UCI Faculty & Researchers Tackle COVID-19 from all Angles

Story courtesy of: Ethan Perez, UCI Beall Applied Innovation
Photos courtesy of: Ryan Mahar and Steve Zylius, UCI Beall Applied Innovation
Illustrations courtesy of: Julie Kennedy, UCI Beall Applied Innovation

Anteaters assemble to find answers and develop solutions to the global pandemic, from personal protective equipment and ventilators to test kits and vaccines.

UC Irvine (UCI) is one of the nation’s premier research universities, so when it became clear that COVID-19 was becoming a global threat, its faculty and researchers took action without skipping a beat.

Much work is needed in the fight against the coronavirus, from diagnostics and ventilators to personal protective equipment and vaccines, and UCI’s brightest will stop at nothing to make Southern California and the world a safer place. Below are a few of the projects developed by the hardworking men and women who make UCI proud.

COVID-19 Coronavirus Antigen Microarray Aims to Speed Up Testing
Director of the Vaccine R&D Center Phil Felgner, and his Protein Microarray Laboratory team at UCI’s School of Medicine’s Institute for Immunology, developed a microarray test to determine if a person has been exposed to COVID-19. With a simple finger stick blood test, results are available in 10 minutes. Felgner, along with clinical research faculty members Dr. Saahir Khan and Dr. Sebastian Schubl, a will conduct a six-month study involving UCI healthcare workers to understand the COVID-19 immune response. Chancellor’s Professor of Mechanical Engineering Marc Madou is also collaborating on this effort to integrate the microarrays onto compact disc-based fluidic platforms, which can speed up the process.

Genome-Wide Pan-Coronavirus Vaccine in Development
Professor of Cellular and Molecular Immunology Lbachir BenMohamed has submitted a grant proposal to develop a safe and efficient Pan-Coronavirus Vaccine. The vaccine would ideally stop and reduce the present SARS-CoV-2 infection and transmissions as well as reduce the severity of COVID-19 disease. In addition, this “preemptive” Pan-Coronavirus Vaccine is designed to stop or modify any upcoming future Coronavirus outbreaks that may be caused by yet another transmission of SARS-like Coronaviruses (SL-CoVs) from bats to humans.

Campus Labs Produce Fluid Required for COVID-19 Test Kits
Test kits for COVID-19 require a liquid called viral transport medium (VTM) that preserves samples so that they can be analyzed in a lab. When the UCI Medical Center asked the UCI campus for assistance in procuring more VTM, many labs across campus stepped up. The Sue & Bill Gross Stem Cell Research Center created a task force and began production in Gross Hall.

Face Shields Designed and Assembled for UCI Medical Center
Collaborators from the medical center, the business community, UCI Beall Applied Innovation, UCI School of Medicine, the Sue & Bill Gross School of Nursing, the Henry Samueli School of Engineering and the Claire Trevor School of the Arts worked together to quickly design, test, evaluate, assemble and deliver thousands of face shields. Design leads Jesse Jackson and Ben Dolan utilized advanced manufacturing facilities on campus to produce the parts in record time.

Bridge Ventilator Consortium Connects Industry Experts
The Bridge Ventilator Consortium (BVC) is a group of physicians, engineers and biomedical device experts from across the country that collaborate virtually to design and build low-cost ventilators. Dr. Brian Wong of the School of Medicine, the Henry Samueli School of Engineering and the Beckman Laser Institute & Medical Clinic (BLIMC) is spearheading the consortium with Dr. Govind Rajan, the director of clinical affairs at the UC Irvine Medical Center, and Thomas Milner, director of the BLIMC. The BVC is collaborating with a number of institutions and organizations, including Virgin Orbit, the University of Texas at Austin, UCI faculty and the University of Southern California. The BVC has now moved beyond ventilator devices and is focused on other projects involving noninvasive ventilation, microwave inactivation, light-based therapies and other technology-based solutions to address COVID-related problems.

Ventilators Created from Repurposed Continuous Positive Airway Pressure (CPAP) Machines
Dr. Matt Brenner, professor of medicine, pulmonologist and interim director of the BLIMC proposed the idea of repurposing CPAP machines to be used as ventilators for COVID-19 patients. Elliot Botvinick and Bernard Choi, professors of Biomedical Engineering and Surgery and core faculty members of the BLIMC, have led the effort to create ventilators based on the machines, commonly used by those who suffer from obstructive sleep apnea.

Team Designs Low-Cost Mechanical Ventilator
With the guidance of medical doctors, Professor of Mechanical and Aerospace Engineering Haithem Taha and his doctoral student Moatasem Fouda have developed a low-cost medical ventilator. In particular, they developed a novel respiratory regulation unit (RRU), which forms the heart of a mechanical ventilator. The RRU operates without the use of electronics and provides greater control compared to the simple, low-cost ventilators recently developed for the COVID-19 crisis.

Team Develops Windshield Wiper Motor-Inspired Ventilator Design
Biomedical Engineering Associate Professor Elliot Hui, along with graduate students Vincent Zaballa and Erik Werner, have developed a low-cost ventilator prototype that utilizes a windshield wiper motor based on a design pioneered by Thomas Milner’s lab at the University of Texas at Austin. The adjustable motor speed allows the ventilator to be adapted to each patient’s specific needs. Parts for this ventilator are being 3D-printed by Luis Ramirez, an undergraduate in Hui’s group, from home.

