Recent advances in capillary microextraction

Accepted Manuscript Title: Recent advances in capillary microextraction Author: Habib Bagheri, Hamed Piri-Moghadam PII: DOI: Reference:

S0165-9936(15)00200-9 http://dx.doi.org/doi: 10.1016/j.trac.2015.04.025 TRAC 14491

To appear in:

Trends in Analytical Chemistry

Please cite this article as: Habib Bagheri, Hamed Piri-Moghadam, Recent advances in capillary microextraction, Trends in Analytical Chemistry (2015), http://dx.doi.org/doi: 10.1016/j.trac.2015.04.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Recent advances in capillary microextraction Habib Bagheri *, Hamed Piri-Moghadam ** Environmental and Bio-Analytical Laboratories, Department of Chemistry, Sharif University of Technology, P.O. Box 11365-9516, Tehran, Iran

HIGHLIGHTS  New developments in capillary microextraction  The preparation of extracting media based on various materials  New approaches toward unbreakable substrates and array capillaries ABSTRACT This review is mostly focused on the recently emerged methodologies for preparing the appropriate extracting media with enhanced capacity, stability and selectivity, which could be used in capillary microextraction (CME). We particularly consider conductive polymers, sol-gel-based materials, monolithic coatings, molecularly-imprinted polymers and xerogels. Moreover, we discuss recent advances in configuration of CME, array capillaries and unbreakable substrates. Keywords: Array capillary Capillary microextraction Conductive polymer Extracting media Molecularly-imprinted polymer Molecularly-imprinted xerogel Monolithic coating Sol-gel technology Solid-phase microextraction Unbreakable substrate * Corresponding author. Tel.: +98 21-66165316; Fax: +98 21-66012983. E-mail address: [email protected] (H. Bagheri) ** Present address: Department of Chemistry, University of Waterloo, 200 University Avenue West Waterloo, Ontario, Canada N2L 3G1

1. Introduction Solid-phase microextraction (SPME) has played a significant role in analytical science since its introduction in the early 1990s by Pawliszyn et al. [1,2]. The extraction efficiency of SPME fibers is determined by different types of intermolecular and steric interaction, such as van der Waals, dipoledipole and hydrogen bonding between the analyte species and the coating. SPME integrates sampling, sample preparation, preconcentration and sample introduction into a single step prior to instrumental analysis. Apart from SPME, several sorbent-based microextraction techniques, including in-tube, in-needle, and in-tip SPME and stir-bar sorptive extraction (SBSE), have been developed. These SPME versions are unique sample-preparation techniques in which a capillary tube, a microsyringe and a pipette tip are used as extraction devices. The capillary tube-based microextraction techniques have 1

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several advantages, such as being time effective, easy to automate, high-throughput and capable of on-line coupling with major analytical instruments. The on-line set-up reduces the loss of analyte during the sampling process. Open-tubular trapping (OTT) was first reported in 1986 as a capillary microextraction (CME) technique using an open-tubular fused-silica capillary column [3]. In OTT, a gaseous or liquid sample was passed through the open capillary and the volatile organic compounds trapped on the capillary coating were analyzed by thermal desorption and gas chromatography (GC). OTT was also used for analysis of polycyclic aromatic hydrocarbons (PAHs) in aqueous samples, coupled with GC [4]. In CME, also called in-tube SPME, the sample solution containing the desired compounds is passed through an open capillary and the desorbed analytes on the capillary coating are analyzed by solvent desorption, coupled on-line with high-performance liquid chromatography (HPLC) [5]. Commercial GC capillary columns were also used as a CME device [6–9]. As Fig.1 shows, CME can be performed by three common configuration types – packed, open tubular and monolithic. Theoretical consideration of CME was also thoroughly studied by Pawliszyn et al. [5]. Moreover, the history of CME and novel CME techniques for off-line and on-line sample preparation were already described in detail [10]. Comprehensive studies for application of CME in different samples were also included in well-documented reviews and papers [10,11]. The development of capillary columns has become a fascinating research field in the chromatographic sciences, and has a great influence on the modes of CME. However, although several commercial capillary columns were applied as CME devices, new methodologies have been used to prepare coatings with the enhanced extraction efficiency and improved thermal and chemical stability, so the main objective of this review is to demonstrate the new developments of CME, particularly in preparation of sorbents using conductive polymers (CPs), sol-gel materials, monolithic coatings, and molecularly-imprinted polymers (MIPs) and xerogels. We also discuss new advances in CME to achieve unbreakable substrates and array capillaries.

2. Preparation of novel coatings An extensive number of coatings for different microextraction methodologies have been reported but, among them, CPs, sol-gel materials, monolithic coatings, MIPs and xerogels are most used for CME applications. 2.1. Conductive polymers CPs are versatile materials in which molecular or analyte recognition can be achieved in different ways, including: (i) incorporating counterions that introduce selective interactions; (ii) utilizing the inherent and unusual multifunctionality (e.g., hydrophobic, base-acid and π-π interactions, polar functional groups, ion-exchange, hydrogen bonding, and electroactivity) of the polymers; (iii) introducing functional groups to the monomers; (iv) codepositing metals or other monomers within the polymer; and, (v) applying appropriate electrochemical potentials. So far, the widely-used CPs are based on polypyrrole (PPy), polythiophene, and polyaniline. Among these three classes of materials, PPy and its derivatives have seen the most use and were intensively studied in recent years, due to their additional advantages: (1) they can be easily polymerized from organic or aqueous media at neutral pH by electrochemical or chemical methods; 2

