By Kenna Simmons | Illustration by Gwen Keraval | Published July 8, 2019
A tiny 3D-printed tracheal splint that makes it possible for babies to breathe. An experimental method of drug delivery that could protect kids from a nasty respiratory virus. An app that screens kids (and adults) for anemia, no blood draws needed.
Not only are these novel discoveries, devices, and projects by Georgia Tech researchers remarkable for their technological innovation, but they also take up a challenge that every pediatrician (not to mention the parent of a sick child) faces: Most medical therapies are designed for adults, not children. These are the exceptions.
A determined approach is part of the unique collaboration between Georgia Tech and Children’s Healthcare of Atlanta. The two institutions have been working together on pediatric research since 2007. In 2012 they formed a $20 million alliance, and in 2015 launched the Children’s Healthcare of Atlanta Pediatric Technology Center at the Georgia Institute of Technology, which pairs academic researchers, scientists, and engineers with clinicians to solve urgent problems in pediatric medicine. In 2016, a $5 million grant from the Imlay Foundation created the Imlay Innovation Endowment Fund at Children’s to further advance the collaboration between the Institute and the pediatric health care system.
This kind of interdisciplinary approach — pairing doctors and engineers on pediatric projects — was new for both institutions, said Sherry Farrugia, chief operating and strategy officer for the Children’s Healthcare of Atlanta Pediatric Technology Center. “We said, ‘Give us your problems and we’ll team you with an engineer who can solve them,’” she said. “Both our institutions believe more funding needs to be dedicated to pediatrics, and we’re both willing to be creative to make that happen.” The relationship has been so fruitful that Georgia Tech aims to use it as a model for how to work with other pediatric institutions.
And both engineers and clinicians relish the interaction. “Even though research is interesting and exciting, I always feel that it’s not fulfilled until you can take it to patients,” said Scott Hollister, who holds the Patsy and Alan Dorris Chair in Pediatric Technology, a joint initiative supported by Georgia Tech and Children’s. “It’s two pieces of a puzzle — they understand the clinical problem, and we can develop the technology to actually solve it.”
"We are so proud of our partnership with Georgia Tech and the groundbreaking research developments we’ve discovered together,” said Lucky Jain, chief academic officer for Children’s Healthcare of Atlanta. “Our clinical researchers are fortunate to work with a leading engineering school like Georgia Tech to find innovative, potentially life-saving treatment options for our patients. We’ve seen firsthand how research can create more effective care at the bedside, and know our meaningful collaboration will continue to improve the future of pediatric care.”
Teams came together in the summer of 2018 to design and create 3D-printed, customized splints, which clinicians at Children’s Healthcare of Atlanta placed around the trachea and bronchi of a 7-month-old child to hold the airways open. Photo by Rob Felt.
A First in Georgia: 3D-Printed Splints Used in Surgery
The 7-month-old boy in the pediatric intensive care unit couldn’t breathe. His airways kept collapsing due to a life-threatening condition called tracheobronchomalacia. He was on a ventilator at the highest setting, but he kept struggling to get air. To save his life, teams from Children’s Healthcare of Atlanta, Emory University, Georgia Tech, and the Global Center for Medical Innovation (GCMI) came together in the summer of 2018 to design and create 3D-printed, customized splints, which clinicians at Children’s placed around his trachea and bronchi to hold the airways open.
The groundbreaking, image-based design and 3D biomaterial printing technology used to create the splints was developed by Scott Hollister, who holds the Patsy and Alan Dorris Chair in Pediatric Technology, a joint initiative supported by Georgia Tech and Children’s. Hollister began his research program into the design and printing technology on 3D-printed splints for pediatric populations at the University of Michigan prior to joining Georgia Tech. Hollister’s continued research and novel design work at Georgia Tech led to the first use of a 3D-printed splint to treat tracheobrachomalacia in Georgia.
Researchers Sarah Jo Crotts and Scott Hollister are shown with a laser sintering system used to create 3D tracheal splints deployed in groundbreaking pediatric surgery. Photo by Rob Felt.
Hollister, who is director of the Center for 3D Medical Fabrication (3DMedFab) at Georgia Tech and a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, and his team (including Harsha Ramaraju and Sarah Jo Crotts) start with CT scans of a child’s airways, then create a digital model of the trachea and bronchi. “From that model, we get the parameters of the length and diameter of the collapsed segment,” said Hollister.