New Pneumatic Ventilator Design Developed
Marc Madou and his bioMEMS team have developed a ventilator that uses a pressurized chamber. The ventilator – created using low-cost electronics – sends compressed air into and out of a patient’s lungs through inhalation and exhalation valves.

Task Force Created to Plan Students Eventual Return to Schools
Dr. Dan Cooper, professor of pediatrics and founding director of the Institute for Clinical Translational Science, is working with a team of educators, policymakers, scientists, clinicians, students and parents to determine how, when and under what conditions public schools should reopen. The task force is called Pediatric Research Organized and Targeted to Eliminate the COVID-19 Threat (PROTECT).

UCI Researchers Team Up to Develop COVID-19 Self-Screening Test
A team of UCI researchers is developing a self-screening test that uses a patient’s saliva to deliver rapid results. The test strips would match with a HIPAA-compliant smartphone app to instruct anonymized patients on next steps as well provide researchers with a heat map of infection zones. Collaborators include Elliot Botvinick; Michelle Khine, professor of biomedical engineering; Chancellor’s Professor Plamen Atanassov; Sean Young, associate professor of emergency medicine and informatics; and Dr. Shahram Lotfipour, professor of emergency medicine and public health.

Professor Explores Inexpensive Point-of-Care COVID-19 Immunity Test
Professor of Electrical Engineering and Computer Science, Biomedical Engineering, and Materials Science and Engineering Peter Burke is investigating a less expensive way to detect antibodies by using short DNA sequences. If successful, easy-to-produce at-home tests could allow patients to determine if they have antibodies to COVID-19, which may in the future indicate immunity. It will be as easy as an at-home pregnancy test.

New System Aims to Understand Virus Mutation
Associate Professor of Biomedical Engineering, Chemistry, and Molecular Biology and Biochemistry Chang Liu and his lab are using an accelerated protein evolution system they developed to mimic how natural immune systems develop antibodies, but at a faster pace. This rapid evolution system allows Liu and team to better understand SARS-CoV-2 and other coronaviruses and to develop ways to detect and neutralize the virus.

Study Reveals Virus Transmission Risks
Professor and Chair of Civil and Environmental Engineering Sunny Jiang, and team, conducted a quantitative microbial risk assessment to investigate the risks of SARS-CoV-2 exposure through contaminated aerosols in bathrooms.

Professor Awarded to Study Diagnostics & Therapeutics for Virus
Professor of Pharmaceutical Sciences John Chaput received a COVID-19 Research award from UCI to develop therapeutic aptamers – or single-stranded DNA or RNA molecules – to treat COVID-19 patients. These reagents represent a new drug class that would prevent the virus from negatively interacting with lung cells.

Award Funds Research on Cell-free, Cellular COVID-19 Vaccine
Professor of Pharmaceutical Sciences, Chemical and Biomolecular Engineering, Biomedical Engineering, and Molecular Biology and Biochemistry Young Jik Kwon received COVID-19 Research awards from UCI to create a novel extracellular vesicle-based vaccine that effectively and comprehensively boost the immune systems against SARS-CoV-2.

Professor Develops Molecules that can Prevent Virus Spread
Professor of Pharmaceutical Sciences, Chemistry, and Molecular Biology and Biochemistry Andrej Luptak received COVID-19 Research awards from UCI to develop molecules that can block the virus from spreading within the lung tissue of a patient, in addition to a diagnostic tool that would detect the virus in patient samples in minutes.

Innovative solutions to understand and combat COVID-19 are still in high demand.

Read full UCI Beall Applied Innovation Rising Tide article.

Inventive Medicine

by Greg Hardesty, UCI

Optics innovator Thomas Milner is back at UCI as director of the Beckman Laser Institute & Medical Clinic

July 17, 2020 – In 1975, when he was a sophomore at Alameda Senior High School in Lakewood, Colorado, Thomas Milner’s literature teacher told him something prophetic.

He can’t recall what book he was reading, but during a discussion about it with his teacher, she said: “I see you being an inventor and doing some great things.”

Milner, who at the time was interested in mathematics, recalls feeling puzzled.

“She was telling me my future,” he says. “And I could tell that she really believed it. And I thought, ‘Gosh, how’s that one going to work out?’”

As it turned out, just fine, thank you.

Milner, the new director of UCI’s Beckman Laser Institute & Medical Clinic, is a pioneering developer of optical-based medical instruments for surgery and diagnostics. He cut his teeth at the clinic in 1992 as a Whitaker Research Fellow, a post he held until late 1997.

In early 1998, Milner and his wife, Jyoti, a high school biology teacher, and their two young children, son Prasaad and daughter Surya, relocated to Austin after he accepted a faculty position in the University of Texas’ biomedical engineering program.

So leading the world-famous Beckman Laser Institute & Medical Clinic, which opened in 1986, is something of a return home for the 60-year-old optical sciences wizard, who holds 55 U.S. patents. He’s also a UCI professor of surgery and biomedical engineering.

COVID-19 creation

A windshield wiper motor from a Toyota Camry recently landed Milner in the news.

Earlier this year, he and a group of researchers at the University of Texas developed an automated breathing unit based on the car part to supplement hospital ventilators used to keep critically ill COVID-19 patients alive.

