Microtechnology and Nanotechnology Advancements Toward Bio-Molecular Targeting

10 Microtechnology and Nanotechnology Advancements Toward Bio-Molecular Targeting Veeradasan Perumal*,†, Norani Muti Mohamed*,‡, Mohamed Salleh Mohamed Saheed*,‡, Mohamed Shuaib Mohamed Saheed*,‡ *Cen tre o f In novative N ano structures an d Nano devices (COINN), Un iversiti Tekn olog i P ET RON A S , Ser i I s ka nda r , M a la y s ia † Mecha ni ca l Engi ne eri ng D ep artment, Universiti Te kn olog i P ET RONAS, Pe rak Darul Ri dzua n, Mala ysi a ‡ De partm ent of Fun dame nta l a nd Appl ied Scie nces, Univ ersi ti T ek nol ogi PE TRONAS , Se ri Isk anda r, Mala ysi a

10.1 Zinc Oxides’ Thin Film Deposition and Growth Techniques Zinc oxide (ZnO) has received much attention over the past decade due to its unique optical and electronic properties as an important metal oxide semiconductor derived from the group II–VI series in the periodic table. ZnO has a wide band gap of 3.37eV and a large exciton binding energy of 60meV (Cui et al., 2013; Flickyngerova et al., 2008). The interest in the use of ZnO is fueled by its use in electro-optical devices due to its direct wide band gap. In addition, ZnO also has been studied widely as a potential material for optoelectronic applications. ZnO has a fairly broad range of advantages due to its high electron mobility and suitability for simple fabrication of various nanostructures, which potentially results in lower-cost ZnO-based devices (Farmanzadeh and Tabari, 2013). During the past decade, an optimized fabrication of ZnO nanostructures has attracted the attention of many researchers. In general, there are two major techniques used in nanofabrication of zinc oxide nanostructures: “top-down” and “bottom-up.” The top-down approach is not a promising method because it contains some limitations, such as low yield assembly, large-scale uniformity, and repeatability issues; whereas the bottom-up approach is superior to the top-down approach in terms of photolithography, and is capable of producing various nanostructures with high yield, fewer defects, and better range ordering (Foo et al., 2014a,b). ZnO nanostructures prepared by the bottom-up approach are catalytically synthesized by the chemical or gas phase route, where structures are assembled from their atomic level (Foo et al., 2013, 2014a,b; Anish Kumar et al., 2011). Hence, ZnO nanostructures created from bottom-up fabrication approaches are preferred, as they possess unique physical, optical, and electrical properties, which are highly suitable for downstream applications. Nanobiosensors for Biomolecular Targeting. https://doi.org/10.1016/B978-0-12-813900-4.00010-5 © 2019 Elsevier Inc. All rights reserved.

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The most available common bottom-up approaches used in the synthesis of zinc oxide are through the chemical and gas phase routes. The gas phase route involves the melting of zinc source material (ZnO or Zn metal) into a vapor phase by using thermal, mechanical, or electrochemical means to subsequently transfer the vapor into the substrate. The gas phase route synthesis of ZnO uses chemical vapor deposition (CVD), radio frequency sputtering (RF), pulse laser deposition (PLD), molecular beam epitaxy (MBE), vapor-solid (VS), vapor-liquid-solid mechanisms (VLS), and so forth (Benramache et al., 2013; Kumar et al., 2013). However, these methods are time-consuming and complicated, as they need highly specialized laboratory setups equipped with high-end instrumentation (Benramache et al., 2013; Kashif et al., 2013). Further, most of the gas phase synthesis process acquires a catalyst that increases the impurities of the end product. On the contrary, spray pyrolysis, sol-gel and hydrothermal methods, and inkjet printing, are the most widely used chemical route methods for their ability to produce highly oriented, transparent, homogenous, repeatable, and low-cost ZnO nanostructures (Polsongkram et al., 2008; Sahoo et al., 2010). The chemical method, also known as the solution-based route, involves the reduction of zinc precursors by an additive in the presence of an alcohol solvent. Among the available chemical routes for the synthesis of highly crystalline ZnO nanostructures, sol-gel and hydrothermal are popular techniques, and have been extensively studied over the years.

10.1.1 Sol-Gel Method The sol-gel method possesses many advantages over other ZnO nanostructure processing techniques, such as its simplicity, low cost, and the ability to function at lower temperatures. The sol-gel process, also known as a soft chemistry/wet chemical reaction, can be defined as assembling of solid materials from the atomic level in the intermediate phase, such as sol or gelation of gel involving the continuous reaction of hydrolysis and condensation (Wang, 2013). Since the first report on ZnO nanostructure synthesis using a novel sol-gel method by Spanhel and Anderson (1991), this method has been adopted to synthesize ZnO nanostructures using a facile chemical route. The author has successfully synthesized and characterized ZnO nanoparticles using a sol-gel route, using zinc acetate dehydrate as a precursor (source) dissolved in ethanol (solvent), which is refluxed under 80°C for 180 min. The report also has suggested two possible growth mechanisms that could result in ZnO nanocrystal formation through a sol-gel process, which are Ostwald ripening and aggregation. The author suggests that Ostwald ripening could be possible; however, this process alone cannot be taken into account without considering the aggregation process. Moreover, the aggregation process can be explained as a growth of unit cells of a ZnO monomer that have combined to form stable primary aggregates. Further, the primary aggregates will subsequently combine to form secondary aggregates, and so on. This series of reactions will result in the formation of large ZnO nanocrystals. The aggregations and the Ostwald ripening mechanism in ZnO crystal formation are illustrated in Fig. 10.1.

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FIG. 10.1 Aggregation and Ostwald ripening in growth of the ZnO. Reproduced from Spanhel, L., Anderson, M.A., 1991. Semiconductor clusters in the sol-gel process: quantized aggregation, gelation, and crystal growth in concentrated zinc oxide colloids. J. Am. Chem. Soc. 113, 2826–2833, ACS.

Generally, the sol-gel process involves three chemical systems; namely, precursors, solvents, and additives (Znaidi et al., 2003). A precursor is a solid material that can be either metal salts or alkoxides. This precursor was dissolved in a solvent (any alcohol) in the presence of an additive (Tokumoto et al., 2003). The function of the additive is as a chelating agent that can be also expanded as a stabilizer (Znaidi, 2010; Znaidi et al., 2003). Therefore, the properties of the end product (thin films) synthesis via a sol-gel route can be influenced by several circumstances, including precursor concentration, effect of the stabilizer ratio, seed layer thicknesses, effect of pH, pre- and postannealing temperature, and type of solvent used (Addonizio et al., 2014; Boudjouan et al., 2015; Tari et al., 2012). Zinc acetate dihydrate and zinc nitrate hexahydrates are the most commonly used precursors in the sol-gel method, although there is a downside in removing the by-product of anionic species after the formation of sol-gel (Quin˜ones Galva´n et al., 2013). This by-product could eventually be removed during the thin film coating process using pre-and post-annealing treatment (Armelao et al., 2001). However, the nitrate and acetate anions play an important role in the formation of monodispersed sol-gel (Matijevic, 1981). Znaidi et al. (2015) investigated the influence of a precursor concentration derived from zinc acetate dihydrate on morphological, structural, and optical properties of a sol-gel synthesized ZnO thin film. The author showed that the lowest surface roughness and strongest texture were obtained for the lowest concentration of precursor.

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The increase in surface roughness, porosity, and particle size also resulted in increasing the precursor concentration. Conversely, the optical results show a good crystallinity quality for the higher precursor concentration. A higher dielectric constant and high polarity solvent are needed to dissolve metal salt precursors in a sol-gel preparation (Znaidi, 2010). This means the solubility of precursors highly depends on the polarity and dielectric constant of a solvent. Most alcohols are preferable in sol-gel synthesis, due to their high polarity (dipolar, amphiprotic) and high dielectric constant, which depends on the carbon number (chain length). Among the most frequently used alcohols in sol-gel preparation are the alcohols with less chain length, such as methanol (MeOH), ethanol (EtOH), isopropyl (IPA), and 2-methoxyethanol (2-ME). Methanol, with one carbon chain, has the highest dielectric constant (
34), which is the most preferable solvent used to dissolve metal salt precursors (Znaidi, 2010; Znaidi et al., 2003). Hosono et al. (2004) investigated the various monool solvent effects on the chemical reaction in forming colloid ZnO. The author used methanol, ethanol, and 2-methoxyethanol as a solvent to dissolve zinc acetate dehydrate under similar conditions. The reports highlight the formation of layered hydroxide zinc acetate as an intermediate, and its role in monodispersed ZnO formation. Further, the author demonstrated the influence of the solvent in reaction time for ZnO precipitation. The higher the chain length, the higher the reaction time needed for precipitation of ZnO. Similarly, a number of papers have studied the effect of different solvents in the preparation of zinc oxide solgel (Foo et al., 2014a,b; Hosono et al., 2004; Popa et al., 2013; Tsay et al., 2010). Foo et al. (2014a,b) studied the effect of different solvents on the structural and optical properties of ZnO thin films synthesized by the sol-gel method. The author concluded that 2-ME has the lowest surface roughness, largest bandgap, high crystallinity, and the highest transmittance in a visible range compared with other different solvents used in ZnO thin film preparation. The additive that is added to the sol-gel during the preparation of monodispersed ZnO colloid plays an important role as a chelating and stabilizing agent (Boudjouan et al., 2015). This additive is composed of a functional group that is responsible for the dissolution of zinc salts in the presence of an alcoholic solvent. The precursor, such as zinc acetate, has limited solubility in alcoholic media such as ethanol or propanol. However, adding an additive to the “sol” may facilitate the complete dissolution of the precursor. Moreover, the additive also prevents the rapid formation of ZnO hydroxide, and inhibits particle agglomeration using steric repulsion, forming a stable and clear sol-gel. Aminoalcohols (MEA, DEA, and TEA), sodium hydroxide, and lattice acid are the most commonly used additives in ZnO sol-gel preparation (Thongsuriwong et al., 2010). The mechanism reaction of the main species involved in “sol” preparation such as precursors, solvents, and additives are illustrated in Fig. 10.2. Thongsuriwong et al. (2010) has studied the effect of the various amino-alcohol additives on the morphology of ZnO thin film. Monoethanolamine (MEA), Diethanolamine (DEA), and triethanolamine (TEA) were added to facilitate the dissolution of zinc nitrate

