Nanoparticle-enhanced liquid-phase microextraction

Accepted Manuscript Title: Nanoparticle-enhanced liquid-phase microextraction Author: Carlos Bendicho, Isabel Costas-Mora, Vanesa Romero, Isela Lavilla PII: DOI: Reference:

S0165-9936(15)00063-1 http://dx.doi.org/doi:10.1016/j.trac.2015.02.007 TRAC 14408

To appear in:

Trends in Analytical Chemistry

Please cite this article as: Carlos Bendicho, Isabel Costas-Mora, Vanesa Romero, Isela Lavilla, Nanoparticle-enhanced liquid-phase microextraction, Trends in Analytical Chemistry (2015), http://dx.doi.org/doi:10.1016/j.trac.2015.02.007. 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.

Nanoparticle-enhanced liquid-phase microextraction Carlos Bendicho *, Isabel Costas-Mora, Vanesa Romero, Isela Lavilla Departamento de Química Analítica y Alimentaria, Área de Química Analítica, Facultad de Química, Universidad de Vigo, Campus As Lagoas-Marcosende s/n, 36310 Vigo, Spain

HIGHLIGHTS  The role of nanomaterials in liquid-phase microextraction  Carbon nanotubes used for reinforcing dispersive liquid-liquid microextraction  Magnetic nanoparticles combined with hollow-fiber liquid-phase microextraction  Affinity probes for matrix-assisted laser desorption/ionization mass spectrometry  Fluorescent nanoparticles used as extraction probes and nanosensors in drop format ABSTRACT Nanostructured materials play roles in different areas of analytical chemistry. Implementation of nanomaterials in liquid-phase microextraction results in a synergic combination yielding enhanced performance. Some significant examples include: carbon nanotubes for improving extraction efficiency; magnetic nanoparticles for retrieval ionic liquids or organic solvents; metal nanoprobes in a solvent microvolume for desalting and ionization in the analysis of proteins and peptides by matrix-assisted laser desorption/ionization-mass spectrometry; in situ generation of noble-metal nanoprobes for extraction of hydride-forming elements prior to their determination by atomic spectrometry; confinement of fluorescent nanoprobes in a microvolume of organic solvent, thereby integrating separation, preconcentration and analyte recognition within a single step; and, solid-phase extraction involving nanomaterials and liquid-phase microextraction in a sequential way. We provide insight into significant advances involving the joint use of nanomaterials and liquid-phase microextraction. Keywords: Affinity Carbon nanotube Liquid-phase microextraction Magnetic nanoparticle Nanomaterials Nanoparticle Nanoprobe Noble metal Oxide nanoparticle Quantum dot Abbreviations: AAS, Atomic absorption spectrometry; APDC, Ammonium pyrrolidine-dithiocarbamate; CE, Capillary electrophoresis; CNT, Carbon nanotube; CPE, Cloud-point extraction; DI-SDME, Direct immersion-single drop microextraction; DLLME, Dispersive liquid-liquid microextraction; D-micro-SPE, Dispersive micro-solid phase extraction; DSDME, Directly suspended drop microextraction; EF, Enrichment factor; ETAAS, Electrothermal atomic absorption spectrometry; ETV-ICP-MS, Electrothermal vaporization-inductively-coupled plasma mass spectrometry; FAAS, Flame-atomic absorption spectrometry; GC-ECD, Gas chromatography-electron capture detector; GC-FID, Gas chromatography-flame ionization detector; GC-MS, Gas chromatography-mass spectrometry; HF, Hollow fiber; HPLC, high performance liquid chromatography; HS-SDME, Headspace-single-drop

1

Page 1 of 23

microextraction; IL, Ionic liquid; LOD, Limit of detection; LPME, Liquid-phase microextraction; MALDI-MS, Matrix-assisted laser desorption/ionization mass spectrometry; MNP, Magnetic nanoparticle; MS, Mass spectrometry; MW, Multi-walled; NP, Nanoparticle; ODT, Octadecane thiol; OS, Organic solvent; PAH, Polyaromatic hydrocarbon; pI, Isoelectric point; QD, Quantum dot; SLPME, Solid/liquid-phase microextraction; SPE, Solid-phase extraction; SDME, Single-drop microextraction; SPME, Solid-phase microextraction; SW, Single-walled; UV, Ultraviolet; VCH, Volatile covalent hydride * Corresponding author. Tel.: +34 986-812281; Fax: +34 986-812556. E-mail address: [email protected] (C. Bendicho)

1. Introduction Nanoscience and nanotechnology are rapidly expanding to almost every area, and new topics are continually emerging. Nanomaterials display unique optical, electronic, magnetic, and catalytic properties and have shown a number of interesting applications in different stages of the analytical process [1]. The spreading use of nanomaterials has also driven the development of analytical approaches suitable for their detection and characterization [2]. In line with their increased surface area and their ability to incorporate different functional groups on their surface, nanomaterials have direct application in liquid-solid sorption processes. Apart from that, other favorable properties include low resistance to diffusion, large adsorptive capability and fast sorption kinetics. Diverse nanomaterials have been tried as novel sorbents for preconcentration in solid-phase extraction (SPE) and solid-phase microextraction (SPME) [3]. Among them, we can highlight C-based materials, so fullerenes, carbon nanotubes (CNTs) and, more recently, sorbents based on graphene, nanodiamonds, nanocones and nanohorns were described as excellent solid phases for sorption. Other nanomaterials include noble-metal nanoparticles (NPs) and metal-oxide NPs. Magnetic solid phases have further advantages, since centrifugation or filtration steps are unnecessary with these sorbents, and the solid phase can be easily separated from the sample solution with the help of an external magnetic field. In recent years, liquid-phase microextraction (LPME) jointly with detection techniques suited for microvolume analysis saw a dramatic increase. Apart from achieving high enrichment factors (EFs), LPME techniques can integrate most pretreatment steps needed prior to analysis, such as matrix separation, filtration, and cleanup. Extractant volumes are minimal in LPME, which enhances the green profile of miniaturized methodologies, in accordance with green analytical chemistry concepts [4]. Several reviews focused on application areas, such as the environment [5], foods [6], and cosmetics [7], or highlighted relevant features, such as the greenness of procedures [8,9], novel extractants [10], automation [11], trace-element speciation [12,13], and combination with different detection techniques [14]. Many liquid extractants [e.g., organic solvents, aqueous solutions, and ionic liquids (ILs)] can be chosen according to the nature of the analytes and the matrices, thus providing a plethora of techniques and extraction modes. Nevertheless, further improvements are possible in order to overcome some drawbacks that may arise in the operation with LPME (i.e., low extraction efficiency, high matrix effects, and difficulties with the phase separation using some organic solvents). Recently, nanomaterials found applications in LPME techniques for different purposes (Fig. 1). Most relevant trends in this area deal with: (i) combination of LPME and SPME approaches in order to increase the potential of LPME – for example, to enhance the overall sorption capacity of solvents using a

2

Page 2 of 23

nanosorbent (e.g., carbon nanotubes apart from the organic solvent) or for retrieval of liquid extractants (e.g., ILs, and organic solvents); (ii) application of nanomaterials dispersed in a microvolume of organic solvent as affinity probes for extraction of peptides and proteins prior to matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS); (iii) use of noble-metal nanoprobes dispersed in a drop for trapping metal species (e.g., hydrides, and elemental Hg) prior to atomic spectrometry analysis; (iv) use of semiconductor nanocrystals [i.e., quantum dots (QDs)] dispersed in a drop for optical sensing with simultaneous preconcentration of target analytes in the drop; (v) sequential application of SPE involving nanostructured sorbents and dispersive liquid-liquid microextraction (DLLME); and, (vi) direct dispersion of NPs in the extractant phase for DLLME applications. Table 1 shows some examples of NPs mostly employed in LPME techniques together with the main advantages and the drawbacks. These approaches can open new avenues to the achievement of efficient, green and simple preconcentration or separation procedures, hence expanding the scope of microextraction techniques in many application areas. In this article, we present an overview of recent developments concerning the implementation of nanomaterials in LPME.

