$750,000
Rapid fingerprinting of cardiac biomarkers
Washington State University
Co Investigators: Prashanta Dutta, Wenji Dong
Cornelius F. (Neil) Ivory earned his B.S. in Chemical Engineering at the University of Notre Dame, his Ph.D. at Princeton University followed by a year as a USRA Visiting Scientist in the Bioseparations group at NASA's Marshall Space Flight Center. In 1987 he found his home in the School of Chemical Engineering and Bioengineering at Washington State University where he and his graduate students develop next-generation instrumentation for biological separations.
This LSDF award will be used to design a miniaturized blood test both for "point of care" and emergency diagnosis of cardiovascular disease based on the mass distribution of a family of cardiac biomarkers, especially the troponins. This instrument will produce a "fingerprint" of the phosphorylation state of these biomarkers which is expected to be both predictive and diagnostic of cardiovascular health.
Miniaturization can change the way that health care is delivered by moving it closer to the patient, by decreasing the blood sample size from a test tube to finger-prick volumes and by reducing the cost-per-test. Miniaturization can dramatically reduce the time it takes to analyze complex samples from more than an hour at medical laboratories to a few minutes at the patient's bedside.
The proposed labchip will use state-of-the-art microfluidics to prepare microliter blood samples for processing, then concentrate and fractionate the target biomarkers before delivering them for analysis on a FRET (Förster resonance energy transfer) array. The optical signal generated by FRET will contain information about the state of each biomarker which will provide a real-time snapshot of the patient's cardiovascular health.
The key challenges to development of this platform are (1) miniaturization and integration of the supporting off-chip instrumentation, (2) on-chip fractionation and concentration of ultra-trace biomarkers, e.g., the phosphorylated troponins, (3) implementation of microscale FRET and (4) automation of the platform optics and electronics.
Grant Update
“We are closing in on the three main objectives of the project: fabrication of a hybrid microchip with separation cascade and optical detection, development of the protocols for purification, sub-fractionation and concentration of the cardiac troponins, and their delivery to an array detector for quantitation of their phosphorylation state. We expect to complete these three objectives and then combine them into a single platform during the next grant period. ”