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FIG. 10.2 Sketch of the chemical equilibria taking place in the initial solutions. Hydrolysis and condensation are spurred by temperature. Soluble or colloidal condensed moieties can result, which can be deposited as film precursors. Reproduced from Znaidi, L., Soler Illia, G.J.A.A., Benyahia, S., Sanchez, C., Kanaev, A.V., 2003. Oriented ZnO thin films synthesis by sol–gel process for laser application. Thin Solid Films 428, 257–262, Elsevier.

hexahydrate in ammonium hydroxide. The group has investigated the steric effect influence on the additive on the crystallite and particle size. The results showed that TEA possessed the highest repulsion force between the molecules, compared with the same mole ratio of MEA and DEA. The author also reported the suppression of c-axis crystal growth of ZnO by increasing the amino alcohols concentration. In addition, the addition of TEA facilitated the a-axis crystal growth of ZnO, compared with MEA and DEA. Recently, the effect of the stabilizer ration on the photoluminescence properties has been discussed by (Boudjouan et al., 2015). In this report, the author demonstrated that the thickness of the ZnO thin film depends on the stabilizer ratio (MEA to zinc ratio ¼ 0.5, 1.0, 1.5, and 2.0). The thickness of the ZnO thin film increases significantly as the MEA ratio increases, which is due to the increase of pH contributed by the amino group. This report suggested the use of a 1:1 ratio of zinc to MEA to sustain excellent structural and optical properties of ZnO thin films.

10.1.2 Hydrothermal Method The use of a chemical route synthesis of a zinc oxide nanostructure via hydrothermal method was first developed in the early 1960s, and is still growing widely (Laudise and Ballman, 1960; Triboulet, 2014). In brief, hydrothermal growth, or otherwise called aqueous solvent route/aqueous chemical growth, offers an interesting way of facilitating ZnO nanostructure growth via hydrolysis and condensation of the precursor, such as zinc salts in the presence of hexamethylenetetramine (stabilizer) under very low temperature and pressure conditions (Greene et al., 2006). This method is advantageous in producing and aligning high-density ZnO nanowire arrays compared with any gas-phase route, which has limitations such as requirements for high-temperatures high-end equipment, and expertise; and results in low product yield and uniformity problems (Wang et al., 2014; Yoon et al., 2015). Hence, the hydrothermal growth method can be widely applied in

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industries that offer convenience for economically large-scale device fabrication with low-cost processes (Park et al., 2016; Wu et al., 2015) The challenging issue in the hydrothermal growth process is the control of morphology/ size, crystal quality, and diameter distribution of fabricated ZnO nanostructures. The growth solution properties such as pH, which greatly affect the stabilizer, growth temperature, growth solution concentration, and growth time are the influence factors in obtaining a highly crystalline, aligned, and dense ZnO nanostructure fabrication (Polsongkram et al., 2008; Wen et al., 2014). Furthermore, the gas-phase route through VLS and CVD has reported a smaller and high crystalline fabricated ZnO nanostructure, compared with the aqueous chemical route (Gautam et al., 2016). Moreover, the hydrothermal growth ZnO nanostructure also results in a higher number of oxygen vacancies, which affect the structural properties of the fabricated ZnO nanostructure (Klubnuan et al., 2016). However, this limitation has turned out to be an advantage in the hydrothermal growth process, as the photocatalytic activity can be enhanced through ZnO nanostructures fabricated with higher oxygen vacancies (Saikia et al., 2015). A novel two-step method in which the combination of seed layer formation (ZnO thin films) through a dip-coating method followed by aqueous solution growth of ZnO thin films forming ZnO nanowire arrays for polymer solar-cell application has been reported by Greene et al. (2005). Since then, there has been a great deal of research conducted on developing and optimizing the two-step hydrothermal growth process for various ZnO nanostructure formations. Its schematic process flow is shown in Fig. 10.3. In brief, most of the two-step methods reported the preparation of ZnO sol-gel followed by spray pyrolysis, deep coating, or spin-coating for the deposition process of the seed layer, which was repeated 3–5 times to obtain a thicker ZnO thin film (ZnO TFs). For each deposition process, the coated ZnO TFs were dried to remove the organic residuals that might exist on the ZnO thin films. The coated ZnO TFs were then annealed to obtain a highly crystallized ZnO. For the hydrothermal growth of ZnO NFs, the prepared substrate with the coated seed layer was submerged backward inside the growth solution using a Teflon sample holder. An equal concentration of growth solution was prepared by mixing both a zinc nitrate hexahydrate and hexamethylenetetramine (1:1) ratio in deionized water.

FIG. 10.3 The schematic illustration of fabrication process of the ZnO nanowire arrays on the ITO glass substrate. Reproduced from Chen, M.-Z., Chen, W.-S., Jeng, S.-C., Yang, S.-H., Chung, Y.-F., 2013. Liquid crystal alignment on zinc oxide nanowire arrays for LCDs applications. Opt. Exp. 21 (24), 29277–29282, Optical Society (OSA).

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The growth process was completed inside an oven (60–90°C). Finally, the prepared hydrothermally grown ZnO NFs were cleaned to remove residual salts prior to annealing in a furnace under ambient air. Wang et al. (2014) investigated the preparing parameter of hydrothermal growth influence on the vertical alignment ZnO nanowire array fabrication. The effect of a parameter such as seed layer, substrate, colloid, and precursor concentration on the alignment of ZnO nanowire arrays has been shown clearly. The results showed that the orientation of the seed layer is the most important factor in influencing the vertical alignment growth of ZnO nanowire arrays. Further, the vertical alignment growth of nanowires was facilitated by increasing the colloid and precursor concentration. Moreover, the ZnO thin film seed coated FTO substrates promote better crystallinity and alignment compared with the Si-substrate. Similarly, Ghayour et al. (2011) have investigated the effect of various seed layer thicknesses (20, 40, 160, and 320 nm) on the vertical alignment and diameter of hydrothermally grown ZnO nanorods. The group has suggested two growth models that are responsible for the alignment and diameter of ZnO nanorods. As the thickness of the seed layer increases, the crystallinity increases, which is attributable to the higher grain size. The larger grain size promotes lower surface roughness, leading to highly aligned vertical nanorods with a higher diameter. In contrast, the lower thickness of the seed layer contributes to lower crystallinity and grain size. Thus, the higher surface roughness can be attributed to badly aligned and smaller-diameter ZnO nanorods.

10.2 Gold Nanoparticles’ Properties and Application The role of gold nanoparticles (AuNPs) in chemical and biological sensing has become dominant due to their distinct physical, optical, electrical, and chemical properties. The emergence of gold nanoparticle-integrated sensors with extremely high sensitivity and selectivity has drawn researchers’ attention in recent years. Gold (Au) has various characteristics, such as suitability with surface chemical functionalization, inert and nontoxic biocompatibility, antioxidative characteristics, high conductivity, and the ability to synthesize uniform and different nano-sizes (Ghosh et al., 2008; Upadhyayula, 2012). These unique characteristics attributed to Au have inspired hope for the development of highly sensitive, stable, and selective analytical devices (Daniel and Astruc, 2004; Saha et al., 2012). First, the biocompatibility characteristics of AuNPs are not only responsible for immobilization of chemical or biological analytes, but also for their inert characteristics toward any organic and nonorganic molecules. This means that the AuNPs do not change or alter any functionality of the analyte, even after the immobilization during self-assembly of the monolayer (Giljohann et al., 2010). Next, the high surface-to-volume ratios are one of the most advantageous characteristics of AuNPs, which are responsible for high numbers of biomolecule immobilization (Giljohann et al., 2010; Saha et al., 2012). Therefore, the conjugate AuNPs enable functionalized biomolecules to bind easily, directly, and selectively.

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These compatibilities increase the chances of selective binding of bio-recognition elements, or probes, to the conjugated AuNP for the specific bio-recognition. Furthermore, the unique optoelectronic properties of AuNPs serve as an excellent scaffold for various transduction methodologies. For example, the interaction between the recognition elements and the specific analyte upon immobilization will result in physicochemical changes on AuNPs, such as conductivity, surface plasmon resonance light scattering or absorption, redox activity, and so forth. These changes are detectable using optical (colorimetric, fluorimetric, etc.) or electrochemical (impedance spectroscopy) transduction methodology (Upadhyayula, 2012). The most common and effective way of synthesizing AuNPs are through bottom-up or self-assembly approaches, which involve nanofabrication by chemical or physical forces operating at the nanoscale level to assemble basic unit units into complete structures. The synthesis of AuNPs or colloidal gold by (Faraday, 1857), opens the door to the possibility of bottom-up synthesis of AuNPs. The author has successfully prepared a colloidal gold solution using a two-phase system that includes phosphorus dissolved in carbon disulfide, which resulted in a reduction of an aqueous solution of chloroaurate (AuCI4  ). Since then, there have been significant efforts made to synthesize the colloidal gold using bottom-up approaches. Indeed, Turkevich and co-workers have reported approaches of synthesis monodispersed colloidal gold using a citrate reduction technique that is still used today (Turkevich et al., 1951). In this work, the chloroauric acid was reduced and stabilized by trisodium citrate in water. Moreover, (Frens, 1973) has adopted Turkevich’s efforts, and made slight changes by controlling the feed ratio of the reducing agent (citrate) to gold salt in order to obtain the desired nano-sizes of AuNPs. It requires significant effort to control the sizes of colloidal gold during the synthesis process. Fig. 10.4 shows the schematic illustration of gold nanoparticle formation reported by (Polte et al., 2010). There are numerous applications that have evolved from the Turkevich report over the past decade (Chow and Zukoski, 1994; Kumar et al., 2007). Liu et al. (2011a) reported an electrochemical impedance route to investigate the advantages of AuNPs in immunosensing applications. This immunosensor was fabricated on a gold electrode by a self-assembled monolayer (SAM) of 4-thiophenol and AuNPs.

