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Dr. Mangilal Agarwal
Dr. Yogesh Joglekar
Dr. Likun Zhu
Dr. Jian Xie
Dr. Rajesh Sardar
Dr. Ruihua Cheng
Dr. Frédérique Deiss
Dr. Maher Rizkalla
Dr. Horia Petrache
Dr. Hazim El-Mounayri
Canine-Inspired Smart Sensor for Detecting Hypoglycemia from Human Breath
Dr. Mangilal Agarwal (PI), Electrical and Computer Engineering, NSF Award # 1502310.

Diabetes is a global and national epidemic and 1 in 10 healthcare dollars in the U.S. is spent on costs directly attributable to diabetes [1]. Persons with type 1 diabetes, especially children and the elderly, can experience sudden drops in blood sugar , that is, they can become hypoglycemic [2,3]. This can be very dangerous if it remains unrecognized. The metabolic processes that lead to hypoglycemia cause the production of specific volatile organic compounds (VOCs) in human breath. This fact is not currently used to monitor diabetes or track the onset of hypoglycemia. However, trained diabetes alert dogs are able to identify these compounds and recognize the onset of hypoglycemia [4,5]. Therefore, this project works towards developing a smart device able to detect the volatile organic compound profile in human breath that correlates to hypoglycemia. This is being accomplished by identifying the hypoglycemic signature breath profile, developing a nanosensor array capable of detecting the identified compounds, and incorporating the nanosensor array into a portable smart device.

In this REU summer project, students will work towards analyzing breath samples using gas chromatography/mass spectroscopy (GC/MS) and will assist in developing nanosensors. Chemical breath sensors for disease represent a new frontier in diagnostic tools [6,7]. These sensors transform concentrations of analytes into electrical signals. Analytes interact with, and cause a change in, the electronic or physical properties of the sensor nanomaterials, leading to a change in conductivity (change in resistance) or a change in the permittivity (change in capacitance) of the sensor. Studies on breath VOCs tied to various human diseases have shown that breath VOCs are at the level of a few hundred parts-per-million (ppm) [8] to a few parts-per-billion (ppb) [6,9]. This requires the fabrication of highly sensitive sensors using nanomaterials such as gold nanoparticles [6,10], carbon nanotubes [11], graphene [12], and metallic nanocrystals. Chemiresistor and field effect transistor (FET)-based sensors are being developed in Dr. Agarwal's lab. A simplified diagram of a FET-based sensor is shown in Figure 1. Highly doped silicon constitutes the gate of the device, gold is patterned for source and drain, oxide constitutes the dielectric, and the sensing nanomaterial film deposited between the two gold electrodes constitutes the channel of the transistor. This project includes approaching problems with innovative solutions, experimental design, development and use of functionalized nanomaterials, instrumentation usage, and results analysis. This will provide the undergraduate students an immersive interdisciplinary research opportunity to gain knowledge and understanding beyond what they learn in their classes.

References:
  1. American Diabetes Association, "Economic Costs of Diabetes in the U.S. in 2012," Diabetes Care, 36, 1033-1046, 2013.
  2. K. A. Wintergerst, B. Buckingham, L. Gandrud, B. J. Wong, S. Kache, and D. M. Wilson, "Association of Hypoglycemia, Hyperglycemia, and Glucose Variability with Morbidity and Death in the Pediatric Intensive Care Unit," Pediatrics 118, 173-179, 2006.
  3. M. N. Munshi, A. R. Segal, E. Suhl, E. Staum, L. Desrochers, A. Sternthal, et al, "Frequent Hypoglycemia among Elderly Patients with Poor Glycemic Control," Archives of International Medicine, 171, 362-364, 2011.
  4. D. L. Wells, S. W. Lawson, and A. N. Siriwardena, "Canine Responses to Hypoglycemia in Patients with Type 1 Diabetes," Journal of Alternative and Complementary Medicine, 14, 1235-1241, 2008.
  5. D. S. Hardin, J. Cattet, W. Anderson, and Z. Skrivanek, "Hypoglycemia Alert Dogs-Innovative Assistance for People with Type 1 Diabetes," 73rd Annual American Diabetes Association Scientific Sessions, Chicago, IL, June 21-25, 2013.
  6. G. Peng, U. Tisch, O. Adams, M. Hakim, N. Shehada, Y. Y. Broza, et al, "Diagnosing Lung Cancer in Exhaled Breath Using Gold Nanoparticles," Nature Nanotechnology, 4, 669-673, 2009.
  7. Y. Y. Broza, and H. Haick, "Nanomaterial-based Sensors for Detection of Disease by Volatile Organic Compounds," Nanomedicine, 8, 785-806, 2013.
  8. V. Y. Kulikov, L. A. Ruyatkina, M. Y. Sorokin, E. S. Shabanova, M. N. Baldin, M. N., Gruznov, et al., "Concentration of Light Hydrocarbons in Exhaled Air Depending on Metabolic Syndrome Risk Factors," Human Physiology, 37, 329-333, 2011.
  9. K. D. van de Kant, L. J. van der Sande, Q. Jöbsis, O. C. van Schayck, and E. Dompeling, "Clinical Use of Exhaled Volatile Organic Compounds in Pulmonary Diseases: A Systematic Review," Respiratory Research, 13, 117, 2012.
  10. O. Barash, N. Peled, F. R. Hirsch, and H. Haick, "Sniffing the Unique 'Odor Print' of Non-Small-Cell Lung Cancer with Gold Nanoparticles," Small, 5, 2618-2624, 2009.
  11. R. Ionescu, Y. Broza, H. Shaltieli, D. Sadeh, Y. Zilberman, X. Feng, et al., "Detection of Multiple Sclerosis from Exhaled Breath Using Bilayers of Polycyclic Aromatic Hydrocarbons and Single-Wall Carbon Nanotubes," ACS Chemical Neuroscience, 2, 687-693, 2011.
  12. G. S. Kulkarni, K. Reddy, Z. Zhong, and X. Fan, "Graphene Nanoelectronic Heterodyne Sensor for Rapid and Sensitive Vapor Detection," Nature Communications, 5, 4376, 2014.