Anal. Chem. 2006, 78, 3859-3874
Fiber-Optic Chemical Sensors and Biosensors Otto S. Wolfbeis
Institute of Analytical Chemistry, University of Regensburg, D-93040 Regensburg, Germany Review Contents Books and Reviews Sensors for Gases, Vapors, and Humidity Ion Sensors Organic Chemicals Biosensors Applications Sensing Schemes Materials Literature Cited
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This biannual review covers the time period from January 2004 to December 2005 and is written in continuation of previous reviews (A1-A3). An electronic search in SciFinder and MedLine resulted in >600 hits. Since the number of citations in this review is limited, a stringent selection had to be made. Priority was given to fiber-optic sensors (FOS) of defined chemical, environmental, and biochemical significance and to new schemes and materials. 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 fiber technology. Unfortunately, certain journals publish articles that represent but marginal modifications of prior art, and it is mentioned here explicitely that the (non-peer-reviewed) Proceedings of the SPIE are particularly uncritical in that respect. The literature search also revealed another aspect: sensor terminology is becoming ambiguous. Researchers (mainly organic chemists) are increasingly using the term sensor for what used to be referred to as a (molecular) probe or an indicator. Conventional indicators (such as for pH or calcium) are being termed even biosensors if used in vivo, or switches (even though they do not switch like electrical switches but rather respond sigmoidally because their responses is governed by the mass action law). Similarly, classical chromoionophores are now being termed ion sensors sometimes (rather than probes or indicators). And what so far used to be the (optical) analysis of a matrix for a certain analyte (by adding an indicator probe) is now referred to as “sensing” (to the surprise of the sensor community). Over time, this has led to the undesirable situation that electronic searches of the literature on sensors results in two sets of data. The first (still larger one) is on true sensors of all kinds (electrochemical, fluorescence, piezo, thermal, surface plasmon resonance, reflectometry, chemo/bioluminescence, IR, and the like). These do meet most of the established definitions of a sensor, while the second set of data is on (mainly) optical probes, which of course is of certain interest for those designing true (i.e., 10.1021/ac060490z CCC: $33.50 Published on Web 04/15/2006
© 2006 American Chemical Society
continuously recording) sensors, but not to those looking for finished sensors for use in their areas of interest. I still believe the following definition of a chemical sensor (which many colleagues refer to as the Cambridge definition) (A4) is a most appropriate one: Chemical sensors are miniaturized devices that can deliver real-time and on-line information on the presence of specific compounds or ions in even complex samples. Fiber optics serve analytical sciences in several ways. First, they enable optical spectroscopy to be performed on sites inaccessible to conventional spectroscopy, over large distances, or even on several spots along the fiber. Second, fiber opticssin being optical waveguidessenable less common methods of interrogation, in particular evanescent wave spectroscopy. Fibers are available now with transmissions over a wide spectral range. Current limitations are not so much in the transmissivity but in the background fluorescence of most of the materials fibers are made from, in particular plastic. Major fields of applications are in medical and chemical analysis, molecular biotechnology, marine and environmental analysis, industrial production monitoring and 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 fields of applications. FOS are based on either direct or indirect (indicator-based) sensing schemes. In the first, the intrinsic optical properties of the analyte are measured, for example, its refractive index, absorption, or emission. In the second, the color or fluorescence of an immobilized indicator, label, or any other optically detectable bioprobe is monitored. Particularly 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, fiber bundles also have been employed for purposes of imaging, for biosensor arrays (along with encoding), or as arrays of nonspecific sensors whose individual signals may be processed via artificial neural networks. The success of SPR in general, and in the form of FOS in particular, is impressive. This review is divided into sections on books and reviews (A), specific sensors for gases and vapors (B), ions and salinity (C), miscellaneous inorganic and organic chemical species (D), and biosensors (E), followed by sections on application-oriented sensor types (F), new sensing schemes (G), and new sensor materials (H), respectively. BOOKS AND REVIEWS Two books have appeared that cover recent trends in optical chemical sensor technology. The first (A5) has a focus on industrial, environmental, and diagnostic applications. It includes chapters on optical technology until the year 2000 (by Wolfbeis); molecularly imprinted polymers for optical sensing devices (by Analytical Chemistry, Vol. 78, No. 12, June 15, 2006 3859
