A polarization sensitive light scattering unit for high throughput screening.

A simple, effective light scattering prototype sensitive to both polarized and depolarized scattering was constructed, and its performance was tested on a variety of pure liquids and optically isotropic and anisotropic polymer solutions and colloidal suspensions. The results, performance, and means to further improvement are reported here. Because of its simplicity and low cost, many identical units can be produced to construct a simultaneous multiple sample light scattering platform that can be used to monitor polymer and colloid solution stability, phase changes, aggregation, degradation, etc.

Identifying protein aggregation mechanisms and quantifying aggregation rates from combined monomer depletion and continuous scattering.

Parallel temperature initial rates (PTIR) from chromatographic separation of aggregating protein solutions are combined with continuous simultaneous multiple sample light scattering (SMSLS) to make quantitative deductions about protein aggregation kinetics and mechanisms. PTIR determines the rates at which initially monomeric proteins are converted to aggregates over a range of temperatures, under initial-rate conditions. Using SMSLS for the same set of conditions provides time courses of the absolute Rayleigh scattering ratio, IR(t), from which a potentially different measure of aggregation rates can be quantified.

Monitoring protein aggregation kinetics with simultaneous multiple sample light scattering.

A simultaneous multiple sample light scattering (SMSLS) prototype instrument was built to simultaneously measure light scattering from many independent monoclonal antibody (mAb) solutions in order to monitor their time-dependent aggregation behavior and to characterize, via absolute Rayleigh scattering ratios, their molecular masses and second, third, and fourth virial coefficients under non-aggregating conditions at concentrations up to 190mg/ml. One stable mAb and another prone to aggregation were studied. Early phase aggregation rates spanned six orders of magnitude over temperatures 30 to 83°C for both mAbs and divided into "Arrhenius" and "Stochastic" regimes.

Simultaneous in-situ monitoring of parallel polymerization reactions using light scattering; a new tool for high-throughput screening.

A recently introduced technique, simultaneous multiple sample light scattering (SMSLS), was used to monitor parallel polymerization reactions in situ. SMSLS is designed for real-time, high-throughput screening and provides a time-dependent light scattering signature for each reaction, which contains both qualitative and semiquantitative information. Qualitatively, the signature immediately indicates whether the reaction occurs or not, whether there is an initial lag period, and how long the reaction takes until it stops.