Proteinchip is a newly developed protein analytical technology with the advantage of integrated, parallel, fast and automatic analysis. The Multi-Optical ProteinChip developed by Professor Gang Jin’s group is a label-free technique that can be used to detect biomolecules and investigate biomolecule interaction with micro biological sample. Great progress has recently been made in chip surface modification and biomedical application of the Optical ProteinChip. 1) One of the most important factors affecting the detection sensitivity of proteinchip is the immobilization of biomolecules and the maintenance of functional configuration on the substrate surface. Protein A is used to modify silicon surface for antibody immobilization, through which the antibody molecules can be selectively immobilized on the chip. This mode of immobilization results in the uniform orientation of the antigen-binding sites, Fab variable regions, up from the surface, well accessible for interaction with the antigen, which maximizes the antigen-binding capability of the antibody and increases the detection sensitivity. