate from the supply chain. That is a challenging problem in this crisis,” explains Culpepper. After testing a few materials that cracked and broke when bent, the team chose polycarbonate and polyethylene terephthalate glycol – known more commonly as PETG – as the shield’s material.

In addition to making more prototypes at the Project Manus Metropolis Makerspace using a laser cutter, Culpepper worked with Professor Neil Gershenfeld and his team at MIT’s Center for Bits and Atoms (CBA) on rapid-prototyping designs for testing using a Zund large-format cutter.

Gershenfeld’s team at CBA is working on a number of projects for coronavirus response using its digital fabrication facility at MIT as well as the global Fab Lab network it launched. “The coronavirus response site is a great resource for those that are interested in working on solutions for PPE and devices for the Covid-19 pandemic,” Culpepper adds.

“It’s been a pleasure in this difficult time collaborating with such an impressive group, drawing on all of the Institute’s strengths to quickly define and refine a solution to an urgent need,” says Gershenfeld. “The work at MIT will be valuable beyond its immediate local impact, as a best-practices reference for the many other face shield projects emerging around the world.”

Testing the shield at local hospitals

With a number of working prototypes built, Culpepper and his team moved to the testing phase after consultation with, and practical feedback from, Edelman, who is also a physician.

“The single greatest insecurity of a health care provider is the thought that we will become infected and in doing so be unable to perform our duties or infect others,” adds Edelman.

Edelman demonstrated how to store, assemble, and use the face shields for nurses and physicians at a number of area hospitals. Participants were then asked to use them in real-life situations and provide feedback using a one-page survey.

The feedback was overwhelmingly positive — participants found that in addition to being easy to assemble and use, the MIT-designed shields provided good protection against coming in contact with virus particles through splashes or aerosolized particles.

Armed with this feedback, Culpepper’s team made a few minor adjustments to the design to maximize coverage around the sides and neck of users. With the design finalized, the project has this week shifted to high-rate mass manufacturing.

High-rate mass manufacturing

The die cutter machines used in mass manufacturing will produce the flat face shields at a rate of 50,000 shields per day in a few weeks. The manufacturer will continue to ramp up and increase the rate of manufacturing further with the ability to fabricate in more than 80 facilities nationwide.

“This process has been designed in such a way that there is the potential to ramp up to millions of face shields produced per day,” explains Culpepper. “This could very quickly become a nationwide solution for face shield shortages.”

MIT plans on purchasing the first 40,000 face shields to donate to local Boston-area hospitals this week and the fabrication facilities will donate 60,000.

“Having an adequate and perhaps even endless supply of PPE is absolutely critical to ensuring the safety of the entire population, especially those who care for Covid-19 patients,” adds Edelman.

Throughout the process, Culpepper’s team received help from a number of colleagues and departments across MIT. This includes MIT’s Office of the Vice President for Research, Professor Elazer Edelman, Tolga Durak, managing director of the MIT Environment, Health and Safety Office, the Center for Bits and Atoms, MIT Procurement Operations, MIT’s Office of the General Counsel, MIT’s Department of Mechanical Engineering, and colleagues from MIT Lincoln Laboratory, who helped source material to build the face shields and supported design iterations. They also received advice from MIT colleagues working with the Massachusetts Technology Collaborative, which is helping organize manufacturers for Covid-19 response.

“This project was a great example of collaboration across MIT and the employment of mind-heart-hand. When we reached out to others, they dropped everything to put their minds and hands to work helping us make this happen quickly,” says Culpepper. “It is also a great example for others to look to safely and rapidly innovate PPE for Covid-19.”

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.

From Harvard Gazette: “From the lab to COVID front lines”

Harvard University

From Harvard Gazette

March 31, 2020
Alvin Powell

Technology developed at Harvard provides early boost to Mass. COVID testing

As Massachusetts rapidly ramps up COVID-19 testing, a technology born in the lab of Harvard AIDS pioneer Max Essex and nurtured by entrepreneurship resources on campus has played an important role in providing the needed reagents and kits that are driving a surge in testing.

At Beth Israel Deaconess Medical Center, which by Tuesday had conducted more than 3,000 tests, the first kits that fed the hospital’s rapid increase in diagnostic results since it started doing them in mid-March came from Watertown-based Aldatu Biosciences. [The Broad Institute also has made rapid, large advances in testing.] The nine-employee company was formed to commercialize this diagnostic technology developed at Harvard and was based at the Pagliuca Harvard Life Lab in Allston until January 2019.

Jeffrey Saffitz, chief of pathology at BIDMC and Mallinckrodt Professor of Pathology at Harvard Medical School, said the hospital’s lab has four high-volume testing machines, but had a shortage — as did other labs in the state — of the customized reagents needed to detect SARS-CoV-2, the virus that causes COVID-19.

