Anal. Chem.

2008, 80, 42694283

Fiber-Optic Chemical Sensors and Biosensors

Otto S. Wolfbeis Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, D-93040 Regensburg, Germany
Review Contents Books and Reviews Sensors for Gases, Vapors, and Humidity Hydrogen Hydrocarbons Oxygen Other Gases Vapors Humidity Sensors for pH and Ions Sensors for Organic Chemicals Organics Biosensors Enzymatic Biosensors Immunosensors DNA Biosensors Bacterial Biosensors Applications Sensing Schemes and Spectroscopies Fiber Optics Capillary Waveguides Microsystems and Microstructures Refractive Index Spectroscopies Literature Cited 4269 4271 4271 4271 4272 4272 4274 4274 4275 4276 4276 4276 4276 4277 4278 4278 4279 4279 4279 4280 4280 4280 4280 4281

This review covers the time period from January 2006 to January 2008 and is written in continuation of previous reviews (13). Data were electronically searched in SciFinder and MedLine. Additionally, references from (sensor) journals were collected by the author over the past 2 years. The number of citations in this review is limited, and a stringent selection had to be made therefore. Priority was given to ber-optic sensors (FOS) of dened chemical, environmental, or biochemical signicance and to new schemes. The review does not include the following: (a) FOS that obviously have been rediscovered; (b) FOS for nonchemical species such as temperature, current and voltage, stress, strain, displacement, structural integrity (e.g., of constructions), liquid level, and radiation; and (c) FOS for monitoring purely technical processes such as injection molding, extrusion, or oil drilling, even though these are important applications of optical ber technology. Unfortunately, certain journals publish articles that represent marginal modications of prior art, and it is mentioned here explicitly that the (nonpeer-reviewed) Proceedings of the SPIE are particularly uncritical in that respect. Fiber optics serve analytical sciences in several ways. First, they enable optical spectroscopy to be performed at sites inaccessible to conventional spectroscopy, over large distances, or even at several spots along the ber. Second, in being optical waveguides, ber optics enable less common methods of interrogation, in particular evanescent wave spectroscopy. Fibers are
10.1021/ac800473b CCC: $40.75 2008 American Chemical Society Published on Web 05/08/2008

available now with transmissions over a wide spectral range. Current limitations are not so much in the transmissivity but in the (usually shortwave) background uorescence of most of the materials bers are made from, in particular plastic. There is an obvious trend toward longwave sensing where background signals are weaker. Major elds of applications are in sensing gases and vapors, in medical and chemical analysis, molecular biotechnology, marine and environmental analysis, industrial production monitoring, bioprocess control, and the automotive industry. Note: In this article, sensing refers to a continuous process, while probing refers to single-shot testing. Both have their elds of applications. FOS are based on either direct or indirect (indicator-based) sensing schemes. In the rst, the intrinsic optical properties of the analyte are measured, for example its refractive index, absorption, or emission. In the second, the color or uorescence of an immobilized indicator, label, or any other optically detectable bioprobe is monitored. Aside from the design of label and probes, active areas of research include advanced methods of interrogation such as time-resolved or spatially-resolved spectroscopy, evanescent wave and laser-assisted spectroscopy, surface plasmon resonance (SPR), and multidimensional data acquisition. In recent years, ber bundles also have been employed for purposes of imaging, for biosensor arrays (along with encoding), or as arrays of nonspecic sensors whose individual signals may be processed via articial neural networks. The success of SPR in general, and in the form of FOS in particular, is impressive. Following the recent sensor hype of (mainly organic) chemists that tend to refer to optical molecular probes as sensors, the literature has become more difcult to sort. This review covers literature on methods that enable sensing of (bio)chemical species as opposed to conventional types of optical assays. Unfortunately, there is a tendency to even refer to conventional indicators (such as for pH or calcium) as biosensors if only used in vivo. Similarly, optical analysis of a solution by adding an appropriate indicator probe is now referred to as sensing (to the surprise of the sensor community). I have outlined the situation in more detail in my previous review (3). BOOKS AND REVIEWS It is obvious that ber optic chemical sensors (FOCS) have had a particular success in areas related to sensing gases and vapors. Many of the systems implemented are based on direct spectroscopies that range from UV to IR, and from absorbance to uorescence and surface plasmon resonance. Optical chemical sensors have been comprehensively reviewed by McDonagh et al. quite recently (4). The article covers sensing platforms, direct (spectroscopic) sensors, reagent-mediated sensors and discusses trends and future perspectives. Fiber-optic UV systems for gas
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and vapor analysis have been reviewed (5). The strong absorbance of vapors and gases in the UV region is advantageous and resulted in a compact detection system of good accuracy. Buchanan has reviewed recent advances in the use of near-IR (NIR) spectroscopy in the petrochemical industry (6) and points out NIR is particularly attractive in this eld because it measures the overtone and combination bands predominately of the C-H stretches. Practical examples include sensing schemes for oxygenates in fuels, determination of octane numbers, the composition of fuels, bitumen analysis, and environmental analysis. Tools for life science research based on ber-optic-linked Raman and resonance Raman spectroscopy were also reviewed (7). One focus is on ber-optic probes for UV resonance Raman spectroscopy that offer several advantages over conventional excitation/collection methods, another on novel probes based on hollow-core photonic band gap bers that virtually eliminate the generation of silica Raman scattering within the excitation optical ber. FOCS for volatile organic compounds have been reviewed by Elosua et al. (8). Such sensors are minimally invasive, lightweight, passive and can be multiplexed. The devices were classied according to their mechanism of operation and in terms of sensing materials. The state of the art in leak detection and localization and respective legal regulations have been reviewed by Geiger (9). Specic aspects include sensor reliability, sensitivity, accuracy, and robustness. Applicability is demonstrated for two examples, a liquid multibatch pipeline and a gas pipeline. Nanostructure-based optical ber sensor systems and examples of their application have been reviewed by Willsch et al. (10). Selected examples of advanced optical ber sensor systems based on subwavelength structured components are presented. These include sensor for humidity and hydrocarbons, for application in the gas industry, and for environmental monitoring using nanoporous thin-lm Fabry-Perot transducer elements or intrinsic ber Bragg grating sensor networks for structural health monitoring. Additionally, new concepts for sensing based on the use of plasmonic metal nanoparticles, photonic crystal bers, and optical nanowires are discussed. Mohr (11) has reviewed recent developments in chromogenic and uorogenic reagents and sensors for neutral and ionic analytes based on covalent bond formation. New indicator dyes for amines and diamines, amino acids, cyanide, formaldehyde, hydrogen peroxide, organophosphates, nitrogen oxide and nitrite, peptides and proteins, as well as for saccharides also are described, and new means (such as color changes of chiral nematic layers) of converting analyte recognition into optical signals are described. Aspects of multiple optical chemical sensing with respect to parameters, materials, and spectroscopies have been reviewe (12). Borisov et al. summarize their research on plastic microparticles and nanoparticles for uorescent chemical sensing and encoding (13). A rather wide and shallow review covers advances in beroptic sensing in medicine and biology (14). Applications range from the use of bers acting as plain light pipes to complex chemical sensors. It is stated (somewhat overoptimistically) that chemical sensing can simply be achieved by transporting light to and from a measurement site with a plain ber light guide for spectrophotometry, uorometry, or SPR. Flowers et al. discussed aspects of ber-optic spectro-electrochemical sensing for in situ determination of metal ions, mainly copper(II) (15). The term
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spectro-electrochemical sensing does not relate to electroluminescence but to electrochemical conversion of an analyte prior to its spectroscopic detection, e.g., by preconcentration, oxidation, reduction, complexation, and optical detection. Given its complexity, it does not come as a surprise that the authors point to the need for further renement of the sensors design and the experimental protocol to improve the methods sensitivity. The performances of interferometry, surface plasmon resonance, and luminescence as biosensors and chemosensors have been critically compared (16). Sensitivity, dynamic range, and resolution were calculated and compared from a range of data from the literature. Theoretical sensitivities of interferometry and SPR are detailed along with parameters affecting these sensitivities. Luminescence is said to offer the best resolutions for sensing of protein and DNA, while interferometry is said to be most suitable for low-molecular weight chemical liquids and vapors if selectivity is not a critical issue. SPR (which is label-free) possibly can sense proteins with a resolution similar to that of luminescence. Borisov and Wolfbeis (17) have presented what appears to be the most comprehensive review on optical biosensors so far. Applications of optical ber (bio)sensors (FOBS) also include areas such as high-throughput screening of drugs (18), the detection of food-borne pathogens (19) (based on either SPR, resonant mirrors, ber-optic systems, arrays, Raman spectroscopy, and light-addressable potentiometry), and in environmental sensing by making use of DNAzymes (20). DNAzymes can selectively identify charged organic and inorganic compounds at ultratrace levels in waste and emissions. In combination with laser based detection, DNAzymes enable accurate quantication of such compounds and thus represent an attractive alternative to stateof-the-art afnity sensors. Signicant strides have been made in terms of selectivity, sensitivity, and catalytic rates of DNAzymes. Challenges remain in the development of efcient signal transduction technology for in situ applications. The state of the art in continuous glucose sensing, a kind of holy grail in FOBS, has been summarized in a book (21), and (ber) optical methods based on the use of glucose oxidase and transduction via oxygen consumption are reviewed in one chapter (22). The trend toward miniaturization is obvious. Nanoscale optical biosensors and biochips for cellular diagnostics have been reviewed by Cullum (23), specically with respect to achievements in employing nanosensors and biochips (e.g., gene chips) in cellular analyses ranging from medical diagnostics to genomics, while optical nanobiosensors and nanoprobes were reviewed by Vo-Dinh (24) with respect to the principles, development, and applications of ber-optic nanobiosensor systems using antibodybased probes. One specic class of FOBS, the tapered ber-optic biosensors (TFOBS) were reviewed (25). In these, part of the ber is tapered so that the evanescent eld of the lightwave can interact with samples. TFOBS are often used with transduction mechanisms such as changes in refractive index, absorption, uorescence, and SPR. A more general review covers recent developments in FOBS (26), whereas Walt (27) describes beroptic biosensor arrays for creating high-density sensing arrays. Femtoliter wells can be loaded with individual beads to create such arrays for multiplexed screening and bioanalysis. Adherent cells may be attached to the ber substrate to provide a method for observing cell migration and for screening antimigratory

