Label-Free Ultrasensitive Memristive Aptasensor

Abstract

We present the very first worldwide ever-reported electrochemical biosensor based on a memristive effect and DNA aptamers. This novel device is developed to propose a completely new approach in cancer diagnostics. In this study, an affinity-based technique is presented for the detection of the prostate specific antigen (PSA) using DNA aptamers. The hysteretic properties of memristive silicon nanowires functionalized with these DNA aptamers provide a label-free and ultrasensitive biodetection technique. The ultrasensitive detection is hereby demonstrated for PSA with a limit of detection down to 23 aM, best ever published value for electrochemical biosensors in PSA detection. The effect of polyelectrolytes on our memristive devices is also reported to further show how positive or negative charges affect the memristive hysteresis. With such an approach, combining memristive nanowires and aptamers, memristive aptamer-based biosensors can be proposed to detect a wide range of cancer markers with unprecedent ultrasensitivities to also address the issue of an early detection of cancer.

Recent Developments and Perspectives for Memristive Devices Based on Metal Oxide Nanowires

“…[295][296][297][298][299] By considering metal-oxide NWs, in 2017 Zhang et al [178] exploited the resistive switching properties of ZnO NWs for the realization of gas sensors with high selectivity and improved recovery speed. Recently, it was shown that the memristive properties of suspended Si NWs realized by a top down approach can be strongly modulated by the presence of biomolecules, making possible the realization of highly sensitive biosensors.…”

Hybrid Silicon Nanowire Devices and Their Functional Diversity

“…Aptamers, for example, are small molecules with either nucleic acid or peptide structure that bind specific ligands, created by an in vitro affinity selection among a large amount of random sequences. [170] Due to their size advantage, there is an increasing interest on them in the FET community, as demonstrated by the large amount of ultrasensitive silicon nanowire-based aptasensors developed during the last years for detection of neuronal potassium ion efflux [57] (Figure 10b), dopamine [171] (Figure 10c), thrombin, [52] PSA, [172] and antivascular endothelial growth factor (VEGF) [173] among others. [170] Due to their size advantage, there is an increasing interest on them in the FET community, as demonstrated by the large amount of ultrasensitive silicon nanowire-based aptasensors developed during the last years for detection of neuronal potassium ion efflux [57] (Figure 10b), dopamine [171] (Figure 10c), thrombin, [52] PSA, [172] and antivascular endothelial growth factor (VEGF) [173] among others.…”

“…Graph shows the real-time measurement where stimulation with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) is followed by K + efflux, while 6,7-dinitroquinoxaline-2,3-dione (DNQX) blocking brings the absence of response upon repeated AMPA stimulation. [172] However, measuring in dry can be irregular, unstable, and with higher variations than measuring directly in a liquid sample using controlled potentials via reference electrode. [57] Copyright 2017, ACS Publications.…”

“…[172] The use of AC excitation to measure beyond the Debye length with FETs was first proposed by Kulkarni and Zhong using carbon nanotube FETs. In the works published by Carrara's group, the binding of molecules at such low concentrations was also confirmed by impedance measurements under alternating current (AC) excitation, which demonstrates that impedance measurements using FETs are valid for ultrasensitive detection.…”

“…Threshold voltage shift 100 × 10 −15 m (10-mer DNA, analog of breast cancer miRNA) [111] Conductance change 1 × 10 −15 m (25-mer Influenza DNA) [159] Memristor (voltage minima gap) 23 × 10 −18 m (prostate-specific antigen) [172] Impedance 33 × 10 −18 m (prostate-specific antigen) [172] Gating hysteresis 20 × 10 −6 m (α-thrombin) [37] Dielectric constant change 20 µg/mL (anti-Avian Influenza antibody) [187] © [190] The CMOS circuitry comprised a sigma-delta modulator and a currentto-frequency converter connected to individual nanowires allowing us to measure up to 16 simultaneous sensors in real time. Later this group demonstrated [188] a monolithic integration of an array of FETs onto a CMOS chip with the readout circuit on the same substrate and conducted cardiac troponin T for ten nanowires.…”