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Fiber-Optic Chemical Sensors and Biosensors

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					Anal. Chem. 2008, 80, 4269–4283




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                                                          available now with transmissions over a wide spectral range.
     Books and Reviews                                           4269    Current limitations are not so much in the transmissivity but in
     Sensors for Gases, Vapors, and Humidity                     4271    the (usually shortwave) background fluorescence of most of the
         Hydrogen                                                4271    materials fibers are made from, in particular plastic. There is an
         Hydrocarbons                                            4271    obvious trend toward longwave sensing where background signals
         Oxygen                                                  4272
                                                                         are weaker. Major fields of applications are in sensing gases and
         Other Gases                                             4272
         Vapors                                                  4274    vapors, in medical and chemical analysis, molecular biotechnology,
         Humidity                                                4274    marine and environmental analysis, industrial production monitor-
     Sensors for pH and Ions                                     4275    ing, bioprocess control, and the automotive industry. Note: In this
     Sensors for Organic Chemicals                               4276
                                                                         article, sensing refers to a continuous process, while probing refers
         Organics                                                4276
     Biosensors                                                  4276    to single-shot testing. Both have their fields of applications.
         Enzymatic Biosensors                                    4276        FOS are based on either direct or indirect (indicator-based)
         Immunosensors                                           4277    sensing schemes. In the first, the intrinsic optical properties of
         DNA Biosensors                                          4278
                                                                         the analyte are measured, for example its refractive index,
         Bacterial Biosensors                                    4278
     Applications                                                4279    absorption, or emission. In the second, the color or fluorescence
     Sensing Schemes and Spectroscopies                          4279    of an immobilized indicator, label, or any other optically detectable
         Fiber Optics                                            4279    bioprobe is monitored. Aside from the design of label and probes,
         Capillary Waveguides                                    4280    active areas of research include advanced methods of interrogation
         Microsystems and Microstructures                        4280
         Refractive Index                                        4280    such as time-resolved or spatially-resolved spectroscopy, evanes-
         Spectroscopies                                          4280    cent wave and laser-assisted spectroscopy, surface plasmon
     Literature Cited                                            4281    resonance (SPR), and multidimensional data acquisition. In recent
                                                                         years, fiber bundles also have been employed for purposes of
   This review covers the time period from January 2006 to               imaging, for biosensor arrays (along with encoding), or as arrays
January 2008 and is written in continuation of previous reviews (1–3).   of nonspecific sensors whose individual signals may be processed
Data were electronically searched in SciFinder and MedLine.              via artificial neural networks. The success of SPR in general, and
Additionally, references from (sensor) journals were collected by        in the form of FOS in particular, is impressive.
the author over the past 2 years. The number of citations in this            Following the recent sensor hype of (mainly organic) chemists
review is limited, and a stringent selection had to be made              that tend to refer to optical molecular probes as “sensors”, the
therefore. Priority was given to fiber-optic sensors (FOS) of             literature has become more difficult to sort. This review covers
defined chemical, environmental, or biochemical significance and           literature on methods that enable sensing of (bio)chemical species
to new schemes.                                                          as opposed to conventional types of optical assays. Unfortunately,
   The review does not include the following: (a) FOS that               there is a tendency to even refer to conventional indicators (such
obviously have been rediscovered; (b) FOS for nonchemical                as for pH or calcium) as biosensors if only used in vivo. Similarly,
species such as temperature, current and voltage, stress, strain,        optical analysis of a solution by adding an appropriate indicator
displacement, structural integrity (e.g., of constructions), liquid      probe is now referred to as “sensing” (to the surprise of the sensor
level, and radiation; and (c) FOS for monitoring purely technical        community). I have outlined the situation in more detail in my
processes such as injection molding, extrusion, or oil drilling, even    previous review (3).
though these are important applications of optical fiber technology.
Unfortunately, certain journals publish articles that represent          BOOKS AND REVIEWS
marginal modifications of prior art, and it is mentioned here                 It is obvious that fiber optic chemical sensors (FOCS) have
explicitly that the (nonpeer-reviewed) Proceedings of the SPIE are       had a particular success in areas related to sensing gases and
particularly uncritical in that respect.                                 vapors. Many of the systems implemented are based on direct
   Fiber optics serve analytical sciences in several ways. First,        spectroscopies that range from UV to IR, and from absorbance
they enable optical spectroscopy to be performed at sites inac-          to fluorescence and surface plasmon resonance. Optical chemical
cessible to conventional spectroscopy, over large distances, or          sensors have been comprehensively reviewed by McDonagh et
even at several spots along the fiber. Second, in being optical           al. quite recently (4). The article covers sensing platforms, direct
waveguides, fiber optics enable less common methods of inter-             (spectroscopic) sensors, reagent-mediated sensors and discusses
rogation, in particular evanescent wave spectroscopy. Fibers are         trends and future perspectives. Fiber-optic UV systems for gas
10.1021/ac800473b CCC: $40.75  2008 American Chemical Society                  Analytical Chemistry, Vol. 80, No. 12, June 15, 2008    4269
Published on Web 05/08/2008
and vapor analysis have been reviewed (5). The strong absorbance         spectro-electrochemical sensing does not relate to electrolumi-
of vapors and gases in the UV region is advantageous and resulted        nescence but to electrochemical conversion of an analyte prior to
in a compact detection system of good accuracy. Buchanan has             its spectroscopic detection, e.g., by preconcentration, oxidation,
reviewed recent advances in the use of near-IR (NIR) spectroscopy        reduction, complexation, and optical detection. Given its complex-
in the petrochemical industry (6) and points out NIR is particularly     ity, it does not come as a surprise that the authors point to “the
attractive in this field because it measures the overtone and             need for further refinement of the sensor’s design and the
combination bands predominately of the C-H stretches. Practical          experimental protocol to improve the method’s sensitivity.”
examples include sensing schemes for oxygenates in fuels,                The performances of interferometry, surface plasmon resonance,
determination of octane numbers, the composition of fuels,               and luminescence as biosensors and chemosensors have been
bitumen analysis, and environmental analysis. Tools for life science     critically compared (16). Sensitivity, dynamic range, and resolution
research based on fiber-optic-linked Raman and resonance Raman            were calculated and compared from a range of data from the
spectroscopy were also reviewed (7). One focus is on fiber-optic          literature. Theoretical sensitivities of interferometry and SPR are
probes for UV resonance Raman spectroscopy that offer several            detailed along with parameters affecting these sensitivities.
advantages over conventional excitation/collection methods, an-          Luminescence is said to offer the best resolutions for sensing of
other on novel probes based on hollow-core photonic band gap             protein and DNA, while interferometry is said to be most suitable
fibers that virtually eliminate the generation of silica Raman            for low-molecular weight chemical liquids and vapors if selectivity
scattering within the excitation optical fiber. FOCS for volatile         is not a critical issue. SPR (which is label-free) possibly can sense
organic compounds have been reviewed by Elosua et al. (8). Such          proteins with a resolution similar to that of luminescence.
sensors are minimally invasive, lightweight, passive and can be              Borisov and Wolfbeis (17) have presented what appears to be
multiplexed. The devices were classified according to their               the most comprehensive review on optical biosensors so far.
mechanism of operation and in terms of sensing materials. The            Applications of optical fiber (bio)sensors (FOBS) also include
state of the art in leak detection and localization and respective       areas such as high-throughput screening of drugs (18), the
legal regulations have been reviewed by Geiger (9). Specific              detection of food-borne pathogens (19) (based on either SPR,
aspects include sensor reliability, sensitivity, accuracy, and robust-   resonant mirrors, fiber-optic systems, arrays, Raman spectroscopy,
ness. Applicability is demonstrated for two examples, a liquid           and light-addressable potentiometry), and in environmental sens-
multibatch pipeline and a gas pipeline. Nanostructure-based optical      ing by making use of DNAzymes (20). DNAzymes can selectively
fiber sensor systems and examples of their application have been          identify charged organic and inorganic compounds at ultratrace
reviewed by Willsch et al. (10). Selected examples of advanced           levels in waste and emissions. In combination with laser based
optical fiber sensor systems based on subwavelength structured            detection, DNAzymes enable accurate quantification of such
components are presented. These include sensor for humidity and          compounds and thus represent an attractive alternative to state-
hydrocarbons, for application in the gas industry, and for envi-         of-the-art affinity sensors. Significant strides have been made in
ronmental monitoring using nanoporous thin-film Fabry-Perot               terms of selectivity, sensitivity, and catalytic rates of DNAzymes.
transducer elements or intrinsic fiber Bragg grating sensor               Challenges remain in the development of efficient signal trans-
networks for structural health monitoring. Additionally, new             duction technology for in situ applications. The state of the art in
concepts for sensing based on the use of plasmonic metal                 continuous glucose sensing, a kind of holy grail in FOBS, has
nanoparticles, photonic crystal fibers, and optical nanowires are         been summarized in a book (21), and (fiber) optical methods
discussed.                                                               based on the use of glucose oxidase and transduction via oxygen
    Mohr (11) has reviewed recent developments in chromogenic            consumption are reviewed in one chapter (22).
and fluorogenic reagents and sensors for neutral and ionic analytes           The trend toward miniaturization is obvious. Nanoscale optical
based on covalent bond formation. New indicator dyes for amines          biosensors and biochips for cellular diagnostics have been
and diamines, amino acids, cyanide, formaldehyde, hydrogen               reviewed by Cullum (23), specifically with respect to achievements
peroxide, organophosphates, nitrogen oxide and nitrite, peptides         in employing nanosensors and biochips (e.g., gene chips) in
and proteins, as well as for saccharides also are described, and         cellular analyses ranging from medical diagnostics to genomics,
new means (such as color changes of chiral nematic layers) of            while optical nanobiosensors and nanoprobes were reviewed by
converting analyte recognition into optical signals are described.       Vo-Dinh (24) with respect to the principles, development, and
Aspects of multiple optical chemical sensing with respect to             applications of fiber-optic nanobiosensor systems using antibody-
parameters, materials, and spectroscopies have been reviewe (12).        based probes. One specific class of FOBS, the tapered fiber-optic
Borisov et al. summarize their research on plastic microparticles        biosensors (TFOBS) were reviewed (25). In these, part of the
and nanoparticles for fluorescent chemical sensing and encoding           fiber is tapered so that the evanescent field of the lightwave can
(13). A rather wide and shallow review covers advances in fiber-          interact with samples. TFOBS are often used with transduction
optic sensing in medicine and biology (14). Applications range           mechanisms such as changes in refractive index, absorption,
from the use of fibers acting as plain light pipes to complex             fluorescence, and SPR. A more general review covers recent
chemical sensors. It is stated (somewhat overoptimistically) that        developments in FOBS (26), whereas Walt (27) describes fiber-
chemical sensing can “simply” be achieved by transporting light          optic biosensor arrays for creating high-density sensing arrays.
