Fiber-Optic Nanotip Sensors for Chemical Detection: Comparison
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Recently, rapid progress has been achieved in the field of nanomaterial preparation and investigation. Many nanomaterials have been employed in optical chemical sensors and biosensors. This entry is focused on fiber-optic nanotip sensors for chemical sensing based on silica and plastic optical fibers. The preparation, materials, and sensing characteristics of selected fiber-optic nanotip sensors are employed to show the performance of such nanosensors for chemical sensing. Some examples of fiber-optic nanotip biosensors are included in order to document the broad sensing performance of fiber-optic nanosensors. The employments of fiber nanotips for surface-enhanced Raman scattering, and in  nanosensors using both electrical and optical principles are also discussed.  

  • nanosensor
  • fiber nanotip
  • chemical sensing
  • preparation
  • characteristics

1. Introduction

In the last forty years, sensors based on optical fibers have been broadly investigated for chemical sensing and biosensing. The progress achieved in the development of such sensors can be understood from several extensive reviews [1][2][3][4][5][6][7]. Such sensors employ electromagnetic (EM) radiation and light in a wavelength range of 0.2–10 µm. However, visible light is frequently used. Generally, a fiber-optic (FO) sensor consists of several parts. The most important sensor part is a fiber-optic detection element with a detection site (see Figure 1a) in which physical characteristics of EM radiation (amplitude, phase, and polarization) change due to the element’s interaction with analytes. The radiation source and radiation detector are also indispensable parts of optical sensors. An output signal from the detector, usually electrical voltage or current, is treated in data-acquisition electronics.
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Figure 1. Fiber-optic chemical sensor; (a) a principal sensor scheme; (b) schematic electrical-intensity distribution in a fundamental guided mode; blue curve-guided-mode intensity in the core, red curve-guided-mode intensity in the cladding, i.e., evanescent wave.
In the detection site, parameters of EM radiation are changed due to changes in optical properties caused by analytes present there. Optical properties such as the refractive index, absorption and emission spectra, and birefringence are usually used in FO chemical sensors. In direct FO sensors, intrinsic optical properties of analytes are employed. However, many analytes have no suitable intrinsic optical properties for detection, and thus, so-called chemical transducers or biotransducers are used in indirect FO chemical sensors or biosensors. Such transducers interact with analytes in detection sites, and this interaction causes changes in optical properties in the site. These changes can be related to changes in the optical properties of the transducer (e.g., in FO pH sensors) or to optical properties of reactants produced by reactions of the transducer and analyte (immunosensors and enzymatic sensors). Examples of chemical transducers include absorption and luminescence dyes for pH or ion sensors [1][2][3][4][5][6][7]. Antibodies, enzymes, DNA chains, cells, etc., are examples of biotransducers used in optical biosensors [1][2][3][4][5][6][7][8].
The access of analytes into detection sites can be controlled using detection membranes [1][2][3][4][5][6][7][9][10][11]. Such membranes control the amount and concentration of analytes in detection sites through their partitioning characteristics [9]. These characteristics are determined by the membrane morphology, chemical composition, and structure, which influence the access of analytes into the membrane. Detection membranes can be fabricated of polymers [11] or dried gels [9][10]. FO sensors provided with porous xerogel membranes have been used for the detection of gaseous aromatic hydrocarbons in mixtures with nitrogen [9] as well as for sensing toluene dissolved in water [10]. Moreover, such detection membranes can be used for the immobilization of opto-chemical transducers in detection sites. Detection membranes also change the refractive index in detection sites and, consequently, the transmission of EM radiation through them. 
In FO sensors, optical fibers are employed as detection elements. In optical fibers used in telecommunications, EM radiation is guided in special EM waves and guided optical modes, mainly in fiber cores (see Figure 1b) [12]. However, these EM waves also penetrate fiber claddings at distances of 500–1000 nm. The part of the guided mode in the cladding is called an evanescent wave. The electrical intensity of the evanescent wave exponentially decreases with the distance from the core/cladding boundary. In addition to the guided modes, there are cladding modes propagating in the cladding, usually on short lengths.
The same guiding mechanism as in standard optical fibers occurs in microstructure fibers, i.e., fibers fabricated from one material (e.g., silica) but with air holes in the cladding [13][14]. These holes decrease the average refractive index of the cladding bellow that of the solid core. On the other hand, the photonic band gap guiding mechanism can be found in hollow-core crystal fibers (HCPCF) [13]. Such fibers consist of a large air core surrounded by the cladding of a periodic grid of air holes or a grid of periodically alternating high- and low-index thin layers. Such grids exhibit the photonic band gap at certain wavelengths, due to which radiation transmitted in the HCPCF is confined to the air core.
Detection sites in fiber-optic detection elements can be found in their optical claddings, as in evanescent-wave sensors, or at distal ends of fibers in contact with their optical cores, as in reflection sensors (see Figure 1a). HCPCFs can employ their air cores for detection. FO sensors with detection sites in the core or cladding can be called intrinsic FO sensors. There are also extrinsic FO sensors in which optical fibers are used for guiding light to and from detection sites.
In the development of FO chemical sensors and biosensors, researchers have mainly employed telecommunication types of optical fibers, such as polymer-clad silica (PCS) fibers and multimode and single-mode silica fibers [1][2][3][4][5][6][7][8][9][10][15][16][17]. Plastic optical fibers (POFs) have also been used [1][2][3][4][5][6][7][15][16][17]. All these fibers are commercially available at reasonable prices. Sensors based on them can profit from easily available light sources, detectors, connectors, couplers, etc. It is worth mentioning that in addition to these silica and plastic optical fibers, chalcogenide optical fibers have also been broadly investigated for chemical sensing and biosensing recently [18][19]. These fibers have an important advantage over silica fibers, because they can be used for sensing in mid-infrared spectral regions where strong and characteristic infrared spectral bands exist. However, special light sources and detectors are used with these fibers, and they are available only from several specialized producers.
In telecommunication fibers, the ratio of power transmitted in evanescent waves is below 1% [12][20]. It means that analytes in the cladding can change a relatively low optical power, and consequently, the response of the fibers caused by analytes is low. Different approaches have been developed for increasing the ratio of optical power transmitted in the cladding. The approaches based on bending PCS or POF fibers to U-shapes, tapering PCS, single-mode (SM), and multimode fibers (MMF) into fiber tapers and tips, exciting only some optical modes in fiber cores, etc., have been employed [1][2][3][4][5][6][7][11][15][16][17][20]. Moreover, fiber gratings such as long-period gratings (LPG) or tilted fiber Bragg gratings (TFBG) are inscribed into SM fibers (see Figure 2) [15][16][17]. Such gratings are based on the coupling of guided modes into cladding modes, which are sensitive to refractive-index changes in the fiber surroundings. All these approaches enable to increase the effects of external optical changes on the intensity, phase, and polarization of optical modes transmitted in such modified fibers. These optical changes are provided by absorbance, luminescence, and refractive-index changes caused by analytes.
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Figure 2. Schemes of the principal structure and output spectrum of (a) tilted fiber Bragg grating and (b) long-period grating. Λ: grating period and λG: principal grating wavelength.
It is necessary to note that refractometric FO sensors based on silica and plastic fibers can be employed for the detection of refractive indices higher than approximately 1.4. Thus, they are not suitable for refractive-index sensing in aqueous solutions, which is important for biology and medicine. This refractive-index limitation can be overcome using a sensing fiber with a nanometer-scaled metallic layer applied onto the core/cladding boundary. Such layers can be found in FO sensors employing surface plasmon resonance (SPR) [15][16]. The SPR phenomenon is related to the excitation of surface plasmons (SPs) in free electrons moving at the layer surface by evanescent waves of optical modes propagating in the fiber core. Excitation conditions depend on the refractive indices of materials in contact with the metallic layer. A similar effect, called localized surface plasmon resonance (LSPR), takes place at the surface of metallic nanoparticles. It has also been used in FO chemical sensors and biosensors [16]. 
A fiber-optic SPR sensor represents a nanosensor in that a novel sensing principle, surface plasmon resonance, is related to the use of nanometer-scale metallic layers applied on the core/cladding boundary. In addition to FOSPR sensors, different approaches for the development of FO chemical nanosensors and nanobiosensors have been investigated in the last thirty years. Such nanosensors are based on fiber-optic tips with apex diameters below 100 nm, nanomaterials such as quantum dots [17][21][22][23], nanoparticles [16][17], nanotubes [17][24][25], nanorods [25], nanolayers [16][17], nanosheets [16][17][26][27][28][29][30][31] etc., applied to fiber-optic cores.  Due to nanometric dimensions in a range of 1–100 nm under the definition, nanomaterials exhibit unique physical and chemical characteristics [32]. Nanostructured sensing optical fibers have enabled to observe novel physical phenomena, such as SPR and LSPR, surface-enhanced Raman scattering (SERS), near-field light effects, etc. Moreover, they offer the performance for sensing in single cells or very small volumes of analytes, typically femtoliters. This entry focusses on fiber-optic chemical nanosensors based on fiber-optic nanotips.

