Owing to its outstanding physical properties, graphene has attracted attention as a promising biosensor material. Field-effect-transistor (FET)-based biosensors are particularly promising because of ...their high sensitivity that is achieved through the high carrier mobility of graphene. However, graphene-FET biosensors have not yet reached widespread practical applications owing to several problems. In this review, the authors focus on graphene-FET biosensors and discuss their advantages, the challenges to their development, and the solutions to the challenges. The problem of Debye screening, in which the surface charges of the detection target are shielded and undetectable, can be solved by using small-molecule receptors and their deformations and by using enzyme reaction products. To address the complexity of sample components and the detection mechanisms of graphene-FET biosensors, the authors outline measures against nonspecific adsorption and the remaining problems related to the detection mechanism itself. The authors also introduce a solution with which the molecular species that can reach the sensor surfaces are limited. Finally, the authors present multifaceted approaches to the sensor surfaces that provide much information to corroborate the results of electrical measurements. The measures and solutions introduced bring us closer to the practical realization of stable biosensors utilizing the superior characteristics of graphene.
Direct laser writing through two‐photon polymerization lithography is used to fabricate 3D nanostructures containing aligned single‐wall carbon nanotubes (SWCNTs). SWCNTs are aligned in the laser ...scanning directions while they are embedded in the structure. The alignment is induced by spatial confinement, volume shrinkage, and the optical gradient force. This method is expected to lead to new applications based on aligned SWCNTs.
We present a method to develop single-wall carbon nanotube (SWCNT)/polymer composites into arbitrary three-dimensional micro/nano structures. Our approach, based on two-photon polymerization ...lithography, allows one to fabricate three-dimensional SWCNT/polymer composites with a minimum spatial resolution of a few hundreds nm. A near-infrared femtosecond pulsed laser beam was focused onto a SWCNT-dispersed photo resin, and the laser light solidified a nanometric volume of the resin. The focus spot was three-dimensionally scanned, resulting in the fabrication of arbitrary shapes of SWCNT/polymer composites. SWCNTs were uniformly distributed throughout the whole structures, even in a few hundreds nm thick nanowires. Furthermore, we also found an intriguing phenomenon that SWCNTs were self-aligned in polymer nanostructures, promising improvements in mechanical and electrical properties. Our method has great potential to open up a wide range of applications such as micro- and nanoelectromechanical systems, micro/nano actuators, sensors, and photonics devices based on CNTs.
Solution-gated graphene field-effect transistors (SG-GFETs) provide an ideal platform for sensing biomolecules owing to their high electron/hole mobilities and 2D nature. However, the transfer curve ...often drifts in an electrolyte solution during measurements, making it difficult to accurately estimate the analyte concentration. One possible reason for this drift is that p-doping of GFETs is gradually countered by cations in the solution, because the cations can permeate into the polymer residue and/or between graphene and SiO2 substrates. Therefore, we propose doping sufficient cations to counter p-doping of GFETs prior to the measurements. For the pre-treatment, GFETs were immersed in a 15 mM sodium chloride aqueous solution for 25 h. The pretreated GFETs showed that the charge neutrality point (CNP) drifted by less than 3 mV during 1 h of measurement in a phosphate buffer, while the non-treated GFETs showed that the CNP was severely drifted by approximately 50 mV, demonstrating a 96% reduction of the drift by the pre-treatment. X-ray photoelectron spectroscopy analysis revealed the accumulation of sodium ions in the GFETs through pre-treatment. Our method is useful for suppressing drift, thus allowing accurate estimation of the target analyte concentration.
Saliva-based biosensors are emerging as viable tools for non-invasive, painless, and easily administered household medical diagnostics. Despite their potential, the complexity of saliva, containing ...various non-target molecules and contaminants, presents significant challenges due to nonspecific interactions with biosensors. This study utilizes surface-charge modulated graphene field-effect transistors (SCM-GFETs) for the detection of C-reactive protein (CRP) in artificial saliva, using portable measurement apparatus. Our findings indicate that SCM-GFETs exhibit nonspecific responses to saliva components. To address this issue, a two-step preprocessing method is implemented: diluting the saliva in phosphate-buffered saline at a 1 : 104 ratio and subsequent membrane filtration. This process significantly reduced nonspecific interactions, enabling CRP detection in saliva samples. These advancements hold promise for enhancing graphene field-effect transistor technology in point-of-care diagnostic devices.