The splints are made using a laser-sintering system. A laser traces the outline of the 3D model, melting a powdery material called polycaprolactone (PCL), which was spread into the build area. The laser follows the pattern scan and fuses the particles together to create the tiny splint layer by layer. Hollister’s team uses PCL because it’s absorbed into the body over time. “With a growing child, we’d like the device to be there for two or three years,” Hollister said. “It slowly resorbs over time so you don’t have to go back and surgically remove it.”
Although it’s carefully designed to be a meticulous fit, multiple versions of each splint are created to ensure that surgeons can select the best possible match. In this case, because the child’s condition was so severe, a cross-functional team of surgeons at Children’s placed three splints around the child’s airways in a 10-hour procedure that also included repairing a heart defect.
The 3D-printed tracheal splint is still experimental, so Children’s received clearance from the FDA to use the device under Expanded Access guidelines. So far, 20 children in the U.S. have received these splints.
Steve Goudy, medical director of pediatric otolaryngology at Children’s, was one of the members of the surgical team. “It’s the close relationships we have with our research collaborators that make this kind of groundbreaking procedure possible,” Goudy said. “A large number of additional physicians, support staff, and outside collaborators worked together on this innovative procedure.”
3D printing has the chance to create a new model for treating children, Hollister said. “It’s difficult for large companies that make devices to economically develop them for kids, especially because their anatomy is so varied, requiring a wide variety for a small number of devices,” he said. “3D printing gives us the potential to design patient-specific devices.”
Hollister continues to work with Children’s physicians on ways to use this technology. And he foresees a day when it’s almost commonplace: “I think it will gradually progress to where hospitals are building 3D-printed devices for their patients on site.”
This research was supported by the National Institutes of Health through awards R21 HD076370 and R01 HD086201. Support was also received from the Children’s Pediatric Research Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsoring agencies.
A Clot-Preventing Connection
For children with severely compromised lungs or heart, a type of life support called extracorporeal membrane oxygenation (ECMO) may be the only option until they can recover or receive an organ transplant. But with an 18% mortality rate in children, ECMO — which was designed for adults, not children — carries enormous risk, too.
With ECMO, the patient’s blood circulates outside the body through tubes where it receives oxygen, so the process takes on the role of both heart and lungs. Pediatric patients on ECMO often develop blood clots that can cause strokes or be fatal, so they are given anticoagulants or blood thinners to keep clots from forming in the tubes. However, that raises the risk of a life-threatening hemorrhage, and it’s difficult to keep a clinical balance between clotting, anticoagulation, and bleeding.
Doctors at Children’s Healthcare of Atlanta’s Cardiac Intensive Care Unit asked Georgia’s Tech’s David Ku for help. They thought the artificial surface used in the tubing was causing clots to form. But Ku, who holds both a Ph.D. from Georgia Tech and an M.D. from Emory University, found something different: More than 90% of the clots were actually forming on the connectors that linked one piece of tubing to another. To be more specific, clots were forming right at the ends of the connectors.
A redesigned connector used in extracorporeal membrane oxygenation (ECMO) may help reduce blood clots in children. The device connector was developed by a team headed by Professor David Ku. Photo by Christopher Moore.
“We thought if we could find out why it is just at the ends of the connectors and fix them, we could get rid of most of the clots,” Ku said. “Then we wouldn’t have to give as much anticoagulant and that would help prevent a bleeding problem.”
When blood pools or flows with very low shear rate, it coagulates. Ku’s team, which specializes in fluid dynamics, found that there were little “steps” up and down where the tubing linked up to the connectors, creating small areas of low shear rate. That’s where the clots were forming. So, the team redesigned the connector to eliminate the steps.
The old connector went inside the tube; the new one goes outside, with a casing around it to allow for perfusion when needed. The new connector is currently being tested, and Ku hopes to submit it to the FDA for approval in about a year.
The project was funded by the Center for Pediatric Innovation and the Atlantic Pediatric Device Consortium (APDC), a collaboration between Children’s, Georgia Tech, Emory, and Virginia Commonwealth University. Ku is executive director of APDC. He also holds the Lawrence P. Huang Chair in Engineering Entrepreneurship in the Ernest Scheller Jr. College of Business, and is a Regents Professor in the George W. Woodruff School of Mechanical Engineering. Ku also serves as director of the Center for Entrepreneurship's Program for Engineering Entrepreneurship at Georgia Tech.