2. Fiber-Optic Nanotip Sensors

Optical, chemical nanosensors and nanobiosensors based on fiber-optic (FO) nanotips can provide with reliable methods for monitoring chemicals in microscopic samples and detecting chemicals within single cells [33]. FO nanotip sensors offer significant improvements over methods of cellular analysis, such as direct loading of cells with fluorescent indicators. These nanosensors exhibit several useful characteristics for cellular analysis. They are biocompatible and can protect the intracellular environment from the effects of dyes injected during direct loading. Their nanometer sizes minimize physical perturbation of the cell, and their small size can provide a fast response time for the sensor. Opto-chemical transducers are immobilized on nanosensor surfaces and do not suffer from diffusion in the cell. The first papers on FO nanotips and nanotip sensors were published around 1990 [34][35][36]. Papers on the development of such sensors can be found approximately until 2010. Since then, the number of articles has decreased. This decrease may be related to the broad use of luminescence nanoparticles (probes embedded in localized environment, PEBBLEs) [37][38][39]. Such nanoparticles have been employed intensively for intercellular chemical analysis [37][38][39]. They can be fabricated by well-elaborated chemical methods, which are probably less complicated than techniques used for the fabrication of FO nanotips. However, their insertion into cells is more complicated than that of FO nanotips. They can also require sophisticated optical instruments for their interrogations. A fiber-optic nanotip is represented by an optical fiber element with one end elongated into a sharp tip with an apex. In this paper, fiber tips with apex diameters in a range of 20–100 nm are considered nanotips. However, in some papers, this term is also used for fiber tips with apex diameters below one micrometer. The term submicrometer tips used in some papers seems more suitable for tips with apex diameters from 100 to 1000 nm. In some papers, published results are not related to precise information on the tip apex diameters. Transducers are usually immobilized in detection sites on the tip apex. Nanometer dimensions of the apex mean that all optical changes in the site take place in the near- field of EM waves transmitted through the site. In fact, FO nanotips have successfully been employed for scanning near-field optical microscopy (SNOM) [40].