Au0

AuIII 1. Step a nucleation

2. Step b growth by aggregation

~2 nm

3. Step c slow further growth

~3 nm

4. Step fast final growth

5.5 nm

d

7.7 nm

FIG. 10.4 Schematic illustration for the deduced process of gold nano-particle formation. Reproduced from Polte, J., Ahner, T.T., Delissen, F., Sokolov, S., Emmerling, F., Thunemann, A.F., Kraehnert, R., 2010. Mechanism of gold nanoparticle formation in the classical citrate synthesis method derived from coupled in situ XANES and SAXS evaluation. J. Am. Chem. Soc. 132, 1296–1301, ACS.

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Subsequently, the biotin derivate was immobilized on AuNPs as a probe for anti-biotin IgG detection. The author has successfully exploited the advantages of AuNPs in immunosensing by comparing the results of SAM with and without AuNPs’ presence. The impedance spectroscopy shows an increase in charge transfer resistance (Rct) with a linear detection range of a 5–500 and 5 ng mL1 limit of detection. Further, the reported limit of detection is lower than that obtained by the same group previously. Thus, the report has presented an interesting addition to the current method for immunosensing. Liu et al. (2011b) has proposed a new method of DNA hybridization evaluation using gold nanoparticles that measure the changes in flexibility of single and duplex DNA strands. The AuNPs were first modified with 1,6-hexanedithiol, forming a self-assembled monolayer for single strand DNA (ssDNA) immobilization (probe). Next, the hybridization of the DNA strand on probe-modified AuNPs was allowed to happen in a gold colloid solution. Electrochemical impedance spectroscopy was employed to monitor the immobilization and hybridization event. The mechanism of this method demonstrated that the surface of the gold electrode was eventually covered due to the adsorption of ssDNA modified AuNPs, which increased the charge transfer resistance (Rct) significantly. In contrast, the stiff nature of hybridized DNA strands will repel the AuNPs from the gold electrode and reduce the Rct. The schematic diagram is presented in Fig. 10.5. The report showed a linear detection range of 1.0–200 nM, with a detection limit of 0.5 nM. The ability of gold nanoparticles to combine with other materials to form a hybrid for bio-sensing is currently considered a rising hope for designing nanosensors. Thus, the hybrid materials composed of gold nanoparticles are a preferred candidate for the fabrication of analytical devices for various applications. (Ryu et al., 2010) reported a new hybrid biosensor for label-free DNA detection using a gold nanoparticle-embedded silicon nanowire transducer. The fabricated silicon nanowire was sputtered with gold (Au), which was eventually modified with thiolated probe DNA. The reported biosensor was able to sense breast cancer DNA down to 1 pM (LOD). This report outlines a major breakthrough in hybrid nanostructure architecture for inexpensive label-free biosensors, avoiding complicated and expensive surface modifications. ZnO nanostructures coupled with metal nanoparticles could improve the optical and electronic properties of the hybrid material. In addition, metal nanoparticles may improve the performance of hybrid nanostructures and enhance the band-edge emission at the expense of defect emissions (Cheng et al., 2010). In this context, gold nanoparticles (AuNPs) appear to be the best counterpart for ZnO thin films because the AuNPs exhibit a higher electron affinity behavior, and the highest Schottky barrier, compared with that of other noble metals. In addition, Au complements ZnO in constructing nanocomposites because of its resistance to surface oxidation, and because it is both catalytically active and optically sensitive (Georgiev et al., 2014; Wang et al., 2012). Therefore, embedding AuNPs onto ZnO nanostructures enables a convenient, direct, and selective binding process for biomolecules (Liu et al., 2008). Further, the presence of the defect emission from the ZnO nanostructure catalyzes the excitation activity of the surface plasmon of AuNPs where the defect emission and surface plasmon absorption are interconnected.

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FIG. 10.5 A schematic diagram depicts the experimental procedures of the proposed method. (A): GNPs functionalization and hybridization; (B): GNPs covered with flexible single-stranded DNA will attach to the electrode and block charge transfer from solution to the electrode; (C): GNPs with stiff double-stranded DNA will not adsorb to the electrode surface, resulting in an only minor charge transfer resistance. Reproduced from Liu, X., Qu, X., Dong, J., Ai, S., Han, R., 2011. Electrochemical detection of DNA hybridization using a change in flexibility. Biosens. Bioelectron. 26, 3679–3682, Elsevier.

The electron recombination in the valence band of the ZnO matrix is made possible due to the transfer of surface plasmon from the conduction band (CB) to the valence band (VB). Due to these appealing characteristics and their suitable optical properties, ZnO/Au has attracted a great deal of attention over the years (Park et al., 2014; Su and Qin, 2015).

10.3 Interdigitated Electrodes Interdigitated electrodes (IDE) often serve as an intermediary between the signal processing system and the biological/chemical analyte. This intermediate electrodes can be directly interfaced with bio-analytes, or in some other cases, the electrode could be coated with a sensing layer, such as metal oxide or polymers, to improve their sensing capabilities

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(Ghafar-Zadeh and Sawan, 2010). The IDE-based sensor has lots of benefits and advantages for biosensor development due to its structural design. The design of IDE consists of twin electrodes that are arranged in a comb-like structure to form gaps between the two electrodes. The IDE-based sensor is largely utilized for gas sensor applications and electrochemical sensors (Ahn et al., 2011; Tamaki et al., 2008). The IDE sensor is also used for signal acquisition as a part of sensor application. The working mechanism of IDE for signal acquisition occurs by measuring the changes of capacitances and impedance values when the anchored species binds with its complementary targets (Laureyn and Lagae, 2009). In order to enhance the sensitivity impedance detection of the IDE sensor, gold IDE is used for bio-molecular detection. Further, in the nano-creation, such as bottom-up fabrication, it is difficult to construct a reliable ohmic contact. Thus, the unique physical and electrical properties of IDE are attributes to the formation of highly sensitive transducing platforms and reliable ohmic contact. The miniature IDE has been widely used in various transduction methods where the ˜ oz-Berbel et al., 2008). sensitivity of the systems has improved extensively (Mun Finot et al. (2003) showed that 100 nm nanoelectrodes fabricated using e-beam lithography successfully characterized single- and double-stranded DNA. These nanoelectrodes have a lower signal to noise ratio (SNR) compared with microelectrodes. The author has characterized a label-free DNA biosensor using an electrochemical method that yields the detection limit of 100 μM. Recently, Fang et al. (2013) fabricated real-time and label-free detection of DNA using IDE electrodes. The contactless impedance measurement on this IDE sensor has a discriminate 1 nM DNA concentration. Hence, over the years, the sensitivity of the IDE electrodes has been improved and optimized to achieve micro to nanomolar range detection. This suitable method for fabricating an IDE sensor has been studied and investigated by researchers intensively over the years. IDE electrodes can fabricate using simple conventional photolithography approaches, such as pattern transfer and a lift-off method. Nevertheless, researchers also often choose standard silicon photolithography combined with deep reactive ion etch (DRIE) approaches to fabricate highly optimized IDE sensors. Moreover, there are groups that have reported the fabrication of highly sensitive IDE sensors using micro-electro-mechanical system (MEMS) technology (Kim et al., 2012). A simple interdigitated gold was fabricated using a combination of e-beam lithography and chemical vapor deposition (CVD) by Bonanni et al. (2010). The author patterned the SiO2 substrate using a lift-off process. Subsequently, a thin layer of titanium for adhesion followed by a 20 nm gold layer was evaporated onto the structures. Eventually, the lift-off sacrificial layer was removed, forming the gold interdigitated nanoelectrodes’ 100 nm width and 250 nm pitch. Conversely, Singh et al. (2010) has successfully fabricated a linear array of 500 nm width gold IDE after testing several different gap combinations. The author showed a simple and conventional lithography method combined with a deep reactive ion etch (DRIE) to developed an IDE sensor. The material that is used for the IDE fabrication process is gold, due to its affinity toward forming self-assembled monolayers and stable electrodes.

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Si

Silicon

(A) SiO2

Silicon

Si SiO2

SiO2

(B) Self-cutoff

Self-cutoff

Self-cutoff

Au SiO2

Si SiO2

Silicon SiO2

(C) FIG. 10.6 Fabrication sequence of the electrodes: (A) photolithography and DRIE, (B) thermal oxidation, and (C) metallization, self-cutoff. Reproduced from Chen, X., Zhang, J., Wang, Z., Yan, Q., 2012. Fabrication of submicrongap electrodes by silicon volume expansion for DNA-detection. Sensors Actuators A Phys. 175, 73–77, Elsevier.