He noted that devices designed for pediatric patients are rare. Although ECMO started as a way to keep adults alive, it actually works better for children, according to Ku. “It saves about 2,000 kids’ lives each year. So we’re starting with pediatrics because it’s where the largest need for ECMO is,” he said. If the new connector is approved, it could provide similar benefits for adults undergoing dialysis or heart bypass surgery. “Those all have the same problem with coagulation,” Ku said. “It’s well known that there’s a problem. But now we know how to fix it.”
Steerable Robotic Instruments Could Help Pediatric Neurosurgeons
Minimally invasive pediatric neurosurgery is among the most challenging of pediatric health care specialties, in part because available endoscopy instruments provide very limited maneuverability for smaller bodies. Now, researchers from Georgia Tech and Children’s Healthcare of Atlanta are working to address that challenge with scaled-down and steerable robotic instruments specifically designed for pediatric patients.
Using 3D-printed components and superelastic Nitinol (nickel-titanium) tips fabricated using unique laser machining equipment, the research team has developed a proof-of-concept device that can reach around obstructions in a child’s brain to treat hydrocephalus — “water on the brain” — and potentially other neurological issues. The tip, which one day will hold miniature scissors, a grasper, or cauterizing probe, is steered by tiny “tendons” built into an endoscope tube just 2 to 3 millimeters in diameter.
“It’s like having a surgeon’s fingers come out of the endoscope to manipulate the instruments,” said Jaydev Desai, director of the Georgia Center for Medical Robotics and a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
Desai is collaborating with Dr. Joshua Chern, a neurosurgeon at Children’s, in research supported by a seed grant from the Imlay Innovation Endowment Fund at Children’s.
“As a surgeon, my first and foremost responsibility is to achieve the best possible outcome for my patients, and whenever possible, to minimize the discomfort and undesirable side effects that are associated with the treatment itself,” Chern said. But the very nature of minimally invasive neurosurgery makes that difficult because procedures must be done through a small corridor in the brain, which limits the access and maneuverability of the rigid instruments that are currently available.
“The size problem is accentuated in the pediatric population, yet one may convincingly argue that these patients stand to benefit the most from minimally invasive surgery,” Chern added. “We are developing novel tools based on robotic principles to be used in these operations. Better instrumentation can expand the range of diseases that can be treated using these minimally invasive techniques.”
Graduate Research Assistant Yash Chetan Chitalia shows steerable robotic instruments under development for minimally invasive pediatric neurosurgery. Photo by Christopher Moore.
The prototype instrument is controlled by a joystick or video game controller, but future versions could use a full control console. The researchers are also looking at a tele-operated control system that might allow surgeons to work from hundreds or thousands of miles away.
“We are interested in developing a whole host of pediatric devices that could be steered by a clinician and applied not just to neurosurgery, but also to cardiovascular and general surgical procedures,” said Desai. “These developments will be driven by what clinicians need. We don’t want to change the clinical work flow; we want surgeons to have better tools.”
For patients, that could mean better outcomes, shorter surgeries, faster recovery times, and lower costs.
While the motors and metal components require special fabrication, the polymer parts are made in a specialized 3D printer in Desai’s laboratory. That fabrication process could one day facilitate production of instruments customized for a specific patient’s procedure, he said.
Designing with the Patient in Mind
Many adults, particularly those with claustrophobia, experience significant anxiety when undergoing an MRI. Imagine being a child with Autism Spectrum Disorder (ASD) — with sensitivity to sounds, touch, and changes in the environment — and needing an MRI on a regular basis.
This presents a challenge for children, parents, and clinicians. When a child with ASD requires an MRI, he or she is commonly sedated to ensure they remain still throughout the scan. There are many inherent risks associated with sedation.
Researchers at the Marcus Autism Center, an affiliate of Children’s Healthcare of Atlanta, utilized an MRI simulator to train the children on what to expect. But children with ASD frequently lack the ability to generalize experiences, and the MRI simulator at Marcus did not closely resemble the actual MRI scanner. This limited the benefits of the training session, and the transition felt like a completely new experience.
