Recent analytical applications of magnetic nanoparticles

Document Type: Review Paper

Author

Faculty of Food Industry and Agriculture, Department of Food science and Technology, Standard Research Institute (SRI), Karaj, Iran

Abstract

Analytical chemistry has experienced, as well as other areas of science, a big change due to the needs and opportunities provided by analytical nanoscience and nanotechnology. Now, nanotechnology is increasingly proving to be a powerful ally of analytical chemistry to achieve its objectives, and to simplify analytical processes. Moreover, the information needs arising from the growing nanotechnological activity are opening an exciting new field of action for analytical chemists. Magnetic nanoparticles have been used in various fields owing to their unique properties including large specific surface area and simple separation with magnetic fields. For Analytical applications, they have been used mainly for sample preparation techniques (magnetic solid phase extraction with different advanced functional groups (layered double hydroxide, β-cyclodextrin, carbon nanotube, graphen, polymer, octadecylsilane) and automation of it, microextraction techniques) enantioseparation and chemosensors. This review summarizes the basic principles and achievements of magnetic nanoparticles in sample preparation techniques, enantioseparation and chemosensors. Also, some selected articles recently published (2010-2016) have been reviewed and discussed.

Keywords


INTRODUCTION

Nanoscience has provided new dimensions to research and development in the modern world [1]. In recent years, nanosized materials have attracted much interest in the research community due to their unique size and physical properties. Nanomaterials have begun to revolutionize the world around us; they have been used in various scientific fields such as biotechnology, engineering, biomedical, environmental, catalysis, drug delivery and material science [1-12]. Nanotechnology has become an important technique that made it possible to work at the molecular and cellular levels to produce many recent advances in the field of research and development.

Among different types of nanomatererials (spheres, nanotubes, nanocages and nanohorns), nanoparticles (NPs) have attracted broad attention due to their potential applications in magnetic resonance imaging, drug delivery, catalysis, hyperthermia treatment, and analytical applications [1-3]. Therefore, during the past decade, great efforts have been devoted to the preparation of MNPs. MNPs have been synthesized with a number of different compositions and phases, including pure metals Fe, Co and Ni; metal oxides, such as Fe3O4 and γ-Fe2O3; ferrites, such as MFe2O4 (M = Cu, Ni, Mn, Mg, etc.); and metal alloys, such as FePt, CoPt [1-3]. During the last few years, a large portion of the published articles about MNPs have described efficient routes to attain shape-controlled, highly stable, and narrow size distribution MNPs. Up to date, several popular methods including co-precipitation, microemulsion, thermal decomposition, solvothermal, sonochemical, microwave-assisted, chemical vapour deposition, combustion synthesis, carbon arc, laser pyrolysis synthesis have been reported for the synthesis of MNPs. The details and advantages of each menthoined synthesis method have been previously reviewed by some research groups [1-3]. 

Analytical chemistry has experienced, as well as other areas of science, a big change due to the needs and opportunities provided by analytical nanoscience and nanotechnology. Now, nanotechnology is increasingly proving to be a powerful ally of analytical chemistry to achieve its objectives, and to simplify analytical processes. Moreover, the information needs arising from the growing nanotechnological activity are opening an exciting new field of action for analytical chemists [13].

The magnetism is nowadays one of the most exciting trends in analytical chemistry. Thus, analytical methodologies have started to take advantage of recent advances in the development of NPs, hybrid magnetic (nano) materials, or magnetic composites, to improve the performance of existing methodologies [13]. Magnetic forces offer great advantages in analytical applications as magnetic interactions are not influenced by chemical variables such as pH, concentration, or surface charges. In addition, they allow controlling fluid motion in microsystems, an important advance for chromatographic separations in microfluidic systems.

Recently, several reviews have summarized the synthesis, functionalization, characterization and application of magnetic nanoparticles in different fields of analytical chemistry, generally of specifically [1-3, 13-23]. In this review, we have summarized and discussed some selected recent applications of the advanced functionalized magnetic nanoparticles in analytical chemistry in sample preparation, enantioseparation and chemosensors techniques.

 

ANALYTICAL APPLICATION OF MAGNETIC NANOPARTICLES

Sample preparation techniques

Magnetic solid-phase extraction (MSPE)

Magnetic separation was first employed by Hẻden [24] in 1972 and he demonstrated the potential of magnetic separation for biologically active proteins. In 1973, Robinson et al. [25] used magnetic supports for the recovery of two enzymes from a stirred reactor. In 1996, Towler et al. [26] reported the preconcentration of Ra, Pb and Po from seawater samples by using a magnetic adsorbent (MnO on magnetite) followed by a collection of the adsorbent using a magnet.

 

Fig. 1. Schematic presentation of magnetic solid phase extraction (MSPE) [4]

 

However, the first analytical application (and the first use of the term M-SPE) was developed in 1999 by Šafařiková and Šafařik for the separation of a copper phthalocyanine dye using silanized magnetite [27]. M-SPE involves the addition of magnetic sorbent particles to the sample solution. The target compound is adsorbed onto the magnetic material and the magnetic particle (containing the analyte) is then separated from the sample solution by the application of an external magnetic field. Finally, the analyte is recovered from the adsorbent by elution with the appropriate solvent and  is subsequently analyzed. A general scheme for the M-SPE procedure is shown in Fig. 1. This approach has several advantages over traditional solid phase extraction: (i) it avoids time-consuming and tedious on-column SPE procedures, (ii) it provides a rapid and simple analyte separation that avoids the need for centrifugation or filtration steps, (iii) the magnetic sorbents synthesized to date have high selectivity, even when complex matrices from environmental or biological fields were, (iv) since the majority of sample impurities are diamagnetic, they do not interfere with magnetic particles during the magnetic separation step, and (v) automation of the whole process is possible with flow injection analysis and other related techniques, which leads to rapid, selective, sensitive and repeatable methods for routine determinations [16]. These advantages could be achieved as results of unique properties of magnetic nanoparticles including [13]:

1. High extraction efficiency because of the high surface area-to-volume ratio of the extraction phase;

2. Fast separation after extraction compared with conventional SPE methods;

3. Convenience of preparation and surface modification of the extraction phase (e.g., bare Fe3O4 can be simply and rapidly prepared by co-precipitation or hydrothermal synthesis, and can be conveniently modified with functional groups because of the abundant hydroxyls on the surface of Fe3O4 NPs);

4. High selectivity of the target analytes and suitability for the complicated matrices (suitable coating not only stabilizes the NPs and prevents their oxidation but also provides specific functionalities that can be selective for analytes);

5. Good reusability (magnetic particles can be reused after appropriate rinsing);

6. Excellent dispersibility in aqueous solution and easy to operate.

 

MSPE involving layered double hydroxide

In recent years, layered double hydroxides (LDHs), also known as hydrotalcite-like compounds and/or anionic clays, have attracted considerable attention as extraction sorbents, stabilizers, drug delivery agents, flame retardants and catalysts due to their special structure and unique properties, such as high anion-exchange capacity [28,29].

