Atomically Thin Sensors Set to Transform Electronic Biosensing

A single sheet of atoms may soon do what entire diagnostic laboratories do today: detect disease markers in blood, identify viral variants, track stress hormones in sweat and even monitor blood pressure continuously without a cuff. That is the central promise examined in a new Perspective published in Nature Reviews Electrical Engineering, in which researchers from the University of Massachusetts Amherst, the University of Strasbourg and the University of California Los Angeles take stock of two-dimensional electronic biosensors and lay out what stands between today’s laboratory demonstrations and tomorrow’s clinical and consumer technologies.

The field’s foundation rests on a remarkable class of substances known as two-dimensional materials: crystals that are only one or a few atoms thick yet can span vast lateral areas. Graphene, the honeycomb lattice of carbon atoms that pioneered the field, remains the most famous example, but the modern catalogue is far larger. Hundreds of such materials have already been experimentally validated and thousands more have been theoretically predicted, ranging from transition-metal dichalcogenides such as molybdenum disulfide to hexagonal boron nitride, elemental X-enes, black phosphorus, MXenes and more. Each brings a different combination of electrical, mechanical, geometrical and chemical properties that can be matched to specific sensing tasks.

The technical appeal of these atomically thin channels for biosensing stems from their geometry and their physics. Because every atom in a two-dimensional material lies at the surface, the entire conduction path is exposed to the surrounding environment. When a biomolecule binds to the surface of a transistor built from such a material, it directly perturbs the flow of charge carriers through the channel, shifting the device’s transfer characteristics in a measurable way. This direct coupling between molecular recognition and charge transport is what enables amplification-free, label-free detection at extraordinary sensitivity, in some devices reaching femtomolar detection limits without enzymes, fluorophores or polymerase chain reaction.

Graphene has led the way. Its exceptional carrier mobility, quantum capacitance, mechanical flexibility and chemical stability have produced electrolyte-gated field-effect transistors capable of detecting pH changes, protein adsorption, DNA, viruses and biomarkers in physiological fluids. Antibody-functionalized graphene transistors have detected SARS-CoV-2 directly in clinical nasopharyngeal swabs without amplification, and flexible graphene electronic tattoos have continuously tracked arterial blood pressure and mapped cortical brain activity wirelessly. Operating graphene transistors near the charge neutrality point, where conductivity is at a minimum and low-frequency noise is favorable, maximizes sensitivity and has clarified how ionic Debye screening constrains signal transduction in salt-rich environments such as blood and sweat.

Yet the authors argue that graphene is only the beginning. Transition-metal dichalcogenides offer a distinct trade-off: unlike gapless graphene, their semiconducting bandgaps allow transistor channels to be fully switched off, reducing background current and enabling different operating regimes. Molybdenum disulfide transistors have detected nucleic acids and proteins with femtomolar sensitivity, and the metallic 1T phase of these materials supports fast heterogeneous electron transfer for enzyme-based electrochemical sensing. Phase engineering, in which the atomic arrangement of the material is switched between semiconducting and metallic forms, adds a further design lever. Beyond the dichalcogenides, black phosphorus brings a tunable gap that varies with layer thickness, indium selenide field-effect transistors have rapidly identified SARS-CoV-2 variants, platinum dichalcogenides have yielded reusable ultrathin electronic tattoos, and MXenes contribute metallic conductivity and rich surface chemistry for biosensing composites.

A recurring theme of the Perspective is that in real devices, structural and chemical variability often outweighs intrinsic material properties in determining performance. Defects, grain boundaries, surface terminations, adsorbed contamination and variations in layer thickness all scatter charge carriers, shift the charge neutrality point and introduce noise and hysteresis. Two nominally identical devices can behave quite differently because of fabrication-related differences invisible to the naked eye. The authors contend that further progress will depend on linking biosensing performance more directly to the intrinsic structures and properties of individual materials, so that sensitivity and stability become predictable design outcomes rather than empirical surprises from batch to batch.

Equally decisive is the biofunctionalization strategy, the chemistry that connects the sensor surface to the biological world. Covalent attachment of receptors provides durable immobilization but can degrade the electronic properties of the underlying channel; non-covalent approaches based on pyrene linkers or supramolecular interactions preserve the lattice while anchoring antibodies, aptamers or enzymes, but may be less stable over time. The choice of linker chemistry and receptor controls the sensor’s stability, drift and usable lifetime. Structure-switching aptamers have even allowed small-molecule detection to overcome the Debye length limitation, by transducing binding-induced charge redistribution close to the channel, and wearable aptamer transistors have achieved non-invasive, continuous cortisol monitoring from sweat. Emerging tools such as CRISPR-Cas9 immobilized on graphene transistors, epitope-imprinted surfaces and DNA origami architectures extend molecular selectivity still further.