2. Nanoparticle-assisted hollow-fiber-liquid-phase microextraction (solid/liquid microextraction) Some LPME approaches can be reinforced using carbon nanotubes (CNTs) and metallic NPs. CNTs are formed by a graphene sheet shaped as a cylinder capped by fullerene-like structures. CNTs can be used in the form of single-walled CNTs (SWCNTs) or multi-walled CNTs (MWCNTs), the latter having enhanced interaction with analytes. CNTs have surfaces areas in the range 150–1500 m2g-1, which accounts for their excellent sorption properties [15]. CNTs have been employed as fiber coatings in the SPME technique, but they have the problem of aggregation, and the sample carryover effect in SPME fibers is difficult to remove [16]. In hollow-fiber-liquid-phase microextraction (HF-LPME), analyte extraction occurs in the pores of a hydrophobic hollow fiber, where the extractant is previously immobilized. This microextraction technique displays improved stability to the extractant phase at high stirring rates in the sample vial. CNTs can be held in the pores of a hollow fiber together with a microvolume of organic solvent (Fig. 2). Typically, for solid/liquid extraction, the pores and the lumen of hollow fibers reinforced with CNTs are filled with a microvolume of 1-octanol and the whole assembly is used for extraction in immersion-sampling mode. The analyte is retained by the organic solvent and CNTs simultaneously, which leads to enhanced extraction efficiency. This constitutes an example of a synergic use of two different extractants (solid/liquid) under the same microextraction mode. The successful application of this technique requires the CNTs to be fixed efficiently into the pores of the hollow fibers without covering their active surface. Immobilization of CNTs in the pores of the hollow fibers can be achieved by sol-gel technology, hence preventing aggregation and removing the carryover effect [16,17]. Some problems inherent to solgel technology include long preparation times and the inconvenience of prior oxidation of CNTs so that they can be efficiently dispersed. This process can affect their sorptive properties.

3

Page 3 of 23

Song et al. [18] dispersed CNTs in water by adding a surfactant and then they were held in the pores of hollow fibers by capillary forces and sonication. CNTs were impregnated with 1-octanol in order to improve their wettability. CNT-reinforced HF-LPME has been applied for the extraction of estrogens [16], pesticides [19], caffeic acid [20], and diuretics [21]. A porous polypropylene hollow fiber filled with organic solvent and reinforced with MWCNTs was sealed at both ends with magnetic stoppers and used a pseudo stir bar for extraction of beta-blockers prior to HPLC [22]. EFs were in the range 25.2–822. Apart from CNTs, other systems, such as TiO2-NPs, were used to reinforce hollowfiber membranes. Functionalized TiO2-NPs were applied to extract tylosin from milk samples with an EF of 540 [23]. TiO2 is easy to prepare and has excellent stability. Recently, Fe3O4/SiO2/TiO2 nanocomposite dispersed in 1-octanol was employed for extraction of non-steroidal anti-inflammatory drugs (NSAIDs) from human hair by HFSPME. The TiO2/SiO2 mixed oxide displays improved adsorptive characteristics in comparison with pure TiO2 [24]. The large surface area and the porosity of the nanosorbent allow EFs in the range 405–2450. HF-LPME with in-situ differential pulse anodic stripping voltammetry was employed for the determination of Hg using AuNPs sol-gel modified Pt-wire as working electrode [25]. An EF of 277 and a limit of detection (LOD) of 12 ng/L Hg were obtained. Table 2 includes a selected number of applications using CNTs in HF-LPME.

3. Magnetic nanoparticles for retrieving solvents in dispersive liquidliquid microextraction In conventional DLLME, organic solvents with higher density than water should be used so that they can be readily separated from the aqueous phase. A disperser solvent with high miscibility in both extractant and aqueous phase, such as methanol or acetone, is generally needed. When extractant and disperser agent are added to the aqueous sample, small droplets are formed, hence facilitating extraction. To recover the sediment phase at the bottom of the vial, it is necessary to centrifuge the cloudy solution. Typically, solvents used in DLLME include chloroform and chlorobenzene, which are very toxic, and extraction efficiency is not good for all analytes. When using low-density organic solvents less toxic than chlorinated solvents (e.g., octanol), additional operations to isolate the extractant phase are required, since, apart from centrifugation, refrigeration and thawing need to be applied [29]. Other extractants with enhanced greenness and potential application in DLLME are ILs. ILs used as extractants in LPME have a number of advantages, such as negligible vapor pressure, good thermal stability, and tunable miscibility with water and organic solvents. The replacement of those solvents by environment-friendly solvents, such as ILs, is therefore very attractive, but centrifugation is still necessary for phase separation. A possibility for the recovery of ILs after DLLME is the combination in sequence of DLLME with dispersive micro-SPE (D-micro-SPE). The latter technique can be considered a miniaturized version of conventional SPE, using dispersion of hydrophobic magnetic NPs (MNPs). Most MNPs contain Fe, Ni, Co and their oxides as the magnetic core [30]. Several applications following this dual extraction have appeared in the literature for polyaromatic hydrocarbons (PAHs) [29], acaricides [31], herbicides [32], pyrethroids [33], and toxic metals [34] (Table 3). In this technique, MNPs are employed as sorbents for retrieving the extractant containing the analytes, which are finally desorbed (e.g., by

4

Page 4 of 23

sonication). MNPs, employed in nanoscale magnetic separations, display a large surface area and high sorption capacity and can be isolated from the sample solution by an external magnetic field. In this way, centrifugation is not needed and extraction solvents are not limited to high-density solvents. In principle, any extractant solvent immiscible with water could be employed in DLLME and the whole procedure could be automated. Moreover, MNPs can be modified for the extraction of different organic solvents. In these applications, the extractant solvent used in DLLME becomes the target phase to be extracted by D-micro-SPE. For example, solvents, such as 1-octanol, have been employed for DLLME of pyrethroids, and the extract subjected to D-micro-SPE with Fe3O4-NPs functionalized with 3-aminopropyl triethoxysilane. [33]. DLLME of Cd(II) after derivatization with ammonium pyrrolidine-dithiocarbamate (APDC) to yield a hydrophobic compound is performed using a non-ionic surfactant and 1-octanol in aqueous medium. The extractant phase is collected by highly hydrophobic polysiloxanecoated core-shell Fe2O3@C-MNPs [40]. Addition of a disperser solvent so that small droplets are formed could be omitted, since high-speed stirring to break 1-octanol into fine droplets could be enough to achieve fast extraction [29]. However, a drawback could be the need for vigorous vortex stirring, which requires the use of specialized vortex apparatus. Giokas et al. [48] reported a two-step extraction technique combining cloud-point extraction (CPE) with D-micro-SPE. Analytes were first extracted by CPE using a nonionic surfactant and then polysiloxane-coated core-shell Fe2O3@C-MNPs were used for retrieving the micellar phase. This approach eliminated the typical stages involved in CPE, such as centrifugation and refrigeration of the micellar phase. The target analytes were back-extracted into water-immiscible organic solvents for their analysis by liquid chromatography. Extractant removal (1-octanol) by Fe3O4-NPs has also been implemented in effervescence-assisted DLLME. The mixture of 1-octanol and Fe3O4-NPs in acetic acid was injected into the aqueous sample, previously fortified with carbonate. CO2 bubbles are in situ generated so that easy dispersion of the extractant solvent is feasible [32]. Magnetic MWCNTs (MMWCNTs) were used for retrieving an IL used for DLLME of Cd and As chelates prior to detection by electrothermal-atomic absorption spectrometry (ETAAS). LODs and precision improved in comparison with those of other preconcentration methods [49].