2.1. Fiber Nanotip Preparation

To prepare fiber-optic nanotips, different methods have been employed. They include high-resolution micromachining, focused ion beam milling (FIB), femtosecond laser machining, lithography, photopolymerization, thermal pulling, and chemical etching. The principles and performance of such techniques have been reviewed elsewhere [33][41]. FIB, lithography, femtosecond laser machining, and high-resolution micromachining require complex and costly devices. The technique based on grinding and polishing is simple and low-cost. However, it is more suitable for the preparation of fiber microtips [41]. High-resolution micromachining has been used only for the fabrication of nanoarrays on the end of a single fiber and not for the preparation of fiber nanotips [41]. Photopolymerization has been employed for the application of sensing nanomembranes on fiber tips but not for tip preparation. Thus, thermal pulling and chemical etching are discussed in detail in this paper. The thermal pulling technique is schematically described in Figure 3. The technique uses a heat source, gas torch, or CO2 laser that heats a bare part of a fiber element while tension is applied along the major axis of the element. The fiber is fixed in clamps so the applied tension can be controlled. By heating silica glass fibers at temperatures above 1600 °C, viscous flows in glass are induced. These flows and the glass surface tension, together with the applied external tensions, cause a decrease in the diameter of the bare fiber part and fiber elongation. A biconical taper is produced at first (see Figure 3b). This taper has a short central part, the waist, with a constant diameter. By continuing the heating, the taper is broken, and two fiber tips are produced (see Figure 3c). By controlling the heating temperature, the tensions applied to the element, and the heating duration, fiber tips with minimum apex diameters of approximately 20 nm can be fabricated by this technique [42]. The thermal pulling process is rapid (~3 s) and produces smooth tips. It is not very reproducible with respect to tip apex diameters and taper cones. It can be realized on a commercially available micropipette puller, which is relatively expensive. An example of a fiber tip produced by the thermal pulling of a silica fiber with an outer diameter of 125 µm to a microtip taper of 0.6 µm in diameter is shown in Figure 4. Such tapers have been fabricated at the author’s laboratories on a laboratory thermal-pulling device.
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Figure 3. Schematic description of thermal pulling technique. (a) An input fiber element. (b) Biconical taper with a waist around the center. (c) Two fiber tips.
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Figure 4.
A photo of a microtip prepared at the author’s laboratories.
The following method for the fabrication of fiber nanotips on the ends of optical fibers is chemical etching, which is an inexpensive and effective alternative to thermal fiber pulling. Chemical etching of silica glass materials is based on chemical reactions of silicon and/or germanium dioxides with hydrofluoric acid described by Equations (1) and (2).
SiO
2
+ 6HF ⇒ H
2
SiF
6
+H
2
O,             
GeO
2
+ 6HF ⇒ H
2
GeF
6
+ H
2
O.         
The formed silicon and germanium hexafluoro acids are adsorbed on the fiber surface. Due to differences in the etching rates of the oxides and solubility of the acids in etching solutions, there are differences in the etching rates of fiber core and cladding. Two different types of the chemical etching method have been reported. The first one is Turner etching [43][44]. This etching is schematically illustrated in Figure 5. It uses an etchant, i.e., an aqueous solution of hydrofluoric acid (HF), and a protective organic solvent that is immiscible with the HF solution (e.g., oil and toluene). These liquids form two phases in a container (see Figure 5). When a bare fiber is dipped into the container, the etchant forms a meniscus with an initial height due to capillary elevation (Figure 5a). As etching proceeds, the meniscus height decreases progressively due to the reduction in the fiber diameter (Figure 5b). This decrease leaves the etched part in contact with the organic solvent. The etching process stops when the fiber part below the solvent is completely etched, forming the tip (Figure 5c). This technique can produce fiber tapers with large taper angles, which increases the radiation power reaching the tip apex. Tip diameters are comparable with those of thermal pulling. Tips exhibit smooth surfaces. However, due to temperature fluctuations and fiber vibrations, the reproducibility of this technique is not high, and tip dimensions can vary from batch to batch.
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Figure 5.
Scheme of Turner etching. (
a
) Beginning of etching. (
b
) Etching in progress. (
c
) Etching end.
In the Turner etching described above, the fiber does not move. However, there is a dynamic etching method [45][46][47] in which the etched fiber moves vertically, either up or down at a certain speed. This speed determines the final tip shape. The dynamic etching method can also use an etchant and a protective organic solvent, as in the Turner method [46][47], or only an etchant solution can be employed [45]. Using the dynamic etching method, tips with short tapers and nanometer apexes can be successfully fabricated. Moreover, multiple tapered tips can be prepared using different dynamic regimes [45]. There is another variant of the dynamic etching method that employs the independent rotations of a container with an etchant, protective solvent, and etched fiber [48][49]. Both the container and fiber rotate around the same axis. Using different dynamic regimes of rotation during this process, it is possible to vary the cone angle, the shape, and the roughness of the nanotips. Hydrodynamic flows during the process are analyzed theoretically [49]. Another type of chemical etching method is called tube etching [50][51]. This technique has less susceptibility to external parameters than the Turner method. Tube etching is schematically described in Figure 6. In this technique, a silica fiber with a polymeric protective jacket is immersed in an aqueous HF solution (see Figure 6a). In the process, HF etches the fiber, not the polymeric jacket. Protective solvents can also be used to prevent HF evaporation. However, it does not contribute to the etching mechanism. During the beginning of the process, HF starts to etch the flat fiber end (see Figure 6a). Outer parts of the fiber end close to the jacket/fiber boundary are etched slightly faster than its central part (see arrows in Figure 6a). This effect can be explained by accelerated diffusion of HF in these parts [51]. When the fiber near the fiber/jacket boundary is etched away, an initial cone is formed, and the jacket acts as a wall. Due to HF concentration gradients around the cone, convective microflows in the etchant are formed (see an arrow in Figure 6b), which causes the fiber to be etched into a tip with a smooth surface. To stop the etching process, the fiber has to be withdrawn from the etching solution. The tip is rinsed with water. The tube etching process is very reproducible.
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Figure 6.
Scheme of tube etching method. (
a
) Beginning of the process. (
b
) Intermediate process stage, e.g., the tip formation.
It is worth mentioning that in addition to etching solutions containing HF (usually approximately 50% wgt.), buffered etching aqueous solutions employing HF and NH4F have also been used for the preparation of fiber nanotips [52]. Chemical reactions during etching with such etching solutions can be generally described by Equations (1) and (2) and by Equations (3) and (4) as well.
H
2
SiF
6
+ 2NH
4
F = (NH
4
)
2
SiF
6
+ 2HF,           
H
2
GeF
6
+ 2NH
4
F = (NH
4
)
2
GeF
6
+ 2HF.         
It was found that tip dimensions are influenced by a volume ratio of HF and NH4F in etching solutions and by etching time [52]. These types of chemical etching take approximately 1–2 h, which is a longer process than thermal pulling. However, they can be realized using the equipment of a standard chemical laboratory. Caution should be expended when working with a rather dangerous HF. Fabricated fiber nanotips are usually coated with a layer of silver, aluminum, gold, carbon, or ceramics in order to ensure the mechanical strength of the taper and support the confining of transmitted radiation in the taper cone. The thickness of such a layer is approximately 50–200 nm. During its deposition onto the tip, it is important to keep the tip apex free of the coated material that allows to bind chemical and biological transducers on the tip apex. However, fiber tips with apex diameters larger than 200 nm have also been employed for the development of fiber tip sensors without any metallic or ceramic layer [53][54][55].

2.2. Fiber Nanotip Sensor Functionalization and Interrogation

The research of fiber nanotip–chemical sensors and biosensors was mainly developed from 1992 to roughly 2010. After the first paper on fiber nanotip pH sensors was published in 1992 [35], a series of papers on chemical sensors and biosensors based on fiber nanotips followed. Fiber nanotips prepared from telecommunication types of optical fiber by thermal pulling or chemical etching can be employed, as well as commercially available SNOM fibers which are provided by metal coatings [40]. In order to employ fiber nanotips for chemical sensing and biosensing, they must be modified with proper sensing membranes and/or opto-chemical transducers or biotransducers. For such modifications, fiber nanotip surfaces are functionalized by silanization. Silanization provides with chemical groups, making strong bonding of membranes and transducers onto tip surfaces possible. Other functionalization approaches, such as surface-assembled monolayers (SAM) [8], have not been applied to the development of fiber nanotip sensors. As sensing membranes for fiber nanotip chemical sensors, photocurable or thermally curable polymers were employed [35][56]. Such membranes immobilize chemical transducers onto fiber tips. Biotransducers are immobilized onto fiber tips by interacting with the silanized tip surface. When using photocuring, a silanized fiber nanotip is dipped into the proper monomer, and curing radiation (e.g., from a 488 nm-Ar laser) is launched into the proximal fiber face. Radiation is guided in the fiber core to the nanotip apex, where photopolymerization occurs near the optical field. A small cone with dimensions comparable to the apex diameter is formed on the apex [57]. Polymers such as acrylates, poly vinyl chloride, and dextran can be used for the fabrication of sensing membranes on fiber nanotips. In the case of thermal curing, a fiber nanotip is immersed in a proper monomer that is subsequently thermally cured. However, this thermal curing usually requires a catalyst and the control of the thickness of the sensing membrane is difficult. It is produced anywhere on the immersed fiber. Changes in luminescence, usually fluorescence, taking place when a fiber nanotip sensor is in contact with detected chemicals, are usually used in fiber nanotip sensors. Because of small sample volumes in contact with sensing nanotips on the order of femtoliters [35], the number of analyte molecules in the excitation volume is also small on the order of several thousands of molecules. Therefore, sensitive devices capable of measuring weak fluorescence signals must be used for analysis. A principal set-up used for measuring with fiber nanotip sensors is schematically shown in Figure 7. A more specific description of such a set-up can be found elsewhere [58]. The main part of the set-up is an inverted fluorescence microscope with a detector such as a photomultiplier tube (PMT) or avalanche photodiode for intensity measurements, a spectrometer for spectra measurements, and/or a CCD camera for target imaging. Dichroic mirrors, filters, and objectives are other parts of the microscope. A fiber nanotip sensor is fixed on a three-way X,Y,Z translational stage, making its precise insertion into a sample possible. Radiation from a laser is launched into the sensor using a fiber coupler. It excites the fluorescence of a transducer immobilized on the sensor nanotip. The emitted fluorescence signal and remaining excitation radiation are collected by the microscope collection objective. The rest of the excitation radiation is filtered out by a notch filter, and fluorescence is detected by PMT or by spectrometer. In this set-up, fluorescence signals emitted in the direction of the tip axis are detected. One can also find another experimental set up used for sensing with fiber-optic nanotip sensors [48]. In the set-up, fluorescence emitted from the sensor nanotip is registered in the direction perpendicular to the tip axis. The fluorescence is collected by a GRIN lens coupled with a multimode optical fiber. The excitation radiation scattered from the tip apex is also filtered out in this set-up.
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Figure 7.
A scheme of a set-up used with fiber nanotip sensors based on an inverted fluorescence microscope.