The Automated Bag Breathing Unit is a “bridge ventilator” that’s much less complex and costly than a standard one. A manufacturer outside Dallas is making 50 ABBUs and is prepared to crank them out en masse should a surge in coronavirus cases occur.

“It’s one of the most rewarding projects I’ve worked on,” Milner says. “All the engineers on the team donated time and work. It was a humanitarian effort.”

Such medical breakthroughs are nothing new for him.

Back when he was a research fellow at UCI, Milner was the co-inventor of “dynamic cooling” technology that revolutionized the approach to certain skin disorders.

The other inventor, Dr. J. Stuart Nelson, is currently medical director of the Beckman Laser Institute & Medical Clinic, which treats patients from around the world for port-wine stain birthmarks, hemangiomas and other vascular malformations.

At the University of Texas, Milner also co-led a team of scientists and engineers that developed the MasSpec Pen, a hand-held, penlike device that can rapidly distinguish tumor tissue from healthy tissue during surgery.

Scientists, engineers and physicians at UCI’s Beckman Laser Institute & Medical Clinic all collaborate – a legacy of scientist, inventor and philanthropist Arnold O. Beckman and the vision of co-founder Michael Berns, whose original work focused on using lasers to perform microsurgery in cells. The scope of research at the facility has since branched out.

One of Milner’s immediate goals as director is to establish a couple of advisory panels.

“When I was here in the 1990s,” he says, “we had a lot of interaction with industry, but the institute has never had industry or academic advisory committees. They’re important to ensure that we’re calibrated right and that we listen to other people’s perspectives.”

Ranch in Montana

Milner, who grew up in Colorado, earned a bachelor’s degree in engineering physics and a master’s degree in physics at the Colorado School of Mines. Before his fellowship at UCI, he obtained a Ph.D. in optical sciences at the University of Arizona Optical Sciences Center.

In February of this year, Milner was at UCI preparing for his new job when COVID-19 hit. He and his family retreated temporarily to their 20-acre ranch in Montana.

“I really like working on the land,” Milner says. “I enjoy doing stuff people did a hundred years ago.”

He also continues to enjoy doing stuff no one has ever done before.

One new invention he’s tackling is a laser-guided wire to clear blocked coronary arteries.

“It’s really cool,” Milner says of the SmartWire, adding: “The field of light and medicine has just exploded over the last 30 years and, in my opinion, will continue to grow.”

Closed for a while due to the coronavirus, UCI’s Beckman Laser Institute & Medical Clinic reopened in early June. Research has been ramping up since mid-June.

Milner, who replaced interim director Dr. Matthew Brenner, oversees 24 core faculty members.

“It’s exciting to me,” he says of his new career, “even though there’s never going to be enough time to do everything that needs to be done. But that’s a good position to be in.”

Read full UCI News article.

Chris Barty and The Bridge Ventilator Consortium featured in UCI Magazine

Dr. Chris Barty, UCI Distinguished Professor of physics & astronomy, is researching the use of diodes from Blu-ray digital video disc devices as deep-ultraviolet laser photon sources to rapidly disinfect surfaces and indoor air.  Such technology would be less expensive than current medical- and scientific-grade systems and easily deployable.  “If these sources are successful, I think you could build them into a mask and clean the air that’s coming in and out of you,” Barty said.  “Or you could set things up in the air circulation ducts of major buildings, and the airflow that goes through could be sterilized.”  They could also function in hand-held wand devices, he said, or as a “light curtain” through which people walk as they enter a room, exposing them to UV-C radiation that – at a wavelength between 200 and 260 nanometers – will destroy viruses and other pathogens but pose minimal risk to humans.

UCI engineers are answering the call for simple and affordable ventilators, using off-the-shelf parts and designing stopgap products to help fill the demand.  Many are participating in the Bridge Ventilator Consortium, a team of physicians, engineers and biomedical device experts from UCI, the University of Texas, Virgin Orbit and Medline Industries.

Read UCI Magazine.

Chen Wins $2.9 Million NIH Grant to Develop Intravascular Imaging System

By Lori Brandt, UCI Samueli School of Engineering

July 6, 2020 – The NIH National Heart Lung and Blood Institute has awarded Zhongping Chen, professor of biomedical engineering, a four-year $2.9 million grant to continue the development of a new imaging technology that will enhance clinicians’ ability to identify vulnerable lesions, tailor interventional therapy and monitor disease progression for patients with cardiovascular disease.

Chen, a pioneer in the field of biophotonics, proposes to make a multimodal intravascular imaging system that combines three sophisticated technologies into a single catheter device. These technologies are the high resolution of optical coherence tomography, deep tissue penetration of ultrasound and the biomechanical contrast of optical coherence elastography (a technique that maps the elastic properties of soft tissue). The collaborative research project involves Pranov Patel, professor of interventional cardiology at the UC Irvine School of Medicine, and Qifa Zhou, professor of biomedical engineering at the USC Viterbi School of Engineering.

According to Chen, cardiovascular disease is responsible for 1 in 4 deaths, or 650,000 Americans, every year. It is the leading cause of death in the United States. Ruptured atherosclerotic plaques are the main cause of acute coronary events, and it is of lethal consequence. Clinically, early detection of the latent vulnerability of plaques is the first line of defense against such deadly circumstances, and it relies on visualizing both the structural and biomechanical properties of tissue. Accurate characterization of a plaque lesion can facilitate better treatment management by furthering understanding of disease progression.

