On-chip integrated graphene aptasensor with portable readout for fast and label-free COVID-19 detection in virus transport medium.

Graphene field-effect transistor (GFET) biosensors exhibit high sensitivity due to a large surface-to-volume ratio and the high sensitivity of the Fermi level to the presence of charged biomolecules near the surface. For most reported GFET biosensors, bulky external reference electrodes are used which prevent their full-scale chip integration and contribute to higher costs per test. In this study, GFET arrays with on-chip integrated liquid electrodes were employed for COVID-19 detection and functionalized with either antibody or aptamer to selectively bind the spike proteins of SARS-CoV-2. In the case of the aptamer-functionalized GFET (aptasensor, Apt-GFET), the limit-of-detection (LOD) achieved was about 103 particles per mL for virus-like particles (VLPs) in clinical transport medium, outperforming the Ab-GFET biosensor counterpart. In addition, the aptasensor achieved a LOD of 160 aM for COVID-19 neutralizing antibodies in serum. The sensors were found to be highly selective, fast (sample-to-result within minutes), and stable (low device-to-device signal variation; relative standard deviations below 0.5%). A home-built portable readout electronic unit was employed for simultaneous real-time measurements of 12 GFETs per chip. Our successful demonstration of a portable GFET biosensing platform has high potential for infectious disease detection and other health-care applications.

Enhancing Structural Properties and Performance of Graphene-Based Devices Using Self-Assembled HMDS Monolayers.

The performance of graphene devices is often limited by defects and impurities induced during device fabrication. Polymer residue left on the surface of graphene after photoresist processing can increase electron scattering and hinder electron transport. Furthermore, exposing graphene to plasma-based processing such as sputtering of metallization layers can increase the defect density in graphene and alter the device performance. Therefore, the preservation of the high-quality surface of graphene during thin-film deposition and device manufacturing is essential for many electronic applications. Here, we show that the use of self-assembled monolayers (SAMs) of hexamethyldisilazane (HMDS) as a buffer layer during the device fabrication of graphene can significantly reduce damage, improve the quality of graphene, and enhance device performance. The role of HMDS has been systematically investigated using surface analysis techniques and electrical measurements. The benefits of HMDS treatment include a significant reduction in defect density compared with as-treated graphene and more than a 2-fold reduction of contact resistance. This surface treatment is simple and offers a practical route for improving graphene device interfaces, which is important for the integration of graphene into functional devices such as electronics and sensor devices.

Carbon-Dot-Enhanced Graphene Field-Effect Transistors for Ultrasensitive Detection of Exosomes.

Graphene field-effect transistors (GFETs) are suitable building blocks for high-performance electrical biosensors, because graphene inherently exhibits a strong response to charged biomolecules on its surface. However, achieving ultralow limit-of-detection (LoD) is limited by sensor response time and screening effect. Herein, we demonstrate that the detection limit of GFET biosensors can be improved significantly by decorating the uncovered graphene sensor area with carbon dots (CDs). The developed CDs-GFET biosensors used for exosome detection exhibited higher sensitivity, faster response, and three orders of magnitude improvements in the LoD compared with nondecorated GFET biosensors. A LoD down to 100 particles/µL was achieved with CDs-GFET sensor for exosome detection with the capability for further improvements. The results were further supported by atomic force microscopy (AFM) and fluorescent microscopy measurements. The high-performance CDs-GFET biosensors will aid the development of an ultrahigh sensitivity biosensing platform based on graphene for rapid and early diagnosis of diseases.

ScFv-modified graphene-coated IDE-arrays for 'label-free' screening of cardiovascular disease biomarkers in physiological saline.

Fatty-acid binding proteins (FABP) and myeloperoxidases (MPO) are associated with many chronic conditions in humans and considered to be important biomarkers for diagnosis of cardiac diseases. Here we assemble a new electrical biosensor platform based on graphene-coated interdigitated electrode arrays (IDE-arrays) towards ultrafast, label-free screening of heart type-FABP and MPO. Arrays of nanoscale (nanoIDE) and microscale (microIDE) electrode-arrays were fabricated on wafer-scale by combining nanoimprint and photolithography processes. Chemical vapor deposition grown multilayer graphene was transferred onto nano/microIDE-arrays and used as a high surface-to-volume ratio electrical transducer. Novel biofunctional layers of specially engineered anti-h-FABP and anti-MPO single-chain fragment variables (scFv) were immobilized onto graphene-coated IDE-array sensor platform for electrical detection of h-FABP and MPO in physiological saline. scFv fragments show increased sensitivity in comparison to the state-of-the-art competitive ELISA for their higher affinity towards target analytes. Deploying FABP and MPO specific scFvs as receptor molecules onto our high-sensitivity graphene-coated IDE-arrays with identical sensor characteristics and assays covering clinically relevant concentrations in physiological saline, we demonstrate realization of a simple and versatile biosensor platform capable of high performance cardiac-bioassays for point-of-care applications.

Microwave Study of Field-Effect Devices Based on Graphene/Aluminum Nitride/Graphene Structures.

Metallic gate electrodes are often employed to control the conductivity of graphene based field effect devices. The lack of transparency of such electrodes in many optical applications is a key limiting factor. We demonstrate a working concept of a double layer graphene field effect device that utilizes a thin film of sputtered aluminum nitride as dielectric gate material. For this system, we show that the graphene resistance can be modified by a voltage between the two graphene layers. We study how a second gate voltage applied to the silicon back gate modifies the measured microwave transport data at around 8.7 GHz. As confirmed by numerical simulations based on the Boltzmann equation, this system resembles a parallel circuit of two graphene layers with different intrinsic doping levels. The obtained experimental results indicate that the graphene-aluminum nitride-graphene device concept presents a promising technology platform for terahertz- to- optical devices as well as radio-frequency acoustic devices where piezoelectricity in aluminum nitride can also be exploited.

Growth of Epitaxial Oxide Thin Films on Graphene.

The transfer process of graphene onto the surface of oxide substrates is well known. However, for many devices, we require high quality oxide thin films on the surface of graphene. This step is not understood. It is not clear why the oxide should adopt the epitaxy of the underlying oxide layer when it is deposited on graphene where there is no lattice match. To date there has been no explanation or suggestion of mechanisms which clarify this step. Here we show a mechanism, supported by first principles simulation and structural characterisation results, for the growth of oxide thin films on graphene. We describe the growth of epitaxial SrTiO3 (STO) thin films on a graphene and show that local defects in the graphene layer (e.g. grain boundaries) act as bridge-pillar spots that enable the epitaxial growth of STO thin films on the surface of the graphene layer. This study, and in particular the suggestion of a mechanism for epitaxial growth of oxides on graphene, offers new directions to exploit the development of oxide/graphene multilayer structures and devices.