A Review on the Recent Progress in Matrix Solid Phase Dispersion

Matrix solid phase dispersion (MSPD) has proven to be an efficient sample preparation method for solid, semi-solid, and viscous samples. Applications of MSPD have covered biological, food, and environmental samples, including both organic and inorganic analytes. This review presents an update on the development of MSPD in the period 2015~June 2018. In the first part of this review, we focus on the latest development in MSPD sorbent, including molecularly imprinted polymers, and carbon-based nanomaterials etc. The second part presents the miniaturization of MSPD, discussing the progress in both micro-MSPD and mini-MSPD. The on-line/in-line techniques for improving the automation and sample throughput are also discussed. The final part summarizes the success in the modification of original MSPD procedures.


Introduction
Sample preparation is the key step in analytical workflow [1]. For solid, semi-solid, and viscous samples, procedures of sample preparation generally start with extracting analytes from matrix into homogeneous liquid solvents. Then a consequent clean-up step may be performed to reduce interference compounds in the extract. Finally, an additional enrichment or concentration step may also be required to meet the sensitivity of the analytical technique. Limitations in the classical method are the use of large volumes of solvent, labor-intensive, and time-consuming through the manipulation. Matrix solid phase dispersion (MSPD), first introduced by Barker et al. [2], provides an alternative approach to reduce solvent use and analysis time for preparing solid, semi-solid, and viscous samples [3].
In a typical MSPD procedure, samples are blended with sorbent to obtain homogeneous mixture. The resulting mixture is transferred and packed into an extraction column. Then solvent is passed through the column to carry out washing and elution step for the extraction and isolation of analytes from the matrix. In some case, an additional co-sorbent could be loaded at the bottom of the column to further clean-up the eluent. Generally, the final extract can be analyzed by chromatography based analytical techniques. Compared with classical solvent extraction method, MSPD eliminates steps of repeated centrifugation and/or filtration, and procedures of re-extraction. Different with solid phase extraction (SPE), in which separated solvent extraction procedure is required to make solid samples suitable for loading into a SPE column, MSPD eliminates the solvent extraction step. These would dramatically reduce the consumption of solvent and the required manipulation time for the preparation. There have been extensive reviews regarding the trends and developments of MSPD [3][4][5][6][7][8][9][10]. In this review, we focus attention on the latest developments in MSPD sorbent, miniaturization of MSPD,

Miniaturization of MSPD
In classical MSPD protocol, the sample amount is typically 0.5 g [3]. The miniaturization of MSPD (micro/mini-MSPD) can significantly reduce the sample amount, and consequently the consumption of sorbent, solvent, and preparation time. Developed micro/mini-MSPD methods are summarized in Table 2. For instance, Guerra et al. developed a method based on micro-MSPD combined with LC-MS/MS for the simple and rapid determination of dyes in cosmetic products [31]. The proposed micro-MSPD was carried by grounding 0.1 g cosmetic sample with 0.3 g anhydrous Na 2 SO 4 (drying agent) and 0.4 g of Florisil. After transferring the mixture into a glass Pasteur pipette, 2 mL of methanol was eluted to extract nine water-soluble dyes. By using micro-MSPD method, time and solvent consumption in the sample preparation could be reduced.
Taking advantage of high sensitive detection methods, sample amount in recently published mini-MSPD could be reduced to the scale of milligram. Chen et al. reported a sensitive quantification of mercury distribution in fish organ based on the mini-MSPD [32]. The sample amount in this research was as low as 1 mg of organ sample. Multiwall carbon nanotubes (MWCNTs) were used as the sorbent, with amount of 0.5 mg. Mercury species were eluted by 100 µL eluent containing HCOOH and L-cysteine. When combined with a sensitive mercury determination method named single-drop solution electrode glow discharge-induced cold vapor generation combined with atomic fluorescence spectrometry, LOD of 0.01 µg/L was achieved. The consumption of sample, adsorbent, and solvent were all dramatically decreased in this mini-MSPD.
Another example of mini-MSPD was reported by Deng et al. [33], in which only 0.30-0.80 mg of plant samples were ground with 2 mg C18 sorbent in liquid nitrogen to obtain the homogenous mixture. Based on this mini-MSPD and the precolumn derivatization coupled with UPLC-MS/MS determination, phytohormone gibberellins were detected with the limits of quantification (LOQs) of 0.54-4.37 pg/mL. As only sub-milligram sample was required for the determination, a spatial distribution of gibberellins in a single Arabidopsis thaliana leaf with resolution of 2 × 2 mm 2 was profiled. MWCNTs, multiwall carbon nanotubes; AFS, atomic fluorescence spectrometry. n.r., not reported.

