Proteins play essential roles in virtually all cellular functions, and accurate profiling of the cellular proteome is critical for understanding biological processes and diagnosing diseases. However, current protein identification methods often lack the sensitivity required to reliably detect low-abundance proteins such as signaling molecules or early-stage biomarkers. Over the past decade, highly sensitive single-molecule protein identification methods, referred to as single-molecule protein sequencing, have been proposed, mainly those based on nanopore and fluorescence techniques. Yet, a fully developed method capable of identifying full-length proteins has not been realized. This Progress Report highlights recent developments in single-molecule protein identification methods using nanomechanical approaches that leverage 2D materials for label-free mass detection. We discuss strategies to enhance nanoelectromechanical resonators for precise mass measurements of single protein molecules and outline the prospects and remaining challenges of protein identification using 2D material-based nanodevices.

Ultrasensitive mass detection is essential across various fields, including environmental monitoring, biosensing, and medical diagnostics. Quartz crystal microbalance (QCM) and nanoelectromechanical system (NEMS) sensors are widely utilized, yet NEMS approaches are hindered by issues of stability and reproducibility, whereas QCMs face fundamental physical limitations in enhancing sensitivity. To address the limitations of current sensing technologies, we demonstrate that increasing the driving force applied to the QCM induces non-linear resonance, and that utilizing the abrupt amplitude drop occurring at this non-linear resonance enables mass detection down to 100 fg. Unlike conventional linear QCM operation, our method significantly enhances mass sensitivity by exploiting amplitude-drop behavior in the non-linear regime, without requiring additional surface functionalization or device modification. We validated this sensing strategy through the detection of micro/nanoparticles and protein-antibody interactions, successfully achieving single micro/nanoparticle detection and reaching a detection limit of 100 fg. Notably, this method enables reliable single micro/nanoparticle detection with high reproducibility. This sensing approach provides a simple yet powerful platform that overcomes key limitations of traditional QCM systems. With the potential for real-time biomolecular diagnostics in aqueous environments and future integration with microfluidic chips, our approach represents a promising strategy for ultra-sensitive mass detection.

Fluorescence imaging is an invaluable tool to investigate biomolecular dynamics, mechanics, and interactions in aqueous environments. Two-dimensional materials offer large-area, atomically smooth surfaces for wide-field biomolecule imaging. Despite the success of graphene for on-chip biosensing and biomolecule manipulation, its strong fluorescence-quenching properties pose a challenge for biomolecular investigations that are based on direct optical readouts. Here, we employ few-layer hexagonal boron nitride (hBN) as a precisely tailorable fluorescence spacer between labelled lipid membranes and graphene substrates. By stacking high-quality hBN crystals in the 10–20 nm thickness range on monolayer graphene, we observe distance-dependent fluorescence intensity variations. Remarkably, with hBN spacers as thin as 20 nm, the fluorescence intensity is comparable to bare SiO₂/Si substrates, while the intensity was reduced to 60 % and 80 % with ~10 nm and ~16 nm hBN thicknesses respectively. We confirm that pre-determined hBN thicknesses can be employed to control the non-radiative energy transfer properties of graphene, with fluorescence quenching following a d⁻⁴ distance-dependent behaviour. This seamless integration of electronically active and dielectric van der Waals materials into vertical heterostructures enables multifunctional platforms addressing the manipulation, localization, and visualization of biomolecules for fundamental biophysics and biosensing applications.

The inherent properties of 2D materials—light mass, high out-of-plane flexibility, and large surface area—promise great potential for precise and accurate nanomechanical mass sensing, but their application is often hampered by surface contamination. Here we demonstrate a tri-layer graphene nanomechanical resonant mass sensor with sub-attogram resolution at room temperature, fabricated by a bottom-up process. We found that Joule-heating is effective in cleaning the graphene membrane surface, which results in a large improvement in the stability of the resonance frequency. We characterized the sensor by depositing Cr metal using a stencil mask and found a mass-resolution that is sufficient to weigh very small particles, like large proteins and protein complexes, with potential applications in the fields of nanobiology and medicine.

Magnetostrictive coupling has recently attracted interest as a sensitive method for studying magnetism in two-dimensional (2D) materials by mechanical means. However, its application in high-frequency magnetic actuators and transducers requires rapid modulation of the magnetic order, which is difficult to achieve with external magnets, especially when dealing with antiferromagnets. Here, we optothermally modulate the magnetization in antiferromagnetic 2D material membranes of metal phosphor trisulfides (MPS₃), to induce a large high-frequency magnetostrictive driving force. From the analysis of the temperature-dependent resonance amplitude, we provide evidence that the force is due to a thermo-magnetostrictive effect, which significantly increases near the Neél temperature, due to the strong temperature dependence of the magnetization. By studying its angle dependence, we find the effect is observed to follow anisotropic magnetostriction of the crystal lattice. The results show that the thermo-magnetostrictive effect results in a strongly enhanced thermal expansion force near the critical temperature of magnetostrictive 2D materials, which can enable more efficient actuation of nano-magnetomechanical devices and can also provide a route for studying the high-frequency coupling among magnetic, mechanical, and thermodynamic degrees of freedom down to the 2D limit.

The electrical properties of a single facet of an individual ZnO microwire were investigated. Electrode patterns with a Hall bar structure were deposited on the surface of the top facet of the ZnO microwire. Using a suspended and cross-linked poly(methyl methacrylate) ribbon structure, it was possible to define the electrical connections only at the top surface, while avoiding those on the other five sides of the ZnO microwire. Current-voltage characteristics were examined, and Hall measurements were conducted with various magnetic fields. Through our device structure, the electrical properties could be directly probed at specific points on the ZnO surface in a reliable manner. The estimated electrical characteristics demonstrate that the carrier concentration and mobility of the ZnO surface varied along the axial direction of the wire. These results indicate that the charge carrier concentration on the surface of the micro-/nanowire can be sensitively changed according to the synthesis environment. In addition, it is worth noting that the nanoscale local Hall probes, fabricated by our technique, could probe the very slight variation of carrier concentration, which is difficult to detect by a standard transport measurement along the wire.

