title: Towards a personalized approach to aromatase inhibitor therapy: a digital microfluidic platform for rapid analysis of estradiol in core-needle-biopsies.
abstract: Despite advances in breast cancer prevention and treatment, variability in patient-response has revealed the need for a more "personalized" approach to medicine, in which treatments are tailored to each patient's biology. Motivated by this idea, we introduce a technique that allows for quantification of small-molecule analytes directly from core needle biopsy (CNB) tissue samples on a miniaturized platform. The new technique, powered by digital microfluidics, integrates tissue-liquid extraction and magnetic bead-based competitive immunoassay for quantification of estradiol in milligram-sized CNB samples. Each measurement (from start to finish) requires ∼40 minutes, a duration consistent with a visit to a doctor's office. The performance of the new technique was validated by the gold-standard analysis method (high performance liquid chromatography coupled to tandem mass spectrometry), and was applied to evaluate human patient samples before and after a course of treatment with aromatase inhibitor therapy. We propose that the new technique has great potential for eventual use for fast, automated, and quantitative analysis of biomarkers in tissue samples, towards a personalized medicine approach.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St George St., Toronto, ON M5S 3H6, Canada. aaron.wheeler@utoronto.ca.
authors.forename: Sara
authors.initials: S
authors.lastname: Abdulwahab
authors.affiliation: Department of Chemistry, University of Toronto, 80 St George St., Toronto, ON M5S 3H6, Canada. aaron.wheeler@utoronto.ca and Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St., Toronto, ON M5S 3G9, Canada and Donnelly Centre for Cellular and Biomolecular Research, 160 College St., Toronto, ON M5S 3E1, Canada.
authors.forename: Alphonsus H C
authors.identifier: http://orcid.org/0000-0003-0074-4598
authors.initials: AHC
authors.lastname: Ng
authors.affiliation: Department of Chemistry, University of Toronto, 80 St George St., Toronto, ON M5S 3H6, Canada. aaron.wheeler@utoronto.ca and Donnelly Centre for Cellular and Biomolecular Research, 160 College St., Toronto, ON M5S 3E1, Canada.
authors.forename: M Dean
authors.initials: MD
authors.lastname: Chamberlain
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario, M5T3H7 Canada.
authors.forename: Hend
authors.initials: H
authors.lastname: Ahmado
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario, M5T3H7 Canada.
authors.forename: Lucy-Ann
authors.initials: LA
authors.lastname: Behan
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario, M5T3H7 Canada.
authors.forename: Hala
authors.initials: H
authors.lastname: Gomaa
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, Ontario, M5T3H7 Canada.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Casper
authors.affiliation: Department of Chemistry, University of Toronto, 80 St George St., Toronto, ON M5S 3H6, Canada. aaron.wheeler@utoronto.ca and Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St., Toronto, ON M5S 3G9, Canada and Donnelly Centre for Cellular and Biomolecular Research, 160 College St., Toronto, ON M5S 3E1, Canada.
authors.forename: Aaron R
authors.identifier: http://orcid.org/0000-0001-5230-7475
authors.initials: AR
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D062005:Biopsy, Large-Core Needle / Q000295:instrumentation* / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D016903:Drug Monitoring / Q000295:instrumentation*; D004867:Equipment Design; D005260:Female; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D051381:Rats
chemical_list: D047072:Aromatase Inhibitors