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The field of biomolecule sensing in the medical field is broad and rapidly evolving. The devices range in size from microns to centimeters across the sensing surface and rely on electronic, optical or other form of signals. If the sensing technology utilizes toxic reagents, then the use is limited to only in vitro application. In this chapter, biomolecule sensing using carbon nanotubes (CNTs) is discussed with specific application to cancer diagnostics.

With advances in biotechnology, genomics, and combinatorial chemistry, a wide variety of new, more potent and specific therapeutics are being created. Because of common problems such as low solubility, high potency, and/or poor stability of many of these new drugs, the means of drug delivery can impact efficacy and potential for commercialization as much as the nature of the drug itself. Thus, there is a corresponding need for safer and more effective methods and devices for drug delivery. Indeed, drug delivery systems—designed to provide a therapeutic agent in the needed amount, at the right time, to the proper location in the body, in a manner that optimizes efficacy, increases compliance and minimizes side effects—were responsible for $47 billion in sales in 2002, and the drug delivery market is expected to grow to $67 billion by 2006.

Nanofabrication techniques for feature sizes less than 100 nm are available for silicon-based materials using high cost, cleanroom-based methods. The high cost may be acceptable for large-throughput manufacturing in the IC industry, but the broader needs and lower volumes in biomedicine require more cost-effective mass-production methods capable of replicating nanostructures in a wide range of materials. However, the properties of silicon (poor impact strength/toughness, poor biocompatibility) are inappropriate for many biomedical devices. For example, the conductivity of silicon is problematic in many micro/nanofluidic applications that require high voltage for electrokinetic flows. Non-conductive glass or quartz devices can be made using the same lithography/etching fabrication techniques. These materials, although less costly than silicon, are still much more expensive than most polymeric materials. In contrast, polymeric materials possess many attractive properties such as high toughness and recyclability. Some possess excellent biocompatibility, are biodegradable, and can provide various biofunctionalities. Proper combination of functional polymers and biomolecules can offer tailored properties for various biomedical applications, but the ability to process them at the nanoscale to form well-defined functional structures is largely underdeveloped. Nanofabrication techniques for feature sizes less than 100 nm are available for silicon-based materials using high cost, cleanroom-based methods. The high cost may be acceptable for large-throughput manufacturing in the IC industry.

Nanotechnology is rapidly opening new possibilities in a wide variety of disciplines. Biomedical micro- and nano-devices, with components geometries as large as hundreds of microns to as small as a few nanometers, have potential uses that range from the analysis of biomolecules to disease diagnosis, prevention and treatment. Exciting technological advances have been made in nanofabrication and in micro- and nano-electromechanical systems [ 1 ] (MEMS, NEMS), microfluidic devices [ 2 ], micro- or nano-optics (diffractive optics [ 3 ], high efficiency multilevel zone plates [ 4 ], photonic crystals [ 5 ]), and innovations in the toolset of biology (microfluidic chips for DNA array [ 6 ]) and medical (microsurgical tools [ 7 ] and drug delivery), provide examples of advancement in nanotechnology. The application of carbon nanotube atomic force microscopy (AFM) imaging enabled multiplex detection of the positions of specific DNA sequences labelled with nanometer-size tags [ 8 ]. This method allowed the direct determination of haplotypes of patient samples, and provided a more accurate assessment of cancer risk from the UGT1A7 gene [ 8 ]. The phage display approach for isolating peptides with high binding affinities to specific crystal types discussed by Whaley et al. [ 9 ] might find use both in synthesis and self-assembly of hetero-structures made from nano-particles. The research in tissue engineering stands to benefit most from our growing ability to fabricate complex nano-structured materials. The enormous potential in nanotechnology is at least a few years from beginning to materialize the products and technologies involved in the medical application of nanotechnology. But the possibility of improved speed, greater sensitivity, reduced cost, and decreased invasiveness, has generated substantial interest in miniaturized devices.

Since the invention of silicon microfabrication technology in early 1960s, the integrated circuit (IC) has changed our world. During last 40 years, the semiconductor industry has come up as the fastest growing industry in our history. From a modest beginning, that allowed few transistors on a chip, we have reached integration level of tens of millions of components in a square cm of silicon. The minimum feature size on silicon is reducing and thus the number of devices per square cm is increasing. The observation made in 1965 by Gordon Moore [ 1 ], co-founder of Intel, that the number of transistors per square inch on integrated circuits had doubled every year since the integrated circuit was invented. Moore predicted that this trend would continue for the foreseeable future. In subsequent years, the pace slowed down a bit, but data density has doubled approximately every 18 months, and this is the current definition of Moore’s Law.