The authors are candid about the field’s persistent weaknesses. Sensitivity alone is no longer sufficient; devices must also deliver selectivity against interfering species, reproducibility across laboratories, minimal baseline drift during long-term operation and stable performance under physiological conditions, including high ionic strength, temperature and protein-rich media. Noise sources such as charge traps and adsorbed water, hysteresis in transfer characteristics and gradual surface fouling all degrade real-world reliability. The diversity of two-dimensional materials complicates comparison, since results obtained on different materials, geometries and test protocols cannot be directly juxtaposed. The Perspective therefore calls for standardized benchmarks and testing workflows as a central requirement for comparing biosensing performance across materials, devices and laboratories, a step the authors regard as essential for the field’s credibility and maturation.

Biocompatibility and scalability round out the remaining challenges. Graphene and several other two-dimensional materials have shown encouraging compatibility with neurons and other cells, with purified neurons surviving on peptide-free graphene layers and graphene-based interfaces leaving target nerve cells unaltered, but toxicity depends strongly on material type, surface reactivity, dose and impurities, and other families such as graphene oxide or certain MXenes require careful assessment. Meanwhile, translating atomically thin sensors from individual hand-built devices to manufacturable technology demands wafer-scale growth, clean transfer processes and quality control, areas where machine learning is increasingly being deployed to optimize fabrication, screen candidate materials and even interpret complex chemical sensor arrays. Technology readiness levels differ widely across applications, with wearable and environmental sensing nearer to market and implantable diagnostics further behind.

If those obstacles can be cleared, the destination is compelling: flexible, portable point-of-care devices and conformal wearables that support continuous health monitoring and feed the Internet of Medical Things, an interconnected ecosystem of bioelectronic devices that collect, transmit and intelligently analyze health data at population scale. The authors frame the moment as a critical inflection point. The sensitivity problem has largely been solved; the selectivity, stability and reproducibility problems are now the frontier. By matching the unique properties of specific two-dimensional materials to specific sensing functions, and by grounding device design in material physics rather than empirical trial and error, the field aims to convert two decades of laboratory brilliance into reliable translational sensing technologies that patients and consumers can actually depend on.

Some of the physical underpinnings of these sensors deserve closer attention. In an electrolyte-gated configuration, the physiological liquid itself acts as the gate, so the electric double layer that forms at the material surface can capacitively modulate the channel with exceptional efficiency. This liquid gating, combined with the sizable quantum capacitance of graphene, means that even minute surface charge changes from adsorbed proteins or nucleic acids produce measurable shifts in device characteristics. At the same time, the ultimate detection floor is set by noise: low-frequency 1/f noise and charge fluctuations from trapped impurities and adsorbed water often dominate the signal, which is why operating points, electrolyte composition and surface cleanliness matter as much as the receptor chemistry itself.

The mechanical and chemical robustness of atomically thin films also underpins their wearable ambitions. Monolayer graphene can endure extreme bending and repeated tension-compression cycles without fracture, remains nearly transparent to visible light, and even acts as a corrosion-inhibiting coating on underlying metals. These attributes allow conformal patches to follow skin topology during motion while maintaining stable electrical contact, a prerequisite for long-term bioimpedance and electrophysiological recordings. Graphene multielectrode arrays have likewise served as versatile tools for extracellular measurements, and graphene oxide electrodes have been shown to elicit distinct calcium signaling in brain astrocytes, illustrating how material form and surface chemistry shape biological response.

Finally, the sheer breadth of the two-dimensional catalogue, documented in comprehensive material atlases, suggests that many sensing niches remain unclaimed. Systematic pairing of bandgap, phase, defect density and surface termination with a given analyte and operating environment offers a rational path forward, provided that cross-laboratory benchmarking becomes routine practice.

Subject of Research: Two-dimensional electronic biosensors based on graphene and related atomically thin materials

Article Title: Engineering two-dimensional electronic biosensors

Article References: Hasan, M. M., Bao, H., Montes-García, V., Zhang, Y., Ping, J., Samorì, P., Duan, X., & Kireev, D. (2026). Engineering two-dimensional electronic biosensors. Nature Reviews Electrical Engineering. https://doi.org/10.1038/s44287-026-00326-2

Image Credits: AI Generated

DOI: 10.1038/s44287-026-00326-2

Keywords: two-dimensional materials, graphene, biosensors, field-effect transistors, transition metal dichalcogenides, biofunctionalization, wearable biosensors, point-of-care diagnostics, Internet of Medical Things, sensor selectivity, sensor drift, MXenes