An optimized filling method for capillary DLS

Capillary dynamic light scattering (DLS) is a new, simple and enabling technique, that increases the size range of DLS by over an order of magnitude in a cheap, disposable, but high optical quality, glass capillary. Sample loading for other capillary-based modalities, such as blood analysis, is typically achieved by dipping the capillary into the bulk sample, however, DLS is exquisitely sensitive to static scattering such as from a fluid meniscus or sample dried on the outside of the capillary and is sometimes used for extended measurement times where evaporation must be avoided. In this work, we carefully validate capillary dipping and sealing with a clay plug for DLS against reference measurements in a high quality 1 cm cuvette and then introduce a simple capillary loading scheme that reproducibly places a >3 μl sample in the correct location for a DLS measurement. We demonstrate the statistically identical characterisation of the new scheme and dipping against the reference measurements, but in sample volumes reduced by 1 and 3 orders of magnitude, respectively, key for high value applications such as pharmaceutical development where sample costs of $100 k per mg are common and in the environmental & medical sciences where samples may be difficult or unethical to collect in bulk. • Use of the capillary method to characterize high value samples in the lowest, reproducible volume. • Pitfalls and subsequent development of the best reproducible method.