Recently, Chen et al. (2012) reported a unique size expansion method to fabricate submicron-gap interdigitated electrodes for highly sensitive DNA detection. In this report, the author combined conventional photolithography and a deep reactive ion etch (DRIE) process to pattern the silicon substrates with micron electrodes. Next, the author applied wet thermal oxidation to induce the growth of SiO2, which subsequently leads to volume expansion. Moreover, a thin layer of gold was evaporated on the patterned IDE structure as illustrated in Fig. 10.6. Hence, the optimization of thermal oxidation has led to fabrication of low-cost batch-production of submicron and nanometer-level interdigitated electrodes (1.8 μm, 1.3 μm, and 600 nm). Finally, the suitability of the fabricated IDE for DNA discrimination was tested. The results showed that the 600 nm narrowed gap IDE has a higher current and sensitivity. The design and optimization of the IDE sensor as a transducer for biomolecule sensing has come a long way since it was first introduced. The IDE sensor geometry, which consists of twin electrodes that are arranged in a comb-like structure to form gaps, has influenced the electrical properties significantly. According to Van Gerwen et al. (1998), the IDE fingers should be as narrow (width (W) and gap (G)) as possible to direct the optimum electric field toward the surface of immobilized and hybridized bio-molecules at the nanoelectrode. In contrast, Singh et al. (2010) showed that the heights (H) of electrodes can largely effect the performance of the IDE sensors. Based on the simulation results, the studies showed that increasing the height (H) and the length (L) of the electrodes increases the sensitivity significantly. This led to more bio-molecule interaction sufficient

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Polyimide Silicon substrate Au electrode FIG. 10.7 Cross-sectional schematic of the newly designed capacitive humidity sensor. Reproduced from Kim, J.H., Moon, B.M., Hong, S.M., 2012. Capacitive humidity sensors based on a newly designed interdigitated electrode structure. Microsyst. Technol. 18, 31–35, Springerlink.

to increase the area of the surface of the electrodes. The literature indicates that IDE sensitivity and stability can be further expanded by adding a coating of photosensitive polymeric film on top of the electrodes, as illustrated in Fig. 10.7 (Kim et al., 2012; Kitsara et al., 2007). The heights of the coated films can play an important role in the performance of IDE sensors. Generally, the fringing electrical field lines of interdigitated electrodes will set randomly around the electrodes for planar IDE sensors. However, the addition of a photosensitive polymer coating on the electrode surface would allow the confinement of the fringing electric field concentrated around the polymer coated area within the sensing layer. Furthermore, Kim et al. (2012) showed that by altering the thickness of the coated polymer layer, the sensitivity of the sensor can be improved significantly compared with the bare IDE sensor. The results also showed that the higher the thicknesses of the polymer layer, the higher the sensitivity. This is because the height of the polymer coating would be able to determine the amount of the confined fringing of the electric field lines. Moreover, Bratov et al. (2008) recently reported a new method to yield higher sensitivity by fabricating a three-dimensional IDE sensor with an insulating barrier separating the electrode digits apart. Fig. 10.8 shows the three-dimensional IDE sensor with an insulating barrier and its fringing electric line field. In this method, the conductivity of the sensor is highly affected by the binding of bio-molecules toward the active sensing area of the transducer. In addition, the three-dimensional IDE sensor is shown to be more efficient compared with the planar IDE. Nevertheless, the author also showed that this threedimensional IDE sensor also can be easily cleaned and reused.

10.4 Zinc Oxides for Nanobiosensors Over the past decade, many important technological advances have provided us with the tools and materials needed to construct biosensor devices. Since the first invention of the Clark Oxygen Electrode sensor, there have been many improvements in the sensitivity, selectivity, and multiplexing capacity of the modern biosensor. Before the various types

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FIG. 10.8 (A) Planar IDEA device, (B and C) cross-section A-A of the planar IDEA device, and (D) IDEA device with insulating barriers between electrode digits. (1) Insulating substrate, (2 and 3) electrodes collector bars, (4) contact pads, (5 and 6) electrode “digits,” (7) electric field lines, (8) immobilized biomolecules, and (9) insulating barrier. Reproduced from Bratov, A., Ramon-Azcon, J., Abramova, N., Merlos, A., Adrian, J., Sannchez-Baeza, F., Marco, M.P., Dominguez, C., 2008. Three-dimensional interdigitated electrode array as a transducer for label-free biosensors. Biosens. Bioelectron. 24, 729–735, Elsevier.

of biosensor technologies and applications are discussed, it is first important to understand and define “biosensor.” According to IUPAC recommendations 1999, a biosensor is an independently integrated receptor transducer device, which is capable of providing selective quantitative or semi-quantitative analytical information using a biological recognition element (Thevenot et al., 1999). Essentially it is an analytical device, which incorporates a biological or biologically derived recognition element to detect a specific bio-analyte integrated with a transducer to convert a biological signal into an electrical signal (Lowe, 2008). The purpose of a biosensor is to provide rapid, real-time, accurate, reliable information about the analyte of interrogation (Perumal and Hashim, 2013). Among various types of nanostructured metal/semiconductor hybrids that have been developed, nanostructured zinc oxide (ZnO) has been intensively studied because of its unique nano-morphology, functional bio-compatibility, chemical stability, sensitivity, non-toxicity, and high catalytic properties (Foo et al., 2013; Jiang et al., 2014; Perumal et al., 2015a,c). In brief, zinc oxide (ZnO) has unique optical and electronic properties as an important metal oxide semiconductor derived from the group II–VI series in the periodic table. ZnO has a wide bandgap of 3.37 eV and a large excitation binding energy of 60 meV. ZnO nanostructures possess excellent electrical properties, which are suitable for fast and accurate sensing applications (Ali et al., 2012; Perumal et al., 2015b, 2016; Tak et al., 2014). The biocompatibility characteristics exhibited by ZnO are highly desired for surface functionalization and interfacing with chemical and biological compounds at pH extremes (Haarindraprasad et al., 2015; Liu et al., 2008; Wang et al., 2010). Moreover, ZnO has an advantage due to its suitability for simple fabrication of various nanostructures, which potentially results in lower cost ZnO-based devices (Bai et al., 2013; Kashif et al., 2013).

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This unique characteristic of ZnO has become a rising hope and a motivation for the development of highly sensitive, stable, and selective analytical devices. Biosensors are normally categorized according to the transduction method they employ. The transducer is a component of the biosensor that has an important role in the signal detection process. Hence, the transducer can be defined as a device that converts a wide range of physical, chemical, or biological effects into an electrical signal with high sensitivity and minimum disturbance to the measurement (Lowe, 2008). There are a number of transducer methods that have been developed over the past decade, and recent literature reviews have highlighted the most common methods of electrochemical transduction. This group can be further divided into four general categories; amperometric, potentiometric, conductometric, and impedance spectroscopy, the latter gaining more prominence recently (Parkinson and Pejcic, 2005). Among these methods of electrochemical transduction, impedance spectroscopy has been reviewed in detail.

10.4.1 Electrochemical Impedance Spectroscopy The electrical impedance spectroscopy (EIS)-based transduction method is not a commonly used method of electrochemical detection, and has only recently become a popular tool for bioreceptor transduction. The term “impedance” refers to the response/resistance to a current flow in a circuit element such as resistor, capacitor, inductor, and so forth, which is driven by alternating voltage or a current as a function of frequency (Macdonald and Johnson, 2005). This method is similar to other electrochemical detection devices, but with a conductivity detection that scans the detection volume with an electrical frequency sweep in the range of 10 kHz and 10 MHz (McGuinness and Verdonk, 2009). Essentially, impedance spectroscopy has major advantages over lower concentration detection methods. A recent study shows that EIS-based transduction has been employed in tumor growth detection in 100–600 fg/mL with a sensitivity/detection limit of 100 fg/mL (Onur and Kemal, 2011). The EIS-type measurement is suitable for real-time monitoring because it is able to provide a label-free or reagentless detection (Parkinson and Pejcic, 2005; Pejcic et al., 2006). In EIS measurement, the sample is placed on the sensing device, such as on the nanogap, and a controlled alternating voltage is applied to the electrode, and the current flow through the sample is monitored. The electrical impedance resulting from the sample is calculated as the ratio of voltage over current. The resulting electrical impedance measurement has both a magnitude and a phase: a complex number. For any time-varying voltage applied, the resulting current can be in phase with the applied voltage (resistive behavior), or out of phase with it (capacitive behavior). The EIS consists of a three electrode system, a potentiostat, and a frequency response analyzer (FRA). The three electrodes are the working electrode, which provides the measurement of current; the counter-electrode that provides current to the cell; and the reference electrode for voltage measurement. The potentiostat functions as a high-input impedance provider in order to maintain the voltage across the electrode (Barsoukov and Macdonald, 2005). Essentially, the FRA is incorporated to supply an excitation

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waveform and to provide a very convenient, high precision, wide band method of measuring the impedance (Barsoukov and Macdonald, 2005). The main advantage of an electrochemical impedance spectroscopy-based biosensor is the representation of the electrochemical cell into a pure electronic model. The electrochemical reaction at the electrode interface can be represented by an electronic circuit using equivalent circuit element analysis (Macdonald and Johnson, 2005). The EIS analysis comprises more information compared with any other direct current (DC) measurement. The system is also highly sensitive to more than one electrochemical reaction taking place. However, the EIS-based biosensor is an expensive and complex method compared with other electrochemical approaches (Barsoukov and Macdonald, 2005; Macdonald and Johnson, 2005). A recent review by Yang and Bashir (2008) discussed the progress and application of the impedance biosensor for food-borne pathogenic bacteria detection. Impedance spectroscopy has been widely used by many research groups to detect cancer/tumor cells, viruses, bacteria, and pathogens (Bayoudh et al., 2008; Diouani et al., 2008; Hong et al., 2012; Kukol et al., 2008; Ohno et al., 2012; Thi et al., 2012). This biosensor could become a powerful tool for clinical diagnostics in the imminent future (Pejcic et al., 2006).

