Fiber optic based sensor for bioanalytical absorbance measurements.
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Bilirubin↗
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Bioanalytical applications of fiber-optic chemical sensors.
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Blood Gas Analysis↗
Continuous monitoring of adriamycin in vivo using fiber optic-based fluorescence chemical sensor.
A novel method using a fiber optic-based fluorescence chemical sensor (FOCS) was developed for the preparation of on-line continuous monitoring of a drug in animals. First, an accurate optical design was used to enhance the intensity of light from a 100-microm optic fiber so the fluorescence signal can be detected. Second, A new sol-gel method was used to fix the fluorescence substance 4-(N,N-dioctyl)amino-7-nitrobenz-2-oxa-1,3-diazole (D-70) on the tip of the fiber. The variation in the quenching means variation in the concentration of Adriamycin (ADM) in rabbit's blood. ADM is determined by FOCS based on fluorescence multiple quenching. In a simple animal model, the carotid artery was catheterized with a cannula, housing a 100-microm optic fiber. The average recovery of all the tested compounds within the set concentration range was 99.4-106.2%; the within-day and between-day repeatability values were acceptable between 6.6-11.4% and 5.9-11.7%. The method permitted detection limits as low as 0.057 microg x mL(-1) at a signal-to-noise ratio of 3. The fiber optic chemical sensor is potentially useful for monitoring blood concentrations of drugs and metabilities in the biomedical field.
Animals↗
Development of an "electroptode" immunosensor: indium tin oxide-coated optical fiber tips conjugated with an electropolymerized thin film with conjugated cholera toxin B subunit.
We demonstrate that it is possible to create surface-conductive fiber optics, upon which may be electropolymerized a biotinylated polypyrrole thin film, which may then be used to affinity coat the fiber with molecular recognition probes. This fiber-optic electroconductive surface modification is done by the deposition of a thin layer of indium tin oxide. Thereafter, biotin-pyrrole monomers are electropolymerized onto the conductive metal oxide surface and then exposed to avidin. Avidin-biotin interactions were used to modify the fiber optics with biotin-conjugated cholera toxin B subunit molecules, for the construction of an immunosensor to detect cholera antitoxin antibodies. The biosensor was tested for sensitivity, nonspecificity, and overall practicality.
Antibodies↗
Real-time determination of picomolar free Cu(II) in seawater using a fluorescence-based fiber optic biosensor.
We report real-time, in situ determination of free copper ion at picomolar levels in seawater using a fluorescence-based fiber optic biosensor. The sensor transducer is a protein molecule, site-specifically labeled with a fluorophore that is attached to the distal end of an optical fiber, which binds free Cu(II) with high affinity and selectivity. The transducer reports the metal's concentration as a change in fluorescence intensity or lifetime, using a frequency domain approach. The transducer's response time is diffusion-limited, with a typical measurement requiring 30 s. The sensor demonstrates a detection limit of 0.1 pM free Cu(II) in a seawater model. Accuracy and precision of the sensor were at least comparable to cathodic ligand exchange/adsorptive cathodic stripping voltammetry. Measurements of tidal flushing of a copper-contaminated inlet are shown.
Biosensing Techniques↗
Multivariate chemometric approach to fiber-optic dissolution testing.
The use of fiber optics in in vitro dissolution testing opens up new possibilities for more powerful data evaluation since an entire UV-Vis spectrum can be collected at each measuring point. This paper illustrates a multivariate chemometric approach to the solution of problems of interfering absorbance of excipients in in vitro dissolution testing. Two different chemometric approaches are tested: multivariate calibration using partial least squares (PLS) regression and curve resolution using multivariate curve resolution alternating least squares (MCR-ALS), generalized rank annihilation (GRAM), and parallel factor analysis (PARAFAC). Multivariate calibration (PLS) can, following the construction of a calibration model from a calibration sample set, give selective and accurate determinations of the active ingredient in dissolution testing despite the presence of interfering absorbance from excipients. Curve resolution (MCR-ALS, GRAM, or PARAFAC) can be applied to dissolution testing data in order to determine the dissolution rate profiles and spectra for the interfering excipients as well as for the active ingredient without any precalibration. The concept of the application of these chemometric methods to fiber-optic dissolution testing data is exemplified by analysis of glibenclamide tablets enclosed in hard gelatin capsules. The results show that, despite highly overlapping spectra and unresolved raw data, it is possible with PLS to obtain an accurate dissolution rate profile of glibenclamide. Applying curve resolution makes it possible to obtain accurate estimates of both dissolution rate profiles and spectra of both the gelatin capsule and the glibenclamide. The application of multivariate chemometric methods to fiber-optic dissolution testing brings a fresh scope for a deeper understanding of in vitro dissolution testing, solving the problem of interfering absorbance of excipients and making it possible to obtain dissolution rate profiles and spectra of these. Obtaining dissolution rate profiles of multiple active pharmaceutical ingredients in tablets consisting of several active compounds is another possibility.
