The DLS detector is embedded in the MALS detector.įield-flow fractionation was invented by Calvin Giddings in 1966 7. FFF-MALS-DLS system components and organization. The entire setup is controlled by the VISION(TM) software suite.įigure 1. For particles above 30 nm in radius, a wide-bore flow cell is installed in the MALS detector in order to provide the most accurate online DLS measurements. The system described here is implemented in Wyatt Technology’s FFF-MALS-DLS platform comprising an Eclipse(TM) FFF flow controller and separation channel, DAWN (R) MALS instrument, WyattQELS(TM) DLS module, Optilab(R) differential refractometer and standard HPLC components, illustrated in Figure 1.
#Dynamic light scattering size exclusion iso
These capabilities of FFF-MALS-DLS provide a pathway to meeting the requirements of regulatory agencies for enhanced characterization of liposomal drug formulations and other nanoparticle delivery systems 1–4 and have led to the development of international standards literature for nanoparticle characterization such as ISO TS 21362 and ASTM WK 68060, as well as methods published by the NCI-NCL and EU-NCL 5,6. It is a unique property of FFF that very little sample preparation is needed, because the separation method itself eliminates most impurities, and inherently performs dialysis into the carrier fluid. Since FFF systems incorporate standard chromatography modules, the measurements are fully automated, and fractions may be isolated and collected for additional off-line analysis. Spectroscopic and other types of online detectors may be added to obtain compositional information and more. Coupling FFF to online multi-angle light scattering (MALS) and DLS detectors provides detailed, quantitative size distributions and structural information, sampled over large ensembles, for good statistical robustness. For example, DLS is simple to use, and can sample a large particle ensemble, but only provides semi-quantitative, low-resolution size distributions on the other hand, TEM offers exquisite structural detail, at the cost of complexity, laborious sample preparation and very small ensembles that lead to high statistical uncertainty.įield-flow fractionation (FFF) is a size-based separation technique covering the entire range of macromolecules and nanoparticles from 1 - 1000 nm in diameter. Standard techniques such as dynamic light scattering (DLS), particle tracking analysis (PTA) and transmission electron microscopy (TEM) typically suffer from tradeoffs between simplicity, detail and sampling efficiency. One of the primary challenges in developing effective formulations for the nanoscale delivery of therapeutics is particle characterization. Transdermal Delivery Kydonieus Foundation Award.Nagai Postdoctoral Research Achievement Award Jorge Heller Journal of Controlled Release Outstanding Paper Award.Drug Delivery and Translational Research Journal Outstanding Paper Award.Drug Delivery and Translational Research.Next Generation Delivery and Diagnostics Symposium.Nanomedicine and Nanoscale Delivery (NND).Consumer & Diversified Products Division.All three approaches of liposome size analysis used here were found to yield useful results, although they were not fully congruent. When designing liposome-based drug carrier systems, a reliable and reproducible analysis of their size and size distribution is of paramount importance: Not only does liposome size influence the nanocarrier’s in-vitro characteristics such as drug loading capacity, aggregation and sedimentation but also it is generally acknowledged that the pharmacokinetic behaviour and biodis-tribution of the carrier is strongly size-dependent. Three sub-micron particle size analysis techniques were employed: (1) fixed-angle quasi-elastic laser light scattering or photon correlation spectroscopy (PCS), (2) size exclusion chromatographic (SEC) fractionation with subsequent (off-line) PCS size-analysis and quantification of the amount of particles present in the sub-fractions, and (3) field-flow-fractionation coupled on-line with a static light scattering and a refractive index (RI)-detector. Such liposomes were chosen since they can be looked at as a prototype of drug nano-carriers. The aim of the current study was to analyse the particle size distribution of a liposome dispersion, which contained small egg phosphatidylcholine vesicles and had been prepared by high-pressure homogenisation, by various size analysis techniques.
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