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(2) they are relatively stable in air and solution; and, (3) pyrrole monomer and some of its derivatives are available commercially. Pawliszyn et al. reported the first application of PPy as the sorbent coated inside a capillary device in 2000 [12]. PPy-coated capillary was used for automated in-tube SPME and determination of βblockers in urine and serum samples when coupled with liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). PPy was chemically prepared and immobilized in the fused-silica capillary by passing first the oxidant solution (0.2 M ferric perchlorate in 0.4 M perchloric acid) and then the monomer solution (pyrrole in isopropanol, 50% v/v) through the capillary with the aid of nitrogen gas. The above procedure could be repeated several times until the shiny, black-colored polymer film formed on the inner surface of the capillary. During polymerization, the color of the capillary changed gradually from yellow to black. It was then washed with methanol or acetone for 2 min and dried with nitrogen. Finally, it was conditioned with mobile phase for 5 min before use. Fig. 2 shows the chemical oxidative polymerization of pyrrole. The extraction efficiency of the developed sorbent with the same Omegawax capillary, a Supel-Q-PLOT capillary, a PPy-coated silica capillary, and a host silica capillary (a GC precolumn without PPy coating) toward β-blockers were compared. The PPy-coated capillary demonstrated the best extraction ability for most of the compounds studied. Due to the multi-functionality and/or multi-interaction properties of pyrrole polymers (i.e., the hydrophobic interactions from the polymer carbon backbone, π-π interactions, hydrogen bonding, interactions resulting from polar group, and counter ion in the polymer and ion exchange due to the positive charge in its oxidized form), a wide range of applications can be expected for PPy-based intube SPME. In another study, the same CME sorbent was used for extraction of three groups of aromatic compounds, including a group of model compounds containing both polar and nonpolar aromatics, a group of 16 PAHs, and a group of six heterocyclic amines. The results demonstrated that the PPy coating had higher extraction efficiency than commercial capillary coatings [13]. The ability of PPy to extract amphetamine and methamphetamine was also evaluated in biological samples [14]. CPs can be prepared using chemical and/or electrochemical methods of polymerization. In the previously reported papers, CPs were coated inside the CME device by chemical reaction. Electrochemically-prepared CPs was first reported by our group in 2014 [15]. Fig. 3a shows PANI exists in three well-defined oxidation states: leucoemeraldine, emeraldine and pernigraniline [16]. Leucoemeraldine and pernigraniline are fully reduced (all the nitrogen atoms are amine) and fully oxidized (all the nitrogen atoms are imine) forms, respectively, and, in emeraldine, the ratio is about 0.5. Fig. 3b shows the mechanism of polymerization of aniline proposed by Wei et al. [17–19]. As metallic substrates are needed to accomplish electrochemical production of polyaniline (PANI), a copper tube was selected as the substrate of a CME device. For synthesizing the sorbent inside the copper tube, 30 µL of aniline, 15 µL trifluoroacetic acid (TFA) and 30 µL H2O were added to 100 µL acetonitrile (ACN) and then the solution was deoxygenized under a stream of nitrogen. Then, pre-treated copper tube was selected as the anode and an aluminum foil was designed as the cathode while a potential of 1.5 V was applied for 30 min. The coating prepared was used for extraction of naproxen and the data obtained showed the superiority of PANI over the sol-gel based coatings. PANI is a special case due to its environmental stability in the conducting form, and its ability to interact with many other components through hydrogen bonding and π–π stacking. Moreover, PANI is considered one of the most popular, versatile CPs due to its promising electrical and electrochemical properties, ease of synthesis, low cost of the monomer, environmental stability and corrosion resistance [16].

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2.2. Monolithic polymers Rigid porous polymer monoliths are a new class of materials that emerged in the early 1990s. These materials are typically prepared using a simple molding process carried out within the confines of a closed mold [20]. For example, polymerization of a mixture comprising monomers, free-radical initiator and porogenic solvent affords macroporous materials with large through-pores that enable applications in a rapid flow-through mode. The versatility of the preparation technique is demonstrated by its use with hydrophobic, hydrophilic, ionizable, and zwitterionic monomers. Several system variables can be used to control the porous properties of the monolith over a broad range and to mediate the hydrodynamic properties of the monolithic devices. A variety of methods, such as direct copolymerization of functional monomers, chemical modification of reactive groups, and grafting of pore surface with selected polymer chains, can be used for the control of surface chemistry. Since all the mobile phase must flow through the monolith, the convection considerably accelerates mass transport within the molded material, and the monolithic devices perform well, even at very high flow rates [20,21]. A monolith-structured column is very suitable for an in-tube SPME medium due to its unique features, including low pressure drop, and total porosity higher than conventional packed columns. These materials usually offer low backpressure, depending on their structure (mesopore and throughpore). They also offer chemical stability over a wide pH range, involve a simple (mostly one-step) preparation method, and enable fixation of the material in a column or plastic tube through chemical modification. This material has some interesting properties when compared to more traditional particulate materials (e.g., high permeability for biological samples). Zero dead volume, ease of preparation and shape control, porosity and selectivity provide many options to perform bioanalytical applications and choose the format of the monolithic coating [22]. Shintani et al. [23] introduced a C-bonded monolithic capillary column, consisting of continuous porous silica having a double-pore structure. They investigated a novel pre-concentration technique using monolithic material as the in-tube SPME medium for extraction of pesticides. The C -bonded monolithic silica column, with a through-pore size of 10 µm and a mesopore size of 12 nm, was prepared by in-situ hydrolysis and polycondensation of alkoxysilane. The column was cut to 150 mm length for the use in in-tube SPME, and mounted in the position of sample loop of a six-port injector. A zero dead-volume union was employed for connecting capillary tubing. For trace analysis of environmental or biological samples, large-volume injection using the in-tube SPME/on-column focusing technique led to higher sensitivity (50 times) than capillary LC techniques. A poly(methacrylic acid–ethylene glycol dimethacrylate) monolithic capillary column was also prepared for in-tube SPME [24]. An on-line monolithic capillary-column SPME method was developed for determination of theobromine, theophylline and caffeine in serum samples. Organic polymer monolithic materials could be easily synthesized in situ by thermal or irradiation initiating the polymerization of certain mixture of monomer, cross-linker and proper porogenic solvent in a “mold”. The pore properties and the surface area of the material could be freely controlled by the type and the composition of the porogenic solvent and the cross-linker percentage. Since many monomers and cross-linkers are available, the polymer monolithic material could be made according to the separation requirement to produce different coatings with various polarity and functional groups. Besides, the procedure to synthesize this type of material is simple and reproducible, while they can be easily sited in stainless-steel columns and cartridges, without a further packing step. These unique features make monolith-based coatings an attractive choice for application as separation and extraction media. Moreover, the poly(methacrylic acid–ethylene glycol dimethacrylate) (MAA–EGDMA) monolithic column could be used readily after in-situ polymerization. For, preparation of a poly(MAA–EGDMA) monolithic capillary column, a fused 4