Diaz-Garcia and Badia); chromogenic and fluorogenic reactands for amines, alcohols, and aldehydes (by Mohr); design, quality control, and normalization of biosensor chips (by Preininger and Sauer); rapid, multiplex optical biodetection for point-of-care applications (by Chuang and Colston); multifunctional biochips for medical diagnostics and pathogen detection (by Vo-Dinh et al.); surface plasmon resonance biosensors for food safety (by Homola); near-infrared dyes for ammonia and HCl sensors (by Simon and Kvasnik); piezooptical dosimeters for occupational and environmental monitoring (by Bearman et al.); interferometric biosensors for environmental pollution detection (by Lechuga et al.); FOCs for humidity monitoring (by Moreno-Bondi et al.); optical sensing of pH in low ionic strength waters (by Swindlehurst and Narayanaswamy); environmental and industrial optosensing with tailored luminescent ruthenium complexes (by Orellana and Garcia-Fresnadillo); total internal reflection array biosensors for environmental monitoring (by Sapsford and Ligler); and optical techniques for determination and sensing of hydrogen peroxide (by Voraberger). The second book (A6), edited by Orellana and Moreno-Bondi, focuses on frontiers in optical sensing and includes the following: chapters on absorbance-based integrated optical sensors (by Puyol et al.); lifetime-based imaging of sensor arrays for highthroughput screening applications (by Schaeferling), cataluminescence-based gas sensors (by N. Nakagawa and Yamashita); hollow waveguide infrared spectroscopy and sensing (by Charlton et al.); combinatorial methods for surface confined sensor design and fabrication (by Basabe-Desmonts et al.); the interplay of indicator, support, and analyte in optical sensor layers (by Orellana et al.); on challenges in the design of optical DNA biosensors (by Massey et al.); gold nanoparticles in bioanalytical assays and sensors (by Thanh et al.); reverse symmetry waveguides for optical biosensing (by Horva´th et al.); materials for luminescent pressure-sensitive paints (by Y. Takeuchi & Y. Amao); optical sensing of enantiomers (by Kasper et al.); and optical sensors for ions and protein based on digital color analysis (by Suzuki and Suzuki). Brogan and Walt have reviewed the state of the art in optical fiber-based sensing as applied to chemical biology (A7). Singlecore optical fiber sensors and optical fiber sensor arrays for sensing nucleic acids and live cells are specifically addressed. Overviews have been given on the fabrication, operating principles, and applications of fiber-optic nanobiosensors with the capability of in vivo analysis at the single-cell level (A8) and on selfassembled nanostructured optical fiber sensors (A9) mainly on pyhysical sensors, but also on chemical sensors. A review on the monitoring and analysis of industrial pollutants (A10) also includes a discussion on fiber-optic chemical sensors. One promising application of FOS is in sensing in highly radioactive environments. Following early significant work by Boisde and by Hirschfeld, there was less activity in the 1990s, but this has changed in the past 5 years. The subject of sensor integration in radioactive environments has been reviewed (A11). Significant progress has been made in the last couple of years in laser-induced breakdown spectrometry (LIBS), and applications of LIBS, including remote material analysis in nuclear power stations, space exploration, diagnostics of archaeological objects, and metal diffusion in solar cells, have been reviewed (A12), with a strong focus on material aspects. More recent applications of LIBS include the development of fiber-optic technologogies and 3860