10.4.1.1 Randles Equivalent Circuits and Nyquist and Bode Plots In electrochemical impedance spectroscopy analysis, the electrochemical cell reaction can be represented as an electronic model using equivalent circuit modeling. The modeling is done by arranging the passive electrical current elements into a network. This circuit element is commonly composed of resistors, capacitors, inductors, and so forth. The complete circuit elements with admittance and impedance are provided in Table 10.1. The impedance measurement can provide real and imaginary impedance components with a phase angle shift as a function of frequency (Macdonald and Johnson, 2005). The equivalent circuit can be derived from a resulting plot from a measurement, and vice versa. The most chemical system from electrochemical impedance at the interfaces can be modeled as Randles cells (Beasley, 2016; Macdonald and Johnson, 2005). The circuit components in Randles cells can easily match any physical phenomena, such as adsorption. The studies of molecular influences on the ZnO thin film electrical transport properties using impedance spectroscopy has been reported by (Sappia et al., 2015).

Table 10.1 The Circuit Elements With Admittance and Impedance (Beasley, 2016) Equivalent Elements

Admittance

Impedance

R C L W (infinite Warburg) Q (CPE)

1/R ȷωC 1/ȷωL Y˳√(ȷω) 1/Y˳√(ȷω)a

R 1/ȷωC ȷωL 1/Y˳√(ȷω) Y˳√(ȷω)a

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The results show that momentous changes in the transport properties were resultant from the composition of the liquid, by means of the charge of the ions. The addition of enzyme GOx and a phosphate buffer solution led to changes in conduction through the thin films. Thus, the conduction through the ZnO thin film was inhibited by the entrapment of carriers at the grain boundaries. The author has constructed an equivalent circuit model for ZnO thin films that are composed of grain and grain boundaries components as shown in Fig. 10.9. Similarly, Foo et al. (2015) represented the physical phenomena of adsorption using Randles equivalent circuits. The modeling of the equivalent circuit was achieved using Zview (commercial software from Scribner Associated Inc). The Randless circuit, which was composed of the series resistor with pairs of parallel capacitors and resistors equating components such as metal contacts, grain, and grain boundaries is illustrated in Fig. 10.10. The author shows the impedance spectroscopy method using an IDE electrode coated with an Au-modified ZnO thin film for successful immobilization and hybridization of nucleic acid. The author also concludes that impedance measurement is a robust and suitable method in label-free biosensor fabrication for biomedical applications. EIS data can be represented as a Nyquist plot (complex plane) or Bode plot. The Nyquist plot is commonly known as a complex plane plot or Cole-Cole plot (Barsoukov Grain boundary Grain

Carrier pathway

CPE (G)

R(G)

CPE (CB)

R(GB)

CPE eq

Req

FIG. 10.9 Assumed structure of the ZnO thin films model of conduction with the different conduction pathways in the ZnO films. Each grain (G) is modeled with a parallel RC circuit, different from a similar circuit used for the grain boundaries (GB). The total conducting path is modeled as the equivalent of two circuits in a series. Reproduced from Sappia, L.D., Trujillo, M.R., Lorite, I., Madrid, R.E., Tirado, M., Comedi, D., Esquinazi, P., 2015. Nanostructured ZnO films: a study of molecular influence on transport properties by impedance spectroscopy. Mater. Sci. Eng. B 200, 124–131, Elsevier.

FIG. 10.10 Impedance spectra by immobilization and hybridization of DNA on Au-modified ZnO thin films. Modeling of impedance arc. Reproduced from Foo, K.L., Hashim, U., Voon, C.H., Kashif, M., Ali, M.E., 2015. Au decorated ZnO thin film: application to DNA sensing. Microsyst. Technol. 1–8, Springerlink.

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FIG. 10.11 Complex plane of Nyquist plot. Reproduced from Gamry Instruments, 2007. Basics of electrochemical impedance spectroscopy. Gamry Instruments, Warminster, PA, Optical Society (OSA).

and Macdonald, 2005). The Nyquist plot can be obtained by plotting imaginary impedance components (Z00 ) against the real impedance component (Z0 ) at each excitation frequency. The Nyquist plot and the Randles equivalent circuit are shown in Fig. 10.11. The frequency is higher at the right-most end of the semicircle, and lowers at the left-most region. The value of ohmic resistance (Ru) can be obtained at the left-most end of the semicircle. Finally, the polarization resistance (Rp) can be obtained by adding the ohmic resistance value to the right-most end of the semicircle (Ru + Rp). EIS data represented using Nyquist plot approaches are favorable due to the simplicity in evaluating the effect of ohmic resistance. However, this plot has major limitations, such as absence of frequency, which prevents the calculation of electron capacitance effects (Raistrick et al., 2005; Reece, 2005). Fig. 10.12 shows the Bode plot for the same Randles equivalent circuit shown in Fig. 10.11. The Bode plot format differs from the Nyquist plot in terms of data presentation where the frequency is explicit. The absolute impedance, j Z j, and the phase shift of the resultant impedance as a function of frequency has been illustrated clearly in the Bode plot format. The distinct advantages of the Bode plot over the Nyquist plot are the frequency-explicit format in which the frequency is shown in one of the axes, where the impedance behavior of a circuit as a function of frequency can be clearly observed (Raistrick et al., 2005). Usually, the Bode plot data is presented in a logarithm of both of their axes to allow wide ranges of data presented on the same set of axes. Thus, the presence of frequency axes on the Bode plot would be advantageous for calculation impedance of capacitive or inductive elements, which strongly depends on a frequency.

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2.30E+03

CDL

Rp

Ru

–Imag (ohm)

1.80E+03

High freq

Low freq

1.30E+03

8.00E+02

3.00E+02

Ru –2.00E+02 0.00E+00

5.00E+02

1.00E+03

Ru + Rp 1.50E+03

2.00E+03

2.50E+03

3.00E+03

3.50E+03

Real (ohm) FIG. 10.12 Complex plane of Bode plot. Reproduced from Gamry Instruments, 2007. Basics of electrochemical impedance spectroscopy. Gamry Instruments, Warminster, PA, Optical Society (OSA).

The value for ohmic resistance (Ru) and the polarization resistance (Ru + Rp) can be yielded by plotting the log absolute impedance, j Zj, and the log phase shift against the log frequency curve as shown in Fig. 10.12. The ohmic resistance (Ru) can be obtained from the horizontal plateau at the right-most end of the highest frequency, as shown in Fig. 10.12. On the other hand, the polarization resistance (Ru + Rp) can be read from the horizontal plateau at the left-most end of the lowest frequency. Moreover, the double layer capacitance (CDL) value can be yielded by exploiting the intermediate frequencies curve. The major drawback of the Bode plot format is the shape of the curve. Unlike the fixed semicircle curve in the Nyquist plot, the shape of the curves are changeable according to the value in this plot (Raistrick et al., 2005). The great advantage of the Bode plot is that the presence of small resultant impedance can be easily identified in the presence of a large impedance (Beasley, 2016). In general, the Bode plot provides a clear alternative to the Nyquist plot for impedance data presentation.

10.5 DNA/Nucleic Acid Biosensor The use of a nucleic acids sequence for a specific diagnostic application was developed in 1953, and is still growing widely (Liu et al., 2012). The highly specific affinity binding’s reaction between two single strand DNA (ssDNA) chains to form double-stranded DNA (dsDNA) is utilized in the nucleic acids-based biosensor, which appoints the nucleic acids as the biological recognition element. This method has promoted the development of a DNA-based sensor from the traditional method, such as coupling of electrophoretic

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separations and radio isotropics, which are expensive, hazardous, time-consuming, and so forth (Parkinson and Pejcic, 2005). This biosensor’s working principle is based on recognition of the complementary strand of ssDNA to form a stable hydrogen bond between two nucleic acids to become dsDNA. In order to achieve this, an immobilized ssDNA is used as a probe in a bioreceptor in which the base sequence is complementary to the target of interest. Exposure of the target to the probe, which results in hybridization of complementary ssDNA to form dsDNA, will result in the production of a biochemical reaction that allows the transducer to amplify the signal into an electrical one. Subsequently, the literature shows that the presence of some linker such as thiol or biotin is needed in the effort to immobilize the ssDNA onto the sensing surface (Cagnin et al., 2009; Lazerges et al., 2012). An important property of DNA is that the nucleic acid ligands can be denatured to reverse binding and regenerated by controlling the buffer ion concentration (Ivnitski et al., 1999). The nucleic acid biological recognition layer that incorporates with the transducer is easily synthesizable, highly specific, and reusable after thermal melting of the DNA duplex (Teles and Fonseca, 2008). In addition, this biosensor possesses a remarkable specificity to provide analytical tools that can measure the presence of a single molecule species in a complex mixture (Brett, 2005). The DNA-based biosensor has potential applications in clinical diagnostics for virus and disease detection (Chua et al., 2011; Lui et al., 2009; Thuy et al., 2012). Moreover, Yeh et al. (2012) recently reported an optical biochip for bacteria detection based on DNA hybridization with a detection limit of 8.25 ng mL1. The development of an electrochemical DNA biosensor has received a great deal of attention lately, and this has largely been driven by the need to develop sensors that offer rapid response, high sensitivity, good selectivity, and experimental convenience (Liu et al., 2012).

10.6 Chapter Summary The review of the ZnO thin film deposition and growth technique for biosensor applications has been presented in this chapter. The ZnO nanostructure can be developed using a novel two-step method where the ZnO thin films synthesized through the sol-gel method and can be further grown using the hydrothermal method. At present, gold nanoparticles are the preferred candidate for the fabrication of hybrid analytical devices for various applications. Further, the unique biocompatibility characteristics of AuNPs offer selfassembly monolayer formation and immobilization of chemical or biological analytes. The IDE electrodes with a coating on the electrode surface would allow the confinement of the fringing electric field concentrated around the coated area within the sensing layer, and allow the enhancement of the transducing signal. The most common transduction method in bio-sensing is the electrochemical transduction method. Among the electrochemical transduction methods, electrochemical impedance spectroscopy has recently

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become a popular tool for bio-receptor transduction. This analysis comprises more information compared with any other direct current (DC) measurement, which becomes the main advantage of electrochemical impedance. The development of an electrochemical DNA biosensor is needed to develop a sensor that offers rapid response, high sensitivity, good selectivity, and experimental analytical devices.