to and from a measurement site with a plain fiber light guide for         Femtoliter wells can be loaded with individual beads to create
spectrophotometry, fluorometry, or SPR. Flowers et al. discussed          such arrays for multiplexed screening and bioanalysis. Adherent
aspects of fiber-optic spectro-electrochemical sensing for in situ        cells may be attached to the fiber substrate to provide a method
determination of metal ions, mainly copper(II) (15). The term            for observing cell migration and for screening antimigratory
4270   Analytical Chemistry, Vol. 80, No. 12, June 15, 2008
compounds, and even individual enzyme molecules can be loaded          composites of the sol-gel type and used in a reversible hydrogen
into the wells, thus enabling single molecule detection via enzyme-    FOCS (37).
catalyzed signal amplification. Optical microarray biosensing               The gasochromic properties of nanostructured tungsten oxide
techniques (28), in turn, provide a powerful tool for the simulta-     films coated with a palladium catalyst were used to sense
neous analyses of thousands of parameters, be they DNA or              hydrogen gas via the change in the optical transmittance at 645
proteins. The review highlights promising microarray techniques        nm, typically caused by 1% hydrogen in argon gas (38). The
either making use of labels or label-free. Rather than miniaturizing   nanomorphology of the surface considerably improves the gaso-
the optical fiber, these may be covered with nanostructured             chromic properties. Two rather similar articles have been pub-
coatings (29). Active and passive coatings, deposited via the          lished by this group (39, 40).
Langmuir-Blodgett and electrostatic self-assembly techniques,              Luna-Moreno et al. have reported on the effect of hydrogen
may be utilized to affect the transmission of optical fibers. While     on a thick film Pd-Au alloy (41). The resulting sensor consists
such sensor elements are mainly aimed for use in telecommunica-        of a multimode fiber in which a short section of single mode fiber
tions systems, it is very likely that chemical sensor and biosensor    is coated with the Pd-Au film. If exposed to hydrogen, the
development may benefit from such research.                             refractive index of the Pd-Au layer becomes smaller and causes
    Jeronimo et al. (30) review optical sensors and biosensors         attenuation on the transmitted light. The Pd-Au film can detect
based on sol-gel films. Applications include sensors for pH, gases,     4% hydrogen with a response time of 15 s. The same material
ionic species and solvents, as well as biosensors. The use of FOCS     was used to design a hydrogen sensor based on core diameter
for on-site monitoring and analysis of industrial pollutants with      mismatch and annealed Pd-Au thin films (42).
respect to detecting the identity, concentrations, and extent of           Palladium-capped magnesium hydride was used as an alterna-
toxic chemical contamination was overviewed (31). Aspects of           tive sensing material in a fiber-optic hydrogen detector (43). A
process monitoring of fiber reinforced composites using optical         drop in the reflectance of this material by a factor of 10 is
fiber sensors were summarized (32), with a focus on thermoset-          demonstrated at hydrogen levels as low as 15% of the lower
ting resins and on spectroscopy-based techniques that can be used      explosion limit. The response occurs within a few seconds.
to monitor the processing of these materials                           Comparing Mg-Ni and Mg-Ti based alloys, the latter has
    A classroom demonstration was described for a portable fiber-       superior optical and switching properties. A gasochromic TiO2-
optic probe multichannel spectrophotometer (33). With the use          based sensing film was used for hydrogen detection by means of
of this instrument, lecture demonstrations can be made of various      a fiber-optic Fabry-Perot interferometric sensor (44). It was
concepts in molecular fluorescence spectroscopy. Concepts in-           applied to monitor hydrogen gas in air below the lower explosion
clude fluorescence spectrophotometer design geometry and the            limit, has a short response time, and regenerates quickly (at room
correlation of color with emission wavelength, excitation, and         temperature).
emission spectra. The history of research on FOCS and FOBS                 Fiber gratings coated with Pd metal were reported to enable
has been summarized (34).                                              sensing of hydrogen gas (45). Fiber Bragg gratings (FBG) and
                                                                       long period gratings (LPG), both coated with Pd nanolayers, were
SENSORS FOR GASES, VAPORS, AND HUMIDITY                                investigated. The sensitivity of the LPG sensor is better by a factor
    This section covers all room-temperature gaseous species           of ∼500. The FBG sensors appear to be pure strain sensors, and
including their solutions in liquids. One major research focus is      LPG sensors are mainly based on the coupling between the
on hydrogen and methane because both are highly explosive when         cladding modes and evanescent or surface plasmon waves. In
mixed with air and may be sensed more safely with FOS than             another type of FBG sensor, a 10 ppm sensitivity for hydrogen
with electrical devices.                                               was reported (along with cross sensitivity to environmental
    Hydrogen. Hydrogen, along with flammable alkanes, remains           conditions) (46). The sensor was used to monitor the aging of
to be the analyte where safety considerations have led to a            certain materials. Optical fibers coated with single-walled carbon
substantial amount of research in terms of fiber-optic sensing.         nanotubes (SWCNTs) were shown to enable determination of
Since hydrogen gas does not display intrinsic absorptions/             hydrogen at cryogenic temperatures (47). SWCNTs were depos-
emissions that could be used for purposes of simple optical            ited by the Langmuir-Blodgett technique at the distal end of the
sensing, it is always detected indirectly. Hydrogen interacts          fibers. Experiments carried out at 113 K revealed the potential of
strongly with metallic palladium and platinum films and with            sensing <5% of gaseous hydrogen with good reversibility and fast
tungsten oxide. The interactions result in both spectral changes       response time.
(an effect sometimes called gasochromism) and in an expansion              Hydrocarbons. Methane and other hydrocarbons are almost
of the materials. Thus, a hydrogen sensor was reported based on        exclusively sensed via their intrinsic absorption in the near-infrared
palladium coated side-polished single mode fiber (35). When             (NIR). These, in contrast to hydrogen or oxygen, can be detected
exposed to 4% hydrogen gas, the optimal change output power            via their intrinsic absorption in the (near) infrared-albeit cross
obtained in this experiment was 1.2 dB (32%) with a risetime of        sections (molar absorbances) remains small or via Raman scatter.
100 s. Improved response times were reported for a similar sensor      One more fiber-optic Raman sensor was reported for sensing
based on the same scheme (36). The authors have studied the            ethanol and methanol in gasoline (48). It employs a frequency
transmission, the time-response, and the initial response velocity     doubled 532 nm Nd:YAG laser and a specially designed fiber-optic
in the range from -30 to 80 °C. Heating the palladium layer with       Raman probe and enables online determination of sample con-
an auxiliary laser diode improves the response time at low             stituents without employing an expensive IR fiber. The sensor is
temperatures. Palladium also was incorporated into silica nano-        capable of monitoring methanol and ethanol in water and gasoline
                                                                              Analytical Chemistry, Vol. 80, No. 12, June 15, 2008     4271
solutions. Surface-enhanced Raman spectroscopy and surface-           quenching of the long-lived delayed fluorescence of fullerene C70
enhanced IR spectroscopy were applied to selective determination      incorporated in thin films of ethyl cellulose or organosilica (59).
of polycyclic aromatic hydrocarbons (49). Molecular recognition       Molecular oxygen in concentrations as low as 200-800 ng/L can
is accomplished by functionalization of the silver nanoparticles      be determined by this method either at single sensor spots or
with appropriate host molecules.                                      spatially resolved over a temperature range of more than 100 °C.
    A modular, mid-IR, evanescent wave fiber-optic sensor for the      The group of Klimant (60) has presented magnetically separable
detection of hydrocarbon pollutants in water was constructed and      optical sensor beads for oxygen. The beads contain Fe3O4 and
tested (50). The setup uses a broadband light source with             can be magnetically fixed at the bottom of a microbioreactor and
backreflecting optics coupled to a fiber-optic sensing element          enable contactless monitoring of oxygen in cultures of Escherichia
coated with an analyte-enriching polymer that preconcentrates the     coli using fiber optics. The same group has presented new and
analyte. Benzene was quantified down to 500 ppm using a PVC            ultrabright fluorescent probes for oxygen that are based on
polymer coating. Three kinds of microstructure fibers (MSFs)           cyclometalated iridium(III) coumarin complexes (61). The probes
for sensing gaseous hydrocarbons were reported (51) that enable       are less cross-sensitive to temperature, have lifetimes on the order
the quantitation of aromatic hydrocarbons. Their surfaces were        of 8-13 µs in the unquenched state, have quantum yields between
modified by xerogel layers. The MSFs with 10-50 µm air holes           0.3 and 1.0, but are less photostable than ruthenium-based probes
were arranged to one sensor. Capillary silica fibers were also         for oxygen.
