Approximately 800,000 Americans are either rendered permanently sick or die every year because of medical misdiagnoses. Millions more, even if they don’t die or suffer significant harm, are misdiagnosed, with one estimate indicating 7.4 million diagnostic errors occurring annually in emergency departments alone.
Michael Girgis, an assistant professor in the Department of Bioengineering in the College of Engineering and Computing and part of the research team at the Center for Molecular Engineering, received $100,000 from the Virginia Innovation Partnership Corporation to better track molecules to ensure accurate diagnoses.
Girgis, who began his career as a pharmacist and earned a PhD at George Mason University in synthetic organic chemistry and spectroscopy, said, “I realized there are some gaps in proper diagnoses; a key challenge is measuring these tiny, tiny concentrations of certain biomolecules that are essential in diagnostics.” He was certain there was a better, less expensive way to measure biomarkers—such as metabolites or proteins—that are used for early detection, diagnosis, and prognosis.
Not being able to keep accurate track of these biomarkers leaves medical professionals with a blind spot of sorts, not knowing what necessarily is happening in the body when drugs are administered in the presence of a particular disease.
Girgis explained that tagging a molecule—adding a special chemical label to it so that instruments can see it more clearly—is a key part of solving this problem. “The only solutions in the market are chemical tags that conjugate (chemically link two molecules together) the biomarkers to allow them to be detected much better,” he said. But existing technology is very expensive. “We want to make a tag that will enhance the sensitivity of the detection, but a lot cheaper.”
The idea is to chemically modify the low-abundant biomarker with the custom-designed tag. The tagging process then allows an instrument like the mass spectrometer to detect and quantify the biomarkers despite the low abundance in biofluids, which can be any fluid taken from the body for analysis.
“These small molecules might be low-abundance molecules or biomarkers or some sort of small peptide that’s very difficult to ionize and be visualized, detected, and quantified. If we ionize it, or give it an electrical charge, we can detect it better, because we can’t see anything that’s not charged in mass spectrometry,” he said. “So we designed the molecule to incorporate a very powerful ionization head, a little tail or a linker, and then we conjugated this through a synthetic technique with a very good, what we call, reporter ion.”
The molecule will then go into the mass spectrometer, have energy applied to it, and the reporter ion will be released and counted. The technique that Girgis developed allows the ion to be released with very little energy, maintaining the integrity of the ion. The more energy required to break the ion away, the less “sensitivity” it has, making finding and counting it more difficult. Girgis said that one additional advantage is that his technique allows for the creation of the molecule tagging process in a single step, allowing for efficient large-scale manufacturing.
Girgis added, “This has a lot of potential and is much cheaper than the one competitor we have in the market.” Potential customers include clinical and diagnostic laboratories, pharmaceutical companies, and hospitals. “Within six months to a year we’ll be doing more testing and hope to bring this to a level where with a bit more modification, we can bring it to market. This will improve the whole field.”