Online coupling of hydrodynamic fractionation with DLS, MALLS and MPS for MPI tracer evaluation

Abstract

INTRODUCTION: Currently, one of the main issues to improve the image quality of Magnetic Particle Imaging (MPI), besides the development of applicable MPI scanner systems and reconstruction methods, is the improvement of magnetic properties of magnetic nanoparticles (MNP), the so-called MPI tracer. Optimized tracers potentially enhance mass sensitivity and spatial resolution of MPI and may be the key for successful clinical MPI [1]. Magnetic Particle Spectroscopy (MPS), the zero-dimensional MPI, has been proven a straightforward technique to study the MPI performance of MNPs [2]. Generally, synthetic MNP preparation routes typically result in a more or less broad distribution of particle sizes with correspondingly different MPI performance [3]. Thus, it is difficult to identify the part of the distribution which contains the most suitable MPI tracer within a sample. To improve this situation we extended the in situ MPS-characterization of MPI tracers by online coupling to hydrodynamic separation (asymmetric flow field-flow fractionation, A4F) of MNP. The A4F-MPS setup was further equipped with online UV detection, dynamic light scattering (DLS) and multi angle laser light scattering (MALLS). Here, we report on the first results applying the extended MPS online detection in the A4F multi-detector setup using the MPI "gold-standard" Resovist®. METHODS:For the MPS online detection a capillary flow cell consisting of quartz glass with 3 turns in the sensitive measurement area (8x8 mm, V cell =8.9 μL) of the MPS (Bruker, GER) was manufactured. The flow cell was tested with respect to flow velocity dependent MPS signal changes using MNP of different sizes. The separation experiment was performed using the precursor of commercially available MNP Resovist ® (DDM128) purchased from Meito Sangyo (JPN). By A4F MNP were separated according to their size, with retention time that is directly proportional to hydrodynamic extension. The A4F (Postnova, GER) was connected directly to the UV detector ( =280 nm), the flow cell of the MALLS (PN3621, Postnova, GER) and the DLS (Zetasizer Nano ZS, Malvern, UK). Furthermore, MPS (B excite =25 mT, f excite =25 kHz) was directly coupled at the end of the detection line. RESULTS:The manufactured flow cell was capable of performing MPS measurements on MNP in flows up to 1 mL/min with no significant MPS signal change. When coupled to the A4F the temporal evolution of the MPS signal could be detected over a broad range of retention times and MNP sizes (see Fig.1). The application of the A4F multi-detector characterization of DDM128 confirmed the presence of a bimodal distribution of sizes which can be deduced from the UV trace (mainly proportional to the iron content) showing two distinct maxima at an elution volume of 4 mL and 11 mL. The hydrodynamic and cluster size measured by DLS and MALLS, respectively, linearly increased with retention time. The MPS signal represented by the third harmonic amplitude μ 3 ranging over two orders of magnitude did not correlate linearly with MNP size. The ...

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