Calibration↗
Optical time-of-flight chemical detection: absorption-modulated fluorescence for spatially resolved analyte mapping in a bidirectional distributed fiber-optic sensor.
A continuous chemically sensitive optical fiber is used with optical time-of-flight chemical detection (OTOF-CD) for spatially resolved analyte mapping. To enhance signal levels and to improve their reproducibility, two novel principles for signal generation and processing are introduced. In the first, the fluorescene of an analyte-insensitive fluorophore is monitored as a function of the evanescent wave absorption of an analyte-sensitive indicator. The resulting signal levels are well above those encountered in optical time domain reflectometry methods that rely upon backscattering for spatially resolved detection. As a result, the method could significantly expand the range of species that can be detected with absorption reagents used in OTOF sensors. The second method raises signal-to-noise ratios by 3-4.5-fold for measurements made at the far ends of the sensing fiber. It functions by sending probe laser pulses into and monitoring their return sequentially from both ends of the sensing fiber. Because the two pulses provide complementary information, only the first half of each of the collected waveforms is used for analyte quantitation. The introduced concepts were experimentally verified with a distributed sensor constructed from a 40-m-long continuous chemically sensitive optical fiber. This sensing element was produced by immobilization of an ammonia-sensitive absorbing reagent (phenol red) and an analyte-insensitive fluorophore (rhodamine 640) into the original silicone cladding of the plastic-clad silica fiber.
Fiber Optic Technology↗
Fiber-optic enzyme biosensor for direct determination of organophosphate nerve agents.
A fiber-optic enzyme biosensor for the direct measurement of organophosphate nerve agents was developed. The basic element of this biosensor is organophosphorus hydrolase immobilized on a nylon membrane and attached to the common end of a bifurcated optical fiber bundle. The enzyme catalyzes the hydrolysis of organophosphate compounds to form stoichiometric amounts of chromophoric products that absorb light at specific wavelengths. The back-scattered radiation of the specific incident radiation was measured using a photomultiplier detector and correlated to the organophosphate concentration. The effects of buffer pH, temperature, and the units of enzyme immobilized on the steady-state and kinetic response of the biosensor were investigated to optimize the operating conditions for the fiber-optic enzyme biosensor. These conditions were then used to measure parathion, paraoxon, and coumaphos selectively without interference from carbamates and triazines. Concentrations as low as 2 microM can be measured in less than 2 min using the kinetic response. When stored in buffer at 4 degreesC the biosensor shows long-term stability.
Biosensing Techniques↗
Chemically stable films for combinatorial fluorosensor arrays.
Sensor arrays are useful for many purposes. Our interests include quasi-distributed intrinsic fiber optic arrays, those distributed along the length of an optical fiber. We have demonstrated an optical time-of-flight approach to distinguishing the fluorescence output of such arrays, as well as a synthesis of combinatorial libraries that takes advantage of a support of linear morphology to make numerous compounds in a simple manner without information loss in the synthesis. To unite these research areas, we needed an optical fiber cladding material that meets demanding synthetic and optical requirements. We have chosen the Meldal SPOCC polymer support as the best candidate for such a material and report here our initial results with this material.
Combinatorial Chemistry Techniques↗
Laser-induced multidimensional fluorescence spectroscopy in Shpol'skii matrixes for the analysis of polycyclic aromatic hydrocarbons in HPLC fractions and complex environmental extracts.
