Magnesium zinc oxide dual gate thin film transistor-based biosensor for monitoring the biofilm formation
Creators: name: Li, Guangyuan
Publisher: name: No Publisher Supplied
Year: 2021

description: Recently, increasing attention has been paid to transistor-based biosensors due to their preferred advantages, especially the high signal gain induced by the active three-terminal device. Thin film transistor (TFT) is a special kind of field-effect transistor (FET) made by depositing thin films over a supporting substrate. Due to its low fabrication temperature, the substrate of TFT can be selected from non-conducting materials such as glass and plastics, which fuels the realization of low-cost flexible and/or wearable electronics for biomedical applications. In the traditional bottom-gate staggered TFT biosensor, the top channel surface acts as the biological receptor. However, such configuration lacks the flexibility on sensing surface modification; furthermore, it is difficult to sense the analyte in aqueous environment. In this dissertation, we demonstrate a magnesium zinc oxide dual gate TFT (MZO DGTFT) with extended nanostructured MZO (MZOnano) modified sensing pad for the dynamic monitoring of biofilm formation. MZOnano is used to enhance the sensitivity and biocompatibility of the biosensor. The MZOnano sensing pad is electrically connected to the top gate of the DGTFT. Such extended sensing pad design allows the separation of the DGTFT device from the harsh biochemical environment and different sensing pads according to the detection tasks can be connected to the same transducer sequentially.The MZO DGTFT biosensor is firstly implemented for the early stage detection of Staphylococcus epidermidis (S. epidermidis) biofilm formation. Biofilm formation is a serious issue in the clinical treatment of bacterial infections, because once matured, biofilms show 500 – 5000 times more tolerant to antibiotics in contrast to the free-floating bacteria of the same kind. Therefore, the earlier the detection, the more effective the treatment will be. S. epidermidis bacteria were cultured in vitro on the MZOnano modified sensing pad. Charge transfer occurs between the microbial cells and the MZOnano during the initial bacterial adhesion stage. Such electrical signals, which represent the onset of biofilm formation, were dynamically detected by the DGTFT where its bottom gate was used for biasing the device into the optimum characteristic region for high sensitivity and stable operation. The testing results show that a current change of ~80% is reached after ~200 minutes of bacterial culturing. The crystal violet staining-based assay shows that tiny bacterial microcolonies just start to form at 200 minutes, and that it would take approximately 24 hours to form matured biofilms. This technology enables medical professionals to act promptly on bacterial infection before biofilms get fully established.Despite the early stage detection, the full-scale dynamic monitoring is also important because the long-term growth kinetic profile of biofilm development can serve as a feedback signal for future medical treatment studies. Therefore, we have developed the MZOnano modified multifunctional biosensing system for the full-scale dynamic monitoring of Pseudomonas aeruginosa (P. aeruginosa) biofilm formation. In this system, the DGTFT serves as an electrical sensor for early stage detection while the quartz crystal microbalance (QCM) as an acoustic sensor for long-term monitoring. The sensing surfaces of both devices were modified with the same MZOnano to enhance the sensitivity and biocompatibility. P. aeruginosa bacteria were cultured in vitro on both sensing surfaces. The early stage detection is realized by sensing the charge transfer from cell membrane to the MZOnano during bacterial adhesion using the DGTFT biosensor while the monitoring of the long-term evolution is achieved through sensing of mass loading and viscoelastic transition during biofilm development using the MZOnano modified QCM. The drain current of DGTFT starts to change at the beginning of the test and levels off after ~6.5 hours of bacterial inoculation, whereas the signals of MZOnano modified QCM become detectable after ~5 hours and then lasts for 24 hours. The full-scale process of biofilm development covering from bacterial adhesion to maturation is thus dynamically monitored using this MZOnano modified multifunctional sensing technology.In addition, MZO DGTFT biosensor is used for the determination of modified folic acid, hexadecyl alkynated folic acid (HAFA). 11-azidoundecanoic acid (AA) was bond onto the MZOnano sensing surface as the linker layer, resulting in negative charges to MZOnano due to carboxylic acid binding chemistry. HAFA was then immobilized on AA/MZOnano via click reaction with AA. HAFA is a polar molecule with the positive end adjacent to AA/MZOnano, and therefore, the electrostatic condition of MZOnano is impacted again. Such changes were detected by DGTFT that displayed significant drain current variations. Fourier-transform infrared spectroscopy (FTIR) imaging confirms such successful chemical processes. This MZO DGTFT biosensor with HAFA is promising for potential applications in the detection of folate receptor (FR) overexpressed cancer cells.Such MZO DGTFT biosensor with extended sensing gate design demonstrates the feasibility of sensing analytes in aqueous environment with modified sensing surface, and it can be potentially applied to various sensing applications where electrochemical reactions occur, such as charge transfer or electrical dipole.