title: Multiplexed cancer biomarker detection using quartz-based photonic crystal surfaces.
abstract: A photonic crystal (PC) surface is demonstrated as a high-sensitivity platform for detection of a panel of 21 cancer biomarker antigens using a sandwich enzyme-linked immunosorbent assay (ELISA) microarray format. A quartz-based PC structure fabricated by nanoimprint lithography, selected for its low autofluorescence, supports two independent optical resonances that simultaneously enable enhancement of fluorescence detection of biomarkers and label-free quantification of the density of antibody capture spots. A detection instrument is demonstrated that supports fluorescence and label-free imaging modalities, with the ability to optimize the fluorescence enhancement factor on a pixel-by-pixel basis throughout the microarray using an angle-scanning approach for the excitation laser that automatically compensates for variability in surface chemistry density and capture spot density. Measurements show that the angle-scanning illumination approach reduces the coefficient of variation of replicate assays by 20-99% compared to ordinary fluorescence microscopy, thus supporting reduction in limits of detectable biomarker concentration. Using the PC resonance, biomarkers in mixed samples were detectable at the lowest concentrations tested (2.1-41 pg/mL), resulting in a three-log range of quantitative detection.
authors.affiliation: Department of Electrical and Computer Engineering, 1406 West Green Street, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
authors.forename: Cheng-Sheng
authors.initials: CS
authors.lastname: Huang
authors.forename: Vikram
authors.initials: V
authors.lastname: Chaudhery
authors.forename: Anusha
authors.initials: A
authors.lastname: Pokhriyal
authors.forename: Sherine
authors.initials: S
authors.lastname: George
authors.forename: James
authors.initials: J
authors.lastname: Polans
authors.forename: Meng
authors.initials: M
authors.lastname: Lu
authors.forename: Ruimin
authors.initials: R
authors.lastname: Tan
authors.forename: Richard C
authors.initials: RC
authors.lastname: Zangar
authors.forename: Brian T
authors.initials: BT
authors.lastname: Cunningham
mesh_terms: D055910:Antibodies, Immobilized / Q000737:chemistry* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D015374:Biosensing Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007118:Immunoassay; D007834:Lasers; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism*; D017785:Photons; D040081:Protein Array Analysis; D011791:Quartz; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
chemical_list: D055910:Antibodies, Immobilized; D014408:Biomarkers, Tumor; D011791:Quartz