compounds, and even individual enzyme molecules can be loaded into the wells, thus enabling single molecule detection via enzymecatalyzed signal amplication. Optical microarray biosensing techniques (28), in turn, provide a powerful tool for the simultaneous analyses of thousands of parameters, be they DNA or proteins. The review highlights promising microarray techniques either making use of labels or label-free. Rather than miniaturizing the optical ber, these may be covered with nanostructured coatings (29). Active and passive coatings, deposited via the Langmuir-Blodgett and electrostatic self-assembly techniques, may be utilized to affect the transmission of optical bers. While such sensor elements are mainly aimed for use in telecommunications systems, it is very likely that chemical sensor and biosensor development may benet from such research. Jeronimo et al. (30) review optical sensors and biosensors based on sol-gel lms. Applications include sensors for pH, gases, ionic species and solvents, as well as biosensors. The use of FOCS for on-site monitoring and analysis of industrial pollutants with respect to detecting the identity, concentrations, and extent of toxic chemical contamination was overviewed (31). Aspects of process monitoring of ber reinforced composites using optical ber sensors were summarized (32), with a focus on thermosetting resins and on spectroscopy-based techniques that can be used to monitor the processing of these materials A classroom demonstration was described for a portable beroptic probe multichannel spectrophotometer (33). With the use of this instrument, lecture demonstrations can be made of various concepts in molecular uorescence spectroscopy. Concepts include uorescence spectrophotometer design geometry and the correlation of color with emission wavelength, excitation, and emission spectra. The history of research on FOCS and FOBS has been summarized (34). SENSORS FOR GASES, VAPORS, AND HUMIDITY This section covers all room-temperature gaseous species including their solutions in liquids. One major research focus is on hydrogen and methane because both are highly explosive when mixed with air and may be sensed more safely with FOS than with electrical devices. Hydrogen. Hydrogen, along with ammable alkanes, remains to be the analyte where safety considerations have led to a substantial amount of research in terms of ber-optic sensing. Since hydrogen gas does not display intrinsic absorptions/ emissions that could be used for purposes of simple optical sensing, it is always detected indirectly. Hydrogen interacts strongly with metallic palladium and platinum lms and with tungsten oxide. The interactions result in both spectral changes (an effect sometimes called gasochromism) and in an expansion of the materials. Thus, a hydrogen sensor was reported based on palladium coated side-polished single mode ber (35). When exposed to 4% hydrogen gas, the optimal change output power obtained in this experiment was 1.2 dB (32%) with a risetime of 100 s. Improved response times were reported for a similar sensor based on the same scheme (36). The authors have studied the transmission, the time-response, and the initial response velocity in the range from -30 to 80 C. Heating the palladium layer with an auxiliary laser diode improves the response time at low temperatures. Palladium also was incorporated into silica nano-

composites of the sol-gel type and used in a reversible hydrogen FOCS (37). The gasochromic properties of nanostructured tungsten oxide lms coated with a palladium catalyst were used to sense hydrogen gas via the change in the optical transmittance at 645 nm, typically caused by 1% hydrogen in argon gas (38). The nanomorphology of the surface considerably improves the gasochromic properties. Two rather similar articles have been published by this group (39, 40). Luna-Moreno et al. have reported on the effect of hydrogen on a thick lm Pd-Au alloy (41). The resulting sensor consists of a multimode ber in which a short section of single mode ber is coated with the Pd-Au lm. If exposed to hydrogen, the refractive index of the Pd-Au layer becomes smaller and causes attenuation on the transmitted light. The Pd-Au lm can detect 4% hydrogen with a response time of 15 s. The same material was used to design a hydrogen sensor based on core diameter mismatch and annealed Pd-Au thin lms (42). Palladium-capped magnesium hydride was used as an alternative sensing material in a ber-optic hydrogen detector (43). A drop in the reectance of this material by a factor of 10 is demonstrated at hydrogen levels as low as 15% of the lower explosion limit. The response occurs within a few seconds. Comparing Mg-Ni and Mg-Ti based alloys, the latter has superior optical and switching properties. A gasochromic TiO2based sensing lm was used for hydrogen detection by means of a ber-optic Fabry-Perot interferometric sensor (44). It was applied to monitor hydrogen gas in air below the lower explosion limit, has a short response time, and regenerates quickly (at room temperature). Fiber gratings coated with Pd metal were reported to enable sensing of hydrogen gas (45). Fiber Bragg gratings (FBG) and long period gratings (LPG), both coated with Pd nanolayers, were investigated. The sensitivity of the LPG sensor is better by a factor of 500. The FBG sensors appear to be pure strain sensors, and LPG sensors are mainly based on the coupling between the cladding modes and evanescent or surface plasmon waves. In another type of FBG sensor, a 10 ppm sensitivity for hydrogen was reported (along with cross sensitivity to environmental conditions) (46). The sensor was used to monitor the aging of certain materials. Optical bers coated with single-walled carbon nanotubes (SWCNTs) were shown to enable determination of hydrogen at cryogenic temperatures (47). SWCNTs were deposited by the Langmuir-Blodgett technique at the distal end of the bers. Experiments carried out at 113 K revealed the potential of sensing <5% of gaseous hydrogen with good reversibility and fast response time. Hydrocarbons. Methane and other hydrocarbons are almost exclusively sensed via their intrinsic absorption in the near-infrared (NIR). These, in contrast to hydrogen or oxygen, can be detected via their intrinsic absorption in the (near) infrared-albeit cross sections (molar absorbances) remains small or via Raman scatter. One more ber-optic Raman sensor was reported for sensing ethanol and methanol in gasoline (48). It employs a frequency doubled 532 nm Nd:YAG laser and a specially designed ber-optic Raman probe and enables online determination of sample constituents without employing an expensive IR ber. The sensor is capable of monitoring methanol and ethanol in water and gasoline
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solutions. Surface-enhanced Raman spectroscopy and surfaceenhanced IR spectroscopy were applied to selective determination of polycyclic aromatic hydrocarbons (49). Molecular recognition is accomplished by functionalization of the silver nanoparticles with appropriate host molecules. A modular, mid-IR, evanescent wave ber-optic sensor for the detection of hydrocarbon pollutants in water was constructed and tested (50). The setup uses a broadband light source with backreecting optics coupled to a ber-optic sensing element coated with an analyte-enriching polymer that preconcentrates the analyte. Benzene was quantied down to 500 ppm using a PVC polymer coating. Three kinds of microstructure bers (MSFs) for sensing gaseous hydrocarbons were reported (51) that enable the quantitation of aromatic hydrocarbons. Their surfaces were modied by xerogel layers. The MSFs with 10-50 m air holes were arranged to one sensor. Capillary silica bers were also fabricated. The response of the sensors to toluene in nitrogen gas results from spectral changes of the output light from the bers at 1600-1800 nm. A detection limit of 0.007 vol.% of toluene was achieved. Oxygen. Oxygen sensing remains another area where FOCS are quite successful. Oxygen almost exclusively is sensed by virtue of the quenching effect it exerts on certain uorophores. Highperformance ber-optic oxygen sensors based on uorinated xerogels doped with quenchable Pt(II) complexes were reported by Chu et al. (52). The sensors yield linear Stern-Volmer plots, and response times range from 4 to 7 s. Rather similar materials resulted in even faster responses as reported in a second paper by this group (53). Most oxygen sensors display nonlinear Stern-Volmer relationship, and this can be described by the socalled two-site model assuming two quenching constants. It has been shown that an articial network also may be applied to model the dynamic quenching of the uorescence of a ruthenium-derived probe (54). A porous plastic sensor was developed for the determination of dissolved oxygen in seawater (55). The luminescent indicator, a ruthenium(II)diimine complex, was copolymerized with a polymerizable monomer, a cross-linking reagent, and a porogen. It did not leach out due to its high hydrophobicity. Sensing is based on dynamic quenching of the uorescence of the ruthenium indicator. The permeability of contact lenses for oxygen can be determined with a ber-optic luminescent sensor system (56). The method is based on kinetic measurements of the oxygen partial pressure inside a chamber sealed by the sample contact lens, where a thin luminescent O2-sensitive lm is being placed. Unlike in electrochemical techniques, the optical sensor is unaffected by the thickness of the contact lens and other effects. Oxygen sensors were used to transduce the activity of catalase (57). This is of interest to characterize the oxidative metabolism in coffee cherries during maturation as it appears to be regulated by the timely expression of redox enzymes such as catalase (CAT), peroxidase, and polyphenoloxidase. The assay allows for the screening of green coffee samples for CAT activities. An evanescent wave ber sensor was used to determine oxygen deciency (58). The sensing dye, methylene blue, was immobilized in the cladding using a sol-gel process. The sensor is said to respond logarithmically linear between 0.6% and 20.9% oxygen. The most sensitive sensor for oxygen known so far exploits the efcient
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quenching of the long-lived delayed uorescence of fullerene C70 incorporated in thin lms of ethyl cellulose or organosilica (59). Molecular oxygen in concentrations as low as 200-800 ng/L can be determined by this method either at single sensor spots or spatially resolved over a temperature range of more than 100 C. The group of Klimant (60) has presented magnetically separable optical sensor beads for oxygen. The beads contain Fe3O4 and can be magnetically xed at the bottom of a microbioreactor and enable contactless monitoring of oxygen in cultures of Escherichia coli using ber optics. The same group has presented new and ultrabright uorescent probes for oxygen that are based on cyclometalated iridium(III) coumarin complexes (61). The probes are less cross-sensitive to temperature, have lifetimes on the order of 8-13 s in the unquenched state, have quantum yields between 0.3 and 1.0, but are less photostable than ruthenium-based probes for oxygen. Fiber optic microsensors with a tip diameter of 140 m were reported for simultaneous sensing of oxygen and pH and of oxygen and temperature (62). The tip of the ber was covered with sensor chemistries based on luminescent microbeads that respond to the respective parameters by a change in the decay time, or the intensity of their luminescence, or both. The use of microbeads enables the ratio of the signals to be easily varied, reduces the risk of uorescence energy transfer between indicator dyes, and reduces the adverse effect of singlet oxygen that is produced in the oxygen-sensitive beads. Arain et al. (63) have characterized microtiterplates (MTPs) with integrated optical sensors for oxygen and pH and have applied them to enzyme activity screening, respirometry, and toxicological assays. Thin hydrophilic sensing lms consisting of an analyte-sensitive indicator and a reference uorophore were deposited on the bottom of the MTPs. Activity screening was demonstrated for glucose oxidase and for monitoring the growth of E. coli and Pseudomonas putida. A toxicological assay also is reported that enables monitoring the respiratory activity of P. putida. In order to compensate for the rather strong effects of temperature on oxygen sensors based on dynamic quenching of luminescence, Borisov et al. (64) have developed a composite luminescent material for dual sensing of oxygen and temperature, where temperature can be measured optically and used to calculate temperature-corrected data for pO2. Quantum dots undergo temperature-dependent changes of the intensity, the peak wavelength, and the spectral width of their luminescence. Hence, they can be used as probes to compensate for effects of temperature in FOCS (65). Effects are almost linear and fully reversible. A resolution of 0.3 C was achieved. Oxygen and carbon dioxide are clinically highly signicant blood gases. A composite uorescent material was described that enables simultaneous sensing and imaging of oxygen and carbon dioxide (66). It relies on the measurement of the phase shift of the luminescence decay time of a material composed of microbeadcontained indicators (with well-separated excitation and emission wavelengths) and polymers with excellent permeation selectivities as well as favorable optical and adhesive properties. A luminescent dual sensor for time-resolved imaging of pCO2 and pO2 in aquatic systems was reported by Schroeder et al. (67). Other Gases. Ozone gas was sensed via its UV and visible absorption (68). Both the UV absorption at 254 nm and the visible absorption at 600 nm were studied. Sensing in the UV region