While BIDMC awaited additional supplies from its regular commercial vendors, Aldatu worked with the hospital’s pathology staff to develop diagnostic kits and get them to the hospital. Saffitz said the rapid increase in COVID testing — as of Tuesday, they’d found 487 positives — was in part thanks to Aldatu’s nimbleness and to the efforts of hospital staff, including clinical microbiologists, laboratory technicians, lab managers, and others. By late last week, Saffitz said the hospital was ready to perform as many as 1,500 tests per day — an amount equal to an entire season’s worth of flu tests.

Test kits from Aldatu Biosciences in Watertown went to Beth Israel Deaconess Medical Center, which by Sunday afternoon had conducted almost 2,500 tests, the most by a hospital-based lab in the state.

“Our machines were able to accommodate the Aldatu test kits. When this happened there was an incredibly effective partnership between our clinical microbiology teams and the Aldatu folks,” Saffitz said. “We worked together to advise them in terms of what they needed to do to make the test kits usable on our machinery. … We did all the validation studies of the test kit to prove that it actually worked, and it worked beautifully. And we were able to run the Aldatu test kits initially at a time before we had received test kits from the major supplier.”

Aldatu’s roots lie in Essex’s long-running Botswana-Harvard Partnership, established in 1996 to fight AIDS. In 2008, infectious diseases physician Christopher Rowley, then a research associate at the Harvard T.H. Chan School of Public Health, was joined there by a postdoctoral fellow, Iain MacLeod. Rowley was working on HIV drug resistance, a continual problem in treating patients with antiretroviral drugs. Frustrated by the cumbersome existing process to determine whether a patient harbored resistant HIV strains, the two developed the PANDAA genotyping platform (Pan Degenerate Amplification and Adaptation), which provided rapid, low-cost HIV genotyping.

“Iain and Chris developed the PANDAA platform for PCR testing of drug resistance for HIV,” Essex said. “The goal was to develop a test that would be cheap enough for widespread use in low- and middle-income countries, where drug resistance testing was often not available.”

Rowley went on to a clinical post at BIDMC, where today he is an assistant professor of medicine and an infectious diseases physician, while MacLeod, interested in developing the technology further, went to Harvard’s Innovation Lab (i-lab).

Founded in 2000 as a way to support student entrepreneurs, the i-lab offers students working space, an entrepreneurial-minded community, and expert advice. At an i-lab workshop, MacLeod met David Raiser, a doctoral student in genetics and a technology assessment fellow at Harvard’s Office of Technology Development (OTD), where he was learning commercialization and marketing strategies for emerging innovations. The two first talked about PANDAA’s potential while waiting outside the i-lab for the shuttle to Harvard’s Longwood campus.

David Raiser (pictured) and Iain MacLeod met at a Harvard i-lab workshop. They later set up Aldatu, which went into full-time operation in 2015. “We were well-positioned to move quickly on the COVID-19 pandemic,” says Raiser.

“David had an intuitive sense that this was a valuable technology with great potential to benefit the public,” said Grant Zimmermann, OTD’s managing director of business development, who worked with Raiser and MacLeod to set up Aldatu. “This was never just a money-making goal for David. He has a genuine desire to help people.”

The two created a business development strategy for Aldatu in 2014 and worked with Zimmermann to develop a license structure to support the company — a step that became official two years later.

“I’m immensely proud of the Aldatu team for being among the first to step up to make testing broadly available,” said Isaac Kohlberg, Harvard’s chief technology development officer and senior associate provost. “The ultimate impact of a new discovery may be difficult to fathom at the outset, but the Aldatu example shows why it’s so important to get promising technologies into the hands of passionate entrepreneurs who can advance and scale up an innovation for the public’s broadest benefit.”

In 2014, Aldatu received additional financial support in the form of the $40,000 Bertarelli Foundation Grand Prize in the Harvard Deans’ Health and Life Sciences Challenge. The team also won a $1.5 million small-business grant from the National Institute of Allergy and Infectious Diseases, which let them begin full-time operation in 2015. The two moved to Kendall Square’s LabCentral in 2016, then returned to Allston to become an early tenant in Harvard’s Life Lab. In January 2019, the company moved into its own facility in Watertown.

“I’ve said for a few years now, Aldatu is a true i-lab story,” Raiser said. “We built very strong and meaningful and valuable relationships out of our time at the i-lab and the Life Lab.”

Aldatu was established as a public benefit corporation — which puts public benefit on a par with profits in the corporate mission — with the aim of providing easy-to-use, low-cost diagnostics for resource-poor areas.

They distributed tests for HIV in Botswana and developed a diagnostic for Lassa fever, another viral disease. In early March, as the lack of COVID-19 testing became acute, Rowley contacted MacLeod and asked whether PANDAA could be used for the disease. They developed the diagnostic in a matter of days and, by the time regulatory guidelines changed on March 16 to let private labs begin testing, they had already begun working with BIDMC to validate the test using blinded patient samples provided by the state.

