A novel method was designed for the determination of trace protein with high sensitivity. This sensing method combined the principle of biomineralization and the resonance scattering (RLS) assay of gold nanoparticles (AuNPs). AuNPs were synthesized in the presence of polpyropylneimine hexadeacamnie dendrimers (PPIHA). Meanwhile, they were superficially modified with the amine group, which was confirmed by Fourier transform infrared spectra (FTIR). The specific covalent coupling between bovine serum albumin (BSA) and amine-AuNPs assembles a hyperefficient crystal core. Based on the principle of biomineralization, Au(3+) ions were reduced to Au at the surface of bioconjugates in the HAuCl(4)-NH(4)OH center dot HCl redox system. Thus, the size of AuNPs-BSA was selectively enhanced. Meanwhile, the concentration signal of BSA was converted to the RLS intensity of AuNPs, which was enhanced through this process. The selective amplification of RLS signal laid the foundation of the detection method, as it intensified with the increase of AuNPs-BSA concentration. Experimental results show that the peak intensity at 548 nm is proportional to the concentration gradient of the bioconjugates from 0.268 mu g/ml to 1.608 mu g/ml under the optimized conditions. Additionally, the method has high sensitivity with detection limit as low as 0.096 mu g/ml. The specific coupling with high sensitivity and good stability of this method indicates its possibility for the assay of other proteins. Moreover, the novel method achieves quantitative detection of trace proteins, suggesting the potential of AuNPs-based analytical methods in further application. (C) 2011 Elsevier Inc. All rights reserved.