Brad Fain’s experience in universal design led him to think there were better solutions. Former director of the Center for Consumer Product Research and Testing at the Georgia Tech Research Institute (GTRI), Fain started with the goal of making the simulator experience match that of the real machine, but he also wanted to explore how to make the environment less frightening for children.
The goal of universal design, he said, is removing barriers in the environment so that everyone can access and use it. “If you design something for a population with special needs, then likely you will benefit the entire population who needs access to that technology as well,” said Fain, who is now executive director of the Georgia Tech Center for Advanced Communications Policy.
GTRI Senior Research Associate Megan Denham led Fain’s team in studying the best approach to making children more comfortable with the procedure. Initially, the team discussed creating a “skin” for the MRI machine with a child-friendly design that reflected children’s interests, such as rocket ships. But by asking the kids what they liked, it was clear that they had different interests.
Research Associate Megan Denham shows a smartphone app that controls lighting around an MRI simulator used to teach children what to expect during the procedure. Photo by Christopher Moore.
“The theme that emerged from talking with these kids and families wasn’t so much about a particular design,” said Denham. “It was the desire for control over their environment.” In stressful situations, the children liked to go to their rooms, where they had things set up the way they wanted them.
The team, which included research scientists Andrew Baranak, Chris Bartlett, and Amanda Foster, searched for a solution that could be customized to each patient, be consistent in both the simulator and procedure locations, and change when needed. They came up with the idea of letting each child choose the color of the lights in the rooms. “Every day they can choose a different color that matches their mood,” said Denham. “It also provides interactions between the trainers and clinicians and the kids, asking them, ‘What color would you like your room today?’” It encourages each child to interact with the environment.
The team also revamped the training simulator, working with a movie prop company to create one that better matched a real MRI machine. “Basically walking into those rooms, the children get an almost identical experience looking at the two units,” she said. “Then they can control the environment.”
Patients from the Marcus Center are not the only ones who may benefit. Other researchers and clinicians can utilize the ambient lighting system to improve the experience for their pediatric and adult patients.
Fain noted that the project is a great example of user-centered design — or patient-centered design, in this case. “We put the patient in the center of the process and then build the technology around them, as opposed to putting the technology in the center and trying to make the patient fit.”
This work was supported by a research collaboration between Children’s and Georgia Tech through the Children’s Healthcare of Atlanta Pediatric Technology Center Quick Wins program. Quick Wins funds projects designed to find fast solutions to unmet needs clinicians face in day-to-day patient care. “The collaboration has been solid,” Fain said. “They are very motivated because they have a need. We are very motivated because we have this really interesting problem to work on. They’ve helped us understand their problems and we’ve brought solutions they didn’t have before.”
Eleven-year-old Kaylee Vered holds a tablet computer running the passport application used to help researchers collect information about children receiving chemotherapy. Photo by Christopher Moore.
Just Ask the Kids
Approaching pediatric patients as partners in care was also the theme of a collaboration between Denham and doctors at the Aflac Cancer and Blood Disorders Center at Children’s. In fact, it was part of the title: “Designing Cancer Care For Kids, By Kids,” where children receiving chemotherapy helped researchers collect quantitative and qualitative data about their visit to the clinic.
Often pediatric cancer patients go through a complicated process in which they see multiple providers for different procedures in different rooms. The kids used a “passport” that was stamped by members of their care team at each step of their treatment. They also wrote and colored in the passport to let researchers know how they were feeling along the way. In essence, said Denham, researchers then had access to the best, but often overlooked, source of information: the patients themselves.
Identifying inefficient processes and long wait times, along with opportunities for improvement in the built environment — like more electrical outlets for parents who spend all day in the clinic with a child — was an important part of the study. So was understanding where and why the kids felt unhappy or scared. “One of the most striking findings was that the locations where they spent the most time were also the places they reported the most negative emotions,” said Denham.
Based on what the kids said, the clinic has already begun to make some changes in its processes and even its physical environment. For example, one thing the researchers heard was that kids wanted “fewer pokes.” Karen Wasilewski-Masker, who is the center’s medical director, a pediatric hematologist, and a champion of the project, found they could reduce the number of blood draws. And after hearing a 12 year old express a desire for “a private bathroom where I could throw up in peace,” Wasilewski-Masker asked architects of their new hospital unit to put more bathrooms in the rooms.
