Insight Into Fiber Optics For Pharmaceuticals Biology Essay

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Fiber optics is the fusion of science and engineering concerned with the design and application of optical fibers. Optical fibers are fine strands of glass or plastic that transmits the radiation by total internal reflection. By the choice of construction materials like silica, fluorides, phosphates and chalcogenide, the fiber will emit ultraviolet, visible or infrared radiations. For the transmission of radiation, the fiber is coated with the material that has refractive index smaller than that of fiber material. The so called optical sensors are luminescent, evanescent, thin film and plastic optical fiber sensors. These sensors have wide range of application ranging from light intensity, temperature, vibration and pH, chemical analysis, medical, pharmaceuticals, plastics and food and beverage industry. Amongst the pharmaceutical industry, optical sensors are used for glucose sensing, protein and dosage form analysis, identification of drugs and DNA oligomers, and the all-round development and quality of the drug product.

Key words: optical fibers, total internal reflection, optical sensors, pharmaceuticals

Fiber optics, though used comprehensively in the modern world, is a fairly simple and old technology. Guiding of light by refraction, the principle that makes fiber optics possible, was first established by Daniel Colladon and Jacques Babinet in Paris in the early 1840s [1]. Fiber optics is mainly used for transmitting radiation from one component to another with help of fibers [2]. Optical fibers are fine strands of glass or plastic that transmits radiation of distances of several hundred feet or more. Where images are to be transmitted, bundles of fibers, fused at the ends, are used. Fiber optics is used not only for observation but also for illumination of objects. Light transmission in an optical fiber takes place by total internal reflection, for that it is necessary that the transmitting fiber is coated with the material that has refractive index smaller than that of fiber material. By the choice of the construction material the fiber will emit either ultra violet, visible or infrared radiations [3].

Light is transmitted along a fibre by total internal reflection. Only certain modes of propagation are permissible. The number of permitted modes depends on the diameter of the fibre and the wavelength of the light used. Two types of fibres are available for a given incident wavelength namely, monomode and multimode. Monomode fibres have a narrow glass core of uniform refractive index profile and transmit only a single mode for light of a specific wavelength range and linearly polarized state. They produce a Gaussian spatial intensity distribution at their distal end. Multimode fibres have a greater core diameter and can transmit many a hundreds of light modes. They may have either a uniform or parabolically profiled cross sectional refractive index profile. It is much easier to launch high intensities into multimodal fibres because of their larger core size and higher numerical aperture, than their monomodal counterparts. They do however, have disadvantages related to modal noise. Any thermal or mechanical disturbance to the fibre affects each transmitted mode in a different way. As a result, although the total light intensity at the fibre exit remains constant, the far field radiation pattern formed by interference of these modes changes with time. Optical fibres are increasingly being used in a variety of sensors [4].

The materials of choice are silica, fluorides, phosphates, chalcogenide over plastic or glass fibers. Standard optical fibers are made by first constructing a large diameter preform, with a carefully controlled refractive index profile, and then pulling the preform to form the long, thin optical fiber. The preform is commonly made by three chemical vapour deposition methods: inside vapour deposition, outside vapour deposition, and vapour axial deposition [5]. Phosphate glasses can be advantageous over silica glasses for optical fibers with a high concentration of doping rare earth ions. A mix of fluoride glass and phosphate glass is fluorophosphates glass [6, 7].

Sensor systems and sensor types

The simplest sub division of optical sensors is into so called intrinsic devices, where the interaction occurs actually within an element of the optical fiber itself and extrinsic devices where the optical fiber is used to couple light, usually to and from the region where the light beam is influenced by the substance which is being measured [8].

Luminescent optical fiber sensors:

The use of luminescent phenomena, concentrating particularly on fluorescence for optical sensing, has been observed with a range of different fiber hosts. Clearly, those rare earths, which have been doped most usually into silica based fibers, or alternatively into fluoride glass or more exotic fiber materials, can equally be applied to the generation of simple fluorescence as to the creation of laser action. However, there is a wide range of other fluorescent materials which have been doped into plastic fibers, offering an alternative medium, particularly for sensing applications, where the loss mechanisms in plastic hosts, usually responsible for quenching laser action, are largely unimportant when the fluorescent output only is used. A major difference between silica and plastic fiber is the extreme flexibility of the latter, which allows it to be bent, often to a greater extent and with a smaller radius than silica fiber [9].