allows for highly sensitive detectors due to its high absorptivity in that region. The visible region has a signicantly lower absorption coefcient but enables monitoring high ozone levels. The UV based sensor can detect 0-1 mg/L of ozone and the longwave sensor 25-126 mg/L. Nitrogen is a species not easily sensed by optical means except by Raman spectroscopy. A respective FOCS to monitor the concentration ratio of nitrogen and oxygen in a cryogenic mixture was reported by Tiwari et al. (69). Spontaneous Raman scattering was used to monitor of the purity of liquid oxygen in the oxidizer feed line during ground testing of rocket engines. The Raman peak intensity ratios for mixtures of liquid nitrogen and liquid oxygen were analyzed for their applicability to impurity sensing using different excitation light sources, and a miniaturized sensing system was developed that responds within a few seconds. A practical sensor for online sensing of atomic nitrogen in direct current glow discharges was reported by Popovic et al. (70). Sensing is accomplished by monitoring the intensities of the atomic nitrogen spectral line at 822 nm and the bandhead at 337 nm, relative to the oxygen line at 845 nm. Measurements were performed using two methods. The rst approach uses a beroptic spectrometer, calibrated with a standard source, to record the desired spectral lines. The second approach uses narrow bandwidth optical lters to detect the emission intensity. Optical data are collected for a range of experimental conditions in a owing glow discharge of N2-O2 mixtures. Sensors for carbon dioxide and, to a lesser extent, ammonia remain another active area of research. Carbon dioxide emissions from a diesel engine can be monitored with the help of a midinfrared optical ber sensor (71). As conventional automotive pollution sensors fail to meet monitoring requirements as specied by the European Community, for various reasons, a low-cost sensor employing compact mid-IR components is presented that was used to measure CO2 in the exhaust of a commercial diesel engine. A novel kind of optical sensor for carbon dioxide makes use of silicone encapsulated ionic liquids (72). The silicone matrix acts as a permeation-selective material for CO2, while the ionic liquid contains a pH probe (in its base form) that undergoes a distinct color change after its (reversible) reaction with CO2. Dissolved CO2 usually is sensed via the effect it exerts on the pH of a buffer immobilized in a matrix. A sulfonated hydroxypyrene named HPTS has been widely used as a pH probe in such CO2 sensors in the past two decades, and one more type of organically modied sol-gel was used to develop one more modication of this kind of sensor (73). Because the gel is partially uorinated, the response is faster. Nanoporous matrixes also may be used to host pH-sensitive phenolic dyes and an alkaline phase transfer agent, reagents typically employed in sensors for CO2 (74). Ammonia in the gas phase may be sensed either via its NIR absorption or (in being a weak base) via the weak pH changes it can induce in immobilized pH indicators. The latter approach is more sensitive. It also is the prefered one in that it is applicable to aqueous solutions (unless extractive phases are employed in IR sensing schemes). A new sensing scheme for ammonia is based on monitoring the optical changes of the Q-band of tetrakis(4sulfophenyl)-porphine (TSPP) at 700 nm, as induced by ammonia in the electrostatic interaction between TSPP and poly(diallyldimethylammonium) chloride (75). Three thin lm samples with