“We had already, over the last six years, developed experience with assay development and applying that test development to infectious disease and working with viruses in outbreak concern areas,” Raiser said. “We were well-positioned to move quickly on the COVID-19 pandemic.”

A week later, Aldatu was not just providing kits to BIDMC, its officers were in conversation with other hospitals about doing the same and preparing to provide COVID-19 testing to partners in sub-Saharan Africa with whom they had been working.

“We’re trying to cast a wide net and fill gaps in testing access and capacity quickly wherever we can do so,” Raiser said.

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

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 University of Toronto: “Eight U of T researchers receive federal grants for COVID-19 projects”

From University of Toronto

March 31, 2020
Rahul Kalvapalle

Vijaya Kumar Murty, a professor in U of T’s department of mathematics, is setting up a COVID-19 task force to predict outbreak trajectories, measure public health interventions and provide real-time advice to policy-makers (photo by Johnny Guatto)

When it comes to assessing the risk of transmission of an infectious disease like COVID-19 and evaluating the effectiveness of measures like physical distancing, mathematics and mathematical modelling are crucial.

“How does the virus spread? How quickly does it multiply? What’s the impact of interventions like social distancing? Mathematical modelling looks at these kinds of questions,” says Vijaya Kumar Murty, a professor in the department of mathematics in the University of Toronto’s Faculty of Arts & Science.

To address such questions, mathematicians like Murty take into account numerous variables involved in the spread of a disease, including the age, occupation or pre-existing health conditions of an individual.

“So what you do is try to build a mathematical quantitative model – taking these factors into account – of what’s going to happen in terms of the propagation dynamics,” says Murty, who is also the director of the Fields Institute for Research in Mathematical Sciences at U of T.

Murty is the recipient of a $666,667 grant from the Canadian Institutes of Health Research (CIHR) that will go towards setting up the COVID-19 Mathematical Modelling Rapid Response Task Force, a network of experts who will work to predict outbreak trajectories for the disease, measure public health interventions and provide real-time advice to policy-makers.

It’s one of eight COVID-19 research projects at U of T to receive support from a recent $25.8-million funding package announced by the Government of Canada, building on an earlier investment of $27 million on March 6 – nearly $6 million of which went to researchers who are based at U of T or one of its affiliated hospitals.

Both rounds of funding are part of the federal government’s larger $275-million investment in research on COVID-19 counter-measures.

“From developing low-cost diagnostic tools to modelling disease transmission and exploring potential drug interventions, researchers at the University of Toronto are attacking the problems posed by COVID-19 from numerous angles,” says Vivek Goel, U of T’s vice-president, research and innovation, and strategic initiatives.

“This latest round of funding from the federal government will help our experts across several disciplines to accelerate research projects that could have a crucial impact in the global fight against this potentially deadly illness.”

Murty’s mathematical modelling task force was inspired by a similar network set up by Mitacs – a national non-profit that designs and delivers research and training programs in partnership with universities, governments and companies – during the 2003 outbreak of Severe Acute Respiratory Syndrome (SARS). It will comprise 14 academics from across the country as well as other partners, including the Public Health Agency of Canada and research institutes in China.

In addition to addressing the pressing issue of the coronavirus epidemic, Murty says mathematical modelling can be applied to the analysis of other infectious diseases as well as the study of social pathogens like opioid abuse.

“It explores the propagation of a pathogen in society or, in general, propagation in networks,” he says. “How something moves from node to node – or person to person – and what interventions will produce what effect on that transmission.”

“This work is of course time-sensitive and critically important right now because of the health situation we find ourselves in. But thinking beyond that, I’m envisaging that this task force will grow so that we can continue to analyze and model public health and disease from a mathematics point of view.”

Darrell Tan, a clinician-scientist at St. Michael’s Hospital and an associate professor in U of T’s Faculty of Medicine and the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health, will look at whether the HIV drug Kaletra could be useful against COVID-19 (photo courtesy of Darell Tan)

While Murty and his collaborators crunch the numbers, Darrell Tan is preparing to run clinical trials to explore whether a popular anti-HIV drug could help prevent the spread of COVID-19.

Tan is an associate professor at the Faculty of Medicine and the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health, and is a clinician-scientist in the infectious diseases division of St. Michael’s Hospital. He secured a $1-million CIHR grant for the trials, which will look at whether Kaletra – a drug that has been used in HIV treatment as well as for uninfected people with high risk of exposure – could be useful against COVID-19.

“In general, whenever we’re trying to actively find new therapies for any medical condition, one of the most efficient ways of doing that is to find existing available drugs that could potentially be re-purposed,” says Tan.

“Because obviously it saves all the steps in drug development and safety assessments if we already have a drug available that we understand the characteristics of very well.”

Tan says that in-vitro studies and animal experiments have suggested Kaletra may have an effect on COVID-19 and other types of coronaviruses such as SARS and MERS (Middle East Respiratory Syndrome), but that there’s a dearth of quality evidence from human studies.

