Dosimetry for Tobacco Smoke Exposure using Biosensors

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Dosimetry for Tobacco Smoke Exposure using
Biosensors

• Natarajan Ganesan, PhD

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Tobacco smoke dosimetry

• Self reports of direct/indirect exposure is
  subjective
• Accurate dosimetry aids molecular epidemiologists
• Cotinine assays from plasma and urine is a
  popular biomarker for nicotine exposure
• Reflects recent exposure (few days)
• Longer exposure needs suitable biomarkers

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Assays for nicotine exposure

• Gas chromatography-Mass spectrometry
• Radioimmunoassay
• Existing procedures are sensitive but
• prone to interferences
• are expensive
• not readily available for field surveys

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B-FIT biosensors

• Measures metabolites in interstitial fluids
• Small patch like devices containing a
  non-intrusive sampling device
• High throughput
• Instant detection using enzymatic and antibody
  reactions
• electrochemical, optical, etc .
• Nicotine and its metabolites can be assayed using
  respective enzymes.

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Proteomic biomarkers

• Early stages
• Sampling using micro-fluidic device
• Intrusive sampling
• Lab on a chip approach
• Integrating 2-D separations
• Mass spec
• Cap electrophoresis

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Nicotine Biosensor

• Identify a stable and suitable biomarker e.g.
  Cotinine, nicotine/cotinine ratio
• Choose a metabolizing enzyme giving an assayable
  product.
• Antibody based detection can also be attempted
• Calibration and validation in
• In vitro
• Actual samples

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Long-term Nicotine exposure

• Biospecimens for tobacco smoke exposure
• Urine, plasma
• These are short term indicators
• Hairs and nails store nicotine
• Growth rate is slow. Long term biomarkers
• Assayed using HPLC coupled to Electrochemical
  detection
• Sensitivity 4-640 ng/mg of hair sample
• Can B-FIT be applied to sample from these sources?

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Nicotine from toenails

• A typical chromatogram from an HPLC reading of
  nicotine levels in toenail (1.7 ng/mg nail)
  compared with 2-phenylimidazole as the internal
  standard.
• Wael K. et al., 11, 1400-1404 November 2002,
  Cancer Epidemiology, Biomarkers and Prevention

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Alternative sampling sources

• Nasal hair (active/passive smoking)
• Teeth (more permanent marker for long term
  dosimetry)
• Arylamines and N-Nitroseamines from above samples
  N-Acetyltransferase assay
• Ther Drug Monit 2001 Aug23(4)341-6

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References

• Wael K. et al., 11, 1400-1404 November 2002,
  Cancer Epidemiology, Biomarkers and Prevention
• Mahoney, G., and Al-Delaimy, W., 753 179187,
  2001. J. Chromatogr. B Biomed. Appl
• Verghese, A. et al., 97 236238, 1990., Chest