“We expect the development of the proposed high-speed, high-penetration-depth and high-sensitivity system and probe to have significant impact to both basic science and clinical understanding of plaque pathogenesis,” said Chen. “This will be a powerful tool for providing a quantitative means to benchmark and evaluate new medical devices and therapies.”

Read full UCI Samueli School of Engineering article.

Miao Wins the American Society for Laser Medicine and Surgery 2020 Best of Session: Genitourinary Health

Imaging-Assisted Vaginal Laser Device Guides Treatment in Real-Time Via Digital Histology and
Angiography

Yusi Miao, Neha T. Sudol, Afiba Arthur, Jason J. Chen, Yan Li, Saijun Qiu, Yona Tadir, Felicia L. Lane,
Zhongping Chen

Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA; University of California –
Irvine, Irvine, CA

Background: Genitourinary Syndrome of Menopause (GSM) affects up to 50% of women with regard to
general health and sexual function. Energy-based treatment such as ablative laser has demonstrated
promising short-term outcomes in relieving GSM symptoms. However, the safety and effectiveness of
energy therapy remain controversial, and most treatment protocols are not backed up by scientific data.
Since invasive biopsy cannot be “ethically” justified, and single samples are not scientifically
representative, histological evidence is lacking in this area. In the present study, we developed a non-
invasive optical biopsy device, integrated within a commercial vaginal laser probe to perform optical
histology and angiography.

Study Design/Materials and Method: This abstract reports on the clinical translation of the image-
assisted laser device, and the on-going human study to evaluate histological and blood vessel changes
post vaginal laser ablation. Imaging data are collected from patients undergoing a fractional-pixel
CO 2  laser treatment. In-house high-speed optical coherence tomography (OCT) imaging system is
integrated into the handle part of the laser treatment device to acquire imaging parameters; epithelium
thickness and blood vessel density in the lamina propria. 3D imaging data from the proximal and distal
vagina are acquired from each patient in parallel to the treatment every 6 weeks.

Results: The proposed imaging-assisted vaginal laser device showed exceptional accuracy, imaging area,
acquisition speed to assess tissue histology and angiogram in real-time. The spatial resolution was 2–3
orders of magnitude higher than the clinical ultrasound imaging device enough to resolve micrometer
changes in tissue. The imaging area from a single acquisition was 12 × 12 mm. The data acquisition
speed was less than 20 seconds with GPU-accelerated advanced processing. Preliminary data
demonstrated that laser treatment effects highly depend on the initial epithelium thickness and vascular
density. Patients with severe atrophy were more sensitive to laser treatment and showed pronounced
tissue proliferation.

Conclusion: The present study demonstrated a non-invasive optical histology technique for assessing
the effects of vaginal rejuvenation device. We anticipate the integrated treatment, monitoring device
will allow both physicians and laser industries to design a safer and more effective laser procedure
based on the histological evidence.

Click here to view the ASLMS 2020 abstracts.

Natasha Mesinkovska receives ICTS pilot study award

UCI Beckman Laser Institute & Medical Clinic’s Dr. Natasha Mesinkovska received a UCI Institute for Clinical & Translational 2020 Science Pilot Studies award for her alopecia areata research.  The ICTS Pilot Studies are designed to support exceptionally innovative and/or unconventional research projects that have the potential to create or overturn fundamental paradigms.

Alopecia areata (AA) is a hair loss disorder caused by an autoimmune attack on the hair follicle. Hair loss can range from small patches of scalp hair loss to total scalp (alopecia totalis) or total body hair loss (alopecia universalis). Genetic factors are thought to play a part in the development of AA, however the exact mechanism behind the disease is not completely understood. One of the key components of AA is over-activity of immune cells. This process is mediated by an intracellular protein, Janus Kinase (JAK), which promotes continuation of the disease process. Given this discovery, JAKs have emerged as highly-effective therapeutic targets for the treatment of AA.

Consistent with literature, many AA patients show strong hair regrowth in response to JAK inhibitors. Through the observation of patients in the Clinic, it has shown that hair regrowth occurs in patches that enlarge over time. This pattern of hair regrowth has been documented in multiple published studies, however not yet explicitly analyzed in humans..

Dr. Mesinkovska proposes that adult human hairs are, in principle, capable of activation of a collective chain reaction-like hair growth pattern. While this ability is not normally apparent in the healthy scalp, it can be obvious during AA resolution, a distinct disease state containing many dormant hair follicles. The first objective of the pilot grant is to collect strong clinical proof for a “spreading wave” pattern of hair regrowth in AA patients. This will be accomplished by non-invasively imaging the hair follicles on the edges of re-growing hair patches. The focus will be on identifying the spatial arrangement of quiescent hair follicles to early growing hair follicles – a telltale sign of spreading hair regrowth waves. This will then be confirmed on histology with biopsies of hair patch edges. For the first time, the data will provide direct support for the ability of human scalp hair follicles to collectively enter the regrowth phase, providing fundamentally new knowledge for the field of human hair and AA research.

The second objective of the research study is to collect RNA sequencing data from the edges of regrowing hair patches to identify novel signaling changes within the hair follicles and surrounding cells. These changes will include proteins that influence hair follicles to initiate regrowth, and thus are potential therapeutic targets for hair growth stimulation. Dr. Mesinkovska anticipates that their findings will lead to the development of new strategies for the treatment of AA; with the potential for the discovery of break-through therapies for additional types of hair loss.