Due to the ease of the exchangeability of LDH interlayer anions with other anions, they have been applied for the adsorption of many harmful organic and inorganic compounds in aqueous. More recently, Sajid and Basheer reviewed LDH applications as emerging sorbent materials for analytical extractions [30].

LDHs have excellent adsorbing properties because of three major reasons:

(i) Large interlayer spaces (high porosity)

(ii) Huge number of exchangeable anions in between the positively charged layers

(iii) Water resistant structure.

LDHs have shown considerable applications as anion exchangers. Their high anion uptakes can be attributed to large surface area, high anion exchange capacities and highly tunable and flexible interlayer spaces. LDHs can adsorb anions via direct adsorption or anion exchange or by hydration of calcined LDH in an anion containing aqueous solution [31].

Layered, magnetic double hydroxide (MLDH) nanoparticles with large surface area, provide a low cost, three-dimensional structure that has demonstrated potential for use in drug delivery, catalysis, sensing, molecules and biology [32-34]. Orientation and dimensionality hierarchical structure as well as the large expandable inter layer free space make it easier to be further modified. Making MLDH magnetic facilitated an otherwise difficult solid–liquid separation, while the shell-type mesoporous structure shortens the diffusion path and increases the effective area, thus improving the adsorption capacity and extraction efficiency. Therefore, MLDH nanomaterials would be an ideal candidate sorbents for MSPE. Fe3O4-LDH has been used as a dissolvable sorbent for extraction of PPCPs [35], phenolic acids [36] and phthalate ester [37]. One of the distinct features of MLDH preparation is its very easy elution step. After adsorption and extraction from water, analytes were eluted from the MLDH by dissolving the double hydroxide layers containing the analytes by changing the pH of the solution.

Recently, Tang et al. [35] have reported an approach to d-SPE using dissolvable magnetic Fe3O4-layered double hydroxide core-shell microspheres as sorbent to enable automation of the integrative extraction and analytical processes. Through magnetic force, the sorbent, after extraction, was isolated from the sample and then dissolved by acid to release the analytes. Thus, the customary analyte elution step in conventional SPE was unnecessary. The automated d-SPE step was coupled to high-performance liquid chromatography (HPLC) with photodiode array detection for determination of several pharmaceuticals and personal care products (PPCPs) [acetylsalicylic acid (ASA), 2,5-dihydroxybenzoic acid (DBA), 2-phenylphenol (PP), and fenoprofen (FP)] in aqueous samples.

In the other research, Saraji and Chani [36] prepared a magnesium-aluminum layered double hydroxide coated on magnetic nanoparticles and used as a sorbent to extract some phenolic acids including p-hydroxy benzoic acid, caffeic acid, syringic acid, ρ-coumaric acid and ferulic acid from fruit juices. After extraction, the elution step was performed through dissolving double hydroxide layers containing the analytes by changing the solution pH. The limits of detection were between 0.44 and 1.3 μg L-1.

 

Fig. 2. Schematic illustration of the preparation of surfactants modified Fe3O4@SiO2@Mg–Al MLDH and its application for enrich analytes as SPE sorbents [28].

 

In other work, Zhao et al. [37] synthesized a novel type of layered, flowerlike magnetic double hydroxide (MLDH) nanoparticles modified by surfactants and applied as an effective sorbent for pre-concentration of several phthalate ester pollutants (PAEs) from water prior to quantification. The MLDH was obtained via a simple ultrasound-assisted method by using silica coated Fe3O4 as the core and anisotropic Mg-Al layered double hydroxide (Mg-Al LDH) nanocrystals as the shell to which analytes were absorbed (Fig. 2). Orientation and dimensionality hierarchical structure as well as the large expandable interlayer free space and positive charge of the Mg-Al LDH shell make it easier to form anionic surfactant micelles on its surface via self-assembly. Due to its high adsorption area, compared with non-mesoporous nano solid-phase extraction agents, mesoporous channel shell and reduction diffusion path, MLDH exhibited high extraction efficiency of organic target residues. Under optimized conditions, the limits of detection were in the range of 12.3-36.5 ng L-1.

MSPE involving β-cyclodextrin

Recently, CDs have gained significant interest as low-cost adsorbents of choice for wastewater treatment, because of their particular structure, physicochemical characteristics, chemical stability, high reactivity and excellent selectivity towards organic compounds and metals [38]. It is widely known that CDs can form inclusion complexes with a wide variety of organic compounds in its hydrophobic cavity through host–guest interactions [38,39]. This molecular encapsulation ability is widely utilized in many industrial products, technology and analytical methods [40]. More recently, Mohammadzadeh Kakhki [20] reviewed application of magnetic nanoparticles modified with cyclodextrins (Fig. 3) as efficient adsorbents in separation systems. In particular, the CD-based polymers are very efficient in removing acids and dyes from aqueous solutions [41]. However, they have low affinity for basic (cationic) dyes. The high surface area to volume ratio and magnetic properties of the MNPs together with the adsorption capabilities of CD through inclusion complex formation would facilitate the extraction of different compounds [20].

 

 

Fig. 3. An illustration for the carboxymethylation and binding of CD onto the Fe3O4 nanoparticles [11]

 

Lia et al. [42] prepared β-cyclodextrin (β-CD) functionalized magnetic reduced graphene oxide composite (Fe3O4/RGO@β-CD) and its application as a selective adsorbent for the determination of the two naphthalene-derived phytohormones (1-naphthalene acetic acid (NAA) and 2-naphthoxyacetic acid (2-NOA)) investigated. Magnetic reduced graphene oxide composite (Fe3O4/RGO) was first synthesized via in situ chemical precipitation method and then β-CD was applied to further functionalize the resultant Fe3O4/RGO composite (Fig. 4). Compared with Fe3O4/RGO, the as-prepared Fe3O4/RGO@β-CD showed better molecular selectivity and higher extraction efficiency for NAA and 2-NOA by dint of the size complementarity brought by the introduction of β-CD. Under the optimal conditions, the limits of detection (LODs) were 0.67 ng g-1 for both NAA and 2-NOA.

