Precise and sensitive protein detection is of great importance inproteomics and medical diagnostics. The fact that the luminescenceresponse of metal NCs to protein adsorption highly depends on thetype of bound protein offers a new platform for protein discrimina-tion where NCs can function as both sensing and reading units. Bycreating a sensor array composed of a series of different stabilizer-protected AuNCs, a distinct luminescence response pattern of eachanalyte protein can be obtained, thus allowing the identificationof proteins in a highly specific manner. Because the brightness ofmetal NCs is only moderate, one can enhance the detection sen-sitivity by plasmon-enhanced fluorescence (Aslan et al., 2005). Asdemonstrated in a recent study , the lumines-cence of AuNCs was enhanced by ca. 20-fold on the surface of asilver substrate, allowing a NC-based sensor array to be constructedthat was capable of detecting 10 different proteins down to 0.2 M.More recently, by using eight dual-ligand co-functionalized AuNCscombined with linear discriminant analysis (LDA), an array-basedluminescent sensor system was developed with which 48 unknownproteins could be discriminated (Fig. 2C). The key to this sensor sys-tem is also based on the specific NC–protein interactions that alterthe luminescence of NCs , the effectiveness ofwhich, however, could be compromised in a more complex envi-ronment. Nevertheless, this work is a further demonstration thatluminescent metal NCs can be utilized in many promising biologicaland biomedical applications.In summary, the findings reported here demonstrate vividlythat protein corona formation on the surfaces of metal NCs cansignificantly change their physicochemical properties and subse-quent biological responses. However, these studies are still only atthe beginning, and further work is required to achieve a thoroughmechanistic understanding of NC–protein interactions. More atten-tion should also be devoted to the study of biological interactionsof ultrasmall NCs within living model organisms, so that NCs canfinally be put to safe and effective use in a wide range of biomedical applications.