Read the full abstract.

UCI Beckman Laser Gets New Director

by Jessie Yount, Orange County Business Journal

The University of California-Irvine Beckman Laser Institute and Medical Clinic has tapped Thomas Milner, a three-time entrepreneur and serial
technology inventor with 55 issued patents, to oversee and expand its research activities.

Milner was recently named director for the photonics institute; he’s the third person to have the position. Milner starts July 1. His plans include prioritizing diversity in faculty and establishing external advisory committees with industry and academic-like entities so that BLIMC is ultimately “recognized by the industry as an excellent partner for both knowledge, intellectual property, scientific and engineering expertise, and as a
source of students who wish to pursue industrial careers,” he said.

Milner has also been granted joint appointments in the departments of biomedical engineering and surgery, and said one major piece of his plan is
working with the UCI Beall Applied Innovation center to convert research into viable commercial ventures that provide value to the community.

He added, “The future is great here in Irvine, and the community will benefit for decades to come.”

Optical Inventions

Milner counts prior ties to UCI; he notes that both his children were born at the University of California-Irvine Medical Center, when he was a Whitaker Research Fellow and research assistant professor at BLIMC from 1992 to 1997.

He’s no stranger to commercial translation. During his time at BLIMC, Milner and J. Stuart Nelson, medical director of the clinic, co-invented a dynamic cooling device that has significantly improved laser dermatological treatments. It was licensed to Wayland, Mass.-based Candela Laser Corp. and has brought UCI more than $40 million in royalties to date.

In 1998, Milner left Irvine to serve as the Joe King Professor at Cockrell School of Engineering at the University of Texas at Austin, where he received the Inventor of the Year award for an optical coherence tomography (OCT) technology that helps physicians diagnose conditions such as glaucoma and heart disease.

His technology led to the birth of two companies: Dermalucent LLC and CardioSpectra Inc., a high-resolution imaging company that sold to San
Diego-based Volcano Corp. for about $25 million in 2007.

Research Pipeline

Milner’s current research focuses on the treatment of chronic total occlusion (CTO), or the complete obstruction of an artery, which today requires an invasive bypass procedure to treat.

Milner has created a guidance and laser system that could treat CTO in a minimally invasive manner. It is currently being tested in animal trials.

While his work took him to Texas, Milner notes that he kept in touch with his colleagues in Irvine. When the pandemic began spreading in the U.S., Milner created a ventilator prototype used by the Bridge Ventilator Consortium group established at UCI.

The team said it expects to receive FDA approval for its low-cost and easy-tomanufacture breathing-assistance device any day now.

COVID-19 research at BLIMC include several ventilator-related projects, as well as a UV sterilization effort led by Chris Barty.

Barty is pioneering a new type of X-ray technology through his Irvine-based company Lumitron Technologies Inc., which was profiled in the May 20 print edition of the Business Journal.

The UCI Office of Research recently transitioned to Phase II of its reopening plan, allowing normal research activities at its various institutes to resume with enhanced sterilization and social distancing in place.

At BLIMC, that means basic research and clinical research can resume once faculty submit risk assessments.

Legacy of Innovators

Milner succeeds Bruce Tromberg, who left BLIMC in 2018 to lead the National Institute of Biomedical Imaging and Bioengineering in Bethesda,
Md.—one indication of the institute’s prominence in the field.

Arnold Beckman, the visionary behind today’s Beckman Coulter Inc., and Michael Berns launched BLIMC in 1982 with the mission to use light (or
photons) to study the basic biology of cells, and apply that knowledge to medical applications.

“Arnold Beckman was an innovator himself, and his legacy is what Beckman Laser Institute is all about—providing innovation to benefit people through new products and devices,” Milner said.

In his new role, Milner said he hopes to push the field of photonics beyond studies in the eyes and skin to cardiology and neurology such as Alzheimer’s disease, in turn providing “a better understanding of our overall health and wellbeing.”

Read full Orange County Business Journal article.

Beckman Laser Institute receives advanced nonlinear optical microscopy funding

Drs. Eric Potma and Mihaela Balu were awarded a $1.6M grant to acquire an innovative multiphoton microscope, offering advanced tissue imaging capabilities at depths beyond what can be achieved with standard optical imaging techniques. Besides its state-of-the-art imaging capabilities, the system is equipped with a custom-engineered modality, making it possible to rapidly capture selective imaging of important tissue components, such as lipids, collagen, melanin and cell metabolites.

The system supports numerous cutting-edge studies for the early detection of melanomas, hypoxia in retinal tissues, skin aging, malaria drug development, muscular dystrophy and many more diseases and conditions.  This unique instrument offers the advanced tissue imaging capabilities needed to propel the science of our research community into the next decade.

The Great Ventilator Rush

by Mark Harris, IEEE Spectrum

Early on in the COVID-19 pandemic, engineers launched extraordinary crash programs that produced scores of ventilator designs. What will happen to them now?

The projections were horrifying. Experts were forecasting upwards of 100 million people in the United States infected with the novel coronavirus, with 2 percent needing intensive care, and half of those requiring the use of medical ventilators.

In early March, it seemed as if the United States might need a million ventilators to cope with COVID-19—six times as many as hospitals had at the time. The federal government launched a crash purchasing program for 200,000 of the complex devices, but they would take months to arrive and cost tens of thousands of dollars each.