References Addonizio, M.L., Aronne, A., Daliento, S., Tari, O., Fanelli, E., Pernice, P., 2014. Sol-gel synthesis of ZnO transparent conductive films: the role of pH. Appl. Surf. Sci. 305, 194–202. Ahn, J., Lee, T.H., Li, T., Heo, K., Hong, S., Ko, J., Kim, Y., Shin, Y.B., Kim, M.G., 2011. Electrical immunosensor based on a submicron-gap interdigitated electrode and gold enhancement. Biosens. Bioelectron. 26, 4690–4696. Ali, S.M.U., Ibupoto, Z.H., Kashif, M., Hashim, U., Willander, M., 2012. A potentiometric indirect uric acid sensor based on ZnO nanoflakes and immobilized uricase. Sensors (Basel) 12, 2787–2797. Anish Kumar, M., Jung, S., Ji, T., 2011. Protein biosensors based on polymer nanowires, carbon nanotubes and zinc oxide nanorods. Sensors (Basel) 11, 5087–5111. Armelao, L., Fabrizio, M., Gialanella, S., Zordan, F., 2001. Sol–gel synthesis and characterisation of ZnObased nanosystems. Thin Solid Films 394, 90–96. Bai, S., Sun, C., Guo, T., Luo, R., Lin, Y., Chen, A., Sun, L., Zhang, J., 2013. Low temperature electrochemical deposition of nanoporous ZnO thin films as novel NO2 sensors. Electrochim. Acta 90, 530–534. Barsoukov, E., Macdonald, J., 2005. Impedance Spectroscopy: Theory, Experiment, and Applications, second ed. A John Wiley & Sons, Inc., Publication. Bayoudh, S., Othmane, A., Ponsonnet, L., Ben, H., 2008. Electrical detection and characterization of bacterial adhesion using electrochemical impedance spectroscopy-based flow chamber. Colloids Surf. A Physicochem. Eng. Asp. 318, 291–300. Beasley, C., 2016. Basics of Electrochemical Impedance Spectroscopy, EIS and Its Application to Battery Analysis. http://www.gamry.com/application?notes/EIS/basics?of?electrochemical?impedance? spectroscopy/ Benramache, S., Benhaoua, B., Chabane, F., Guettaf, A., 2013. A comparative study on the nanocrystalline ZnO thin films prepared by ultrasonic spray and sol-gel method. Opt. - Int. J. Light Electron Opt. 124, 3221–3224.
rez-Murano, F., Alegret, S., Del Valle, M., 2010. DNA Bonanni, A., Ferna´ndez-Cuesta, I., Borris
e, X., Pe hybridization detection by electrochemical impedance spectroscopy using interdigitated gold nanoelectrodes. Microchim. Acta 170, 275–281. Boudjouan, F., Chelouche, A., Touam, T., Djouadi, D., Khodja, S., Tazerout, M., Ouerdane, Y., Hadjoub, Z., 2015. Effects of stabilizer ratio on photoluminescence properties of sol-gel ZnO nano-structured thin films. J. Lumin. 158, 32–37. Bratov, A., Ramon-Azcon, J., Abramova, N., Merlos, A., Adrian, J., Sannchez-Baeza, F., Marco, M.P., Dominguez, C., 2008. Three-dimensional interdigitated electrode array as a transducer for label-free biosensors. Biosens. Bioelectron. 24, 729–735. Brett, A.M., 2005. DNA based biosensors. In: Gorton, L. (Ed.), Biosensors and Modern Biospecific Analytical Techniques. Elsevier. Cagnin, S., Caraballo, M., Guiducci, C., Martini, P., Ross, M., Santaana, M., Danley, D., West, T., Lanfranchi, G., 2009. Overview of electrochemical DNA biosensors: new approaches to detect the expression of life. Sensors (Basel) 9, 3122–3148.

246

NANOBIOSENSORS FOR BIOMOLECULAR TARGETING

Chen, X., Zhang, J., Wang, Z., Yan, Q., 2012. Fabrication of submicron-gap electrodes by silicon volume expansion for DNA-detection. Sensors Actuators A Phys. 175, 73–77. Cheng, C.W., Sie, E.J., Liu, B., Huan, C.H.A., Sum, T.C., Sun, H.D., Fan, H.J., 2010. Surface plasmon enhanced band edge luminescence of ZnO nanorods by capping Au nanoparticles. Appl. Phys. Lett. 96, 3–5. Chow, M.K., Zukoski, C.F., 1994. Gold sol formation mechanisms: role of colloidal stability. J. Colloid Interface Sci. 165, 97–109. Chua, A., Yean, C.Y., Ravichandran, M., Lim, B., Lalitha, P., 2011. A rapid DNA biosensor for the molecular diagnosis of infectious disease. Biosens. Bioelectron. 26, 3825–3831. Cui, L., Wang, G.-G., Zhang, H.-Y., Sun, R., Kuang, X.-P., Han, J.-C., 2013. Effect of film thickness and annealing temperature on the structural and optical properties of ZnO thin films deposited on sapphire (0001) substrates by sol–gel. Ceram. Int. 39, 3261–3268. Daniel, M.C.M., Astruc, D., 2004. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size related properties and applications toward biology, catalysis and nanotechnology. Chem. Rev. 104, 293–346. Diouani, M.F., Helali, S., Hafaid, I., Hassen, W.M., Snoussi, M.A., Ghram, A., Jaffrezic-Renault, N., Abdelghani, A., 2008. Miniaturized biosensor for avian influenza virus detection. Mater. Sci. Eng. C Mater. Biol. Appl. 28, 580–583. Fang, X., Jin, Q., Jing, F., Zhang, H., Zhang, F., Mao, H., Xu, B., Zhao, J., 2013. Integrated biochip for label-free and real-time detection of DNA amplification by contactless impedance measurements based on interdigitated electrodes. Biosens. Bioelectron. 44, 241–247. Faraday, M., 1857. Experimental relations of gold (and other metals) to light. Philos. Trans. 147, 145–181. Farmanzadeh, D., Tabari, L., 2013. Electric field effects on the adsorption of formaldehyde molecule on the ZnO nanotube surface: a theoretical investigation. Comput. Theor. Chem. 1016, 1–7. Finot, E., Bourillot, E., Meunier-Prest, R., Lacroute, Y., Legay, G., Cherkaoui-Malki, M., Latruffe, N., Siri, O., Braunstein, P., Dereux, A., 2003. Performance of interdigitated nanoelectrodes for electrochemical DNA biosensor. Ultramicroscopy 97, 441–449. Flickyngerova, S., Shtereva, K., Stenova, V., Hasko, D., Novotny, I., Sutta, P., Vavrinsky, E., 2008. Structural and optical properties of sputtered ZnO thin films. Appl. Surf. Sci. 254, 3643–3647. Foo, K.L., Kashif, M., Hashim, U., 2013. Study of zinc oxide films on SiO2/Si substrate by sol–gel spin coating method for pH measurement. Appl. Mech. Mater. 284–287, 347–351. Foo, K.L., Hashim, U., Muhammad, K., Voon, C.H., 2014a. Sol–gel synthesized zinc oxide nanorods and their structural and optical investigation for optoelectronic application. Nanoscale Res. Lett. 9, 1–10. Foo, K.L., Kashif, M., Hashim, U., Liu, W.-W., 2014b. Effect of different solvents on the structural and optical properties of zinc oxide thin films for optoelectronic applications. Ceram. Int. 40, 753–761. Foo, K.L., Hashim, U., Voon, C.H., Kashif, M., Ali, M.E., 2015. Au decorated ZnO thin film: application to DNA sensing. Microsyst. Technol. 22 (4), 903–910. Frens, G., 1973. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nature 241, 20–22. Gautam, K., Singh, I., Bhatnagar, P.K., Peta, K.R., 2016. The effect of growth temperature of seed layer on the structural and optical properties of ZnO nanorods. Superlattice. Microst. 93, 101–108. Georgiev, P., Kaneva, N., Bojinova, A., Papazova, K., Mircheva, K., Balashev, K., 2014. Effect of gold nanoparticles on the photocatalytic efficiency of ZnO films. Colloids Surf. A Physicochem. Eng. Asp. 460, 240–247. Ghafar-Zadeh, E., Sawan, M., 2010. Capacitive sensing electrodes. In: CMOS Capacitive Sensors for Lab-On-Chip Applications: A Multidisciplinary Approach. pp. 25–33.