Although 2D materials hold great potential for next-generation pressure sensors, recent studies revealed that gases permeate along the membrane-surface interface, necessitating additional sealing procedures. In this work, we demonstrate the use of free-standing complex oxides as self-sealing membranes that allow the reference cavity beneath to be sealed by a simple anneal. To test the hermeticity, we study the gas permeation time constants in nanomechanical resonators made from SrRuO3 and SrTiO3 membranes suspended over SiO2/Si cavities which show an improvement up to 4 orders of magnitude in the permeation time constant after annealing the devices. Similar devices fabricated on Si3N4/Si do not show such improvements, suggesting that the adhesion increase over SiO2 is mediated by oxygen bonds that are formed at the SiO2/complex oxide interface during the self-sealing anneal. Picosecond ultrasonics measurements confirm the improvement in the adhesion by 70% after annealing.

In this paper, the effect of boron doping on the electrical, morphological and structural properties of free-standing nanocrystalline diamond sheets (thickness ~ 1 μm) was investigated. For this purpose, we used diamond films delaminated from a mirror-polished tantalum substrate following a microwave plasma-assisted chemical vapor deposition process, each grown with a different [B]/[C] ratio (up to 20,000 ppm) in the gas phase. The developed boron-doped diamond (BDD) films are a promising semiconducting material for sensing and high-power electronic devices due to band gap engineering and thermal management feasibility. The increased boron concentration in the gas phase induces a decrease in the average grain size, consequently resulting in lower surface roughness. The BDD sheets grown with [B]/[C] of 20,000 ppm reveal the metallic conductivity while the lower doped samples show p-type semiconductor character. The charge transport at room temperature is dominated by the thermally activated nearest-neighbor hopping between boron acceptors through impurity band conduction. At low temperatures (<300 K), the Arrhenius plot shows a non-linear temperature dependence of the logarithmic conductance pointing towards a crossover towards variable range hopping. The activation energy at high temperatures obtained for lowly-doped sheets is smaller than for nanocrystalline diamond bonded to silicon, while for highly-doped material it is similar. Developed sheets were utilized to fabricate two types of diamond-on-graphene heterojunctions, where boron doping is the key factor for tuning the shape of the current-voltage characteristics. The graphene heterojunction with the low boron concentration diamond sheet resembles a Schottky junction behavior, while an almost Ohmic contact response is recorded with the highly doped BDD sheet of metallic conductivity. The free-standing diamond sheets allow for integration with temperature-sensitive interfaces (i.e. 2D materials or polymers) and pave the way towards flexible electronics devices.

Nanomechanical resonator devices are widely used as ultrasensitive mass detectors for fundamental studies and practical applications. The resonance frequency of the resonators shifts when a mass is loaded, which is used to estimate the mass. However, the shift signal is often blurred by the thermal noise, which interferes with accurate mass detection. Here, we demonstrate the reduction of the noise interference in mass detection in suspended graphene-based nanomechanical resonators, by using applied machine learning. Featurization is divided into image and sequential datasets, and those datasets are trained and classified using 2D and 1D convolutional neural networks (CNNs). The 2D CNN learning-based classification shows a performance with f1-score over 99% when the resonance frequency shift is more than 2.5% of the amplitude of the thermal noise range.

In this study, high-performance few-layered ReS₂ field-effect transistors (FETs), fabricated with hexagonal boron nitride (h-BN) as top/bottom dual gate dielectrics, are presented. The performance of h-BN dual gated ReS₂ FET having a trade-off of performance parameters is optimized using a compact model from analytical choice maps, which consists of three regions with different electrical characteristics. The bottom h-BN dielectric has almost no defects and provides a physical distance between the traps in the SiO₂ and the carriers in the ReS₂ channel. Using a compact analyzing model and structural advantages, an excellent and optimized performance is introduced consisting of h-BN dual-gated ReS₂ with a high mobility of 46.1 cm² V⁻¹ s⁻¹, a high current on/off ratio of ≈10⁶, a subthreshold swing of 2.7 V dec⁻¹, and a low effective interface trap density (N_t,eff) of 7.85 × 10¹⁰ cm⁻² eV⁻¹ at a small operating voltage (<3 V). These phenomena are demonstrated through not only a fundamental current–voltage analysis, but also technology computer aided design simulations, time-dependent current, and low-frequency noise analysis. In addition, a simple method is introduced to extract the interlayer resistance of ReS₂ channel through Y-function method as a function of constant top gate bias.

Mechanical resonance properties of porous graphene resonators were investigated by simulation studies. The finite element method was utilized to design the porous graphene membrane pattern and to calculate the mechanical resonance frequency and quality factor. The changes in the resonance frequency and quality factor were systematically studied by changing the size, number, and relative location of pores on the graphene membrane. Mass loss and carbon-carbon bond break were found to be the main competing parameters for determining its mechanical resonance properties. The correlation between the geometry and the damping effect on the mechanical resonance of graphene was considered by suggesting a model on the damping factor and by calculating the membrane deflections according to the pore location. Based on the simulation results, an optimal porosity and porous geometry were found that gives the maximum resonance frequency and quality factor. Suspended graphene with various number pore structures was experimentally realized, and their mechanical resonance behaviors were measured. The trend of changes in resonance frequency and quality factor according to the number of pores in the experiment was qualitatively agreed with simulation results.