His trial will deploy what’s known as a “ring design,” where “rings” of people who came into close contact with COVID-19 patients will be identified.

“Once we identify a case, one could draw a ring of close contacts surrounding that ‘index case,’ and, of course, those people would be the individuals who would be at greatest risk and therefore the ones we would most immediately want to intervene on in order to prevent transmission from happening,” says Tan.

Individuals selected for the study will be randomly assigned to a 14-day course of either Kaletra or a placebo and will be tested periodically to see if they develop COVID-19.

“If you have an intervention that does turn out to work, you can imagine effectively drawing a ring around a person and intervening on that ring of exposed contacts to create a buffer between the infection we already know about and the rest of the population,” said Tan.

The trials could begin as early as the first week of April, in what Tan said is a testament to the seriousness and speed of Canada’s regulatory authorities in supporting COVID-19 research projects.

“The process of having a clinical trial approved by Health Canada can usually take up to 30 days,” says Tan. “In this case, Health Canada received our application, reviewed it and issued approval within less than 24 hours over a weekend, which is quite remarkable.”

In a statement, federal Minister of Health Patty Hajdu emphasized the importance of research in tackling COVID-19 in Canada and around the world.

“The outbreak of COVID-19 evolves quickly, and protecting the health of Canadians is our priority. The additional teams of researchers receiving funding today will help Canada quickly generate the evidence we need to contribute to the global understanding of the COVID-19 illness,” Hajdu said.

“Their essential work will contribute to the development of effective vaccines, diagnostics, treatments, and public health responses.”

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Founded in 1827, the University of Toronto has evolved into Canada’s leading institution of learning, discovery and knowledge creation. We are proud to be one of the world’s top research-intensive universities, driven to invent and innovate.

Our students have the opportunity to learn from and work with preeminent thought leaders through our multidisciplinary network of teaching and research faculty, alumni and partners.

The ideas, innovations and actions of more than 560,000 graduates continue to have a positive impact on the world.

From Duke University School of Medicine: “Duke leverages cryo-electron microscope facility in the race for coronavirus vaccine”

From Duke University School of Medicine

March 26, 2020
Lindsay Key

Priyamvada Acharya, PhD, an associate professor of surgery in the School of Medicine and director of the Division of Structural Biology at the Duke Human Vaccine Institute, works in the cryo-electron microscope faciity on Duke’s campus.

Although most research laboratories at Duke University are shuttered to prevent future transmission of the Covid-19 coronavirus, one of the few to remain open houses a powerful machine that Duke researchers think will be instrumental in developing a vaccine for the virus.

The multimillion-dollar cryo-electron microscope (cryo-EM for short), the Titan Krios, is able to “see” proteins in atomic level detail by taking hundreds of thousands of molecular images of a biological specimen and then classifying and averaging them with powerful software to create a 3D image, and ultimately, a model of the protein.

In the case of the coronavirus, Duke scientist Priyamvada Acharya and her team are using the machine to determine structures of the coronavirus spike protein —the part of the virus that sticks out, attaches with the host, and helps the virus enter into human cells.

“We are using the information to learn, at a basic level, details of how the spike functions, and translate this knowledge for vaccine design,” said Acharya, PhD, an associate professor of surgery in the School of Medicine and director of the Division of Structural Biology at the Duke Human Vaccine Institute.

Better understanding of the structure and function of the spike will also help the team develop molecular hooks to pull out antibodies from the blood of COVID-19 patients, which could be used for vaccine development.

Acharya has been using a similar approach in her quest to develop a vaccine for HIV.

“Cryo-EM helps you rapidly figure out the fine details of intermolecular interactions, thereby giving you the tools to manipulate those interactions to make the best vaccines to trigger the immune system to make protective antibodies,” she said.

“As we move towards the development of a safe and effective vaccine for COVID-19, it’s absolutely imperative that we understand which parts of the virus we need to use for immunization,” said Colin Duckett, vice dean for basic sciences in the School of Medicine. “The right parts will train the immune system to kill virally-infected cells without harmful side effects, but we can only figure that out if we know the active structure of the key proteins, especially the spike protein. That’s where Dr. Acharya’s group comes in. The progress that Dr. Acharya and her team have made so rapidly is nothing short of remarkable.”

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Established in 1930, Duke University School of Medicine is the youngest of the nation’s top medical schools. Ranked among the best in the nation, the School takes pride in being an inclusive community of outstanding learners, investigators, clinicians, and staff where traditional barriers are low, interdisciplinary collaboration is embraced, and great ideas accelerate translation of fundamental scientific discoveries to improve human health locally and around the globe.

Composed of more than 2,500 faculty physicians and researchers, the Duke University School of Medicine along with the Duke University School of Nursing and Duke University Health System create Duke Health. Duke Health is a world-class health care network. Founded in 1998 to provide efficient, responsive care, the health system offers a full network of health services and encompasses Duke University Hospital, Duke Regional Hospital, Duke Raleigh Hospital, Duke Primary Care, Private Diagnostic Clinic, Duke Home and Hospice, Duke Health and Wellness, and multiple affiliations.

