A novel biosensor based on hafnium oxide: Application for early stage detection of human interleukin-10

Measurement of interleukin-10 (IL-10) has subsequently become a crucial tool to identify end-stage heart failure (ESHF) patients prone to adverse outcomes during the early phase of left ventricular assisted device (LVAD) implantation. In this context, label-free detection using a novel substrate based on hafnium oxide (HfO2) grown by atomic layer deposition (ALD) on silicon was applied. Here, we studied the interaction between recombinant human (rh) IL-10 with the corresponding monoclonal antibody (mAb) for early cytokine detection of an anti-inflammatory response due to LVAD implantation. For this purpose, HfO2 has been functionalized using an aldehyde–silane ((11-(triethoxysilyl) undecanal (TESUD)) self-assembled monolayer (SAMs), to directly immobilize the anti-human IL-10 mAb by covalent bonding. The interaction between the antibody–antigen (Ab–Ag) was characterized by fluorescence patterning and electrochemical impedance spectroscopy (EIS). Confirmation for the bio-recognition of the protein was achieved by fluorescence patterning, while Nyquist plots have shown a stepwise variation due to the polarization resistance (Rp) between the Ab activated surfaces with the detection of the protein. For early expression monitoring, commercial proteins of rh IL-10 were analyzed between 0.1pg/mL and 50ng/mL. Protein concentrations within the linear range of 0.1–20pg/mL were detected, and these values formulated a sensitivity of 0.49(ng/mL)−1. These preliminary results demonstrated that the developed biosensor was sensitive to the detection of rh IL-10, and the measured limit of 0.1pg/mL in phosphate buffered saline (PBS) was clearly detectable, which displays the high sensitivity of EIS. On analysis of an interference attributable to non-specific binding of other cytokine biomarkers; tumor necrosis factor-α (TNF-α) and IL-1β were analyzed without causing an interference to the IL-10 mAb. This established that selective sensitivity was responsive only to rh IL-10. To our knowledge, this is the first biosensor that has been based on HfO2 for Ag detection by EIS. In time, the HfO2 insulator will be incorporated into the gate of silicon-based ion-sensitive field-effect transistors (ISFETs) and developed as a portable real time detection system for the IL family of biomarkers in human serum.