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silica capillary (20 cm × 0.25 mm, i.d.), was first activated by NaOH and then HCl. A 3(triethoxysilyl) propyl methacrylate methanolic solution (50% (v/v)) was used to fill the activated capillary and kept for 12 h at 40 C. The pre-polymerization mixture consisted of monomer MAA, cross-linker EGDMA, porogenic solvent toluene and dodecanol, and initiator AIBN. The capillary was immediately sealed with silicone rubber and the reaction was initiated at 60C for 16 h. Following polymerization, the capillary was washed with methanol to remove the unreacted components and porogenic solvent. The commonly-used open-tubular extraction capillary provides insufficient extraction efficiency, since the ratio of its coating volume to that of the capillary void volume is relatively small, while the monolithic columns with greater phase ratio combined with convective mass transfer provide the possibility to improve the extraction efficiency with shorter capillary length. As the main chains of poly(MAA–EGDMA) are hydrophobic, acidic pendant groups make it a superior material for extraction of basic analytes from aqueous matrix (Fig. 4). A poly(MAA–EGDMA) monolithic capillary column was also prepared for in-tube SPME coupled to HPLC for direct determination of ketamine [25] and amphetamines [26]. Besides of poly(MAA-EGDMA), several monolithic capillaries were prepared with different reagents [27–29]. A weak anion-exchange polymer monolith based on poly(4-vinylpyridine-co-ethylene dimethacrylate) [poly(VP-co-EDMA)] was prepared in a capillary by Feng et al. [30]. To expand the application of the monolith capillary containing vinylpyridine in SPME, it is still necessary to adjust the polymerization mixture. Changing porogen type and concentration is an effective, direct method to adjust the structure of the monolith. Poly(ethyleneglycol) (PEG) is more and more valued as a porogen because it has good solubility in some solvents and, due to its molecular weight, can be selected as a porogen. Meanwhile, compared with methylene bisacrylamide as cross-linker, EDMA exhibits higher hydrophobicity, so PEG with a different molecular weight was tested as a porogen and EDMA was used as cross-linker, and we expect that to improve the hydrophobicity, the mechanical strength and the specific surface area over previous monolithic materials containing vinylpyridine. The use of PEG as porogen and EDMA as crosslinking monomer helps to increase the specific surface area and to enhance the hydrophobicity of the target monolith. Based on the use of poly(VP-co-EDMA) monolith as extraction medium and integration of sample extraction, LC separation and MS detection was developed in a single system – a fast, sensitive method for analysis of three non-steroidal anti-inflammatory drugs in human plasma and environmental water. A novel bimodal porous N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AAPTS)-silica monolithic capillary was prepared by sol-gel technology, and used as a CME column for aluminum fractionation by electrothermal vaporization inductively coupled plasma MS (ETV)–ICP-MS with the use of polytetrafluoroethylene (PTFE) slurry as fluorinating agent [31]. For preparation of AAPTS-silica sol, CTAB and TMOS were dissolved in ethanol/H2O (v/v = 3+1). Afterwards, AAPTS was added and this led to the formation of AAPTS-silica sol. Prior to the preparation, the fused-silica capillary was preactivated. The monolithic AAPTS-silica was prepared by in-situ hydrolysis and polycondensation of alkoxysilane in a fused-silica capillary (60 cm, 450 μm, i.d.). Due to the functional group of –NH–CH2–CH2–NH2, N-(2-aminoethyl)-3aminopropyltrimethoxysilane (AAPTS) had been used as a silylating reagent to modify mesoporous sol-gel silica via covalent grafting. The proposed method was claimed to be simple, rapid, selective, miniaturized, sensitive, and a potential alternative for Al fractionation analysis in various samples with complicated matrix and low concentration. In 2009, Wu et al. [32] reported a novel MIP monolith in a capillary column to establish a simple, sensitive, and low-cost approach for urinary trace 8-hydroxy-2′-deoxyguanosine (8-OHdG) determination using in-tube MIP SPME with HPLC/UV detection. The MIP monolithic capillary column was prepared using guanosine (template), acrylamide and 4-vinylpyridine (functional monomers), and N,N-methylene bisacrylamide (cross-linker) dissolved in DMSO and dodecanol 5

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(porogenic solvents). A non-imprinted polymer (NIP) monolithic capillary was prepared at the same time without guanosine in the mixture. This novel MIP monolithic column exhibited very high extraction efficiency and selectivity for 8-OHdG. Immunoaffinity monolithic CME was also reported by Hu et al. [33]. They developed a new method for immunoassay by coupling immunoaffinity monolithic CME to micro-concentric nebulizer (MCN)-ICP-MS with quantum-dot (QD) labels. The unique properties of high quantum yields, large extinction coefficients, pronounced photostability and broad absorption spectra coupled to narrow size-tunable photoluminescent emission spectra make QDs (CdS, PbS, ZnS, CuS and CdSe) attractive for use in fluorescence immunoassays. Due to the intrinsic redox properties of QDs and sensitive electrochemical-stripping analysis of the metal components, quantification in QD-based immunoassay could also be based on electrochemical detection. An aminopropyltriethoxysilane (APTES)-silica hybrid monolithic capillary was prepared with room-temperature ionic liquid (RTIL)-mediated non-hydrolytic sol-gel (NHSG) technique and employed for primary antibody immobilization. After that, the sandwich immunocomplex was formed of primary antibody, antigen and secondary antibody labeled with CdSe-QDs, and the concentration of IgG antigen was quantified by MCN-ICP-MS analysis of Cd or Se in CdSe-QDs conjugated with secondary antibody. The proposed method was applied to the determination of human IgG antigen in human serum and the analytical result was in good agreement with that obtained by the commonly-used clinical method of immunoturbidimetry (Fig. 5). The immunoaffinity CME-ICP-MS immunoassay based on non-isotopic QD labeling was fast, sensitive, selective, and CdSe-QDs labels combined with a multi-elemental ICP-MS detection made this method more accurate. 2.3. Sol-gel coatings Inorganic polymerization corresponds to a general method of preparation of oxides under mild conditions. The sol-gel process is important because it allows the incorporation of thermolabile entities coming from all other fields (organic, macromolecular, coordination, bioorganic and biological) of chemistry. Silicate precursor is one the most common reagents in the sol-gel process since it is very versatile, stable and inexpensive. Reaction of Si(OR)4 (R = Me, Et, iPr) solution with water, at room temperature and in the presence of a catalyst (acid, base or nucleophile), gives a transparent solid occupying the entire volume. This solid is not a precipitate, but a gel enclosing the solvent and sticking to the walls of the recipient (Fig. 6a). After a lapse of time, which varies with the experimental conditions, phase demixing occurs so that the solid SiO2 expels the solvent and becomes denser. This stage is called syneresis. In practice, the sol-gel process is very simple at the macroscopic scale. In one step and at room temperature, it transforms a molecule into a material ready for shaping. At the nanoscopic and microscopic scales, it is a very complex process consisting of several transformations of very different natures involving three states of solution, colloid and solid [34] (Fig. 6b). Application of sol-gel technology for preparation of coatings inside a CME device was first reported by Malik et al. [35]. They introduced sol-gel technology to overcome the existing shortcomings of conventional CME. Usually, the pieces of fused-silica capillary columns used for intube SPME could provide thin coatings leading to limited sample capacity and subsequent lower sensitivity. Developing an alternative technique to provide higher coating thickness suitable for intube SPME applications was therefore rather important. The lack of chemical bonds between the stationary-phase coatings and substrate in fused-silica capillaries was another issue limiting the stability and the life-time of the CME device. When such extraction devices are coupled to GC, reduced thermal stability of the non-bonded coatings leads to incomplete sample desorption and 6

