title: Label-free electrochemical impedance biosensor to detect human interleukin-8 in serum with sub-pg/ml sensitivity.
abstract: Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture protein based on a cystatin scaffold that displays high affinity for human IL-8 with a KD of 35 ± 10 nM and excellent ligand specificity. The change in the phase of the electrochemical impedance from the serum baseline, ∆θ(ƒ), measured at 0.1 Hz, was used as the measure for quantifying IL-8 concentration in the fluid. Optimal sensor signal was observed after 15 min incubation, and the sensor exhibited a linear response versus logarithm of IL-8 concentration from 900 fg/ml to 900 ng/ml. A detection limit of around 90 fg/ml, which is significantly lower than the basal clinical levels of 5-10 pg/ml, was observed. Our results are significant for the development of point-of-care and early diagnostics where high sensitivity and short time-to-results are essential.
authors.affiliation: School of Electronic and Electrical Engineering, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Deacon
authors.affiliation: School of Electronic and Electrical Engineering, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.
authors.forename: D
authors.initials: D
authors.lastname: Nowak
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: George
authors.affiliation: School of Electronic and Electrical Engineering, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Szymonik
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK; BioScreening Technology Group, Astbury Building, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: A A S
authors.initials: AAS
authors.lastname: Tang
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK; BioScreening Technology Group, Astbury Building, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Tomlinson
authors.affiliation: School of Electronic and Electrical Engineering, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Davies
authors.affiliation: School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK; BioScreening Technology Group, Astbury Building, University of Leeds, Leeds LS2 9JT, UK. Electronic address: M.J.McPherson@leeds.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: McPherson
authors.affiliation: School of Electronic and Electrical Engineering, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK. Electronic address: C.Walti@leeds.ac.uk.
authors.forename: C
authors.initials: C
authors.lastname: Wälti
mesh_terms: D015415:Biomarkers / Q000097:blood*; D015374:Biosensing Techniques; D017097:Electric Impedance; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D057230:Limit of Detection
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016209:Interleukin-8
keywords: Antibody mimetic protein; CXCL8; Electrochemical impedance spectroscopy; Interleukin-8; Label-free biosensor; Point-of-care diagnostics