4. Affinity nanoprobes for liquid-phase microextraction of biomolecules LPME has proved useful for separation and preconcentration of organic compounds (i.e., amino acids, pesticides, and surfactants), but extraction of large biomolecules, such as peptides and proteins, is troublesome. For proteomics, protein-digestion reactions can be carried out in solution or in gel and the fragments can be detected by MALDI-MS. Severe matrix effects can limit the power of this analytical technique, so sample clean-up is the most important step for isolation of interferents from complex biological samples. The combination of nanomaterials and LPME techniques can provide efficient miniaturized analytical approaches to accomplish fast bioassays by MALDI-MS. Some metal NPs can serve as affinity probes for bioanalysis by MALDI-MS. Teng et al. [50] first described the use of AuNPs as probes for trapping target species from the sample prior to MALDI-MS. The trapping mechanism lies in the electrostatic interaction between charged stabilizers at the surface of AuNPs and the oppositely-

5

Page 5 of 23

charged species from the sample (e.g., proteins and peptides). In addition, a magnetic field can be applied for fast separation when AuNPs adhere to magnetite through S-Au bonds. Apart from preconcentration, a further effect is removal of interferences due to salts and surfactants in the sample. Tan et al. [51] employed TiO2-coated Fe3O4-NPs as capture probes and matrix removal for the analysis of phosphopeptides. The NPs were retained by physical adsorption onto the stainless-steel target. This approach allowed significant simplification of analytical operations and reduced sample loss. Hasan et al. [52] reported the use of TiO2-NPs as multifunctional nanoprobes (desalting, accelerating and affinity probes) for the analysis of phosphoproteins. Due to the photocatalytic properties of TiO2-NPs, absorption of microwave radiation can boost digestion of phosphoproteins and facilitate ionization of phosphopeptides. Sudhir et al. [53] reported the use of AuNPs coated with tetraalkylammonium bromide in toluene as electrostatic probes in direct immersion-single-drop microextraction (DI-SDME) for the preconcentration of peptides in biological samples, such as urine prior to MALDI-MS. In DI-SDME, an immiscible extractant drop is directly exposed to the aqueous sample (Fig. 3). This constitutes an inexpensive, easyto-operate, quick approach to identify peptides. An efficient clean-up is also achieved by excluding matrix components. Samples can be directly deposited onto target plates for MALDI-MS analysis without sample loss. It is based on the phenomenon of isoelectric point (pI) of peptides. Above their pIs, peptides and proteins display a positive charge. AuNPs coated with tetralkylammonium bromide display a positive charge due to the tetraalkylammonium ions located at the surface of the AuNPs. The same authors [54] pointed out that AgNPs exhibited higher affinity to extract sulfur-bearing peptides. In this way, neutral peptides were not extracted. The method is useful for rapid analysis of peptide mixtures in the presence of matrix concomitants. Moreover, there is no need to wash or to separate the NPs after extraction, which prevents sample losses. Samples can be directly deposited onto target plates for MALDI-MS analysis. AgNPs coated with hydrophobic ligands, such as dodecanethiol and octadecanethiol, were also tried with the aim of extracting neutral peptides and proteins via hydrophobic interactions. Nevertheless, these interactions take a long time for extraction (1.5 h). Electrostatic interactions are stronger than hydrophobic interactions, and the extraction time can be reduced from 1.5 h to 2 min. Shrivas and Wu [55] used AgNPs coated with hydrophobic ligands in toluene for separation and preconcentration of proteins, such as gramicidin and larger proteins (myoglobin, ubiquitin and BSA). In this case, directly suspended drop microextraction (DSDME) was employed. AgNPs prevented sample losses, facilitated the sample cleanup and assisted signal enhancement of peptides and proteins in MALDI-MS analysis. Co3O4-NPs modified with cetyltrimethylammonium and dispersed in toluene were employed by Srivas and Wu for extraction of proteins [56]. These metal-oxide NPs have very high affinity for binding to phosphate-compounds, such as DNA, RNA, phosphopeptides and phosphoproteins. Sensitivity is enhanced and extraction is speeded up in comparison with other NPs used for microextraction prior to MALDI-MS. Bhat and Wu [57] used PdNPs modified with octadecane thiol (ODT) in toluene for selective extraction of proteins (insulin, ubiquitin, and lysozyme) from a variety of samples (e.g., pancreas, mushroom, and milk). The pH for the highest extraction efficiency was found at pH = pI, as a result of the hydrophobic interactions between proteins with Pd-ODT-NPs.

6

Page 6 of 23

Kailasa and Wu [58] used Ag2Se-NPs coated with octadecanethiol and 11mercaptoundecanoic acid to extract peptides in the presence of high concentrations of matrix interferences (urea, triton X-100 and NaCl]. These workers used Mg(OH)2-NPs modified with oleic acid as hydrophobic affinity probes for extraction and preconcentration of some proteins (e.g., lipoproteins, membrane proteins, and waterinsoluble proteolipids from E. coli and B. subtilis) prior to MALDI-MS [59]. 12hydroxy octadecanoic acid (HQA)-modified BaTiO3-NPs were also studied as multifunctional probes as the matrix for phospholipids and as hydrophobic affinity probes for LLME of proteins in E. coli prior to their determination by MALDI-MS [60]. Shastri et al. [61] used AuNPs modified with 4-mercaptophenyliminomethyl)-2methoxyphenol in toluene as multifunctional probes (binary matrix, preconcentration, affinity and desalting) to detect peptides and proteins by MALDI-MS. High sensitivity is reached for the detection of proteins and peptides at low concentration (fmol range) by mixing the organic matrix with the microdroplets containing AuNPs. Table 4 shows a selected number of applications related to the use of affinity probes for LPME prior to MALDI-MS.

5. Noble-metal nanoprobes for liquid-phase microextraction Our group developed in-situ synthesized PdNPs confined in an aqueous drop for efficient trapping of volatile covalent hydrides (VCHs) for headspace (HS)-SDME. In this microextraction technique, an extractant drop is exposed from the needle tip of a syringe to the headspace above the sample. Nanosized Pd is formed as a result of the reduction of Pd(II) contained in the drop by hydrogen, which evolves following the decomposition of NaBH4 added for hydride generation. Catalytic decomposition of several VCHs has been demonstrated with this approach (Fig. 4). Advantages of this approach include high EFs, fast multiphase equilibrium, low matrix effects, removal of organic solvents for preconcentration and the possibility of metal speciation. The enriched drop can be easily analyzed by ETAAS for determination of several elements (e.g., As, Se, Hg, and Sb) [62–64]. Multielemental determinations are feasible when enriched drops are analyzed by electrothermal vaporization-inductively coupled plasma-mass spectrometry (ETV-ICPMS) [65]. This methodology is well suited to determination of trace levels of toxic elements in complex matrices. Seawater analysis is remarkably feasible without the problems inherent in the high salt contents that occur in the ETAAS technique. Thus, for the determination of Se by ETAAS [63], matrix effects caused by saline waters due to nitrate, sulfate and chloride are overcome. The removal of matrix effects makes possible Se determination in seawater by ETAAS without resorting to sophisticated background correction (e.g., based on the Zeeman effect), a system equipped with D2background correction being suitable. Moreover, an additional advantage is that the reduced noble metal behaves as a matrix modifier in the furnace, hence simplifying the whole methodology in ETAAS. Speciation analysis is also feasible {e.g., Sb(III) and total Sb [66], Se(IV) and total Se [63] and methylmercury [64]}. Green procedures for hydride (and cold-vapor) generation followed by SDME have also been reported. Thus, generation of Se vapors using photochemistry prior to collection by a Pd-containing aqueous drop eliminates the instability of drops located within the pressurized headspace due to the hydrogen excess. This approach achieves much better EFs and LODs compared to using chemical reducing agents, such as

7

Page 7 of 23

NaBH4 [67]. Other noble-metal ions, such as Pt(IV), can also be used, instead of Pd(II) [64].