The first passport was paper-based and supported through the Children’s Healthcare of Atlanta Pediatric Technology Center. Now with additional funding from the Imlay Innovation Endowment Fund at Children’s, established to foster collaboration between Children’s and Georgia Tech, Denham’s team is working on an app that would have additional functionality. For example, at the Aflac Survivorship Clinic, children may move not only from room to room but facility to facility. “They may go upstairs to get an echocardiogram, across the street to get a PET scan,” Denham said. “It would be difficult to track that on paper.” Ideally, the app could be flexible enough to use in other clinics and pediatric hospitals.
The idea for the project came from one of Wasilewski- Masker’s patients, Kiersten, who spoke to an evidence-based design class at Georgia Tech a few years ago and talked about her experiences and the many things she couldn’t control. That encouraged Denham and her team to think about solving problems with patients instead of for them. “Every time we would get stuck on something, we would remember, ‘We need to ask the kids,’” she said.
Unfortunately, not all pediatric cancer patients survive; Kiersten died before her 21st birthday, and in some ways, Denham sees the project as her legacy. “We keep in touch with her family and let them know what we’re doing, and they know Kiersten is the one who inspired all of this work,” she said. “I think that kind of legacy is important for families when they are robbed of a life that has barely begun.”
Researchers Robert Mannino and Wilbur Lam show how smartphones can be used to non- invasively assess anemia levels. Photo by Christopher Moore.
Trading Sticks for Pics
It’s something all Ph.D. students can relate to: searching for the right thesis project. For Robert Mannino, now a postdoctoral fellow in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, it meant becoming the embodiment of the collaboration between Children’s Healthcare of Atlanta, Emory University, and Georgia Tech.
Mannino, who was born with a blood disorder (beta thalassemia major) that causes anemia, grew up getting life-saving blood transfusions at the Aflac Cancer and Blood Disorder Center every month. As an undergraduate at Georgia Tech, he knew he wanted to research blood disorders (his younger brother also has the condition). When he asked his hematologist at Children’s for guidance, she pointed him to Wilbur Lam, a physician on staff who is also an associate professor in the Coulter Department. Mannino began working in the Lam Lab soon after, applying computational solutions to biological problems.
After a positive experience working with Lam, Mannino decided to pursue a Ph.D. in the Coulter Department. As a graduate student, he created a smartphone app that can non-invasively screen people for anemia without the traditional blood test, the current gold standard for diagnosis. Patients use the phone’s camera to take a photograph of their fingernails. Since people with anemia often appear pale, the app uses an algorithm to analyze the color of a person’s fingernails to measure their blood hemoglobin level. The levels are then displayed on the screen for the patient or their health care provider to review.
Nail beds are ideal for imaging because they have little melanin, so skin tone doesn’t affect the results, though nail polish does. Background lighting doesn’t reduce accuracy, either. The algorithm controls for irregularities like camera flash reflections or white spots on the nails (leukonychia).
How it works
Mannino saw the correlation himself. “My hemoglobin level will start high after a transfusion and then drop significantly until I need another one,” he said. “So I was able to take pictures of my fingers over the course of a transfusion cycle and correlate the colors of my fingers to my actual hemoglobin levels.”
He validated the system with a clinical study of 337 pediatric and adult patients at Children’s and Emory University, respectively. They ranged in age from 1 to 60. The study was special for Mannino, the ex-patient. “I was working directly with the nurses and doctors who used to treat me while I was at Children’s,” he said. “My childhood hematologist was one of the principal investigators for the study.”
The results, published in the journal Nature Communications, found that the app could accurately determine hemoglobin levels across a variety of conditions, including sickle cell disease, cancer, and other causes of anemia. “It doesn’t really matter what the condition is as long as you have an unobstructed view of the fingernails,” Mannino said.
That makes the app well-suited for screening anemia at the point of care and could reduce the number of “sticks” or blood draws that are a particular bane for pediatric patients and their parents. But more than that, it could also be valuable in remote areas where access to medical care is limited. Anemia is a symptom of many conditions, so a person could use their smartphone to screen for low hemoglobin levels and then go see a doctor.
Mannino took the 2017 Massachusetts General Hospital Primary Care Technology Competition prize and the Cisco Global Problem Solver prize at the Rice Business Plan Competition, receiving $200,000 for research and development of the app. The project also received support from the National Science Foundation and National Institutes of Health.