fabricated. The response of the sensors to toluene in nitrogen            Fiber optic microsensors with a tip diameter of ∼140 µm were
gas results from spectral changes of the output light from the        reported for simultaneous sensing of oxygen and pH and of
fibers at 1600-1800 nm. A detection limit of 0.007 vol.% of toluene    oxygen and temperature (62). The tip of the fiber was covered
was achieved.                                                         with sensor chemistries based on luminescent microbeads that
    Oxygen. Oxygen sensing remains another area where FOCS            respond to the respective parameters by a change in the decay
are quite successful. Oxygen almost exclusively is sensed by virtue   time, or the intensity of their luminescence, or both. The use of
of the quenching effect it exerts on certain fluorophores. High-       microbeads enables the ratio of the signals to be easily varied,
performance fiber-optic oxygen sensors based on fluorinated             reduces the risk of fluorescence energy transfer between indicator
xerogels doped with quenchable Pt(II) complexes were reported         dyes, and reduces the adverse effect of singlet oxygen that is
by Chu et al. (52). The sensors yield linear Stern-Volmer plots,      produced in the oxygen-sensitive beads. Arain et al. (63) have
and response times range from 4 to 7 s. Rather similar materials      characterized microtiterplates (MTPs) with integrated optical
resulted in even faster responses as reported in a second paper       sensors for oxygen and pH and have applied them to enzyme
by this group (53). Most oxygen sensors display nonlinear             activity screening, respirometry, and toxicological assays. Thin
Stern-Volmer relationship, and this can be described by the so-       hydrophilic sensing films consisting of an analyte-sensitive indica-
called two-site model assuming two quenching constants. It has        tor and a reference fluorophore were deposited on the bottom of
been shown that an artificial network also may be applied to model     the MTPs. Activity screening was demonstrated for glucose
the dynamic quenching of the fluorescence of a ruthenium-derived       oxidase and for monitoring the growth of E. coli and Pseudomonas
probe (54).                                                           putida. A toxicological assay also is reported that enables monitor-
    A porous plastic sensor was developed for the determination       ing the respiratory activity of P. putida. In order to compensate
of dissolved oxygen in seawater (55). The luminescent indicator,      for the rather strong effects of temperature on oxygen sensors
a ruthenium(II)diimine complex, was copolymerized with a              based on dynamic quenching of luminescence, Borisov et al. (64)
polymerizable monomer, a cross-linking reagent, and a porogen.        have developed a composite luminescent material for dual sensing
It did not leach out due to its high hydrophobicity. Sensing is       of oxygen and temperature, where temperature can be measured
based on dynamic quenching of the fluorescence of the ruthenium        optically and used to calculate temperature-corrected data for pO2.
indicator. The permeability of contact lenses for oxygen can be       Quantum dots undergo temperature-dependent changes of the
determined with a fiber-optic luminescent sensor system (56). The      intensity, the peak wavelength, and the spectral width of their
method is based on kinetic measurements of the oxygen partial         luminescence. Hence, they can be used as probes to compensate
pressure inside a chamber sealed by the sample contact lens,          for effects of temperature in FOCS (65). Effects are almost linear
where a thin luminescent O2-sensitive film is being placed. Unlike     and fully reversible. A resolution of 0.3 °C was achieved.
in electrochemical techniques, the optical sensor is unaffected by        Oxygen and carbon dioxide are clinically highly significant
the thickness of the contact lens and other effects.                  blood gases. A composite fluorescent material was described that
    Oxygen sensors were used to transduce the activity of catalase    enables simultaneous sensing and imaging of oxygen and carbon
(57). This is of interest to characterize the oxidative metabolism    dioxide (66). It relies on the measurement of the phase shift of
in coffee cherries during maturation as it appears to be regulated    the luminescence decay time of a material composed of microbead-
by the timely expression of redox enzymes such as catalase (CAT),     contained indicators (with well-separated excitation and emission
peroxidase, and polyphenoloxidase. The assay allows for the           wavelengths) and polymers with excellent permeation selectivities
screening of green coffee samples for CAT activities. An evanes-      as well as favorable optical and adhesive properties. A luminescent
cent wave fiber sensor was used to determine oxygen deficiency          dual sensor for time-resolved imaging of pCO2 and pO2 in aquatic
(58). The sensing dye, methylene blue, was immobilized in the         systems was reported by Schroeder et al. (67).
cladding using a sol-gel process. The sensor is said to respond           Other Gases. Ozone gas was sensed via its UV and visible
logarithmically linear between 0.6% and 20.9% oxygen. The most        absorption (68). Both the UV absorption at 254 nm and the visible
sensitive sensor for oxygen known so far exploits the efficient        absorption at 600 nm were studied. Sensing in the UV region
4272   Analytical Chemistry, Vol. 80, No. 12, June 15, 2008
allows for highly sensitive detectors due to its high absorptivity     different thicknesses were prepared layer-by-layer, all showing a
in that region. The visible region has a significantly lower            linear sensitivity to NH3 in the 0-100 ppm range and a response
absorption coefficient but enables monitoring high ozone levels.        time of around 30 s. The sensor was regenerated by rinsing with
The UV based sensor can detect 0-1 mg/L of ozone and the               water.
longwave sensor 25-126 mg/L.                                               Most ammonia sensors reported so far make use of its effect
    Nitrogen is a species not easily sensed by optical means except    on appropriate pH probes. This is also true for one more sensor
by Raman spectroscopy. A respective FOCS to monitor the                that makes use of a sol-gel matrix (76). Both NH3 vapor and
concentration ratio of nitrogen and oxygen in a cryogenic mixture      trace NH3 dissolved in water can be detected. The indicator was
was reported by Tiwari et al. (69). Spontaneous Raman scattering       immobilized in porous SiO2 which then was deposited on the
was used to monitor of the purity of liquid oxygen in the oxidizer     surface of a bent optical fiber core. In combination with a silicone
feed line during ground testing of rocket engines. The Raman           protection coating, ammonia can be sensed in watery samples.
peak intensity ratios for mixtures of liquid nitrogen and liquid       The limit of detection is 13 ppb in gas samples and 5 ppb in water
oxygen were analyzed for their applicability to impurity sensing       samples. This is comparable to previously reported probes
using different excitation light sources, and a miniaturized sensing   exploiting the same effect. The scheme was extended to sensing
system was developed that responds within a few seconds. A             ammonia via fiber-optic microsensors at 2-100 µg/L levels that
practical sensor for online sensing of atomic nitrogen in direct       are known to be highly toxic to fish and other organisms (77). A
current glow discharges was reported by Popovic et al. (70).           fluorescent pH indicator placed in a cellulose ester matrix at the
Sensing is accomplished by monitoring the intensities of the           tip of an optical microfiber is deprotonated by ammonia, thereby
atomic nitrogen spectral line at 822 nm and the bandhead at 337        undergoing a large change in fluorescence intensity. The resulting
nm, relative to the oxygen line at 845 nm. Measurements were           ammonium ion is stabilized by a cation trap. The detection limit
performed using two methods. The first approach uses a fiber-            is reported to be 0.5 µg/L. The microsensors were used to
optic spectrometer, calibrated with a standard source, to record       establish ammonia microprofiles of high spatial resolution. Inter-
the desired spectral lines. The second approach uses narrow            ference by trimethylamine was minimized using an 18-crown-6
bandwidth optical filters to detect the emission intensity. Optical     ether as a cation trap and by the permeability properties of the
data are collected for a range of experimental conditions in a         polymer matrix. Cross-sensitivities toward protons and alkali ions
flowing glow discharge of N2-O2 mixtures.                               were prevented by coating the sensor with a layer of Teflon.
    Sensors for carbon dioxide and, to a lesser extent, ammonia            Ammonia also was sensed with the help of silica nanocom-
remain another active area of research. Carbon dioxide emissions       posites doped with silver nanoparticles and deposited on an optical
from a diesel engine can be monitored with the help of a mid-          fiber waveguide (78). The SiO2 nanocomposite was prepared by
infrared optical fiber sensor (71). As conventional automotive          the sol-gel technique in the presence of (3-mercaptopropyl)tri-
pollution sensors fail to meet monitoring requirements as specified     methoxysilane) and doped with 25 µm silver nanoparticles. The
by the European Community, for various reasons, a low-cost             material was deposited onto the surface of a bent silica fiber by
sensor employing compact mid-IR components is presented that           the dip-coating technique. Exposure to gas containing ammonia
was used to measure CO2 in the exhaust of a commercial diesel          enhances the attenuation of light power guided through the fiber
engine. A novel kind of optical sensor for carbon dioxide makes        probe. Sub-ppm levels of NH3 can be continuously monitored by
use of silicone encapsulated ionic liquids (72). The silicone matrix   this technique.
acts as a permeation-selective material for CO2, while the ionic           Oberg et al. (79) have designed a simple optical sensor for
liquid contains a pH probe (in its base form) that undergoes a         vapors of organic amines based on silica microspheres dyed with
distinct color change after its (reversible) reaction with CO2.        pH indicators such as bromocresol green (a probe reported to
Dissolved CO2 usually is sensed via the effect it exerts on the pH     be useful for sensing ammonia by others several times before).
of a buffer immobilized in a matrix. A sulfonated hydroxypyrene        It can detect organic amine vapors down to 1-2 ppb levels. The
named HPTS has been widely used as a pH probe in such CO2              response to aliphatic amines is linear up to 2 ppm. The micro-
sensors in the past two decades, and one more type of organically      sphere sensor is said to be more sensitive than other optical amine
modified sol-gel was used to develop one more modification of            sensor described in the literature but heavily interfered by
this kind of sensor (73). Because the gel is partially fluorinated,     ammonia. The group of Mohr reports (80) that functional liquid
the response is faster. Nanoporous matrixes also may be used to        crystal films can selectively recognize amine vapors and thereby
host pH-sensitive phenolic dyes and an alkaline phase transfer         undergo a change in their color. Molecular recognition is ac-
agent, reagents typically employed in sensors for CO2 (74).            complished by cholesteric liquid crystals combined with molecules
    Ammonia in the gas phase may be sensed either via its NIR          carrying a trifluoroacetyl group. Note: sensors for amines in fluid
absorption or (in being a weak base) via the weak pH changes it        phases are treated in section D on sensors for organic molecules.
can induce in immobilized pH indicators. The latter approach is            One more fiber-optic probe was reported for the selective
more sensitive. It also is the prefered one in that it is applicable   determination of NO2 in air samples (81). Signal generation is
to aqueous solutions (unless extractive phases are employed in         based on the spectroscopic changes of a reagent contained in the
IR sensing schemes). A new sensing scheme for ammonia is based         nanopores of a sol-gel element that undergoes an irreversible
on monitoring the optical changes of the Q-band of tetrakis(4-         chromogenic reaction. Two fiber-optic designs are described.