2.3. Fiber Nanotip Chemical Sensors

Fiber nanotip chemical sensors have been tested for the detection of pH, different ions, nitric oxide, etc. Selected examples of such sensors are reported in Table 1. They were developed using fiber-optic tips with apex diameters of 50–700 nm. These tips were fabricated from multimode [53][54][59] and single-mode optical fibers [54][60] using thermal pulling methods or the tube etching technique [54]. Commercially available nanotip fibers (SNOM) were also used [53][54]. Only some of these nanotip fibers were provided with metal layers of aluminum [53][54][60] or silver [59]. Some fiber tips were used without any metal coating [53][54][55]. Fiber nanotip chemical sensors have employed different chemical transducers (see examples in Table 1). In pH, oxygen, and Ca2+ FO nanosensors, simple fluorescence transducers, acryloylfluorescein, Ru(II) phenanthroline complexes, and calcium green-1dextran dye, respectively, were employed. Other dextran-immobilized transducers, such as 2′,7′-bis-(carboxyethyl)-5(6′)-carboxyfluorescein (BCECF) pH transducer, were also employed in fiber nanotip chemical sensors [61]. 
Table 1.
Examples of fiber nanotip and submicrometer-tip chemical sensors.
Analyte Transducer Tip Apex Diameter [nm] Polymer  Reference
pH Fluoresceinamine derivative 100 polyacrylamide [35][56]
Ca2+ Calcium green-dextran 100 - [59]
Oxygen Ru complex 1 100 polyacrylamide [62]
pH BTB-Ru complex 1 50 and 300 polyHEMA [53]
Cl− Cl− carrier-CTAB and

Chromoionophore 1		 50 and 300 PVC [53]
Cl− Indium porphyrine and

chromoionophore 2		 300–700 PVC [60]
NO2− vitamin B12 derivative and

chromoionophore 3		 300–700 PVC [60]
K+ Valinomycin and chromoionophore 4 50 and 300 PVC copolymer [54]
RI - 50 - [55]
In Table 1, the fluoresceinamine derivative is acryloylfluorescein, and calcium green-dextran is calcium green dye immobilized on dextran polymer. BTB—bromothymol blue, Ru complex 1-Ru(II)-tris(1,10-phenanthroline), polyHEMA—poly(2-hydroxyethyl methacrylate), chromoionophore 1—ion pair BTB and Ru(II)-tris(4,40-diphenyl-2,20-bipyridyl)2+, chromoionophore 2-9-(diethylamino)-5-[(2-octyldecyl)imino]benzo[a]phenoxazine, chromoionophore 3-9-dimethylamino-5-[4-(16-butyl-2,14-dioxo-3,15-dioxaeicosyl)-phenylimino]-5H-benzo[a]phenoazine, chromoionophore 4 4′,5′-dibromfluorescein octadecyl ester, PVC copolymer–copolymer of vinyl chloride, vinyl acetate, and vinyl alcohol. RI abbreviates the refractive index.
Fiber nanotip chemical ion sensors based on the ion-exchange concept have also been employed in fiber nanotip ion sensors [53][54][60]. Such a sensor employs a PVC membrane containing ionophore (ion carrier) and chromoionophore together with some additives. Fluorescence pH indicators are used as chromoinophores [53][54]. In some experiments, the reference fluorescence dye, Nile red, was immobilized in the membrane. It enabled ratiometric fluorescence measurements [54]. The ion pair of BTB and Ru complex 1 was also employed as a chromoionophore [53]. In this case, fluorescence resonance energy transfer (FRET) occurred from the complex to BTB. As the absorbance of the BTB basic form overlapped the Ru(II) complex emission, the fluorescence decay time of this complex was reduced. This reduction is related to the concentration of protons in the membrane that is correlated with the concentration of the detected ion. A commercially available fluorescence dye, Calcium green, immobilized on dextran, was tested for selective Ca2+ detection [59] and in pH sensors [53]. A pH sensor based on two fluorescence dyes immobilized in photocurable polymer on a fiber nanotip was also reported [61]. A fiber nanotip sensor has already been tested for refractive index detection [55]. In such a sensor, neither the sensing membrane nor the transducer was applied on the sensor nanotip. The intensity of light transmitted from the tip apex through a sample to a detector was registered. It was found that the sensor was capable of measuring refractive-index changes in aqueous solutions. A high detection sensitivity of 8000%/RIU was determined from a calibration curve. Moreover, the pH dependence of the transmitted intensity was determined from measurements with aqueous solutions of acetic acid. Developed fiber nanotip chemical sensors were characterized on bulk samples. It was found that a pH nanotip sensor based on a fluoresceinamine derivative was capable of measuring pH changes when inserted in 10 µm-diameter pores of polycarbonate membrane [56]. The response time of such a nanosensor was 300 ms. The sensor was reversible and stable concerning pH changes. Fiber nanotip chemical sensors have been successfully tested for sensing inside biological samples. The first paper on such an application was reported in 1992 and dealt with pH sensing in blood cells, frog cells, and rat embryos [35]. In experiments with rat embryos, the nanotip pH sensor was inserted into the extraembryonic space of a rat embryo and used for measurements of pH values there. Results were successfully compared with pH values obtained by measuring microscopic samples containing approximately 1000 such embryos. Fiber nanotip chemical sensors have also been employed for measurements of nitrite and chloride ion levels in rat conceptuses [60]. A four-time increase in the chloride activity due to exposing the cells to pure nitrogen was determined. Another paper reported on fiber nanotip chemical sensors for measurements of pH and sodium ion concentrations inside a single mouse oocyte [63]. Effects of stimulating the cells with kainic acid on relative Na concentrations were observed. Measurements of Ca2+ concentrations have also been performed in single, living smooth muscle cells and single, living cardiomyocytes using a nanosensor based on Calcium green dye [59]. Effects of the cell stimulations with potassium buffer on the measured fluorescence intensity were observed. Submicrometer fiber tip chemical sensors were also tested for pH sensing in live neural colonies and mouse brain slices [64]. In the paper, fiber sensors of pH, Ca2+, and oxygen H2S are reported without details regarding the transducers used. The tips with apex diameters from 200 to 800 nm were used for the preparation of the sensors. In another paper, a fiber nanotip without any chemical modification was employed for monitoring concentration changes in Ca2+ in differentiated mouse neuroblastoma X rat glioma hybrid cells and vascular smooth muscle cells using fiber nanotips with apex diameters in the range of 50–500 nm [65]. The cells were loaded with fluorescence dye sensitive to changes in Ca2+ concentration. In experiments, a fiber nanotip was inserted into the cells and used for local fluorescence excitation. The fluorescence intensity was measured by an avalanche photodiode. By moving the tip inside the cell, an image of the fluorescence intensity was registered. Temporal effects of the stimulations of the cells with drugs, such as ionomycin and bradykinin, on the fluorescence intensity were also monitored with fiber nanotips 50–100 nm in diameter.