Owing to their nano-dimensions, rich electronic states, large surface area, high mechanical strength, and excellent chemical and thermal stability, carbon nanotubes have attracted a great deal of interest [ 1 ]. Among the many potential applications [ 1 , 2 ], carbon nanotubes have recently become promising functional materials for the development of advanced biosensors with novel features. It has been demonstrated that carbon nanotubes could promote electron-transfer with various redox active proteins, ranging from glucose oxidase [ 3 , 4 ] with a deeply embedded redox center to cytochrome c [ 5 , 6 ] and horseradish peroxidase [ 7 , 8 ] with surface redox centers. For the use of carbon nanotubes in biosensing applications, however, the ability to immobilize biomolecules on the carbon nanotube structure without diminishing their bioactivity is indispensable. Therefore, a number of intriguing physicochemical approaches have recently been devised for functionalization of carbon nanotubes with biomolecules [ 9 – 15 ]. Consequently, many biological species, such as DNA, proteins and enzymes, have been immobilized onto carbon nanotubes either on their sidewalls or at the end-caps [ 16 – 20 ]. While the carbon nanotube bioconjugates are functional materials essential for the development of advanced nanotube biosensors, the device design and fabrication also play an important role in regulating their biosensing performance. For many electrochemical biosensing applications, randomly entangled carbon nanotubes have been physically coated onto conventional electrodes [ 17 , 21 – 24 ]. The use of vertically aligned carbon nanotubes [ 25 ], coupled with well-defined chemical functionalization, should offer additional advantages for facilitating the development of advanced biosensors with a high sensitivity and good selectivity [ 20 , 26 – 28 ].

Nanotechnology is considered a fascinating subject not only by scientists, but also by people not involved in research. Likely, the appeal derives from common people thinking of nanotech devices as “invisible, mysterious objects”, capable of accomplishing complex tasks. Such a mysterious feeling can be explained by the fact that nanodevices features cannot be entrapped, because of their dimensions, by the common experience of human sensing, like other systems, exhibiting much more complex structures or functions, but macroscopic dimensions (e.g. airplanes, robots, skyscrapers).

The combination of a nonmaterial, magnetic nanoparticles, with magnetic resonance imaging, is yielding major advances in diverse areas of biology and medicine. This review will present a short history of iron oxide based nanoparticles, and review important new developments in the fields of magnetic nanoparticles and MRI. Magnetic nanoparticles are currently used in approved MRI contrast agents for imaging hepatic metastases and show considerable potential in clinical testing for imaging nodal metastases. New applications of magnetic nanoparticles include (i) ex-vivo labeling of cells with nanoparticles, followed by MR imaging in vivo, (ii) magnetic nanoparticles as biosensors termed magnetic relaxation switches, to measure a wide range of analytes in vitro, (iii) magneto/optical nanoparticles providing a fluorescent signal in addition to their magnetic character and (iv) biomolecule targeted magnetic nanoparticles for the imaging of specific molecular targets by MRI. This review will cover each of these diverse developments.

Gene therapy continues to hold promise in treating a variety of inherited and acquired diseases. The great majority of gene therapy trials rely on viral vectors for gene transduction because of their high efficiency. Viruses remain the vectors of choice in achieving high efficiency of gene transfer in vivo. Viral vectors, however, pose safety concerns unlikely to abate in the near future [ 1 – 3 ]. Issues of immunogenicity and toxicity remain a challenge. Limitations of cell mitosis for retrovirus, contamination of adenovirus, and packaging constraints of adeno-associated virus (AAV) also lessen their appeal. Non-viral vectors, although achieving only transient and lower gene expression level, may be able to compete on potential advantages of ease of synthesis, low immune response, and unrestricted plasmid size [ 4 – 9 ]. They have the potential to be administered repeatedly with minimal host immune response. They can also satisfy many of the pharmaceutical issues better than the viral vectors, such as scale-up, storage stability, and quality control. However, non-viral gene delivery is still too inefficient to be therapeutic for many applications. Development of safe and effective non-viral gene carriers is still critical to the ultimate success of gene therapy.

Since the 1950s, Scanning Electron Microscopy (SEM) has been commercially available and used to measure feature sizes below1 micron. Modified SEMs have been employed since the 1960s to perform sub-micron lithography, which then made rapid advances in the 1990s to a process, known as electron beam lithography (EBL). Since the 1980s, Surface Tunneling Microscopy (STM) and Atomic Force Microscopy (AFM) have ushered the era of nanotechnology where it is possible to measure and control the manipulation of matter on the 100nm scale and below. These techniques are broadly classified as “Scanning Probe Microscopy (SPM)”. The earliest forms of nanofabrication using STM based approaches were used to pattern “hard” materials (such as silicon-dioxide; as opposed to “soft” materials such as polymers or biological materials) and restricted to single layer processing. These methods were initially motivated by applications in the semi-conductor industry.