sulfophenyl)-porphine (TSPP) at 700 nm, as induced by ammonia          Another FOCS for NO2 makes use of poly(3-octylthiophene) as a
in the electrostatic interaction between TSPP and poly(diallyldim-     sensing material (82). This material undergoes large spectral
ethylammonium) chloride (75). Three thin film samples with              changes at 543 nm if exposed to NO2. The sensor is not very stable
                                                                             Analytical Chemistry, Vol. 80, No. 12, June 15, 2008   4273
in that the response decreases after each exposure to NO2 but is      (90) that uses birefringent porous glass oriented between two
rapid, highly selective, and sensitive. Vehicle exhaust emissions     crossed polarizers and serving as the basis for this broad-spectrum
such as NO2, NO, SO2 were detected using an ultraviolet optical       sensor. VOCs such as acetonitrile vapors can be detected at
fiber based sensor (83). It is used to simultaneously measure their    concentrations of >50 ppm. The optical effects resulting from
concentrations, with lower limits of detection of 2 ppm for NO2, 2    exposure to various VOCs are reversible and may result from
ppm for SO2, and 20 ppm for NO. Response times are <4 s. Optical      adsorption of VOCs with attendant reduction of anisotropy. The
sensitivity to NO2, carbon monoxide, and hydrogen (all in dry         sensor can make use of ambient light as a light source and the
air) was observed for a layer of a metal oxide multilayer of the      eye as a detector to register the resulting color changes and thus
type InxOyNz covered with gold nanoclusters (84). The incorpora-      is capable of real time monitoring of VOCs. Also see ref 91.
tion of the gold nanoclusters leads to a broad absorption peak in         A fiber-optic nanosensor for volatile alcoholic compounds has
the visible (purple) due to the excitation of localized surface       been described by Elosua et al. (92). It is based on a new
plasmons. The maximum of the peak is shifted on exposure to           vapochromic red powder consisting of a silver metal organic
oxidizing or reducing gases.                                          compound. Its color and refractive index change when exposed
    An irreversible active core fiber-optic probe was developed for    to vapors of VOCs. The process is fully reversible. The sensor
determination of trace H2S at high temperature using a cadmium        consists of a nanometer-scale Fizeau interferometer doped with
oxide doped porous silica fiber as a transducer (85). If exposed       the vapochromic material and placed at the cleaved end of a
to a gas sample at high temperatures, trace H2S in the sample         multimode fiber-optic pigtail. The response of the material toward
diffuses into the porous fiber and reacts with cadmium oxide to        different alcohols was measured at 850 nm, and changes up to 3
form cadmium sulfide (CdS), and this is detected at around 370         dB in the reflected optical power were registered. The authors
nm with a fiber-optic spectrometer. The CdS formed also emits          have used the same material in a Fabry-Perot interferometer with
strong fluorescence, with a peak emission at around 500 nm, but        a nanosized cavity along with a optical fiber pigtail system (93).
this signal is quenched at 450 °C, so that fluorescence can only           The performance of a carbon nanotube (CNT) based thin films
be used for probing trace H2S at low temperature. Fuel gases such     fiber-optic for VOCs was described (94). Single-walled CNT
as H2, CH4, and CO were found not to interfere. The toxic             multilayer coatings were used that cause a response toward
industrial chemicals hydrogen cyanide, hydrogen sulfide, and           toluene and xylene vapors. The Langmuir-Blodgett technique was
chlorine can be sensed with waveguides coated with doped              applied to deposit the CNTs directly onto the optical and acoustic
polymer materials in the form of arrays (86). The polymers are        sensors substrates. The results demonstrate ppm to ppb sensitiv-
patterned on glass substrates and undergo color changes that can      ity, fast response, and high repeatability. In a related paper, the
be interrogated at different wavelengths. Miniature waveguide         incorporation of CNTs into hollow core fiber optics is reported
channels result in enhanced sensitivity owing to the increased        (95).
path length. The sensors have response times (t90) of less than           King et al. (96) report on a microsensor for VOCs where a
20 s. Certain cross interferences observed can be eliminated by       photonic crystal of porous silicone is attached to the distal end of
applying a signal processing algorithm that also reduces false        an optical fiber. Activated carbon is used as a prefilter, and any
alarms. Elemental iodine, unlike chlorine, exerts a quenching         breakthrough of the VOC through the carbon results a large
effect on a derivative of aminobenzanthrone, and this effect was      change in the reflectivity of the porous silica.
used in a respective fiber-optic sensor (87). It can detect iodine         Humidity. Optical humidity sensors are a kind of evergreen
with a rather high concentration detection limit of 6 µM.             given their highly different applications. Numerous materials
    An optical biosniffer for methyl mercaptan, one of the smelling   including Nafion films doped with crystal violet responding to
principles in halitosis, was reported (88). Monoamine oxidase         humidity by a change in their reflectance (97). Relative humidity
(MAO) was immobilized at the tip of a fiber-optic oxygen sensor        (RH) between 0 and 0.25% can be determined with the respective
with a luminescent oxygen probe (excitation at 470 nm, emission       sensor, with a detection limit as low as 0.018% RH (equal to ∼4
peaking at 600 nm). The sensing scheme is based on the detection      ppm). The response is fully reversible (with some hysteresis) in
of the oxygen consumed as a result of enzymatic oxidation of          dry nitrogen. Reversal times depend on exposure time and % RH.
methyl mercaptan (MM) by MAO. The output of the sniffer was           The sensor can detect moisture in process gases such as nitrogen
amplified by substrate regeneration via reduction with ascorbic        and HCl. In another kind of RH sensor, Ru(II) complexes were
acid. MM levels between 9 and 11 000 ppb were detectable. The         employed since their luminescence decay time depends on RH.
pathological threshold is 200 ppb, the limits of human perception     The analytical information is obtained via phase-sensitive deter-
are on the order of 10 ppb.                                           mination of the decay time (98). The ruthenium probe was
    A rather complex method for optical sensing of sulfur dioxide     immobilized on a Teflon support. The operational range is from
in wines (89) employs a dinuclear palladium ligand complex            4 to 100% RH at 20 °C. Its response time is shorter than 2 min
immobilized in a PVC membrane plasticized with o-nitrophenyl-         (recovery time <1.2 min). Signal stability was verified for >2.5
octylether (o-NPOE). Both free and total SO2 can be determined.       years of discontinuous measurement. The sensor was applied to
Linear responses up to 50 and 150 mg/L were obtained for free         measure RH in food and in a weather station.
and total SO2, with detection limits of 0.37 and 0.70 mg L-1,             Certain porphyrins deposited in Nafion films undergo water-
respectively.                                                         induced tautomerism. This forms the basis of a novel type of fiber-
    Vapors. Vapors, often referred to as volatile organic com-        optic RH sensor (99). It exhibits long-term stability and a linear
pounds (VOCs), often are sensed by optical means in order to          response over the humidity range from 0 to 4000 ppm. Another
reduce the risk of explosion. An FOCS for VOCs was reported           fiber-optic RH sensor reported (100) is based on large-core
4274   Analytical Chemistry, Vol. 80, No. 12, June 15, 2008
quartz/polymer optical fiber pairs. Examples of vapors that              cence lifetimes, photostabilities, and acidity constants were
interfere (or may be sensed with this device) include those of          determined in organic solvents and in PVC. The Schiff bases can
acetone and ethanol. In other words: it is not specific for RH.          be photoexcited at 556 and 570 nm, respectively, and respond to
    The sensitivity of a tapered optical fiber relative humidity (RH)    pH in the range from 8.0-12.0 and 7.0-12.0, respectively.
sensor was optimized by means of tuning the thickness of                    A novel wide pH range sensing system was described that is
nanostructured sensitive coatings (101). A single mode tapered          based on a sol-gel encapsulated amino-functionalized corrole
fiber was coated with a specific nanostructured polymer whose             (109). An amino modified fluorescent aminophenylcorrole im-
thickness was controlled so to optimize sensitivity to RH. The          mobilized in a sol-gel SiO2 matrix undergoes large changes in
sensor displays a 27 times better sensitivity to RH than a              fluorescence intensity owing to multiple steps of protonation and
comparable overlay, this enabling monitoring human breathing.           deprotonation, thereby allowing larger pH ranges (1-11) to be
Huang et al. report (102) that a thermoplastic polyimide when           covered than via respective tetraphenylporphyrins. Dong et al.
deposited on a fiber-optic Bragg grating can act as a material           (110) have obtained wide-range pH optical sensor by immobilizing
sensitive to RH in that it undergoes reversible expansion and           three indicators in a sol-gel matrix that was deposited in a fiber
shrinkage.                                                              optic waveguide and optically interrogated by evanescent wave
                                                                        absorptiometry. The sensors have a dynamic range from pH 4.5
SENSORS FOR pH AND IONS                                                 to 13.0.
    This section covers sensors for all kinds of inorganic ions
                                                                            A scheme for measurement of very high pH values as they
including the proton (i.e., pH), cations, and anions. Optical sensing
                                                                        occur in chemical processing was presented by Gotou et al. (111).
of pH remains to be of greatest interest even though all optical
                                                                        It is used to establish a health monitoring method for chemically
sensors suffer from cross sensitivity to ionic strength. The number
                                                                        exposed fiber reinforced plastic structures in that it can detect
of articles on pH sensors is decreasing, though, which does not
                                                                        the penetration of corrosive solutions into plastics. A high-pH
come as a surprise in view of the state of the art and the fact that
                                                                        indicator is used along with an optical fiber connected to a
certain pH FOS are commercially available. On the other side,
                                                                        spectrophotometer.
sensing of pH values below 1 and above 12 still represents a
                                                                            Seki et al. describe a pH sensor based on a heterocore
substantial challenge in terms of material sciences. Optical pH
                                                                        structured fiber optic (112). It consists of multimode fibers and
sensors respond over a limited range of pH only (in most cases).
