From left: Will Savage, Jason Fiering (a Draper lab collaborator on Savage’s project) and Sophia Koo, winners of this year’s BWH Health and Technology Innovation Fund grants

The BWH Health and Technology Innovation Fund, supported by the Brigham Research Institute and the BWH Health & Technology Sub-Committee, recently awarded Sophia Koo, MD, of the Division of Infectious Diseases, and Will Savage, MD, PhD, of the Department of Pathology, each $50,000 grants to fund their research projects.

The fund seeks applications from clinicians and scientists yearly on the basis of basic, clinical and translational science-focused projects, as well as commercialization-oriented research projects. Selection of the grant recipients was determined by input from the review committee and recommendation from the BRI Executive Committee. During a live-pitch “Shark Tank” session, the finalists delivered five-minute overviews of their projects and answered questions from entrepreneurs and scientific experts. The judges were looking to fund high-reward, high-impact and cutting-edge innovation that is on the cusp of research in the present day, and selected both Koo and Savage for their highly collaborative and bold projects to diagnose infectious disease and improve blood treatments, respectively.

Sophia Koo, Innovator in Diagnostics

Diagnosing infectious diseases such as pneumonia can be challenging. Koo knows this facet of her job all too well. She describes this challenge as “empiric therapy”—an educated guessing game that physicians play in order to treat patients they believe have pneumonia. Pneumonia can result from bacteria, viruses or fungi that infect the lungs and cause the lung’s air sacs to fill with fluid or pus. The ability to distinguish between bacterial and viral pneumonia rapidly would guide antimicrobial treatment decisions at the point of care, reducing antibiotic prescribing in patients who do not have bacterial pneumonia and slowing the emergence of antimicrobial resistance.

Sophia Koo presents at the 2016 “Shark Tank” session.

Koo, fueled by her desire to provide better care for her patients, has been using a newly developed device to administer a rapid breath test to detect invasive aspergillosis, a fungal infection of the lungs. Funding from the Health and Technology grant will help her to use the same device to detect bacterial versus viral pneumonia.

Koo will use the device, developed by Draper Laboratory, to test patients with suspected bacterial or viral pneumonia. In short, Koo collects breath samples from patients who come into the hospital with symptoms of pneumonia and examines differences in metabolites – small molecules produced by the body in reaction to infection and by bacteria in the lungs – in breath samples from these patients to classify whether the infection is bacterial or viral.

Koo hopes that the device will allow physicians to prescribe antibiotics to those who need them, based on better diagnostic testing. She noted that there are several consequences to the overuse of antibiotics, including resistance on a global scale.

“Bacteria are clever, and they learn new ways around the antibiotics,” she said. “Taking antibiotics changes the microbiome inside your gut and can precipitate further hospitalizations for other conditions, like Clostridium difficile, a common hospital pathogen that can cause serious diarrheal illness and even death in patients.”

The award comes at a pivotal time in Koo’s research. Her project to distinguish between viral and bacterial pneumonia is currently underway, but it is limited by the time required by staff to identify suitable subjects and analyze the large quantity of data in each of these breath samples. “The grant will help us dedicate more time to identifying good candidates for collecting breath samples, analyzing data, and, ultimately, identifying the differences between the two patient groups.”

Koo hopes that her work will someday be applicable to pediatric patients. The mortality rate for pneumonia is high in children under 5 years of age, especially in high-burden areas such as southeast Asia and Africa, where antibiotic treatment decisions are made based on clinical symptoms, without accurate diagnostic tools.

“We are hoping that this testing can bring some precision to how long we treat infectious diseases and help us determine if someone is responding to the antibiotics and antifungal drugs so we can personalize how we treat patients and how long we subject them to these drugs,” said Koo.

Will Savage, Champion of Better Blood Treatment

Will Savage presents at the 2016 “Shark Tank” session.

Apheresis is an interventional procedure where blood is separated into its different components and the desired portion is removed or replaced. The procedure has myriad uses. An example is removing antibodies that attack one’s own organs in a variety of autoimmune diseases, such as myasthenia gravis, an autoimmune disease that weakens muscles. Therapeutic uses of apheresis also include collection of healthy cells, such as for stem cell transplants.

Commonly, this technique usesa centrifuge, which separates the plasma and cells according to density. This device, however, tends to be cumbersome for the provider and costly. It also requires long, highly supervised sessions in the hospital at the expense of the patient’s comfort.

Savage, in conjunction with Draper Laboratory, has developed a device to combat the challenges of centrifuge-based apheresis. His device separates blood cells and plasma by using ultrasound waves. The technique is known as acoustic apheresis.

“Our device has the potential to create a new paradigm for how we perform apheresis,” said Savage. The device Savage and his team are developing will have the ability to run continuously for 24 hours, creating less of a burden for critically ill patients who might otherwise need multiple appointments for discrete treatments.

The project is still in pre-production as a single microfluidic channel, a small tube system that blood flows through while ultrasound waves separate blood cells and plasma. The grant comes at a timely point in Savage and Draper’s partnership and will allow them to design and test a multichannel device. In order for the device to be successful for patients, there would need to be up to 30 or 40 channels for a comprehensive range of blood flow rates from neonates to adults.

In describing the collaboration with Draper, Savage said, “It is fun for both groups; we, on the clinical side, are in awe of their engineering ability, and they are in awe of the clinical complexity when engineering approaches get applied. There is great synergy when we work together.”

Savage envisions several clinical benefits for acoustic apheresis. Patients who utilize catheters may have the opportunity to have smaller, less intrusive catheters because the flow rate for the technique would be lower than the centrifuge-based method. This is a particular advantage for neonates and small children. Also, shorter hospital stays are a possibility if continuous apheresis comes to fruition.

“We have an optimized design, and now [through funding], we can test and design a multichannel device in order to make this a clinical reality for all patients, especially neonates. With a smaller, simpler device that can be operated continuously, patients won’t have to wait between treatments, and we can remove more disease-causing antibodies and blood cells than is currently feasible,” said Savage.