ABC Spotlight on magnetic composite nanoparticles in analysis: increased sensitivity at decreased analysis time
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Virtually, any protocol in instrumental analysis requires sample preparation for multiple purposes: These include pre-concentrating target species, separating them from their matrix, and transferring them into solvent systems that are compatible with further analysis steps.
Sensors and arrays face a slightly different challenge: Even if they are inherently highly sensitive, one has to make sure that sufficient numbers of target molecules meet the sensitive area within a realistic time frame.
Solid phase (micro) extraction SP(M)E has successfully tackled these issues and fundamentally improved the analytical process. Nonetheless, rapid progress in synthesizing tailor-made nanoparticles has opened up unprecedented opportunities for improving it. Among these, functionalized magnetic nanoparticles (MNP) have attracted special interest and made way for a range of novel application scenarios. This has been driven by their ferromagnetism, which allows for separating them from sample solutions by applying external magnetic fields. The beauty of the approach lies in the fact that magnetic fields usually do not affect any species present in the sample and thus are also compatible with biological matrices.
These examples also highlight the use of a variety of functionalization strategies to achieve selectivity, namely modification with sodium oleate , coating with poly-dopamine , with molecularly imprinted polymers (MIP) , and aptamers , respectively. They cover the entire range from broad-band affinity to high selectivity during extraction. Among selective functionalization methods, molecular imprinting has attracted considerable attention (see for instance [4, 5, 6]), because it allows for generically designing polymer matrices with tailor-made selectivity. Kong et al.  even succeeded in generating a multi-selective matrix: Instead of utilizing their target analyte for imprinting—which would be the “standard” way of doing MIP—2,4-diamino-6-methyl-1,3,5-triazine served as a so-called pseudo-template. This allowed them to synthesize multi-selective particles for enriching melamine (MEL), cyromazine (CYR), triamterene (TAT), diaveridine (DVD), and trimethoprim (TME) with the same particles to analyze them by HPLC-MS.
As previously mentioned, MNPs have also played an important role in developing sensors and assays. In these cases, MNPs are usually fully integrated into the sensing protocols. For instance, Che et al.  published an assay utilizing MNPs for magnetically enriching pathogenic bacteria prior to fluorescence analysis. They modified SiO2@Fe3O4 MNPs with aminopropyl triethoxysilane (APTES), a well-established strategy to functionalize particle surfaces with –NH2 groups. The resulting particles were 90–105 nm in diameter and inherently affine to the outer shell of, e.g., E.coli. Due to the difference in sizes between MNPs and bacteria, several MNPs bound to each bacterium, which made it possible to separate them from unreacted particles by PEG-based magnetophoretic chromatography followed by labelling with a fluorescence marker and analysis. This lead to detection limits of 100 cfu, which is close to current LoDs obtained by PCR-based DNA analysis.
In a sensor setting, using MNPs makes most sense when combining them with highly sensitive detection. Aside from electrochemical techniques, fluorescence obviously plays an important role there, usually in sandwich immunoassay formats. A very recent paper on the detection of alpha-fetoprotein  beautifully exemplifies the benefits of the approach: Again, MNPs are coated with a capture antibody and fluorescent nanoparticles (Rhodamine 6G@SiO2) with a secondary antibody. The main advantage of this approach is to mix the MNPs with the sample followed by shaking/stirring and magnetic separation. This leads to lower detection limits and wider linear range than ELISA: The latter requires reactions on the substrate surface, rather than in the bulk volume of the sample. For the same reason, the MNP assay reduces analysis time to one-third of that required by ELISA. All these approaches pre-concentrate the target analyte by the means of MNPs. However, there are also reports for removing the matrix : There, authors succeeded in detecting folic acid in food samples by removing most of the unwanted background by C6-modified MNPs and thus replacing a stationary SPME cartridge.
Overall, MNPs hence are a powerful tool to improve sample preparation and assay strategies, because they help analysts to “bring receptors to the samples” rather than the other way round. This either means that larger sample volumes can be extracted in shorter time, than through cartridges, or that sensing processes can make use of the entire sample volume rather than only the sensor surface. This also means that they are highly useful tools in overcoming a fundamental problem in sensing at low concentration: MNPs make it possible that there is realistic chance of a target analyte meeting a nanoparticle in the agitated sample within a reasonable amount of time. In that sense, ABC will continue to cover this important aspect of analysis and sample preparation.
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