 

Fig. 4. Scheme of the synthetic route for Fe3O4/RGO@β-CD and their application for the MSPE [32]

 

At the same work, Abdolmohammad-Zadeh and Talleb [43] developed magnetic solid phase extraction method based on β-cyclodextrin (β-CD) grafted graphene oxide (GO)/magnetite (Fe3O4) nano-hybrid as an innovative adsorbent for the separation and pre-concentration of gemfibrozil prior to its determination by spectrofluorometry. The as-prepared β-CD/GO/Fe3O4 nano-hybrid possesses the magnetism property of Fe3O4 nano-particles that makes it easily manipulated by an external magnetic field. On the other hand, the surface modification of GO by β-CD leads to selective separation of the target analyte from sample matrices. Under the optimized experimental conditions, the limit of detection and enrichment factor for gemfibrozil were 3  pg  mL-1  and 100, respectively.

Yang et al. [44] presents a novel microextraction technique combining magnetic solid-phase microextraction (MSPME) with ionic liquid dispersive liquid–liquid microextraction (IL-DLLME) to determine four fungicides (azoxystrobin, chlorothalonil, cyprodinil and trifloxystrobin) in environmental water samples by high-performance liquid chromatography. Under the optimum conditions, the limits of detection were between 0.02 and 0.04 µg L-1.

In other research, Gong et al. [45] prepared carboxymethyl-hydroxypropyl-β-cyclodextrin polymer modified magnetic particles Fe3O4 (CM-HP-β-CDCP-MNPs) and applied to magnetic solid phase extraction of rutin combined with UV–Visible spectrometry detection. Calibration curve was linear in the range of 0.05–8.00  μg  mL-1 and the limit of detection was 7.0  ng  mL-1.

 

MSPE involving carbon nanotube (CNT)-based magnetic nanoparticles

Because of their excellent mechanical, electrical, and thermal properties, carbon nanotubes (CNTs) have been the focus of intensive study since their discovery by Iijima in 1991 [46].

Because of their relatively large specific area, CNTs have attracted researchers’ interest as a new type of powerful solid-phase extraction adsorbent. However, the poor solubility of CNTs and the difficulty of collecting them from their dispersing media can cause much inconvenience in their practical application. To simultaneously overcome these two disadvantages, functionalization of the CNTs becames necessary. Addition of the property of magnetism to CNTs enables convenient separation of the sorbent in addition to high adsorption capacity [47].The prepared magnetic CNTs can be well dispersed in water and easily separated from the medium by the use of a magnet [48]. Different strategies for the preparation of the M-CNT composite by the combination of the MNP and CNTs are shown in Fig. 5 [49]. More recently (2015), Herrero-Latorre et al have reviewed magnetic solid-phase extraction using carbon nanotubes as sorbents [16]. CNT-modified MNPs have been used for the extraction of thiamine [50], estrogens [51], flavonoids [52], fluoroquinolones [53], gatifloxacin [54], naproxen [55], sulfonamide antibiotics [56,57], aconitines [58], methylprednisolone [59], puerarin [60], pyrethroids [61], aryloxyphenoxy-propionate herbicides [62], bisphenol A [63], linear alkylbenzene sulfonates [64] and 4-nonylphenol [65] from different matrices.

 

Fig. 5. Different strategies for the preparation of the M-CNT composite by the combination of the M-NP and CNTs. a) Endohedral functionalization; b) Exohedral functionalization; c) Preparation of M-CNT composites  by exohedral functionalization. Schematic description of the self-assembly of magnetite beads along MWCNTs in the hydrothermal synthesis [39]

 

Daneshvar Tarigh and Shemirani [50] proposed an ultrasound-assisted dispersive solid phase extraction method with MWCNT-Fe3O4 as the sorbent and subsequent spectrofluorimetric determination of thiamine (Vitamin B1) in diverse biological, pharmaceutical and foodstuff samples. The sensitivity and precision obtained are comparable to, or even better than those of other methods for the determination of Vitamin B1 and, in addition, the sample clean up system proved to be an excellent procedure for complex matrices. Different types of estrogens have been determined in milk [51].

An interesting way to increase the selectivity of M-CNTs for target analytes is by modification of their surface in different ways by chemical or physical functionalization. This approach can be used to introduce diverse functional groups, biomolecules and onto the surface. It is clear that this functionalization (through both chemical and physical strategies) seems to be one of the future trends in M-SPE. The attachment of functional groups with directed selectivity for some analytes (or even specific ones in the case of molecularly imprinted polymers: MIPs) appears to be one of the most interesting approaches for future developments. Zhang et al. [63] applied this strategy by developing an M-SPE procedure based on the synthesis of a MWCNT-Fe3O4-MIPs composite for the extraction of bisphenol A. In spite of the complex synthesis method for the MIP-based sorbent material, involving  several steps, the high selectivity and binding capacity of the composite make this a very interesting sorbent for analytical separations.

Other functionalization methods have been employed for analytical separations of different natural substances. Xiao et al. [52] functionalized MWCNT-Silica/Fe3O4 with 1-hexadecyl-methylmidazolium bromide (C16MIM Br) for the separation of flavonoids from human urine.

Three different pyrethroids (insecticides used in the majority of commercial household formulations) were also determined after magnetic extraction with MWCNT-Fe3O4. Betacyfluthrin, cyhalothrin and cyphenothrin were successfully separated from tea samples and were subsequently measured by HPLC [61]. The authors stated that magnetic nanotubes are ideal vehicles for loading pyrethroids and they proposed the extension of these studies to organophosphorus pesticides in complex matrices.

Recently, Luo et al. [62] have proposed a new method for the HPLC and UHPLC-MS/MS determination of four aryloxyphenoxy-propionate herbicides (AOPPs) and their metabolites in water samples using a novel magnetic ionic liquid modified carbon nanotube (M-IL-MWCNTs) as a sorbent for magnetic extraction. The appropriate π-π electron-donor/acceptor interactions and anion exchange ability allowed the sorbent to be used for the simultaneous extraction of analytes with different polarities, namely non-polar AOPP esters and their polar acid metabolites. This approach compares favorably with similar procedures in which M-MWCNTs and other M-NPs are employed as sorbents. The authors suggested that the MWCNT part of the M-IL-MWCNT has a similar adsorption mechanism to M-MWCNT, while the ionic liquid part not only changed the polarity of the MWCNT but also offered an anion exchange group to interact with ionic analytes. Therefore, the sorption of analytes onto the M-IL-MWCNT can be explained by a variety of adsorption mechanisms, including π-π, van der Waals and ionic interactions.

