Functionalized Graphene-Coated Cobalt Nanoparticles for Highly

Sep 27, 2012 - Hiroshi Moriwaki , Takumi Otsuka , Yukari Kawabe , Issey Osaka , Akio Miyazato , Junpei Maruo , Osamu Yamada. International Journal of ...
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Functionalized Graphene-Coated Cobalt Nanoparticles for Highly Efficient Surface-Assisted Laser Desorption/Ionization Mass Spectrometry Analysis Hideya Kawasaki,*,† Keisuke Nakai,† Ryuichi Arakawa,† Evagelos K. Athanassiou,‡ Robert N. Grass,‡ and Wendelin J. Stark*,‡ †

Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita-shi, Osaka 564-8680, Japan ‡ Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang Pauli Strasse 10, HCI E 107, Zurich, Switzerland S Supporting Information *

ABSTRACT: Graphene-coated cobalt nanoparticles surfacefunctionalized with benzylamine groups (CoC−NH2 nanomagnets) were shown to effectively enrich analytes for surfaceassisted laser desorption/ionization mass spectrometry (affinity SALDI-MS) analysis. These CoC−NH2 nanomagnets are highly suited for use with affinity SALDI-MS because their mean diameter of 30 nm, high specific surface area of 15 m2 g−1, and high-strength saturation magnetization of 158 emu g−1 led to efficient extraction of analytes by magnetic separation, which in turn enabled excellent SALDI-MS performance. Surface modification of CoC nanomagnets with benzylamine groups increased the yield of peptide ions and decreased fragmentation of benzylpyridinium ions, so-called “thermometer ions” formed through soft ionization. The CoC−NH2 nanomagnets were used to extract perfluorooctanesulfonate from large volumes of aqueous solutions by magnetic separation, which was identified directly by SALDI-MS analysis with high sensitivity even at the sub-part-per-trillion level (∼0.1 ng/L). The applicability of CoC−NH2 nanomagnets in conjunction with SALDI-MS for the enrichment and detection of pentachlorophenol, bisphenol A, and polyfluorinated compounds (PFCs) with varying chain length, which are environmentally significant compounds, as well as small drugs, was also evaluated.

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Compared to the extensive studies of SALDI-MS for biological analysis, there are few reports on the use of SALDI-MS for environmental analysis of small molecules. This is surprising, as SALDI-MS offers the advantage of simultaneous measurement of highly polar and nonpolar compounds, which is difficult to accomplish with traditional methods based on gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/electrospray mass spectrometry (LC/ESI-MS). Previously, we demonstrated the utility of SALDI-MS for environmental analysis using highly oriented pyrolytic graphite polymer film containing various environmental pollutants31 and porous silicon, known as desorption/ionization on silicon mass spectrometry (DIOSMS).32 In practice, the use of SALDI-MS for environmental samples, however, requires extraction and cleanup for analytes starting from large volumes of aqueous samples (liter scale) in order to overcome matrix effects due to ion suppression as well as to enhance the detection efficiency of analytes prior to

atrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used extensively in bioanalysis.1−3 Despite the success of MALDI-MS, it suffers from several problems associated with the use of organic matrixes: (1) matrix optimization, (2) uneven analyte distribution in the matrix, and (3) matrix interference. In particular, MALDI mass spectra exhibit high chemical background noise in the low-mass region (m/z < 500) due to the formation of matrix ion clusters or degradation products. As a result, MALDI-MS is infrequently used for the analysis of small molecules such as drugs and environmental toxins. To solve these problems, surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using inorganic nanoparticles and nanostructured substrates has been developed as an organic matrix-free alternative approach. The term SALDI-MS was established by Sunner et al., who used graphite as the matrix for samples analyzed with MALDI-TOF-MS.4 More recently, the applicability of SALDI-MS has been demonstrated using various nanomaterials, including carbon-based materials,4−8 metal or metal oxide-based materials,9−22 and silicon-based materials.23−29 Several review articles on SALDI-MS have been published recently.30 © 2012 American Chemical Society

Received: July 20, 2012 Accepted: September 27, 2012 Published: September 27, 2012 9268

