Johns Hopkins Gazette | May 26, 2009
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The newspaper of The Johns Hopkins University May 26, 2009 | Vol. 38 No. 36
Award Supports Development of Lifesaving Diagnostic Tool

Samuel Yang hopes to develop a faster way to adiagnose sepsis in children.
Photo by Will Kirk / HIPS

By Margaret Hindman
Development and Alumni Relations

A 6-year-old boy wakes up in the night. He's vomiting and has mild abdominal discomfort, lethargy and fever. In the morning, his pediatrician tells the parents their son has viral syndrome and sends them home, but the boy's condition worsens throughout the day. By the time he is taken to a local emergency room that evening, he's dehydrated and developing a rash. The doctor on call suspects sepsis — an acute and highly contagious bloodstream infection often mistaken for the flu. The hospital begins aggressive antibiotic treatment, but it's too late to turn things around. The child goes into cardiac arrest and dies early the next morning.

It's a case that made an indelible impression on Samuel Yang, assistant professor in Emergency Medicine at Johns Hopkins, when he was just beginning his medical career. After the fact, the youngster's blood culture revealed that he had meningococcemia, one of many causes of sepsis. More than 4,300 children in the United States, and millions around the globe, die every year from sepsis.

"It's a leading cause of death for children and infants worldwide, and early diagnosis greatly improves the chances of recovery," Yang said. Unfortunately, the early symptoms, especially in youngsters, are often mistaken for flu or other illnesses that are not life-threatening, and a blood culture to produce a diagnosis takes at least 18 hours, which is too late in most cases to guide treatment.

The Hartwell Foundation recently awarded Yang a grant to support development of an innovative "point of care" diagnostic tool that will tell caregivers — within minutes — if sepsis is present and also identify the specific pathogen.

To avoid the tragic consequences of delaying treatment, many doctors order broad-spectrum intravenous antibiotic therapy and inpatient observation for all children with flulike symptoms. "This conservative approach may sound like a good idea," Yang said, "but it carries significant risks: Children may suffer iatrogenic complications associated with unnecessary treatment and hospitalization, and overuse of antibiotics leads to the development of increased rates of multidrug-resistant organisms. It's also quite costly."

Yang's proposal has the potential to revolutionize care for children with sepsis and save many lives. Collaborating with colleagues at the Whiting School of Engineering and the School of Medicine, he will use molecular and nano technologies to create a "lab on a chip," a glass-and-silicon wafer about the size of a microscope slide. "Ultimately," he said, "all the physician will need to do is to load the patient's blood sample onto the chip and, a few minutes later, read the results."

The Hartwell Foundation selected Yang and 11 other researchers nationwide for Hartwell Individual Biomedical Research Awards. "We are honored to provide financial support to these exceptional researchers pursuing applied biomedical research to advance children's health," said Fred Dombrose, foundation president. "The Hartwell Foundation seeks to inspire innovation and achievement by funding early-stage, transformative ideas with the potential to benefit kids in the United States," he added.

Advances in DNA testing for pathogen detection have set the stage for improving sepsis detection time and accuracy, Yang said. In a simple "sample-in and answer-out" format, the proposed chip will process a patient's blood sample, detect the presence of any bacterial DNA and analyze the sequence to identify and characterize the detected pathogen. PCR (polymerase chain reaction) is a key technique in molecular genetics that permits the analysis of DNA without having to clone it, providing very rapid results. His group has already developed a "molecular triage tool," based on PCR technology, that is capable of diagnosing life- or limb-threatening bacterial infections in patients.

Yang proposes a sample processing system based on electrokinetic forces, an innovation in the relatively new field of lab chip technology. He said he believes this approach will ensure not only diagnostic accuracy but also efficiency; the latter has been a problem with most sample processing platforms so far developed because they are made up of a collection of complex functional components connected into a system in a piecemeal fashion. A variety of electrokinetic forces, which are generated based on the strategic arrangement of electrodes embedded in Yang's chip, will allow cells and biomolecules to be manipulated in microscale with high precision and efficiency, he explained. In addition, he and his collaborators will incorporate nanoparticle quantum dots, which offer unique photophysical properties that can dramatically enhance the detection sensitivity and speed of chip- based PCR. All the functional components will be microfabricated on a single, disposable glass-and- silicon wafer.

Yang's collaborators are Tza-Huei "Jeff" Wang, associate professor in Mechanical Engineering and Biomedical Engineering; Richard Rothman, associate professor in Emergency Medicine and Infectious Diseases; and Charlotte Gaydos, professor in Infectious Diseases.

The Hartwell Foundation also has provided Johns Hopkins with funding for a Hartwell Fellowship, which the university has awarded to Nilay Shah. A clinical fellow in Pediatric Oncology, Shah is researching the genetic underpinnings of the childhood cancer neuroblastoma. This is the third consecutive year that Johns Hopkins has received funding for a Hartwell Fellowship, which is intended to foster the career development of a young biomedical scientist whose work focuses on improving children's health.

For more information, see the foundation's Web site:


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