Zinc Oxide Nanorods and Their Application to Intracellular Glucose Measurements (2012)

The application of nanotechnology to medicine, referred to as nanomedicine, has the potential to provide fundamental understanding of phenomena and materials that at the nanoscale have novel properties and functions. Nanotechnology and nanoscience have the capacity to make a new wave of medical techniques through the manufacturing of bioactive nanoscale structures. It can bring fundamental changes to the study and understanding of biological processes in health and disease, as well as enable novel diagnostics and interventions for treating diseases like diabetes. The size domains of the components involved with nanotechnology are similar to that of biological structures. For example, a quantum dot is about the same size as a protein (&lt;10 nm) and drugcarrying nanostructures are the same size as some viruses (&lt;100 nm). Because of this similarity in scale and certain functional properties, nanotechnology is a natural progression of research such as synthetic and hybrid nanostructures that can sense and repair biological lesions anddamage, similarly to biological nanostructures. Nanotechnology offers sensing technologies that provide more accurate medical information more rapidly for diagnosing disease, and miniature devices that can manage treatment automatically (Arya et al. 2008). Nanotechnology has introduced new and exciting opportunities by using newly prepared nanostructure materials, for instance glucose biosensors. Because of its ubiquitous role in biology and medicine glucose is one of the most targeted analytes in bioanalysis whether it is in medicine or biotechnology. In biosensor based analysis glucose has attracted a clearly dominating interest due to the importance of glucose measurement for control of diabetes. The huge potential market for an artifi cial pancreas to optimally treat diabetes by continuously delivering the required concentration of insulin in the patient´s blood has stimulated the development of a large variety of glucose biosensors since the presentation of the fi rst glucose sensor by (Clarke and Lyons 1962) based on an amperometric oxygen electrode in combination with the enzyme GOD. Since then many different variations of glucose sensors have been proposed but amperometry has continued to be the dominating transducer technology and GOD the most commonly used enzyme. Enzymes are biological recognition molecules commonly employed in research and development because most chemical reactions in living systems are catalyzed by very specifi c enzymes. Earlier biosensors based on GOD measured the decrease in oxygen concentration but with time this concept was replaced by measuring the formation of hydrogen peroxide which provided more sensitive determinations. Similar amperometric electrode systems as for oxygen could be used but with reversed polarity. Among other glucose-specifi c enzymes, hexokinase has found widespread use especially in colorimetric analysis. GDH, such as NAD-dependent GDH and GDH-PQQ (with pyrroloquinoline quinone as cofactor that may be bound to the enzyme) have also attracted interest in order to avoid dependence on dissolved oxygen as for GOD. However, GOD is usually preferred since it is highly stable and specifi c and also cheap. It can also be used with other electron acceptors than oxygen, such as different quinones and ferrocene (Cass et al. 1984). The development of new amperometric glucose sensors have continued in different directions towards screen-printed devices, miniaturized and implantable devices and sensors incorporating nanomaterials (Santos et al. 2010). Nevertheless the long term stability of the sensors continues to be a serious limitation and in many cases sensors are fabricated only for single measurements and for a short period of time (hours). As a consequence, immobilization strategies for enzymes are important to preserve their biological activity (Wink et al. 1997). In contrast most other biosensors, thermal biosensors operating with a small fl ow-reactor with immobilized GOD/catalase can work with thousands of samples and year-long stability (Ramanathanand Danielsson 2001). There are many processes and methodologies developed for creating new glucose biosensors such as alternative electrochemical methods (Wang et al. 2008), colorimetry (Morikawa et al. 2002), conductometry (Miwa et al. 1994), optical methods (Mansouri et al. 1984), and fl uorescent spectroscopy (Pickup et al. 2005). Among them, the electrochemical glucose sensors have attracted most attention over the last 40 years because of their excellent sensitivity and selectivity. Moreover, electrochemical techniques show lower detection limit, faster response time, better long term stability and inexpensiveness (Mahbubur Rahman et al. 2010). Nanostructure metal-oxides such as ZnO have been extensively investigated to develop biosensors with high sensitivity, fast response time, and stability for the determination of glucose by electrochemical oxidation. In this chapter we demonstrate a functionalized ZnO nanostructure-based electrochemical sensor for selective detection of glucose in single human adipocytes and frog oocytes. Hexagonal ZnO nanorods were grown on the tip of a silver-covered borosilicate glass capillary (diameter 0.7 µm) to make possible microinjection of specifi c reagents, which can interrupt or activate signal transmission to glucose, into the relatively large cells of adipocytes and oocytes (Asif et al. 2010).