(387g) Award Submission: Cardiac Troponin I Detection Using Antibody-Immobilized Disposable Cover Glass and AlGaN/GaN High Electron Mobility Transistors

Cardiac troponin I (cTnI) detection was demonstrated using a functionalized disposable cover glass connected to an AlGaN/GaN high electron mobility transistors (HEMT). Cardiovascular disease is one of the leading causes of mortality in the US, and it has caused tremendous hardship for both individual health and finance in United States. Every year, over 800,000 Americans die due to the cardiovascular diseases.^[1] Troponins are released when the cardiac and skeletal muscles are damaged. There are three types of troponins; troponin I, troponin T, and troponin C. . Troponin I is extremely cardio-specific, and the elevation of troponin I concentration in the blood stream indicates the cardiac muscle damage. Troponin T is also a biomarker for myocardial infarction patient, however it is not exclusive. Studies have shown the elevated troponin T were also detected for patients with muscular dystrophy and renal disease. With the non-cardio specific nature of troponin C, it has never been used for clinical practice as a myocardial necrosis marker. ^[2,3,4] Currently, all the detection methods and systems for cTnI are time consuming, expensive and require a well-trained technician to perform and complete the tests.

The challenge for cardiac Troponin I (cTnI) detection method in clinical practice is to develop a hand-held, low cost, accurate, and real-time biosensors for myocardial infarction patients. The combination of functionalized cover glass and AlGaN/GaN high electron mobility transistors (HEMT) detection method has overcome the primary difficulty of biomarker solution with high ionic strength in traditional HEMT biosensors. In this approach, the HEMT device is not exposed to the bio-solution, which can be used repeatedly. The sensor functionalization was performed on a low cost disposable glass slide, which can be viewed as testing strips. Furthermore, the cover glass could be replaced by plastic or paper for cTnI detection, which can be more cost-effective. To test the cTnI concentration, pulsed bias-voltages are applied to a functionalized electrode on the cover glass and the drain terminal of the HEMT device. The electrical pulse would result in the formation of the electrical double layers (EDL) on the active sensing area, and different cTnI concentration would lead to different charge potential that is applied onto the conducting channel of this HEMT device. The detected cTnI concentration range was achieved from 0.1 ng/ml to 100 ng/ml. This covers wide range of cTnI concentration for the myocardial infraction, such as the elevated cTnI concentration of 10ng/ml or higher for acute myocardial infraction (AMI), and 0.5 ng/ml to 2.0 ng/ml cTnI concentration for early stage of AMI patients. The static drain current changes as a function of cTnI concentrations were modeled with the Langmuir extension model. Also, the spring relaxation model was employed for the dynamic modeling of the time-dependent current response for different biomarker concentrations. The results in this study demonstrated that the functionalized cover glass approach is a very attractive cTnI detection technology for inexpensive cartridge-type heart attack biosensors, and this technology can be applied to other sensing areas such as cancer detection, environmental monitoring, and food safety.

1. Benjamin, E.J., Blaha, M.J., Chiuve, S.E., Cushman, M., Das, S.R., Deo, R., de Ferranti, S.D., Floyd, J., Fornage, M., Gillespie, C., Isasi, C.R., Jiménez, M.C., Jordan, L.C., Judd, S.E., Lackland, D., Lichtman, J.H., Lisabeth, L., Liu, S., Longenecker, C.T., Mackey, R.H., Matsushita, K., Mozaffarian, D., Mussolino, M.E., Nasir, K., Neumar, R.W., Palaniappan, L., Pandey, D.K., Thiagarajan, R.R., Reeves, M.J., Ritchey, M., Rodriguez, C.J., Roth, G.A., Rosamond, W.D., Sasson, C., Towfighi, A., Tsao, C.W., Turner, M.B., Virani, S.S., Voeks, J.H., Willey, J.Z., Wilkins, J.T., Wu, J.H., Alger, H.M., Wong, S.S., Muntner, P., 2017. Heart disease and stroke statistics—2017 update: a report From the American Heart Association. Circulation (2017)
2. Mythili and N. Malathi, Diagnostic markers of acute myocardial infarction. Biomed. Rep. 3, 743 (2015).
3. Amitava Dasgupta and Amer Wahed, Chapter 8 - Cardiac Markers, In Clinical Chemistry, Immunology and Laboratory Quality Control, Elsevier, San Diego, 2014, Pages 127-144, ISBN 9780124078215
4. Allan S. Jaffe, Vlad C. Vasile, Margherita Milone, Amy K. Saenger, Kalen N. Olson, Fred S. Apple, Diseased Skeletal Muscle: A Noncardiac Source of Increased Circulating Concentrations of Cardiac Troponin T, Journal of the American College of Cardiology, Volume 58, Issue 17, Pages 1819-1824 (2011)