Across the United States and around the world, engineers sat up and took notice. At NASA’s Jet Propulsion Laboratory (JPL), in Pasadena, Calif., a chance meeting between engineers at a coffee machine led to a prototype low-cost ventilator in five days. At Virgin Orbit, a rocket startup in nearby Long Beach, engineers assembled their own ultrasimple but functional ventilator in three days.

And in Cleveland, a team at the Dan T. Moore Company, a holding company with an impressive portfolio in industrial R&D, had its first prototype up and running in just 12 hours. “It was made out of plywood and very crude,” says senior engineering manager Ryan Sarkisian. “But it gave us a good understanding of what the next steps would be for a rapid response–style solution.”

From the largest universities to domestic garages, hundreds of teams and even individuals scrambled to build ventilators for the expected onslaught. An evaluation of open-source ventilator projects has tracked 116 efforts globally, and it is far from comprehensive.

Meanwhile, the U.S. Food and Drug Administration (FDA) rushed through rules at the end of March that would allow, if the worst-case scenarios came to pass, new ventilators and other medical devices intended to treat COVID-19 to be deployed without the usual years-long safety assessments. Around the same time, General Electric and Ford announced that they were joining forces to rapidly manufacture 50,000 ventilators based on one of GE’s existing designs.

With hundreds of thousands of traditional ventilators on order and potentially even more DIY devices coming soon, President Trump boasted in a speech on 29 April, “We became the king of ventilators, thousands and thousands of ventilators.”

Now, though, before most of the DIY ventilators could make it to production, let alone treat a patient, the need for them has faded away. Aggressive social distancing and isolation policies have slowed transmission of the coronavirus, while hospitals and state governments readily shared surplus ventilators with locations that were suffering the worst outbreaks, like New York City.

Today, some hospitals are even quieter than they were before COVID-19. “This morning in Cincinnati, there were 12 COVID-19 patients on a ventilator,” said Richard Branson, a professor of surgery emeritus at the University of Cincinnati College of Medicine. In a phone interview with IEEE Spectrum in late April, Branson, who is also editor in chief of the journal Respiratory Care, added “We usually have more patients on ventilators than that on a regular day, but we canceled all the [elective] surgeries.”

No one is complaining about having too many ventilators, of course. The story line, starting with the earnest pleas and the ensuing media frenzy, and continuing with the massive engineering response, certainly has a heartwarming ring. Countless engineers dropped what they were doing and worked long hours to design, build, and test impressive machines in weeks, rather than months or years. But an unforeseen twist in that story line raises some vexing questions. What has become of all these rapid-response ventilator projects and the tens of thousands of home-brewed devices they planned to produce? Has it all been a well-intentioned waste of time and money, a squandering of resources that could have been better put toward producing protective equipment or other materials? And even if any of these devices do find their way into hospitals, for example, in developing countries with a real need for ventilators, will they be safe and effective enough to actually use?

“There was one particular day where I was scrolling through Facebook, and one, two, three friends had lost a friend or family member to COVID-19,” remembers Wallace Santos, cofounder of Maingear, a maker of high-performance gaming computers based in Kenilworth, N.J. “That’s when I thought, Holy crap, this is really happening.

So when Rahul Sood, the chairman of Maingear’s board and a longtime tech entrepreneur, suggested that Maingear build a ventilator itself, Santos was interested—if skeptical. “I didn’t know if we could do it, but we started to investigate,” he says. “And the truth is that if we can build really complex and beautiful liquid-cooling systems [for computers], we can build a ventilator as well. It’s not that hard actually.”

Like most medical gear, ventilators come in different types and sizes, and with different features, capabilities, and levels of complexity. They all perform the same basic function: getting oxygen into, and in some cases clearing carbon dioxide away from, the lungs of people who are having trouble breathing or who have ceased to be able to breathe at all. In relatively mild cases, physicians may use a noninvasive type, in which a tight-fitting mask, akin to a full-face scuba mask, provides pressurized air to the patient’s nose and mouth.

More severe cases are treated with an invasive system, meaning they make use of a tube through the mouth or through an opening in the neck into the patient’s windpipe (trachea). With this setup, the patient is usually sedated or kept unconscious for the days or weeks it can take for the patient’s body to fight off the infection and regain the ability to breathe independently.

Ventilators must carry out several functions with extreme reliability. They must, of course, supply oxygen at higher-than-ambient pressure and allow carbon dioxide to be exhaled and cleared away from the patient’s lungs. The air they provide to the patient must be warm and moist, and yet free of bacteria and other pathogens. Also, they must be equipped with sensors and software that detect if the breathing mask or tube has been dislodged, if the patient’s breathing has become erratic or weaker, or if the breathing rate has simply changed. Finally, the machines must be designed so that they can be thoroughly cleaned and also contain, as much as possible, any pathogens in the patient’s exhalations. The systems must also be compatible with existing hospital infrastructure and procedures.

Consider Maingear’s design, which was based on an emergency ventilator that had already been used in Italy and Switzerland. To repurpose it for COVID-19, engineers made the part that touches a patient disposable rather than cleanable, to reduce the risk of cross infection. Maingear also rewrote some of its software and designed a tough PC-style case so that it could either be housed in a standard medical equipment rack, or moved about on wheels. “This thing is seven grand out the door,” says Sood. “And we can manufacture them very quickly in New York or New Jersey once we get FDA approval.”