On-Line/In-Line MSPD
On-line/in-line sample preparation techniques that couple sample preparation step and chromatography separation are regarded as a promising technique with advantages of automatable high sample throughput, reducing sample manipulation and contamination, improving precision, and lower regent consumption [42]. On-line/in-line MSPD provides a potential automated way for the sample preparation of solid, semi-solid, and viscous samples.
Rajabi et al. reported an in-line micro-MSPD method for the determination of Sudan dyes in spices [43]. In this in-line MSPD, the filled MSPD column was placed in the mobile phase pathway before the analytical column. Then the mobile phase passed through the MSPD column to elute analytes and subsequently separated in a reverse-phased HPLC. Since the in-line method integrated extraction and separation into one step, this proposed approach was much faster than other reported methods for the determination of Sudan dyes.
Gutiérrez-Valencia et al. developed an on-line MSPD-SPE sample preparation method combined with HPLC-FLD for the analysis of PAHs in bovine tissues [44]. The bovine liver sample (50 mg) was dispersed on C18 sorbent (200 mg). Then the obtained homogenous mixture was packed into a stainless steel cartridge which was connected to a MSPD-SPE-HPLC-FLD system. The SPE column was used to trap and pre-concentrate the target compounds eluted from the MSPD cartridge. Acetonitrile (ACN)-water mixture and pure ACN solution were applied to wash and elute the MSPD cartridge, respectively. However, ACN extract exhibited poor retention of analytes in C18 SPE column. Thus a dynamic mixing chamber was required to dilute the ACN extract with water before pre-concentration to quantitatively transfer PAHs from MPSD cartridge to the SPE column. Finally, the analytes pre-concentrated on the SPE column were eluted through the guard-column and the analytical column with mobile phase and detected by FLD. Compared with off-line MSPD, the on-line MSPD method showed advantages of lower consumption of sample amount and saving of analysis time.
Additionally, an on-line MSPD-HPLC-ICP-MS method for the determination of mercury speciation in fish was reported by Deng et al. [45]. In this on-line MSPD performance, 1 mg fish sample was blended with 2 mg of MWCNTs, then the mixture was transferred into a stainless steel column which was prior loaded with 0.20 g of C18. The eluent solution containing HCl (2%, v/v) and L-cysteine (1.5%, m/v) was loaded by a 100 µL loop through the six-port valve. Then mobile phase flushed the eluent to pass through the MSPD column for the extraction of analytes, which were further separated and detected by HPLC-ICP-MS. It is interesting to notice that the on-line MSPD system consisting of two sequential valves and six stainless steel MSPD columns to improve sample throughput. This on-line system shows the potential of automatable high sample throughput in MSPD method.