6. Quantum-dot-based nanoprobes for luminescent assays following single-drop microextraction Quantum dots (QDs) have unique electronic, catalytic and optical properties as a result of the confinement of excited electrons and holes. QDs compare favorably to conventional organic fluorophores, since they display a broad absorption spectrum, a narrow, tunable and symmetric emission spectrum, large luminescence quantum yields, and stability against photobleaching. As fluorescent NPs, QDs have found application in several areas, such as chemistry, medicine and biology [68]. Interest has increased in the application of QDs to trace-element analysis [69]. A recognition event can occur in the drop when fluorescent NPs are confined in it. QDs of different composition (e.g., CdSe, and CdSe/ZnS) confined within an organic drop constitute a new platform for sensing some toxic elements after their conversion into volatile hydrides in the sample vial [70,71]. QDs are mostly applied in aqueous phase, but functionalization is needed to make them soluble, and that can lead to a decrease in the emission quantum yield and stability. Ideally, QDs can be employed in the organic phase where they perform better. Then, the challenge is how to put into contact the analyte to be detected and the QD in the organic phase so that a recognition event can occur. Thus, core-shell CdSe/ZnS QDs stabilized with hexadecylamine have been applied directly in an organic droplet for the detection of some volatile species in combination with a portable micro-fluorospectrometer [70]. Volatile species were incorporated into the sensing drop following HS-SDME. This integrated system allowed isolation of the target analyte, preconcentration and recognition in a single step. This approach allows a decrease by a factor of 500 in the consumption of QDs compared with QD-based assays in aqueous phase. Consequently, toxic wastes containing toxic elements from the QD composition (e.g., Cd, and Se) are kept to a minimum. Besides, no functionalization of QDs is needed, their dispersion in the organic solvent being enough for sensing. The system has proved to be sensitive to Se(IV), methylmercury (MeHg+), ionic mercury, methylcyclopentadienyl-Mntricarbonyl (MMT) and H2S. Those species caused the fluorescence quenching following solubilization in the drop containing QDs. The quenching mechanism has been studied in depth for Se(IV) using different characterization techniques (e.g., luminescence lifetime, transmission electron microscopy, and atomic force microscopy) [71]. Trapping SeH2 in an organic drop containing CdSe causes binding between Se(-II) and Cd2+ present in the surface of QDs (Fig. 5). The latter process causes the stabilizing hexadecylamine groups to be lost, hence provoking the aggregation of QDs, and, in turn, fluorescence quenching. An LOD of 0.08 μg/L and a repeatability expressed as relative standard deviation of 4.6% were obtained for the detection of Se. Luminescence enhancement has been reported by the Valcarcel’s group for the detection of volatile trimethylamine in fish following the above technique. In this case, the sensing drop contained an IL apart from CdSe/ZnS QDs [72]. A LOD of 14 μg/L can be achieved. QDs can also cause chemiluminescence when they react with an oxidant. The presence of certain chemical species can, in turn, cause enhancement or inhibition of the chemiluminescent reaction. CdSe-QDs have been immobilized onto glass microvials to

8

Page 8 of 23

produce solid-state chemiluminescence. [73]. This approach has proved sensitive for Sb(III), Se(IV) and Cu(II). For an adequate selectivity of the process, liquid-LLME has been implemented prior to the chemiluminescent reaction. With this approach, the chemiluminescent signal increased 100-fold compared with assays carried out in bulk solution. Sb speciation in waters can be easily performed and an LOD of 6 ng/L Sb achieved.

7. Sequential approaches using solid and liquid-phase extraction The combination of SPE and DLLME has provided further improvements in EFs, which is advantageous for detection at ultratrace levels. SPE using MWCNTs/Fe3O4 composites was employed for preconcentration of azide. After elution, DLLME was employed on the eluate. Finally, azide in the extractant organic solvent was determined by UV-vis spectrophotometry [74]. An EF of 250 was obtained. Zhao et al. [75] combined SPE using MWCNTs and DLLME for analysis of herbicides by GC-MS, with an EF of 6000 and LODs in the range 0.002–0.006 μg/L. Mirzael et al. [76] used SPE with MWCNTs followed by DLLME based on solidification of floating organic drop (SFO) for determination of organochlorine pesticides (OCPs) by gas chromatography with electron-capture detection (GC-ECD). EFs in the range 8280–28,221 were obtained. Mehdinia et al. [77] developed sequential extraction of PAHs using Au-immobilized magnetic mesoporous silica NPs for magnetic SPE followed by DLLME with chloroform. Detection was carried out by GC-flame-ionization detection (GC-FID). This combined procedure allows achieving EFs in the range of 5519-6271 and LODs of 0.002–0.004 μg/L.

8. Dispersive liquid-liquid microextraction using nanoparticles directly dispersed in the extractant phase Different nanomaterials can be directly dispersed in an organic extractant and applied to the preconcentration of analytes following the DLLME technique. For example, Martinis et al. [78] reported the dispersion of PdNPs in toluene for the determination of Hg(II) in waters. For this purpose, dodecanethiolate-coated Pd monolayer-protected clusters were previously synthesized. Once Hg was extracted in the organic phase, it was directly determined by ETAAS. An enhancement factor of 95 and an LOD of 7.5 ng/L Hg were obtained. Motevally et al. [79] reported a DLLME method using tetraalkylammonium bromide-coated AgNPs prepared in chloroform as electrostatic probes for the preconcentration of terazosin. The settled phase was transferred to a micro-cell for fluorimetric determination. It was pointed out that electrostatic forces caused by AgNPs were much stronger than hydrophobic forces. Shi et al. [80] described a new LPME approach based on the use of silica-coated MNPs and 1-octanol as the extractant solvent for the preconcentration of 16 PAHs prior to determination by GC-MS. 1-octanol was efficiently confined within the silica-coated NPs, which prevented it from being lost. EFs and LODs were in the range 102–173 and 16.8–56.7 ng/L, respectively. Agitation by reciprocating movement of the external magnet was applied so as to facilitate microextraction. Lopez-Garcia et al. [81] reported application of CPE in the presence of AgNPs to speciation of Cr by ETAAS at the ng/L level. An EF of 1150 was obtained. When

9

Page 9 of 23

ethylenediamine tetraacetate was added to the medium, the content of Cr(VI) was measured. Without addition of complexing agent, the concentration of total Cr was obtained. The content of Cr(III) was estimated by difference. Polo-Luque et al. [82] combined CNTs and ILs directly coupled in-line to CE for sample pre-treatment. The synergic combination was used for preconcentration of nitrophenols. Limits of quantification in the range 0.65–0.83 μg/L were obtained. Abbasghorbani et al. [83] used solvent-assisted micro-SPE for the determination of parabens in water and cosmetic samples. Aminopropyl-functionalized MNPs together with hexyl acetate were used. EFs in the range 217–1253 were achieved with LODs in the range 50–300 ng/L.

