Multicore Magnetic Nanoparticles (MMNPs) Doped with Cs and FITC

Mar 27, 2014 - Multicore Magnetic Nanoparticles (MMNPs) Doped with Cs and FITC for the Determination of Biomarker in Serum using ICP-MS. Jungaa Ko and...
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Technical Note pubs.acs.org/ac

Multicore Magnetic Nanoparticles (MMNPs) Doped with Cs and FITC for the Determination of Biomarker in Serum using ICP-MS Jungaa Ko and Heung Bin Lim* Department of Chemistry, NSBI, Dankook University, 126 Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701, Korea S Supporting Information *

ABSTRACT: Multicore magnetic nanoparticles (MMNPs) doped with Cs and FITC (Cs/FITC-doped MMNPs) were synthesized for the extraction and determination of biomarkers using inductively coupled plasma-mass spectrometry (ICPMS). For demonstration, the MMNPs were used for magnetic separation to extract CA19-9 in serum nonspecifically, and the doped Cs was used as an internal standard for the ratiometric measurement of the tagged particle. This ratiometric method compensated for the particle loss in a magnetic separation and suppressed the signal fluctuation which increased the calibration linearity significantly. The obtained detection limit was 0.02 units/mL of CA19-9, which is more than 300 times lower than that reported by the ICP-MS with element tagging and about 500-fold improved compared to ELISA.

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their large size for centrifugation and the preservation of the superparamagnetic force. In addition, since the doped Cs and FITC act with magnetic cores during the magnetic separation, the signal changes of Cs in ICP-MS will be related to the number of particles. Therefore, for the analytical platform of either nonspecific or sandwich-type extraction, the measured Cs signal can be used as a reference for the measurement of tagged particles. Furthermore, the doped Cs can be substituted by the other metals for multiplex detection that can be an important issue for cancer diagnosis using biomarkers and mass cytometry. Noticeably, the 56Fe and 57Fe peaks of the MMNPs suffer from the heavy molecular interference of 40 16 + Ar O and 40Ar16OH+ for the ratiometric measurement in ICP-MS. As a demonstration, the synthesized MMNPs were used to determine CA19-9 in serum and the analytical result was compared with that of ELISA for validation. Many analytical methods have been developed to determine CA199 quantitatively (Table S-1 of the Supporting Information).9−15 ELISA is the simple and widely used analytical technique but suffers from high detection limits and poor linearity, depending upon what it is used to detect.16 Although electrochemical detection showed the lowest limit of detection with a large dynamic range (i.e., 0.04 units/mL using ZnO quantum dot with the dynamic range of 0.1−180 units/mL),11,14 it had a limitation in selectivity and multiplex detection. Recently ICPMS with element tagging performed the detection limit of 6 units/mL, which was relatively high compared to the other methods.13 Now, the developed method using the Cs/FITC-

ecently, element tagging with inductively coupled plasma mass spectrometry (ICP-MS) showed the potential to achieve multiplex analysis for massive bioassays and clinical diagnosis by mass cytometry,1,2 although it still suffers from low sensitivity and difficulties in tagging elements. Particle tagging can substitute for the element tagging because it requires no ligand and inherently improves the sensitivity due to more atoms for a target.3−5 Two different types of sample treatment platform are possible (i.e., nonspecific extraction and sandwichtype extraction). The selection of the platform depends upon the functional group of the target molecule. For both platforms, the magnetic separation inherently suffered from particle loss during a washing step, which caused measurement errors, signal fluctuation, and poor sensitivity.6 Now, with the promise of ICP-MS with particle tagging for clinical diagnosis and mass cytometry, and the consequent inevitability of sample treatment using MNPs, the limitations in accurate and reliable quantification might be overcome. In this work, we synthesized multicore magnetic nanoparticles doped with Cs and FITC (Cs/FITC-doped MMNPs) for application as analytical platforms. The designed MMNPs can have multifunctional characters, such as the preservation of superparamagnetic property for magnetic separation, multicores with a size of a few tens of nanometers for activity, the doped metal for an interference-free signal in ICP-MS, the FITC for fluorescence monitoring, and the silica shell for surface modification. Among these, the multicores and the doped Cs metal are important features in this analytical platform. The superparamagnetic NPs, with a size of