Younger than most other prestigious U.S. research universities, Duke University consistently ranks among the very best. Duke’s graduate and professional schools — in business, divinity, engineering, the environment, law, medicine, nursing and public policy — are among the leaders in their fields. Duke’s home campus is situated on nearly 9,000 acres in Durham, N.C, a city of more than 200,000 people. Duke also is active internationally through the Duke-NUS Graduate Medical School in Singapore, Duke Kunshan University in China and numerous research and education programs across the globe. More than 75 percent of Duke students pursue service-learning opportunities in Durham and around the world through DukeEngage and other programs that advance the university’s mission of “knowledge in service to society.”

From MIT News: “MIT-based team works on rapid deployment of open-source, low-cost ventilator”

From MIT News

March 26, 2020
David L. Chandler

Clinical and design considerations will be published online; goal is to support rapid scale-up of device production to alleviate hospital shortages.

The new device fits around an Ambu bag (blue), which hospitals already have on hand in abundance. Designed to be squeezed by hand, instead they are squeezed by mechanical paddles (center) driven by a small motor. This directs air through a tube which is placed in the patient’s airway. Images: courtesy of the researchers.

This shows the setup used for preliminary testing of an earlier version of the low-cost prototype design that could provide rapid deployment to hospitals facing shortages of the vital equipment Images: courtesy of the researchers.

Test setup in the lab shows the most recent version of the device undergoing initial testing.Images: courtesy of the researchers.

One of the most pressing shortages facing hospitals during the Covid-19 emergency is a lack of ventilators. These machines can keep patients breathing when they no longer can on their own, and they can cost around $30,000 each. Now, a rapidly assembled volunteer team of engineers, physicians, computer scientists, and others, centered at MIT, is working to implement a safe, inexpensive alternative for emergency use, which could be built quickly around the world.

The team, called MIT E-Vent (for emergency ventilator), was formed on March 12 in response to the rapid spread of the Covid-19 pandemic. Its members were brought together by the exhortations of doctors, friends, and a sudden flood of mail referencing a project done a decade ago in the MIT class 2.75 (Medical Device Design). Students working in consultation with local physicians designed a simple ventilator device that could be built with about $100 worth of parts. They published a paper detailing their design and testing, but the work ended at that point. Now, with a significant global need looming, a new team, linked to that course, has resumed the project at a highly accelerated pace.

The team, called MIT E-Vent (for emergency ventilator), was formed on March 12 in response to the rapid spread of the Covid-19 pandemic. Its members were brought together by the exhortations of doctors, friends, and a sudden flood of mail referencing a project done a decade ago in the MIT class 2.75 (Medical Device Design). Students working in consultation with local physicians designed a simple ventilator device that could be built with about $100 worth of parts. They published a paper detailing their design and testing, but the work ended at that point. Now, with a significant global need looming, a new team, linked to that course, has resumed the project at a highly accelerated pace.

The key to the simple, inexpensive ventilator alternative is a hand-operated plastic pouch called a bag-valve resuscitator, or Ambu bag, which hospitals already have on hand in large quantities. These are designed to be operated by hand, by a medical professional or emergency technician, to provide breaths to a patient in situations like cardiac arrest, until an intervention such as a ventilator becomes available. A tube is inserted into the patient’s airway, as with a hospital ventilator, but then the pumping of air into the lungs is done by squeezing and releasing the flexible pouch. This is a task for skilled personnel, trained in how to evaluate the patient and adjust the timing and pressure of the pumping accordingly.

The innovation begun by the earlier MIT class, and now being rapidly refined and tested by the new team, was to devise a mechanical system to do the squeezing and releasing of the Ambu bag, since this is not something that a person could be expected to do for any extended period. But it is crucial for such a system to not damage the bag and to be controllable, so that the amount of air and pressures being delivered can be tailored to the particular patient. The device must be very reliable, since an unexpected failure of the device could be fatal, but as designed by the MIT team, the bag can be immediately operated manually.

The team is particularly concerned about the potential for well-meaning but inexperienced do-it-yourselfers to try to reproduce such a system without the necessary clinical knowledge or expertise with hardware that can operate for days; around 1 million cycles would be required to support a ventilated patient over a two-week period. Furthermore, it requires code that is fault-tolerant, since ventilators are precision devices that perform a life-critical function. To help curtail the spread of misinformation or poorly-thought-out advice, the team has added to their website verified information resources on the clinical use of ventilators and the requirements for training and monitoring in using such systems. All of this information is freely available at e-vent.mit.edu.

“We are releasing design guidance (clinical, mechanical, electrical/controls, testing) on a rolling basis as it is developed and documented,” one team member says. “We encourage capable clinical-engineering teams to work with their local resources, while following the main specs and safety information, and we welcome any input other teams may have.”