Fluorescence measurements are easily made with the aid of a cryogenic fiber optic probe. Emission wavelength time matrixes, excitation emission matrixes, and time-resolved excitation emission matrixes are rapidly collected with a pulsed tunable dye laser, a spectrograph, and an intensified charged-coupled device. Compound identification is based on spectral and lifetime information. The potential of this approach for supporting high-performance liquid chromatography analysis and for the direct determination of benzo[a]pyrene without previous separation is demonstrated.
Chromatography, High Pressure Liquid↗
Total protein measurement using a fiber-optic evanescent wave-based biosensor.
A novel method and instrumental system to determine the total protein concentration in a liquid sample is described. It uses a fiber optic total protein sensor (FOPS) based on the principles of fiber optic evanescent wave spectroscopy. The FOPS applies a dye-immobilized porous glass coating on a multi-mode optical fiber. The evanescent waves at the fiber optic core-cladding interface are used to monitor the protein-induced changes in the sensor element. The FOPS offers a single-step method for quantifying protein concentrations without destroying the sample. The response time and reusability of the FOPS are evaluated. This unique sensing method presents a sensitive and accurate platform for the quantification of protein.
Biosensing Techniques↗
The potential of Raman spectroscopy as a process analytical technique during formulations of topical gels and emulsions.
PURPOSE: The primary objective of this study is to investigate the possibility of using Raman spectroscopy as a process analytical technique (PAT) for quality control during manufacturing of topical dosage forms. METHODS: A fiber-optic Raman probe was used to monitor the formulation of pharmaceutical gel and emulsion in laboratory scale. Raman shifts of typical commercial raw materials used in topical dosage forms were measured to ascertain the potential of this technique for monitoring and analyzing topical products. Spectra of some well-characterized topical gels manufactured in our laboratory were also measured. RESULTS: Commercial raw materials were found to be Raman sensitive. Due to the difference in chemical composition, raw materials exhibit characteristic peaks that can be exploited to monitor formulation processes. Spectra taken during formulation of an emulsion using Carbopol Ultrez as thickener and Tefose as emulsifying agent show changes in Raman shifts immediately after major formulation steps. CONCLUSIONS: The findings from this work suggest that Raman spectroscopy can be a valuable process analytical technique for quality control of topical gel and cream formulations.
Acrylic Resins↗
Fluorescent organofilms for oxygen sensing in organic solvents using a fiber optic system.
Oxygen quenching of the luminescence of the tris(2,2'-bipyridyl)ruthenium(II) complex [Ru(bpy)3]2+, entrapped in gelatin-containing microemulsion-based organogels, has been shown to be an accurate and precise method for measuring oxygen concentrations in organic solvents (such as toluene, hexane and isooctane). Film composition was investigated in order to obtain sensing phases with high sensitivity to oxygen and suitable response times. Using a fiber optic design combined with a continuous flow system configuration, the dynamic response of oxygen-sensing films was less than 1 min for a full signal change. A detection limit of 0.2 ppm of oxygen in hexane-5% chloroform was found.
Fiber Optic Technology↗
Development of an in situ fiber optic Raman system to monitor hydrothermal vents.
The development of a field portable fiber optic Raman system modified from commercially available components that can operate remotely on battery power and withstand the corrosive environment of the hydrothermal vents is discussed. The Raman system is designed for continuous monitoring in the deep-sea environment. A 785 nm diode laser was used in conjunction with a sapphire ball fiber optic Raman probe, single board computer, and a CCD detector. Using the system at ambient conditions the detection limits of SO(4)(2-), CO(3)(2-) and NO(3)(-) were determined to be approximately 0.11, 0.36 and 0.12 g l(-1) respectively. Mimicking the cold conditions of the sea floor by placing the equipment in a refrigerator yielded slightly worse detection limits of approximately 0.16 g l(-1) for SO(4)(-2) and 0.20 g l(-1) for NO(3)(-). Addition of minerals commonly found in vent fluid plumes also decreased the detection limits to approximately 0.33 and 0.34 g l(-1) respectively for SO(4)(-2) and NO(3)(-).
Animals↗
Coupling micelle-mediated extraction using mixtures of surfactants and fluorescence measurements with a fiber-optic for the screening of PAHs in seawater.