                                                                        a short piece of single mode fiber which was inserted into the
It also needs to be stated that many pH sensors presented in the
                                                                        multimode fibers. The pH indicator phenol red was immobilized
past few years are modifications only of existing sensing schemes
                                                                        in a sol-gel matrix at the surface of the heterocore portion. pH
and materials, and that authors often do not properly cite previous
                                                                        changes were detected by measuring the loss spectra at 575 and
work on the subject. In the worst case, sensors are presented
that are inferior to others described before. Such sensors are not      545 nm, respectively. It is noted at this point by the author of this
treated here.                                                           review that sol-gels and other condensates of that kind are known
    The group of Scheper has introduced a scheme for referenced         not to provide a temporally stable matrix but rather to change
sensing of pH that is based on spectral analysis of fluorescence         their microstructure over periods of typically a few months. This
(103). pH is calculated by chemometric means from selected data         is rarely addressed by authors of respective work.
points of the fluorescence spectra of aminofluorescein at high                Indicator loaded microbeads that are permeation selective for
concentration so that a strong inner filter is operative. Martin et      either protons or dissolved oxygen were used in a respective
al. describe a new organic pH indicator dye (mercurochrome)             dually sensing membrane and a single fiber-optic sensor (113).
that was immobilized in a sol-gel matrix placed at the end of a         The pH probe (a carboxyfluorescein) and the oxygen probe (a
fiber optic and enables measurement of pH in the pH 4-8 range            ruthenium complex) were incorporated into two kinds of micro-
(104). The sensor is constructed from low cost fiber optic and           particles, viz. an amino-modified poly(hydroxyethyl methacrylate)
optoelectronic components including a blue light emitting diode         and an organically modified sol-gel, respectively. Both kinds of
and a photodiode. The sensing scheme relies on the measurement          beads were then dispersed into a hydrogel matrix and placed at
of the fluorescence intensity of the pH indicator that is related to     the distal end of an optical fiber waveguide for optical interroga-
the intensity of the blue excitation light reflected by the sensing      tion. A phase-modulated blue-green LED served as the light source
phase. The ratio between the two signals is proportional to pH          for exciting luminescence whose average decay times or phase
but independent of excitation light intensity. The applicability of     shifts served as the analytical information. Data are evaluated by
this sensor was tested for its performance in pH analysis in tap        a modified dual luminophore referencing method which relates
and bottled mineral water (105). The same group also has                the phase shift (as measured at two different frequencies) to pH
developed sol-gel matrixes by controlled hydrolysis of a titanium       and to O partial pressure.
tetraalkoxide (106). The resulting sol-gel (TiO2) is said to be             In related work but using different materials (for optoelectronic
more resistant and to have a longer lifetime than SiO2 films. The        reasons), microsensors were described for simultaneous sensing
matrix was doped with various pH indicator dyes, each being             of pH and oxygen (114). This is important in clinical chemistry
sensitive to different pH ranges.                                       and if minute sample volumes are only available. The microsensors
    Congo red and neutral red on a cellulose acetate support have       with a tip diameter of ∼140 µm make use of luminescent
been reinvented as a material for sensing the 4.2-6.3 and 4.1-9.0       microbeads that respond to the respective parameters by a change
pH range, respectively (107). Two aromatic Schiff bases were            in the decay time, intensity, or both. A complex algorithm enables
studied for their suitability in terms of sensing alkaline pH values    precise calculation of pH even if the spectra of the indicator dyes
(108). Absorption and emission spectra, quantum yields, fluores-         (for pH and oxygen) overlap.
                                                                               Analytical Chemistry, Vol. 80, No. 12, June 15, 2008    4275
    An evanescent wave direct spectroscopic sensor for chromate         a covalent bond between their boronic acid moiety and the diol
anion reported by Tao & Sarma (115) uses a flexible fused silica         moiety of saccharides. This causes their fluorescence to increase.
light guiding capillary as a transducer. The capillary has a cladding   The probe can be photoexcited at around 460 nm, emits with a
layer and a protective polymer coating on its outside surface. The      peak at 600 nm, and can be used at near neutral pHs. For a review,
cladding layer ensures the ability of the capillary to guide light,     on probes for saccharides and glycosylated biomolecules see ref
while the protective coating increases its mechanical strength. Like    125.
similar sensors described before, the sensor is based on the                Tri-n-propylamine and the drugs benzhexol and procyclidine
intrinsic evanescent wave absorption by chromate ions in a water        were determined via electrochemiluminescence (ECL) in a sensor
sample inside the capillary. A 30 m long capillary has the capability   constructed by the screen-print technique (126). Ruthenium(II)-
of detecting as little as 31 ppm of chromate.                           tris(bipyridine) on Nafion was immobilized on a carbon electrode,
    A fluorescence-based calcium nanosensor was described (116)          and its ECL resulting from the interaction with the analytes was
that exploits silica nanoparticles (prepared by inverse microemul-      measured. Limits of detection are as small as 30 nM. Polymer
sion polymerization) doped with the calcium(II) probe calcein as        membranes containing a chromogenic functional azo dye undergo
both a recognition and transduction element for optical determi-        color changes on (reversible) interactions with amines in organic
nation of calcium in blood serum. Traces of vanadium(V) ion can         solvents (127). The dye (covalently linked to the polymer matrix)
been determined by using an irreversible chromogenic reaction           recognizes the analyte via covalent binding. Binding constants of
between vanadium ion and a hydroxamic acid immobilized in a             the various amines depend on the kind of solvent and are highly
poly(vinyl chloride) (PVC) membrane (117). A quenchable                 different, this resulting in strongly varying limits of detection.
fluorescent benzofurane derivative in the plasticized PVC matrix         Dissolved amines also can be sensed by incorporating an amine-
served as the indicator dye in an FOCS for ferric ion (118).            carrying chromoionophore into a sol-gel matrix (128). Both acid-
Response time, reversibility, limits of detection (poor), dynamic       and base-catalyzed sol-gel processes were studied, but the former
range, and interferences were studied. The same group has               were found not to respond at all. Stable ormosil layers were
synthesized a fluorescent semicarbazone and demonstrated its             obtained using various fractions of organically modified sol-gel
applicability as a selective probe in an FOCS for copper(II) (119).     precursors, e.g., methyl triethoxysilane. Base-catalyzed sensor
PVC and ethyl cellulose acted as sensor matrixes, and both              layers underwent large signal changes, with response times of
absorption and emission spectrometry can be applied. Aluminum           around 1-2 min, and rather high detection limits (0.1 mM).
ion in aqueous media can be probed with a regenerable sensor                Organics. A fluorescent dosimeter for formaldehyde deter-
that uses a molecularly imprinted polymer (MIP) as the recogni-         mination in water utilizes the Nash reagent incorporated into silica
tion receptor (120). The MIP was prepared with Al(III) ion acting       gel beads (129). On reaction with formaldehyde, a fluorescent
as the template, and 8-hydroxyquinoline sulfonate acted as a            product is formed that can be detected instrumentally or visually.
fluorogenic ligand. The MIP was synthesized from acrylamide,             The dosimeter does not respond to primary alcohols, ketones,
2-hydroxyethyl methacrylate, and ethylene glycol dimethylacrylate       and other common substances. The detection limit is reported to
as a cross-linker. At pH 5, Cu(II) and Zn(II) interfere to some         be 30 µg/L. Dissolved organics in water samples can be sensed
extent. The dynamic range at pH 5 is linear up to 0.1 mM, the           with a nanoporous zeolite thin film-based fiber sensor (130). A
limit of detection is 4 µM. Mercury(II) ions were optically probed      Fabry-Perot interferometric system was developed containing a
by Li et al. (121). They report on a luminescent nanosensor for         thin layer of nanoporous zeolite synthesized on the cleaved end
Hg(II) where the fluorescence of carnitine capped quantum dots           face of a single mode fiber. The sensor is operated by monitoring
made from CdSe/ZnS is quenched by Hg(II) ions with an                   changes in the thickness of the thin film caused by the adsorption
efficiency that resulted in a detection limit of 0.2 µM. In related      of organic molecules by white light interferometry. Methanol,
work it is reported (122) that Pb(II) ions can be (irreversibly)        2-propanol, and toluene were detected with high sensitivity. A
probed by a similar method but using CdTe quantum dots capped           FOCS for toluene in water was described by Consales et al. (131).
with thiols. The detection limit is virtually the same.                 It makes use of single-walled carbon nanotubes whose reflectivity
                                                                        changes in the presence of toluene. System features include good
SENSORS FOR ORGANIC CHEMICALS                                           stability of the steady-state signal, sensitivity, and rapid response.
   This chapter covers sensors for organic species (mainly
saccharides), pollutants, agrochemicals, nerve agents, drugs and        BIOSENSORS
pharmaceuticals, and miscellaneous other organics. Mid-IR laser             This section covers biosensors based on the use of enzymes,
spectroscopy was performed by either using cryogenically cooled         antibodies, nucleic acids, and whole cells. Biosensors make use
lead salt lasers or quantum cascade lasers operating at room            of biological components in order to sense a species of interest
temperature and applied to reagentless (enzymeless) sensing of          (which by itself need not be a “biospecies”). On the other side,
glucose (123). Aqueous solutions of glucose were analyzed by            chemical sensors not using a biological component but placed in
fiber based attenuated total reflection spectroscopy and by               a biological matrix are not biosensors by definition. It should be
transmission spectroscopy. Both methods have the potential to           noted that some of the biosensors can be found in other chapters
be utilized in small fiber sensors that may be inserted into             if this was deemed to be more appropriate.
subcutaneous tissue. Concentrations as low as 0.1 mg/mL were                Enzymatic Biosensors. Sensing glucose remains to be an
detectable.                                                             evergreen. Unlike in the case of electrochemical schemes where
   Mohr et al. (124) describe fluoro-reactands for the enzymeless        direct electron shuttle from the substrate to the electrode has
determination of saccharides. They are based on hemicyanine             become possible as a result of enzyme wiring, no such approach
dyes containing a boronic acid receptor and are capable of forming      is possible in optical sensors. Hence, these still rely on (a)
4276   Analytical Chemistry, Vol. 80, No. 12, June 15, 2008
transduction via metabolic coreactants (such as oxygen or NAD+);        the fluorescent pH indicator carboxynaphthofluorescein. Hydroly-
(b) of coproducts (such as protons, hydrogen peroxide, or NADH);        sis of organophosphates by OPH causes the pH to fall, and this
or (c) on affinity binding (such as to concanavalin A). Compre-          is reported by the pH probe. The dynamic range for determination
hensive reviews have appeared (132). The group of Klimant has           of paraoxon is from 1 to 800 µmol/L.