Evanescent wave fluorescent sensor:

A negative fibre is a leaky fibre in which the power loss strongly depends on the length of the fibre and can be optimised for fluorescence collection efficiency into the positive fibre attached to output end of the negative fibre. This is in contrast to the use of a positive fibre, in which the collection efficiency is independent of fibre length and depends on refractive index difference between core and cladding and the structure of the fibre. The sensor described is based on a fibre having two different structures, one guiding and other non-guiding. The combination of a guiding fibre (positive fibre) and a non-guiding fibre (negative fibre) can detect fluorescence emitted from molecules attached to the surface of the core of the negative fibre. The collection efficiency of a positive fibre increases as the refractive index difference between core and cladding increases [10, 11]. The fiber based evanescent wave sensor is shown in the fig.1.

Thin film sensors:

A different approach for IR fiber optical chemical sensors was realized by immobilizing enzyme layers like glucose oxidase on chalcogenide fibers to analyze glucose in complex aqueous matrices. The sensing scheme is based on following the catalyzed turnover reaction of glucose to gluconic acid and hydrogen peroxide. The monitoring of the concentration of the reaction products in the surrounding aqueous solution by evanescent wave spectroscopy presumes an enzyme layer thinner than the penetration depth of the Irradiation but with maximum reactivity of the catalytically active surface to provide a fast sensor response. Hence a careful treatment of the fiber surface with 3 aminopropyltriethoxysilane (APTS)/ glutaraldehyde before immobilizing the enzyme is evident [12, 13]. A new approach to improve the enzyme density on the fiber surface was developed by immobilizing glucose oxidase via bacterial S- layer protein [14].

Fluorescent plastic optical fiber sensors:

Fibers in this category are typically doped with organic dyes, of the type used extensively in the printing industry and for display. They are frequently used for decorative purposes, but clad and coated fibers with a fluorescent core are often exploited in sensing and measurement as a result of their ability to capture light, which excites them over their whole length. They can be used to measure mean ambient lighting, monitor faults in electrical circuits and switches [15] and for level detection [16]. Other important applications involve environmental sensing with plastic fibers, such as the humidity sensor [17] and the sensor developed for detecting gaseous pollutants [18].

Applications

Fibre optic sensors have many applications in various branches of science and engineering, as is evident from a vast range of properties which has been sensed optically, ranging from light intensity, vibration, temperature, pressure, calibration of accelerometers, strain, liquid level, pH, chemical analysis, concentration, density, refractive index of liquids etc [19, 20]. Optical refractive index is an inherent characteristic of a substance. Refractometers are frequently used for the study of molecular structure, identification of organic compounds, medical, pharmaceutical, plastic, food, industrial fluid, and petrochemical and beverage industry applications [21, 22].

Glucose sensor:

Initially the sensor made use of ultra violet visible wavelength and immobilized probes for detection [23, 24]. A fiber based pH meter has been developed in which the fiber cladding (10 cm) is replaced with a polymer (polyaniline) which has a broad band of sensitivity to pH [25]. As only a single broad band is measured, the system lends itself well to an IR laser diode system offering potential for miniaturization and greater portability. A modification of this sensor using glucose oxidase immobilised on the polyaniline polymer surface (an enzyme which converts glucose to glucuronic add, resulting in a pH change) allowed prediction of glucose concentrations [26].

Laminate cure analysis:

The small dimensions and durability of these probes makes them ideal for monitoring reactions in hostile environments. Fiber optic probes can be introduced into an autoclave (via the usually standard thermocouple calibration port) and thus can continuously monitor the progress of reactions (e.g. degradation) as a function of the operating conditions. This approach has previously been applied to the monitoring of processes in other industries, notably to monitor cure rates of polymer laminates at high temperatures and pressures [27, 28].

Protein analysis:

FTIR is useful for protein analysis since high quality spectra can be obtained from low concentrations of analyte in a variety of environments and in association with other components. Interference due to light scattering or fluorescence is not problematic. In addition, FTIR can be quite useful in assignment of absorbance peaks to the major structural features of a molecule, rather than just at one site (as with a chromophore or probe molecule). Globular proteins usually exhibit regions of secondary structure including alpha helices, P-sheets, turns and non-ordered regions. Each of these conformational entities contributes to the IR spectrum in the amide I contour region. In addition to the study of protein in its dried state, FTIR has been particularly useful for the study of soluble proteins, whose structures had not previously been elucidated using X-ray diffraction or NMR spectroscopy [29, 30].

