Construction And Application Of Piezoelectric Pharmaceutical Bulk Acoustic Wave Sensor And Nano-structured Biosensors

Owing to its advantages, such as broad sensing spectrum, high sensitivity, simple construction, low cost, convenient operation and integrated digital function, piezoelectric quartz crystal (PQC) bulk acoustic wave sensing techniques have been applied to numerous fields covering analytical chemistry, pharmaceutical science, biochemistry, molecular biology, and environmental monitoring. In this thesis, the piezoelectric sensing techniques were applied in the fields of pharmaceutical detection and bioanalytical chemistry, and the main work could be summarized as follows:1. By combining the sensitive mass response of piezoelectric quartz crystal with the selective adsorption of pharmaceutical solid film, a kind of phenytoin anion-selective piezoelectric sensor was proposed for the first time. What's more, we have deduced the response model and applied the sensor to real sample analysis successfully.2. The behavior of the bare gold, dithiol modified and nanogold-structured sensors during the binding process between primaquine phosphate and bovine serum albumin (BSA) have been investigated in real time by piezoelectric impedance technique. Compared with other real-time techniques, such as flow-injection analysis and surface plasmon resonance, piezoelectric impedance technique has the ability to provide the multidimensional information about the interaction between drug and protein. The changes of the equivalent circuit parameters demonstrate the changes of physical and chemical properties at the sensor/liquid interface. It is found that the frequency response to the adsorption of protein can be expressed by a sum of two exponential functions. On the other hand, gold is the most suitable metal for biotechnological SPR applications because of its optical and chemical properties, but direct adsorption of protein onto bulk metal surfaces frequently results in denaturation and loss of bioactivity. The result from this paper indicates that nanogold particles are excellent substrate suitable for the immobilization of biomolecules. From the results of three different cases, the electrode modified with dithiol/nanogold bears increased capacity, more bioactivity and maintained biocompatibility for the binding of primaquinephosphate to protein compared with bare gold and thiol-modified electrodes. All these may have biological significance and paVe the way for the further clinical studies of the Pharmaceuticals.3. Piezoelectric quartz crystal impedance (PQCI), cyclic voltammetry, and electrochemical impedance analyses were combined to study the interaction between diazepam and HSA. Biocompatible Au nanoparticles were used as an active matrix for the immobilization of protein. Electrochemical data showed that the adsorption of HSA could increase the Nyquist diameter and under the same concentration, the Au-colloid modified electrode has a bigger diameter. As for the interaction between HSA and diazepam, with the increment of the drug's concentration, the Nyquist diameter and double-layer capacitance will increase too. The results elucidate that colloid nanoparticles can play the role of an efficient electron-conducting tunnel and have a very high ratio of surface to volume. The piezoelectric impedance technique was used to confirm the results obtained by electrochemical data and to provide real-time and direct information for protein-drug binding. Additionally, the kinetics of the binding process was also studied.4. PQCI analysis was applied to study the binding of L-tryptophan to HSA, which was immobilized on the matrix of bare gold electrode/chitosan/ glutaraldehyde/cysteamine/nanogold particles to maintain biocompatibility, increase capacity and allow renewing the electrode. The real-time courses of the resonant frequency and equivalent circuit parameters of the sensor during the protein-amino acid binding and the competition between L-tryptophan and serum solutes extracted from uremic patients undergoing hemodialysis by ultrafiltration before dialysis treatment were investigated for the first time by the piezoelectr...