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sample-carry-over problems. Low solvent stability of conventionally-prepared coatings could be a major limitation when in-tube SPME is coupled with HPLC as an organic or organo-aqueous mobilephase is being used for the analyte desorption. These researchers used an in-house designed liquidsample dispenser to facilitate gravity-fed flow of the aqueous samples through the sol-gel microextraction capillary. The sol solution was prepared by dissolving appropriate amounts of a solgel precursor, such as methyltrimethoxysilane, tetramethoxysilane, a sol gel-active organic polymer including hydroxy-terminated PDMS, and trimethoxysilyl-terminated PEG, a surface deactivation reagent (HMDS, polymethylhydrosiloxane,), and TFA as a catalyst in an appropriate solvent. Ultratrace-level detection was achieved for polar and non-polar analytes. In another work [36], a benzyl-terminated, dendron-based, sol-gel coating was employed. Dendrimers are highly branched macromolecules that can easily overcome many of the inherent shortcomings of linear polymers. The branched architecture of dendrimers has made them promising candidates for use as extraction sorbents with distinct advantages over linear polymers. The main objective of this work was to investigate the possibility of using benzyl-terminated dendrimers as a novel extraction medium for SPME. This was accomplished by creating immobilized dendrimer coatings on the fused-silica capillary inner surface using the principles of sol-gel column chemistry. Sol-gel dendron coatings showed excellent thermal and solvent stability in CME coupled with chromatographic analysis. Satisfactory analytical data were achieved in CME-GC for polar and nonpolar analytes, including polyaromatic hydrocarbons (PAHs), aldehydes, ketones, phenols, and alcohols. Several other studies also improved sorptive capacity, and thermal and solvent stability of the prepared sorbent by sol-gel technology. Materials, such as poly-tetrahydrofuran [37], cyanoN-(2-aminoethyl)-3polydimethylsiloxane [38], mesoporous titania [39], aminopropyltrimethoxysilane (AAPTS)-silica [40], 3-mercaptopropyltrimethoxysilane (3MPTMOS) [41] and polydimethyldiphenylsiloxane [42], have been reported as new coatings. Coatings containing covalently-attached octadecyl, octyl, and methyl groups prepared from octadecyltrimethoxysilane (C18TMS), octyltrimethoxysilane (C8TMS), or methyltrimethoxysilane (MTMS) [43] and 3MPTMOS chemically bonded to PEG [44] also extended the versatility of solgel. There was a comprehensive study of the role of precursors and coating polymers in efficiency and selectivity of CME sorbents [45]. Ten different fiber coatings were synthesized and five of them contained only the precursor and the other five were prepared using both precursor and coating polymer. All the coatings were chemically bonded to the inner surface of copper tubes, intended to be used as the CME device and already functionalized by self-assembly monolayers of 3(mercaptopropyl)trimethoxysilane (3MPTMOS). The selected precursors included tetramethoxysilane (TMOS), 3-(trimethoxysilyl)propylmethacrylate (TMSPMA), 3-(triethoxysilyl)propylamine (TMSPA), 3MPTMOS and [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane (EPPTMOS), while PEG was chosen as the coating polymer. The effects of different precursors on extraction efficiency and selectivity were studied by selecting a list of compounds ranging from nonpolar to polar (i.e. PAHs, herbicides, estrogens and triazines). The results from CME-HPLC analysis revealed that there is no significant difference between precursors, except TMOS, which has the lowest extraction efficiency. Most of the selected precursors have rather similar interactions toward the selected analytes, which include van der Waals, dipole-dipole and hydrogen bond, while TMOS has only dipole-dipole interaction and therefore the lowest efficiency. TMOS is silica but the other sorbents are organically modified silica (ORMOSIL). This investigation revealed that it is impossible to prepare a selective coating using conventional sol-gel methodologies. The application of ILs to preparation of sorbent for CME by sol-gel technology was reported by Malik et al. in 2009 [46]. In recent years, ILs (organic salts that melt at or below 100°C) gained 7

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popularity in a number of fields due to their perceived advantages over traditional solvents. They are considered rather “green” solvents because they are remarkably less hazardous than their conventional counterparts due to their negligible vapor pressures, low flammability, good thermal stability, “tunable viscosities”, low corrosion tendencies, and varying degrees of solubility with water and organic solvents [47]. In analytical microextraction, IL-mediated sol-gel hybrid organic–inorganic sorbents were shown to have potential since they are likely to possess favorable material characteristics, such as porous morphology, enhanced surface area, improved stability, and thus better extraction efficiency and superior sample-preconcentration effects compared to currently available extracting phases. Malik et al. [46] investigated IL-mediated PDMS, PEG, poly(tetrahydrofuran), and bis[(3methyldimethoxysilyl)propyl] polypropylene oxide (BMPO) sol-gel coatings for CME. The effects of two ILs, [i.e., trihexyltetradecylphosphonium tetrafluoroborate (TTPT) and N-butyl-4methylpyridinium tetrafluoroborate (BMPT)] were studied. IL-mediated sol-gel PDMS coatings provided consistent performance in CME-GC analysis compared with sol-gel PDMS coatings prepared without an IL. PDMS and BMPO IL-mediated sol-gel coatings also provided lower limits of detection (LODs) than analogous sol-gel coatings prepared without an IL. Scanning electron microscopy (SEM) results suggest that ILs can provide the porous morphology for sol-gel extraction media when they are incorporated into the sol-gel-coating solution. Enhancement of porosity alone was not enough to provide effective extraction of analytes. For investigation of the role of ILs in coatings, one has to remember that ILs are known to act as porogens in sol-gel systems. Thus, the IL-mediated sol-gel coatings provided enhanced GC peak areas because they were more porous than the non-IL-mediated BMPO sol-gel. The decomposition of both these ILs occurred at 190C. Since the CME capillaries were thermally conditioned above decomposition temperatures of these ILs (i.e., 280C and 300C), it was assumed that the ILs had decomposed and the decomposition products had been carried away from the capillary by the flow of helium. It was also claimed that the ILs used did not participate in the extraction process and that extraction of analytes from the sample matrix occurred by interaction with the organic-inorganic hybrid sol-gel coating. The low stability of pH in in-tube SPME coatings practically excludes the application of this technique to basic samples or analytes that require high-pH solvent systems for desorption from the CME device. The instability of pH is a major drawback of silica-based stationary phases and extraction media. The siloxane bond (Si-O-Si) on the silica surface hydrolyzes at pH >8 and it happens rapidly under elevated temperatures. Developing sorbents with a wide range of pH stability was an important research area in sample-preparation technologies. Application of non-silicate precursors (metal oxides) was also reported by Malik et al. [48,49] for preparing high-pH-resistant sorbents (Fig. 7a). Transition-metal oxides (e.g., zirconia and titania) are well known for the stability of their pH [50–52], and appear to be logical candidates for exploration how to overcome the drawbacks associated with silica-based materials. Titanium alkoxides differ significantly from silicon alkoxides in terms of their chemical reactivity and complex-forming ability. These differences dictate the adoption of different strategies for the creation of titania-based sol-gel sorbents compared with those for silica-based analogs. While sol-gel reactions in a silica-based system are rather slow and often require the use of catalysts to accelerate the process, titania-based sol-gel reactions are very fast. This is explained by titanium alkoxides being very reactive toward nucleophilic reagents, such as water. Zirconia possesses much better alkali resistance than other metal oxides, such as alumina, silica, and titania (Fig. 7b). It is practically insoluble within a wide pH range (1–14) [53–55]. Zirconia also shows outstanding resistance to dissolution at high temperatures. Besides the extraordinary stability of its pH, excellent chemical inertness and high mechanical strength are two other attractive features 8