9. Conclusions At present, nanostructured materials play an important role in the development of novel microextraction approaches. The need to accomplish faster, simpler and more efficient LPME applications has led to the use of mixed techniques involving NPs for different purposes. Thus, higher preconcentration factors and better LODs can be achieved in comparison with using conventional LPME techniques. Many operations required for sample preparation prior to analysis are reduced and/or removed. Some examples shown in this overview include the use of multifunctional NPs for analysis of proteins and peptides by MALDI-MS, NPs as trapping probes and matrix modifiers in ETAAS, NPs as solid sorbents that boost the extraction ability of organic solvents, and NPs as sensing probes integrated in LPME. We expect that further advances in the preparation of NPs with improved properties (e.g., composite NPs) in combination with LPME techniques will drive innovative research in different areas of interest. Additional studies to enhance the stability of NPs confined in solvent microvolumes and investigations on simpler, more efficient approaches to immobilization onto solid substrates should also be undertaken. Acknowledgements Financial support from the Spanish Ministry of Economy and Competitiveness (Project CTQ2012-32788) and the European Commission (FEDER) is gratefully acknowledged. The Spanish Ministry of Education, Culture and Sport is acknowledged for financial support through an FPU Predoctoral Grant to V. Romero. References [1] R. Lucena, B.M. Simonet, S. Cárdenas, M. Valcárcel, Potential of nanoparticles in sample preparation, J. Chromatogr. A 1218 (2011) 620-637 [2] C. Blasco, Y. Picó, Determining nanomaterials in food, TrAC, Trends Anal. Chem, 30 (2011) 84-99 [3] K. Pyrzynska, Use of nanomaterials in sample preparation, TrAC, Trends Anal. Chem. 43 (2013) 100-108 [4] A. Gałuszka, Z. Migaszewiski, J. Namieśnik, The 12 principles of green analytical chemistry and the significance mnemonic of green analytical practices, Trends Anal. Chem. 50 (2013) 78-84

10

Page 10 of 23

[5] C. Mahugo-Santana, Z. Sosa-Ferrera, M.E. Torres-Padron, J.J. Santana-Rodriguez, Application of new approaches to liquid-phase microextraction for the determination of emerging pollutants, TrAC, Trends Anal. Chem. 30 (2011) 731-748 [6] P. Viñas, N. Campillo, I. López-García, M. Hernández-Cordoba, Dispersive liquidliquid microextraction in food analysis. A critical review, Anal. Bioanal. Chem. 406 (2014) 2067-2099 [7] N. Cabaleiro, I. De La Calle, C. Bendicho, I. Lavilla, An overview of sample preparation for the determination of parabens in cosmetics, TrAC, Trends Anal. Chem. 57 (2014) 34-46. [8] F. Pena-Pereira, I. Lavilla, C. Bendicho, Liquid-phase microextraction techniques within the framework of green chemistry, TrAC, Trends Anal. Chem. 29 (2010) 617628 [9] A. Spietelun, L. Marcinkowski, M. de la Guardia, J. Namiesnik, Green aspects, developments and perspectives of liquid phase microextraction techniques, Talanta 119 (2014) 34-45 [10] M. Trujillo-Rodriguez, P. Rocio-Bautista, V. Pino, A.M. Afonso, Ionic liquids in dispersive liquid-liquid microextraction, TrAC, Trends Anal. Chem. 51 (2013) 87-106 [11] F. Maya, B. Horstkotte, J.M. Estela, V. Cerdá, Automated in-syringe liquid-liquid microextraction, TrAC, Trends Anal. Chem. 59 (2014) 1-8 [12] F. Pena-Pereira, I. Lavilla, C. Bendicho, Miniaturized preconcentration methods based on liquid-liquid extraction and their application in inorganic ultratrace analysis and speciation: A review, Spectrochim. Acta Part B 64 (2009) 1-15 [13] A.N. Anthemidis, C. Mitani, Advances in liquid phase microextraction for metal, metalloid and organometallic species determination, Curr. Anal. Chem. 9 (2013) 250278 [14] F.J. Pena-Pereira, I. Lavilla, C. Bendicho, Liquid-phase microextraction approaches combined with atomic detection: A critical review, Anal. Chim. Acta 669 (2010) 1-16 [15] B.-T. Zhang, X. Zheng, H.-F. Li, J.-M. Lin, Application of carbon-based nanomaterials in sample preparation: A review, Anal. Chim. Acta 784 (2013) 1-17. [16] Y. Yang, J. Chem, Y.-P. Shi, Determination of diethylstilbestrol in milk using carbon nanotube-reinforced hollow fiber solid-phase microextraction combined with high performance liquid chromatography, Talanta 97 (2012) 222-228 [17] H. Bagheri, Z. Ayazi, A. Aghakhani, A novel needle trap sorbent based on carbon nanotube-sol–gel for microextraction of polycyclic aromatic hydrocarbons from aquatic media, Anal. Chim. Acta , 683 (2011) 212-220.

11

Page 11 of 23

[18] X.-Y. Song, Y.-P. Shi, J. Chen, Carbon nanotubes-reinforced hollow fiber solidphase microextraction couple with high performance liquid chromatography for the determination ofcarbamate pesticides in apples, Food Chem., 139 (2013) 246-252 [19] G. Zhao, C. Wang, Q. Wu, Z. Wang, Determination of carbamate pesticides in water and fruit samples using carbon nanotube reinforced hollow fiber liquid-phase microextraction followed by high performance liquid chromatography, Anal. Meth. 3 (2011) 1410-1417. [20] Z. Es’haghi, M.A. Golsefidi, A. Saify, A.A. Tanha, Z. Rezaeifar, Z. Alian-Nezhadi, Carbon nanotube reinforced hollow fiber solid/liquid phase microextraction: A novel extraction technique for the measurement of caffeic acid in Echinacea purpurea herbal extracts combined with high-performance liquid chromatography, J. Chromatogr. A 1217 (2012) 2768-2775. [21] T.-T. Ho, Z.-G. Li, H.-Y. Lin, M.-R. Lee, Determination of diuretics in urine using immobilized multi-walled carbon nanotubes in hollow fiber-liquid-phase microextraction combined with liquid chromatography-Tandem mass spectrometry, J. Chin. Chem. Soc. 60 (2013) 1033-1042 [22] A. Sarafraz-Yazdi, M. Reza, Z. Es’haghi, Preconcentration and determination of beta-blockers using carbon nanotube-assisted pseudo-stirbar hollow fiber solid-/liquidphase microextraction and high-performance liquid chromatography with fluorescence detection, J. Liq. Chromatogr. R T 36 (2013) 750-769 [23] N. Sehati, N. Dalali, S. Soltanpour, M.S.S. Dorraji, Extraction and preconcentration of tylosin from milk samples through functionalized TiO2 nanoparticles reinforced with a hollow fiber membrane as a novel solid/liquid-phase microextraction technique, J. Sep. Sci. 37 (2014) 2025-2031 [24] Z. Es’hagui, E. Esmaeli-Shahri, Sol–gel-derived magnetic SiO2/TiO2 nanocomposite reinforced hollowfiber-solid phase microextraction for enrichment of non-steroidal anti-inflammatory drugs from human hair prior to high performance liquid chromatography, J. Chromatogr. B, 973, 2014, 142-151). [25] A. A. Ensafi, A. R. Allafchian, M.Saraji, B.Farajmand, In situ differential pulse anodic stripping voltammetry combined with hollow fiber-based liquid-three phase microextraction for determination of mercury using Au-nanoparticles sol-gel modified Pt-wire, Talanta, 99 (2012) 335-341 [26] Z. Es’haghi, M.A.-K. Khooni, T. Heidari, Determination of brilliant green from fish pond water using carbon nanotube assisted pseudo-stir bar solid/liquid microextraction combined with UV-vis spectroscopy-diode array detection, Spectrochim. Acta Part A 79 (2011) 603-607 [27] X.-Y. Song, Y.-P. Shi, J. Chen, A novel extraction technique based on carbon nanotubes reinforced hollow fiber solid/liquid microextraction for the measurement of piroxicam and diclofenac combined with high performance liquid chromatography, Talanta 100 (2012) 153-161.