The researchers emphasize that this is not a project for typical do-it-yourselfers to undertake, since it requires specialized understanding of the clinical-technical interface, and the ability to work in consideration of strict U.S. Food and Drug Administration specifications and guidelines.

Such devices “have to be manufactured according to FDA requirements, and should only be utilized under the supervision of a clinician,” a team member said. “The Department of Health and Human Services released a notice stating that all medical interventions related to Covid-19 are no longer subject to liability, but that does not change our burden of care.” he said. “At present, we are awaiting FDA feedback” about the project. “Ultimately, our intent is to seek FDA approval. That process takes time, however.”

The all-volunteer team is working without funding and operating anonymously for now because many of them have already been swamped by inquiries from people wanting more information, and are concerned about being overwhelmed by calls that would interfere with their work on the project. “We would really, really like to just stay focused,” says one team member. “And that’s one of the reasons why the website is so essential, so that we can communicate with anyone who wants to read about what we are doing, and also so that others across the world can communicate with us.”

“The primary consideration is patient safety. So we had to establish what we’re calling minimum clinical functional requirements,” that is, the minimum set of functions that the device would need to perform to be both safe and useful, says one of the team members, who is both an engineer and an MD. He says one of his jobs is to translate between the specialized languages used by the engineers and the medical professionals on the team.

That determination of minimum requirements was made by a team of physicians with broad clinical backgrounds, including anesthesia and critical care, he says. In parallel, the group set to work on designing, building, and testing an updated prototype. Initial tests revealed the high loads that actual use incurs, and some weaknesses that have already been addressed so that, in the words of team co-leads, “Even the professor can kick it across the room.” In other words, early attempts focused on super “makability” were too optimistic.

New versions have already been fabricated and are being prepared for additional functional tests. Already, the team says there is enough detailed information on their website to allow other teams to work in parallel with them, and they have also included links to other teams that are working on similar design efforts.

In under a week the team has gone from empty benches to their first realistic tests of a prototype. One team member says that in the less than a week full they have been working, motivated by reports of doctors already having to ration ventilators, and the intense focus the diverse group has brought to this project, they have already generated “multiple theses worth” of research.

The cross-disciplinary nature of the group has been crucial, one team member says. “The most exciting times and when the team is really moving fast are when we have an a design engineer, sitting next to a controls engineer, sitting next to the fabrication expert, with an anesthesiologist on WebEx, all solid modeling, coding, and spreadsheeting in parallel. We are discussing the details of everything from ways to track patients’ vital signs data to the best sources for small electric motors.”

The intensity of the work, with people putting in very long hours every day, has been tiring but hasn’t dulled their enthusiasm. “We all work together, and ultimately the goal is to help people, because people’s lives understandably hang in the balance,” he said.

The team can be contacted via their website.

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

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 San Diego: “Coronavirus Massive Simulations Completed on Supercomputer”

From UC San Diego

Mar 26, 2020
Jorge Salazar

UC San Diego biochemist leads new simulations that can help researchers design new drugs and vaccines to combat the coronavirus.

Scientists are preparing a massive computer model of the coronavirus that they expect will give insight into how it infects in the body. They’ve taken the first steps, testing the first parts of the model and optimizing code on the Frontera supercomputer at the University of Texas at Austin.

TACC Frontera Dell EMC supercomputer fastest at any university

The knowledge gained from the full model can help researchers design new drugs and vaccines to combat the coronavirus.

UC San Diego’s Rommie Amaro is leading efforts to build the first complete all-atom model of the SARS-COV-2 coronavirus envelope, its exterior component.

“If we have a good model for what the outside of the particle looks like and how it behaves, we’re going to get a good view of the different components that are involved in molecular recognition,” said Amara, a professor of chemistry and biochemistry.

Molecular recognition involves how the virus interacts with the angiotensin converting enzyme 2 (ACE2) receptors and possibly other targets within the host cell membrane.

The coronavirus model is anticipated by Amaro to contain roughly 200 million atoms, a daunting undertaking, as the interaction of each atom with one another has to be computed. Her team’s workflow takes a hybrid, or integrative modeling approach.

“We’re trying to combine data at different resolutions into one cohesive model that can be simulated on leadership-class facilities like Frontera,” Amaro said. “We basically start with the individual components, where their structures have been resolved at atomic or near atomic resolution. We carefully get each of these components up and running and into a state where they are stable. Then we can introduce them into the bigger envelope simulations with neighboring molecules.”

On March 12-13, the Amaro Lab ran molecular dynamics simulations on up to 4,000 nodes, or about 250,000 processing cores, on Frontera at the Texas Advanced Computing Center at the University of Texas at Austin.

Amaro’s work with the coronavirus builds on her success with an all-atom simulation of the influenza virus envelope, published in ACS Central Science, in February 2020. She said that the influenza work will have a remarkable number of similarities to what they’re now pursuing with the coronavirus.