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that add value to zirconia in use as a support material in chromatography [56]. The developed sol-gel zirconia-PDMDPS coating demonstrated exceptional pH stability: its extraction characteristics remained practically unchanged after rinsing with a 0.1 M solution of NaOH (pH 13) for 24 h. Another pH-resistant coating was also reported based on sol-gel hybrid germania [57]. The sol-gel germania-PDMS coating showed excellent pH stability. After coating and conditioning, we conducted two sets of experiments, in which we rinsed the sol-gel germania-PDMS capillaries for 24 h with (a) 0.05 M HCl and (b) 0.1 M NaOH (pH 13). The results suggested that sol-gel germaniaPDMS coating retain its excellent extraction capability after being subjected to prolonged rinsing with a strong base or acid and therefore had excellent pH stability (Fig. 7c). Sol-gel chemistry in SPME and CME were studied in well-documented reviews [58,59]. 2.4. Selective coating in CME Although most problems related to the stability of coatings and substrates have been resolved, the selectivity of fiber coatings has remained a challenge. To enhance extraction selectivity, new materials based on molecular recognition have been developed. Immobilization of the antibody into the fused-silica capillary was studied by Queiroz et al. in 2007 [60]. Highly-selective sorbents have been obtained using materials involving antigen–antibody interactions, thus providing selective extraction methods based on molecular recognition. Antibodies are covalently bonded onto an appropriate sorbent to form a so-called immunosorbent. Thanks to the high affinity and high selectivity of the antigen–antibody interactions, they allow a high degree of molecular selectivity preconcentration that is essential for the analysis of complex samples, such as biological matrices. Antibodies against fluoxetine were raised in rabbits using BSA-fluoxetine conjugate as the immunogen. The conjugate was prepared by incubating 10 mg of BSA with 40 mg of fluoxetine in 2.0 mL of 0.3 M 2-(N-morpholino)ethanesulfonic acid buffer, pH 5.5, containing 0.1 M 1-ethyl-3(3dimethylaminopropyl) carbodiimide for 5 h at room temperature, under stirring. The conjugate was recovered by centrifugation of a heavy precipitate that formed during the carbodiimide-catalyzed coupling reaction, washed eight times by vortexing the precipitate with 2.0 mL of 0.15 M NaCl, and stored at 4C until use. The immunization protocol consisted of three successive injections of 1.0 mg of the BSA-fluoxetine conjugate, one every 3 weeks. After initial priming with the antigen in complete Freund’s adjuvant, booster doses of the conjugate were given in Freund’s adjuvant and saline, respectively. Animals were bled 1 week later and samples of 1 mL of each serum were individually diluted 1:1 with 50 mM tris-HCl buffer, pH 8.1, containing 100 mM NaCl, and chromatographed over a DEAE-Sepharose column (10 cm × 1 cm) equilibrated and developed with 25 mM tris-HCl buffer, pH 8.1, containing 50 mM NaCl. Under these conditions, the bulk of the rabbit IgG was recovered in the protein fraction that eluted unretarded from the column, concentrated to 2 mL by ultrafiltration under N2 pressure, and stored at -20C in the presence of 30% glycerol until use. A sensitive, selective, and reproducible immunoaffinity in-tube SPME coupled with liquid chromatography-MS (in-tube SPME/LC-MS) method was developed, and validated for fluoxetine analysis in human serum [60]. These materials are often composed of immunosorbents whose affinities and selectivities stem from antigen–antibody types of interactions. However, the development of immunosorbents is time consuming, they are difficult to use and have a relatively high cost. An alternative technology, based on the use of MIPs, is currently being investigated by many researchers. A very pronounced difference in selectivity toward the target analyte can be achieved with a MIP material. MIPs are extensively cross-linked polymer materials containing synthetic cavities or recognition sites with a predetermined selectivity. The imprinting process involves polymerizing functionalized monomers in the presence of a template molecule, which is typically the target or a molecule of similar size and 9

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chemical functionality. Once the template is removed, a molecular recognition site of appropriate size and chemical functionality is produced to bind the target. The first attempt to use MIPs in CME (in-tube SPME) was reported by Pawliszyn et al. [61]. An automated, online MIP-SPME method was developed for the determination of propranolol in biological fluids and showed improved selectivity compared to in-tube stationary-phase materials, so overcoming the limitations of the existing coating materials for SPME. Preconcentration of the sample by the MIP adsorbent increased the sensitivity, yielding low LODs. Besides many advantages, MIP technology still needs some development to overcome limitations, such as template leakage, poor accessibility of the binding sites, low binding capacity and nonspecific binding. Swelling of sorbents in the presence of water and solvents is one of the most important problems of conventional MIP structures, which can lead to blockage and deformation of the sorbent-selective cavities. Moreover, the applications of MIPs are also restricted to the use of organic solvents for the dissolution of acrylate or acrylic-type polymers, which are most commonly used for preparing MIPs [62,63]. To overcome these drawbacks, sol-gel methodology is a good alternative. Hu et al. [64] synthesized an Mn(II)-imprinted 3-mercaptopropyltrimethoxysilane (MPTS)-silica coated capillary by the sol-gel technique using a double-imprinting concept. The resultant capillary was employed for CME of trace Mn(II) followed by on-line detection by ICP-MS. This coating was created in situ on the inner wall of a tetramethoxysilane (TMOS)-coated silica capillary using a sol solution containing MPTS as the functional precursor, ethanol as the solvent and both Mn(II) and surfactant micelles (cetyltrimethylammonium bromide, CTAB) as the templates (Fig. 8). The method was rapid, selective, sensitive and applicable to the on-line analysis of trace and ultra-trace manganese in biological samples, especially biological samples with limited sample volume. Bagheri et al. [65] also reported a molecularly-imprinted xerogel (MIX) based on silica organically modified (ORMOSIL) by sol-gel technology for CME in 2012. To prepare the xerogel, it was essential to prepare the sol by adding 3PMTMOS (precursor) to atrazine, as the template molecule under acidic conditions in the presence of an appropriate quantity of water. Then, the sol was kept at room temperature for 3 h for imprinting the atrazine template. After ageing and drying, a xerogel of amorphous silica was obtained. A solution of methanol and acetic acid (9:1) was passed through the prepared loop until the complete removal of the template from the xerogel network was successfully achieved (Fig. 9). A non-imprinted xerogel was also prepared under similar conditions when no atrazine template was used. Sol-gel imprinting is an emerging field, due to its straightforward synthesis path. Silica-based materials are extremely rigid because of the high degree of cross-linking in their network. This property is very important and influential in designing and synthesizing the imprinted materials, since both size and shape of the cavities created by the template molecule should be retained after template removal. High thermal stability of sol-gel derived materials and the possibility of using high temperatures assist the removal process. In addition, sol-gel glasses are structurally porous and can be engineered to have extremely large surface areas. These properties make the silica sol-gel matrix an appropriate imprinting host. In practice, the sol-gel process is rather simple. In one step and at room temperature, it transforms a molecule into a material ready for shaping. Application of MIX for extraction of fentanyl from complex media, such as urine and blood plasma samples, were also studied and the satisfactory relative recovery obtained by the prepared sorbent exhibited the ability of the selective coating developed [66]. The main problem of the sol-gel process could be attributed to the long gelation time of several weeks or months. To overcome this drawback, Bagheri et al. reported in-situ electro-entrapment of PANI in EPPTMOS-derived xerogel to be an easy methodology for MIX [15]. Naproxen was employed as the template analyte to evaluate the coating developed. Addition of PANI to a solution 10

