Salt-triggered liquid phase separation and facile nanoprecipitation of aqueous colloidal gold dispersion in miscible biofluids for direct chromatographic measurement

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Abstract
With the recent tremendous increase of adapting gold nanoparticles (GNPs) for various biomedical applications, developing analytical tools for nanoseparation is an attractive focus and creates a challenge for the direct measurement of analytes of interest from the complex biomatrix–nanodispersion mixture. Herein, we report a new and green salt-induced phase segregation and nanoprecipitation method to remove water-soluble nanoparticles and to extract analytes from complex GNP-containing bio-samples into an organic phase for direct liquid chromatographic quantification, instead of traditional GNP-based colorimetric biosensing assays and energy-intensive separation approaches. This facile and efficient procedure involves a joint addition of sodium chloride and magnesium sulfate into a miscible mixture of biofluid/acetonitrile (1:1, v/v) to trigger the rapid salting-out extraction of analytes from the aqueous phase and the spontaneous direct-in-plate precipitation of nanoparticles plus biomatrix components coexisting in real samples with a single step. Relative UV-vis absorbance was evaluated as an indicator for determining nanoprecipitation efficiency towards colloidal GNPs in the size range of 5–100 nm under different electrolyte/organic solvent conditions. The feasibility of the validated method for removing nanoparticles and extracting analytes from human serum samples and liver microsomal reaction mixture highlights great the potential of the proposed strategy to isolate analyte molecules from colloidal nanoparticles in a broad variety of bio-fluids and water samples.

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