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In the present study, we first examined the effect of the benzylamine surface modification of CoC nanomagnets on SALDI-MS analysis by comparing the results obtained using modified and unmodified CoC nanomagnets to enrich the analyte and serve as the SALDI matrix. Second, we investigated the applicability of CoC−NH2 nanomagnets to SALDI-MS analysis of various small-molecule drugs and aromatic compounds. Finally, we demonstrated the use of CoC−NH2 nanomagnets for affinity SALDI-MS using perfluorooctanesulfonic acid (PFOS) as a model analyte. PFOS enriched by the CoC−NH2 nanomagnets from a dilute aqueous solution was identified by directly introducing the nanomagnets into the mass spectrometer for SALDI-MS analysis without prior elution, and high detection sensitivity of PFOS was achieved (approximately sub-part-per-trillion level, 10−10 g L−1). The applicability of CoC−NH2 nanomagnets to affinity SALDI-MS for polyfluorinated compounds (PFCs) with different chain lengths was also evaluated.

SALDI-MS analysis. The most popular sample pretreatment method for extraction and enrichment of analytes is solid-phase extraction (SPE). However, SPE is limited by analyte loss during elution from the analyte-binding solid as well as significant consumption of organic solvents required for elution. Magnetic nanoparticles (NPs) have proven to be an efficient means of capturing analytes due to their high surface area and their potential for functionalization to create affinity for the specific analyte of interest. Analytes enriched by magnetic NPs can be identified by introducing the loaded NPs directly into the mass spectrometer for SALDI-MS analysis without the need for elution (affinity SALDI-MS).33−35 Most magnetic NPs used currently are metal oxide nanoparticles containing a superparamagnetic such as iron oxide so that they can be magnetized by an external magnetic field and immediately redispersed once the magnet is removed.36 Achieving highly efficient capture of analyte from solution requires the balance of large surface area (to maximize analyte adsorption) and high saturation magnetization (efficient separation of NPs by a magnet); in most cases, these properties are inversely correlated, and favoring one too greatly over the other usually results in the ineffective recovery of the magnetic NPs from suspension. In this study, we demonstrated that graphene-coated cobalt nanoparticles with benzylamine surface functionalization (CoC−NH2 nanomagnets) serve effectively to enrich target analytes and as the SALDI matrix. The one-step, large-scale (>30 g h−1) production and the detailed characterization of CoC−NH2 nanomagnets (CoC mean diameter = 30 nm, specific surface area = 15 m2 g−1) have been reported by Grass et al.37 Herein, we describe the application of CoC−NH2 nanomagnets to affinity SALDI-MS for the first time. CoC−NH2 nanomagnets provide several important advantages for use in affinity SALDI-MS. (1) CoC−NH2 nanomagnets have a core/shell structure with Co/graphene. Cobalt NPs are known to be an efficient SALDI matrix, as demonstrated by the early work of Tanaka et al. who used cobalt NPs in glycerol to analyze proteins and synthetic polymers.2 Graphene has attracted considerable interest and become the focus of much research because of its outstanding material, physical, and chemical properties.38 Very recently, graphene was also demonstrated to be a useful SALDI matrix for the facile analysis of small molecules with high sensitivity.39 (2) The surface graphene of the CoC−NH2 nanomagnets is modified with benzylamine groups. It has been reported that the surface modification of gold nanoparticles with aminobenzene groups increased ion yields, decreased ion fragmentation, and increased the useful analyte mass range as compared to citrate-modified gold nanoparticles.40 Thus, surface modification of CoC−NH2 nanomagnets with benzylamine groups should also increase ion yields and decrease ion fragmentation. (3) The CoC−NH2 nanomagnets exhibit excellent magnetic properties, including a saturation magnetization of 158 emu g−1.37 This is, when calculated as saturation magnetization per unit metal, close to the bulk saturation magnetization (165 emu g−1) of metallic cobalt due to the high purity of the metallic core (i.e., no oxidation of Co nanoparticle). These superior magnetic properties of CoC−NH2 nanomagnets enabled the fast and complete recovery of the nanomagnets from suspension.37 On the basis of these characteristics, CoC− NH2 nanomagnets are a promising candidate for use in affinity SALDI-MS analysis of small molecules.

