DNA plays an important role in many cellular processes like replication, homologous recombination and transcription. Besides its genomic information, DNA exhibits very interesting biophysical and physicochemical properties which are essential for proper functioning of the biomolecular processes involved. Biochips, particularly those based on DNA are powerful devices that integrate the specificity and selectivity of biological molecules with electronic control and parallel processing of information. This combination will potentially increase the speed and reliability of biological analysis. Microelectronic technology is especially suited for this purpose since it enables low-temperature processing and thus allows fabrication of electronics devices on a wide variety of substances like glass, plastic, stainless steel and silica wafer. Fundamental phenomena like molecular elasticity, binding to protein, supercoilling and electronic conductivity also depends on the numerous possible DNA confirmations and can be investigated nowadays on a single molecule level. Experiments with single DNA have been reported with scanning tunneling microscopy (Guckenberger et al., 1994), fluorescence microscopy (Yanagida et al., 1983), fluorescence correlation spectroscopy (Wannmalm et al., 1997), optical tweezers (Smith et al., 1996), bead techniques in magnetic fields (Wang et al., 1997), optical microfibers (Strick et al., 1996), electron holography (Smith et al., 1992a) and atomic force microscopy (Cluzel et al., 1996; Fink et al., 1999; Hansma et al., 1991). All these methods provide, directly or indirectly, information on molecular structure and function. They differ, however, in the molecular properties they probe, their spatial and temporal resolution, their molecular sensitivity and working environment.
Fluorescently labeled oligonucleotide probes are in regular use for nucleic acid sequencing (Mirzabekov, 1994), sequencing by hybridization (SBH) (Speel et al., 1999), fluorescence in situ hybridization (FISH) (Lakowicz et al., 1999), fluorescence resonance energy transfer (FRET) (Selvein, 2000), molecular beacons (Singh et al., 2000), taqman probes (Broude, 2002), and chip-based DNA arrays (Wittwer et al., 1997). This has made fluorescent probes an important tool for clinical diagnostics and made possible real-time monitoring of oligonucleotide hybridization. Furthermore, fluorescent-based diagnostics avoid the problem of storage, stability, and disposal of radioactive labels (Schena, 2000; Drobyshov et al., 1997).
Knowledge of structural and physical properties in microbial cells and microbial cell components is required to obtain a comprehensive understanding of cellular process and their dynamics. The need for a nondestructive method was satisfied with the development of the Atomic Force Microscope (AFM). The last 15 years have witnessed the extraordinary growth of structural studies in biology, and the impact is being felt in almost all areas of biological research. Several groups have used microscopy for the analysis of DNA, protein, and DNA-protein interactions. Until recently, electron microscopy was used as the main tool for imaging DNA; however this technique can be harsh on biological samples, making successful analysis extremely difficult. Approximately a decade ago, scientists began to use AFM for the analysis of biological samples. AFM allowed the analysis of biological molecules to be performed faster, easier and more accurately yielding successful characterization of biological specimens. The development of the AFM and its introduction for imaging biological samples has provided scientists with a very powerful tool to explore many aspects of protein-protein, protein-DNA and many other interactions (Fritz et al., 2000).
Various methods can be employed to bind DNA to different hosts. An array of substances, including catalytic antibodies, DNA, RNA, antigens, live bacterial, fungal, plant and animal cells, and whole protozoa, have been encapsulated in silica, organosiloxane and hybrid sol-gel materials. Sol-gel immobilization leads to the formation of advanced materials that retain highly specific and efficient functionality of the guest biomolecules within the stable host sol-gel matrix (Hench et al., 1990). The protective action of the sol-gel cage prevents leaching and significantly enhances stability of biomolecules within the sol-gel. The advantages of these ‘living ceramics’ might give them applications as optical and electrochemical sensors, diagnostic devices, catalysts, and even bio-artificial organs. With rapid advances in sol-gel precursors, nanoengineered polymers, encapsulation protocols and fabrication methods, this technology promises to revolutionize bioimmobilization. Biosensors using immobilized receptors are finding ever-increasing application in a wide variety of fields such as clinical diagnostics, environmental monitoring, food and drinking water safety, and monitoring of illicit drugs (Brinker et al., 1985). One of the most challenging aspects in development of these sensors is immobilization and integration of biological molecules in the sensor platform. Numerous techniques, including physical covalent attachment, and entrapment in polymer and inorganic matrices, have been explored over the past decade. Sol-gel processes are promising host matrices for encapsulation of biomolecules such as enzymes, antibodies, and cells (Kumar et al., 2000).
Porous silicon (PS) was discovered in 1956 by Uhlir (Uhlir, 1956) while performing electropolishing experiments on Silicon wafers using a hydrofluoric acid (HF)-containing electrolyte. Uhlir found that by increasing the current over a certain threshold, a partial dissolution of the silicon wafer started to occur. Porous Silicon formation can be obtained by electrochemical dissolution of Silicon wafers in aqueous or ethanoic HF solutions.
Microcavities are of interest for a wide range of fundamental and applied studies, including investigations of cavity quantum electrodynamics (Smith et al., 1992b), optical elements for telecommunications (Goryachev et al., 2003), single-photon sources (Chan et al., 2000), and chemical or biological sensors (Isola et al., 1998). Microfabrication techniques allow reproducible fabrication of resonators with lithographically controlled dimensions. Using a combination of lithography and etching, semiconductor microcavities have been obtained.
Almost all children under two years of age are infected by RSV. Children with weaker immune systems are at greater risk. For better health of all infants, infants with symptoms of common cold, wheezing, pneumonia and bronchiolitis need to be diagnosed for the RSV infection. All hospitals and physicians providing pediatric health care need RSV diagnosis kits. Current methods of detection are based on one single technology, i.e., immunological assays and they are very expensive and have low sensitivity and specificity. A new more robust technology is needed to diagnose children infected with RSV with higher sensitivity and specificity and at a very lower cost.
USPTO Backgrounds
USPTO Backgrounds