different thicknesses were prepared layer-by-layer, all showing a linear sensitivity to NH3 in the 0-100 ppm range and a response time of around 30 s. The sensor was regenerated by rinsing with water. Most ammonia sensors reported so far make use of its effect on appropriate pH probes. This is also true for one more sensor that makes use of a sol-gel matrix (76). Both NH3 vapor and trace NH3 dissolved in water can be detected. The indicator was immobilized in porous SiO2 which then was deposited on the surface of a bent optical ber core. In combination with a silicone protection coating, ammonia can be sensed in watery samples. The limit of detection is 13 ppb in gas samples and 5 ppb in water samples. This is comparable to previously reported probes exploiting the same effect. The scheme was extended to sensing ammonia via ber-optic microsensors at 2-100 g/L levels that are known to be highly toxic to sh and other organisms (77). A uorescent pH indicator placed in a cellulose ester matrix at the tip of an optical microber is deprotonated by ammonia, thereby undergoing a large change in uorescence intensity. The resulting ammonium ion is stabilized by a cation trap. The detection limit is reported to be 0.5 g/L. The microsensors were used to establish ammonia microproles of high spatial resolution. Interference by trimethylamine was minimized using an 18-crown-6 ether as a cation trap and by the permeability properties of the polymer matrix. Cross-sensitivities toward protons and alkali ions were prevented by coating the sensor with a layer of Teon. Ammonia also was sensed with the help of silica nanocomposites doped with silver nanoparticles and deposited on an optical ber waveguide (78). The SiO2 nanocomposite was prepared by the sol-gel technique in the presence of (3-mercaptopropyl)trimethoxysilane) and doped with 25 m silver nanoparticles. The material was deposited onto the surface of a bent silica ber by the dip-coating technique. Exposure to gas containing ammonia enhances the attenuation of light power guided through the ber probe. Sub-ppm levels of NH3 can be continuously monitored by this technique. Oberg et al. (79) have designed a simple optical sensor for vapors of organic amines based on silica microspheres dyed with pH indicators such as bromocresol green (a probe reported to be useful for sensing ammonia by others several times before). It can detect organic amine vapors down to 1-2 ppb levels. The response to aliphatic amines is linear up to 2 ppm. The microsphere sensor is said to be more sensitive than other optical amine sensor described in the literature but heavily interfered by ammonia. The group of Mohr reports (80) that functional liquid crystal lms can selectively recognize amine vapors and thereby undergo a change in their color. Molecular recognition is accomplished by cholesteric liquid crystals combined with molecules carrying a triuoroacetyl group. Note: sensors for amines in uid phases are treated in section D on sensors for organic molecules. One more ber-optic probe was reported for the selective determination of NO2 in air samples (81). Signal generation is based on the spectroscopic changes of a reagent contained in the nanopores of a sol-gel element that undergoes an irreversible chromogenic reaction. Two ber-optic designs are described. Another FOCS for NO2 makes use of poly(3-octylthiophene) as a sensing material (82). This material undergoes large spectral changes at 543 nm if exposed to NO2. The sensor is not very stable
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in that the response decreases after each exposure to NO2 but is rapid, highly selective, and sensitive. Vehicle exhaust emissions such as NO2, NO, SO2 were detected using an ultraviolet optical ber based sensor (83). It is used to simultaneously measure their concentrations, with lower limits of detection of 2 ppm for NO2, 2 ppm for SO2, and 20 ppm for NO. Response times are <4 s. Optical sensitivity to NO2, carbon monoxide, and hydrogen (all in dry air) was observed for a layer of a metal oxide multilayer of the type InxOyNz covered with gold nanoclusters (84). The incorporation of the gold nanoclusters leads to a broad absorption peak in the visible (purple) due to the excitation of localized surface plasmons. The maximum of the peak is shifted on exposure to oxidizing or reducing gases. An irreversible active core ber-optic probe was developed for determination of trace H2S at high temperature using a cadmium oxide doped porous silica ber as a transducer (85). If exposed to a gas sample at high temperatures, trace H2S in the sample diffuses into the porous ber and reacts with cadmium oxide to form cadmium sulde (CdS), and this is detected at around 370 nm with a ber-optic spectrometer. The CdS formed also emits strong uorescence, with a peak emission at around 500 nm, but this signal is quenched at 450 C, so that uorescence can only be used for probing trace H2S at low temperature. Fuel gases such as H2, CH4, and CO were found not to interfere. The toxic industrial chemicals hydrogen cyanide, hydrogen sulde, and chlorine can be sensed with waveguides coated with doped polymer materials in the form of arrays (86). The polymers are patterned on glass substrates and undergo color changes that can be interrogated at different wavelengths. Miniature waveguide channels result in enhanced sensitivity owing to the increased path length. The sensors have response times (t90) of less than 20 s. Certain cross interferences observed can be eliminated by applying a signal processing algorithm that also reduces false alarms. Elemental iodine, unlike chlorine, exerts a quenching effect on a derivative of aminobenzanthrone, and this effect was used in a respective ber-optic sensor (87). It can detect iodine with a rather high concentration detection limit of 6 M. An optical biosniffer for methyl mercaptan, one of the smelling principles in halitosis, was reported (88). Monoamine oxidase (MAO) was immobilized at the tip of a ber-optic oxygen sensor with a luminescent oxygen probe (excitation at 470 nm, emission peaking at 600 nm). The sensing scheme is based on the detection of the oxygen consumed as a result of enzymatic oxidation of methyl mercaptan (MM) by MAO. The output of the sniffer was amplied by substrate regeneration via reduction with ascorbic acid. MM levels between 9 and 11 000 ppb were detectable. The pathological threshold is 200 ppb, the limits of human perception are on the order of 10 ppb. A rather complex method for optical sensing of sulfur dioxide in wines (89) employs a dinuclear palladium ligand complex immobilized in a PVC membrane plasticized with o-nitrophenyloctylether (o-NPOE). Both free and total SO2 can be determined. Linear responses up to 50 and 150 mg/L were obtained for free and total SO2, with detection limits of 0.37 and 0.70 mg L-1, respectively. Vapors. Vapors, often referred to as volatile organic compounds (VOCs), often are sensed by optical means in order to reduce the risk of explosion. An FOCS for VOCs was reported
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(90) that uses birefringent porous glass oriented between two crossed polarizers and serving as the basis for this broad-spectrum sensor. VOCs such as acetonitrile vapors can be detected at concentrations of >50 ppm. The optical effects resulting from exposure to various VOCs are reversible and may result from adsorption of VOCs with attendant reduction of anisotropy. The sensor can make use of ambient light as a light source and the eye as a detector to register the resulting color changes and thus is capable of real time monitoring of VOCs. Also see ref 91. A ber-optic nanosensor for volatile alcoholic compounds has been described by Elosua et al. (92). It is based on a new vapochromic red powder consisting of a silver metal organic compound. Its color and refractive index change when exposed to vapors of VOCs. The process is fully reversible. The sensor consists of a nanometer-scale Fizeau interferometer doped with the vapochromic material and placed at the cleaved end of a multimode ber-optic pigtail. The response of the material toward different alcohols was measured at 850 nm, and changes up to 3 dB in the reected optical power were registered. The authors have used the same material in a Fabry-Perot interferometer with a nanosized cavity along with a optical ber pigtail system (93). The performance of a carbon nanotube (CNT) based thin lms ber-optic for VOCs was described (94). Single-walled CNT multilayer coatings were used that cause a response toward toluene and xylene vapors. The Langmuir-Blodgett technique was applied to deposit the CNTs directly onto the optical and acoustic sensors substrates. The results demonstrate ppm to ppb sensitivity, fast response, and high repeatability. In a related paper, the incorporation of CNTs into hollow core ber optics is reported (95). King et al. (96) report on a microsensor for VOCs where a photonic crystal of porous silicone is attached to the distal end of an optical ber. Activated carbon is used as a prelter, and any breakthrough of the VOC through the carbon results a large change in the reectivity of the porous silica. Humidity. Optical humidity sensors are a kind of evergreen given their highly different applications. Numerous materials including Naon lms doped with crystal violet responding to humidity by a change in their reectance (97). Relative humidity (RH) between 0 and 0.25% can be determined with the respective sensor, with a detection limit as low as 0.018% RH (equal to 4 ppm). The response is fully reversible (with some hysteresis) in dry nitrogen. Reversal times depend on exposure time and % RH. The sensor can detect moisture in process gases such as nitrogen and HCl. In another kind of RH sensor, Ru(II) complexes were employed since their luminescence decay time depends on RH. The analytical information is obtained via phase-sensitive determination of the decay time (98). The ruthenium probe was immobilized on a Teon support. The operational range is from 4 to 100% RH at 20 C. Its response time is shorter than 2 min (recovery time <1.2 min). Signal stability was veried for >2.5 years of discontinuous measurement. The sensor was applied to measure RH in food and in a weather station. Certain porphyrins deposited in Naon lms undergo waterinduced tautomerism. This forms the basis of a novel type of beroptic RH sensor (99). It exhibits long-term stability and a linear response over the humidity range from 0 to 4000 ppm. Another ber-optic RH sensor reported (100) is based on large-core

quartz/polymer optical ber pairs. Examples of vapors that interfere (or may be sensed with this device) include those of acetone and ethanol. In other words: it is not specic for RH. The sensitivity of a tapered optical ber relative humidity (RH) sensor was optimized by means of tuning the thickness of nanostructured sensitive coatings (101). A single mode tapered ber was coated with a specic nanostructured polymer whose thickness was controlled so to optimize sensitivity to RH. The sensor displays a 27 times better sensitivity to RH than a comparable overlay, this enabling monitoring human breathing. Huang et al. report (102) that a thermoplastic polyimide when deposited on a ber-optic Bragg grating can act as a material sensitive to RH in that it undergoes reversible expansion and shrinkage. SENSORS FOR pH AND IONS This section covers sensors for all kinds of inorganic ions including the proton (i.e., pH), cations, and anions. Optical sensing of pH remains to be of greatest interest even though all optical sensors suffer from cross sensitivity to ionic strength. The number of articles on pH sensors is decreasing, though, which does not come as a surprise in view of the state of the art and the fact that certain pH FOS are commercially available. On the other side, sensing of pH values below 1 and above 12 still represents a substantial challenge in terms of material sciences. Optical pH sensors respond over a limited range of pH only (in most cases). It also needs to be stated that many pH sensors presented in the past few years are modications only of existing sensing schemes and materials, and that authors often do not properly cite previous work on the subject. In the worst case, sensors are presented that are inferior to others described before. Such sensors are not treated here. The group of Scheper has introduced a scheme for referenced sensing of pH that is based on spectral analysis of uorescence (103). pH is calculated by chemometric means from selected data points of the uorescence spectra of aminouorescein at high concentration so that a strong inner lter is operative. Martin et al. describe a new organic pH indicator dye (mercurochrome) that was immobilized in a sol-gel matrix placed at the end of a ber optic and enables measurement of pH in the pH 4-8 range (104). The sensor is constructed from low cost ber optic and optoelectronic components including a blue light emitting diode and a photodiode. The sensing scheme relies on the measurement of the uorescence intensity of the pH indicator that is related to the intensity of the blue excitation light reected by the sensing phase. The ratio between the two signals is proportional to pH but independent of excitation light intensity. The applicability of this sensor was tested for its performance in pH analysis in tap and bottled mineral water (105). The same group also has developed sol-gel matrixes by controlled hydrolysis of a titanium tetraalkoxide (106). The resulting sol-gel (TiO2) is said to be more resistant and to have a longer lifetime than SiO2 lms. The matrix was doped with various pH indicator dyes, each being sensitive to different pH ranges. Congo red and neutral red on a cellulose acetate support have been reinvented as a material for sensing the 4.2-6.3 and 4.1-9.0 pH range, respectively (107). Two aromatic Schiff bases were studied for their suitability in terms of sensing alkaline pH values (108). Absorption and emission spectra, quantum yields, uores-

