Two-dimensional material-based nanosensors for detection of low-molecular-weight molecules
Creators: Zhu, Yibo
Publisher: name: Columbia University
Year: 2018
Subjects: subject: Nanotechnology
subject: FOS: Nanotechnology
subject: Applied physics
subject: Materials science
subject: Biosensors

description: Low-molecular-mass small molecules play important roles in biological processes and often serve as disease-related biomarkers for diagnosis. Accurate detection of small molecules remains challenging for conventional sensors due to their limited sensitivities. Two-dimensional (2D) materials, thanks to their atomic level thickness, can be extraordinarily sensitive to external perturbations and therefore well-suited for sensing applications. This dissertation explores the use of 2D materials, including primarily graphene and transition metal dichalcogenides, in the detection of low-molecular-weight and low-charge molecules. 
      This work starts with the study of methods that allow for efficient and clean transfer of graphene grown on Cu using chemical vapor deposition (CVD), which is a critical step for achievement of large-area and high-quality graphene for device fabrication. In addition to the conventional wet-etching transfer method, we have studied on the method of electrochemical delamination, which is more time-efficient and allows for recycling of the Cu foil. Generation of bubbles during the electrochemical reaction is minimized by tuning the experimental parameters, thereby minimizing transfer-induced damages to graphene. 
      We then fabricate the graphene-based field effect transistor (FET) and use the graphene FET as biosensors. First, the sensor is configured as an electrolyte-gated FET. With appropriate biochemical functionalization of the graphene, the FET sensors have been used to detect multiple small-molecule biomarkers including glucose and insulin via their affinity binding with receptors. Then, on a flexible substrate, we demonstrate real-time measurement of tumor necrosis factor alpha, a signal protein that regulates immune cells. We then simplified the sensor structure using a bottom local-gate to replace the external electrode as required in the previous electrolyte gated FET. Using the bottom local-gated FET sensor we have carried out real-time monitoring of the variation of pH in solutions. 
      In addition to the electrical sensors, highly sensitive and multifunctional plasmonic sensors have also been developed by combining the unique optical properties of graphene with engineered metallic metasurfaces. The plasmonic sensors operating in mid-infrared region are configured as either metallic metasurface or hybrid graphene-metallic metasurface. Using a metallic metasurface, we demonstrate simultaneous quantification and fingerprinting of protein molecules. Using a hybrid graphene-metallic metasurface, we demonstrate optical conductivity-based ultrasensitive biosensing. In contrast to refractive-index-based sensors, the sensitivity of the hybrid metasurface sensor is not limited by the molecular masses of analytes. A monolayer of the sub-nanometer chemicals can be readily detected and differentiated on the hybrid metasurface. Reversible detection of glucose is carried out via the affinity binding of glucose with boronic acid immobilized on the graphene of the hybrid metasurface. The lowest detection limit achieved in our work is 36 pg/mL, which is considerably lower than that for the existing optical sensors.
      Despite the high sensitivity of graphene, the zero band-gap of graphene fundamentally impedes its use in digital electronic devices. In contrast, two-dimensional semiconductors, such as transition metal dichalcogenide (TMDC) with non-zero band gaps, holds great potential for developing practical electronic devices and sensors. Monolayers of TMDC materials are particularly attractive for development of deeply scaled devices, although the contact resistance between metal and the monolayer TMDC has been so large to significantly limit the performance of the devices. We present a high-performance monolayer MoS2 FET with a monolayer graphene as bottom local gate. The graphene gate is found to significantly improve the dielectric strength of the oxide layer compared to the lithographically patterned metal gate. This in turn allows for the use of very thin gate dielectric layer (~5 nm) and application of a strong displacement field to lower the contact resistance. Benefiting from the low contact resistance, the monolayer MoS2 FET offers a high on/off ratio (108) and low subthreshold slope (64 mV/decade). Additionally, thanks to the highly efficient electrostatic coupling through the ultrathin gate dielectric layer, short-channel (50 nm and 14 nm) devices are realized that exhibit excellent switching characteristics.
      In summary, this dissertation presents significant contributions to 2D material-based electronic and optoelectronic nanosensors, especially for detection of small molecules. Perspectives are made in the end of the thesis, on future studies needed to realize practical applications of these sensors and other 2D material-based products.