Chapter 10 • Microtechnology and Nanotechnology Advancements

247

Ghayour, H., Rezaie, H.R., Mirdamadi, S., Nourbakhsh, A.A., 2011. The effect of seed layer thickness on alignment and morphology of ZnO nanorods. Vacuum 86, 101–105. Ghosh, P., Han, G., De, M., Kim, C.K., Rotello, V.M., 2008. Gold nanoparticles in delivery applications. Adv. Drug Deliv. Rev. 60, 1307–1315. Giljohann, D.A., Seferos, D.S., Daniel, W.L., Massich, M.D., Patel, P.C., Mirkin, C.A., 2010. Gold nanoparticles for biology and medicine. Angew. Chem. Int. Ed. 49, 3280–3294. Greene, L.E., Law, M., Tan, D.H., Montano, M., Goldberger, J., Somorjai, G., Yang, P., 2005. General route to vertical ZnO nanowire arrays using textured ZnO seeds. Nano Lett. 5, 1231–1236. Greene, L.E., Yuhas, B.D., Law, M., Zitoun, D., Yang, P., 2006. Solution-grown zinc oxide nanowires. Inorg. Chem. 45, 7535–7543. Haarindraprasad, R., Hashim, U., Gopinath, S.C.B., Kashif, M., Veeradasan, P., Balakrishnan, S.R., Foo, K.L., Poopalan, P., 2015. Low temperature annealed zinc oxide nanostructured thin film-based transducers: characterization for sensing applications. PLoS ONE 10, 1–20. Hong, J., Lan, K., Jang, L., 2012. Electrical characteristics analysis of various cancer cells using a microfluidic device based on single-cell impedance measurement. Sensors Actuators B Chem. 173, 927–934. Hosono, E., Fujihara, S., Kimura, T., Imai, H., 2004. Non-basic solution routes to prepare ZnO nanoparticles. J. Sol-Gel Sci. Technol. 29, 71–79. Ivnitski, D., Abdel-hamid, I., Atanasov, P., Wilkins, E., 1999. Biosensors for detection of pathogenic bacteria. Biosens. Bioelectron. 14, 599–624. Jiang, R., Li, B., Fang, C., Wang, J., 2014. Metal/semiconductor hybrid nanostructures for plasmonenhanced applications. Adv. Mater. 26, 5274–5309. Kashif, M., Ali, M.E., Ali, S.M.U., Hashim, U., Hamid, S.B.A., 2013. Impact of hydrogen concentrations on the impedance spectroscopic behavior of Pd-sensitized ZnO nanorods. Nanoscale Res. Lett. 8, 1–9. Kim, J.H., Moon, B.M., Hong, S.M., 2012. Capacitive humidity sensors based on a newly designed interdigitated electrode structure. Microsyst. Technol. 18, 31–35. Kitsara, M., Goustouridis, D., Chatzandroulis, S., Chatzichristidi, M., Raptis, I., Ganetsos, T., Igreja, R., Dias, C.J., 2007. Single chip interdigitated electrode capacitive chemical sensor arrays. Sensors Actuators B Chem. 127, 186–192. Klubnuan, S., Suwanboon, S., Amornpitoksuk, P., 2016. Effects of optical band gap energy, band tail energy and particle shape on photocatalytic activities of different ZnO nanostructures prepared by a hydrothermal method. Opt. Mater. (Amst) 53, 134–141. Kukol, A., Li, P., Estrela, P., Ko-ferrigno, P., Migliorato, P., 2008. Label-free electrical detection of DNA hybridization for the example of influenza virus gene sequences. Anal. Biochem. 374, 143–153. Kumar, S., Gandhi, K.S., Kumar, R., 2007. Modeling of formation of gold nanoparticles by citrate method †. Ind. Eng. Chem. Res. 46, 3128–3136. Kumar, V., Singh, N., Mehra, R.M., Kapoor, A., Purohit, L.P., Swart, H.C., 2013. Role of film thickness on the properties of ZnO thin films grown by sol-gel method. Thin Solid Films 539, 161–165. Laudise, R.A., Ballman, A.A., 1960. Hydrothermal synthesis of zinc oxide and zinc sulfide. J. Phys. Chem. 64, 688–691. Laureyn, W., Lagae, L., 2009. Microelectronics-based biosensors for the detection of proteins and nucleic acids. In: Baraton, M.-I. (Ed.), Sensors for Environment, Health and Security: Advanced Materials and Technologies. Springer Netherlands, Dordrecht, pp. 319–332. Lazerges, M., Perrot, H., Rabehagasoa, N., Compe`re, C., 2012. Thiol- and biotin-labeled probes for oligonucleotide quartz crystal microbalance biosensors of microalga Alexandrium minutum. Biosensors 2, 245–254.

248

NANOBIOSENSORS FOR BIOMOLECULAR TARGETING

Liu, Y., Zhong, M., Shan, G., Li, Y., Huang, B., Yang, G., 2008. Biocompatible ZnO/Au nanocomposites for ultrasensitive DNA detection using resonance Raman scattering. J. Phys. Chem. B 112, 6484–6489. Liu, G., Liu, J., Davis, T.P., Gooding, J.J., 2011a. Electrochemical impedance immunosensor based on gold nanoparticles and aryl diazonium salt functionalized gold electrodes for the detection of antibody. Biosens. Bioelectron. 26, 3660–3665. Liu, X., Qu, X., Dong, J., Ai, S., Han, R., 2011b. Electrochemical detection of DNA hybridization using a change in flexibility. Biosens. Bioelectron. 26, 3679–3682. Liu, A., Wang, K., Weng, S., Lei, Y., Lin, L., Chen, W., Lin, X., Chen, Y., 2012. Development of electrochemical DNA biosensors. Trends Anal. Chem. 37, 101–111. Lowe, C.R., 2008. Overview of biosensor and bioarray technologies. In: Handbook of Biosensors and Biochips. John Wiley & Sons, Ltd. Lui, C., Cady, N.C., Batt, C.A., 2009. Nucleic acid-based detection of bacterial pathogens using integrated microfluidic platform systems. Sensors 9, 3713–3744. Macdonald, J.R., Johnson, W.B., 2005. Fundamentals of impedance spectroscopy. In: Impedance Spectroscopy: Theory, Experiment, and Applications. second ed. John Wiley & Sons, Inc., pp. 1–26 Matijevic, E., 1981. Monodispersed metal (hydrous) oxides—a fascinating field of colloid science. Acc. Chem. Res. 14, 22–29. McGuinness, R.P., Verdonk, E., 2009. Electrical impedance technology applied to cell-based assays. In: Cooper, M.A. (Ed.), Label-Free Biosensors: Techniques and Applications. Cambridge University Press, p. 251. ˜ oz-Berbel, X., Godino, N., Laczka, O., Baldrich, E., Mun˜oz, F.X., Del Campo, F.J., 2008. ImpedanceMun based biosensors for pathogen detection. In: Principles of Bacterial Detection: Biosensors, Recognition Receptors and Microsystems. Springer-Verlag, New York, pp. 341–376. Ohno, R., Ohnuki, H., Wang, H., Yokoyama, T., Endo, H., Tsuya, D., Izumi, M., 2012. Electrochemical impedance spectroscopy biosensor with interdigitated electrode for detection of human immunoglobulin A. Biosens. Bioelectron. 40, 422–426. Onur, Z., Kemal, M., 2011. A novel, ultra sensible biosensor built by layer-by-layer covalent attachment of a receptor for diagnosis of tumor growth. Anal. Chim. Acta 706, 343–348. Park, S., Mun, Y., An, S., In Lee, W., Lee, C., 2014. Enhanced photoluminescence of Au-functionalized ZnO nanorods annealed in a hydrogen atmosphere. J. Lumin. 147, 5–8. Park, J.-S., Mahmud, I., Shin, H.J., Park, M.-K., Ranjkesh, A., Lee, D.K., Kim, H.-R., 2016. Effect of surface energy and seed layer annealing temperature on ZnO seed layer formation and ZnO nanowire growth. Appl. Surf. Sci. 362, 132–139. Parkinson, G., Pejcic, B., 2005. Using Biosensors to Detect Emerging Infectious Diseases. Prepared for The Australian Biosecurity Cooperative Research Centre, pp. 1–80, Retrieved from: http://www.abcrc.org. au/pages/project.aspx?projectid¼75. Pejcic, B., De Marco, R., Parkinson, G., 2006. The role of biosensors in the detection of emerging infectious diseases. Analyst 131, 1079–1090. Perumal, V., Hashim, U., 2013. Advances in biosensors: principle, architecture and applications. J. Appl. Biomed. 12, 1–15. Perumal, V., Hashim, U., Gopinath, S.C.B., Haarindraprasad, R., Foo, K.L., Balakrishnan, S.R., Poopalan, P., 2015a. “Spotted Nanoflowers”: gold-seeded zinc oxide nanohybrid for selective bio-capture. Sci. Rep. 5, 12231. Perumal, V., Hashim, U., Gopinath, S.C.B., Haarindraprasad, R., Liu, W.W., Poopalan, P., Balakrishnan, S.R., Thivina, V., Ruslinda, A.R., 2015b. Thickness dependent nanostructural, morphological, optical and impedometric analyses of zinc oxide-gold hybrids: nanoparticle to thin film. PLoS ONE 10, 1–24.