Modification of Original MSPD
The original MSPD can be modified or combined with other extraction methodologies to improve the extraction yields or simplify the MSPD procedures. The schematic procedure of the original and representative modification of MSPD is shown in Figure 1. For instance, ultrasonic-assisted MSPD (UA-MSPD) was first reported by Ramos et al. to improve the extraction yields by putting MSPD column into ultrasonic bath or sonoreactor after the extraction solvent was loaded into the MSPD column [46]. As summarized in Table 3, UA-MSPD has been introduced for the analysis of multi-class organic contaminants. For example, Albero et al. developed an UA-MSPD method for the analysis of 17 emerging contaminants in vegetables [47]. In this modified method, vegetable samples (2 g) was blended with Florisil (4 g) and magnesium sulfate anhydrous (1 g), then the homogenous mixture was transferred into a 20 mL glass column. Extraction solution of 8 mL EtAc:MeOH (9:1, v/v) containing 3% of NH 4 OH were added to the column. After that, column was sonicated for 15 min in an ultrasonic water bath at room temperature for the extraction. Finally, extract was collected under vacuum manifold. Results indicated that better recoveries were obtained with the assistance of sonication. 5-HMF, 5-hydroxymethy furfurol. n.r., nor reported. Vortex-assisted MSPD (VA-MSPD), in which the step of column elution is replaced by vortex, has been developed to reduce the solvent consumption and analysis time. This simplified MSPD procedure has been found applications in the analysis of phytochemical compounds and organic contaminants (Table 3). For instance, Caldas et al. reported the analysis of antifouling booster biocides in marine sediments by employing VA-MSPD [52]. In the sample preparation procedure, the homogenized mixture of sample and sorbent was added into a centrifuge tube. Then the extraction solvent was added, and the sample was vortexed for 1 min. Finally, the mixture was centrifuged, and the supernatant was collected for the LC-MS/MS analysis. Compared with other extraction methods including ultrasonic extraction, SPE, and microwave extraction, this VA-MSPD exhibited the advantages of shorter extraction time and less solvent consumption.
Another recent progress of the modification is the magnetically-assisted MSPD (MA-MSPD) developed by Fotouhi et al. for the extraction of parabens from breast milks [57]. Modified magnetic nanoparticles were used as the sorbent in the MA-MSPD. Milk sample (200 µL) was blended with poly(indole-thiophene) coated magnetic graphene oxide (MGO@PIT, 50 mg) and drying salt Na2SO4 (550 mg). After blending, the homogenous mixture was transferred into water solution and mechanically stirred for the adsorption of parabens. Then the MGO@PIT with target compounds were isolated from the solution by magnet. Subsequently, analytes were desorbed from the sorbent with methanol. Compared with the magnetic liquid-solid extraction (MLSE) [58,59], a hot topic of nanomaterials in sample preparation, the major difference between MA-MSPD and MLSE is the manipulation of sample. For MLSE, analytes in solid sample are extracted into the liquid solution prior to the introduction of magnetic sorbent. While in MA-MSPD, the solid sample is blended with magnetic nanoparticles to obtain the homogenous mixture. The similarity of these two methods is the replacement of column packing and elution with simple magnetic isolation. This would simplify the preparation step and reduce the extraction time. More importantly, magnetic nanoparticles have been demonstrated to be reusable in the liquid-solid extraction [58]. Thus MA-MSPD may provide a solution for the reusability of sorbent in MSPD. Vortex-assisted MSPD (VA-MSPD), in which the step of column elution is replaced by vortex, has been developed to reduce the solvent consumption and analysis time. This simplified MSPD procedure has been found applications in the analysis of phytochemical compounds and organic contaminants (Table 3). For instance, Caldas et al. reported the analysis of antifouling booster biocides in marine sediments by employing VA-MSPD [52]. In the sample preparation procedure, the homogenized mixture of sample and sorbent was added into a centrifuge tube. Then the extraction solvent was added, and the sample was vortexed for 1 min. Finally, the mixture was centrifuged, and the supernatant was collected for the LC-MS/MS analysis. Compared with other extraction methods including ultrasonic extraction, SPE, and microwave extraction, this VA-MSPD exhibited the advantages of shorter extraction time and less solvent consumption.
Another recent progress of the modification is the magnetically-assisted MSPD (MA-MSPD) developed by Fotouhi et al. for the extraction of parabens from breast milks [57]. Modified magnetic nanoparticles were used as the sorbent in the MA-MSPD. Milk sample (200 µL) was blended with poly(indole-thiophene) coated magnetic graphene oxide (MGO@PIT, 50 mg) and drying salt Na 2 SO 4 (550 mg). After blending, the homogenous mixture was transferred into water solution and mechanically stirred for the adsorption of parabens. Then the MGO@PIT with target compounds were isolated from the solution by magnet. Subsequently, analytes were desorbed from the sorbent with methanol. Compared with the magnetic liquid-solid extraction (MLSE) [58,59], a hot topic of nanomaterials in sample preparation, the major difference between MA-MSPD and MLSE is the manipulation of sample. For MLSE, analytes in solid sample are extracted into the liquid solution prior to the introduction of magnetic sorbent. While in MA-MSPD, the solid sample is blended with magnetic nanoparticles to obtain the homogenous mixture. The similarity of these two methods is the replacement of column packing and elution with simple magnetic isolation. This would simplify the preparation step and reduce the extraction time. More importantly, magnetic nanoparticles have been demonstrated to be reusable in the liquid-solid extraction [58]. Thus MA-MSPD may provide a solution for the reusability of sorbent in MSPD.
Recently, we reported the combination of Soxhlet extraction and MSPD to develop a Soxhlet assisted MSPD (SA-MSPD) method [60,61]. In this modification method, sample was blended with silica gel following the original MSPD protocol and loaded into a column of constant pressure funnel. Then elution solvent was heated and continuous refluxed and passed through the column for the extraction and isolation of flavonoids. By comparing with conventional solvent extraction and Soxhlet extraction method, SA-MSPD showed the higher extraction yield with shorter extraction time and less consumption of solvent. Moreover, the introduction of sorbent into the Soxhlet enabled this classical method to be with clean-up ability. More recently, this SA-MSPD method was further combined with acid-hydrolysis for the quantification of flavonoid aglycones in bee pollen [61]. The acid hydrolysis SA-MSPD procedure accomplished the extraction and hydrolysis of flavonoid glycosides into one step, and provided a more efficient sample preparation method for the quantification of flavonoid aglycones.

Conclusion Remarks
Application fields of MSPD have been extended from the first reported drug residues in biological tissues to the food and environmental analysis, both for organic and inorganic analytes. Development of new sorbent materials for improving the capacity or selectivity is still the exciting research area in MSPD. One of the drawbacks of MSPD is the reusability of the extraction column. Among the emerging MSPD sorbents, modified magnetic nanoparticles are expected to provide the possibility of reusability. Combining high efficient sorbents with ultra-sensitive analytical technologies, miniaturization of MSPD might be found great interests in the analysis of limited or small size samples. Especially, the mini-MSPD may provide more information on the evolution or the spatial distribution of analytes in the sample matrices. In addition, on-line MSPD has shown the possibility of high-throughput analysis in MSPD. This would also be the trend of automation in MSPD. The modification of the original MSPD appears to be simplified the MSPD procedure and could be help for improving the reproducibility of the manipulation.