2.4. Fiber Nanotip Biosensors

Fiber-optic nanotips have been successfully employed in optical biosensors. The reader can find reviews on such nanobiosensors elsewhere [33][66]. Several examples of nanobiosensors discussed below can illustrate the performance of fiber-optic nanotips for biosensing, particularly in cells. A fiber nanotip biosensor was reported for the detection of benzo[a]pyrene tetrol (BPT) [67][68]. It is known that BPT is one of the metabolites of benzo[a]pyrene in cells. It can form adducts with DNA which can be related to its carcinogenic effects. BPT has an intrinsic fluorescence that can be employed for its detection. Fiber-optic tips with apex diameters of 25–40 nm were used for sensor fabrications. In the sensor, the tip was functionalized with BPT antibody by covalent binding on the silanized tip. This antibody allows to selectively bind BPT due to immunoreaction. The sensor was excited by a HeCd laser at 325 nm and emitted BPT fluorescence was detected by a detector (PMT). The sensor was characterized on mammary carcinoma cells and rat liver epithelial cells incubated with BPT. These cells are spherical with diameters of approximately 10 µm. A dynamic range of 0.006–1.6 nM and a limit of detection of 0.006 nM were determined from calibration curves [69]. From these curves, an average detection sensitivity of approximately 7000 nM−1 can be estimated. Several other fiber nanotip biosensors have been developed, as can be found in review articles [33][66]. These biosensors include those for the detection of nitric oxide [70], caspase-9 [69], glutamate [71], cytochrome c’ [72], DNA [48], etc. Biotransducers for some fiber nanotip biosensors are shown in Table 2. Caspase-9 was detected using a modified enzymatic assay based on leucine–glutamic acid–histidine–aspartic acid ↔ 7-amino-4-methylcoumarin (LEDH ↔ AMC) that is immobilized on the fiber nanotip [69]. Caspase-9 cleaves nonfluorescent LEDH ↔ AMC and the fluorescence of free AMC is detected in the sensor. Anti-cytochrome c’–biotin immobilized on the sensor nanotip is used to bind cytochrome c’ to the tip [72]. An enzyme-linked immunoassay sorbent is used for the detection of cytochrome c’ bound on this antibody.
Table 2.
Examples of fiber nanotip and submicrometer tip biosensors.
Analyte Transducer Tip Apex Diameter [nm] Linear Range Reference
BPT BPT antibody 25–60 0.06–1.6 nM [68]
NO2 Cytochrome c’ 200 0.02–1 mM [70]
Glutamate Glutamate dehydrogenase 30–500 15–30 µM [71]
DNA Molecular beacon 30 0.57–10,000 nM [48]

2.5. Fiber-Optic Nanotip Sensors for Raman Spectroscopy

The sensing performance of fiber nanotip chemical sensors and biosensors can be further enhanced by coating them with metallic nanoparticles or metal islands. Such fiber-optic structures enable to employ surface-enhanced Raman scattering (SERS) for detection. It is well known that Raman spectroscopy allows to investigate molecules, cells, viruses, etc., at molecular, nanoscopic, and microscopic levels [73]. This spectroscopy employs inelastic Raman scattering. Both qualitative and quantitative information can be obtained from Raman spectra. While the qualitative information can be directly determined from the wavelength position of vibrational spectral bands, the quantitative information can be limited by low Raman scattering cross-sections. This limitation can be overcome, and the cross-sections can be highly increased using nano-textured surfaces in SERS sensors. In addition to common nanostructured substrates, electrodes, sols, metal films, and nanomaterial-modified fiber nanotips have also been employed in SERS sensors. Such sensors were fabricated by applying silver and gold nanoparticles or nanoislands on surfaces of tips obtained by chemical etching. For such applications, fiber nanotips were silanized to enhance the binding of metal nano-objects on the surface. Electron beam evaporation [74] and wet chemical synthesis [75][76][77] were employed for the fabrication of such nano-objects. It is known that metal nano-objects (nanoparticles, nanorods, and nanoislands) support the excitation and propagation of localized surface plasmons (LSPs) [16][73]. If an absorption spectrum of LSP overlaps with excitation and emission SERS wavelengths, Raman scattering is highly enhanced. Confocal microscopes [73], inverted fluorescence microscopes [77], and Raman spectrometers were used to measure Raman spectra. A pH sensor based on SERS was developed [74]. The sensor used a tip with an apex diameter below 100 nm that was coated with a silver layer of 6 nm in thickness using electron beam evaporation. The layer with such a small thickness was not continuous, but it was formed of silver islands. As a pH transducer, p-mercaptobenzoic acid (MBA) was bound to these islands. The nanotips were interrogated by confocal microscopy. A spectral band of 1425 cm−1, shifting due to pH changes, was employed in this pH sensor. The sensor was also used for pH measurements in cells. In another paper [75], gold nanoparticles with diameters in the range of 50–60 nm prepared by chemical wet synthesis were applied onto a fiber nanotip with an apex diameter of 40 nm. Such fibers were successfully employed for measuring Raman spectra of Rhodamine 6G in aqueous solutions. The excitation radiation from a 633 nm laser was launched into the proximal fiber face. The excited SERS radiation was detected at the proximal face, too. A remote interrogation scheme was also used for measurements with a fiber nanotip SERS sensor employing silver nanoparticles coated on the tip [76]. A double-tapered fiber tip was prepared by the Turner method. However, there is no specific information regarding the tip dimensions in the current literature. The sensor was used for measuring Raman spectra of solutions of crystal violet at concentrations higher than 1 nM. Silver nanoparticles modified with 4-mercaptopyridine (Mpy) were also used for the development of a SERS fiber nanotip sensor [77]. The modified nanoparticles were coated on a fiber nanotip using laser-induced Ag deposition from silver nitrate and Mpy solution. Nanoparticles with diameters of approximately 100 nm were applied. Such fiber nanotip SERS sensors were used for pH detection. An inverted microscope was used to register SERS radiation from samples that were excited by the tips. Results of theoretical modeling of fiber nanotip SERS sensors based on Au nanoparticles and MBA were reported [78]. It was found that the nanoparticle diameter has a high effect on the electrical-field enhancement between nanoparticles. On the other hand, tip dimensions do not exhibit significant effects on MBA spectra. Based on this modeling, fiber nanotips with an apex diameter of 50 nm coated with gold nanoparticles of 60 nm in diameter were experimentally realized

2.6. Fiber-Optic Nanotips for Electro-Optical Detection

It is worth mentioning that metal-coated fiber nanotips have been investigated for electro-optical nanosensing [79]. Such nanoprobes allow to detect both electrical and optical signals in real-time with high spatial resolution. The approach was employed in living cells for detecting hydrogen peroxide using amperometry. The intrinsic fluorescence was detected optically to evaluate the intracellular redox state. Effects of cell stresses were detected in such experiments. Fiber nanotips used in experiments had an apex diameter of 100 nm. They were coated with a gold layer of 100 nm in thickness. A copper nanowire was connected with the gold layer that enabled electrical contact with a reference Ag/AgCl electrode.