At Dan T. Moore, engineering manager Sarkisian had a similarly abrupt introduction to ventilators. Before working on its ventilator, dubbed SecondBreath, his team had been developing lightweight, high-strength metal matrix composites for automotive brake pads. “We’re fairly green when it comes to medical devices,” he admits. “But understanding that manual resuscitation bags are readily available and already have FDA approval, we wanted to utilize that concept as a way to transfer breath to a patient.”

Just as it sounds, a manual resuscitation bag allows a trained medic to provide ventilation by squeezing on a rubberized bag attached to a face mask. Originally designed in the 1950s, these bags are simple and flexible, but they do require a trained operator. To bring the tactic into the modern age, Dan T. Moore’s engineers focused on automating, controlling, and monitoring that squeezing process.

After building a bag-squeezing prototype in 12 hours, Sarkisian’s team of nine automotive engineers refined the design by talking to local doctors and experimenting with different components. “We were trying to make it as cheap as possible, and to really understand the features that it needs to have to keep people alive,” Sarkisian says.

At a minimum, that meant a system that could reliably squeeze a bag for hours, or even days, on end, be readily usable by doctors accustomed to working with more sophisticated ventilators, and have a suite of alarms should anything go wrong.

“We had about two weeks working through prototypes, adding more alarms and different sensors to optimize our system,” says Sarkisian. “Then a little over a week testing out the system, and another two to three days at a local hospital on lung-simulator machines.” It took just 21 days from the first SecondBreath prototype to submitting the device to the FDA, and the company hopes to sell its devices for around US $6,000.

“It just shows you that medical devices are pretty dang expensive,” says Andrew Dorman, an engineer who worked on the SecondBreath project. “When people learn that we can make these ventilators in three weeks and can sell them for a fraction of the price, they might take a look at [the traditional] medical system and say, something’s wrong here.”

Virgin Orbit also made a bag-squeezing ventilator after its CEO, Dan Hart, offered his factory and workers to California governor Gavin Newsom. Newsom connected Hart to the California Emergency Medical Services Authority (EMSA), which identified ventilators as its key need at the time. “A consortium of physicians, scientists, and engineers led by the University of California, Irvine, and the University of Texas at Austin directed us [to] go and make the simplest possible ventilator,” says Virgin Orbit vice president for special projects Will Pomerantz. “We essentially took all the people who were going to be building next year’s rockets and said, ‘Next year’s rockets can probably wait a little bit—you’re going to be building or testing ventilators.’ ”

As a manufacturer of air-launched rockets for small satellites, Virgin Orbit realized that one of the bigger challenges was going to be dealing with supply chains disrupted by COVID-19 itself. “We tried to build it without requiring anything complex or specialized, or if it was, from an industry that does not touch upon medical devices at all,” says Pomerantz.

For example, instead of building a motor from scratch, the Virgin Orbit team utilized something they could find in almost any small town: the windshield wiper motor from one of the country’s most ubiquitous cars, a 2010 Toyota Camry.

This concern for manufacturability also drove the scientists and engineers at NASA’s JPL. They wanted their ventilator, an open-source design, to be within the reach of almost any competent mechanic, anywhere in the world. “Our target was that if a person had all the parts sitting in front of them, they could put it together alone in about 45 minutes, with as few tools as possible,” says Michael R. Johnson, a spacecraft mechatronics expert who served as chief mechanical engineer for the JPL’s ventilator, called VITAL (Ventilator Intervention Technology Accessible Locally). “We couldn’t make them fast enough. Not that anybody was saying anything—it was just understood.”

In the end, the JPL actually designed two different low-cost, easy-to-assemble ventilators, neither of which relied on existing resuscitation bags. A pneumatic device uses stored energy in the hospital gas supply to power the ventilation, while a design that uses a separate compressor serves situations where pressurized gases are unavailable. Not only would the two designs serve different needs, they would also reduce the chance of component shortages halting production entirely. A single circuit board serves both designs, using a simple microcontroller assembly running Arduino code.

The pneumatic ventilator was ready first and was sent straight to the Icahn School of Medicine at Mount Sinai, in New York City, for testing on human simulator machines and by medical staff. “The whole time it was there, we had a Zoom meeting running, and we were watching them use it,” says Johnson. “We would watch things like how they were pushing the buttons. There was one they were pushing really hard, and I thought, okay, let’s add a couple more support screws to the circuit board. Or we’d hear someone say how it wasn’t adjusting quite the way they’d like, so we made a note to change the sensitivity.”

Beyond the engineering work, preparing the descriptive and safety paperwork required by the FDA involved a significant investment of time and resources. Most efforts used outside lawyers and experts, with the JPL’s comprehensive submission running to 505 pages. “A big thing for the FDA is the failure modes and effects analysis, which we do all the time for our spacecraft,” says Johnson. “We asked a couple of medical companies if they could send us examples, and it turns out they’re actually less rigorous than what we do for our space missions.”

Probably best prepared for the administrative burden of developing a new ventilator in a matter of weeks was the team at the University of Minnesota’s Earl E. Bakken Medical Devices Center. For their day jobs, the engineers here work with industrial partners to come up with ideas for, and develop prototypes of, medical devices.

