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.

Label-free detection of interleukin-6 using electrolyte gated organic field effect transistors

“…6,7 The last years have witnessed a large number of studies attempting at developing label-free biosensors alternative to currently used platforms based on optical response. [8][9][10][11][12][13][14][15] As for IL-6, the latest reported biosensors that allow for a real-time monitoring of the cytokine levels without requiring secondary [33][34][35][36][37] .…”

Strategies for the Development of Metallic‐Nanoparticle‐Based Label‐Free Biosensors and Their Biomedical Applications

“…Labeling techniques are varied, such as fluorescencel abeling, radiolabeling, and isotope labeling. [4,5] The enzyme-linked immunosorbent assay (ELISA) is at echnique based on al abel-based biosensor that uses an antibody and color-changing substance in the detection and quantificationo fantigen. [6] Label-free biosensors rely on the biophysical properties of molecules, such as the weighto ft he molecules, the chargeo n the molecular surface, or refractive index differences.…”

“…[25] Lorentz-Mie theory [26] wasu sed for the theoretical calculation of the plasmonic resonanceo fM NPs. By using Equations (1), (2), (3), (4), and (5), total extinction (Q ext )a nd scattering efficiency (Q sca )f or ah omogenouss pherec an be estimated:…”

Sensitive and selective Affimer-functionalised interdigitated electrode-based capacitive biosensor for Her4 protein tumour biomarker detection

“…Unlike antibodies, Affimers display robust characteristics of low molecular weight, high thermostability, and resistance to extreme pH conditions, ease of site specific functionalization, low production cost with high reproducibly using E. coli recombinant protein expression systems (Arrata et al 2017;Bedford et al 2017;Koutsoumpeli et al 2017;Kyle et al 2015;Raina et al 2015;Rawlings et al 2015;Tiede et al 2014;Vazquez-Lombardi et al 2015;Wang et al 2017b). Of key relevance, there is recent work demonstrating the application of Affimers for biosensing applications (Estrela et al 2010;Ko Ferrigno 2016;Koutsoumpeli et al 2017;Raina et al 2015;Sharma et al 2016;Wang et al 2017b).…”