- We developed and characterized a platform based on gold (Au) nanoparticles (NPs) coated with poly(acrylic acid) (PAA) for harvesting positively charged, low molecular weight (LMW) proteins. The particles are synthesized using a layer by layer (LbL) procedure: first the gold NPs are coated with positively charged polyethylenimine (PEI) and subsequently with PAA. This simple procedure produces stable PAA-PEI-Au (PPAu) NPs with high selectivity and specificity. PPAu NPs successfully harvested, separated, and detected various LMW proteins and peptides from serum containing a complex mixture of abundant high molecular weight (HMW) proteins, including bovine serum albumin (BSA) and Immunoglobulin G (IgG). In addition, PPAu NPs selectively harvested and separated LMW proteins from serum in the presence of another positively charged competing protein. Furthermore, PPAu NPs successfully harvested a LMW biomarker in a mock diseased state. This system can be applied in various biomedical applications where selective harvesting and identifying of LMW proteins is required. A particularly useful application for this system can be found in early cancer diagnosis as described hereinafter.