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of EPPTMOS resulted in a significant decrease in gelation time to a few hours (while, for conventional EPPTMOS sol-gel, the gelation time could ranged from a few days to a few weeks). Reduction in the gelation time provided a convenient, easy approach to prepare the selective media. There is a relationship between gelation time and conductive polyaniline loading. The gelation time in some cases was as long as one week for pure EPPTMOS and it was sharply decreased to a few hours when PANI was added to the solution. The main reason for the acceleration in the gelation process of EPPTMOS is that the conductive polyaniline is weakly acidic, which is beneficial for accelerating hydrolysis and condensation of EPPTMOS. The xerogel based on electro-entrapped PANI into the silica was expected to show great stability originating from silica-based xerogel as well as good extraction efficiencies, which are due to the presence of CPs. Selectivity and high extraction efficiency of the prepared MIX were also investigated by comparing the results of MIX/NIX for the imprinted analyte, naproxen, with some selected compounds (i.e., furosemide, clodinafop-propargyl and haloxyfop-etotyl). 2.5. Miscellaneous 2.5.1. Nano approach Carbon nanotubes (CNTs) comprise special kinds of carbon nanomaterial, which can be simply described as a nanometer-sized tubes, including single-walled CNTs (SWCNTs) and the coaxial multi-walled CNTs (MWCNTs). The diameter of CNTs is generally from a few to tens of nanometers. They have large specific surface area, high mechanical strength, good flexibility, excellent electrical conductivity and the spiral state of the layer(s) decides the semiconducting and metallic properties of CNTs. They can act with organic and inorganic analytes through different types of interactions, such as π–π and van der Waals. Application of oxidized MWCNTs as an in-tube SPME was reported by Zhang et al. in 2008 [67]. The MWCNT-COOH materials were prepared and coated onto the fused-silica capillary (20 cm) in the method. Then the fused-silica MWCNT-COOH-coated capillary was inserted into PEEK tubing (20 cm length), which was fixed on the six-port injection valve to substitute for the injection loop. It exhibited excellent extraction characteristics for aromatic amines. The experimental results demonstrated that combination of in-tube SPME with MWCNT-COOH coating with HPLC-UV could achieve low LODs of aromatic amines in environmental water samples. Preparation of a Congo red-modified SWCNT (CR-SWCNT)-coated fused silica was reported for CME of lanthanum (La), europium (Eu), dysprosium (Dy) and yttrium (Y) in human hair [68]. Application of gold nanoparticles for CME of monohydroxy-PAHs in synthetic urine samples by capillary-zone electrophoresis (CZE) was also reported [69]. 2.5.2. Biocompatible coatings Biocompatibility is the ability to be in contact with a living system without producing an adverse effect. Many SPME coatings lack biocompatibility. Direct SPME of drugs from biological samples often requires additional sample preparation, such as ultra-centrifugation, in order to eliminate the protein component in samples. Direct exposure of the extraction coating to biological samples is complicated by the presence and the adsorption of interferences, such as proteins, which has consequently limited the wide application of SPME for bioanalysis. One promising class of biocompatible extraction phases are restricted access materials (RAMs), which fractionate a sample into the protein matrix and the analyte component on the basis of size [70–73]. Simultaneous with this size-exclusion process, low-molecular-mass compounds are extracted and enriched, via partition, into the interior of the phase. 11

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The first work on a RAM applied as a biocompatible coating for CME was reported by Pawliszyn et al. in 2002 [74]. Alkyl-diol-silica (ADS) was used to prepare a highly bio-compatible sorbent for direct injection and simultaneous extraction of several benzodiazepines in biological samples. The ADS particles were slurried in 2-propanol and packed into a 50 mm length of polyether ether ketone (PEEK) tubing (1.59 mm o.d., 30.76 mm i.d.). The biocompatibility of ADS was important to permit the direct, untreated and multiple exposure of complicated matrices, such as biological fluids. The material possessed two different chemical surfaces and a pore size that restricted large molecules, such as proteins, from accessing the inner surface. In combination with the size-exclusion process, the presence of hydrophilic electroneutral diol groups bound to the external surface of the spherical particles further protected the extraction phase from contamination by surface adsorption of proteins. The inner surface of the porous ADS material was modified with a C18 alkyl hydrophobic bonded phase that was responsible for the simultaneous extraction of the target compounds (Fig. 10). Table 1 shows possible monomers for preparing biocompatible materials are summarized [75]. Poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic material is used widely in the biomedical field due to its biocompatibility [75]. Poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic CME as a biocompatible coating coupled to HPLC was first reported by Feng et al. [24,25]. Application of this kind of material was thoroughly discussed in sub-section 2.3. 2.5.3. Electrochemically-assisted coatings There are a few papers about electrochemically-coated CME. Study of a CME based on an anodized alumina capillary tube was reported by Djozan et al. in 2004 [76]. The inner surface of a long, small-bore aluminum tube was electrochemically coated by Al2O3 and used as a CME device for pre-concentration and analysis of phenol and biphenyl. The proposed method is simple and has a short sample-preparation time and low cost. It was also used for reliable determination of L-dopa and L-dopamine [77]. Bagheri et al. also reported electrochemical coating of aniline to prepare PANI on the inner surface of a copper tube [15]. Table 2 shows the advantages and the disadvantages of the coating materials prepared by different methods.

