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.
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 CO
2 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.
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.
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).
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.
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.
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 NH
4F 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.
It was found that tip dimensions are influenced by a volume ratio of HF and NH
4F 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.
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 Ca
2+ 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.
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 Ca
2+ 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 Ca
2+ 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, Ca
2+, and oxygen H
2S 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 Ca
2+ 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 Ca
2+ 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.
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.