12

Page 12 of 23

[28] C. Wang, Q. Wu, C. Wu, Z. Wang, Determination of some organophosphorus pesticides in water and watermelon samples by microextraction prior to highperformance liquid chromatography, J. Sep. Sci. 34 (2011) 3231-3239 [29] Z.-G. Shi, H.K. Lee, Dispersive liquid-liquid microextraction coupled with dispersive micro-solid-phase extraction for the fast determination of polycyclic aromatic hydrocarbons in environmental water samples, Anal. Chem. 82 (2010) 1540-1545. [30] M. Wierucka, M. Biziuk, Application of magnetic nanoparticles for magnetic solidphase extraction in preparing biological, environmental and food samples, TrAC, Trends Anal. Chem. 59 (2014) 50-58 [31] J. Zhang, M. Li, Y. Li, Z. Li, F. Wang, Q. Li, W. Zhou, R. Lu, H. Gao, Application of ionic-liquid-supported magnetic dispersive solid-phase microextraction for the determination of acaricides in fruit juice samples, J. Sep. Sci. 36 (2013) 3249-3255 [32] G. Lasarte-Aragones, R. Lucena, S. Cardenas, M. Valcárcel, Effervescence assisted dispersive liquid-liquid microextraction with extractant removal by magnetic nanoparticles, Anal. Chim. Acta 807 (2014) 61-66. [33] S. Mukdasai, C. Thomas, S. Srijaranai, Two-step microextraction combined with high performance liquid chromatographic analysis of pyrethroids in water and vegetable samples, Talanta 120 (2014) 289-296. [34] N. Jalbani, M. Solyak, Separation-preconcentration of nickel and lead in food samples by a combination of solid-liquid dispersive extraction using SiO2 nanoparticles, ionic liquid-based dispersive liquid-liquid microextraction, Talanta 131 (2015) 361-365. [35] J. Zhang, M. Li, M. Yang, B. Peng, Y. Li, W. Zhou, H. Gao, R. Lu, Magnetic retrieval of ionic liquids: fast dispersive liquid-liquid microextraction for the determination of benzoylurea insecticides in environmental water samples, J. Chromatogr. A 1254 (2012) 23-29. [36] M. Li, J. Zhang, Y. Li, B. Peng, W. Zhou, H. Gao, Ionic liquid-linked dual magnetic microextraction: A novel and facile procedure for the determination of pyrethroids in honey samples, Talanta 107 (2013) 81-87. [37] E. Yilmaz, M. Soylak, Ionic liquid-linked dual magnetic microextraction of Pb(II) from environmental samples prior to its micro-sampling flame atomic absorption spectrometric determination, Talanta 116 (2013) 882-886. [38] K. Soo-Tay, N.A. Rahman, M.R. Bin-Abas, Magnetic nanoparticle assisted dispersive liquid-liquid microextraction for the determination of 4-n-nonylphenol in water, Anal. Meth. 5 (2013) 2933-2938. [39] S. Mukdasai, C. Thomas, S. Srijaranai, Enhancement of sensitivity for the spectrophotometric determination of carbaryl using dispersive liquid-microextraction combined with dispersive u-solid phase extraction, Anal. Meth. 5 (2013) 789-796.

13

Page 13 of 23

[40] K.M. Giannoulis, D.L. Giokas, Q. Zhu, G.Z. Tsogas, A.G. Vlessidis, Q. Pan, Surfactant-enhanced liquid-liquid microextraction coupled to micro-solid phase extraction on highly hydrophobic magnetic nanoparticles, Microchim. Acta 180 (2013) 775-782. [41] H. Fu, L. Wang, C. Fan, X. Li, B. Liang, Determination of log P by dispersive liquid/liquid microextraction coupled with derivatized magnetic nanoparticles predispersed in 1-octanol phase, Anal. Sci. 28 (2012) 589-594. [42] K. Motevalli, Z. Yaghoubi, Trace determination of gatifloxacin in pharmaceutical and biological samples using hydrophobic magnetic nanoparticles-assisted ionic liquid microextraction coupled with spectrofluorimetry, Int. J. Nano Dimens. 4 (2013) 13-20. [43] S. Khan, T.G. Kazi, M. Soylak, Rapid ionic liquid-based ultrasound assisted dual magnetic microextraction to preconcentrate and separate cadmium-4-(2-Thiazolylazo)resorcinol complex from environmental and biological samples, Spectrochim. Acta Part A 123 (2014) 194-199. [44] M. Hasehmi, Z. Taherimaslak, S. Parvizi, M. Torkejokar, Spectrofluorimetric determination of Zearalenone using dispersive liquid-liquid microextraction coupled to micro-solid phase extraction onto magnetic nanoparticles, RSC adv. 4 (2014) 4506545073 [45] Y. Li, X. Yang, J. Zhang, M. Li, X. Zhao, K. Yuan, X. Li, R. Lu, W. Zhou, H. Gao, Ultrasound-assisted emulsification magnetic microextraction: a fast and green method for the determination of triazole fungicides in fruit juice, Anal. Meth. 6 (2014) 83288336 [46] M.A. Habila, Z.A. Alothman, M. Soylak, Fe3O4 nanoparticles and ultrasound assisted dispersive liquid-liquid microextraction of lead(II) for its microsampling flame atomic absorption spectrometric determination in food and environmental samples, RSC adv. 4 (2014) 55610-55614. [47] Z. Taherimaslak, M. Amoli-Diva, M. Allahyari, K. Pourghazi and M. H. Manafi, Low density solvent based dispersive liquid–liquid microextraction followed by vortexassisted magnetic nanoparticle based solid-phase extraction and surfactant enhanced spectrofluorimetric detection for the determination of aflatoxins in pistachio nuts, RSC Adv., 2015, 5, 12747-12754 [48] D.L. Giokas, Q. Zhu, Q. Pan, A. Chisvert, Cloud point-dispersive micro-solid phase extraction of hydrophobic organic compounds onto highly hydrophobic core-shell Fe2O3@C magnetic nanoparticles, J. Chromatogr. A 1251 (2012) 33-39. [49] M. Shirani, A. Semnani, S. Habibollahi and H. Haddadi, Ultrasound-assisted, ionic liquid-linked, dualmagnetic multiwall carbon nanotube microextraction combined with electrothermal atomic absorption spectrometry for simultaneous determination of Cd and As in food samples, J. Anal. At. Spectrom. 2015, DOI: 10.1039/c4ja00481g.