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EXPERIMENTAL SECTION Reagents and Materials. Methanol, citric acid, sodium dihydrogen phosphate dihydrate, trifluoroacetic acid, pyrene, anthracene, sodium iodide, angiotensin II, α-cyano-4-hydroxycinnamicacid (CHCA), acetylsalicylic acid, ibuprofen, warfarin sodium, phenformin hydrochloride, N-propranolol hydrochloride, ranitidine hydrochloride, verapamil hydrochloride, perfluorooctanesulfonate (PFOS, C8), perfluorohexanesulfonate (PFHxS, C6), perfluorobutanesulfonate (PFBS, C4), pentachlorophenol (PCP), and bisphenol A (BPA) were purchased from Wako Pure Chemicals Industry, Ltd. (Osaka, Japan). All chemicals were used as received, except for methanol which was dried before use in the silanization process. Milli-Q purified water was used for all experiments. 4Chloro-benzylpyridinium chloride was synthesized according to methods published in our previous study.41,42 Synthesis of CoC Nanomagnets. Graphene-coated nanoparticles (CoC nanomagnets) were prepared via flame spray pyrolysis, which proceeds by the combustion of a suitable metal containing an organic precursor;37 currently, this method accounts for the preparation of several million tons of carbon, silica, and titania. The surface of the CoC nanomagnets was functionalized with benzylamine groups according to previously reported procedures.37 SALDI-MS with CoC−NH2 Nanomagnets with No Enrichment of Analytes (Method 1). SALDI-MS spectra were acquired in linear mode on an AXIMA-CFR time-of-flight mass spectrometer (Shimadzu/Kratos, Manchester, U.K.), with a pulsed nitrogen laser (λ = 337 nm). The mass spectra of 100 different profiles of a single sample spot were averaged. One hundred laser shots were used to acquire the mass spectra. The analyte ions were accelerated at 20 kV under delayed extraction conditions. The two-layer sample preparation method was employed for SALDI-MS with CoC−NH2 nanomagnets: first, nanomagnet solution was prepared by dispersing nanomagnets in water by vortexing and then spotting 1 μL of solution onto a stainless steel plate, followed by drying. Then, 1 μL of solution containing analyte was spotted onto the plate. The SALDI performance using bare CoC was also investigated following this procedure, using toluene as dispersal media for the NPs. Sample Extraction with CoC−NH2 Nanomagnets Followed by SALDI-MS Detection (Method 2). A schematic summary of affinity SALDI-MS using CoC−NH2 nanomagnets is shown in Figure 1. The CoC−NH2 nano9269

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Figure 1. Schematic summary of affinity SALDI-MS using CoC−NH2 nanomagnets.

solution (triammonium citrate (50 mM)/citric acid (100 mM), 3:1 (v/v)) was used as a proton source. Figure 2 shows the

magnets were used to enrich analytes from aqueous solution, followed by detection using SALDI-MS. Amounts of 50−100 μL of 10 mg/mL solution of CoC−NH2 nanomagnets were added to 500−1000 mL of analyte in aqueous solution (step 1, Figure 1). The mixture was stirred using a MMS-210 agitator (EYELA, Tokyo, Japan) for 1 h or 10 min (step 2, Figure 1). The analyte-bound nanomagnets were separated from the supernatant using an external magnetic field (step 3, Figure 1) and then washed with water three times (steps 3 and 4, Figure 1). Finally, 1 μL of the aqueous solution including the analytebound nanomagnets (10−50 mg/mL) was deposited on a MALDI plate for analysis by SALDI-MS (step 5, Figure 1).