He is now working to continue the data collection process, make the user interface more intuitive, and planning to have users test the app themselves. The technology might also be leveraged to screen for jaundice or cyanosis.
“Rob was really the only person who could pull his project off,” said Lam, because of his “brilliant” computer coding skills and his own experiences with anemia. “Our lab’s affiliations with Emory and Children’s gave him easy access to anemic patients in my clinic and my colleagues’ clinics, which really accelerated the patient accrual process.”
“It was really rewarding that I was able to directly relate my research to my personal motivation for doing it,” Mannino said. “To work in the same place that I was treated was amazing. It was like completing a whole cycle.”
This research was supported by the National Science Foundation under Graduate Research Fellowship DGE-1650044 and by the National Institutes of Health under award R21-EB025646-01. The research also received support through a Children’s Healthcare of Atlanta Petit Scholar award through the Pediatric Technology Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors.
A stitched confocal microscopy image shows an RSV-infected mouse lung. RSV nucleoprotein and fusion proteins appear red and green, respectively. Cell nuclei appear blue.
A Novel Way to Prevent RSV Infection
Mention RSV and parents start nodding their heads. That’s because almost every child gets respiratory syncytial virus before they’re 2. For most kids, it causes a pesky cold — but for premature babies or those with weakened immune systems it can be deadly. Sometimes even a small number of healthy babies develop more severe short-term problems like bronchiolitis or pneumonia or long-term pathologies including asthma. Every year about 57,000 children under 5 are hospitalized with RSV.
Currently there’s no vaccine, and a medication used to prevent RSV, an antibody called palivizumab, isn’t always effective (plus it has to be given as an intramuscular shot, often monthly). Philip Santangelo, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, brought together two of his research targets — RSV and messenger RNA — to tackle the problem.
Graduate student Daryll Vanover, Professor Philip Santangelo, and Postdoctoral Fellow Pooja Tiwari were coauthors on a study that used mRNA-expressed antibodies to prevent RSV infection in mice.
When a child gets an intramuscular injection of palivizumab, only a small amount of the antibody makes it into the airways, where RSV (like flu) tends to infect epithelial cells. “If we expressed it in the lung, could we improve its efficacy?” Santangelo wondered. “Could this be another way to use this antibody?”
The answer was yes. In a study of mice, Santangelo’s team used synthetic messenger RNA (mRNA) to deliver antibodies — palivizumab and another experimental protein — directly to the lungs via aerosol. Two forms of palivizumab were used, the whole secreted form (sPali) and one that was engineered with a glycosylphosphatidylinositol (GPI) membrane anchor or linker (aPali), which should allow it to stay longer on the surface of epithelial cells. The experimental antibody (a VHH camelid antibody), which was previously shown to be more potent than palivizumab but is not currently used to prevent RSV, was also tested with and without the linker. Each method protected the mice from RSV infection.
The study, published in the journal Nature Communications, showed two things, said Santangelo: Delivering the antibodies directly to the lungs using mRNA was effective at preventing RSV. And adding the linker enabled the antibodies to be tethered to the epithelial cells for a longer period, increasing the time they protected against the virus.
“With palivizumab, that may or may not be as critical — we noticed that even with the secreted version we were able to block the virus reasonably well,” said Santangelo. “But single-chain antibodies, which are very small, have short half-lives. You have to give them frequently, which doesn’t seem practical. When we put this linker on the smaller antibody, we were able to see it on the epithelial cells 28 days later. That was really exciting to us.”
In fact, Santangelo suspects that using the linker could cause smaller antibodies to last for a few months. “You could see administering this right after a child is born, when they are most vulnerable,” he said.
The team used mRNA because it was a safe way to deliver the antibodies, especially crucial for pediatric patients. “Using a transient, nucleic acid-based method that doesn’t end up in the cell nucleus is really important,” said Santangelo, whose study was funded by the Children’s Healthcare of Atlanta Pediatric Technology Center on Georgia Tech’s campus, and a Defense Advanced Research Projects Agency (DARPA) grant. “We do want this to be transient, so if it lasted even a month, that would protect newborns in the hospital where they may be exposed to RSV. And if you could protect kids for a few months at a time, that’s really all you would need to do.”
The research was funded by DARPA grant W911NF-15-0609. The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. government.
