Developing piezoelectric biosensing methods

Lai, Ming-Liang (2015) Developing piezoelectric biosensing methods. PhD thesis, University of Glasgow.

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Biosensors are often used to detect biochemical species either in the body or from collected samples with high sensitivity and specificity. Those based on piezoelectric sensing methods employ mechanically induced changes to generate an electrical response. Reliable collection and processing of these signals is an important aspect in the design of these systems. To generate the electrical response, specific recognition layers are arranged on piezoelectric substrates in such a way that they interact with target species and so change the properties of the device surface (e.g. the mass or mechanical strain). These changes generate a change in the electrical signal output allowing the device to be used as a biosensor. The characteristics of piezoelectric biosensors are that they are competitively priced, inherently rugged, very sensitive, and intrinsically reliable. In this study, a compound label-free biosensor was developed. This sensor consists of two elements: a Love wave sensor and an electrochemical impedance sensor. The novelty of this device is that it can work in both dry and wet measurement conditions. Whilst the Love wave sensor aspect of the device is sensitive to the mass of adsorbed analytes under both dry and wet conditions with high sensitivity, the sensitivity coefficients in these two conditions may be different due to the different (mechanical) strengths of interaction between the adsorbed analyte and the substrate. The impedance sensor element of the device however is less sensitive to the mechanical strength of the bond between the analyte and the sensing surface and so can be used for in-situ calibration of the number of molecules bound to the sensing surface (with either a strong or weak link): conventional Love wave sensors are not sensitive to material loosely bound to the surface. Thus, a combination of results from these two sensors can provide more information about the analyte and the accuracy of the Love wave sensor measurements in a liquid environment. The device functions with label-free molecules and so special reagents are not needed when carrying out measurements. In addition, the fabrication of the device is not too complicated and it is easy to miniaturise. This may make the system suitable for point-of-care diagnostics and bio-material detection.
The substrate used in these sensors is 64°Y–X lithium niobate (LiNbO3) which is a kind of piezoelectric material. On the substrate, there is a pair of interdigital transducers (IDTs) which are composed of 100 Ti/Au split-finger pairs with a periodicity (λ) of 40μm. The acoustic path length, between both IDTs, is 200λ and the aperture between the IDTs is 100λ. On top of the substrate and IDTs, there is a PMMA guiding layer with an optimised thickness ranging from 1000 nm to 1300 nm. In addition, a gold layer with thickness 100 nm is deposited on the guiding layer to act as the electrodes for the electrochemical impedance sensor.
The biosensor in this study has been used to measure Protein A, IgG, and GABA molecules.
Protein A is often coupled to other molecules such as a fluorescent dye, enzymes, biotin, and colloidal gold or radioactive iodine without affecting the antibody binding site. In addition, the capacity of Protein A to bind antibodies with such high affinity is the driving motivation for its industrial scale use in biologic pharmaceuticals. Therefore, measuring Protein A binding is a useful method with which to verify the function of the biosensor.
IgG is the most abundant antibody isotype found in the circulation. By binding many kinds of pathogens including viruses, bacteria, and fungi, IgG protects the body from infection. Also, IgG can bind with Protein A well so the biosensor here could also measure IgG after a Protein A layer is immobilised on the sensing area.
GABA is the main inhibitory neurotransmitter in the mammalian central nervous system. It plays an important role in regulating neuronal excitability throughout the nervous system. The conventional method to measure concentrations of GABA under the extracellular conditions is by using liquid chromatography. However, the disadvantages of chromatographic methods are baseline drift and additions of solvent and internal standards. Therefore, it is necessary to develop a simple, rapid and reliable method for direct measurement of GABA, and the sensor here is an attractive choice.
When the Love wave sensor works in the liquid media, it can only be used to measure the mass of analytes but does not provide information about the conditions of molecules bound with the sensing surface. In contrast, electrochemical impedance sensing based on the diffusion of redox species to the underlying metal electrode can provide real-time monitoring of the surface coverage of bound macromolecular analytes regardless of the mechanical strength of the analyte-substrate bond: the electrochemical impedance measurement is sensitive to the size and extent of the diffusion pathways around the adsorbed macromolecules used by the redox species probe i.e. it is sensitive to the physical area of the surface covered by the macromolecular analyte and not to the mass of material that is sensed through a mechanical coupling effect (as in a Love wave device). Although electrochemical impedance measurements under the dry state are quite common when studying batteries and their redox/discharge properties, these are quite different sorts of systems to the device in this study. Therefore, integrating these two sensors (Love wave sensor and electrochemical impedance sensor) in a single device is a novel concept and should lead to better analytical performance than when each is used on their own. The new type of biosensor developed here therefore has the potential to measure analytes with greater accuracy, higher sensitivity and a lower limit of detection than found when using either a single Love wave sensor or electrochemical impedance sensor alone.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: biosensor, Love wave sensor, impedance sensor, piezoelectric sensing, label-free, IDTs, Protein A, IgG, Anti-GABA, GABA.
Subjects: Q Science > Q Science (General)
R Medicine > RZ Other systems of medicine
T Technology > TK Electrical engineering. Electronics Nuclear engineering
Colleges/Schools: College of Science and Engineering > School of Engineering
Supervisor's Name: Cooper, Professor Jonathan and Glidle, Dr. Andrew
Date of Award: 2015
Depositing User: Mr Ming-Liang Lai
Unique ID: glathesis:2015-6109
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Feb 2015 12:50
Last Modified: 13 Feb 2015 12:56

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