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RESULTS AND DISCUSSION Characterization of Modified and Unmodified CoC Nanomagnets. Reducing flame synthesis derived Co/C nanomagnets are characterized by metallic cobalt cores with an average diameter of ∼30 nm.37 Each of these cores is coated by a thin layer of 3−5 graphene-like carbon sheets, which corresponds to an ∼2 nm thick carbon layer, as visible under transmission electron microscopy (Figure S1a in the Supporting Information) and measurable via CHN microanalyis (5 wt % C). The CoC nanoparticles are not of monodisperse size, but their size distribution follows a log-normal behavior as shown in Supporting Information Figure S1b. The saturation magnetization of the particles does not depend on the size distribution in this particle size range (>10 nm). Functionalization of these carbon coated nanomagnets with 4-aminobenzylamine via a diazonium chemistry approach37 yields benzylamine functionalized nanomagnets with a functional loading of ∼0.1 mmol/g (0.16 wt % N, 6 wt % C in microanalysis). Each functionality is covalently bound to the surface of the carbon surface and cannot be washed off or desorbed.43 The presence of the benzylamine functionality can be further proven by the FT-IR spectrum with peaks characteristic of benzylamine (Supporting Information Figure S2).37 Affinity SALDI-MS Using Modified and Unmodified CoC−NH2 Nanomagnets. We investigated SALDI performance using modified and unmodified CoC−NH2 nanomagnets to elucidate the influence of the benzylamine surface modification of CoC nanomagents, using angiotensin II as a model analyte. Angiotensin II is a typical peptide molecule used for initial screening of SALDI performance. A citrate buffer

Figure 2. SALDI mass spectra (method 1) of angiotensin II (5 pmol) obtained using (a) modified CoC nanomagents, (b) bare CoC nanomagnets, and (c) no nanoparticles.

SALDI mass spectra of angiotensin II obtained using modified and bare CoC nanomagnets. The sample analyzed with the use of CoC nanomagnets produced a peak for the protonated ion of angiotensin II ([M + H]+, m/z = 1047, Figure 2, parts a and b), whereas the sample analyzed without the use of these nanomagnets did not produce a peak (Figure 2c). This indicates that CoC nanomagnets work as laser desorption/ ionization (LDI)-assisting nanoparticles. Compared to bare CoC nanomagnets, surface-modified CoC−NH2 nanomagnets increased the ion yield of angiotensin II, as assessed through an increase in the signal-to-noise (S/N) ratio (47 for bare CoC versus 313 for CoC−NH2). This is consistent with a previous report in which the surface modification of gold nanoparticles with amino-benzene groups increased the ion yields of peptides.40 In the SALDI process, excess energy may be transferred to individual molecules, leading to undesired fragmentation instead of the soft desorption sought in MALDI. To examine the degree of internal energy transfer in the desorption process, we measured the survival yield (SY) of a model substance, 9270