“It’s a brilliant test of our methods and our abilities to adapt to new data and to get this up and running right off the fly,” Amaro said. “It took us a year or more to build the influenza viral envelope and get it up and running on the national supercomputers. For influenza, we used the Blue Waters supercomputer, which was in some ways the predecessor to Frontera. The work, however, with the coronavirus obviously is proceeding at a much, much faster pace. This is enabled, in part because of the work that we did on Blue Waters earlier.”

According to Amaro, these simulations will provide new insights into the different parts of the coronavirus that are required for infectivity.

“And why we care about that is because if we can understand these different features, scientists have a better chance to design new drugs; to understand how current drugs work and potential drug combinations work. The information that we get from these simulations is multifaceted and multidimensional and will be of use for scientists on the front lines immediately and also in the longer term,” Amaro explained. “Hopefully, the public will understand that there’s many different components and facets of science to push forward to understand this virus. These simulations on Frontera are just one of those components, but hopefully an important and a gainful one.”

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

The University of California, San Diego (also referred to as UC San Diego or UCSD), is a public research university located in the La Jolla area of San Diego, California, in the United States.[12] The university occupies 2,141 acres (866 ha) near the coast of the Pacific Ocean with the main campus resting on approximately 1,152 acres (466 ha).[13] Established in 1960 near the pre-existing Scripps Institution of Oceanography, UC San Diego is the seventh oldest of the 10 University of California campuses and offers over 200 undergraduate and graduate degree programs, enrolling about 22,700 undergraduate and 6,300 graduate students. UC San Diego is one of America’s Public Ivy universities, which recognizes top public research universities in the United States. UC San Diego was ranked 8th among public universities and 37th among all universities in the United States, and rated the 18th Top World University by U.S. News & World Report ‘s 2015 rankings.

From UC San Diego: “UC San Diego Engineers and Doctors Team Up to Retrofit and Build Ventilators with 3D-Printing”

From UC San Diego

Mar 26, 2020
By Alison Caldwell

Students, staff and faculty address one of the key challenges of COVID-19 outbreak.

Engineering students and faculty are developing a simple device using 3D-printed parts and off-the-shelf components to convert an existing manual ventilator system into an automatic one.

Even as university campuses close across the nation in an effort to slow the spread of the novel coronavirus, a team of engineers and physicians at the University of California San Diego is rapidly developing simple, ready-to-use ventilators to be deployed if the need arises.

The project kick-started several weeks ago when news started to trickle in that communities in Northern Italy with widespread COVID-19 were in dire straits.

“One of the biggest things we heard was that there weren’t enough ventilators to treat all of the patients coming into the hospitals,” said James Friend, a professor in the Department of Mechanical and Aerospace Engineering and the Department of Surgery at UC San Diego. “It’s clear that if we’re not careful, we might end up in the same situation.”

Ventilators are medical devices that push air in and out of a patient’s lungs when they are unable to breathe on their own. One of the primary symptoms of COVID-19 is difficulty in breathing; approximately 1 percent of people who contract the virus require ventilation to support their recovery—sometimes for weeks.

The situation in Italy spurred Dr. Lonnie Petersen, an assistant professor in the Department of Mechanical and Aerospace Engineering at UC San Diego and an adjunct with UC San Diego Health, to reach out to her medical and engineering colleagues, proposing a new collaboration to quickly produce simple ventilators that could be easily built and readily used to support patients in a crisis.

“We immediately had a lot of support from staff and faculty, all working to get this project off the ground,” Petersen said. “Our community is taking this threat very seriously and acting accordingly.”

The first step was to seek consensus with anesthetists and respiratory therapists about minimum requirements for a ventilator. The next was to determine whether engineers could reasonably produce them, and how quickly.

Within days, a team of researchers from the Friend and Petersen labs, including graduate students Aditya Vasan, William Connacher, Jeremy Sieker and Reiley Weekes, began building devices using premade parts and 3D printers. Their first goal was to convert an existing manual ventilator model to automatic, able to provide breathing assistance without human intervention.

The existing manual design features a mask fitted over a patient’s face and a bag that can be squeezed by hand to push air into the patient’s lungs. The team is designing a machine that can do the squeezing instead, freeing doctors and nurses to address other concerns.

“We’re 3D-printing parts that can be attached to a motor to compress the bag of the manual ventilator,” said Ph.D. student Vasan. “This allows us to control the speed and volume of the compressions to help patients breathe.”

The advantage of 3D printing is that it can be used to quickly produce customized parts. Devices can be made on a small scale much faster than by traditional manufacturing methods.

“As long as the correct materials are used, 3D printing can be used to produce a wide variety of tools in the fight against COVID-19,” said Shaochen Chen, a professor of nanoengineering at the Jacobs School of Engineering. “It’s not good for, say, entire N95 masks, but it can be used for producing testing swabs or even face shields for healthcare workers.”