14

Page 14 of 23

[50] C.-H. Teng, K.-C. Ho, Y.-S. Lin, Y.-C. Chen, Gold nanoparticles as selective and concentrating probes for samples in MALDI-MS analysis, Anal. Chem. 76 (2004) 43374342. [51] F. Tan, Y. Zhang, J. Wang, J. Wei, P. Qin, Y. Cai, X. Qian, Specific capture of phosphopeptides on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry targets modified by magnetic affinity nanoparticles, Rapid Commun. Mass Spectrom. 21 (2007) 2407-2414. [52] N. Hasan, H.-F. Wu, Y.-H. Li, M. Nawaz, Two-step on-particle ionization/enrichment via a washing- and separation- free approach: multifunctional TiO2 nanoparticles as desalting, accelerating and affinity probes for microwave-assisted tryptic digestion of phosphoproteins in ESI-MS and MALDI-MS: comparison with microscale TiO2, Anal. Bioanal. Chem. 396 (2010) 2909-2919. [53] P.-R. Sudhir, H.-F. Wu, Z.-C. Zhou, Identification of peptides using gold nanoparticle-assisted single-drop microextraction coupled with AP-MALDI Mass Spectrometry, Anal. Chem. 77 (2005) 7380-7385. [54] P.R. Sudhir, K. Shrivas, Z.-C. Zhou, H.-F. Wu, Single drop microextraction using silver nanoparticle as electrostatic probes for peptide analysis in atmospheric pressure matrix-assisted lase desorption/ionization mass spectrometry and comparison with gold electrostatic probes and silver hydrophobic probes, Rapid Commun. Mass Spectrom. 22 (2008) 3076-3086. [55] K. Shrivas, H.-F. Wu, Modified silver nanoparticle as a hydrophobic affinity probe for analysis of peptides and proteins in biological samples by using liquid-liquid microextraction coupled to AP-MALDI-Ion trap and MALDI-TOF mass spectrometry, Anal. Chem. 80 (2008) 2583-2589. [56] K. Shrivas, H.-F. Wu, Rapid and highly sensitive protein extraction via cobalt oxide nanoparticle-based liquid-liquid microextraction coupled with MALDI mass spectrometry, Analyst 137 (2012) 890-895. [57] A.R. Bhat, H.-F. Wu, Synthesis, characterization and application of modified Pd nanoparticles as preconcentration probes for selective enrichment/analysis of proteins via hydrophobic interactions from real-world samples using nanoparticle-liquid-liquid microextraction coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Rapid Commun. Mass Spectrom. 24 (2010) 3547-3552. [58] S.K. Kailasa, H.-F. Wu, Surface modified silver selinide nanoparticles as extracting probes to improve peptide/protein detection via nanoparticles-based liquid phase microextraction coupled with MALDI mass spectrometry, Talanta 83 (2010) 527-534. [59] S.K. Kailasa, H.-F. Wu, Dispersive liquid-liquid microextraction using functionalized Mg(OH)2 NPs with oleic acid as hydrophobic affinity probes for the analysis of hydrophobic proteins in bacteria by MALDI-MS, Analyst 137 (2012) 44904496.

15

Page 15 of 23

[60] S.K. Kailasa, H.-F. Wu, Surface modified BaTiO3 nanoparticles as the matrix for phospholipids and as extracting probes for LLME of hydrophobic proteins in Escherichia coli by MALDI-MS, Talanta 114 (2013) 283-290. [61] L. Shastri, S.K. Kailasa, H.-F. Wu, Nanoparticle-single drop microextraction as multifunctional and sensitive nanoprobes: Binary matrix approach for gold nanoparticles modified with (4-mercaptophenyliminomethyl-2-methoxyphenol for peptide and protein analysis in MALDI-TOF-MS, Talanta 81 (2010) 1176-1182. [62] S. Fragueiro, I. Lavilla, C. Bendicho, Headspace sequestration of arsine onto a Pd(II)-containing aqueous drop as a preconcentration method for electrothermal atomic absorption spectrometry, Spectrochim. Acta Part B 59 (2004) 851-855. [63] S. Fragueiro, I. Lavilla, C. Bendicho, Hydride generation-headspace single-drop microextraction-electrothermal atomic absorption spectrometry method for determination of selenium in waters after photoassisted prereduction, Talanta 68 (2006) 1096-1101. [64] S. Gil, S. Fragueiro, I. Lavilla, C. Bendicho, Determination of methylmercury by electrothermal atomic absorption spectrometry using headspace single-drop microextraction with in situ hydride generation, Spectrochim. Acta Part B 60 (2005) 145-150. [65] S. Gil, M.T.C. de Loos-Vollebregt, C. Bendicho, Optimization of a single-drop microextraction method for multielemental determination by electrothermal vaporization inductively coupled plasma mass spectrometry following in situ vapor generation, Spectrochim. Acta Part B 64 (2009) 208-214. [66] F. Pena-Pereira, I. Lavilla, C. Bendicho, Headspace single-drop microextraction with in situ stibine generation for the determination of antimony (III) and total antimony by electrothermal-atomic absorption spectrometry, Microchim. Acta 164 (2009) 77-83 [67] R. Figueroa, M. García, I. Lavilla, C. Bendicho, Photoassisted vapor generation in the presence of organic acids for ultrasensitive determination of Se by electrothermalatomic absorption spectrometry following headspace single-drop microextraction, Spectrochim. Acta Part B 60 (2005) 1556-1563. [68] Q. Ma, X. Su, Recent advances and applications in QDs-based sensors, Analyst 136 (2011) 4883-4893. [69] I. Costas-Mora, V. Romero, I. Lavilla, C. Bendicho, An overview of recent advances in the application of quantum dots as luminescent probes to inorganic-trace analysis, TrAC, Trends Anal. Chem. 57 (2014) 64-72 [70] I. Costas-Mora, V. Romero, F. Pena-Pereira, I. Lavilla, C. Bendicho, Quantum dotbased headspace single-drop microextraction technique for optical sensing of volatile species, Anal. Chem. 83 (2011) 2388-2393. [71] I. Costas-Mora, V. Romero, F. Pena-Pereira, I. Lavilla, C. Bendicho, Quantum dots confined in an organic drop as luminescent probes for detection of selenium by

16

Page 16 of 23

microfluorospectrometry after hydridation: study of the quenching mechanism and analytical performance, Anal. Chem. 84 (2012) 4452-4459. [72] C. Carrillo-Carrión, B. Simonet, M. Valcárcel, (CdSe/ZnS QDs)-ionic liquid-based headspace single drop microextraction for the fluorimetric determination of trimethylamine in fish, Analyst 137 (2012) 1152-1159. [73] I. Costas-Mora, V. Romero, I. Lavilla, C. Bendicho, Solid-state chemiluminescence assay for ultrasensitive detection of antimony using on-vial immobilization of CdSe quantum dots combined with liquid-liquid-liquid microextraction, Anal. Chim. Acta 788 (2013) 114-121. [74] A.R. Zarei, R. Hajiaghabozorgy, Solid-phase extraction combined with dispersive liquid-liquid microextraction for the spectrophotometric determination of ultra-trace amounts of azide ion in water samples, Anal. Meth. 6 (2014) 5784-5791. [75] R.-S. Zhao, C.-P. Diao, Q.-F. Chen, X. Wang, Sensitive determination of amide herbicides in environmental water samples by a combination of solid-phase extraction and dispersive liquid-liquid microextraction prior to GC-MS, J. Sep. Sci. 32 (2009) 1069-1074 [76] M. Mirzael, M. Rakh, Preconcentration of organochlorine pesticides in aqueous samples by dispersive liquid-liquid microextraction based on solidification of floating organic drop after SPE with multiwalled carbon nanotubes, J. Sep. Sci. 37 (2014) 114119. [77] A. Mehdinia, E. Khojasteh, T. Baradaran-Kayyal, A. Jabbari, Magnetic solid-phase extraction using gold immobilized magnetic mesoporous silica nanoparticles coupled with dispersive liquid-liquid microextraction for determination of polycyclic aromatic hydrocarbons, J. Chromatogr. A 1364 (2014) 20-27. [78] E.M. Martinis, L.B. Escudero, R. Salvarezza, M.F. Calderón, F.J. Ibañez, R.G. Wuilloud, Liquid-liquid microextraction based on a dispersion of Pd nanoparticles combined with ETAAS for sensitive Hg determination in water samples, Talanta 108 (2013) 46-52. [79] K. Motevally, M. Zeeb, Dispersive liquid-liquid microextraction using silver nanoparticles as electrostatic probes for preconcentration and quantitative analysis of terazosin, Int. J. Nano Dimens. 1 (2011) 187-201. [80] Z.-G. Shi, Y. Zhang, H.-K. Lee, Ferrofluid-based liquid-phase microextraction, J. Chromatogr. A 1217 (2010) 7311-7315. [81] I. López-García, Y. Vicente-Martínez, M. Hernández-Córdoba, Nonchromatographic speciation of chromium at sub-ppb levels using cloud point extraction in the presence of unmodified silver nanoparticles, Talanta 132 (2015) 23-28. [82] M.L. Polo-Luque, B.M. Simonet, M. Valcárcel, Solid-phase extraction of nitrophenols in water by using a combination of carbon nanotubes with an ionic liquidcoupled in-line to CE, Electrophoresis 34 (2013) 304-308.