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portable instrumentation. A review on materials for fluorescencebased optical chemical sensors (A13) focuses on materials aspects and stresses that fact that FOS development was often hampered more by the lack of appropriate materials than by spectroscopic schemes. Applications of distributed optical fiber sensing and fluorescent assays of linear combinatorial arrays have been reviewed (A14). Other reviews that have appeared cover (i) optical fiber coatings for chemical and biochemical sensing, with a focus to the surface properties and structure of sol-gels (A15), and (ii) principles and selected applications of direct optical sensors (A16), the optical detection schemes including measurement of light remission, microrefractivity, microreflectivity, and optical interference. A review by Maragos (A17) on emerging technologies for mycotoxin detection focuses on recent development in evanescent wave technologies (surface plasmon resonance, fiber-optic sensors), lateral flow and dipstick devices, fluorescence polarization and time-resolved fluorescence, microbead assays, and capillary electrophoretic immunoassays. Yotter et al. (A18) have reviewed sensor technologies for monitoring metabolic activity in single cells by optical methods in the context of the development of labon-a-chip research instrumentation. Specifically, optical sensors are described that can detect intracellular metabolites including ATP, nicotinamide adenine dinucleotide, reduced FAD, oxygen, carbon dioxide, and glucose. Choi et al. (A19) have reviewed the progress made in enzyme-based biosensors using optical transducers, with a particular focus on the integration of the enzyme with the support or immobilized materials to the extent that the biocatalytic transformation is either optically or electronically transduced. Enzyme-based biosensors using various optical detection methods such as absorptiometry, luminometry, chemiluminescence, evanescent wave, and surface plasmon resonance are also included. Monk and Walt have reviewed the state of the art in optical fiber-based biosensing from 2001 to 2003 (A20). Specifically, they treat the use of biological recognition elements including enzymes, antibodies, nucleic acids, whole cells, and biomimetic systems that may be used for a variety of analytes ranging from metal ions to organic chemicals. SENSORS FOR GASES, VAPORS, AND HUMIDITY This section covers all gaseous species including their solutions in liquids. One 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. 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 films, and the interaction results in both optical changes and in expansion. This scheme recently has been extended to distributed determination of hydrogen (B1). The sensor consists of a subwavelengthdiameter tapered optical fiber coated with an ultrathin palladium film. When the device is exposed to hydrogen, the absorption at 1550 nm of the evanescent waves change. Palladium also undergoes a volume expansion, and this has been exploited (B2) to sense a low concentration of hydrogen which is the result of aging of polymer materials. A comparison of three types of fiber-optic hydrogen sensors (B3) revealed strengths and weaknesses of the respective sensors in terms of reproducibility, repetitiveness, robustness, multiplexability, response time, and cost. It is con-
cluded that the fiber Bragg grating sensor is the most reliable one among those considered, and the preferred one for space applications (B4). Hydrogen concentrations below the lower explosive limit can be detected (B5) using a simple and inexpensive optical fiber sensor that consists of a palladium-coated cladded multimode tapered fiber. The working mechanism is based on the absorption changes of the evanescent waves at 850 nm. Concentrations of 50 ppm. A nanometer-thick SPR sensor for gaseous HCl was reported (B29). The interaction of HCl with a 2-nm layer of poly(N-methylaniline) on gold leads to the shift of the surface plasmon resonance. The effect is caused by an increase of the imaginary component of the refractive index and is selective and quasi-reversible. Hydrogen cyanide was quantified with a distributed FOS based on a fairly selective chromogenic reaction (B30). Similarly, intrinsic chemical sensor fibers were used for extended-length chlorine detection (B31). The fiber consists of an SiO2 core and a chlorine-sensitive cladding. Upon exposure to Cl2, the cladding very rapidly changes color and this results in an attenuation of the light throughput of the fiber. A 2-m portion of sensor fiber responds to 10 ppm Cl in milliseconds and to 1 ppm in several seconds. The method was extended to sense chlorine and hydrogen sulfide (B32). An organo-palladium/PVC membrane was introduced for sensing sulfur dioxide (B33). The reflectivity of the film at 530 nm changed significantly on exposure to SO2, and 3.5 ppm is detectable. CO, which interferes in solution, remains inert to the sensor membrane. Optical sensing of HCl was accomplished with phenol red-doped sol-gels (B34). The response is based on an increase of the absorption band at 510 nm when exposed to HCl due to protonation of the dye. The detection limit of moisturized gaseous HCl is 12 ppm. Organic vapors can be sensed (B35) by optical fiber and acoustic wave sensors using single-walled carbon nanotubes. The scheme is based on light reflectometry at a wavelength of 1310 nm. Highly sensitive, repeatable, and very fast responses to 3862