designed a fiber-optic flow through sensor for online monitoring              Single molecules of galactosidase were monitored (140) using
of glucose in patients in intensive care units (133). A tubing as       a 1 mm diameter fiber-optic bundle with individually sealed
used in microdialysis contains an integrated fiber-optic sensor.         femtoliter microwell reactors. Unlike in so-called “ensemble”
Glucose is sensed via oxygen consumption which occurs as a              responses in which many analyte molecules give rise to the
result of the oxidation of glucose catalyzed by immobilized GOx.        measured signal, the buildup of fluorescent products from single
The gas permeable tubing warrants constant air saturation in the        enzyme molecules catalysis over the array of reaction vessels can
flow cell. A reference oxygen sensor is used to detect changes in        be observed, and a digital concentration readout can be obtained
oxygen supply caused by adverse effects such as bacterial growth,       by application of statistical analysis. This approach should prove
temperature fluctuations, or failure of the peristaltic pump. The        useful for single molecule enzymology and ultrasensitive bioas-
sensor was evaluated in a 24 h test on a healthy volunteer. Endo        says. A similar approach (141) was applied to 24 000 individual
et al. describe a needle-type enzyme sensor system for determin-        reaction chambers to sense DNA and antibodies and again is
ing glucose levels in fish blood (134). A hollow needle was used         expected to be applicable to assays that utilize an enzyme label
that also was comprised of an immobilized enzyme membrane               to catalyze the generation of a fluorescent signal.
and a optic fiber probe with a quenchable ruthenium-based oxygen             A fiber-optic enzymatic biosensor was described for determi-
indicator. The calibration curve was linear for glucose in fish          nation of 1,2-dichloroethane (DCA) (142). Haloalkane dehaloge-
plasma. One assay was completed within 3 min. A good reproduc-          nase in whole cells of Xanthobacter autotrophicus immobilized in
ibility was observed 60 times without exchange of the enzyme            calcium alginate at the tip of a fiber-optic coverts the haloalkanes
membrane. The group of Nann (135) found that the luminescence           into acidic products (i.e., lowers the pH), and this is detected via
of silica coated quantum dots is dynamically quenched by                the pH probe fluorescein immobilized at the tip of the FOBS. DCA
hydrogen peroxide (H2O2), and this was exploited in a optical           was quantified at levels as low as 11 mg/L, with a linear response
glucose assay using the enzyme GOx. This is one of the few              at ∼65 mg/L. Like most cell-based catalytic biosensors, the
reversible optical methods that are based on the transduction of        response time is slow (8-10 min). Rajan et al. report on the
oxidase based reactions via H2O2. The quantum dots have a rather        fabrication and characterization of a surface plasmon resonance
high specific surface area which enables a relatively large amount       based enzymatic FOBS for detection of the bittering component
of GOx to be immobilized. On the basis of the previous work on          naringin (143). The sensing area was coated over ∼1 cm length
sensing H2O2 via the amount of oxygen formed by catalytic               with silver and then with the enzyme naringinase. The SPR
decomposition of H2O2, Mills et al. (136) have designed a robust        wavelength maximum increases with the concentration of naringin.
and reversible sensor where ruthenium(IV)dioxide is used as a               Immunosensors. Antinuclear antibodies can be quantified
catalyst. The amount of oxygen liberated is determined via the          with an optical fiber biosensor modified with colloidal gold (144).
quenching effect it exerts on the luminescence of a ruthenium(II)       The unclad portion of an optical fiber was covered with self-
ligand complex.                                                         assembled gold colloids whose surface was functionalized with
    Luminescent yeast cells were entrapped in hydrogels in order        antigens. Antinuclear antibodies in serum can be determined
to optically detect estrogenic endocrine disrupting chemicals           quantitatively, and the results agree well with the accepted ELISA
(137). Genetically modified Saccharomyces cerevisiae cells contain-      method. This sensing platform is label-free, enables real-time
ing the estrogen receptor expression of the luc reporter gene were      detection, and does not require a secondary antibody. Its sensitiv-
immobilized in hydrogel matrixes. The chemicals induce a                ity is higher by at least 1 order of magnitude than that of the
chemiluminescence to be emitted by the cells. Concentrations            ELISA method.
down to 80 ng/L of the chemicals were detectable. The probe                 Antibodies against the F1 antigen of Yersinia pestis (the cause
was stored for 1 month at -80 °C but full activity was attained         for plague and a potential terroristic agent) can be detected by a
again at room temperature. The data obtained with this sensor           sandwich immunoassay on the surface of an optical fiber (145).
roughly correlated with LC-MS/MS analytical results.                    Autoantibodies to ovarian and breast cancer-associated antigens
    Fiber optic absorbance spectroscopy was compared with               are detectable with high sensitivity by using a chemiluminescence
surface plasmon optical detection methods for lactamases bound          based optical fiber immunosensor (146). The protein GIPC-1 was
to interfacial structures via biotin-avidin coupling (138). Quantita-   conjugated to the tip of an optical fiber. A human monoclonal IgM
tive comparisons were made between the five matrixes and                 isolated from breast cancer patients targets the GIPC-1 protein
between the binding strategies. All matrixes were suited, in            and thus can be detected in concentrations down to 30 pg/mL,
principle, for the binding of the protein. Results obtained by SPR      which is 50 times lower than the chemiluminescent ELISA and
and optical waveguide measurements correlate excellently. Real          ∼500 times lower than the colorimetric ELISA. Sera from 11
time activity assays of -lactamase were performed by a detection        ovarian cancer patients, 22 breast cancer patients, and asymp-
scheme that combines an affinity test and a catalytic sensor.            tomatic controls were tested for the presence of IgM anti-GIPC-1
    Organophosphate pesticides and chemical warfare agents can          autoantibodies by the two methods.
be sensed with a FOBS that exploits the enzyme organophosphate              A waveguide based immunosensor for the food toxins aflatoxin
hydrolase (OPH) as the biorecognition element (139). Conjugated         B1 and ochratoxin A uses either the competitive or the direct
to biotin, it was attached to a polystyrene waveguide along with        immunoassay format (147). The antibody conjugate was im-
                                                                               Analytical Chemistry, Vol. 80, No. 12, June 15, 2008   4277
mobilized on a sensor chip and exposed to the analytes in a flow             Surface plasmon resonance (SPR) spectroscopy was used for
injection analyzer. The detection range of the competitive detection    detecting target sequences in genomic DNA differing in terms of
method was between 0.5 and 10 ng/mL. The indirect method was            copies in the relative genome (154). Following fragmentation with
used to sense toxins in barley and wheat flour samples. Results          restriction enzymes and denaturation, the interaction of the two
are in good agreement with those obtained by ELISA.                     strands is found to be specific both with oligonucleotides and
    DNA Biosensors. A fiber-optic DNA microarray for simulta-            with genomic nonamplified DNA. The usual amplification step
neous determination of multiple harmful algal bloom species was         is found not to be necessary. In another type of DNA biosensor,
reported by Ahn et al. (148). Algal blooms are a serious threat to      localized SPR spectroscopy was coupled to interferometry
coastal resources, causing a variety of impacts on public health,       (155). A gold layer was deposited on porous anodic alumina
regional economies, and ecosystems. The sandwich hybridization          and interrogated by both interferometry and localized SPR. The
assay combines fiber-optic array technology with appropriate             intensity of light reflected by the chip resulted in an optical
oligonucleotide probes immobilized on microspheres. Hybridiza-          pattern that was highly sensitive to changes in the effective
tion was visualized using fluorescently labeled secondary probes.        thickness of the layer on the surface, specifically oligonucle-
A detection limit as low as 5 cells is achieved, the assay time being   otides and hybridized oligonucleotides.
45 min without a separate amplification step. An elegant diagnostic          In a novel kind of DNA biosensor, the electrochemilumines-
device for the detection of the hepatitis B virus was presented         cence (ECL) of the Ru(II) bipyridyl complex (a weak intercalator)
(149). An isothermal amplification method is employed so to              is used to generate optical analytical information (156). If ds-DNA
detect the viral DNA in a 25 µL reaction volume following several       binds to intercalators such as doxorubicin or daunorubicin, an
automated handling steps.                                               easily detectable ECL is generated in the presence of the
    Bacterial transcriptional regulators are known to be dose-          ruthenium complex at +1.19 V (vs Ag/AgCl), while ss-DNA
dependently released from their operators upon binding of specific       (which is not intercalated) does not give this effect. Given the
classes of antibiotics. In another approach, Link et al. (150) use      sensitivity of ECL-based methods, this approach may be quite
a generic dipstick-based technology for rapid determination of          powerful. Several pathogens (including hepatitis virus) were
tetracycline, streptogramin, and macrolide antibiotics in food          detected by this technique.
samples. The dipstick assay consists of a membrane support strip            Bacterial Biosensors. Bioavailable mercury and arsenic in
coated with streptavidin and immobilized biotinylated operator          soil and sediments were determined with fiber-optic bacterial
DNA, which acts as capture DNA to bind hexa-histidine (His6)-           biosensors (157). Alginate-immobilized recombinant luminescent
tagged bacterial biosensors. Antibiotics present in specific samples     bacteria were immobilized on optical fibers and enabled lumines-
triggered the dose-dependent release of the capture DNA-biosensor       cent quantification of 2.6 µg/L of Hg(II), 141 µg/L of As(V), and
interaction. Dipping the stick into two reagent solutions results       18 µg/L of As(III). The pesticide methyl parathion was shown to
in a correlated conversion of a chromogenic substrate by a His6-        be detectable using Flavobacterium sp. adsorbed on glass fiber
targeted enzyme complex. It has detection limits as low as 1/40         filters as a disposable biocomponent (158). The flavobacterium
of the licensed threshold. In a comparable approach, antibiotics        contains a hydrolase that hydrolyzes methyl parathion into
in seafood were screened for a fiber-optic fluorometric assay based       optically detectable p-nitrophenol. Only 75 µL of sample are
on competitive binding of the analyte and an intercalating dye to       needed to detect 0.3 nmol/L concentrations of methyl parathion.