 

MSPE  involving  graphene-based  magnetic nanoparticles

Graphene (G) is another carbon-based material with many unique features, including a two-dimensional planar structure coupled with one-atom thickness, large surface area, and extraordinary electrical, thermal, and mechanical properties [66]. Because of its large delocalized π-electron system, G can form a strong π-stacking interaction with the benzene ring and might be a good adsorbent for theextraction of benzenoid compounds [67]. Introduction of magnetic properties into G could combine its high adsorption capacity with the separation convenience of magnetic materials [68]. Therefore, it is believed that magnetic graphene nanoparticles would have good functionality and performance in separation applications [69-81].

Wang’s group synthesized a G-based magnetic nanocomposite (Fe3O4–G) and successfully applied it in MSPE for preconcentration of some benzenoid compounds, for example neonicotinoid insecticides [70], imide fungicides [71], carbamate pesticides [72], fuchsine [73], triazine herbicides [74], chloroacetanilide herbicides [75] and triazoles [76] in environmental water samples. Also, G-based magnetic nanocomposite have been used for extraction of PAHs [77], sulfonamide antibiotics [78], polychlorinated biphenyls, polyaromatic hydrocarbons and phthalates [79], perfluoroalkyl and polyfluoroalkyl substances [80] and preservatives [81] by other research goups.

Very recently, a kind of Fe3O4–G has been prepared and used as adsorbent for preconcentration of four neonicotinoid insecticides (thiamethoxam, imidacloprid, acetamiprid, and thiacloprid) from environmental water samples [70]. In this study, pure Fe3O4 MNPs and two different magnetic carbon materials, i.e., Fe3O4–G and Fe3O4–MWCNT, were all tested as adsorbents for extraction of the target analytes. The results indicated that Fe3O4 nanoparticles alone barely extract the target compounds from sample solution, and that MWCNT or G was responsible for adsorption of the neonicotinoids. The results also showed that the extraction efficiency of Fe3O4–G (225 m2 g-1) was much better than that of Fe3O4–MWCNT (196 m2 g-1), which could be attributed to its slightly larger surface area and the high adsorption ability of G. The research group also used Fe3O4–G for efficient enrichment of some trace triazoles from environmental water samples [76].

It is well known that graphene oxide (GO) sheets are highly negatively charged when dispersed in aqueous solution, as a result of ionization of carboxylic acid and phenolic hydroxyl groups on the GO sheets. Han et al. reported a facile strategy for preparing Fe3O4–GO nanocomposites by electrostatic interaction—simple addition of Fe3O4, which has a positively charged surface. This synthesis of Fe3O4–GO nanocomposites was mild, rapid, and no toxic reagents were used; the procedure is illustrated schematically in Fig. 6 [77]. The hybrid materials obtained were used as MSPE sorbent to preconcentrate several PAHs in environmental water samples before HPLC–UV analysis. To avoid tedious chemical modification, an easy-to-handle approach was devised by Luo et al. With the aid of sonication, graphene was easily immobilized on the silica-coated magnetite particles (denoted Fe3O4-G) [78]. Thus, the Fe3O4-SiO2–G had magnetic properties, enabling easy removal of the material after dispersion. The graphene in the Fe3O4-SiO2–G magnetic sorbent still had its own properties, indicating potential adsorption ability. This synthesized Fe3O4-SiO2–G was used to extract six sulfonamide antibiotics (SAs) from water samples.

 

Fig. 6. Schematic illustration of fabrication of the Fe3O4-GO nanocomposite [67]

 

More recently, chem. et al. [81] synthesized size-controlled magnetite nanoparticles with a graphene and polymeric ionic liquid coating (Fe3O4@SiO2@G@PIL). The adsorbent (Fig. 7) used as the modified QuEChERS adsorbent for the determination of 20 preservatives residues in vegetables by gas chromatography/mass spectrometry (GC–MS) analysis. It not only exerted the nanometer features of magnetic nanoparticles, but also displayed the large specific surface area of graphene (G) and the solvent effects of polymeric ionic liquids (PILs). Various experimental parameters have been investigated. Under the optimized conditions, the detection limits of the proposed method for 20 preservatives ranged from 0.82 to 6.64 µg/kg.

 

Fig. 7. Preparation of magnetite nanoparticles by a graphene and polymeric ionic liquid coating [71]

 

MSPE  involving  polymer-coated  magnetic nanoparticles

Magnetic polymer composites can be prepared by coating or encapsulating the magnetic inorganic particles, for example magnetite (Fe3O4), with natural or synthetic polymers. These polymer-modified MNPs combine the high extraction capacity of polymer with the easy separation property of MNPs, and can be used for the sample preparation. Recently, some recent applications of magnetic polymer composites and magnetic molecularly imprinted polymers have been reviewed by some research groups [13,15,17].

Hybrid polymer-magnetic NPs can be powerful materials for (micro) the extraction. These hybrid MNPs coated with a polymer network can be anchored by electrostatic interaction [82,83] or by covalent bonding [84-88]. Covalent bonding is usually involved when polypyrrole [84,87], polythiophenes [88], polyaniline [75] or molecularly imprinted polymers (MIPs) [54,89-108] are used as polymeric coatings, whereas electrostatic interactions occur when such biopolymers as chitosan [82] or alginate [83] are used. In the latter case, the biopolymers are usually used to enhance the dispersibility of the derivatized MNPs.

Zhang et al. reported the preparation of chitosan-coated octadecyl-functionalized MNPs [82]. The magnetite NPs were first modified with an octadecyl group by silylation; the surface of the Fe3O4-C18 was then further coated with a layer of hydrophilic chitosan–tripolyphosphate polymer by ionotropic gelation. The resultant materials have an interior hydrophobic octadecyl group and exterior hydrophilic chitosan polymer coating. Another method used to solve the problem of Fe3O4-C18 being difficult to disperse in aqueous solution is to coat a hydrophilic barium-alginate (Ba2+-ALG) polymer on the surface of C18 [83]. The sorbents were used to preconcentrate PAHs and phthalate ester pollutants from environmental water samples. It required only 30 min to extract trace levels of analytes from 500 mL water samples compared with 2-3 h for a traditional SPE column equipped with a vacuum pump.

There has recently been increasing interest in the use of conducting polymers as extractants [84-87]. Conducting polymers are multifunctional materials with a variety of interesting properties, for example extraordinary stability and simplicity of the synthesis from an inexpensive monomer. Polypyrrole (PPy)-coated Fe3O4 magnetic microspheres have been successfully synthesized and used as a magnetic sorbent to extract and concentrate the phthalates from water samples on the basis of formation of π–π complexes and hydrophobic interaction between polypyrrole and analytes [84]. For a similar reason, Fe3O4-PPy showed excellent performance in estrogen extraction [87]. Estrogens could be captured directly by Fe3O4-PPy from milk samples without protein precipitation.