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ethanol and ethyl acetate, with concentrations in the range 10500 ppm, were observed. A fiber-optic surface plasmon resonance sensor for vapors (B36) enables direct refractive index (RI) measurements of samples. The sensor was modified for sensitivity to changes near 1.0008 (i.e., the RI of air). The tapered silicabased fiber SPR sensors can determine the RI changes of gas species and the density change of dry air. A high-sensitivity optical sensor for chloroform vapors (B37) utilizes nanometer films of the δ-form of syndiotactic polystyrene. Reflectivity measurements with a fiber-optic refractometer coated with a nanometric (73 nm) film were performed at pressures of chloroform between 0.2 and 5 Torr. Caron et al. (B38) have constructed a device that uses porous glass optical fibers to detect the saturation of activated charcoal inside cartridges. The fibers display a significant drop in light transmittance when exposed to solvent vapors. Toluene vapors at a few thousand ppm are detectable, for example. Sensing humidity remains a major area of activity. Xu et al. (B39) report on a respective FOC sensor that is based on evanescent wave scattering. Porous sol-gel silica was coated on to the surface of a silica optical fiber core. The evanescent waves that penetrate the coating layer are increasingly strongly scattered as the humidity of the surrounding air increases. Alternatively, poly(vinyl alcohol) may be used as a coating (B40). Miniaturized optical vapor sensors were reported (B41) that utilize bacteriorhodopsin-based biochromic films. These were fabricated by dispersing nanosize fragments of BR in gelatine. When the ambient relative humidity was increased from 12 to 85%, the optical absorption of the films doubled. The cobalt(II) chloride-based FOS for humidity was reinvented (B41). ION SENSORS This section covers sensors for all kinds of inorganic ions including the proton (i.e., pH), cations, and anions, as well as salinity. Optical sensing of pH remains 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, there is still a substantial need for FOS for many other cations, and even more so for anions, not the least for reasons of selectivity and reversibility of existing sensors. Gao et al. (C1) report on a novel nano-pH sensor based on doped silica nanoparticles. These were developed by encapsulating rhodamine-B isothiocyanate in a hydrophilic SiO2 shell The fluorescent core-shell nanoparticles are pH-sensitive, and the sensing range is between pH 5.0 and 10.0. The sol-gel technique also was used (C2) to design one more pH sensor based on a bromothymol blue in a sol-gel silica layer on an optical fiber. Novel lipophilic fluorescein esters carrying one negative charge were embedded (C3) in an uncharged, highly proton-permeable hydrogel to give optical pH sensors that show a negligible crosssensitivity toward ionic strength. If their spectral properties are similar, two indicators may be used in one sensor. This results in an optical pH sensor with a dynamic range that extends from pH 4.5 to 8. A new microchip absorption technique was developed (C4) and applied to the determination of calcium ions in urine. The hybrid microdevice incorporates optical fibers and a ball lens. A reflective mode was employed to increase sensitivity. Calcium ions are sensed via their interaction with arsenazo III to form a
complex with an adsorption maximum at 668 nm. The linear range is from 0.125 to 2.5 mM calcium at pH 9, with a limit of detection of 0.085 mM. Optical “sensors” (mostly regenerable by adding certain reagents) have been reported for the ions calcium/magnesium (water hardness) (C5), barium (C6), mercury (C7), and uranium (C8). They all rely on indicators immobilized in various ionpermeable membranes and suffer from the same limitations (such as pH-sensitivity, and in terms of selectivity, and sensitivity) as the indicators when used in aqueous solutions. Many authors also are of the opinion that their sensors are superior to formerly described “sensors” (more realistically test stripes). Wygladacz et al. (C9) have demonstrated that microspheres can be used for very sensitive analysis of silver ions. The system is based on the ion-exchange method using a selective ionophore. An array of FOS was fabricated using plasticized PVC-based micrometer-scale fluorescent microspheres that were produced via a sonic particle casting device. The response time of the microsensor array is
