Interfacing aptamers, nanoparticles and graphene in a hierarchical structure for highly selective detection of biomolecules in OECT devices

Abstract

In several biomedical applications, the detection of biomarkers demands high sensitivity, selectivity and easy-to-use devices. Organic electrochemical transistors (OECTs) represent a promising class of devices combining a minimal invasiveness and good signal transduction. However, OECTs lack of intrinsic selectivity that should be implemented by specific approaches to make them well suitable for biomedical applications. Here, we report on a biosensor in which selectivity and a high sensitivity are achieved by interfacing, in an OECT architecture, a novel gate electrode based on aptamers, Au nanoparticles and graphene hierarchically organized to optimize the final response. The fabricated biosensor performs state of the art limit of detection monitoring biomolecules, such as thrombin-with a limit of detection in the picomolar range (≤ 5 pM) and a very good selectivity even in presence of supraphysiological concentrations of Bovine Serum Albumin (BSA-1mM). These accomplishments are the final result of the gate hierarchic structure that reduces sterich indrance that could contrast the recognition events and minimizes false positive, because of the low affinity of graphene towards the physiological environment. Since our approach can be easily applied to a large variety of different biomarkers, we envisage a relevant potential for a large series of different biomedical applications.

Figure 1

(A) layout of the PMLG gated OECT; (B) related $I_{\mathit{ds}}$—$I_0$ versus $V_{\mathit{ds}}$ (from 0 to − 0.6 V) recorded using PBS 10 mM as electrolyte (here, $I_0$ is the current measured at $V_{\mathit{ds}}=0$ V) and fixing $V_{\mathit{gs}}$ in the range − 0.2 to 0.8 V, step 0.1 V, for each curve; (c) PMLG OECT’s transfer characteristics obtained at $V_{\mathit{ds}}=-0.25$ V for different types of gate electrodes and (D) related gate currents (Ag wire -black line, Au wire—red line and PMLG sheet—blue line). The inset of (C) shows a magnification of PMLG response.

Figure 2

(A) comparison between the transfer curves for the different gate electrodes (i.e. unfolded TBA15-functionalized AuNPs-PMLG gate electrode (concentration 1 μM—green lines), bare PMLG (red lines) and AuNPs-PMLG (black lines)) and (B) related gate currents. Relative peaks are indicated with (2) for the AuNPs-PMLG and (3) for TBA15-functionalized AuNPs-PMLG gate electrode; (C) Optimization of the $I_{\mathit{apt}}-I_{\mathit{blank}}$ parameter as a function of the aptamer concentration (fitting curve:Langmuir isotherm,red line); (D) C1s core level XPS analysis of PMLG/AuNPs/TBA-15. Single components are described in the legend.

Figure 3

(A) comparison between typical transfer curves obtained for thrombin-incubated and non-incubated gate electrodes (TBA15-functionalized AuNPs-PMLG, blue line; unfolded TBA15-functionalized AuNPs-PMLG, concentration 1 μM -green line; bare PMLG, red line, and AuNPs-PMLG, black line. In the inset: proposed detection method) and (B) related gate currents. Relative peaks are indicated with (2) for the AuNPs-PMLG, (3) for TBA15-functionalized AuNPs-PMLG and (4) for TBA15-functonalized AuNPs-PMLG gate electrode; (C) typical device response to different concentrations of thrombin ($C_{\mathit{Thr}}$) described by introducing the $\mathrm{\Delta }ratio$ parameter; (D) selectivity test: the signal recorded in the presence of higher concentration of BSA (1 mM) is compared with the one obtained in presence of very low thrombin concentration (100 pM).