Applications of Nanomaterials in Sensors and Diagnostics

Recent progress in synthesis and fundamental understanding of properties of nanomaterials has led to significant advancement of nanomaterial-based gas/chemical/biological sensors. This book includes a wide range of nanomaterials including nanoparticles, quantum dots, carbon nanotubes, graphene, molecularly imprinted nanostructures, nanometal structures, DNA-based structures, smart nanomaterials, nanoprobes, magnetic-based nanomaterials, phthalocyanines, and porphyrins organic molecules for various gas/chemical/biological sensing applications. Perspectives of new sensing techniques such as nanoscaled electrochemical detection, functional nanomaterial-amplified optical assay, colorimetric, fluorescence, and electrochemiluminescense are explored.

With recent advances in novel nanomaterial development, electroanalytical biosensors are undergoing a paradigm shift. New nanomaterial-based electrochemical biosensors can detect specific biomolecules at previously unattainable ultra-low concentrations. This chapter lists the existing biosensor technologies, describes the mechanisms, and applications of two types of electroanalytical biosensors, and then identifies the barriers in developing these biosensors and concludes by illustrating how nanomaterials can help overcome these limitations. A key feature of the electrochemical impedance sensor is that biomolecules detection can occur in real time without any pre-labeling. Specifically, this chapter summarizes the state of knowledge of the impedance sensor as applied in cancer and bone disease studies, which are clinically relevant.

We describe and discuss the different components necessary for the construction of a microfluidic system including micropump, microvalve, micromixer and detection system. For the microfluidic detector, we focus on carbon nanotube (CNTs) based electrochemical sensors. The properties, structure and nomenclature of CNTs are briefly reviewed. CNT modification and the use of CNTs in conjunction with electrochemical microfluidic detection are then extensively discussed.

Graphene is a novel and promising material for chemical and biosensing due to its extraordinary structural, electronic, and physiochemical properties. Recently, a large number of graphene-based chemical and biosensors with different structures and fabrication methods have been reported. In this chapter, graphene’s synthesis methods, properties, and applications in chemical and biosensing are extensively surveyed. Graphene-based chemical and biosensors may similarly be classified into three main groups including chemoresistive, electrochemical, and other sensing platforms. Chemoresistive graphene-based chemical sensors have been widely developed for ultrasensitive gas-phase chemical sensing with single molecule detection capability. Graphene-based electrochemical sensors for chemical and biosensing have shown excellent performances toward various non-bio and bio-analytes compared to most other carbon-based electrodes due to its very high electron transfer rate of highly dense edge-plane-like defective active sites, excellent direct electrochemical oxidation of small biomolecules and direct electrochemistry of enzyme while graphene FET chemoresistive biosensors for detections of DNA, protein/DNA mixture, and other antibody-specific biomolecules have been reported with high sensitivity and specificity. In addition, the graphene’s performance considerably depends on synthesis method and surface functionalized graphene oxides prepared by chemical, thermal, and particularly electrochemical reductions are demonstrated to be highly promising for both electrochemical and chemoresistive sensing platforms. However, large-scale economical production of graphene is still not generally attainable and graphene-based chemical and biosensors still suffer from poor reproducibility due to difficulty of controlling graphene sensor structures. Therefore, novel methods for well-controlled synthesis and processing of graphene must be further developed. Furthermore, effective doping methods should be developed and applied to enhance its sensing behaviors. Lastly, graphene’s chemical and biological interaction and related charge transport mechanisms are not well understood and should be further studied.

An introduction into the growing field of molecular imprinting is given, and some principle questions for the design of novel artificial molecular recognition polymers (MIPs) are raised. The limitations of the classical non-covalent imprinting approach are discussed in a brief form. Some novel strategies for the molecular imprinting of macromolecules, especially proteins, are reviewed, as well as new concepts for the integration with transducers and sensors. Two case studies from our own laboratory highlight the question of improving the performance of MIPs by the use of complementary functional monomers and demonstrate a new electrochemical approach to the imprinting of peptides and proteins.

Progress in nanotechnology has enjoyed exponential growth in the past couple of decades. We have seen design and synthesis of metal nanoparticles (NPs) tailored specifically for biomedical diagnosis. In particular, noble metals have attracted lots of attention. Because of their unique optical and electronic properties, Au and Ag NPs have been exploited in the fabrication of localized surface plasmon resonance (LSPR) chips for detection of biomolecules. They impart increased sensitivity and also allow development of analytical platforms for label-free detection. These metal NPs show specific changes in their absorbance responses in the visible region of the spectrum upon binding with various molecules such as nucleic acids or proteins. In addition, the electronic properties, in particular, of Au and Ag NPs have been employed as labels for detection of proteins and other target molecules. In this chapter, we will focus on the use of Au NPs in LSPR-based biosensor technology. We will discuss the principles and applications of how these NPs have been and can be exploited for medical diagnostics by providing examples, mainly to the work we have conducted in our research group.

This chapter describes DNA sensors (genosensors) that employ electrochemical impedance signal as transduction principle. With this principle, hybridization of a target gene with the complementary probe is the starting point to detect clinical diagnostic-related genes or gene variants. Electrochemical impedance spectroscopy permits, then, a labeless detection, by simple use of a redox probe. As current topic, it will focus on the use of nanocomponents to improve sensor performance, mainly carbon nanotubes integrated in the sensor platform, or nanoparticles, for signal amplification. The different formats and variants available for detecting genes in diagnostic applications will be reviewed.

Cell-based immunotherapy has emerged as a promising therapy for the treatment of cancer. Measuring the changes in tumor volume and tumor markers post treatment has been the most common means of evaluating the therapeutic efficacy. In order to assess the consequences of a given therapy in real time, the development of efficient molecular probes and imaging modalities are urgently needed. Efficient molecular probes and imaging modalities will provide qualitative and quantitative real-time images with long-term stability in physiological conditions as well as low toxicity and high sensitivity for in vivo monitoring of the transplanted cells. Therapeutic cells can be intrinsically or extrinsically modified with proper molecular probes, amplified in vitro, and transferred back into the host. In this chapter, we will discuss the relative strengths and weaknesses of multiple molecular imaging modalities as well as recent advances in molecular imaging probes. We will also address their application in relation to in vivo tracking of dendritic cells (DCs), natural killer (NK) cells, and T cells. Noninvasive molecular imaging techniques have great potential in the diagnostic and prognostic assessments of patients.

With the increase in demands and applications, techniques to create electrochemical microdevices have made a remarkable progress over the last four decades. Key components of the electrochemical devices are electrodes that are easily fabricated by microfabrication techniques. Because of this, miniaturization, batch-fabrication, and integration with other components can easily be realized. This is a contrast to devices based on other detection principles. Miniaturization of the devices also brings with it additional advantages such as very small consumption of sample and reagent solutions, rapid mixing, and parallel processing. On the other hand, however, a challenging issue we often encounter is that it becomes increasingly difficult to maintain the performance that has been achieved by conventional electrochemical devices used in laboratories. To cope with the problem, nanotechnology provides good solutions. Numerous papers have been published to demonstrate the effectiveness of nanotechnology. Therefore, it is impossible to cover all the contents. However, a convincing conclusion is that nanotechnology really has surprising effects on sensing performance. With the wealth of knowledge of nanotechnology, their application to microfabricated devices will be the subject of the next stage. In this chapter, nanotechnologies applicable to the improvement of the performance of existing microfabricated electrochemical devices will be introduced. Although various techniques have been developed for single independent electrodes, those that may be difficult to apply to microfabricated devices are excluded. On the other hand, those that are applicable to nanoelectrodes are included.