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the CoC−NH2 nanomagnets was still smaller than that observed in the MALDI process (SY = 0.98). Thus, we concluded that the use of CoC−NH2 nanomagnets increased ion yield and decreased ion fragmentation as compared to bare CoC nanomagnets. The applicability of CoC−NH2 nanomagnets to SALDI-MS for the analysis of the small molecule drugs phenformin hydrochloride, N-propranolol hydrochloride, ranitidine hydrochloride, verapamil hydrochloride, acetylsalicylic acid, and ibuprofen as well as the environmentally significant compounds PFOS, PCP, and BPA was also evaluated. Figure 4 shows the SALDI mass spectra of these small molecules obtained using CoC−NH2 nanomagnets. Phenformin hydrochloride, Npropranolol hydrochloride, ranitidine hydrochloride, verapamil hydrochloride, PFOS, PCP, and BPA were successfully detected using this approach. However, detection of the small acidic drug molecules acetylsalicylic acid and ibuprofen (Figure 4) and the polyaromatic molecules pyrene and anthracene (not shown) was not achieved. However, the third polyaromatic molecule, warfarin sodium, was detected. The reason for the low sensitivity to these molecules was not clear. Extraction of PFOS from Water Using CoC−NH2 Nanomagnets and SALDI-MS Detection. PFOS (C8F17SO3−) is widely used in various applications, including polymer additives, lubricants, fire retardants and suppressants, pesticides, and surfactants.44 Polyfluorinated compounds (PFCs) such as PFOS are metabolically and photochemically inert, resisting both biotic and abiotic degradation.45 Widespread accumulation of PFCs in wildlife and humans has attracted attention and is an emerging environmental problem worldwide.46 In most cases, liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) is the most commonly used analytical method for detection of PFCs. More recently, MALDI-MS of PFCs has been developed.47 In the present study, we selected PFOS as a model analyte to evaluate the performance of affinity SALDI-MS using CoC−NH2 nanomagnets for the detection of PFCs in general. Because the amino groups act as proton acceptors, the CoC−NH2 nanomagnets were anticipated to strongly absorb any available protons from PFOS to form protonated amines, resulting in analyte binding to the CoC−NH2 nanomagnets via electrostatic attraction. Furthermore, the hydrophobic character of both the benzyl groups and the graphene surface of the CoC−NH2 nanomagnets was expected to enhance the adsorption of PFOS via hydrophobic interactions. We determined that the CoC− NH2 nanomagnets effectively enriched anionic PFOS from dilute aqueous solution through the combination of electrostatic attraction and hydrophobic interactions, as shown in a schematic figure of Supporting Information Figure S3. First, we optimized the adsorption of PFOS to the CoC− NH2 nanomagnets by modulating the solution pH and the amount of CoC−NH2 nanomagnets added during the enrichment in steps 1 and 2 in Figure 1, as these two factors affect the ion yield of PFOS. The pH of the aqueous PFOS solution was adjusted within the range of 3.0−11.0 using NaOH or HCl. Then, PFOS was enriched from 1 ppt PFOS solutions with different pH values using the CoC−NH2 nanomagnets, followed by SALDI-MS analysis. Figure 5a shows the S/N ratio of the ion peak intensity of PFOS in the mass spectra after enrichment from solutions with varying pH. It was found that the S/N ratio of the ion peak intensity remained constant at pH values less than 7 (i.e., acidic conditions); however, a slight decrease in peak intensity at pH

benzylpyridine (BP), which afforded a series of benzylpyridinium ions, the so-called “thermometer ions.41,42 We performed SY measurements on BP as a function of laser power (LP) using the modified or unmodified CoC nanomagnets and SALDI-MS. The SALDI mass spectrum of BP exhibited two primary peaks: a molecular ion M+ peak (m/z 204) and the corresponding fragment F+ peak (benzyl cation,

Figure 3. (a) SALDI mass spectrum (method 1) of BP using CoC− NH2 nanomagnets exhibited two primary peaks: a molecular ion M+ peak (m/z 204) and the corresponding fragment F+ peak (benzyl cation, m/z 125). (b) The SY values of BP at different laser fluencies using modified and unmodified CoC nanomagnets. For comparison, SY measurements were carried out on CHCA in MALDI.

m/z 125), as shown in Figure 3a. The SY values at different laser fluencies were determined from the following equation:

SY = IM /(IM + IF)

(1)

where IM and IF are the experimentally measured intensities of the M+ and F+ peaks, respectively. The internal energy is inversely proportional to the SY. For comparison, SY measurements were carried out on CHCA with MALDI. As shown in Figure 3b, the CoC−NH2 nanomagnets had a major impact on the SY value (∼0.92), leading to a decrease in the degree of fragmentation compared to bare CoC NPs (∼0.85). This SY value was larger than those for other carbon nanomaterials previously characterized, including graphene oxide (SY = 0.38) and a hybrid film of poly(allylamine hydrochloride)-functionalized graphene oxide and gold nanoparticles (SY = 0.78).39h In addition, the threshold for ion production using CoC−NH2 nanomagnets was achieved at a low laser fluence (LP = 55) compared to that using bare CoC nanomagnets (LP = 70). However, the SY value obtained using 9271

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Figure 4. (a) SALDI mass spectra (method 1) of phenformin hydrochloride (100 pmol), N-propranolol hydrochloride (100 pmol), ranitidine hydrochloride (100 pmol), verapamil hydrochloride (100 pmol), acetylsalicylic acid (100 pmol), ibuprofen (100 pmol), warfarin sodium (100 pmol), PFOS (100 pmol), PCP (486 pmol), and BPA (75 pmol) obtained using the CoC−NH2 nanomagnets. The closed circles are the peaks of interest.

