title: Quantification of a cardiac biomarker in human serum using extraordinary optical transmission (EOT).
abstract: Nanoimprinting lithography (NIL) is a manufacturing process that can produce macroscale surface areas with nanoscale features. In this paper, this technique is used to solve three fundamental issues for the application of localized surface plasmonic resonance (LSPR) in practical clinical measurements: assay sensitivity, chip-to-chip variance, and the ability to perform assays in human serum. Using NIL, arrays of 140 nm square features were fabricated on a sensing area of 1.5 mm x 1.5 mm with low cost. The high reproducibility of NIL allowed for the use of a one-chip, one-measurement approach with 12 individually manufactured surfaces with minimal chip-to-chip variations. To better approximate a real world setting, all chips were modified with a biocompatible, multi-component monolayer and inter-chip variability was assessed by measuring a bioanalyte standard (2.5-75 ng/ml) in the presence of a complex biofluid, human serum. In this setting, nanoimprinted LSPR chips were able to provide sufficient characteristics for a 'low-tech' approach to laboratory-based bioanalyte measurement, including: 1) sufficient size to interface with a common laboratory light source and detector without the need for a microscope, 2) high sensitivity in serum with a cardiac troponin limit of detection of 0.55 ng/ml, and 3) very low variability in chip manufacturing to produce a figure of merit (FOM) of 10.5. These findings drive LSPR closer to technical comparability with ELISA-based assays while preserving the unique particularities of a LSPR based sensor, suitability for multiplexing and miniaturization, and point-of-care detections.
authors.affiliation: Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Tao
authors.initials: T
authors.lastname: Ding
authors.affiliation: Department of Electrical and Computer Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Minghui
authors.initials: M
authors.lastname: Hong
authors.affiliation: Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.affiliation: Institute of Materials Research Engineering, A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.
authors.forename: Ten It
authors.initials: TI
authors.lastname: Wong
authors.affiliation: Institute of Materials Research Engineering, A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Chester Lee
authors.initials: CL
authors.lastname: Drum
mesh_terms: D015415:Biomarkers / Q000097:blood; D006403:Hematologic Tests / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D050997:Nanomedicine / Q000295:instrumentation / Q000379:methods*; D012680:Sensitivity and Specificity; D013057:Spectrum Analysis / Q000295:instrumentation / Q000379:methods; D020349:Surface Plasmon Resonance / Q000295:instrumentation / Q000379:methods*; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D020107:Troponin T