Mehdinia et al. [85] reported the application of polyaniline-coated Fe3O4 nanoparticles (Fe3O4-PANI NPs) with diameters between 50 and 100 nm for extraction of methylmercury. In this research, hydrophobic and π–π interactions were important in the extraction of anionic ionizable compounds. Recently, Fe3O4 nanoparticles coated with sulfate-doped PANI have been synthesized and used for sampling the ionizable compounds parabens [86]. Because sulfate-doped PANI is positively charged, electrostatic interactions and hydrophobic and π–π interactions have a significant role in adsorption of target analytes by the sorbent.

In recent years, because of their chemical stability in air and/or humid environments, polythiophenes have been coated on Fe3O4 NPs (Fe3O4-PTh NPs) and used as efficient sorbents for extraction and preconcentration of several typical plasticizers from environmental water samples before gas chromatography with flame-ionization detection (GC–FID) [88]. Coating of NPs with polythiophene not only increased adsorption capacity for the target analytes but also improved the stability of the NPs and their dispersibility in aqueous media.

Molecular imprinting of highly cross-linked materials imitates the recognition mechanism of antigens and antibodies. The imprinting process uses a template molecule and a functional monomer for co-polymerization in the presence of a cross-linking agent, leading to formation of a polymer with a three-dimensional structure. After removal of the imprinted molecules, the imprinted cavities enable the polymer to selectively rebind the imprint molecule and its analogues from a mixture. Magnetic molecularly imprinted polymer microspheres prepared by molecular imprinting of magnetic nanoparticles have combined the advantages of both molecular imprinting and magnetic separation. These molecularly imprinted polymers (MIPs)-modified magnetic NPs have both good superparamagnetism and highly selective adsorption and are very promising as selective sorbents for SPE. In continue, some most recently published magnetic molecularly imprinted polymer methods have been reviewed [89-109].

 

Fig. 8. Scheme of the synthetic route for MCNTs@MIP and their application for SPE of GTFX with the help of an applied magnetic field [44]

 

Fig. 9. Synthesis route of surface-imprinted core-shell magnetic beads and their application for the extraction of BPA [79]

 

Xiao et al. [54] synthesized a novel composite imprinted material, on the basis of magnetic carbon nanotubes (MCNTs)-incorporated layer using gatifloxacin as a template, methacrylic acid as a functional monomer, glycol dimethacrylate as a cross-linker, by a surface imprinting technique (Fig. 8). The results showed that magnetic carbon nanotubes molecularly imprinted polymers (MCNTs@MIP) display a rapid dynamic adsorption and a high adsorption capacity of 192.7 µg/mg toward GTFX. Applied MCNTs@MIP as a sorbent, a magnetic solid phase extraction method coupled with high performance liquid chromatography (MSPE-HPLC) was developed for the determination of GTFX in serum samples. The recoveries from 79.1 ± 4.8% to 85.3 ± 4.2% were obtained. MCNTs@MIP can not only be collected and separated fast by external magnetic field but also have high surface-to-volume ratio, outstanding mechanical properties and specific recognition toward template molecule. In addition, the MCNTs@MIP could be regenerated, which could be used for five cycles with lost of less than 7.8% of its recovery on average.

Yuan et al. [89] introduced a new strategy for the extraction of bisphenol A (BPA) from milk  using surface-imprinted core-shell magnetic beads. In order to obtain highly selective recognition cavities, they chose an enhanced imprinting method based on binary functional monomers, e.g. 4-vinylpyridine (4-VP) and β-cyclodextrin β-CD), for BPA imprinting (Fig. 9). The adsorption experiments revealed that Fe3O4-MIPs showed better extraction capacity and selectivity toward BPA and its analogues than the non-imprinted polymers (NIPs). In milk samples, the present method displayed a lower detection thresholds, down to 3.7 µg/L.

 

Fig. 10. Schematic illustration for the preparation process of the PM-MIMs, possible mechanism of photoregulated uptake and release and the extraction procedure [80]

 

Fig. 11. (A) Schematic illustrations of the preparation process and temperature-regulated shrinking/swelling behavior (in the dotted box) of WC-TMMIPs (a), and their applications to MSPE (b) and packed SPE (c). (B) Schematic representation of the adsorption and release process of BPA by the WC-TMMIPs and possible molecular recognition mechanism regulated by temperatures [94].

 

More recently, Peng et al. [90] prepared photonic-magnetic responsive molecularly imprinted microspheres (PM-MIMs) by seed polymerization, through suitable functionalization of magnetic nanoparticles for further coating with photoresponsive functional monomer and imprinted layers (Fig. 10), and then successfully applied to the fast and selective extraction of 17β-estradiol (17β-E2) from milk powder and drinking water samples by HPLC-UV. The PM-MIMs displayed excellent photoresponsive properties and could be rapidly separated from solutions under an external magnet. The PM-MIMs proved to be an ideal photoswitch with the ability of reversible uptake and release of 17β-E2 upon alternate 365 and 440 nm irradiation: 45.0% of 17β-E2 released from the PM-MIMs upon 365 nm irradiation, and 94.0% of the released 17β-E2 was rebound to the PM-MIMs at 440 nm. The method limit of detection (LOD, S/N = 3) for 17β-E2 was 0.18 µmol L-1. The proposed method reasonably combined photonic response, magnetic separation and surface imprinting, which endowed the PM-MIMs with significant advantages of high adsorption capacity and fast binding kinetics, convenient separation and recycled use, and simple rapid eco-benign adsorption/elution processes for template molecules.

