Electrochemical impedence spectroscopy enabled CA125 detection; toward early ovarian cancer diagnosis using graphene biosensors

Abstract

With current diagnostic methods detection of stage 1 or 2 ovarian cancer using CA125 is possible in only 75% of cases. The ability to detect CA125 at lower concentrations could significantly improve such early stage diagnosis. Here, the use of screen‐printed graphene biosensors as a label‐free detection platform for CA125 was evaluated. The sensor was fabricated through deposition of a polyaniline layer via electropolymerisation on to a graphene screen‐printed electrode. The sensor surface was functionalised with anti‐CA125 antibody via covalent cross linking to polyaniline. The fabrication process was characterised through cyclic voltammetry and electrochemical impedance spectroscopy. The limit of detection achieved was 0.923 ng/μL across a dynamic range of 0.92 pg/μL–15.20 ng/μL and represents the most sensitive CA125 detection reported to date. With sensitivity limits at this level, it will now be possible to conduct clinical trials using serum samples collected from early stage ovarian cancer patients and at risk individuals.

POISED-5, a portable on-board electrochemical impedance spectroscopy biomarker analysis device

“…Previously we have demonstrated the utility of screen-printed graphene biosensors as a label-free platform for the detection of CA125 using EIS measurements on the Metrohm FRA platform (Gazze et al 2018). The sensor was fabricated through deposition of a polyaniline layer via electropolymerization on to a graphene screen-printed electrode functionalized with anti- CA125 antibody via covalent cross linking to polyaniline.…”

“…To establish equivalency of the graphite-based sensor to graphene sensors, an established calibration procedure (Gazze et al 2018) was performed on anti-CA125 antibody functionalized graphene and graphite SPEs. Sensor impedance was determined by fitting to an R(RC) equivalent circuit using Nova analysis software.…”

“…These loads represent idealized systems rather than real sensor behavior to avoid variations from electrochemical sources. As many impedimetric biosensors report biomarker specific R ct ranges test load values were selected to match typical R s and R ct values from an experimental impedimetric biosensor for CA125 measurement (Gazze et al 2018). The test load C dl value was limited by unpolarized capacitor size that remained constant for all loads since R ct was assumed to have greater effect on impedance magnitude changes than C dl in a faradaic sensor system.…”

“…To demonstrate compatibility of the proposed device with an existing experimental biosensor, measurements were performed on three CA125 biosensors functionalized according to the method detailed in Gazze et al 2018. Briefly, the sensor is constructed by electropolymerizing aniline monomers (product #242284, Sigma Aldrich) dissolved at 0.1 M into a 1 M sulphuric acid solution (product code S/9240/PB17, Fisher Scientific) onto a commercial screen-printed graphene-modified carbon electrode (DRP-110GPH, Metrohm UK).…”

Direct monitoring of breast and endometrial cancer cell epigenetic response to DNA methyltransferase and histone deacetylase inhibitors

“…Gold and carbon -based electrode systems remain the most utilized working electrode materials, despite many other materials having been evaluated (Krejcova et al, 2017), and have been used in screen printed formats that offer low cost per unit, and do not require extensive preparation to obtain a pristine surface prior to use. Graphene as a working electrode offers a high signal to noise ratio, and is easily functionalized with antibodies when coated with polyaniline, which also serves a conductive polymer and is used as an additive transducer layer to avoid the introduction of graphene surface defects (Gazze et al, 2018;Teixeira et al, 2014a). Graphene offers a further advantage over gold electrodes for the detection and quantification of DNA as it lacks the inherent absorption properties for unmodified DNA that are displayed by gold surfaces due to affinity interactions (Koo et al, 2015).…”