of PFOS from aqueous solution followed by SALDI-MS detection. Next, we examined the effect of varying the concentration of CoC−NH2 nanomagnets used for PFOS enrichment (steps 1 and 2 of Figure 1) on the ion yield of PFOS analyzed with SALDI-MS. Increasing the amount of adsorbed PFOS per nanoparticle increases the ion yield of PFOS in SALDI-MS; hence, the optimum relative ratio of CoC−NH2 nanomagnets to PFOS is achieved using the smallest amount of CoC−NH2 nanomagnets that can accommodate all the available PFOS. Several solutions of CoC−NH2 nanomagnets were prepared in the range of 0.25−10 mg/L and then used to enrich PFOS from a 1 ppt solution at pH 6.5, followed by SALDI-MS detection. Figure 5b shows the S/N ratio of the PFOS ion peak

3.0 was observed, while a significant decrease in the S/N ratio was observed at pH 11 (i.e., alkaline conditions). Since the pKa value for PFOS is very low at −3.27,48 PFOS predominantly exists in anionic form over the whole pH range used in this study. In solutions at pH < 7, the amino groups on the CoC− NH2 nanomagnets may be responsible for the uptake of anionic PFOS through electrostatic interactions in addition to the hydrophobic interactions between PFOS and the graphene or benzyl groups of the nanomagnets. At pH 11, protonation of the amino groups on the CoC−NH2 nanomagnets is inhibited, resulting in the reverse effect on the uptake of anionic PFOS in terms of electrostatic interactions. On the basis of these results, pH 6 was selected as the desired condition for the enrichment 9272

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Figure 5. (a) Signal-to-noise ratio of peak intensities (method 2) of PFOS measured using affinity SALDI-MS after enrichment from solutions of varying pH using CoC−NH2 nanomagnets (1 mg/L). (b) The signal-to-noise ratio of peak intensities of PFOS measured using affinity SALDI-MS after enrichment from solution at pH of 6.5 using CoC−NH2 nanomagnets at various concentrations.

Figure 6. SALDI mass spectra (method 2) of (a) PFBS:C4, (b) PFHxS:C6, and (c) PFOS:C8 obtained using affinity SALDI-MS after enrichment of the analytes from solution at pH 6 using 1 mg/L CoC−NH2 nanomagnets. The closed circles are the peaks of interest.

Extraction of PFCs with Different Chain Lengths from Water Using CoC−NH2 Nanomagnets, Followed by SALDI-MS Detection. Recently, perfluoroalkylsulfonic acid compounds with chains shorter than C8 have been used as an alternative to PFOS. We investigated how variations in the chain length of these PFCs influence their ion yield in SALDIMS when no extraction is performed (i.e., direct deposition of analyte onto CoC−NH2 nanomagnets on the MALDI plate). Figure 7 shows the peak intensities of (a) PFBS:C4, (b) PFHxS:C6, and (c) PFOS:C8 obtained using SALDI-MS. As the chain length increased from C4 to C8 (C8 corresponding to PFOS), the signal intensities increased, indicating that the desorption efficiency of PFCs increased with chain length. First, we expected that the ion yields decrease with the chain length because of the stronger interaction of the PFCs with longer chain to the CoC−NH2 surface, but the result was opposite tendency. The reason for this is not clear at present. PFCs with longer chains were also expected to have higher extraction efficiencies with CoC−NH2 nanomagnets because of their stronger hydrophobic interactions. We confirmed significantly higher detection sensitivity of PFCs with longer carbon chain with affinity SALDI MS using CoC−NH2 nanomagnets. The detection sensitivities of PFCs from 1 L of aqueous solution were 0.1 ppt for PFOS (C8, Figure 6c), 10 ppt for PFHxS (C6, Figure 6b), and 10 ppt for PFBS (C4, Figure 6a). Thus, our method was most suitable for the detection of PFOS with its longer chain because of the high