“We have iterative design processes that I’ve both learned and taught here, so I knew that this was possible if you took the right approach,” says Aaron Tucker, lead engineer for the university’s Coventor ventilator project. “We boiled it down to the key concepts—what you need on a bare minimum to survive when you’re being ventilated.”

The Coventor is another design that compresses commercially available ventilation bags, paring the parts down to just $150 of readily available components housed in plain sheet metal. The Coventor team worked closely with Boston Scientific, a large manufacturer of medical devices, to label their device so as to mitigate the risks around its limited capabilities. “Our experience and our ability to collaborate was why we ended up being [one of the first] approved for use by the FDA,” says Tucker. The Coventor’s selling price will be less than $1,000 when Boston Scientific moves it into production shortly.

By mid-May, the FDA had approved six new ventilators for emergency use, including devices from Coventor, SecondBreath, Virgin Orbit, and the JPL. All are limited to use during the pandemic, and only when standard ventilators are unavailable.

SecondBreath has manufactured 36 devices so far, while Virgin Orbit has produced a couple of hundred. Coventor and Boston Scientific have an order for 3,000 of their ventilators from UnitedHealth Group, a health care company in Minnesota. As of early June, none had been deployed in the United States.

“I don’t think any of these devices will ever be used in the United States,” says Branson, the University of Cincinnati surgery professor. “I give these people a lot of credit. They’re trying to do something positive. They’re very smart, they’re motivated, they’re well meaning, but they don’t know what they don’t know.”

In 2014, Branson coauthored a prescient paper for the journal Chest called “Surge Capacity Logistics: Care of the Critically Ill and Injured During Pandemics and Disasters.” In it, he and 10 colleagues came up with evidence-based recommendations for coping with a pandemic respiratory disease like COVID-19, including stockpiling ventilators that met a list of minimum requirements.

“Several of the ventilators the government is purchasing don’t meet these requirements,” Branson says. “Some barely meet not even half of them.” The ventilators authorized by the FDA for emergency use seem to similarly fall short, often in multiple areas. Branson notes that the bag-squeezing designs, in particular, are problematic.

“If everybody had paralyzed respiratory muscles and normal lungs, as in polio, a bag squeezer would work,” he says. “But this is an acute respiratory distress syndrome with parts of the lung that are stiff right next to parts of the lung that aren’t. If you’re not careful with how you deliver the breath, areas that are stiff get very little gas, and areas that are not get too much gas, and that injures them.”

Another problem is that most of the DIY ventilators do not allow for patients to breathe on their own, requiring them to be heavily sedated. “But in New York City [at the height of the outbreak], they ran out of drugs to sedate people,” Branson notes. “And paralyzing people has its own negative consequences,” he adds. “In general, the less sophisticated the device is, the more sophisticated the caregiver has to be.”

But in the kind of crises where emergency ventilators will be needed, medical staff will already be stretched dangerously thin. Branson believes that asking them to suddenly start using unfamiliar new devices that lack traditional protective features and alarms is a recipe for disaster. “You can’t change the standards of care to meet the requirements of the ventilator,” he says.

With the need for ventilators down sharply in North America, and with many medical professionals there reluctant to use home-brewed ventilators, what will become of all this work? Some DIY ventilator teams are already looking overseas. Indeed, Coventor, SecondBreath, and the JPL all designed their devices with an eye on developing countries. “We know that the ‘Cadillac’ ventilators we’re used to in the U.S. are not available in many countries, for cost and other reasons,” says Coventor’s Tucker. “We’re thinking about whether and how we can start to move the Coventor overseas. Nothing prevents it from being used globally. We even picked a global power supply.”

Virgin Orbit has already found a manufacturer in South Africa to produce at least 1,000 of its resuscitators for use by the African Union.

Whether the U.S. startups can sail past foreign regulators as swiftly as they did the FDA remains to be seen. And there are already plenty of engineers innovating overseas, of course. In India, for example, AgVa Healthcare has been marketing a compact ventilator for less than $3,000 and claims to be building 10,000 units a month.

None of the organizations Spectrum spoke with would put a dollar amount on their DIY ventilator efforts, but the combined total is very likely well into the millions. Branson suggests that some of those funds might have been better deployed in proven technologies. “The answer would be to have money and resources given to people who already make FDA-approved devices, to make more of them,” he says. Other tech companies also focused on much simpler items that are still in short supply, such as protective masks and gloves.

For now, as the adrenaline rush from having produced their first ventilators ebbs, some of the ventilator teams are experiencing a welcome lull. “It did a lot for employee morale to feel like we were all putting our shoulders to it and pushing together,” says Virgin Orbit’s Pomerantz. “If the world needs our ventilators, we’ll keep building them. And if it doesn’t, thank goodness. We’re happy to get back to our day jobs.”

Not everyone is convinced that the worst is over. Sood is keen to keep Maingear’s development effort on track. “Based on everything that we’ve seen and all the data we looked at, this is just wave one of a multiwave process,” he says. “We think that wave two, sometime in the fall, might even be worse, and they’re going to start asking for ventilators again. We want to get our machines prepared and ready ahead of time.”

Sood’s pessimism has plenty of company. When the JPL recently invited firms to ask for (free) licenses to manufacture NASA’s open-source ventilators, it received more than 200 applications from organizations all over the world. The best-case scenario, from all perspectives, is that such efforts continue to be a magnificent waste of time and money.

Read the full article on IEEE Spectrum.