Li Gao

Two-dimensional-material-based FET biosensors have gained attention for being label-free and having ultra-sensitive detection capability. The high carrier mobility and large surface-to-volume ratio of 2D materials enable low detection limits under buffer conditions; however, practical detection still faces many challenges. Current reviews have largely summarized materials, functionalization routes, or target classes separately, but a clearer framework linking interface design, device architecture, and practical sensing performance is still needed. In this review, we examine how interfacial engineering and device architecture govern signal transduction and sensing behavior in 2D material FET biosensors. We also analyze the major barriers to real-sample detection, including Debye screening, nonspecific adsorption, and signal drift, together with commonly used mitigation strategies. On this basis, an “interface–device–performance” framework is discussed as a conceptual approach for understanding the relationship between molecular recognition, electrical response, and sensing performance. This review mainly focuses on the key challenges of 2D material FET biosensors in practical medical applications, discusses the differences between material and application perspectives, and examines the major factors limiting clinical translation.

Mercury ions (Hg²⁺) are highly toxic and pose severe risks to human health and ecosystems, necessitating sensitive detection methods for environmental monitoring. Here, we report a paper-based graphene sensor functionalized with single-stranded DNA (ssDNA) probes for Hg²⁺ detection based on T-Hg²⁺-T coordination chemistry. To elucidate the effect of probe structure on sensing performance, we designed DNA constructs with varying numbers of guanine (G) bases (3–6, designated DNA2–DNA5) in the bridging fragment and systematically evaluated their influence on hairpin stability, Hg²⁺ binding affinity, and sensor response. The DNA3-based sensor (four G bases) exhibited optimal electronic stability and sensitivity, achieving a detection limit of 0.673 pM with effective real-time monitoring capability in aqueous media. These findings highlight the critical role of DNA sequence design in T-Hg²⁺-T-based biosensors and provide a promising strategy for sensitive and selective Hg²⁺ detection in environmental samples.

Pancreatic function tests are used to determine the presence of chronic pancreatitis, particularly in the early stage of the disease. Chymotrypsin is an indicator of pancreatic function and is thus related to pancreatic diseases. However, these methods often require specific equipment and cannot always meet on-site analysis requirements. Consequently, a highly sensitive detection method needs to be developed. This research employed graphene oxide modified with NHS sensors and peptides (RRHFFGC: Arginine-Arginine-Histidine-Phenylalanine-Phenylalanine-Glycine-Cysteine) tagged with gold nanoclusters (Au NCs) for the detection of chymotrypsin. The N-Hydroxysuccinimide-(Polyethylene Glycol)₄-Dibenzocyclooctyne (NHS-PEG₄-DBCO) and graphene oxide (GO)-N₃ click reaction yielded GO-NHS material, appropriate for fluorescence quenching. The peptide chain was accurately broken with the introduction of chymotrypsin, and the Au NCs were situated far from the GO-NHS surface. The detection limit was 2.014 pg/mL. The results showed that the detection method had high sensitivity in comparison with the previous studies. This method is relevant to real samples due to its potential efficacy. Therefore, it is a promising method in the biomedical field.

To enhance the sensitivity of graphene-DNA sensors for Hg²⁺ detection, a novel graphene nanoribbon-DNA sensor was fabricated using a template-assisted approach. Silicon nanowires served as templates to decorate the graphene device, followed by plasma etching to delineate graphene nanoribbons. After template removal, the resulting sensors based on silicon nanowire templates were successfully constructed. DNA sequences containing four guanine bases were conjugated with graphene sensors prepared using the templates. The carboxyl groups on the edges of the graphene nanoribbons were activated with EDC/NHS chemistry to facilitate covalent bonding with amino-modified DNA. The kinetic response and Hg²⁺ detection capability of the fabricated sensors were characterized using a semiconductor parameter analyzer. Results indicated that the silicon nanowire-templated graphene nanoribbon sensor exhibited high sensitivity, with a detection limit of 3.62 pM. This innovative approach further improved the sensitivity of graphene-DNA sensors for Hg²⁺ detection.

In recent years, the amount of mercury discharged by human activities has continued to increase. Most of the mercury in surface water settles into the sediment, where it can be directly or indirectly transformed into mercury ion (Hg²⁺) compounds (such as dimethylmercury) under the action of microorganisms. Hg²⁺ display high toxicity and bioaccumulation in food, such as fish and rice, and thus the contamination of mercury ion is a serious concern for human health. Practical Hg²⁺ detection methods are usually limited by the sensitivity and selectivity of the used methods, such as colorimetric determination and fluorescence biosensor based on the solution phase. Therefore, it is urgent to develop Hg²⁺ detection methods in the practical environment with high sensitivity and selectivity. DNA is low-cost, relatively stable, and has been used for different fields. In this study, DNA for Hg²⁺detection was absorbed on the surface of single-walled carbon nanotubes (SWNTs) by using 1,5-diaminonaphthalene (DAN) based on field-effect transistor (FET) biosensors. The interaction between DNA and Hg²⁺ can be directly converted into electrical signals based on the SWNTs biosensors. The experimental results showed that the limit of detection (LOD) of Hg²⁺ without the phase-locked amplifier was about 42.6 pM. The function of the phase-locked amplifier is to achieve fast detection of the biosensor with strong anti-noise ability. Intriguingly, the sensitivity of the biosensor combined with a phase-locked amplifier to detect Hg²⁺ was further improved to be 5.14 pM compared with some current methods of biosensors. Furthermore, this biosensor has an excellent selectivity and practical detection in tap water, which demonstrates its high performance and low cost in practical application in Hg²⁺ detection. These results show this method for Hg²⁺ detection using SWNTs biosensors with a phase-locked amplifier is promising.

Ecosystem pollution by mercury ions (Hg²⁺) is a major health concern, yet classical analytical methods for mercury analysis are limited. This paper reviews the advances in Hg²⁺ detection using DNA as recognition elements in the sensors. DNA as a recognition molecule is inexpensive, simple, and appropriate for real-time detection of Hg²⁺. This paper discusses the DNA-based sensors that were used for the detection of Hg²⁺. These can be carried out by electrochemistry, field effect transistors (FET), Raman spectroscopy, colorimetry, and fluorescence resonance energy transfer (FRET). The detection principles and the advantages of DNA in these sensors are also revealed. Finally, the paper provides an overview of prospects and potential challenges in the field.

Alpha-fetoprotein (AFP) is a crucial biomarker for detecting certain tumors across various demographics, including men, non-pregnant women, and children. However, existing detection methods often lack the desired sensitivity, necessitating the development of a straightforward, dependable, and highly sensitive AFP detection method. In this study, a novel approach utilizing a sandwich sensor system designed around the GDYO@AuNPs@PCN (graphdiyne oxide, gold nanoparticle, and porous coordination network) composite was proposed. The results revealed that this composite material, comprising three key components, offers superior quenching capabilities and heightened sensitivity to AFP compared to DNA sensors employing different nanomaterials. Leveraging the distinctive advantages and properties of the composite material, a “three in one” structure was devised by integrating two aptamers with AFP to form an efficient “sandwich” configuration for AFP capture. Additionally, the inclusion of antifouling peptides in the system effectively mitigates non-specific adsorption of AFP on the sensing interface, ensuring a high signal-to-noise ratio. Notably, the sandwich sensor employing the “three in one” composite with peptides achieves a limit of detection (LOD) of 1.51 pg mL⁻¹, indicative of its ability to reduce background signals, facilitate efficient AFP binding, and enhance sensitivity. Furthermore, the sensor exhibited promising performance and demonstrated consistent results in serum samples, emphasizing its promising practical applications.