Nicotine Exposure in the U.S. Population: Total Urinary Nicotine Biomarkers in NHANES 2015-2016.

We characterize nicotine exposure in the U.S. population by measuring urinary nicotine and its major (cotinine, trans-3'-hydroxycotinine) and minor (nicotine 1'-oxide, cotinine N-oxide, and 1-(3-pyridyl)-1-butanol-4-carboxylic acid, nornicotine) metabolites in participants from the 2015−2016 National Health and Nutrition Examination Survey. This is one of the first U.S. population-based urinary nicotine biomarker reports using the derived total nicotine equivalents (i.e., TNEs) to characterize exposure. Serum cotinine data is used to stratify tobacco non-users with no detectable serum cotinine (−sCOT), non-users with detectable serum cotinine (+sCOT), and individuals who use tobacco (users). The molar concentration sum of cotinine and trans-3'-hydroxycotinine was calculated to derive the TNE2 for non-users. Additionally, for users, the molar concentration sum of nicotine and TNE2 was calculated to derive the TNE3, and the molar concentration sum of the minor metabolites and TNE3 was calculated to derive the TNE7. Sample-weighted summary statistics are reported. We also generated multiple linear regression models to analyze the association between biomarker concentrations and tobacco use status, after adjusting for select demographic factors. We found TNE7 is positively correlated with TNE3 and TNE2 (r = 0.99 and 0.98, respectively), and TNE3 is positively correlated with TNE2 (r = 0.98). The mean TNE2 concentration was elevated for the +sCOT compared with the −sCOT group (0.0143 [0.0120, 0.0172] µmol/g creatinine and 0.00188 [0.00172, 0.00205] µmol/g creatinine, respectively), and highest among users (33.5 [29.6, 37.9] µmol/g creatinine). Non-daily tobacco use was associated with 50% lower TNE7 concentrations (p < 0.0001) compared with daily use. In this report, we show tobacco use frequency and passive exposure to nicotine are important sources of nicotine exposure. Furthermore, this report provides more information on non-users than a serum biomarker report, which underscores the value of urinary nicotine biomarkers in extending the range of trace-level exposures that can be characterized.

Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays.

The analysis of disease-specific biomarker panels holds promise for the early detection of a range of diseases, including cancer. Blood-based biomarkers, in particular, are attractive targets for minimally-invasive disease diagnosis. Specifically, a panel of organ-specific biomarkers could find utility as a general disease surveillance tool enabling earlier detection or prognostic monitoring. Using arrays of chip-integrated silicon photonic sensors, we describe the simultaneous detection of eight cancer biomarkers in serum in a relatively rapid (1 hour) and fully automated antibody-based sandwich assay. Biomarkers were chosen for their applicability to a range of organ-specific cancers, including disease of the pancreas, liver, ovary, breast, lung, colorectum, and prostate. Importantly, we demonstrate that selected patient samples reveal biomarker "fingerprints" that may be useful for a personalized cancer diagnosis. More generally, we show that the silicon photonic technology is capable of measuring multiplexed panels of protein biomarkers that may have broad utility in clinical diagnostics.

Development and validation of an immunosensor for monocyte chemotactic protein 1 using a silicon photonic microring resonator biosensing platform.

OBJECTIVES: We report the development of an optical immunosensor for the detection of monocyte chemotactic protein 1 (MCP-1) in serum samples. MCP-1 is a cytokine that is an emerging biomarker for several diseases/disorders, including ischemic cardiomyopathy, fibromyalgia, and some cancers. DESIGN AND METHODS: The detection of MCP-1 was achieved by performing a sandwich immunoassay on a silicon photonic microring resonator sensor platform. The resonance wavelengths supported by microring sensors are responsive to local changes in the environment accompanying biomarker binding. This technology offers a modularly multiplexable approach to detecting analyte localization in an antibody-antigen complex at the sensor surface. RESULTS: The immunosensor allowed the rapid detection of MCP-1 in buffer and spiked human serum samples. An almost 2 order of magnitude linear range was observed, between 84.3 and 1582.1pg/mL and the limits of blank and detection were determined to be 0.3 and 0.5pg/mL, respectively. The platform's ability to analyze MCP-1 concentrations across a clinically-relevant concentration range was demonstrated. CONCLUSIONS: A silicon photonic immunosensor technology was applied to the detection of clinically-relevant concentrations of MCP-1. The performance of the sensor was validated through a broad dynamic range and across a number of suggested clinical cut-off values. Importantly, the intrinsic scalability and rapidity of the technology makes it readily amenable to the simultaneous detection of multiplexed biomarker panels, which is particularly needed for the clinical realization of inflammatory diagnostics.

Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays.

Ricin is a lethal protein toxin derived from the castor bean plant. Given its notorious history as a biowarfare agent and homicidal weapon, ricin has been classified as a category B bioterrorism agent. Current ricin detection methods based on immunoassays lack the required sensitivity and specificity for many homeland security surveillance applications. Importantly, many conventional antibody-based methodologies are unable to distinguish ricin from RCA 120, a nontoxic protein also found in the castor bean plant. Single domain antibodies (sdAbs), which are recombinantly derived from immunized llamas, are known to have high affinities for ricin A or B chains and low cross-reactivity with RCA 120. Herein, we demonstrate the use of silicon photonic microring resonators for antibody affinity profiling and one-step ricin detection at concentrations down to 300 pM using a 15 min, label-free assay format. These sdAbs were also simultaneously compared with a commercial anti-RCA IgG antibody in a multicapture agent, single target immunoassay using arrays of microrings, which allowed direct comparison of sensitivity and specificity. A selected sdAb was also found to exhibit outstanding specificity against another biotoxin, saporin, which has mechanism of action similar to ricin. Given the rapidity, scalability, and multiplexing capability of this silicon-based technology, this work represents a step toward using microring resonator arrays for the sensitive and specific detection of biowarfare agents.