double stranded DNA (151). The antibiotics affect the binding of            Microbially available dissolved organic carbon was quantified
the intercalator to the double stranded nucleic acid, thereby           with a microsensor (159) containing microorganisms in a poly-
changing the fluorescence intensity. The concentration of the            urethane hydrogel. A strain was used that displays low substrate
analyte is indirectly determined by the decrease in fluorescence         selectivity and responded to mono- and disaccharides, to fatty
intensity. A DNA of 48.5 kb was found to be a suitable sensing          acids, and to amino acids. The 90% response time was 1-5 min.
nucleic acid. Sulfathiazole and chloramphenicol in shrimps were         Another optical fiber biosensor for biochemical oxygen demand
sensed by this method with detection limits from 0.5 to 1 ng/mL.        (BOD) is based on microorganisms coimmobilized in an ormosil
    An optical biosensor for real-time detection of DNA interactions    matrix (160). The consumption of dissolved oxygen is measured
was demonstrated with a long-period fiber-grating biosensor (152).       with a fluorescent optical fiber sensor. The BOD values obtained
The probe DNA was immobilized on the silanized surface of the           correlate well with those determined by the conventional BOD5
grating and then hybridized with the complementary (target)             method for seawater samples.
DNA. The sensor is reusable because the target DNA can be                   Genetically engineered bioluminescent bacteria were applied
stripped off the grating surface after the assay. Wang et al. report    to the detection of toxicants in surface waters (161). The
on a DNA detection protocol utilizing the opacity of self-assembled     multichannel system developed is based on mini-bioreactors
nanometallic particles (NPs) and the optical response of a CMOS         containing four kinds of recombinant bioluminescent bacteria and
image sensor (153). The authors exploit the fact that DNA               is connected to a luminometer via a fiber-optic cable. The system
fragments attached to NPs precipitate them only at locations            can be continuously operated due to the separation of the bacteria
where cDNA strands exist. Hence, the opacity of the chip surface        culture reactor from the test reactor without system shutdown
changes due to the accumulation of NPs and this can be used to          by abrupt inflows of severe pollutants. Bioluminescent signatures
detect targeted DNA fragments. The approach is very sensitive,          were delivered from four channels by switching one at once. The
detecting even single-base mismatched DNA targets in concentra-         system is now being implemented to a drinking water reservoir
tions down to 10 pM.                                                    and river for remote sensing as an early warning system.
4278   Analytical Chemistry, Vol. 80, No. 12, June 15, 2008
APPLICATIONS                                                             Reflectance spectra in the 1250-2500 nm region for the skin of
    This section comprises sensors for environmental, industrial,        volunteers reveal large regional differences of water content. There
biotechnological, food, pharmaceutical, medical, and related ap-         was a difference in the ratio of the two water bands centered near
plications of FOCS and FOBS. Thus, a newly developed miniatur-           1450 and 1900 nm between the contact and noncontact measure-
ized diamond ATR probe has been described that displays high             ments. Most regional differences of water content were calculated
chemical and pressure resistance. In combination with robust and         from the peak height of the 1900 nm water band normalized to
flexible fiber-optics, it enables inline chemical reaction monitoring      the peak height of the 2175 nm amide band.
(162).                                                                       One large area of application of FOCS is in monitoring the
    Huber et al. (163) reports on the measurement of the ingress         mechanical and chemical integrity of concrete structures. Aside
of oxygen into PET bottles using oxygen sensor technology. A             from sensing mechanical integrity (not treated here), changes in
noninvasive fiber-optic oxygen meter detects oxygen permeability          chemical composition are of high interest given the health risk
of PET bottles for soft drinks by measuring trace levels of oxygen       and costs associated with disintegrated structures. Optical fiber
inside the bottle. Permeation rates are obtained without piercing        sensors have been used to monitoring the ingress of moisture in
the package or bottle which is ideally suited for assurance,             structural concrete (170). The humidity sensors were fabricated
production, and quality control applications. Sensing is based on        using fiber Bragg gratings coated with moisture sensitive poly-
quenching of the fluorescence by oxygen of a sensor spot placed           mers and are employed in detecting the movement of moisture
on the inner wall of the transparent bottle. A fiber-optic cable is       through standardized cubes made from samples of different types
positioned outside and measures changes in luminescence life-            of structural concrete. Data obtained can give information on the
time. Gaseous or dissolved oxygen can be detected in the ppm to          properties of different types of concrete but also on the migration
ppb range.                                                               of dissolved salts, such as sodium chloride which is important in
                                                                         view of their deleterious effects on reinforcement bars within
    Near-infrared reflectance spectroscopy was applied to quanti-
                                                                         concrete. The optical fiber sensors reacted to the ingress of water
tate Ca, K, P, Fe, Mn, Na, Zn, protein, and moisture in alfalfa (164).
                                                                         by detecting the moisture migrating through the sample, indicated
The method allows immediate analysis of alfalfa without prior
                                                                         by a shift in the Bragg wavelength of the sensor. A similar
sample treatment. A partial least-squares regression method was
                                                                         approach was introduced by Yeo et al. (171).
employed. The prediction capacity of the model and the robust-
                                                                             Chloride ion in concrete can be sensed with a long-period fiber
ness of the method were checked in the external validation in
                                                                         grating (LPFG) (172). The LPFG device is sensitive to the
alfalfa samples of unknown compounds.
                                                                         refractive index of the medium around the cladding surface of
    The biocompatibility of Te-As-Se (TAS) glass fibers for use
                                                                         the sensing grating, thus offering the possibility of detecting a
in infrared sensors was studied by Wilhelm et al. (165). The fibers
                                                                         change in chemical concentration. The authors measured chloride
are used for IR direct spectroscopy of cultivated mammalian cells.
                                                                         ions in a typical concrete sample immersed in salt water solutions
TAS fibers undergo oxidation on air to form a water-soluble
                                                                         in concentrations ranging from 0 to 25%. The sensor exhibited a
nanometer-thin layer that is soluble in water. The glass underneath
                                                                         linear decrease in the transmission loss and resonance wavelength
this layer is, however, stable in water over several days. Hence,
                                                                         shift when the chloride was increased. The limit of detection for
oxidized fibers that can release arsenate ions are toxic, while
                                                                         chloride ions is ∼0.04%. Sensitivity was further enhanced by
freshly prepared or washed fibers are not. Glasses displaying less
                                                                         coating a monolayer of colloidal gold nanoparticles as the active
strong interfering vibrations in the 2-5 µm spectral region were
                                                                         material on the grating surface of the LPFG which increase the
prepared from TeO2-BaO-Bi2O3 mixtures (166). IR and Raman
                                                                         sensitivity by a factor of 2.
spectroscopic studies were carried out, and the temperature
                                                                             pH sensors for concrete are needed to detect any (highly
dependence of the viscosities of the glasses is reported.
                                                                         adverse) changes in the rather high pH (>11) of concrete. An
    A fiber-optic sensor for measurements of interstitial pH was
                                                                         fiber-optic pH sensor was developed that can be incorporated into
further improved (167). The interstitial sample fluid drawn
                                                                         concrete and thus is capable of early detection of the danger of
subcutaneously from adipose tissue flows through a microfluidic
                                                                         corrosion in steel-reinforced concrete structures (173).
circuit formed by a microdialysis catheter in series with a glass
capillary. The pH indicator phenol red is covalently immobilized         SENSING SCHEMES AND SPECTROSCOPIES
on the inner wall of the capillary. Optical fibers are used to connect       This section reports on improved or novel sensing schemes
the interrogating unit to the sensing capillary. A resolution of 0.03    based on the use of fiber optics and related waveguides. Aside
pH units and an accuracy of 0.07 pH units were obtained.                 from their use as plain waveguides, fibers have been used for
Preliminary in vivo tests were carried out in pigs with altered          evanescent wave excitation of fluorescence or Raman scatter, for
respiratory function.                                                    imaging and sensor array purposes, in microsensors and nanosen-
    Data on pH, carbon dioxide, and oxygen as obtained with fiber-        sors, and for distributed sensing, to mention only the more
optic sensors on intramuscular and venous blood during rhythmic          important ones. The current success of (fiber optic) surface
handgrip exercise were compared (168). A fiber-optic sensor was           plasmon resonance (SPR) is obvious.
inserted into muscle for continuous measurement of intramuscular            Fiber Optics. New in-line fiber-optic structures for environ-
data. Blood samples were taken from the forearm every minute             mental sensing applications were described (174). Sensors based
during each exercise bout. The data for venous and arterial blood        on the interaction of surface plasmons or evanescent waves with
were found to be highly different when exercising.                       the surrounding environment are usually obtained by tapering an
    Regional differences in the water content of human skin can          optical fiber. A fiber-optic structure is presented that maintains
be studied by diffuse reflectance near-infrared spectroscopy (169).       the structural integrity of the optical fiber. Graded index optical
                                                                                Analytical Chemistry, Vol. 80, No. 12, June 15, 2008   4279
fiber elements are used as lenses, and a coreless optical fiber acts         Analog signal acquisition from computer optical disk drives
as the interaction area. These elements are fused by an optical        was demonstrated to be useful in chemical sensing (182). Signals
fiber splicer. Two optical system designs were compared for fiber-       were obtained from optical sensor films deposited on conventional
optic chemical sensor applications (175). A single grating spec-       CD and DVD optical disks. Almost any optical disk can be
trograph with fiber-optic input and photodiodes at three different      employed for deposition and readout of sensor films. The disk
wavelengths was compared to a system comprising 1-3 fiber-              drives also perform the function of reading and writing digital
optic splitters and photodiode detectors with integrated interfer-     content to optical media. Such a sensor platform is quite universal
ence filters. Three types of splitters were tested, and it is found     and can be applied to sensing and combinatorial screening.