17

Page 17 of 23

[83] M. Abbasghorbani, A. Attaran, M. Payehghadr, Solvent-assisted dispersive microSPE by using aminopropyl-functionalized magnetite nanoparticle followed by GC-PID for quantification of parabens in aqueous matrices, J. Sep. Sci. 36 (2013) 311-319.

Captions Fig. 1. Representative examples of nanomaterials applied in liquid-phase microextraction. Fig. 2. Carbon-nanotube-reinforced hollow-fiber-liquid-phase microextraction. {Based on [19]}. Fig. 3. Gold nanoparticles (AuNPs) coated with tetraalkylammonium bromide and dispersed in toluene as electrostatic probes for the preconcentration of large biomolecules prior to matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). {Based on [53]}. Fig. 4. Trapping methylmercury hydride in an aqueous drop containing Pd(II). (Reactions for hydridization of methylmercury to yield volatile CH3HgH and reduction of Pd(II) to Pd(0) in the drop are shown). {Based on [64]}. Fig. 5. CdSe quantum dots confined in an organic drop for optical sensing Se(IV) following single-drop microextraction of selenium hydride. {Based on [71]}.

Table 1. Representative examples for the joint use of nanoparticles (NPs) and liquid-phase microextraction (LPME) techniques along with their advantages and drawbacks Type of NP Advantages Carbon nanotubes Improved EF and

LPME technique * Drawbacks HF-LPME Difficulties in the

Fe3O4 any organic

Analytical techniques ** HPLC, UV-vis Spectrophotometry

DLLME+ GC, HPLC, Need for vigorous stirring D-micro-SPE FAAS, ETAAS, (specialized vortex simplification of UV-Vis spectrometry, Procedures (no centrifugation) apparatus) Fluorimetry

LOD Use of solvent;

Au, Ag, Pd, Ag2Se, DI-SDME, DSDME, MALDI-MS Efficient cleanup; Extraction efficiency and BaTiO3; Co3O4, DLLME GC, ETAAS, diminished sample loss; signal enhancement can

18

Page 18 of 23

etc.). enhancement. (Organic drop)

strongly depend on

Pd, Pt HS-SDME preconcentration Drop instability in (Aqueous drop) hydride-forming elements Sb, etc.) and Hg; in situ

Vapor dilution in

modification

H2 excess.

Fluorimetry

signal

ETAAS

Efficient

ETV-ICP-MS the headspace;

of (As, Se, matrix

TiO2 DSDME MALDI-MS Improved digestion of Less sorptive HF-LPME UV-vis spectrometry signal properties than other enhancement in MALDI-MS; SiO2 surface area; sorption ability

proteins;

oxides (e.g., SiO2)

DLLME+ FAAS Need for centrifugation D-micro-SPE after D-micro-SPE

Large good

Quantum dots HS-SDME Fluorimetry Preconcentration; cleanup; Many variables (CdSe, CdSe/ZnS) sensing affecting fluorescence

in situ

* LPME techniques in which NPs have been implemented. ** Typical analytical techniques for which applications combining NPs and LPME have been described in the literature.

Table 2. Combination of liquid-phase microextraction (LPME) and solid-phase microextraction (SPME) [hollow-fiber (HF)-SLPME] using organic solvents and carbon nanotubes (CNTs) as sorbents.

Analytical technique

Analyte

Sample

19

Extractant phase*

EF

Page 19 of 23

LO

HPLC

Diethylstilbestrol

Milk

MWCNTs in HF-SPME

--

5.1

HPLC-DAD

Pesticides

Water, Fruit

OS+ MWCNTs

75-119

0.1

HPLC

Caffeic acid

OS+ MWCNTs

2018

0.0

LC-MS/MS

Diuretics

Urine

OS+ MWCNTs

---

0.1

HPLC

beta-blockers

Water

OS+ MWCNTs

25-822

1-1

Milk

OS+TiO2

540

0.2

OS+ Fe3O4/SiO2/TiO2

405-2450

---

OS+ MWCNTs

---

0.5

Herbal extracts

UV-vis spectrometry Tylosin

HPLC

Anti-inflammatory drugshuman hair

UV-vis spectrometry Brilliant green

Fish, pond water

HPLC

Piroxicam, Diclofenac

Water

OS+ MWCNTs

47/184

4.6

HPLC-DAD

Organophosphorus pesticides

Water watermelon

OS+ MWCNTs

--

0.1 1-1

OS, Organic solvent

Table 3.

20

Page 20 of 23

Combination of dispersive liquid-liquid microextraction (DLLME) and dispersive micro-solid-phase extraction (D-micro-SPE) using magnetic nanoparticles (MNPs) as sorbent

Analytical technique

Analyte

Sample

GC-MS

PAHs

Water

Octanol+ MNPs

HPLC

Acaricides

Fruit juice

IL+ Barium ferrite NPs

GC-MS

Triazine Herbicides

Water

Octanol+ Fe3O4 NPs

21-185

0.0

HPLC-UV

Pyrethroids

Water, vegetables

Octanol+ Fe3O4 NPs

51-108

0.0

FAAS

Pb (II), Ni (II)

Food samples

IL + SiO2 NPs

125

0.1 0.7

HPLC

Benzoylurea, Insecticides

Waters

IL+ Fe3O4 NPs

--

0.0

HPLC

Pyrethroids

Honey

IL+Fe3O4 NPs

--

0.0

AAS

Pb(II)

----

IL+Fe3O4 NPs

160

0.5

HPLC

4-n-nonylphenol

Water--

Octanol+C8MNPs

--

13.

Water, Fruits

Octanol+ Fe3O4 NPs

2730

8

UV-Vis spectrometry Carbaryl

21

Extractant phase*

EF

LO

110-186

11.

--

Page 21 of 23

0.0

FAAS

Cd(II)

Water

Octanol+ Fe2O3@C NPs

8

2.4

HPLC

Partition coefficients

Water

Octanol+ MNPs

--

--

Spectrofluorimetry

Gatifloxacin

Pharmaceutical, biological

IL + Fe3O4 NPs

50

0.0

FAAS

Cd(II)

Water, biological Samples

IL + Fe3O4 NPs

100

0.4

Spectrofluorimetry

Zearalenone

Corn samples

1-heptanol+ MNPs

--

0.2

GC-FID

Triazole fungicides

Fruit juice

Octanol+MNPs

--

1.8

FAAS

Pb (II)

Food, Environment

DLLME+ Fe3O4

--

8.5

Spectrofluorimetry

Aflatoxins

Pistachio nuts

1-heptanol+ MNPs

0.0

* IL, Ionic liquid; MNPs, Magnetic nanoparticles

Table 4. Affinity

probes

for

desorption/ionization

analysis

mass

of

biomolecules

spectrometry

by

(MALDI-MS)

matrix-assisted following

laser

liquid-phase

microextraction (LPME) Analytical technique

Analyte

Solvent

Affinity Microextraction probe

MALDI-MS

Peptides

Toluene

Au NPs

DI-SDME

MALDI-MS

Peptides

Toluene

Ag NPs

DI-SDME

22

mode

Page 22 of 23

MALDI-MS

Peptides, proteins

Toluene

Ag/ NPs,

DSDME

MALDI-MS

Proteins

Toluene

Co3O4 NPs

DSDME

MALDI-MS

Proteins

Toluene

Pd NPs

DSDME

MALDI-MS

Peptides/proteins

Toluene

Ag2Se

DSDME

MALDI-MS

Proteins

Toluene

Mg(OH)2 NPs

DLLME

MALDI-MS

Phospholipids

Toluene

BaTiO3 NPs

DSDME

MALDI-MS

Proteins

Toluene

Au NPs

DI-SDME

23

Page 23 of 23