Versatile molecularly imprinted polymers (MIPs) have been widely applied to various sample matrices, however, molecular recognition in aqueous media is still difficult. Stimuli-responsive MIPs have received increasing attentions due to their unique feature that the molecular recognition is regulated by specific external stimuli. More recently, Wu et al. [104] prepared water-compatible temperature and magnetic dual-responsive MIPs (WC-TMMIPs) with hydrophilic brushes prepared via reversible addition-fragmentation chain transfer precipitation polymerization for reversible and selective recognition and extraction of bisphenol A (BPA). The resultant WC-TMMIPs (Fig. 11) showed excellent thermosensitivity and simple rapid magnetic separation. Controlled adsorption and release of BPA by temperature regulation were investigated systematically, and the maximum adsorption and removal efficiency toward BPA in aqueous solutions were attained at 35ºC and 45ºC, respectively, as well as a good recoverability which exhibited a  precision less than 5% through five adsorption–desorption cycles. Using the two modes followed by HPLC-UV determination, excellent linearity was attained in the range of 0.1–14.5 µM and 1.3–125 nM, with low detection limits of 0.02 µM and 0.18 nM, respectively. Satisfactory recoveries for spiked seawater samples were achieved ranging from 86.3–103.5% and 96.2–104.3% with RSD within 2.12–4.33%. The intelligent WC-TMMIPs combining water-compatibility, molecular recognition, magnetic separation, and temperature regulation proved potentially applicable for selective identification, controlled adsorption/release and high-efficiency enrichment/removal of trace targets in complicated aqueous media.

 

MSPE involving Octadecylsilane(ODS)-modified magnetic nanoparticles

ODS-modified NPs have been widely used for preconcentration of environmental pollutants because of their favorable separation ability, excellent stability, and long lifetime [99]. ODS modified magnetic NPs are therefore expected to have excellent performance in adsorption and separation of substances from complex samples. One of the most promising and advanced composite materials is Fe3O4-silica nanoparticles coated with alkyl C18 (Fe3O4-SiO2-C18). Sha et al. reported Fe3O4-SiO2-C18 magnetic nanoparticles for extraction and determination of ergosterol in tobacco [110] for the first time. After that C18-functionalized MNPs were used for the extraction of PAHs [111,112], methylprednisolone (MP), lidocaine, or puerarin in rat plasma [113–115], phthalates [116], sudan dyes [117], OPPs [118], phthalates esters [119], fat-soluble vitamins [120], pesticides residues [111] and anionic perfluorinated compounds [122].

By fabricating a C18-functionalized mesoporous silica shell on the surface of a Fe3O4-SiO2 core, Zhang et al. also synthesized Fe3O4-SiO2-SiO2-C18 magnetic microspheres [112]. These microspheres had high extraction efficiency for PAHs and efficiently prevented interference from natural organic matter, thus enabling easy isolation from the aqueous solution after extraction. When Fe3O4-SiO2-SiO2 microspheres without modification by use of C18 groups were used for comparison, PAHs were hardly extracted over the whole pH range, indicating that the C18 group is mainly responsible for adsorption of PAHs on the Fe3O4-SiO2-SiO2-C18 magnetic sorbent.

Sorbents with mixed functional ligands may  enhance adsorption ability toward targets with different functional groups. Zhang et al. developed novel silica-coated MNPs functionalized with both C18 and NH2 groups, and used as the extractant for anionic organic pollutants under acidic conditions [112]. Owing to the hydrophobic interaction and electrostatic attraction of the anionic perfluorinated compounds jointly provided by the mixed groups on the surface, more than 90 % of the targets can be extracted from 500 mL aqueous solution by 0.1 g Fe3O4-SiO2-C18+NH2 NPs at pH 3.

Ultrafine Fe3O4 NPs prepared by chemical coprecipitation have a smaller diameter, and larger surface area that can be more easily dispersed in aqueous samples compared with those prepared by solvent-thermal method. These C18-functionalized ultrafine magnetic silica nanoparticles were utilized as adsorbent to extract four kinds of Sudan dye (Sudan I, II, III, and IV) from water samples before determination by UFLC [116]. The LODs for Sudan I, II, III, and IV were 0.066, 0.070, 0.120, and 0.120 ng mL-1 respectively.

Application of magnetite nanoparticles for cleanup and enrichment of pesticides is a relatively new area of research. Maddah et al. reported a method for sample preparation of trace amounts of organophosphorus pesticides (OPPs) in environmental water using magnetite octadecylsilane nanoparticles as adsorbent [117]. The enrichment factors of this method were 172 and 184 and the LODs for both analytes, enitrothion and diazinon, were 0.014 and 0.019 ng mL-1 with good precision—relative standard deviations (RSD) were 5.4 % and 7.2 %, respectively.

 

Automation of M-SPE

As stated previously, it is clear that M-SPE has advantages over standard column SPE due to the simplicity of the solid sorbent separation. However, in spite of the minimal sample manipulation required for M-SPE, automation involving the use of flow injection analysis (FIA) and related procedures would constitute an appreciable contribution to improve the analytical figures of merit of M-SPE-based methods. These ameliorations are focused on analysis time (by faster sample throughput) as well as on precision and accuracy (by reduction of human intervention). In addition, other benefits for the analytical process provided by automation include a reduction in the consumption of reagents and solvents and minimization of the analysis time, all of which have associated cost savings.

In general, automation of M-SPE involves the use of an FIA (or related technique) system in which the magnetic sorbent is immobilized onto a microcolumn by applying a magnetic field generated by magnets arranged around the column. The main two drawbacks of this approach are (i) the effective immobilization of a magnetic sorbent by the application of an external magnetic field alone continues to be a great challenge [123] and (ii) the uniformity and strength of the magnetic field are critical factors to achieve a well-packed column and to avoid the formation of undesired channels in the magnetic sorbent [21]. The first attempt to automate M-SPE was carried out by Lee et al. [124] in 2009. These authors proposed a new method for the determination of multiple heavy metals by inductively coupled plasma mass spectrometry (ICP-MS) employing an M-SPE sample preparation procedure in which iron based magnetic nanoparticles modified with polyacrylic acid were used as the sorbent. In this case, in addition to the magnetic field, frits and plugs at both ends of the microcolumn were used  to immobilize the magnetic material and to avoid material losses. An FIA on-line M-SPE process in which the magnetic sorbent was coated onto the inner walls of a laboratory-made knotted reactor (KR) was developed for selective chromium speciation [125] and for the preconcentration and determination of several trace noble metals [126], with detection by ICP-MS. In both cases, the particular design of the reactor, combined with the magnetic field applied, was sufficient to immobilize the magnetic sorbent and avoid the need for any frits or plugs. Another recently applied strategy is the lab-on-chip M-SPE method [127-129]. In these cases, integrated microfluidic chips consisting of reaction, mixing and extraction units along with two magnets, were designed and fabricated for M-SPE.

In addition to the general benefits of M-SPE, the principal advantages of this approach are the miniaturization of the procedure, which in turn leads to a very low sample requirement, very low consumption of solvents and reagents, and good compatibility with biological samples (such as cells). In contrast, the preparation of microfluidic devices with several inlet and outlet flow channels, microvalves and magnets is highly specialized and involves soft lithography and rapid prototyping with polydimethylsilicone technology [128].