3. Recent approaches 3.1. Unbreakable capillaries As mentioned above, most of the drawbacks of coatings, such as low recommended operating temperatures, generally in the range 240–280C, instability and swelling in organic solvents (greatly restricting their use with HPLC), have been overcome by sol-gel technology, but they can still be broken easily and their coatings stripped due to the brittleness of the fused-silica substrate. Application of sol-gel technology to prepare coatings is limited to –OH-functionalized substrate, so metallic substrates with no functionality could be used as CME device. An unbreakable sol-gel-based CME approach was developed by Bagheri et al. [44] to reduce the possibility of breakage of the fused-silica substrate and therefore the sol-gel coating during installation, operation and handling. They used a copper tube as the unbreakable substrate and to obviate the problem relating to the lack of functionality of the copper tube to accomplish the sol-gel process; the SAM technique was used to functionalize the inner surface of the CME device. SAMs are ordered monomolecular films, which are spontaneously formed by immersing a solid substrate in a solution containing amphifunctional molecules. The amphifunctional molecule has a head group, which usually has a high affinity for the solid surface, a tail (typically an alkyl chain) and a terminal 12

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group that can be used to control the surface properties of the resultant monolayer. The molecular forces between the tails are mainly responsible for the order of the monolayer. The most extensively studied SAMs are silanes, which are used to modify hydroxyl-terminated surfaces, and organosulfur compounds. The affinity of sulfur for gold, platinum, copper and silver could be therefore justified [78]. For formation of SAMs, the thiol groups are chemisorbed on the inner surface of the copper tube via the formation of the copper-thiol bond to produce a densely-packed, highly-ordered monolayer. The copper tube was placed in a solution of 0.001 M of 3MPTMOS to perform the functionalization and 3MPTMOS solution was withdrawn into the copper tube to be adsorbed on the inner surface of the copper tube spontaneously, a process that continues for 15 h (Fig. 11). After functionalizing the copper tube, the sol-gel process was easily performed on its inner surface. The loop prepared was used for online CME of some selected PAHs, as model compounds, from the aquatic media. Although there has been extensive progress, SAMs are amenable to only a few metals such as Cu, Ag and two expensive metals (Au and Pt). Aryl-diazonium salt was employed for functionalizing different metallic and non-metallic substrates [79]. Chemical and electrochemical reduction of aryldiazonium salts was used to functionalize different substrates and subsequently a rather stable sorbent was prepared by the sol-gel process. Aryl-diazonium salts constitute an important series of compounds in organic chemistry because the diazonium group activates nucleophilic aromatic substitutions and provides a general pathway for introducing halogens, CN, OH, H into an aromatic ring to form a wide range of compounds [80]. Carbon, metallic, semi-conductor and reduced polymer surfaces can be modified by the electrochemical reduction of aryl-diazonium salts with the general formulae A−, +N2-C6H4-R, where A− is the anion and R stands for different functional groups [81]. The interest in using aryl-diazonium salts lies in their ease of preparation, rapid (electro)reduction, large choice of reactive functional groups, and strong aryl-surface covalent bonding [82,83]. Aryldiazonium salts are excellent alternatives to traditional silanes and thiols, as silanes bind polymers mostly to ceramics whereas thiols are mainly limited to the surface of gold, copper and platinum [84]. To prepare an unbreakable sol-gel CME device using aryl-diazonium salts, different metallic substrates, such as copper, brass and stainless-steel tubes (0.7 mm i.d.), and copper, ferronickel and stainless-steel wires were selected to be functionalized. PTFE was also used as a non-metal substrate. It is worth noting that the latter must be accomplished under chemical reduction. In all experiments, the capillary tube was used as the HPLC sample-introduction loop. The next step includes functionalizing the substrate, which involved the electrochemical reduction of 4-amino phenyl acetic acid for in-situ generation of the aryl-diazonium cation [85]. 4-Amino phenyl acetic acid (2 mM) was solubilized in aqueous HCl (0.5 M), and then sodium nitrite (2 mM) was added to solution. Then, it was placed at room temperature for about 5 min, for completion of the reaction, prior to the electrochemical functionalizing process. Next, the substrates were inserted into the electrolyte solution to act as the cathode and a piece of aluminum foil was used as the anode. A peristaltic pump was used to deliver the electrolyte solution through the tube (wires only immersed), while a potential of -1.5 V was applied for 15 min. Fig. 12 shows the electroreduction of aryl-diazonium cation on the inner surface of the copper tubing. To functionalize the PTFE, a representative of non-metallic substrates, it was immersed into the solution of aryl-diazonium cation and iron powder was then added. Instantaneously, small bubbles were observed in the flask corresponding to dihydrogen and dinitrogen evolution, as iron reduced protons and diazonium salts in solution [86]. The sol-gel process was then performed to coat the sorbent inside the capillaries chemically. Investigation reveals that there is no limitation to selecting any substrate type in preparing unbreakable CME devices. Good relative recoveries for the selected analytes were obtained from tap and agricultural water samples, while the method developed had low 13

