Northwestern University Feinberg School of Medicine

William Funk Lab

Heavy Metals and Cotinine in DBS

Toxic metals, including arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), are ubiquitous environmental pollutants that are listed as the 1st, 2nd, 3rd, and 7th most important hazardous substances on the 2011 Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) priority list of 275 substances, respectively. Exposure to heavy metals can occur through a variety of exposure routes, including inhalation as dust and fumes, and ingestion from food and water, and can cause a wide spectrum of health problems including convulsions, coma, renal failure, injuries to the lungs and neurologic system, memory loss, delirium, diabetes, kidney damage, and a variety of cancers. Exposures are of particular concern with pediatric populations and younger children, for whom the developmental consequences of heavy metal exposure can be particularly severe. Toxic metals can be quantified in blood to estimate internal dose, which is essential for investigating links between environmental exposures and health outcomes. However, the requirement for venous blood, which is costly and invasive, is an obstacle for assessing heavy metal exposures. Over the past seven years our lab has pioneered the use of DBS sampling for estimating exposures to toxic metals using a new metals-free collection methodology (Pending US Patent Numbers 62/340261 & 61/803674). Using this new methodology we are currently working on two NIH funded studies to evaluate adverse health outcomes associated with heavy metal exposures (R01 HD075957-01A1, UG3/UH3 RFA-OD-16-003).

In addition, we recently developed a sensitive, high-throughput method for extracting and quantifying cotinine in DBS samples as a biomarker of tobacco smoke. Our sample preparation incorporates a pressure barocycler to extract up to 48 samples in parallel in less than 10 minutes, making it amenable for high throughput processing. We also use a state-of-the-art nanochip-LC interface and QQQ mass spectrometer for maximum sensitivity using a minimal sample volume, respectively. With this method, we can quantify cotinine levels using a single 3.2 mm DBS punch.