3. Conclusions

This contribution deals with fiber nanotip sensors for chemical sensing based on silica or plastic optical fibers. The contribution shows the fabrication of such sensors, their material characteristics, and their sensing performance for chemical detection in gases, solutions, cells, bacteria, pores, etc. Examples of biosensors employing such nanosensors are also reported in order to document their broad sensing performance.

Fiber nanotip sensors can employ commercially available SNOM nanotips, or they can be prepared by thermal pulling or chemical etching. While the thermal pulling requires a sophisticated device, the etching can be realized in a chemical laboratory provided that safety rules for working with hydrofluoric acid are kept. However, nanotips prepared by chemical etching need to be metalized to preserve their mechanical stability. On the other hand, SNOM nanotips are metalized. Nanotips with apex diameters bellow 100 nm can be employed for intracellular measurements. However, in this field, they will compete with PEBBLES (probes embedded in biologically localized environments). Thus fiber-optic nanotip and microtip sensors can be useful for chemical detection in pores, cell tissues, and small drops. Chemical sensing in plant tissues and drops of exudates from plants is possible with fiber microtip sensors[80] and can provide us with information on chemical mechanisms in plant tissues, leaves, etc. Information about concentrations of chemicals in material pores can be employed for investigations of solid catalysts, metal corrosion, etc. One can also expect that fiber-optic microtips and nanotips will be employed for the development of optical tweezers and coupling devices. Fiber nanotips coated with metallic nanoparticles or nanoislands exhibit a very good performance for SERS-based chemical analysis which still is not fully employed.

 

