Adaptation of a Novel Portable GC to Determine Breath Biomarkers of Lung Cancer

Research Trainee: Qiongyan (Judy) Zhong, MS, PhD Student, Dept. of Environmental Health Sciences at the University of Michigan

Faculty Researcher: Edward T. Zellers, PhD, Professor of Environmental Health Sciences and Chemistry at the University of Michigan

This proposal seeks funding to adapt a high-performance portable gas chromatograph, containing several novel design and operating features, to the determination of volatile organic compounds in human breath that have been identified in several studies as potential biomarkers of lung cancer. Although resurgent interest in this non-invasive bio-monitoring technique is evident from the literature, current approaches rely on large, expensive instruments that are not suitable for untrained persons or on so-called ‘electronic noses’ (i.e., stand alone multi-sensor arrays) that generally lack sufficient resolution to provide reliable results. The research proposed here will explore the feasibility of monitoring breath biomarkers that have been associated with a specific disease, lung cancer, at clinically relevant concentrations in actual breath samples. Lung cancer is the leading cancer killer in both men and women, and the most frequent occupational cancer. Detection and treatment of lung cancer at an early stage can increase the 5-year survival rate greatly. Having a portable, turn-key instrument capable of identifying and quantifying lung cancer biomarkers would provide a means of screening workers at low cost in a matter of minutes in a field or clinical setting. This instrument is about the size of a laptop computer and incorporates state-of-the-art features, including a multi-stage preconcentrator, series-coupled separation columns with pressure and temperature tunable retention, and a detector comprising an integrated array of chemiresistor (CR) microsensors that provides a digital “spectrum” of eluting vapors. Its use for the determination of ppt levels of two environmental tobacco smoke markers in a complex mixture of prominent co-contaminants has recently been demonstrated. This project will determine its feasibility for the more challenging problem of identifying and quantifying lung cancer biomarkers in breath. This will be achieved by developing sampling/preconcentration methods to achieve desired detection limits while also rejecting or compensating for background humidity, establishing conditions for separating biomarkers from other endogenous and exogenous interfering compounds, calibrating the sensor arrays, and applying chemometric techniques tailored for this particular problem to confirm method reliability. Finally, the instrument will be tested with actual breath samples, and performance will be assessed through side-by-side tests with GC-MS.

 

Publications resulting from this project:
Zhong Q, Steinecker WH, Zellers ET. Characterization of a high-performance portable GC with a chemiresistor array detector. Analyst. 2009;134(2):283-293. doi:10.1039/b810944c.

 

Research trainee’s current position:
Judy Zhong completed her PhD in 2008 and is currently a Senior Research Scientist at Exponent, the Center for Occupational & Environmental Health.