The screening of PAHs from seawater samples using cloud-point extraction (CPE) as a step prior to their determination by fluorescence measurements with a fiber-optic is proposed. The CPE is carried out with the nonionic surfactants mixture POLE and Brij 30. The fluorescence measurement parameters were optimized, allowing selection of benzo(a)pyrene (B(a)Py) and benzo(k)fluoranthene (B(k)Ft) as the target analytes for the screening. The reproducibility of the whole screening system, expressed as relative standard deviation, was 9.0% for B(a)Py and 12.1% for B(k)Ft (both for n = 7). The reliability of the method was established at five concentrations for B(a)Py (between 0.5 and 3.3 times the detection limit: 0.31 ng ml(-1)) and at three concentrations for B(k)Ft (between 0.6 and 2.5 times the detection limit: 0.56 ng ml(-1)). The resolution of binary mixtures of these PAHs at different levels of concentration, and a study of the interferences with the rest of the PAHs were also carried out.
Fiber Optic Technology↗
Fiber-optic surface plasmon resonance for vapor phase analyses.
Fiber-optic sensors based on surface plasmon resonance (SPR) for direct refractive index (RI) measurements of samples with the RI between 1.00 and 1.30 are described. Most applications of SPR sensors are designed to function near the refractive index of water (1.3330 RI). The RI changes of aqueous solution (RI, ca. 1.34) can easily be monitored by silica-fiber (RI, 1.4601 at 550 nm) based SPR sensor. With regard to gas species detection, the fiber-optic SPR sensor must be modified for sensitivity to changes in refractive index near 1.0008 (i.e., RI of air). However, the silica waveguide has a prohibitively high RI for unmodified monitoring of the RI changes of gas. The silica-fiber based SPR probe design presented here is based upon the modification of the probe geometry to the ability to tune the SPR coupling wavelength/angle pair. In this study, the tapered silica-based fiber SPR sensors are shown to directly determine the RI changes of gas species and the density change of dry air.
Fiber Optic Technology↗
Development of catheters with low fiber background signals for Raman spectroscopic diagnosis applications.
Utilization of optical-fiber catheters can turn the Raman spectroscopy system into a powerful remote biomedical diagnostic probe. An in vivo (a qualitative and a quantitative) biochemical diagnosis of biotissues is possible by developing the Raman-fiber probes with a good flexibility and less background signals generated in the probes themselves. Considering the isotropic nature of Raman scattering, the amount of Raman signal guided through the fiber is expected to depend on the numerical aperture (NA) of the fiber. To study the dependence for catheter probes experimentally, various flexible probes (with small diameter fibers) with different combinations of numerical apertures and with different assembling materials (biocompatible) have been developed. The catheter probes have been characterized by collecting the near infrared excited Raman scattered light from cholesterol powder. The results demonstrate that the catheters with a combination of lower NA (0.12) fibers used for laser excitation and relatively higher NA (0.22) fibers for Raman signal collection will have lower background signals generated in the probes. Furthermore, the catheters with a black Teflon tubing cover and black epoxy resin adhesives were found to give better results.
Adhesives↗
[What is new in nasopharyngeal video fiber optic endoscopy in the diagnosis of snoring and patients with obstructive apnea?].
Videoendoscopy of the oropharynx was performed in 57 patients with habitual snoring and obstructive sleep apnoea syndrome. Endoscopy was done in waking supine subjects relaxed and during voluntary snoring, Esmarch's and modified Müller's manoeuvre. Evaluation of results for the first time was semiquantitative. Statistical analysis showed significant correlations (p less than 0.004) between movements of the base of the tongue and the modified Müller's manoeuvre. For the first time it could be shown that the dynamic changes in the pharyngeal walls during voluntary snoring are identical with those in the modified Müller's manoeuvre (p less than 0.006). Frame-by-frame analysis demonstrated epiglottic movements in the inspiratory cycle of snoring which result in a massive occlusion of the airway in 65% of our patients. Videoendoscopy is able to provide valuable information on anatomical details and potential obstructive sites but cannot predict the success of surgical interventions like UPPP. Videoendoscopy due to its high resolution in the time domain can demonstrate pathophysiological events which are otherwise inaccessible. For the experienced examiner videoendoscopy is a fast tool for obtaining live information on the surgical site.
Airway Obstruction↗