Chapter 10 • Microtechnology and Nanotechnology Advancements

249

Perumal, V., Hashim, U., Gopinath, S.C.B., Haarindraprasad, R., Poopalan, P., Liu, W.-W., Ravichandran, M., Balakrishnan, S.R., Ruslinda, A.R., 2015c. A new nano-worm structure from gold-nanoparticle mediated random curving of zinc oxide nanorods. Biosens. Bioelectron. 78, 14–22. Perumal, V., Hashim, U., Gopinath, S.C.B., Rajintra Prasad, H., Wei-Wen, L., Balakrishnan, S.R., Vijayakumar, T., Rahim, R.A., 2016. Characterization of gold-sputtered zinc oxide nanorods—a potential hybrid material. Nanoscale Res. Lett. 11, 31. Polsongkram, D., Chamninok, P., Pukird, S., Chow, L., Lupan, O., Chai, G., Khallaf, H., Park, S., Schulte, A., 2008. Effect of synthesis conditions on the growth of ZnO nanorods via hydrothermal method. Phys. B Condens. Matter 403, 3713–3717. Polte, J., Ahner, T.T., Delissen, F., Sokolov, S., Emmerling, F., Thunemann, A.F., Kraehnert, R., 2010. Mechanism of gold nanoparticle formation in the classical citrate synthesis method derived from coupled in situ XANES and SAXS evaluation. J. Am. Chem. Soc. 132, 1296–1301. Popa, M., Mereu, R.A., Filip, M., Gabor, M., Petrisor Jr., T., Ciontea, L., Petrisor, T., 2013. Highly c-axis oriented ZnO thin film using 1-propanol as solvent in sol–gel synthesis. Mater. Lett. 92, 267–270.
nez, I.M., Tototzintle Huitle, H., Herna´ndez, L.A., Moure Flores, F., ˜ ones Galva´n, J.G., Sandoval Jime Quin
n Cervantes, A., Zelaya Angel, O., Araiza Herna´ndez Hernandez, A., Campos Gonza´lez, E., Guille Ibarra, J.J., 2013. Effect of precursor and annealing temperature on the physical properties of solgel deposited ZnO thin films. Results Phys. 3, 248–253. Raistrick, I.D., Franceschetti, D.R., Macdonald, J.R., 2005. Theory. In: Barsoukov, E., Macdonald, J.R. (Eds.), Impedance Spectroscopy: Theory, Experiment, and Applications. second ed., Wiley Online Library, pp. 27–128. Reece, C., 2005. An Introduction to Electrochemical Impedance Spectroscopy. https://www.jlab.org/ conferences/tfsrf/Thursday/Th2_1-EISintroReece.pdf. Accessed March 15, 2016 Ryu, S.-W., Kim, C.-H., Han, J.-W., Kim, C.-J., Jung, C., Park, H.G., Choi, Y.-K., 2010. Gold nanoparticle embedded silicon nanowire biosensor for applications of label-free DNA detection. Biosens. Bioelectron. 25, 2182–2185. Saha, K., Agasti, S.S., Kim, C., Li, X., Rotello, V.M., 2012. Gold nanoparticles in chemical and biological sensing. Chem. Rev. 112, 2739–2779. Sahoo, T., Kim, M., Lee, M.-H., Jang, L.-W., Jeon, J.-W., Kwak, J.S., Ko, I.-Y., Lee, I.-H., 2010. Nanocrystalline ZnO thin films by spin coating-pyrolysis method. J. Alloys Compd. 491, 308–313. Saikia, L., Bhuyan, D., Saikia, M., Malakar, B., Dutta, D.K., Sengupta, P., 2015. Photocatalytic performance of ZnO nanomaterials for self sensitized degradation of malachite green dye under solar light. Appl. Catal. A Gen. 490, 42–49. Sappia, L.D., Trujillo, M.R., Lorite, I., Madrid, R.E., Tirado, M., Comedi, D., Esquinazi, P., 2015. Nanostructured ZnO films: a study of molecular influence on transport properties by impedance spectroscopy. Mater. Sci. Eng. B 200, 124–131. Singh, K.V., Whited, A.M., Ragineni, Y., Barrett, T.W., King, J., Solanki, R., 2010. 3D nanogap interdigitated electrode array biosensors. Anal. Bioanal. Chem. 397, 1493–1502. Spanhel, L., Anderson, M.A., 1991. Semiconductor clusters in the sol-gel process: quantized aggregation, gelation, and crystal growth in concentrated zinc oxide colloids. J. Am. Chem. Soc. 113, 2826–2833. Su, L., Qin, N., 2015. A facile method for fabricating Au-nanoparticles-decorated ZnO nanorods with greatly enhanced near-band-edge emission. Ceram. Int. 41, 2673–2679. Tak, M., Gupta, V., Tomar, M., 2014. Flower-like ZnO nanostructure based electrochemical DNA biosensor for bacterial meningitis detection. Biosens. Bioelectron. 59, 200–207. Tamaki, J., Hashishin, T., Uno, Y., Dao, D.V., Sugiyama, S., 2008. Ultrahigh-sensitive WO3 nanosensor with interdigitated Au nano-electrode for NO2 detection. Sensors Actuators B Chem. 132, 234–238.

250

NANOBIOSENSORS FOR BIOMOLECULAR TARGETING

Tari, O., Aronne, A., Luisa, M., Daliento, S., Fanelli, E., Pernice, P., 2012. Sol–gel synthesis of ZnO transparent and conductive films: a critical approach. Sol. Energy Mater. Sol. Cells 105, 179–186. Teles, F., Fonseca, L., 2008. Trends in DNA biosensors. Talanta 77, 606–623. Thevenot, D.R., Toth, K., Durst, R.A., Wilson, G.S., 1999. Electrochemical biosensors: recommended definitions and classification. Pure Appl. Chem. 71, 2333–2348. Thi, B., Nguyen, T., En, A., Peh, K., Yue, C., Chee, L., Fink, K., Chow, V.T.K., Ng, M.M.L., Toh, C., 2012. Electrochemical impedance spectroscopy characterization of nanoporous alumina dengue virus biosensor. Bioelectrochemistry 88, 15–21. Thongsuriwong, K., Amornpitoksuk, P., Suwanboon, S., 2010. The effect of aminoalcohols (MEA, DEA and TEA) on morphological control of nanocrystalline ZnO powders and its optical properties. J. Phys. Chem. Solids 71, 730–734. Thuy, N.T., Tam, P.D., Tuan, M.A., Le, A.-T., Tam, L.T., Van Thu, V., Van Hieu, N., Chien, N.D., 2012. Detection of pathogenic microorganisms using biosensor based on multi-walled carbon nanotubes dispersed in DNA solution. Curr. Appl. Phys. 12, 1553–1560. Tokumoto, M.S., Briois, V., Santilli, C.V., Pulcinelli, S.H., 2003. Preparation of ZnO nanoparticles: structural study of the molecular precursor. J. Sol-Gel Sci. Technol. 26, 547–551. Triboulet, R., 2014. Growth of ZnO bulk crystals: a review. Prog. Cryst. Growth Charact. Mater. 60, 1–9. Tsay, C.Y., Fan, K.S., Wang, Y.W., Chang, C.J., Tseng, Y.K., Lin, C.K., 2010. Transparent semiconductor zinc oxide thin films deposited on glass substrates by sol-gel process. Ceram. Int. 36, 1791–1795. € stu € n, B.V., Turkevich, J., 1951. A study of the nucleation and Turkevich, J., Stevenson, P.C., Hillier, J., Enu growth processes in the synthesis of colloidal gold, Discuss. Faraday Soc. 11, 55. J. Am. Chem. Soc. 85, 3317 (1963). Upadhyayula, V.K.K., 2012. Functionalized gold nanoparticle supported sensory mechanisms applied in detection of chemical and biological threat agents: a review. Anal. Chim. Acta 715, 1–18. Van Gerwen, P., Laureys, W., Huyberechts, G., De Baeck, M., Baert, K., Suis, J., Varlan, A., Sansen, W., Hermans, L., Mertens, R., 1998. Nanoscaled interdigitated electrode arrays for biochemical sensors. Sensors Actuators B Chem. 49, 73–80. Wang, J., 2013. Electrochemical transduction. In: Handbook of Chemical and Biological Sensors. Academic Press. Wang, L., Sun, Y., Wang, J., Wang, J., Yu, A., Zhang, H., Song, D., 2010. Water-soluble ZnO-Au nanocomposite-based probe for enhanced protein detection in a SPR biosensor system. J. Colloid Interface Sci. 351, 392–397. Wang, X.J., Wang, W., Liu, Y.L., 2012. Enhanced acetone sensing performance of au nanoparticles functionalized flower-like ZnO. Sensors Actuators B Chem. 168, 39–45. Wang, M., Xing, C., Cao, K., Meng, L., Liu, J., 2014. Alignment-controlled hydrothermal growth of well-aligned ZnO nanorod arrays. J. Phys. Chem. Solids 75, 808–817. Wen, J., Hu, Y., Zhu, K., Li, Y., Song, J., 2014. High-temperature-mixing hydrothermal synthesis of ZnO nanocrystals with wide growth window. Curr. Appl. Phys. 14, 359–365. Wu, H., Hu, Z., Li, B., Wang, H., Peng, Y., Zhou, D., Zhang, X., 2015. High-quality ZnO thin film grown on sapphire by hydrothermal method. Mater. Lett. 161, 565–567. Yang, L., Bashir, R., 2008. Electrical/electrochemical impedance for rapid detection of foodborne pathogenic bacteria. Biotechnol. Adv. 26, 135–150. Yeh, C.-H., Chang, Y.-H., Lin, H.-P., Chang, T.-C., Lin, Y.-C., 2012. A newly developed optical biochip for bacteria detection based on DNA hybridization. Sensors Actuators B Chem. 161, 1168–1175.

Chapter 10 • Microtechnology and Nanotechnology Advancements

251

Yoon, Y., Park, K., Kim, S., 2015. Effects of low preheating temperature for ZnO seed layer deposited by sol–gel spin coating on the structural properties of hydrothermal ZnO nanorods. Thin Solid Films 597, 125–130. Znaidi, L., 2010. Sol–gel-deposited ZnO thin films: a review. Mater. Sci. Eng. B 174, 18–30. Znaidi, L., Soler Illia, G.J.A.A., Benyahia, S., Sanchez, C., Kanaev, A.V., 2003. Oriented ZnO thin films synthesis by sol–gel process for laser application. Thin Solid Films 428, 257–262. Znaidi, L., Chauveau, T., Tallaire, A., Liu, F., Rahmani, M., Bockelee, V., Vrel, D., Doppelt, P., 2015. Textured ZnO thin films by sol–gel process: synthesis and characterizations. Thin Solid Films 617, 156–160.

Further Reading Chen, M.-Z., Chen, W.-S., Jeng, S.-C., Yang, S.-H., Chung, Y.-F., 2013. Liquid crystal alignment on zinc oxide nanowire arrays for LCDs applications. Opt. Express 21 (24), 29277–29282. Gamry Instruments, 2007. Basics of Electrochemical Impedance Spectroscopy. Gamry Instruments, Warminster, PA.