Meanwhile, Petersen’s team is awaiting a few more parts to build a more sophisticated ventilator using an electric pump. “Our aim is to have functional devices as soon as possible,” she said. “Once we’ve got the bare bones system up and running, we can start adding layers of sophistication and automation. Those additional layers will include advanced regulation of air pressure and flow to allow for a more disease-specific and patient-tailored respiratory support.”

The first ventilators will be simple, but the goal is to have something readily at hand when the need arises.

But a simple design isn’t the team’s only goal.

A broader goal and volunteers needed

Dr. Sidney Merritt displays an in-house pressure measurement device, currently in testing for use on a system designed to split a single ventilator to serve up to four patients.

“We are preparing for a shortage of both ventilators and specialized staff to run them,” said Petersen. “The questions quickly became ‘How can we tweak the ventilators that are available to support multiple patients? How can we create more ventilators that are easier for staff to use?’”

Other projects include collecting and inventorying oxygen supplies in preparation for increased demand by local hospitals; converting other air pressure machines, such as CPAPs and Bi-PAPs into ventilators; and adapting existing ventilators to serve more patients.

The team hopes to have functional prototypes within a few days and are ready to test them in simulators, in collaboration with anesthesiologists, before potentially applying to patients.

“Normally, the production timeline on something like this would be months, or even years,” said Petersen. “By building on existing technology and taking multiple steps at once, we aim to reduce that timeline to weeks.”

While grappling with challenges in locating parts that can’t be 3D-printed and obtaining them from outside vendors, the biggest roadblock right now is gathering enough people to assemble the devices.

The UC San Diego campus is largely closed and empty, due to efforts to minimize coronavirus exposure and slow the spread of COVID-19. The graduate student team continues work, thanks to a special exception granted by the Dean of the Jacobs School of Engineering.

“This is a team effort,” said Petersen. “And we can use the assistance of other engineers. We would love to hear from students, staff, and faculty with hands-on engineering experience who can help us with this project.”

Qualified volunteers should email: UCSDVentilatorEngHelp@gmail.com

Splitting ventilators

Meanwhile, Petersen’s colleague Dr. Sidney Merritt, an associate clinical professor of anesthesiology at UC San Diego Health, is working with a team that includes U.S. Navy and Lockheed Martin personnel to develop a 3D-printable system for splitting a ventilator designed for one patient so that it can be used by up to four patients at a time.

“We found a file online that showed us how it could be done,” said Merritt. “We’ve been working with the Navy and others to print them in different materials and test them on a ventilator, and, so far, it works. We were able to get enough pressure on each line that it should be adequate for serving four patients at a time.”

The challenge now is finding valves that can regulate the pressure for each patient on the system and monitor individual air pressure for each one, allowing for the fine control needed to support each patient’s specific needs. “As soon as we have the valves worked out, we’ll be just a couple days out from getting them set up and running,” said Merritt.

Using 3D-printed parts, Dr. Sidney Merritt and a team at the U.S. Navy and Lockheed Martin are developing a system to convert ventilators designed for a single patient to be used by up to four patients at a time.

“This situation is going to be very severe,” she continued. “We need to have every tool available to us, so we are ready to treat patients because we still don’t know how many people will get sick.”

Despite obstacles, the team said it has been overwhelmed by support and advocacy from colleagues and university leadership. For example, the Institute on Global Conflict and Cooperation at UC San Diego has contributed $50,000 to assist in the development of prototypes.

“The UC San Diego family is really pulling together on this one,” said Petersen. “From the dean, through chairs, faculty and students, regardless of who we’ve spoken to, everyone has gone above and beyond to help with this project as much as they can. It’s really bringing the community together. Everyone is moving in the same direction. While the work may be preparing for something unpleasant, it’s very good to be working in such a supportive environment.”

Other members of the continuously growing team include Dr. Daniel Lee; Dr. Preetham Suresh; Dr. William Mazzei; Dr. Matthew Follansbee; Dr. Micheal Vanietti; Dr. Hemal Patel; Theodore Vallejos of UC San Diego Health; Mark Stambaugh of the Qualcomm Institute; and Tania Morimoto, a professor in the Department of Aerospace and Engineering at the Jacobs School.

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Stem Education Coalition

The University of California, San Diego (also referred to as UC San Diego or UCSD), is a public research university located in the La Jolla area of San Diego, California, in the United States.[12] The university occupies 2,141 acres (866 ha) near the coast of the Pacific Ocean with the main campus resting on approximately 1,152 acres (466 ha).[13] Established in 1960 near the pre-existing Scripps Institution of Oceanography, UC San Diego is the seventh oldest of the 10 University of California campuses and offers over 200 undergraduate and graduate degree programs, enrolling about 22,700 undergraduate and 6,300 graduate students. UC San Diego is one of America’s Public Ivy universities, which recognizes top public research universities in the United States. UC San Diego was ranked 8th among public universities and 37th among all universities in the United States, and rated the 18th Top World University by U.S. News & World Report ‘s 2015 rankings.