An Oligonucleotide‐Distortion‐Responsive Organic Transistor for Platinum‐Drug‐Induced DNA‐Damage Detection

Abstract

Organic transistor with DNA‐damage evaluation ability can open up novel opportunities for bioelectronic devices. Even though trace amounts of drugs can cause cumulative gene damage in vivo, the extremely low occurrence proportion makes them hardly transduced into detectable electric signals. Here, an ultrasensitive DNA‐damage sensor based on an oligonucleotide‐distortion‐responsive organic transistor (DROT) is reported by creating controllable conformation change of double‐stranded DNA on the surface of organic semiconductors. In combination with interfacial charge redistribution and efficient signal amplification, the DROT provides an ultrasensitive single‐site DNA‐damage response with 20.5 s even upon 1 × 10−12 m cisplatin. The high generalizability of this DROT to three generations of classical platinum drugs and gene‐relevant DNA damage is demonstrated. A biochip is further designed for intelligent damage analysis in complex environments, which holds the potential for high‐throughput biotoxicity evaluation and drug screening in the future.

Natural Material Inspired Organic Thin-Film Transistors for Biosensing: Properties and Applications

“…(f) Represent signal response of organic transistor with and without oligonucleotide DNA receptor as a function of cisplatin concentration. Reprinted from ref . Copyright 2021 John Wiley and Sons.…”

“…When the natural materials with functional groups are adopted as reaction units in OTFTs, outstanding selectivity can be realized due to the formation of chemically active bonds. On the basis of the coordinate bonds between guanine and cisplatin, Di et al reported an oligonucleotide-distortion-responsive organic transistor and realized ultrasensitive single-site DNA damage detection (Figure e,f) . Even when triggered by pM cisplatin, a current response was successfully achieved with a short response time of 20.5 s.…”

“…In this case, physical/chemical binding interactions with the analytes occur in the semiconductor layer, resulting in enhanced sensitivity and selectivity. The biosensors inspired by natural materials, employing this strategy, are evaluated from small molecules to biomacromolecules. ,,,, On the basis of this mechanism, Bao et al reported a series of OTFT-based biosensing systems for use in environmental and healthcare monitoring. They grafted DNA aptamers on the OSC surface and realized selective Hg 2+ detection in seawater with a detection limit of 100 pM thrombin protein in situ. , Compared to the interface engineering at the surface of the semiconductor or gate electrode, there are limited reports on grafting natural materials on source-drain electrodes and the dielectric layer (Figure c,d).…”

“…The other method is the creation of binding sites on the surface of the active layer, followed by covalently immobilizing receptors. Maleic anhydride (ppMa), a 1,6-hexanedithiol (HDT) self-assembled monolayer, and Au nanoparticles have been proposed for the covalent attachment of different receptors for sensitive detection of biomolecules. ,, Later, an in situ plasma-assisted-interfacial-grafting method was developed by Di and Zhu et al, which offered an excellent approach for the induction of functional groups on the OSCs layer without damaging the carrier transport . With this method, the author successfully grafted a molecular antenna with apyrase onto the semiconductor layer and realized excellent sensitivity and selectivity.…”

A sensitive platform for DNA detection based on organic electrochemical transistor and nucleic acid self-assembly signal amplification

“…DNA amplification can provide an alternative way to resolve the above issue. 20–22 So far, a variety of signal amplification strategies have been established, such as rolling circle amplification (RCA), 23 loop-mediated amplification 24 and hybridization chain reaction (HCR). 25,26 Among these methods, HCR-based nucleic acid self-assembly signal amplification, a type of toehold mediated strand displacement reaction, has attracted enormous attention due to its simple operation and excellent amplification efficiency.…”