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LOD and LOQ values and acceptable RSD%. Finally, the method developed could easily provide the possibility for an on-line coupling of the sol-gel-based CME with HPLC to have a simple, quite rapid and inexpensive method [79]. 3.2. Array CME Recently, an array capillary in-tube SPME (ACIT-SPME) cartridge for fast sample preparation based on the in-tube SPME technique was developed for fast enrichment of organic contaminants from water samples [87]. The cartridge consisted of a bundle of glass capillary tubes coated with extraction phase and placed inside a quartz liner. For preparation of the ACIT-SPME device the quartz liner (66 mm length × 6 mm o.d. × 4 mm i.d.) with a neck of 2.5 mm i.d. near the outlet was used as the container of the ACIT-SPME cartridge (Fig. 13). The PDMS extraction phase was prepared by the sol-gel method. Phenyltriethoxysilane (PTES) was also added as the precursor to introduce - interaction between the PAHs and the phenyl group in the sol-gel network. The sample solution was loaded and passed through the ACIT-SPME cartridge by gravity. Then, the cartridge was centrifuged for 1 min at 3000 rpm to remove the water residue in the array capillary. Subsequently, the cartridge was placed into the thermal-desorption unit (Fig. 13D). Rapid extraction could be ascribed to the parallel multi-channel structure and high extraction surface area of the ACIT-SPME cartridge. Analytes were absorbed into a thin extraction layer coated on both sides of the array capillaries in the cartridge, and then desorbed by thermal desorption. Both the internal and external surfaces of the array capillary tubing were coated with the extraction phase 2–5 µm thick, which provided a large extraction surface area of up to 30 cm2 for a cartridge containing 19 glass capillaries. The large surface area and thin extraction phase improved greatly both the masstransfer process of extraction and the thermo-desorption process, leading to fast extraction and fast desorption. The cartridge was applied to extract PAHs in water samples using PDMS as extraction phase. Extraction was completed in 2 min for a 350-mL water sample, and thermally desorbed in 5 min, resulting LODs in the ppt range using ACIT-SPME/GC-FID. The main advantages of ACITSPME are the rapid extraction, high enrichment factor, and easy operation. It is especially suitable for on-site analysis of the abundant environmental water and drinking water. Due to its lower flow resistance from capillary array design, a larger volume of water could be loaded and extracted in a very short time, resulting very low LODs. In order to improve the extraction efficiency per unit extraction time, ACIT-SPME cartridges with capillary tubes of different inner diameters (mm i.d.) of 0.53, 0.32, 0.25, and 0.10 were fabricated and compared systematically with chlorobenzenes (CBs) and nitrochlorobenzenes (NCBs) [88]. The results indicated that the ACIT-SPME with larger bore diameter was more suitable for rapid extraction of analytes in an abundant water sample, while ACIT-SPME with smaller bore diameter had a higher absolute recovery (Fig. 14).

4. Conclusion and future prospects 14

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In CME, sample solution containing the desired analytes is passed through an open capillary and these analytes are then released by solvent desorption in conjunction with HPLC on-line. This configuration allows the analytes to be introduced into a HPLC via an on-line set-up, making the whole procedure more sensitive. This is due to the introduction of whole desorbed analytes into the chromatographic system or other analytical instruments. The use of capillary columns has a great influence on the extraction modes of CME and new methodologies have been used to prepare coatings with enhanced extraction efficiency and improved thermal and chemical stability. This methodology has great potential for ultra-trace determination of components in different matrices, while the extracting media could also have some degree of selectivity toward the desired analytes. CME could easily be employed on-line in combination with several instrumentations and it has therefore great potential for automation. Its coupling with HPLC for analysis of drugs and pharmaceutical compounds in real matrices would be quite promising. Another prospect for this technique could be its direct coupling to ambient MS. Copper tube or other metal tubes could be used as the ESI tip when appropriate materials are coated inside the metal capillary. References [1]

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Captions Fig. 1. Typical formats of capillary microextraction including packed capillary, open-tubular capillary and monolithic capillary. Fig. 2. Chemical oxidative polymerization of pyrrole [12]. Fig. 3. a) Three well-defined oxidation states of PANI: leucoemeraldine, emeraldine and pernigraniline. b) Mechanism of polymerization of aniline [16]. Fig. 4. SEM images of the cross section of the monolithic capillary: a) 400 x; and, b) 2000 x [24]. Fig. 5. Sandwich-type immunoassay based upon capillary microextraction: a) antibody immobilized onto hybrid monolithic capillary; b) the capillary is blocked with BSA; c) human IgG antigen is incubated; d) the secondary antibody with CdSe-nanoparticle labels is bound; and, e) the label is dissolved by eluent (PBS + formic acid, pH:2) and released Cd and Se are detected by MCN-ICP-MS [33]. Fig. 6. a) Hydrolysis reaction of ethyl silicate. b) The formation of oligomers that change into cross-linked polymers, then into micrometric colloids constituting the sol [34]. Fig. 7. Hydrolysis of a) titanium (IV) isopropoxide; b) zirconium (IV) butoxide; and, c) TMOG. Fig. 8. Preparation of Mn(II)-imprinted MPTS-coated capillary [64]. Fig. 9. Preparation of the selective MIX by sol-gel technology. Fig. 10. Bonded phase topography of alkyl thiol silica. n = 15 (C18-ADS). Fig. 11. On-line extraction/desorption using CME-HPLC. Fig. 12. (A) Functionalization of any metal or non-metal substrates prior to the treatment and after treatment with aryl diazonium; and, (B) coating of the sol-gel sorbent on the inner surface of the functionalized HPLC loop. SEM of the bare (a) brass, (c) copper, (e) ferronickel, (g) stainless steel and (i) PTFE wires and electro-grafted (b) brass, (d) copper, (f) ferronickel, (h) stainless steel and (j) PTFE wires. Fig. 13. Photograph of ACIT-SPME cartridge (A), its cross section (B), PDMS sol coating device for ACIT-SPME (C); and, thermal desorption and GC analysis (D) [87]. Fig. 14. Capillary tubes of different inner diameters.

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Table 1. The possible monomers for preparation of biocompatible materials Abbreviation Monomer HEMA Hydroxyethyl methacrylate HEEMA Hydroxyethoxyethyl methacrylate HDEEMA Hydroxydiethoxyethyl methacrylate MEMA Methoxyethyl methacrylate MEEMA Methoxyethoxyethyl methacrylate MDEEMA Methoxydiethoxyethyl methacrylate EGDMA Ethylene glycol dimethacrylate NVP N-vinyl-2-pyrrolidone NIP AAm N-isopropyl AAm VAc Vinyl acetate AA Acrylic acid MMA Methylmethacrylate HPMA N-(2-hydroxypropyl)methacrylamide EG Ethylene glycol PEGA PEG acrylate PEGMA PEG methacrylate PEGDA PEG diacrylate PEGDMA PEG dimethacrylate

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Table 2. Comparison of the coating materials Coating materials Advantages Conductive polymers

Monolithic polymers

Sol-gel technique

Selective coatings

Nano materials Biocompatible material Electrochemical technique

Disadvantages

Good extraction ability through π-ᴫ interaction and hydrogen bonding, high porosity, low cost, chemical and electrochemical preparation, wide range of thickness, facile synthesis, long lifetime low pressure drop, total porosity higher than the conventional packed columns, chemical stability over a wide pH range, zero dead volume, high porosity Excellent thermal and chemical and pH stability, good porosity, low thickness, chemical bonding to substrates, ability to use wide range of precursors, coating polymers and modifiers like ionic liquids, low cost, long lifetime Good selectivity towards the template analytes Higher extraction efficiencies

Ref.

Low thermal stability

[12–19]

It is difficult to have low thickness coating, usually limited to packed capillary

[22–30]

Relatively low dynamic range, long preparation procedure

[35–59]

Difficult and long preparation methods Difficult to avoid agglomeration during synthesis of coating and therefore retain their nano properties

[60–66]

[67–69]

In-vivo analysis

-

[24,25,70–75]

Easy to control the thickness

Limited coating materials

[12–15,76,77]

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