cence lifetimes, photostabilities, and acidity constants were determined in organic solvents and in PVC. The Schiff bases can be photoexcited at 556 and 570 nm, respectively, and respond to pH in the range from 8.0-12.0 and 7.0-12.0, respectively. A novel wide pH range sensing system was described that is based on a sol-gel encapsulated amino-functionalized corrole (109). An amino modied uorescent aminophenylcorrole immobilized in a sol-gel SiO2 matrix undergoes large changes in uorescence intensity owing to multiple steps of protonation and deprotonation, thereby allowing larger pH ranges (1-11) to be covered than via respective tetraphenylporphyrins. Dong et al. (110) have obtained wide-range pH optical sensor by immobilizing three indicators in a sol-gel matrix that was deposited in a ber optic waveguide and optically interrogated by evanescent wave absorptiometry. The sensors have a dynamic range from pH 4.5 to 13.0. A scheme for measurement of very high pH values as they occur in chemical processing was presented by Gotou et al. (111). It is used to establish a health monitoring method for chemically exposed ber reinforced plastic structures in that it can detect the penetration of corrosive solutions into plastics. A high-pH indicator is used along with an optical ber connected to a spectrophotometer. Seki et al. describe a pH sensor based on a heterocore structured ber optic (112). It consists of multimode bers and a short piece of single mode ber which was inserted into the multimode bers. The pH indicator phenol red was immobilized in a sol-gel matrix at the surface of the heterocore portion. pH changes were detected by measuring the loss spectra at 575 and 545 nm, respectively. It is noted at this point by the author of this review that sol-gels and other condensates of that kind are known not to provide a temporally stable matrix but rather to change their microstructure over periods of typically a few months. This is rarely addressed by authors of respective work. Indicator loaded microbeads that are permeation selective for either protons or dissolved oxygen were used in a respective dually sensing membrane and a single ber-optic sensor (113). The pH probe (a carboxyuorescein) and the oxygen probe (a ruthenium complex) were incorporated into two kinds of microparticles, viz. an amino-modied poly(hydroxyethyl methacrylate) and an organically modied sol-gel, respectively. Both kinds of beads were then dispersed into a hydrogel matrix and placed at the distal end of an optical ber waveguide for optical interrogation. A phase-modulated blue-green LED served as the light source for exciting luminescence whose average decay times or phase shifts served as the analytical information. Data are evaluated by a modied dual luminophore referencing method which relates the phase shift (as measured at two different frequencies) to pH and to O partial pressure. In related work but using different materials (for optoelectronic reasons), microsensors were described for simultaneous sensing of pH and oxygen (114). This is important in clinical chemistry and if minute sample volumes are only available. The microsensors with a tip diameter of 140 m make use of luminescent microbeads that respond to the respective parameters by a change in the decay time, intensity, or both. A complex algorithm enables precise calculation of pH even if the spectra of the indicator dyes (for pH and oxygen) overlap.
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An evanescent wave direct spectroscopic sensor for chromate anion reported by Tao & Sarma (115) uses a exible fused silica light guiding capillary as a transducer. The capillary has a cladding layer and a protective polymer coating on its outside surface. The cladding layer ensures the ability of the capillary to guide light, while the protective coating increases its mechanical strength. Like similar sensors described before, the sensor is based on the intrinsic evanescent wave absorption by chromate ions in a water sample inside the capillary. A 30 m long capillary has the capability of detecting as little as 31 ppm of chromate. A uorescence-based calcium nanosensor was described (116) that exploits silica nanoparticles (prepared by inverse microemulsion polymerization) doped with the calcium(II) probe calcein as both a recognition and transduction element for optical determination of calcium in blood serum. Traces of vanadium(V) ion can been determined by using an irreversible chromogenic reaction between vanadium ion and a hydroxamic acid immobilized in a poly(vinyl chloride) (PVC) membrane (117). A quenchable uorescent benzofurane derivative in the plasticized PVC matrix served as the indicator dye in an FOCS for ferric ion (118). Response time, reversibility, limits of detection (poor), dynamic range, and interferences were studied. The same group has synthesized a uorescent semicarbazone and demonstrated its applicability as a selective probe in an FOCS for copper(II) (119). PVC and ethyl cellulose acted as sensor matrixes, and both absorption and emission spectrometry can be applied. Aluminum ion in aqueous media can be probed with a regenerable sensor that uses a molecularly imprinted polymer (MIP) as the recognition receptor (120). The MIP was prepared with Al(III) ion acting as the template, and 8-hydroxyquinoline sulfonate acted as a uorogenic ligand. The MIP was synthesized from acrylamide, 2-hydroxyethyl methacrylate, and ethylene glycol dimethylacrylate as a cross-linker. At pH 5, Cu(II) and Zn(II) interfere to some extent. The dynamic range at pH 5 is linear up to 0.1 mM, the limit of detection is 4 M. Mercury(II) ions were optically probed by Li et al. (121). They report on a luminescent nanosensor for Hg(II) where the uorescence of carnitine capped quantum dots made from CdSe/ZnS is quenched by Hg(II) ions with an efciency that resulted in a detection limit of 0.2 M. In related work it is reported (122) that Pb(II) ions can be (irreversibly) probed by a similar method but using CdTe quantum dots capped with thiols. The detection limit is virtually the same. SENSORS FOR ORGANIC CHEMICALS This chapter covers sensors for organic species (mainly saccharides), pollutants, agrochemicals, nerve agents, drugs and pharmaceuticals, and miscellaneous other organics. Mid-IR laser spectroscopy was performed by either using cryogenically cooled lead salt lasers or quantum cascade lasers operating at room temperature and applied to reagentless (enzymeless) sensing of glucose (123). Aqueous solutions of glucose were analyzed by ber based attenuated total reection spectroscopy and by transmission spectroscopy. Both methods have the potential to be utilized in small ber sensors that may be inserted into subcutaneous tissue. Concentrations as low as 0.1 mg/mL were detectable. Mohr et al. (124) describe uoro-reactands for the enzymeless determination of saccharides. They are based on hemicyanine dyes containing a boronic acid receptor and are capable of forming
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a covalent bond between their boronic acid moiety and the diol moiety of saccharides. This causes their uorescence to increase. The probe can be photoexcited at around 460 nm, emits with a peak at 600 nm, and can be used at near neutral pHs. For a review, on probes for saccharides and glycosylated biomolecules see ref 125. Tri-n-propylamine and the drugs benzhexol and procyclidine were determined via electrochemiluminescence (ECL) in a sensor constructed by the screen-print technique (126). Ruthenium(II)tris(bipyridine) on Naon was immobilized on a carbon electrode, and its ECL resulting from the interaction with the analytes was measured. Limits of detection are as small as 30 nM. Polymer membranes containing a chromogenic functional azo dye undergo color changes on (reversible) interactions with amines in organic solvents (127). The dye (covalently linked to the polymer matrix) recognizes the analyte via covalent binding. Binding constants of the various amines depend on the kind of solvent and are highly different, this resulting in strongly varying limits of detection. Dissolved amines also can be sensed by incorporating an aminecarrying chromoionophore into a sol-gel matrix (128). Both acidand base-catalyzed sol-gel processes were studied, but the former were found not to respond at all. Stable ormosil layers were obtained using various fractions of organically modied sol-gel precursors, e.g., methyl triethoxysilane. Base-catalyzed sensor layers underwent large signal changes, with response times of around 1-2 min, and rather high detection limits (0.1 mM). Organics. A uorescent dosimeter for formaldehyde determination in water utilizes the Nash reagent incorporated into silica gel beads (129). On reaction with formaldehyde, a uorescent product is formed that can be detected instrumentally or visually. The dosimeter does not respond to primary alcohols, ketones, and other common substances. The detection limit is reported to be 30 g/L. Dissolved organics in water samples can be sensed with a nanoporous zeolite thin lm-based ber sensor (130). A Fabry-Perot interferometric system was developed containing a thin layer of nanoporous zeolite synthesized on the cleaved end face of a single mode ber. The sensor is operated by monitoring changes in the thickness of the thin lm caused by the adsorption of organic molecules by white light interferometry. Methanol, 2-propanol, and toluene were detected with high sensitivity. A FOCS for toluene in water was described by Consales et al. (131). It makes use of single-walled carbon nanotubes whose reectivity changes in the presence of toluene. System features include good stability of the steady-state signal, sensitivity, and rapid response. BIOSENSORS This section covers biosensors based on the use of enzymes, antibodies, nucleic acids, and whole cells. Biosensors make use of biological components in order to sense a species of interest (which by itself need not be a biospecies). On the other side, chemical sensors not using a biological component but placed in a biological matrix are not biosensors by denition. It should be noted that some of the biosensors can be found in other chapters if this was deemed to be more appropriate. Enzymatic Biosensors. Sensing glucose remains to be an evergreen. Unlike in the case of electrochemical schemes where direct electron shuttle from the substrate to the electrode has become possible as a result of enzyme wiring, no such approach is possible in optical sensors. Hence, these still rely on (a)

