Carbon-nanotube enhanced piezoelectric biosensors [thesis]

Ting Xu
Recently, biosensors with high sensitivity, compact size, rapid response and easy operation are urgently required to effectively detect, monitor and control the fast-spreading epidemics, such as influenza A (HIN I ), dengue fever, bird flu, and hand-foot-and-mouth disease (HFMD). The micro-piezoelectric biosensor is believed to be one of the candidates to fulfill the abovementioned demands due to its compact size, high sensitivity and easy integration with analysis circuit. Among the numerous
more » ... mong the numerous reports available in the literature, cantilever and quartz-crystal microbalance system (QCMS) type biosensors are found to be the most representative piezoelectric biosensors due to their many advantages such as high sensitivity, label-free detection, robust structure and high reproducibility; however, some drawbacks, including fragile structure, low quality factor and lack of integration limit their applications in monitoring and rapidly detecting the fastspreading epidemics. In this thesis, a new type of micro-piezoelectric diaphragm-based biosensor array is presented. Besides the benefits arise from the micro-piezoelectric biosensors mentioned above, this new device is able to simultaneously detect multiple biological materials, which significantly shorten the diagnosis time and lower the cost. In the theoretical analysis part, a novel analytical model for the resonant frequency of a micro-machined piezoelectric diaphragm working in a mixed mode of tension and flexural rigidity is established based on the classic plate theory. The gravimetric and mass sensitivity are derived and the theoretical calculation and finite element analysis results show that the gravimetric sensitivity 11 ATTENTION: The Singapore Abstract is independent of the tension and flexural rigidity and only determined by the total diaphragm thickness. By considering the sensitivity and difficulty of biomaterial immobilization, the designed diaphragm diameter varies from 600 J.lm to 1000 J.lm with a thickness of about 1 J.lm. After the sensor designs based on the theoretical analysis, two novel micro-piezoelectric diaphragm-based sensor chips are then developed in the first part of this project. The fIrst square sensor array with 7 individual sensors with dimension of 500 J.lm x 500 J.lm successfully detect antigoat immunoglobulin G (IgG) with 7 different concentrations. The gravimetric and mass sensitivity are calculated to be -16.5 m 2 /kg and 6.25 Hz/ng, respectively. To increase the mass sensitivity and fabrication yield of the piezoelectric biosensors, the second circular-type sensor array is developed and demonstrated to be able to simultaneously detectHBsAg, AF-P and HBcAg. A real determination of HBsAg and AFP with the limit of detection of 0.1 ng/ml in the concentration range of 0.1 to 10000 ng/ml can be confIrmed by this immunochip. The mass sensitivity for detection of HBsAg and AFP are found to be 16.05 Hz/ng and 15.97 Hz/ng, respectively. Both the gravimetric (-45.33 m 2 /kg) and mass sensitivity are more than two times higher than those obtained from the square sensor array. These preliminary results confIrm the possibility of applying these piezoelectric sensors for biosensing. To further improve the mass sensitivity of the developed sensor array chip, the sensing surfaces are covered by carbon nanotubes (CNTs). CNTs possess very high specific surface areas and can capture more analytes to improve detection signals. As a result, the sensitivity and dynamic range of detection can be greatly increased. Hence, in the second part of this project, CNTs were incorporated with the 111 ATTENTION: The Singapore Abstract piezoelectric diaphragm to develop a CNT-enhanced mass-sensitive biosensor. After a systematic and comprehensive optimization on the influences of various synthesis parameters, a high quality of long CNT with length up to 380 J-lm was successfully synthesized. Development of CNT-enhanced piezoelectric biosensors was implemented in the following two approaches. CNTs can be either directly grown or deposited onto the diaphragm to enhance the performance of the biosensors. In the fIrst experiment, CNTs are directly grown on the reverse side of the sensor diaphragm; unfortunately, most of the sensors are damaged due to the high CNT growing temperature. Thus, in the second experiment, CNTs are pre-synthesized and deposited onto the sensing surface of the individual sensors. The developed CNT-incorporated immunochip is able to simultaneously detect anti-goat IgGs with 8 different concentrations and possess a detection limit of 0.1 ng/ml and a dynamic range of 0.1 to 10000 ng/ml; whereas the detection limit and dynamic range for a non-CNT enhanced immunosensor chip are 1 ng/ml and 1 to 10000 ng/ml, respectively. More importantly, the mass sensitivity of a CNT incorporated biosensor is nearly 4 times higher than that without CNT enhancement. The results demonstrate that the developed CNT-enhanced piezoelectric biosensor array has significant advantages over the conventional one. Moreover, the developed biosensor chip has more robust structure, high fabrication yield and high quality factor comparing with the micropiezoelectric cantilever biosensors; its limit of detection is hundred times higher than the QCMS. The key advantage of the developed CNT-enhanced piezoelectric biosensor array lies in its multiple detection capability with high sensitivity; the diagnosis speed can be at least 8 times faster than the normal cantilever biosensor IV ATTENTION: The Singapore Abstract and QCMS. Furthermore, the undesired cross interactions between the biological materials caused by human errors can be maximally avoided because of the integrated diagnose processes; hence, the accuracy and reliability of the test results are increased. The preliminary results achieved in this project indicate that the CNT enhanced micro-machined piezoelectric diaphragm-based biosensor array has very compact size, high sensitivity, high quality factor, rapid response and multiple detection capability. With further calibration and optimization, it can be potentially used as low cost disposable immunosensor.
doi:10.32657/10356/46254 fatcat:zpjlrvgovvg2hixqi637fqkz4u