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To understand which organic molecules are capable of binding to gold nanoparticles and/or inducing nanoparticle aggregation, we investigate the interaction of gold nanoparticles with small molecules and amino acids at variable pH. Dynamic Light Scattering (DLS) and ultraviolet-visible (UV-vis) spectra were measured on mixtures of colloidal gold with small molecules to track the progression of the aggregation of gold nanoparticles. We introduce the 522 to 435 nm UV-vis absorbance ratio as a sensitive method for the detection of colloidal gold aggregation, whereby we delineate the ability of thiol, amine, and carboxylic acid functional groups to bind to the surfaces of gold nanoparticles and investigate how combinations of these functional groups affect colloidal stability. We present models for mechanisms of aggregation of colloidal gold, including surface charge reduction and bridging linkers. For all molecules whose addition leads to the aggregation of gold nanoparticles, the aggregation kinetics were accelerated at acidic pH values. Colloidal gold is maintained only in the presence of anionic carboxyl groups, which are neutralized by protonation at lower pH. The overall reduced charge on the stabilizing carboxyl groups accounts for the accelerated aggregation at lower pH values.

The present manuscript describes a biomarker capturing strategy based on nanoporous silica particles. The method is shown to enrich the yield of species in the low‐molecular weight proteome (LMWP), allowing detection of small peptides in the low‐nanomolar range. Plasma samples were exposed to the silica particles, and the captured molecular species were profiled using MALDI‐TOF. Mass spectra of the silica‐treated human plasma samples showed a significant enrichment in MALDI‐TOF protein profiles in the LMWP. Preliminary results indicated good level of reproducibility in plasma profiles with CVs on peak heights ranging from 6.3 to 14.7%. The MALDI‐TOF signature changed significantly when the characteristics of the nanoporous silica were altered. The facile sample pretreatment before MS analysis, coupled to the potential for tailoring the surface properties of silica supports, hold promise for improving the recovery of low‐abundance serum biomarkers.

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