References

  1. Wolfbeis, O.S. Fiber-Optic Chemical Sensors and Biosensors. Anal. Chem. 2002, 74, 2662–2678.
  2. Wolfbeis, O.S. Fiber-Optic Chemical Sensors and Biosensors. Anal. Chem. 2004, 76, 3269–3284.
  3. Wolfbeis, O.S. Fiber-Optic Chemical Sensors and Biosensors. Anal. Chem. 2006, 78, 3859–3874.
  4. Wolfbeis, O.S. Fiber-Optic Chemical Sensors and Biosensors. Anal. Chem. 2008, 80, 4269–4283.
  5. Wang, X.-D.; Wolfbeis, O.S. Fiber-Optic Chemical Sensors and Biosensors (2008−2012). Anal. Chem. 2013, 85, 487–508.
  6. Wang, X.-D.; Wolfbeis, O.S. Fiber-Optic Chemical Sensors and Biosensors (2013−2015). Anal. Chem. 2016, 88, 203–227.
  7. Wang, X.-D.; Wolfbeis, O.S. Fiber-Optic Chemical Sensors and Biosensors (2015−2019). Anal. Chem. 2020, 92, 397–430.
  8. Borisov, S.M.; Wolfbeis, O.S. Optical Biosensors. Anal. Chem. 2008, 108, 423–461.
  9. Abdelmalek, F.; Lacroix, M.; Chovelon, J.M.; Jaffrezic-Renault, N.; Berkova, D.; Matejec, V.; Kasik, I.; Chomat, M.; Gagnaire, H. Consequences of TiO2 doping on the optical properties of porous silica layers coated on silica optical fibers. Thin Sol. Film. 1999, 340, 280–287.
  10. Skokankova, J.; Mrazek, J.; Matejec, V.; Hayer, M.; Kasik, I.; Chomat, M.; Berkova, D.; Barau, A.; Zaharescu, M.; Raileanu, M. Properties of xerogel layers for the detection of toluene in water. Mater. Sci. Eng. C 2006, 26, 208–213.
  11. Abdelghani, A. Jaffrezic-Renault, N. SPR fibre sensor sensitised by fluorosiloxane polymers. Sens. Actuators B-Chem. 2001, 74, 117–123.
  12. Snyder, A.W.; Love, J.D. Optical Waveguide Theory. Part II Electromagnetic Analysis of Optical Waveguides; Springer: New York, NY, USA, 1983; pp. 203–353.
  13. Monro, T.M.; Belardi, W.; Furusawa, K.; Baggett, J.C.; Broderick, N.G.R.; Richardson, D.J. Sensing with microstructured optical fibres. Meas. Sci. Technol. 2001, 12, 854–858.
  14. Matejec, V.; Mrázek, J.; Hayer, M.; Podrazký, O.; Kaňka, J.; Kašík, I. Sensitivity of microstructure fibers to gaseous oxygen. Meas. Sci. Eng. 2008, 28, 876–881.
  15. Elsherif, M.; Salih, A.E.; Gutiérrez Munoz, M.; Alam, F.; AlQattan, B.; Antonysamy, D.S.; Fawzi Zaki, M.; KYetisen, A.; Park, S.; Wilkinson, T.D.; et al. Optical Fiber Sensors: Working Principle, Applications, and Limitations. Adv. Photonics Res. 2022, 3, 2100371.
  16. Gupta, B.D.; Kant, R. Recent advances in surface plasmon resonance based fiber optic chemical and biosensors utilizing bulk and nanostructures. Opt. Laser Technol. 2018, 101, 144–161.
  17. Li, M.; Singh, R.; Wang, Y.; Marques, C.; Zhang, B.; Kumar, S. Advances in Novel Nanomaterial-Based Optical Fiber Biosensors—A Review. Biosensors 2022, 12, 843.
  18. Boussard-Plédel, C. Chalcogenide waveguides for infrared sensing. In Chalcogenide Glasses: Preparation, Properties and Applications; Adam, J.-L., Zhang, X., Eds.; Woodhead Publishing Series in Electronic and Optical Materials; Woodhead Publishing Limited: Oxford, UK; Cambridge, UK; London, UK; Philadelphia, PA, USA; New Delhi, India, 2014; Volume 44, pp. 381–410.
  19. Bureau, B.; Boussard, C.; Cui, S.; Chahal, R.; Laure Anne, M.; Nazabal, V.; Sire, O.; Loréal, O.; Lucas, P.; Monbet, V.; et al. Chalcogenide optical fibers for midinfrared sensing. Opt. Eng. 2014, 53, 027101.
  20. Matějec, V.; Chomát, M.; Hayer, M.; Kašik, I.; Berková, D. Development of special optical fibers for evanescent-wave chemical sensing. Czech. J. Phys. 1999, 49, 883–888.
  21. Wu, W.; Huang, J.; Ding, L.; Lin, H.; Yu, S.; Yuan, F.; Liang, B. A real-time and highly sensitive fiber optic biosensor based on the carbon quantum dots for nitric oxide detection. J. Photochem. Photobiol. A 2021, 405, 112963.
  22. Ding, L.; Fan, C.; Zhong, Y.; Li, T.; Huang, J. A sensitive optic fiber sensor based on CdSe QDs fluorophore for nitric oxide detection. Sens. Actuators B-Chem. 2013, 185, 70–76.
  23. Ding, L.Y.; Ruan, Y.L.; Li, T.; Huang, J.; Warren-Smith, S.C.; Ebendorff-Heidepriem, H.; Monro, T.M. Nitric oxide optical fiber sensor based on exposed core fibers and CdTe/CdS quantum dots. Sens. Actuators B-Chem. 2018, 273, 9–17.
  24. Pathak, A.; Gupta, B.D. Fiber-Optic Plasmonic Sensor Utilizing CTAB-Functionalized ZnO Nanoparticle-Decorated Carbon Nanotubes on Silver Films for the Detection of Catechol in Wastewater. ACS Appl. Nano Mater. 2020, 3, 2582–2593.
  25. Fallah, H.; Asadishad, T.; Parsanasab, G.-M.; Harun, S.W.; Mohammed, W.S.; Yasin, M. Optical Fiber Biosensor toward E-coli Bacterial Detection on the Pollutant Water. Eng. J. 2021, 25, 1–8.
  26. Sun, Y.; Guo, X.; Moreno, Y.; Sun, Q.; Yan, Z.; Zhang, L. Sensitivity adjustable biosensor based on graphene oxide coated excessively tilted fiber grating. Sens. Actuators B-Chem. 2022, 351, 130832.
  27. Wang, R.; Ren, Z.; Kong, D.; Hu, B.; He, Z. Highly sensitive label-free biosensor based on graphene-oxide functionalized micro-tapered long period fiber grating. Opt. Mater. 2020, 109, 110253.
  28. Cao, Z.; Yao, B.; Qin, C.; Yang, R.; Guo, Y.; Zhang, Y.; Wu, Y.; Bi, L.; Chen, Y.; Xie, Z.; et al. Biochemical sensing in graphene enhanced microfiber resonators with individual molecule sensitivity and selectivity. Light Sci. Appl. 2019, 8, 107.
  29. Yu, H.; Chong, Y.; Zhang, P.; Ma, J.; Li, D. A D-shaped fiber SPR sensor with a composite nanostructure of MoS2-graphene for glucose detection. Talanta 2020, 219, 121324.
  30. Li, W.; Miao, Y.; Guo, T.; Zhang, K.; Yao, J. Nb2CTx MXene-tilted fiber Bragg grating optofluidic system based on photothermal spectroscopy for pesticide detection. Biomed. Opt. Express 2021, 12, 7051–7063.
  31. Yi, D.; Wang, C.; Gao, L.; Chen, Y.; Liu, F.; Geng, Y.; Zhang, H.; Li, X. Ti3CN MXene-based ultra-sensitive optical fiber salinity sensor. Opt. Lett. 2022, 47, 138–141.
  32. Baig, N.; Kammakakam, I.; Falathabe, W. Nanomaterials: A review of synthesis methods, properties, recent progress, and challenges. Mater. Adv. 2021, 2, 1821–1871.
  33. Berneschi, S.; Barucci, A.; Baldini, F.; Cosi, F.; Quercioli, F.; Pelli, S.; Righini, G.C.; Tiribilli, B.; Tombelli, S.; Trono, C.; et al. Optical Fibre Micro/Nano Tips as Fluorescence-Based Sensors and Interrogation Probes. Optics 2020, 1, 213–242.
  34. Betzig, E.; Trautman, J.K.; Harris, T.D.; Weiner, J.S.; Kostelak, R.L. Breaking the Diffraction Barrier: Optical Microscopy on a Nanometric Scale. Science 1991, 251, 1468–1470.
  35. Tan, W.; Shi, Z.-Y.; Smith, S.; Birnbaum, D.; Raoul Kopelman, R. Submicrometer Intracellular Chemical Optical Fiber Sensor. Science 1992, 258, 778–781.
  36. Lewis, A.; Lieberman, K. The optical Near Field and Analytical Chemistry. Anal. Chem. 1991, 63, 625A–638A.
  37. Lee, S.; Jiao, M.; Zhang, Z.; Yu, Y. Nanoparticles for Interrogation of Cell Signaling. Annu. Rev. Anal. Chem. 2023, 16, 333–351.
  38. Clark, H.A.; Hoyer, M.; Philbert, M.A.; Kopelman, R. Optical Nanosensors for Chemical Analysis inside Single Living Cells. 1. Fabrication, Characterization, and Methods for Intracellular Delivery of PEBBLE Sensors. Anal. Chem. 1999, 71, 4831–4836.
  39. Clark, H.A.; Kopelman, R.; Tjalkens, R.; Philbert, M.A. Optical Nanosensors for Chemical Analysis inside Single Living Cells. 2. Sensors for pH and Calcium and the Intracellular Application of PEBBLE. Anal. Chem. 1999, 71, 4837–4843.