transduction via metabolic coreactants (such as oxygen or NAD+); (b) of coproducts (such as protons, hydrogen peroxide, or NADH); or (c) on afnity binding (such as to concanavalin A). Comprehensive reviews have appeared (132). The group of Klimant has designed a ber-optic ow through sensor for online monitoring of glucose in patients in intensive care units (133). A tubing as used in microdialysis contains an integrated ber-optic sensor. Glucose is sensed via oxygen consumption which occurs as a result of the oxidation of glucose catalyzed by immobilized GOx. The gas permeable tubing warrants constant air saturation in the ow cell. A reference oxygen sensor is used to detect changes in oxygen supply caused by adverse effects such as bacterial growth, temperature uctuations, or failure of the peristaltic pump. The sensor was evaluated in a 24 h test on a healthy volunteer. Endo et al. describe a needle-type enzyme sensor system for determining glucose levels in sh blood (134). A hollow needle was used that also was comprised of an immobilized enzyme membrane and a optic ber probe with a quenchable ruthenium-based oxygen indicator. The calibration curve was linear for glucose in sh plasma. One assay was completed within 3 min. A good reproducibility was observed 60 times without exchange of the enzyme membrane. The group of Nann (135) found that the luminescence of silica coated quantum dots is dynamically quenched by hydrogen peroxide (H2O2), and this was exploited in a optical glucose assay using the enzyme GOx. This is one of the few reversible optical methods that are based on the transduction of oxidase based reactions via H2O2. The quantum dots have a rather high specic surface area which enables a relatively large amount of GOx to be immobilized. On the basis of the previous work on sensing H2O2 via the amount of oxygen formed by catalytic decomposition of H2O2, Mills et al. (136) have designed a robust and reversible sensor where ruthenium(IV)dioxide is used as a catalyst. The amount of oxygen liberated is determined via the quenching effect it exerts on the luminescence of a ruthenium(II) ligand complex. Luminescent yeast cells were entrapped in hydrogels in order to optically detect estrogenic endocrine disrupting chemicals (137). Genetically modied Saccharomyces cerevisiae cells containing the estrogen receptor expression of the luc reporter gene were immobilized in hydrogel matrixes. The chemicals induce a chemiluminescence to be emitted by the cells. Concentrations down to 80 ng/L of the chemicals were detectable. The probe was stored for 1 month at -80 C but full activity was attained again at room temperature. The data obtained with this sensor roughly correlated with LC-MS/MS analytical results. Fiber optic absorbance spectroscopy was compared with surface plasmon optical detection methods for lactamases bound to interfacial structures via biotin-avidin coupling (138). Quantitative comparisons were made between the ve matrixes and between the binding strategies. All matrixes were suited, in principle, for the binding of the protein. Results obtained by SPR and optical waveguide measurements correlate excellently. Real time activity assays of -lactamase were performed by a detection scheme that combines an afnity test and a catalytic sensor. Organophosphate pesticides and chemical warfare agents can be sensed with a FOBS that exploits the enzyme organophosphate hydrolase (OPH) as the biorecognition element (139). Conjugated to biotin, it was attached to a polystyrene waveguide along with

the uorescent pH indicator carboxynaphthouorescein. Hydrolysis of organophosphates by OPH causes the pH to fall, and this is reported by the pH probe. The dynamic range for determination of paraoxon is from 1 to 800 mol/L. Single molecules of galactosidase were monitored (140) using a 1 mm diameter ber-optic bundle with individually sealed femtoliter microwell reactors. Unlike in so-called ensemble responses in which many analyte molecules give rise to the measured signal, the buildup of uorescent products from single enzyme molecules catalysis over the array of reaction vessels can be observed, and a digital concentration readout can be obtained by application of statistical analysis. This approach should prove useful for single molecule enzymology and ultrasensitive bioassays. A similar approach (141) was applied to 24 000 individual reaction chambers to sense DNA and antibodies and again is expected to be applicable to assays that utilize an enzyme label to catalyze the generation of a uorescent signal. A ber-optic enzymatic biosensor was described for determination of 1,2-dichloroethane (DCA) (142). Haloalkane dehalogenase in whole cells of Xanthobacter autotrophicus immobilized in calcium alginate at the tip of a ber-optic coverts the haloalkanes into acidic products (i.e., lowers the pH), and this is detected via the pH probe uorescein immobilized at the tip of the FOBS. DCA was quantied at levels as low as 11 mg/L, with a linear response at 65 mg/L. Like most cell-based catalytic biosensors, the response time is slow (8-10 min). Rajan et al. report on the fabrication and characterization of a surface plasmon resonance based enzymatic FOBS for detection of the bittering component naringin (143). The sensing area was coated over 1 cm length with silver and then with the enzyme naringinase. The SPR wavelength maximum increases with the concentration of naringin. Immunosensors. Antinuclear antibodies can be quantied with an optical ber biosensor modied with colloidal gold (144). The unclad portion of an optical ber was covered with selfassembled gold colloids whose surface was functionalized with antigens. Antinuclear antibodies in serum can be determined quantitatively, and the results agree well with the accepted ELISA method. This sensing platform is label-free, enables real-time detection, and does not require a secondary antibody. Its sensitivity is higher by at least 1 order of magnitude than that of the ELISA method. Antibodies against the F1 antigen of Yersinia pestis (the cause for plague and a potential terroristic agent) can be detected by a sandwich immunoassay on the surface of an optical ber (145). Autoantibodies to ovarian and breast cancer-associated antigens are detectable with high sensitivity by using a chemiluminescence based optical ber immunosensor (146). The protein GIPC-1 was conjugated to the tip of an optical ber. A human monoclonal IgM isolated from breast cancer patients targets the GIPC-1 protein and thus can be detected in concentrations down to 30 pg/mL, which is 50 times lower than the chemiluminescent ELISA and 500 times lower than the colorimetric ELISA. Sera from 11 ovarian cancer patients, 22 breast cancer patients, and asymptomatic controls were tested for the presence of IgM anti-GIPC-1 autoantibodies by the two methods. A waveguide based immunosensor for the food toxins aatoxin B1 and ochratoxin A uses either the competitive or the direct immunoassay format (147). The antibody conjugate was imAnalytical Chemistry, Vol. 80, No. 12, June 15, 2008 4277

