Twisted graphene precisely aligned with gold nanodisks and coupled with CRISPR achieves attomolar detection of cancer biomarkers, revealing a new path for low light molecular diagnostics.
(Nanowerk Spotlight) The search for faster and more sensitive disease diagnostics has drawn together two highly specialized areas of research: advanced materials science and molecular biology. Detecting trace biomolecules such as fragments of genetic material can reveal disease before symptoms appear, but most biosensors still struggle to detect signals at extremely low concentrations.
Optical techniques such as surface plasmon resonance, which measure changes in reflected light when molecules bind to a surface, offer real-time detection without chemical labels, yet they falter when the target molecules are present in very small amounts.
Quantum materials such as twisted bilayer graphene and molecular biology tools such as CRISPR have developed along separate paths, yet research at their intersection is expanding. Collaborative studies in biosensors, bioelectronics, and nanomedicine are beginning to explore how the optical and electronic properties of two-dimensional materials can interact with biological recognition systems. These converging efforts are redefining how molecular information can be translated into physical signals.
In parallel, materials scientists have been exploring how the properties of atomically thin materials can be tuned by rotating stacked layers relative to each other. This field, known as twistronics, has shown that small twist angles can transform ordinary graphene into a structure with remarkable electronic behavior. At specific angles, the overlapping atomic lattices create repeating patterns called moiré superlattices that reshape how electrons and light interact.
Meanwhile, nanophotonics has produced metal nanostructures capable of trapping and intensifying light at scales smaller than a wavelength, and molecular biologists have developed CRISPR enzymes that identify and cut genetic material with great precision. DNA origami, a method for folding DNA strands into controlled shapes, allows engineers to arrange molecules and particles with nanometer accuracy.
These separate advances have now begun to intersect. A study in National Science Review (“Ultrasensitive optoelectronic biosensor arrays based on twisted bilayer graphene superlattice”) describes a device that combines all four technologies into a single platform. The work presents an optoelectronic biosensor that integrates twisted bilayer graphene, formed from two graphene sheets rotated by a small angle, with patterned gold nanodisks and a CRISPR Cas12a detection system attached through DNA origami scaffolds.
The result is a system that turns a specific molecular recognition event into an electrical signal strong enough to detect genetic markers of cancer at attomolar concentrations while operating under faint light.
Construction of the structure. (a) Schematic diagram depicting the heterostructure composed of AuNPs, DNA origami, Au nanodisks and tBLG. (b) Illustration of the principle of exciton−plasmon coupling. (c) Illustration of the principle for miRNA-21 detection using the CRISPR-Cas12a system. (Image: Reprinted from DOI:10.1093/nsr/nwaf357, CC BY) (click on image to enlarge)
The study centers on the precise spectral alignment between the van Hove singularity in twisted bilayer graphene and the plasmonic resonance of patterned gold nanodisks. This alignment enables a form of exciton plasmon coupling that strengthens light–matter interactions and underpins the sensor’s high sensitivity under minimal illumination.
Twisted bilayer graphene lies at the center of this design. When two graphene sheets are rotated slightly out of alignment, their atomic lattices interfere to form a larger repeating pattern. This superlattice changes how electrons move between layers, producing new energy states known as van Hove singularities. These states create spikes in the number of available electronic states at certain energies, making the material absorb light much more strongly at those energies.
The researchers selected a twist angle of 9.4 degrees, which gives a characteristic energy of about 1.84 electron volts, the same as light with a wavelength near 660 nanometers. Aligning the optical system with this resonance ensures the strongest possible response.
To intensify light absorption further, the team placed arrays of gold nanodisks directly on top of the twisted graphene. Gold nanostructures can trap incoming light as collective oscillations of electrons called plasmons, concentrating electromagnetic energy in small regions known as hot spots. When the resonance of these nanodisks matches the absorption band of the underlying graphene, the two effects reinforce one another.
By carefully tuning the twist angle to 9.4 degrees, the researchers aligned the energy of the van Hove singularity with the plasmonic resonance peak of the gold nanodisks. This deliberate spectral match created a highly efficient exciton plasmon coupling that amplified the device’s response to light.
Measurements confirm this synergy. The combined structure reaches a photoresponsivity of 14.64 milliamperes per watt, which is about six times higher than that of the same graphene without gold nanodisks. It also achieves an external quantum efficiency of 27.51 percent, meaning that more than a quarter of incoming photons are converted into measurable current. Importantly, all this occurs under a light intensity of only 60 microwatts, far below the levels typically required for such devices.