that that the systems have similar characteristics, also if used in    Specifically, colorimetric calcium-sensitive films were deposited
a colorimetric CO2 sensor.                                             onto a DVD, exposed to different concentrations of Ca(II), and
    Capillary Waveguides. Tao et al. (176) described the ap-           quantified in the optical disk drive.
plication of a light guiding flexible tubular waveguide in evanescent       Ink jet printing technology was applied to fabricating micro-
wave absorption based sensing. A light guiding flexible fused silica    sized optical fiber imaging sensors (183). An array of photopo-
capillary (FSCap) was used that is similar to a conventional silica    lymerizable sensing elements containing a pH sensitive indicator
fiber in that it can guide light in the wavelength region from UV       was deposited on the surface of an optical fiber image guide. The
to near IR. The inner surface of the FSCap capillary was coated        reproducibility of the microjet printing process was found to be
with a reagent doped polymer to design a FOCS. Techniques were         excellent for micrometer-sized sensor spots. Hanko et al. (184)
developed for activating the inner surface of an FSCap, coating        showed that nanophase-separated amphiphilic networks represent
the inner surface of the FSCap with a polymer, connecting the          versatile matrixes for optical chemical and biochemical sensors.
coated FSCap to a light source and a photodetector, and delivering     They consist of nanosized domains of hydrophilic and hydrophobic
a sample through the FSCap were developed. Sensors for Cu(II),         polymers (comparable to a polyacrylamide-co-polyacrylonitrile
                                                                       copolymer referred to as Hypan and previously introduced by
toluene in water samples and ammonia in a gas sample were
                                                                       others). Because of the spatial separation, there are domains in
fabricated and tested. Similarly, the waveguiding properties of a
                                                                       which the indicator reagents are immobilized and domains where
FCSap for chemical sensing applications were investigated by
                                                                       diffusive transport of the analyte occurs. Various prototypes of
Keller et al. (177). Absorbance within the tubing was measured
                                                                       sensors were prepared, e.g., for sensing gaseous chlorine (based
by optically coupling the FSCap to a spectrophotometer. The
                                                                       on a chromogenic reaction), vapors of acids (based on immobilized
FSCap operated evanescently or as a liquid core waveguide
                                                                       bromophenol blue), and peroxides (based on immobilized horse-
depending upon the refractive index of the sample solution within
                                                                       radish peroxidase and a chromogenic substrate).
the capillary. Evanescent absorbance was linear with the concen-
                                                                           Refractive Index. High-sensitivity optical chemosensors were
tration of a nonpolar dye but nonlinear with ionic dyes due to
                                                                       implemented by exploiting fiber Bragg grating structures in
adsorption to the capillary wall. Absorbance measurements in 50,
                                                                       D-shape, single-mode, and multimode fibers and postsensitized
150, and 250 µm inner diameter FSCaps show that greater
                                                                       by HF etching treatment (185). Hence, the intrinsically insensitive
sensitivity is achieved in thinner walled tubings because of more
                                                                       Bragg grating became sensitive to refractive index (RI). The
internal reflections. A FSCap for pH is demonstrated.
                                                                       resulting devices were used to measure the concentrations of
    A liquid-filled hollow core microstructured polymer optical fiber
                                                                       sugar solutions. A self-temperature-referenced sensor based on
(178) is said to be opening up many possibilities in FOCS. It is
                                                                       nonuniform thinned fiber Bragg gratings was described (186).
demonstrated how the band gaps of such a hollow core polymer           The sensor consists of a Bragg grating where the cladding layer
optical fiber scale with the refractive index of a liquid introduced    is removed along half of the grating length. This perturbation leads
into the holes of the microstructure. The fiber is then filled with      to a wavelength-splitting in two separate peaks: the peak at lower
an aqueous solution of (L)-fructose, and the resulting optical         wavelengths corresponds to the thinned region and is dependent
rotation is measured. Hence, hollow core microstructured polymer       on the outer RI and the local temperature, while the peak at longer
optical fibers can be used for sensing chiral species. A distributed    wavelength responds to thermal changes only. The sensor was
fiber-optic polarimetric sensor was reported by Caron et al. (179).     characterized in terms of thermal and RI sensitivities. A photonic
The sensor is based on evanescent wave polarimetric interferom-        band gap fiber for measurement of RI was described by Sun and
etry and is intended for use in gas chromatography. It allows real-    Chan (187).
time monitoring of the displacement of a chemical substance along          Spectroscopies. Fiber optic (bio)sensors were reported that
a capillary.                                                           are based on localized surface plasmon resonance (SPR) (188).
    Microsystems and Microstructures. A sub-nanoliter spec-            The sensor measures the light intensity of the internally reflected
troscopic gas sensor was described (180) and compared to               light at a fixed wavelength from an optical fiber where the
existing sensors designs. This novel gas sensor has the capability     extinction cross-section of self-assembled gold nanoparticles on
of gas detection with a cell volume in the sub-nanoliter range. A      the unclad portion of the optical fiber changes with the refractive
study of the capabilities of microstructure fibers for evanescent       index of a sample near the gold surface. Sensing of the Ni(II) ion
wave vapor sensing is presented in ref 181. Toluene vapor in           and label-free detection of streptavidin and staphylococcal entero-
nitrogen gas was investigated. It causes a change in the refractive    toxin B is demonstrated at picomolar levels. A related reflection
index changes of the xerogel fiber cladding at 670 nm. Moreover,        based localized SPR fiber-optic probe was developed to determine
specific changes in absorbance due to C-H overtone absorptions          refractive indexes and, thus, chemical concentrations at high
of toluene at 1600-1800 nm were exploited.                             pressure conditions (189). Sensing is based on the measurement
4280   Analytical Chemistry, Vol. 80, No. 12, June 15, 2008
of the intensity of internal light reflection at a fixed wavelength          acted as the (co)organizer of several conferences related to fluorescence
from an optical fiber. The light attenuation caused by the                  spectroscopy (MAF) and to chemical sensors and biosensors (Europtrode).
                                                                           He acts on the board of several journals including Angewandte Chemie
absorption of self-assembled gold nanoparticles on the unclad              and is the Editor-in-Chief of Microchimica Acta. His research interests
portion of the optical fiber changes with a different refractive index      are in optical chemical sensing and biosensing, in fluorescent probes and
of the environment near the gold surface. The probe demonstrated           labels, in fluorescence-based analytical formats including imaging, in
                                                                           biosensors based on thin metal films using capacitive or SPR interrogation,
a stable and repeatable response for sequential operations of              and in the design of advanced (nano)materials (including fluorescence
pressurization and depressurization at 0.1-20.4 MPa at 308 K. A            upconverters) for use in (bio)chemical sensing.
new concept of an SPR fiber-optic sensor was presented (190). A
significant variation of the spectral transmittance of the device is
                                                                           LITERATURE CITED
produced as a function of the concentration of the analyte by
tuning the plasmon resonance to a wavelength for which the outer           BOOKS AND REVIEWS
medium is absorptive. With this mechanism, selectivity can be                (1)   Wolfbeis, O. S. Anal. Chem. 2002, 74, 2663–2677.
                                                                             (2)   Wolfbeis, O. S. Anal. Chem. 2004, 76, 3269–3284.
achieved without the need of any functionalization of the surfaces
                                                                             (3)   Wolfbeis, O. S. Anal. Chem. 2006, 78, 3859–3873.
or the use of recognizing elements, which is an important feature            (4)   McDonagh, C.; Burke, C. S; MacCraith, B. D. Chem. Rev. 2008, 108,
for any kind of FOCS or FOBS.                                                      400–422.
    Cavity ringdown (CRD) absorption spectroscopy enables spec-              (5)   Eckhardt, H. S.; Klein, K.-F.; Spangenberg, B.; Sun, T.; Grattan, K. T. V.
                                                                                   Journal of Physics: Conference Series; 2007; Vol. 85, no pages given, on-
troscopic sensing of gases with a high sensitivity and accuracy. The               line computer file; CAN 148:44768.
limits of sensitivity were further pushed (191). This continuous-wave        (6)   Buchanan, B. Practical Spectroscopy. Handbook of Near-Infrared Analysis,
CRD spectrometer uses a rapidly swept cavity of simple design.                     3rd ed.; CRC Press: Boca Raton, FL, 2008, Vol. 35, pp 521-527.
                                                                             (7)   Blades, M. W.; Schulze, H. G.; Konorov, S. O.; Addison, C. J.; Jirasek,
Measurements in the near IR from 1.51 to 1.56 µm yield sub-ppb                     A. I.; Turner, R. F. B. New Approaches in Biomedical Spectroscopy; ACS
(v/v) sensitivity in the gas phase for CO2, CO, H2O, NH3, C2H2, and                Symposium Series 963; American Chemical Society: Washington, DC,
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                                                                                   1440–1465.
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cost, and compact instrument. The geometry of a fiber-optic surface-         (10)   Willsch, R.; Ecke, W.; Schwotzer, G.; Bartelt, H. Proc. SPIE-Int. Soc. Opt.
enhanced Raman scattering (SERS) sensor was optimized with                         Eng. 2007, 65850B/1–65850B/8. (Optical Sensing Technology and
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the number of internal reflections at the interface between silica and       (12)   Nagl, S.; Wolfbeis, O. S. Analyst 2007, 132, 507–511.
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                                                                                   C.; Nagl, S.; Schaeferling, M.; Stich, M. I.; Kocincova, A. S.; Wolfbeis,
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instrument can be deployed in-field.                                                Berberan, M. N. Ed.; Springer Series in Fluorescence, Vol. 4; Springer:
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(193). The method is based on the difference between the                    (16)   Ince, R.; Narayanaswamy, R. Anal. Chim. Acta 2006, 569, 1–20.
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a dually emitting indicator (an aluminum-ferron complex). The                      108, 423–461.
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was constructed using low-cost optoelectronics including a light            (20)   Vannela, R.; Adriaens, P. Crit. Rev. Environ. Sci. Technol. 2006, 36, 375–
                                                                                   403.
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                                                                                   Springer: New York, 2006; pp 351-375.
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