mobilized on a sensor chip and exposed to the analytes in a ow injection analyzer. The detection range of the competitive detection method was between 0.5 and 10 ng/mL. The indirect method was used to sense toxins in barley and wheat our samples. Results are in good agreement with those obtained by ELISA. DNA Biosensors. A ber-optic DNA microarray for simultaneous determination of multiple harmful algal bloom species was reported by Ahn et al. (148). Algal blooms are a serious threat to coastal resources, causing a variety of impacts on public health, regional economies, and ecosystems. The sandwich hybridization assay combines ber-optic array technology with appropriate oligonucleotide probes immobilized on microspheres. Hybridization was visualized using uorescently labeled secondary probes. A detection limit as low as 5 cells is achieved, the assay time being 45 min without a separate amplication step. An elegant diagnostic device for the detection of the hepatitis B virus was presented (149). An isothermal amplication method is employed so to detect the viral DNA in a 25 L reaction volume following several automated handling steps. Bacterial transcriptional regulators are known to be dosedependently released from their operators upon binding of specic classes of antibiotics. In another approach, Link et al. (150) use a generic dipstick-based technology for rapid determination of tetracycline, streptogramin, and macrolide antibiotics in food samples. The dipstick assay consists of a membrane support strip coated with streptavidin and immobilized biotinylated operator DNA, which acts as capture DNA to bind hexa-histidine (His6)tagged bacterial biosensors. Antibiotics present in specic samples triggered the dose-dependent release of the capture DNA-biosensor interaction. Dipping the stick into two reagent solutions results in a correlated conversion of a chromogenic substrate by a His6targeted enzyme complex. It has detection limits as low as 1/40 of the licensed threshold. In a comparable approach, antibiotics in seafood were screened for a ber-optic uorometric assay based on competitive binding of the analyte and an intercalating dye to double stranded DNA (151). The antibiotics affect the binding of the intercalator to the double stranded nucleic acid, thereby changing the uorescence intensity. The concentration of the analyte is indirectly determined by the decrease in uorescence intensity. A DNA of 48.5 kb was found to be a suitable sensing nucleic acid. Sulfathiazole and chloramphenicol in shrimps were sensed by this method with detection limits from 0.5 to 1 ng/mL. An optical biosensor for real-time detection of DNA interactions was demonstrated with a long-period ber-grating biosensor (152). The probe DNA was immobilized on the silanized surface of the grating and then hybridized with the complementary (target) DNA. The sensor is reusable because the target DNA can be stripped off the grating surface after the assay. Wang et al. report on a DNA detection protocol utilizing the opacity of self-assembled nanometallic particles (NPs) and the optical response of a CMOS image sensor (153). The authors exploit the fact that DNA fragments attached to NPs precipitate them only at locations where cDNA strands exist. Hence, the opacity of the chip surface changes due to the accumulation of NPs and this can be used to detect targeted DNA fragments. The approach is very sensitive, detecting even single-base mismatched DNA targets in concentrations down to 10 pM.
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Surface plasmon resonance (SPR) spectroscopy was used for detecting target sequences in genomic DNA differing in terms of copies in the relative genome (154). Following fragmentation with restriction enzymes and denaturation, the interaction of the two strands is found to be specic both with oligonucleotides and with genomic nonamplied DNA. The usual amplication step is found not to be necessary. In another type of DNA biosensor, localized SPR spectroscopy was coupled to interferometry (155). A gold layer was deposited on porous anodic alumina and interrogated by both interferometry and localized SPR. The intensity of light reected by the chip resulted in an optical pattern that was highly sensitive to changes in the effective thickness of the layer on the surface, specically oligonucleotides and hybridized oligonucleotides. In a novel kind of DNA biosensor, the electrochemiluminescence (ECL) of the Ru(II) bipyridyl complex (a weak intercalator) is used to generate optical analytical information (156). If ds-DNA binds to intercalators such as doxorubicin or daunorubicin, an easily detectable ECL is generated in the presence of the ruthenium complex at +1.19 V (vs Ag/AgCl), while ss-DNA (which is not intercalated) does not give this effect. Given the sensitivity of ECL-based methods, this approach may be quite powerful. Several pathogens (including hepatitis virus) were detected by this technique. Bacterial Biosensors. Bioavailable mercury and arsenic in soil and sediments were determined with ber-optic bacterial biosensors (157). Alginate-immobilized recombinant luminescent bacteria were immobilized on optical bers and enabled luminescent quantication of 2.6 g/L of Hg(II), 141 g/L of As(V), and 18 g/L of As(III). The pesticide methyl parathion was shown to be detectable using Flavobacterium sp. adsorbed on glass ber lters as a disposable biocomponent (158). The avobacterium contains a hydrolase that hydrolyzes methyl parathion into optically detectable p-nitrophenol. Only 75 L of sample are needed to detect 0.3 nmol/L concentrations of methyl parathion. Microbially available dissolved organic carbon was quantied with a microsensor (159) containing microorganisms in a polyurethane hydrogel. A strain was used that displays low substrate selectivity and responded to mono- and disaccharides, to fatty acids, and to amino acids. The 90% response time was 1-5 min. Another optical ber biosensor for biochemical oxygen demand (BOD) is based on microorganisms coimmobilized in an ormosil matrix (160). The consumption of dissolved oxygen is measured with a uorescent optical ber sensor. The BOD values obtained correlate well with those determined by the conventional BOD5 method for seawater samples. Genetically engineered bioluminescent bacteria were applied to the detection of toxicants in surface waters (161). The multichannel system developed is based on mini-bioreactors containing four kinds of recombinant bioluminescent bacteria and is connected to a luminometer via a ber-optic cable. The system can be continuously operated due to the separation of the bacteria culture reactor from the test reactor without system shutdown by abrupt inows of severe pollutants. Bioluminescent signatures were delivered from four channels by switching one at once. The system is now being implemented to a drinking water reservoir and river for remote sensing as an early warning system.

APPLICATIONS This section comprises sensors for environmental, industrial, biotechnological, food, pharmaceutical, medical, and related applications of FOCS and FOBS. Thus, a newly developed miniaturized diamond ATR probe has been described that displays high chemical and pressure resistance. In combination with robust and exible ber-optics, it enables inline chemical reaction monitoring (162). Huber et al. (163) reports on the measurement of the ingress of oxygen into PET bottles using oxygen sensor technology. A noninvasive ber-optic oxygen meter detects oxygen permeability of PET bottles for soft drinks by measuring trace levels of oxygen inside the bottle. Permeation rates are obtained without piercing the package or bottle which is ideally suited for assurance, production, and quality control applications. Sensing is based on quenching of the uorescence by oxygen of a sensor spot placed on the inner wall of the transparent bottle. A ber-optic cable is positioned outside and measures changes in luminescence lifetime. Gaseous or dissolved oxygen can be detected in the ppm to ppb range. Near-infrared reectance spectroscopy was applied to quantitate Ca, K, P, Fe, Mn, Na, Zn, protein, and moisture in alfalfa (164). The method allows immediate analysis of alfalfa without prior sample treatment. A partial least-squares regression method was employed. The prediction capacity of the model and the robustness of the method were checked in the external validation in alfalfa samples of unknown compounds. The biocompatibility of Te-As-Se (TAS) glass bers for use in infrared sensors was studied by Wilhelm et al. (165). The bers are used for IR direct spectroscopy of cultivated mammalian cells. TAS bers undergo oxidation on air to form a water-soluble nanometer-thin layer that is soluble in water. The glass underneath this layer is, however, stable in water over several days. Hence, oxidized bers that can release arsenate ions are toxic, while freshly prepared or washed bers are not. Glasses displaying less strong interfering vibrations in the 2-5 m spectral region were prepared from TeO2-BaO-Bi2O3 mixtures (166). IR and Raman spectroscopic studies were carried out, and the temperature dependence of the viscosities of the glasses is reported. A ber-optic sensor for measurements of interstitial pH was further improved (167). The interstitial sample uid drawn subcutaneously from adipose tissue ows through a microuidic circuit formed by a microdialysis catheter in series with a glass capillary. The pH indicator phenol red is covalently immobilized on the inner wall of the capillary. Optical bers are used to connect the interrogating unit to the sensing capillary. A resolution of 0.03 pH units and an accuracy of 0.07 pH units were obtained. Preliminary in vivo tests were carried out in pigs with altered respiratory function. Data on pH, carbon dioxide, and oxygen as obtained with beroptic sensors on intramuscular and venous blood during rhythmic handgrip exercise were compared (168). A ber-optic sensor was inserted into muscle for continuous measurement of intramuscular data. Blood samples were taken from the forearm every minute during each exercise bout. The data for venous and arterial blood were found to be highly different when exercising. Regional differences in the water content of human skin can be studied by diffuse reectance near-infrared spectroscopy (169).