In addition to FIA, the other related technique employed for MSPE automation is sequential injection analysis (SIA). Over the past few years the use of SIA has been extended to encompass a variety of complex online sample manipulation and pretreatment procedures. For example, Giakisikli and Anthemidis [122] recently developed an SIA-M-SPE approach for the preconcentration of aqueous cadmium samples prior to determination by electrothermal atomic absorption spectrometry (ETAAS). A schematic diagram of the proposed system is shown in Fig. 12.

 

Fig. 12. Schematic diagram of the SI-MSPE-ETAAS system for cadmium determination. SV, selection valve; SP1, SP2, SP3, syringe pumps; HC, holding coil; CC1, CC2, confluence connectors; DT, delivery tube; C, microcolumn; GF, graphite furnace of ETAAS; IBMK, isobutylmethylketone; DDTC, diethyldithiocarbamate [113]

 

One of the drawbacks of the repeated use of permanently packed M-SPE columns in FIA and SIA networks is that this might lead to several problems such as contamination, deactivation of the surface and even loss of analyte retention capability. Furthermore, incomplete elution of the retained species from the magnetic sorbent might produce carry-over effects between consecutive runs. Therefore, in both FIA and SIA procedures it is essential to use magnetic materials that are robust to a large number of adsorption/ elution cycles without performance loss. A new SIA-approach, namely sequential injection analysis-bead injection-solid phase extraction (SIA-BI-SPE), has recently been developed to overcome the aforementioned drawbacks by facilitating the renewal of the solid sorbents [130].

 

Magnetic nanoparticles in microextraction techniques

Magnetic nanoparticles for retrieving solvents in dispersive liquid-liquid microextraction

In conventional DLLME, organic solvents with higher density than water should be used for easily separation 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. On the other hand, 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 [131]. 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 [1-3].

Several applications following this dual extraction have appeared in the literature for polyaromatic hydrocarbons (PAHs) [131], triazine Herbicides [132], pyrethroids [133,134], benzoylurea, insecticides [135], lead [136,137], 4-n-nonylphenol [138], carbaryl [139], cadmium [140,141], gatifloxacin [142], zearalenone [143], triazole fungicides [144], aflatoxins [145], fungicides [146], aflatoxin M1 [147] and arsenic [148]. In this technique, MNPs are employed as sorbents for retrieving the extractant containing the analytes, which are finally desorbed (e.g., by 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 Fe2O3-NPs functionalized with 3-aminopropyl triethoxysilane. [131]. 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 polysiloxane-coated core-shell Fe3O2 @C-MNPs [140].

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 [121]. However, a drawback could be the need for vigorous vortex stirring, which requires the use of specialized vortex apparatus.

Yang et al. [146] proposed a novel effervescence-assisted microextraction technique based on ionic liquid-dispersive liquid–liquid microextraction with the magnetic retrieval of the extractant for the detection of four fungicides. Magnetic effervescent tablet composed of Fe3O4 magnetic nanoparticles, sodium carbonate, sodium dihydrogen phosphate and 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonimide) was used for extractant dispersion and retrieval. The limits of detection were between 0.02 and 0.10 μg L−1 and the intra-day precision and inter-day precision both are lower than 4.9%.

Amoli-Diva et al [147] developed simple and fast low-density solvent based dispersive liquid–liquid microextraction (LDS-DLLME) followed by vortex-assisted dispersive solid phase extraction (VA-D-SPE) as a new approach for extraction and preconcentration of aflatoxin M1 in milk samples prior to its micelle enhanced spectrofluorimetic determination. In VA-D-SPE approach, hydrophobic oleic acid modified Fe3O4 nanoparticles were used to retrieve the analyte from the DLLME step. It is noteworthy that the target of VA-D-SPE was 1-heptanol rather than the aflatoxin M1 directly. Under the optimum conditions, the method was linear in the range from 0.02 to 200 µg L-1 with the correlation coefficient (R2) of 0.9989 and detection limit of 13 ng L-1.

 

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. Ebrahimpour et al. [149] used MSPE with nano polypyrrole-coated magnetic nanopaerticles followed by dispersive liquid phase microextraction (DLLME) for trace determination of megestrol acetate and levonorgestrel by liquid chromatography/ultraviolet detection in biological and wastewater samples. After magnetic solid phase extraction, the eluent of MSPE was used as the disperser solvent for DLLME. Emulsion resulted from DLLME procedure was passed through the in-line filter for phase separation. Finally the retained analytes in the filter was washed with mobile phase of liquid chromatography and transferred to the column for separation. This approach offers the preconcentration factors of 3680 and 3750 for megestrol acetate and levonorgestrel, respectively. This guarantees determination of the organic compounds at trace levels.

Mukdasai et al. [133] developed dispersive liquid microextraction (DLME) combined with dispersive µ-solid phase extraction (D-µ-SPE) as a new approach for the extraction of four pyrethroids (tetramethrin, fenpropathrin, deltamethrin and permethrin) prior to the analysis by high performance liquid chromatography (HPLC) with UV detection. 1-Octanol was used as the extraction solvent in DLME. Magnetic nanoparticles (Fe3O4) functionalized with 3-aminopropyl triethoxysilane (APTS) were used as the dispersive in DLME and as the adsorbent in D-µ-SPE. Under the optimum conditions, the enrichment factors were in the range of 51–108. Also, detection limits were 0.05–2 ng mL-1 (water samples) and 0.02–2.0 ng g-1 (vegetable samples).

Yamini et al [150] prepared octadecyl functionalized Fe3O4@Si O2 as sorbent for the use in solid-phase extraction combined with dispersive liquid-liquid microextraction (DLLME) for the extraction of the plasticizers dibutyl phthalate, di(2-ethylhexyl) adipate and di(2-ethylhexyl) phthalate from water samples by GC-FID. Under optimal conditions, the calibration plots are linear in the range from 0.01 to 100 μg∙L-1, and very high enrichment factors (mean value ~20,000) were obtained. As a result of the high enrichment factors, the detection limits were as low as 2–3 ng∙L-1.

Mehdinia et al. [151] 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.

 

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, Shi et al. [152] introduced 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.