An Easier Scrub for the Hub
Central lines are lifesavers — literally. They’re used to draw blood or give medication to critically ill patients, both adult and pediatric, in hospitals. Inserted into a major vein near the heart, they may need to stay operational for weeks or longer. But they can also be the source of life-threatening infections, called central line-associated bloodstream infections (CLABSI).
To avoid this deadly problem, the catheter hubs, luer locks, and needleless intravenous (IV) connectors must be kept clean. Doctors and nurses are supposed to follow the “scrub the hub” protocol that requires scrubbing the access port for 15 seconds with an isopropyl alcohol-saturated prep pad, and then letting it dry for 30 seconds. But the hub has tiny threads and other small orifices that are hard to clean, and the protocol is rarely followed because of the amount of time and effort it takes. Hundreds of thousands of patients in the U.S. die each year because of CLABSIs.
Jud Ready, deputy director of Innovation Initiatives at Georgia Tech’s Institute for Materials, and his team came up with an invention that can reduce those numbers. Called easySCRUB, it’s a micro-abrasive melamine foam sponge that’s saturated with isopropyl alcohol. About the size of a sugar cube, it can be used to more effectively “scrub the hub” because the foam conforms to the spaces between the threads to lift and trap bacteria that cause infection.
It doesn’t require any additional training for clinicians to use and it’s thrown away after a single use to prevent contamination. It even makes a noise — Ready described it as a squeak — when used properly, so the clinician has confirmation.
Researcher Jud Ready demonstrates how easySCRUB would be used to clean a catheter hub connector. The hubs must be kept clean to help prevent central line infections. Photo by Rob Felt.
The secret is in the material used in the sponge. Initial proof-of-concept tests against two types of bacteria (Staphylococcus aureus and Pseudomonas aeruginosa) that often cause pediatric hospital-acquired infections showed that the microabrasive makeup of the melamine foam removed orders of magnitude more bacteria colony forming units from the luer lock threads on the needleless IV connector compared to the traditional prep pad. (Luer locks are industry standard in medicine.)
Ready said the team looked at a wide variety of materials. “To be commercially viable, we need to make hundreds of millions of these cubes per year for pennies each. The melamine foam is commercially available at the right price and made in huge quantities,” he said. “Its original purpose, from the 1980s, is to be used as acoustic tiles.”
The project had its genesis through a friendship: Ready and his childhood pal Ned Frisbee have known each other since they played soccer together as kids. When Frisbee’s wife, a nurse in North Carolina, was talking about CLASBI, Frisbee suggested he call “his friend at Georgia Tech who knows materials,” as Ready put it. That got Ready started, and he investigated a number of prototypes through the years before working with an interdisciplinary design team to come up with easySCRUB in 2016. Students who participated were from biomedical engineering, mechanical engineering, and materials science and engineering.
In 2016, the team won the $5,000 first prize at Georgia Tech’s spring Capstone Design Expo, then in 2017 received a $50,000 first prize from the "Make Your Medical Device Pitch for Kids!" competition sponsored by the National Capital Consortium for Pediatric Device Innovation, which is funded by the Food and Drug Administration (FDA). Now incorporated as a biotech startup called Hub Hygiene, things have moved even faster. The team partnered in 2018 with BASF, which manufactures the melamine foam in commercial quantities. FDA clearance activities are underway, and are expected to conclude this year.
Hub Hygiene recently received a patent for the device (#10,166,085), with more on the way. The company is currently doing packaging, sterility, and biocompatibility testing prior to filing a 510K for FDA clearance for use on humans. Once that clearance is received, clinical trials will follow.
“It’s been a whirlwind,” said Ready, who is also a principal research engineer at the Georgia Tech Research Institute and an adjunct professor in the School of Materials Science and Engineering. “To go from college seniors doing a paper study in 2016 to a life-saving, FDA-cleared medical device in 2019 is incredibly fast and virtually unheard of in the medical product space.”
If easySCRUB gains traction, it could also be evaluated for use with PICC (peripherally inserted central catheter) lines, which are also prone to infection, as well as for maintenance of IVs used in dialysis, chemotherapy, and anesthesia, among other health care applications. Ready hopes Hub Hygiene goes from startup to successful company, but he knows there’s more at stake. “Hopefully two kids playing soccer can end up saving thousands of lives four decades later,” he said.
The research has received funding from Children’s National Health System and BASF.