C-reactive protein (CRP) is an important biomarker of infection and inflammation, as CRP is one of the most prominent acute-phase proteins. CRP is usually detected using anti-CRP antibodies (Abs), ...where the intermolecular interactions between CRP and the anti-CRP Ab are largely affected by the pH and ionic strength of environmental solutions. Therefore, it is important to understand the environmental effects of CRP–anti-CRP Ab interactions when designing highly sensitive biosensors. Here, we investigated the efficiency of fluorescently labeled CRP–anti-CRP monoclonal antibody (mAb) interactions at different pHs and ionic strengths. Our results indicate that the affinity was insensitive to pH changes in the range of 5.9 to 8.1, while it was significantly sensitive to ionic strength changes. The binding affinity decreased by 55% at an ionic strength of 1.6 mM, when compared to that under a physiological condition (~150 mM). Based on the isoelectric focusing results, both the labeled CRP and anti-CRP mAb were negatively charged in the studied pH range, which rendered the system insensitive to pH changes, but sensitive to ionic strength changes. The decreased ionic strength led to a significant enhancement of the repulsive force between CRP and the anti-CRP mAb. Although the versality of the findings is not fully studied yet, the results provide insights into designing highly sensitive CRP sensors, especially field-effect transistor-based sensors.
Due to its high carrier mobility, graphene is considered a suitable material for use in field-effect transistors. However, its application to immunosensing of small molecules is still elusive. To ...investigate the potential of graphene field effect transistors (G-FET) as a sensor for small molecules with small or no charge, we applied the open-sandwich immunoassay (OS-IA), which detects low-molecular-weight antigens noncompetitively, to G-FET. Using an antibody variable fragment VL immobilized on graphene and a hyperacidic region of amyloid precursor protein fused to the other variable fragment VH, we successfully detected a small antigen peptide consisting of 7 amino acids (BGP-C7), with a more than 100-fold increase in sensitivity compared with that measured by enzyme-linked OS-IA. Furthermore, we succeeded in detecting BGP-C7 in the presence of human serum with similar sensitivity, suggesting its potential application in clinical diagnostics.
Direct laser writing (DLW) via two-photon polymerization (TPP) has been established as a powerful technique for fabrication and integration of nanoscale components, as it enables the production of ...three dimensional (3D) micro/nano objects. This technique has indeed led to numerous applications, including micro- and nanoelectromechanical systems (MEMS/NEMS), metamaterials, mechanical metamaterials, and photonic crystals. However, as the feature sizes decrease, an urgent demand has emerged to uncover the mechanics of nanosized polymer materials. Here, we fabricate coil spring shaped polymer nanowires using DLW via two-photon polymerization. We find that even the nanocoil springs follow a linear-response against applied forces, following Hooke's law, as revealed by compression tests using an atomic force microscope. Further, the elasticity of the polymer material is found to become significantly greater as the wire radius is decreased from 550 to 350 nm. Polarized Raman spectroscopy measurements show that polymer chains are aligned in nanowires along the axis, which may be responsible for the size dependence. Our findings provide insight into the nanomechanics of polymer materials fabricated by DLW, which leads to further applications based on nanosized polymer materials.
SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such ...mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on three ACE2 glycosylation sites (53, 90 and 322) that are geometrically close to spike binding sites and investigated the effect of their glycosylation pattern on spike affinity. These glycosylation deletions caused distinct site-specific changes in interactions with the spike and acted cooperatively. Of note, the particular interaction profiles were conserved between the SARS-CoV-2 parental virus and the variants of concern (VOCs) Delta and Omicron. Our study provides insights for a better understanding of the importance of ACE2 glycosylation on ACE2/SARS-CoV-2 spike interaction and guidance for further optimization of soluble ACE2 for therapeutic use.
PDF