intensity after enrichment using varying concentrations of CoC−NH2 nanomagnets, with the maximum value occurring at 1 mg/L. As the concentration of CoC−NH2 nanomagnets increased above 1 mg/L, the amount of adsorbed PFOS per nanoparticle decreased, leading to a decrease in PFOS ion yield. On the other hand, very low concentrations of CoC−NH2 nanomagnets (0.25 mg/L) resulted in ineffective recovery of the magnetic NPs from suspension, also leading to a decrease in PFOS ion yields. Thus, a concentration of 1 mg/L of CoC− NH2 nanomagnets and pH 6 were selected as the optimal enrichment conditions for PFOS enrichment. Using these conditions, we found that detection of PFOS with affinity SALDI-MS using CoC−NH2 nanomagnets achieved high sensitivity, detecting 0.1 ppt PFOS from 1 L of solution, as shown in Figure 6c. This high detection sensitivity can be attributed to the interaction of PFOS with the benzylamine groups on the surface of CoC−NH2 nanoparticles, as well as the complete recovery of the CoC−NH2 nanomagnets from suspension due to the strong magnetic properties of the CoC NPs. The recovery ratio of PFOS from 1 L of 10 ppt PFOS aqueous solution using CoC−NH2 nanomagnets was more than 99%. To assess the performance of this method on an environmental sample, we analyzed a tap water sample including a spiked PFOS with affinity SALDI-MS using CoC−NH2 nanomagnets. The PFOS was detected in the tap water sample at a concentration of 5 ppt PFOS (Supporting Information Figure S4). 9273

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ASSOCIATED CONTENT

S Supporting Information *

Additional information as noted in text. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. (H.K.); wendelin.stark@chem. ethz.ch. (W.J.S.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This study was supported in part by the Strategic Project to Support the Formation of Research Bases at Private Universities with matching Fund Subsidy from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. This study was also partially supported by Grants-in-Aid for Scientific Research (Nos. 23360361, 23655074, and 22350040) from the Japan Society for the Promotion of Science (JSPS) and MEXT.

Figure 7. Peak intensities of (a) PFBS:C4, (b) PFHxS:C6, and (c) PFOS:C8 in SALDI-MS spectra (method 1) from deposition of 1 μL of 10 ppb PFC solution onto CoC−NH2 nanomagnets on the MALDI plate.

extraction and high desorption efficiency achieved with this analyte.

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CONCLUSIONS We have demonstrated that CoC−NH2 nanomagnets work well in tandem with SALDI-MS as a LDI-assisting material and for the extraction/enrichment of analytes from dilute solution. The core/shell structure with Co/graphene and the aminobenzyl surface modification of the CoC−NH2 nanomagnets both contribute to their compatibility with SALDI-MS. The benzylamine surface modification of the CoC nanomagnets was shown to increase the ion yield of angiotensin II and decrease ion fragmentation of benzylpyridinium ions. SALDI-MS using CoC−NH2 nanomagnets enabled the detection of various small molecule drugs including phenformin hydrochloride, N-propranolol hydrochloride, ranitidine hydrochloride, verapamil hydrochloride, and warfarin sodium, as well as the environmentally significant compounds PFOS, PFBS, PFHxS, PCP, and BPA. However, the detection of the small acidic drug molecules acetylsalicylic acid and ibuprofen were not achieved with this approach. We determined that the CoC−NH2 nanomagnets effectively enriched anionic PFCs from dilute aqueous solution through the combination of electrostatic attraction and hydrophobic interactions, which were then identified directly by SALDI-MS analysis (i.e., affinity SALDI-MS). The detection sensitivities of PFCs were 0.1 ppt for PFOS (C8), 10 ppt for PFHxS (C6), and 10 ppt for PFBS (C4). Thus, our method was suitable for the detection of all three PFCs but worked best for PFOS because of its longer chain, which enabled higher extraction and desorption efficiencies. In future work, it may be interesting to detect aromatic compounds as aqueous environmental samples using affinity SALDI-MS with CoC−NH2 nanomagnets, since it is expected that π−π stacking interactions between the benzylamino groups of CoC−NH2 and the aromatic compound will occur. In fact, preliminary experiment indicated that the detection of pentachlorophenol (20 ppb) in water, which is an organochlorine compound used as a pesticide and a disinfectant, was accomplished by the use of affinity SALDIMS with CoC−NH2 nanomagnets (Supporting Information Figure S5).

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