More recently, Casado-Carmona et al. [153] synthesized Fe3O4@SiO2 functionalized with ionic liquid methylimidazolium hexafluorophosphate (MIM-PF6) and  evaluated its potential in dispersive microextraction for the isolation of 11 endocrine disrupting compounds (benzophenones, bisphenol A and parabens) from water samples by liquid chromatograph with tandem mass spectrometric detection (HPLC-MS/MS) for analyte separation and quantification. The proposed microextraction method allows the determination of the target compounds with limits of detection in the range from 0.16 to 1.21 μg/L and the linearity was maintained between the limits of quantification and 500 μg/L. The precision, expressed as the relative standard deviation, was better than 8.3%. The recovery study was performed on different water samples obtaining percentages higher than 87%,  demonstrating the applicability of the hybrid sorbent for the selected analytical problem

Reyes-Gallardo et al. [154] synthesized magnetic nanoparticles-nylon 6 composite and applied in the microextraction field. The extraction performance of the composite under a dispersive micro solid phase extraction format has been evaluated by determining four polycyclic aromatic hydrocarbons (benzo[b]fluoranthene, fluoranthene, indeno[1,2,3-cd]pyrene and phenanthrene) in water using ultra performance liquid chromatography (UPLC) combined with photo diode array detection. The developed methodology allows the determination of the analytes with limits of detection in the range from 0.05 μg/L (benzo[b]fluoranthene) to 0.58 μg/L (phenanthrene). The repeatability of the method was better than 6.9% at the limit of quantification level. The relative recoveries varied in the interval 80–111%.

In other research, Abbasghorbani et al. [155] 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.

Bouri et al. [156] used a magnetic material based on N-methylimidazolium ionic liquid (ILs) and Fe3O4 MNPs incorporated in a silica matrix to extract and preconcentrate sulfonylurea herbicides (SUHs), such as thifensulfuron methyl, metsulfuron methyl, triasulfuron, tribenuron methyl and primisulfuron methyl from polluted water samples. It was reported that hydrophobic interaction became predominant as the five SUHs were absorbed by the ionic liquid magnetic sorbent at pH of 5. The results obtained allow concluding that the ILs-MNPs can be a very suitable alternative for the clean-up and the preconcentration of pesticide residue analyses.

 

Nanoparticle-assisted hollow-fiber-liquid-phase microextraction (solid/liquid microextraction)

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 an improved stability to the extractant phase at high stirring rates in the sample vial. Reviewing literature showed that carbon nanotubes have been extensively used in HF-LPME techniques as reviewed by Bendicho et al. [157]. however  magnetic nanoparticles more recently have been used in this technique [158].

Es’haghi and Esmaeli-Shahri [158] developed Fe3O4/SiO2/TiO2 nanocomposite dispersed in 1-octanol as a novel  highly efficient sorbent in hollow fiber-solid phase micro-extraction (HF-SPME) technique for the extraction and determination of six non-steroidal anti-inflammatory drugs; acetylsalicylic acid, naproxen, piroxicam, diclofenac, indomethacin and mefenamic acid, in hair samples. The TiO2 mixed oxide displays improved adsorptive characteristics in comparison with pure TiO2. The large surface area and the porosity of the nanosorbent allow EFs in the range 405–2450.

Martinez et al. [22] reported in-tube solid phase microextraction approach, named magnetic in-tube solid phase microextraction (magnetic-IT-SPME). This system, taking advantage of magnetic microfluidic principles, was developed  to improve the extraction efficiencies of acetylsalicylic acid, atenolol, acetaminophen, diclofenac, and ibuprofen, yielding to extraction capacities between 70 and 100%, which are much higher than those achieved using an IT-SPME approach (in the range of 10–30%).

 

Magnetic nanoparticles in enantioseparation

Chirality is an important, universal phenomenon in nature. For the in-depth study of pharmacology and biology, efficient enantioselective technologies are indispensable. Nanomaterials with large surface-to-volume ratio and specific physical and chemical properties have demonstrated great potential in chiral discrimination [159]. At the same time, by applying magnetic nanoparticles introduce another important advantage, easy and fast collection of the complexes from the solution by applying magnetic field [160] which compared with conventional separation methods, this process is noted for its speed, simplicity and cost effectiveness. Many publications show that utilization of nanomaterials could improve the selectivity, stability and efficiency of enantioseparation which some of them have been reviewed in ref [159].

MNPs, immobilized with an appropriate chiral selector, have been successfully used for enantioseparation [161–164]. MNPs tagged with an appropriate chiral selector were expected to interact selectively with a single enantiomer and form complexes, which were easily removed by an external magnet. Ghosh et al. [161] synthesized carboxymethyl-β-cyclodextrin-bonded Fe3O4/SiO2 core-shell NPs, and applied these MNPs in the enantioselective adsorption of chiral amino acids. Adsorption-equilibrium experiments demonstrated that the adsorption capacities were higher for L-enantiomers than the corresponding D-enantiomers. However, the enantioselective adsorption ability for racemic solution has not been investigated yet.

Choi et al. [162] developed a method employing racemic amino-acid solutions as model compounds for further study. First, MNPs with (S)-chiral selector (MNPs/(S)-CS) were added into the racemic solution for enantioselective adsorption. The enantiomeric excess was evaluated by chiral HPLC and confirmed the enantioselectivity of MNPs/(S)-CS. However, the enantioselectivity was not stratified. Consequently, another method was developed, employing equal non-magnetic silica particles tagged to the antipode (R)-chiral selector (MNPs/(R)-CS) and MNPs/(S)-CS at the same time. After extraction, the MNPs/(S)-CS-enantiomer complexes were collected by a magnet, while the MNPs/(R)-CS-enantiomer complexes were collected by decantation after centrifugation.

These results of chiral HPLC separation demonstrated that the enantioselectivity is improved when MNPs/(R)-CS is simultaneously used. This method indicated that the two contrary chiral selectors could have some synergistic effects for enantioseparation and provides a new insight to the development of a highly efficient enantioselective method.

In most conditions, washing to retrieve the target molecules is necessary for further experiments.  However, elution made the method complicated, and the organic solvent was not economic or environmentally friendly. As an alternative, Chen et al. [163] developed a photo-controlled inclusion-and-exclusion method to induce the release of the adsorbed enantiomers in reverse (Fig. 13). The chiral selective system also employed β-CD-functionalized Fe3O4 NPs as chiral adsorbents. After extraction, pure optical enantiomer adsorbed on the NPs was released via the photo-controlled inclusion-and exclusion reactions of azobenzene derivatives with β-CD. The reversible photo-controlled inclusion-and-exclusion process enabled recycled use of β -CD-functionalized Fe3O4 NPs in enantioseparation. It is worth mentioning that after more than 5 times repetitions β-CD modified Fe3O4 NPs still showed good enantioselectivity for L-tryptophan, indicating that β-CD-modified Fe3O4 NPs were highly applicable in repeated recycling.