The study also explores the timing of these light-induced processes. Using ultrafast spectroscopy, the researchers observed that carriers in pure twisted graphene relax within about 1.14 picoseconds after excitation. When coupled with gold nanodisks, the relaxation accelerates to roughly 0.37 picoseconds while the total current increases significantly. This suggests that the nanodisks not only enhance the optical field but also provide faster pathways for carriers to reach the electrodes.
Control over the twist angle turns out to be crucial. Devices fabricated at several angles show that only the 9.4 degree structure aligns perfectly with the chosen light energy, producing the largest and most easily tuned photocurrent. The data indicate that this particular angle yields a high in-plane dielectric constant, which is a measure of how the material responds to electric fields, allowing stronger confinement of the optical and electrical fields where they are most effective.
The biological sensing function is built upon this physical foundation. The researchers linked the optical component to a programmable molecular system based on the CRISPR Cas12a enzyme. Cas12a uses a short guide sequence of RNA to find a matching stretch of DNA or RNA. Once it binds to the correct target, it cuts not only that sequence but also nearby single-stranded DNA. This secondary cutting activity, called trans cleavage, provides a way to translate target recognition into a structural change at the sensor surface.
To harness this property, the team used DNA origami to attach small gold nanoparticles to the nanodisk array at controlled heights and spacing. In the resting state, these nanoparticles disrupt the optical coupling between the gold nanodisks and the twisted graphene, reducing the device’s response to light.
When the target genetic sequence, such as microRNA 21 which is linked to several cancers, is present, the Cas12a enzyme cuts the DNA linkers holding the nanoparticles in place. The particles are released, restoring the optical resonance and allowing light to pass and generate a stronger current. This reversible shift in coupling becomes the measurable signal that indicates the presence of the target molecule.
Spectral measurements show how the absorption band moves depending on whether the nanoparticles are attached or removed. Before cleavage, the resonance peak shifts toward longer wavelengths and its intensity decreases; after cleavage, it returns to its original position and regains intensity. This shift directly reflects the change in the local dielectric environment created by the biochemical reaction.
The team tested the system across concentrations of target DNA ranging from 100 picomolar to 10 attomolar. They measured the change in current after each reaction stage and calculated a limit of detection of 44.63 attomolar using standard statistical methods. The entire assay took less than an hour and required no external amplification such as polymerase chain reaction.
Tests with real plasma samples from lung cancer patients showed results that closely matched those obtained by quantitative PCR, the clinical standard for measuring nucleic acids. Additional fluorescence assays demonstrated that the sensor could distinguish between perfectly matching and mismatched sequences differing by only one base, confirming its high specificity.
Because the electrical output directly tracks molecular recognition, the device bridges the gap between optical and electronic sensing. It captures the benefits of plasmonic light concentration but translates the signal into a simple current that can be read with basic electronics. Operating at low optical power reduces heating and photodamage, which can otherwise distort biological samples.
The fixed geometry provided by DNA origami makes each sensing site nearly identical, improving reproducibility across tests. The system also retained its performance after storage in physiological solutions, pointing to stable interfaces between the nanomaterials and the biomolecular components.
The underlying principles are flexible. The CRISPR enzyme can be reprogrammed with new guide sequences to recognize different targets, while the DNA origami scaffold can be redesigned to host other functional groups. This modularity suggests that the same architecture could be used for detecting many kinds of nucleic acids and possibly extended to proteins or other biomolecules by changing the surface chemistry.
The work originates from Professor Zhang’s research group at Shenzhen University, which focuses on advanced materials, nanophotonics, and low-dimensional systems. The team has contributed to several notable studies in optoelectronic devices and materials science. This National Science Review study demonstrates how careful engineering at the atomic and nanoscale can solve practical sensing problems.
By matching the optical resonances of twisted graphene and gold nanostructures and linking them to a programmable molecular switch, the researchers turned subtle quantum-scale effects into a tool for clinical diagnostics. The data show a clear relation between twist angle, light absorption, and electrical response, confirming that precise geometric control can deliver measurable gains in sensitivity.
The integration of twistronics, plasmonics, and CRISPR chemistry points toward devices that could one day provide rapid, label-free tests for disease biomarkers using minimal light and power. Such systems would not replace established laboratory methods immediately, but they could expand the reach of precision diagnostics to settings where simplicity and speed matter most. The study provides strong experimental evidence that physical control over two-dimensional materials and biological specificity can coexist in a single, scalable design.
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