Studying Soft-matter and Biological Systems over a Wide Length-scale from Nanometer and Micrometer Sizes at the Small-angle Neutron Diffractometer KWS-2.

The KWS-2 SANS diffractometer is dedicated to the investigation of soft matter and biophysical systems covering a wide length scale, from nm to µm. The instrument is optimized for the exploration of the wide momentum transfer Q range between 1x10-4 and 0.5 Å-1 by combining classical pinhole, focusing (with lenses), and time-of-flight (with chopper) methods, while simultaneously providing high-neutron intensities with an adjustable resolution. Because of its ability to adjust the intensity and the resolution within wide limits during the experiment, combined with the possibility to equip specific sample environments and ancillary devices, the KWS-2 shows a high versatility in addressing the broad range of structural and morphological studies in the field. Equilibrium structures can be studied in static measurements, while dynamic and kinetic processes can be investigated over time scales between minutes to tens of milliseconds with time-resolved approaches. Typical systems that are investigated with the KWS-2 cover the range from complex, hierarchical systems that exhibit multiple structural levels (e.g., gels, networks, or macro-aggregates) to small and poorly-scattering systems (e.g., single polymers or proteins in solution). The recent upgrade of the detection system, which enables the detection of count rates in the MHz range, opens new opportunities to study even very small biological morphologies in buffer solution with weak scattering signals close to the buffer scattering level at high Q. In this paper, we provide a protocol to investigate samples with characteristic size levels spanning a wide length scale and exhibiting ordering in the mesoscale structure using KWS-2. We present in detail how to use the multiple working modes that are offered by the instrument and the level of performance that is achieved.

Tuning the instrument resolution using chopper and time of flight at the small-angle neutron scattering diffractometer KWS-2.

Following demand from the user community regarding the possibility of improving the experimental resolution, the dedicated high-intensity/extended Q-range SANS diffractometer KWS-2 of the Jülich Centre for Neutron Science at the Heinz Maier-Leibnitz Center in Garching was equipped with a double-disc chopper with a variable opening slit window and time-of-flight (TOF) data acquisition option. The chopper used in concert with a dedicated high-intensity velocity selector enables the tuning at will of the wavelength resolution Δλ/λ within a broad range, from 20% (standard) down to 2%, in a convenient and safe manner following pre-planned or spontaneous decisions during the experiment. The new working mode is described in detail, and its efficiency is demonstrated on several standard samples with known properties and on a completely new crystallizable copolymer system, which were investigated using both the conventional (static) and TOF modes.

Fasted-state simulated intestinal fluid "FaSSIF-C", a cholesterol containing intestinal model medium for in vitro drug delivery development.

A set of biorelevant media "fasted-state simulated intestinal fluid with cholesterol (FaSSIF-C)" for the in vitro study of intestinal drug dissolution in the duodenum was developed. These contain cholesterol at the same levels as in human bile: the cholesterol content of FaSSIF-7C is equivalent to healthy female, FaSSIF-10C to healthy male persons, and FaSSIF-13C to several disease cases that lead to gallstones. The fluids were studied in three aspects: biocompatibility, intestinal nanostructure, and solubilizing power of hydrophobic drugs of the BCS class II. The biocompatibility study showed no toxic effects in a Caco-2 cell system. The drug-solubilizing capacity toward Fenofibrate, Danazol, Griseofulvin, and Carbamazepine was assessed as example. It varied with the cholesterol content widely from a fourfold improvement to a twofold reduction. The nanostructure study by dynamic light scattering and small-angle neutron scattering indicated vesicles as the main component of FaSSIF-C in equilibrium (>1 h), but at high cholesterol content, larger particles were observed as a minor contribution. The neutron experiments indicated the presence of complex micelle-vesicle mixtures, even after 1 h development of fed-state bile model to FaSSIF. The results indicate that cholesterol affects some drugs in solubilization and particle size in intestinal model fluids.