  40. Kopelman, R.; Smith, S.; Tan, W.; Zenobi, R.; Lieberman, K.; Lewis, A. Spectral analysis of surfaces at subwavelength resolution, Proc. SPIE Environ. Process Monit. Technol. 1992, 1637, 33–40.
  41. Paiva, J.S.; Jorge, P.A.S.; Rosa, C.C.; Cunha, J.P.S. Optical fiber tips for biological applications: From light confinement, biosensing to bioparticles manipulation—Review. Biochim. Biophys. Acta (BBA)-General. Subj. 2018, 1862, 1209–1246.
  42. Valaskovic, G.A.; Holton, M.; Morrison, G.H. Parameter control, characterization, and optimization in the fabrication of optical fiber near-field probes. Appl. Opt. 1995, 34, 1215–1228.
  43. Turner, D.R. Etch Procedure for Optical Fibers. US Patent 4,469,554, 4 September 1984.
  44. Hoffmann, P.; Dutoit, B.; Salathe, R.-P. Comparison of mechanically drawn and protection layer chemically etched optical fiber tips. Ultramicroscopy 1995, 61, 165–170.
  45. Anderson, G.P.; Golden, J.P.; Ligler, F.S. A fiber tapered optic biosensor: Combination fibers designed for improved signal acquisition. Biosens. Bioelectr. 1993, 8, 249–256.
  46. Muramatsu, H.; Homma, K.; Chiba, N.; Yamamoto, N.; Egawa, A. Dynamic etching method for fabricating a variety of tip shapes in the optical fibre probe of a scanning near-field optical microscope. J. Microscop. 1999, 194, 383–387.
  47. Lazarev, A.; Fang, N.; Luo, Q.; Zhang, X. Formation of fine near-field scanning optical microscopy tips. Part I. Rev. Sci. Instrum. 2003, 74, 3679–3683.
  48. Giannetti, A.; Barucci, A.; Cosi, F.; Pelli, S.; Tombelli, S.; Trono, C.; Baldini, F. Optical fiber nanotips coated with molecular beacons for DNA detection. Sensors 2015, 15, 9666–9680.
  49. Griffini, D.; Insinna, M.; Salvadori, S.; Barucci, A.; Cosi, F.; Pelli, S.; Righini, G.C. On the CFD analysis of a stratified taylor-couette system dedicated to the fabrication of nanosensors. Fluids 2017, 2, 8.
  50. Lambelet, P.; Sayah, A.; Pfeffer, M.; Philipona, C.; Marquis-Weible, F. Chemically etched fiber tips for near-fieldoptical microscopy: A process for smoother tips. Appl. Opt. 1998, 37, 7289–7292.
  51. Stὅckle, R.; Fokas, C.; Deckert, V.; Zenobia, R.; Sick, B.; Hecht, B.; Wild, U.P. High-quality near-field optical probes by tube etching. Appl. Phys. 1999, 75, 160–162.
  52. Pangaribuana, T.; Jiang, S.; Ohtsu, M. Highly Controllable Fabrication of Fiber Probe for Photon Scanning Tunneling. Scanning 1994, 16, 362–367.
  53. Koronczi, I.; Reichert, J.; Ache, H.J.; Krause, C.; Werner, T.; Wolfbeis, O.S. Submicron sensors for ion detection based on measurement of luminescence decay time. Sens. Actuators B-Chem. 2001, 74, 47–53.
  54. Koronczi, I.; Reichert, J.; Heinzmann, G.; Ache, H.J. Development of a submicron optochemical potassium sensor with enhanced stability due to internal reference. Sens. Actuators B-Chem. 1998, 51, 188–195.
  55. Tai, Y.-H.; Wei, P.-K. Sensitive liquid refractive index sensors using tapered optical fiber tips. Opt. Lett. 2010, 35, 944–946.
  56. Tan, W.; Shi, Z.Y.; Kopelman, R. Development of submicron chemical fiber optic sensors. Anal. Chem. 1992, 64, 2985–2990.
  57. Munkholm, C.; Walt, D.R.; Milanovich, F.P.; Klainer, S.M. Polymer Modification of Fiber Optic Chemical Sensors as a Method of Enhancing Fluorescence Signal for pH Measurement. Anal. Chem. 1986, 58, 1427–1430.
  58. Vo-Dinh, T.; Kasili, P.; Wabuyele, M. Nanoprobes and nanobiosensors for monitoring, and imaging individual living cells. Nanomed. Nanotechnol. Biol. Medic. 2006, 2, 22–30.
  59. Wanga, S.; Ye, F.; Lang, X.; Fei, D.; Ge, Y.; Turner, A.P.F. Detection of changes in sub-plasma membrane microdomains in a single living cell by an optical fiber-based nanobiosensor. Austin J. Nanomed. Nanotechnol. 2014, 2, 1022.
  60. Barker, S.L.R.; Bjorn, A.; Thorsrud, B.A.; Kopelman, R. Nitrite- and Chloride-Selective Fluorescent Nano-Optodes and in Vitro Application to Rat Conceptuses. Anal. Chem. 1998, 70, 100–104.
  61. Tan, W.; Shi, Z.-Y.; Kopelman, R. Miniaturized fiber-optic chemical sensors with fluorescent dye-doped polymers. Sens. Actuators B-Chem. 1995, 28, 157–165.
  62. Rosenzweig, Z.; Kopelman, R. Development of a submicrometer optical fiber oxygen sensor. Anal. Chem. 1995, 67, 2650–2654.
  63. Tan, W.; Kopelman, R.; Barker, S.L.R.; Miller, M.T. Peer Reviewed: Ultrasmall Optical Sensors for Cellular Measurements. Anal. Chem. 1999, 71, 606A–612A.
  64. Hossein-Zadeha, M.; Delgado, J.; Schweizer, F.; Lieberman, R. Sub-micron Opto-Chemical Probes for Studying Living Neurons. In Proceedings of the SPIE 10051, Neural Imaging and Sensing, San Francisco, CA, USA, 8 February 2017. 100510G; paper 100510G(9pp).
  65. Bui, J.D.; Zelles, T.; Lou, H.J.; Gallion, V.L.; Phillips, M.I.; Tan, W. Probing intracellular dynamics in living cells with near-field optics. J. Neurosc. Methods 1999, 89, 9–15.
  66. Vo-Dinh, T.; Kasili, P. Fiber-optic nanosensors for single-cell monitoring-Review. Anal. Bioanal. Chem. 2005, 382, 918–925.
  67. Alarie, J.P.; Vo-Dinh, T. Antibody-Based Submicron Biosensor for BenzoPyrene DNA Adduct. Polycycl. Arom. Compd. 1996, 8, 45–52.
  68. Cullum, B.M.; Griffin, G.D.; Miller, G.H.; Vo-Dinh, T. Intracellular Measurements in Mammary Carcinoma Cells Using Fiber-Optic Nanosensors. Anal. Biochem. 2000, 277, 25–32.
  69. Kasili, P.M.; Song, J.M.; Vo-Dinh, T. Optical Sensor for the Detection of Caspase-9 Activity in a Single Cell. J. Am. Chem. Soc. 2004, 126, 2799–2806.
  70. Barker, S.L.R.; Kopelman, R. Development and Cellular Applications of Fiber Optic Nitric Oxide Sensors Based on a Gold-Adsorbed Fluorophore. Anal. Chem. 1998, 70, 4902–4906.
  71. Cordek, J.; Wang, X.; Tan, W. Direct Immobilization of Glutamate Dehydrogenase on Optical Fiber Probes for Ultrasensitive Glutamate Detection. Anal. Chem. 1999, 71, 1529–1533.
  72. Song, J.M.; Kasili, P.M.; Griffin, G.D.; Vo-Dinh, T. Detection of Cytochrome c in a Single Cell Using an Optical Nanobiosensor. Anal. Chem. 2004, 76, 2591–2594.
  73. Petry, R.; Schmitt, M.; Popp, J. Raman spectroscopy—A prospective tool in the Life Sciences. Chem. Phys. Chem. 2003, 4, 14–30.
  74. Jonathan, P.; Scaffidi, J.P.; Gregas, M.K.; Seewaldt, V.; Vo-Dinh, T. SERS-based plasmonic nanobiosensing in single living cells. Anal. Bioanal. Chem. 2009, 393, 1135–1141.
  75. Chen, Z.; Dai, Z.; Chen, N.; Liu, S.; Pang, F.; Lu, B.; Wang, T. Gold Nanoparticles-Modified Tapered Fiber Nanoprobe for Remote SERS Detection. IEEE Phot. Technol. Lett. 2014, 26, 777–780.
  76. Lucotti, A.; Zerbi, G. Fiber-optic SERS sensor with optimized geometry. Sens. Actuators B-Chem. 2007, 121, 356–364.
  77. Wang, J.; Geng, Y.; Shen, Y.; Shib, W.; Xu, W.; Xu, S. SERS-active fiber tip for intracellular and extracellular pH sensing in living single cells. Sens. Actuators B-Chem. 2019, 290, 527–534.
  78. Hutter, T.; Elliot, S.R.; Mahajan, S. Optical fibre-tip probes for SERS: Numerical study for design considerations. Opt. Express 2018, 26, 15539–15550.
  79. Zheng, X.T.; Hua, W.; Wang, H.; Yang, H.; Zhoud, W.; Li, C.M. Bifunctional electro-optical nanoprobe to real-time detect local biochemical processes in single cells. Biosens. Bioelectron. 2011, 26, 4484–4490.
  80. Kasik, I., Mrazek, J., Martan, T., Pospisilova. M.., Podrazky, O., Matejec, V., Hoyerova, K., Kaminek, M. Fiber-optic pH detection in small volumes of biosamples. Anal. Bioanal. Chem. 2010, 398, 1883–1889.
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