Reectance spectra in the 1250-2500 nm region for the skin of volunteers reveal large regional differences of water content. There was a difference in the ratio of the two water bands centered near 1450 and 1900 nm between the contact and noncontact measurements. Most regional differences of water content were calculated from the peak height of the 1900 nm water band normalized to the peak height of the 2175 nm amide band. One large area of application of FOCS is in monitoring the mechanical and chemical integrity of concrete structures. Aside from sensing mechanical integrity (not treated here), changes in chemical composition are of high interest given the health risk and costs associated with disintegrated structures. Optical ber sensors have been used to monitoring the ingress of moisture in structural concrete (170). The humidity sensors were fabricated using ber Bragg gratings coated with moisture sensitive polymers and are employed in detecting the movement of moisture through standardized cubes made from samples of different types of structural concrete. Data obtained can give information on the properties of different types of concrete but also on the migration of dissolved salts, such as sodium chloride which is important in view of their deleterious effects on reinforcement bars within concrete. The optical ber sensors reacted to the ingress of water by detecting the moisture migrating through the sample, indicated by a shift in the Bragg wavelength of the sensor. A similar approach was introduced by Yeo et al. (171). Chloride ion in concrete can be sensed with a long-period ber grating (LPFG) (172). The LPFG device is sensitive to the refractive index of the medium around the cladding surface of the sensing grating, thus offering the possibility of detecting a change in chemical concentration. The authors measured chloride ions in a typical concrete sample immersed in salt water solutions in concentrations ranging from 0 to 25%. The sensor exhibited a linear decrease in the transmission loss and resonance wavelength shift when the chloride was increased. The limit of detection for chloride ions is 0.04%. Sensitivity was further enhanced by coating a monolayer of colloidal gold nanoparticles as the active material on the grating surface of the LPFG which increase the sensitivity by a factor of 2. pH sensors for concrete are needed to detect any (highly adverse) changes in the rather high pH (>11) of concrete. An ber-optic pH sensor was developed that can be incorporated into concrete and thus is capable of early detection of the danger of corrosion in steel-reinforced concrete structures (173). SENSING SCHEMES AND SPECTROSCOPIES This section reports on improved or novel sensing schemes based on the use of ber optics and related waveguides. Aside from their use as plain waveguides, bers have been used for evanescent wave excitation of uorescence or Raman scatter, for imaging and sensor array purposes, in microsensors and nanosensors, and for distributed sensing, to mention only the more important ones. The current success of (ber optic) surface plasmon resonance (SPR) is obvious. Fiber Optics. New in-line ber-optic structures for environmental sensing applications were described (174). Sensors based on the interaction of surface plasmons or evanescent waves with the surrounding environment are usually obtained by tapering an optical ber. A ber-optic structure is presented that maintains the structural integrity of the optical ber. Graded index optical
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ber elements are used as lenses, and a coreless optical ber acts as the interaction area. These elements are fused by an optical ber splicer. Two optical system designs were compared for beroptic chemical sensor applications (175). A single grating spectrograph with ber-optic input and photodiodes at three different wavelengths was compared to a system comprising 1-3 beroptic splitters and photodiode detectors with integrated interference lters. Three types of splitters were tested, and it is found that that the systems have similar characteristics, also if used in a colorimetric CO2 sensor. Capillary Waveguides. Tao et al. (176) described the application of a light guiding exible tubular waveguide in evanescent wave absorption based sensing. A light guiding exible fused silica capillary (FSCap) was used that is similar to a conventional silica ber in that it can guide light in the wavelength region from UV to near IR. The inner surface of the FSCap capillary was coated with a reagent doped polymer to design a FOCS. Techniques were developed for activating the inner surface of an FSCap, coating the inner surface of the FSCap with a polymer, connecting the coated FSCap to a light source and a photodetector, and delivering a sample through the FSCap were developed. Sensors for Cu(II), toluene in water samples and ammonia in a gas sample were fabricated and tested. Similarly, the waveguiding properties of a FCSap for chemical sensing applications were investigated by Keller et al. (177). Absorbance within the tubing was measured by optically coupling the FSCap to a spectrophotometer. The FSCap operated evanescently or as a liquid core waveguide depending upon the refractive index of the sample solution within the capillary. Evanescent absorbance was linear with the concentration of a nonpolar dye but nonlinear with ionic dyes due to adsorption to the capillary wall. Absorbance measurements in 50, 150, and 250 m inner diameter FSCaps show that greater sensitivity is achieved in thinner walled tubings because of more internal reections. A FSCap for pH is demonstrated. A liquid-lled hollow core microstructured polymer optical ber (178) is said to be opening up many possibilities in FOCS. It is demonstrated how the band gaps of such a hollow core polymer optical ber scale with the refractive index of a liquid introduced into the holes of the microstructure. The ber is then lled with an aqueous solution of (L)-fructose, and the resulting optical rotation is measured. Hence, hollow core microstructured polymer optical bers can be used for sensing chiral species. A distributed ber-optic polarimetric sensor was reported by Caron et al. (179). The sensor is based on evanescent wave polarimetric interferometry and is intended for use in gas chromatography. It allows realtime monitoring of the displacement of a chemical substance along a capillary. Microsystems and Microstructures. A sub-nanoliter spectroscopic gas sensor was described (180) and compared to existing sensors designs. This novel gas sensor has the capability of gas detection with a cell volume in the sub-nanoliter range. A study of the capabilities of microstructure bers for evanescent wave vapor sensing is presented in ref 181. Toluene vapor in nitrogen gas was investigated. It causes a change in the refractive index changes of the xerogel ber cladding at 670 nm. Moreover, specic changes in absorbance due to C-H overtone absorptions of toluene at 1600-1800 nm were exploited.
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Analog signal acquisition from computer optical disk drives was demonstrated to be useful in chemical sensing (182). Signals were obtained from optical sensor lms deposited on conventional CD and DVD optical disks. Almost any optical disk can be employed for deposition and readout of sensor lms. The disk drives also perform the function of reading and writing digital content to optical media. Such a sensor platform is quite universal and can be applied to sensing and combinatorial screening. Specically, colorimetric calcium-sensitive lms were deposited onto a DVD, exposed to different concentrations of Ca(II), and quantied in the optical disk drive. Ink jet printing technology was applied to fabricating microsized optical ber imaging sensors (183). An array of photopolymerizable sensing elements containing a pH sensitive indicator was deposited on the surface of an optical ber image guide. The reproducibility of the microjet printing process was found to be excellent for micrometer-sized sensor spots. Hanko et al. (184) showed that nanophase-separated amphiphilic networks represent versatile matrixes for optical chemical and biochemical sensors. They consist of nanosized domains of hydrophilic and hydrophobic polymers (comparable to a polyacrylamide-co-polyacrylonitrile copolymer referred to as Hypan and previously introduced by others). Because of the spatial separation, there are domains in which the indicator reagents are immobilized and domains where diffusive transport of the analyte occurs. Various prototypes of sensors were prepared, e.g., for sensing gaseous chlorine (based on a chromogenic reaction), vapors of acids (based on immobilized bromophenol blue), and peroxides (based on immobilized horseradish peroxidase and a chromogenic substrate). Refractive Index. High-sensitivity optical chemosensors were implemented by exploiting ber Bragg grating structures in D-shape, single-mode, and multimode bers and postsensitized by HF etching treatment (185). Hence, the intrinsically insensitive Bragg grating became sensitive to refractive index (RI). The resulting devices were used to measure the concentrations of sugar solutions. A self-temperature-referenced sensor based on nonuniform thinned ber Bragg gratings was described (186). The sensor consists of a Bragg grating where the cladding layer is removed along half of the grating length. This perturbation leads to a wavelength-splitting in two separate peaks: the peak at lower wavelengths corresponds to the thinned region and is dependent on the outer RI and the local temperature, while the peak at longer wavelength responds to thermal changes only. The sensor was characterized in terms of thermal and RI sensitivities. A photonic band gap ber for measurement of RI was described by Sun and Chan (187). Spectroscopies. Fiber optic (bio)sensors were reported that are based on localized surface plasmon resonance (SPR) (188). The sensor measures the light intensity of the internally reected light at a xed wavelength from an optical ber where the extinction cross-section of self-assembled gold nanoparticles on the unclad portion of the optical ber changes with the refractive index of a sample near the gold surface. Sensing of the Ni(II) ion and label-free detection of streptavidin and staphylococcal enterotoxin B is demonstrated at picomolar levels. A related reection based localized SPR ber-optic probe was developed to determine refractive indexes and, thus, chemical concentrations at high pressure conditions (189). Sensing is based on the measurement

of the intensity of internal light reection at a xed wavelength from an optical ber. The light attenuation caused by the absorption of self-assembled gold nanoparticles on the unclad portion of the optical ber changes with a different refractive index of the environment near the gold surface. The probe demonstrated a stable and repeatable response for sequential operations of pressurization and depressurization at 0.1-20.4 MPa at 308 K. A new concept of an SPR ber-optic sensor was presented (190). A signicant variation of the spectral transmittance of the device is produced as a function of the concentration of the analyte by tuning the plasmon resonance to a wavelength for which the outer medium is absorptive. With this mechanism, selectivity can be achieved without the need of any functionalization of the surfaces or the use of recognizing elements, which is an important feature for any kind of FOCS or FOBS. Cavity ringdown (CRD) absorption spectroscopy enables spectroscopic sensing of gases with a high sensitivity and accuracy. The limits of sensitivity were further pushed (191). This continuous-wave CRD spectrometer uses a rapidly swept cavity of simple design. Measurements in the near IR from 1.51 to 1.56 m yield sub-ppb (v/v) sensitivity in the gas phase for CO2, CO, H2O, NH3, C2H2, and other hydrocarbons. By measuring at 1.525 m, acetylene gas can be detected at limits as low as 19 nTorr(!). The CRD spectrometer therefore is a high performance sensor in a relatively simple, low cost, and compact instrument. The geometry of a ber-optic surfaceenhanced Raman scattering (SERS) sensor was optimized with respect to trace detection (192). As a result, its active surface and the number of internal reections at the interface between silica and silver is largely increased. The probe was used to detect crystal violet and malachite green at ppb levels. Response is fast, and the instrument can be deployed in-eld. A luminescent ratiometric method in the frequency domain with dual phase-shift measurements was applied to oxygen sensing (193). The method is based on the difference between the lifetimes of the phosphorescence and uorescence emissions of a dually emitting indicator (an aluminum-ferron complex). The intensity ratio of the long-lived and short-lived emissions, respectively, serves as the analytical information. A ber-optic prototype was constructed using low-cost optoelectronics including a light emitting diode and a photodiode detector. A modied dual lifetime ratiometric (DLR) method was introduced for simultaneous luminescent determination and sensing of two analytes simultaneously (194). Two luminescent indicators are needed in this scheme that have overlapping absorption and emission spectra but largely different decay times. They are excited by a single light source, and both emissions are measured simultaneously. In the frequency domain m-DLR method, the phase of the shortlived uorescence of a rst indicator is referenced against that of the long-lived luminescence of the second indicator. The analytical information is obtained by measurement of the phase shifts at two modulation frequencies. The method was demonstrated to work for the case of dually sensing oxygen and carbon dioxide.
Otto S. Wolfbeis holds a Ph.D. in chemistry. After having spent several years at the Max-Planck Institute of Radiation Chemistry in Muelheim and at the University of Technology at Berlin, he became an Associate Professor of Chemistry in 1981 at Karl-Franzens University in Graz, Austria. Since 1995 he is a Full Professor of Analytical and Interface Chemistry at the University of Regensburg, Germany. He has authored around 470 papers and reviews on optical (ber) chemical sensors, uorescent probes, and bioassays, has (co)edited several books, and has

acted as the (co)organizer of several conferences related to uorescence spectroscopy (MAF) and to chemical sensors and biosensors (Europtrode). He acts on the board of several journals including Angewandte Chemie and is the Editor-in-Chief of Microchimica Acta. His research interests are in optical chemical sensing and biosensing, in uorescent probes and labels, in uorescence-based analytical formats including imaging, in biosensors based on thin metal lms using capacitive or SPR interrogation, and in the design of advanced (nano)materials (including uorescence upconverters) for use in (bio)chemical sensing.

LITERATURE CITED BOOKS AND REVIEWS

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AC800473B
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