Dosage form analysis:

Dreassi and co workers have reported the application of an optical fiber probe for quality control in the pharmaceutical industry [31]. Their system was used to quantitatively determine the content of a number of pharmaceutical solid dosage forms containing ibuprofen, and powders containing benzydamine and an analogue of cetrimide. A team from Burroughs-Wellcome have taken this one step further and have performed identification tests on tablets through the plastic wall of the blister packaging [32]. The system allowed the discrimination between film coated and uncoated tablets and between active and placebo forms. The technique fulfilled the requirements of a confirmation of identity test prior to use in a clinical trial [33].

Fiber optical scanning in TLC for drug identification:

A systematic toxicological analysis procedure using high-performance thin layer chromatography in combination with fibre optical scanning densitometry for identification of drugs in biological samples is done. The identifications were carried out by an automatic measurement and computer based comparison of in situ UV spectra with data from a compiled library of reference spectra using the cross-correlation function. The technique allows parallel recording of chromatograms [34].

Determination of DNA oligomers:

The binding of DNA oligonucleotides to immobilized DNA targets using a fibre optic fluorescence sensor is demonstrated. 13mer oligonucleotides were attached to the core of a multimode fibre. The complementary sequence was detected by use of a fluorescent double strand specific DNA ligand. The evanescent field was employed to distinguish between bound and unbound species. The template DNA oligomer was immobilized either by direct coupling to the activated sensor surface or using the avidin biotin bridge. Single base mismatches in the target sequence were detected [35].

Pesticide detection:

Fabrication and characterization of a surface plasmon resonance based fiber-optic sensor for the detection of organophosphate pesticide have been reported. The probe is prepared by immobilizing acetyl cholinesterase (AChE) enzyme on the silver coated core of plastic cladded silica (PCS) fiber. The detection is based on the principle of competitive binding of the pesticide (acting as inhibitor) for the substrate (acetyl thiocholine iodide) to the enzyme AChE. It has been observed that the SPR wavelength decreases with the increase in the concentration of the pesticide for the fixed concentration of substrate in the fluid around the probe. It has been found that the sensitivity decreases with the increase in the concentration of the pesticide while reverse is the case for detection accuracy [36].

Effluent monitoring:

Many processes in pharmaceutical manufacture use chlorinated hydrocarbons which constitute an environmental hazard [37, 38]. Chlorohydrocarbons have their strongest absorption bands and therefore polycrystalline silver halide fibers are of value as light guides. For quantitative measurements, the 10 cm fiber collectors were coupled to the FTIR and samples monitored. Comparative analysis of tetrachlorethylene and waste water samples showed good agreement with standard gas chromatographic techniques [39].

Other applications:

Fiber optic probe is also used for the determination of water by near infrared reflectance spectroscopy [40] and determination of penicillamine in pharmaceuticals and human plasma by capillary electrophoresis with in column fiber optics light emitting diode induced fluorescence detection [41]. DFB fiber lasers are used for the spectroscopic applications, military applications, biological and biomedical applications and highly sensitive airborne trace gas detection [42, 43].

Applications that are made possible by the use of filtered fiber optic Raman probes include such things as measuring high levels of organic solvent contaminants in soils and aquifers, chemical process monitoring of petrochemicals and distillation products, monitoring polymer cure reactions in situ and many others [44, 45, 46].

In spectroscopy, optical fiber bundles are used to transmit light from a spectrometer to a substance which cannot be placed inside the spectrometer itself, in order to analyze its composition. A spectrometer analyzes substances by bouncing light off of and through them. By using fibers, a spectrometer can be used to study objects that are too large to fit inside, or gasses, or reactions which occur in pressure vessels [47].

Future perspectives

With such an ongoing demand of optic fibers in the science world, novel techniques like such fiber optic probes in Raman and Attenuated Total Reflectance can be used for communications, military and defense, sensing and biomedical imaging. These probes can also help in the authentication of the drug product, and thus preventing the drug counterfeit.

Conclusion

An optical fiber made up of a core carries the light pulses which are not only used for sensing but also for the illumination purpose. Fiber optic probes undergo total internal reflection and assist in possible future biomedical applications to carry out the simultaneous collection and analysis of samples from clinical studies for drug safety evaluation. It also helps in the sensing of biomolecules, drug identification, effluent monitoring and overall pharmaceutical quality control of the product. Probes aid in the development of kinetics profile and are associated with short sample times, allowing the identification and measurement more accurate and reliable.

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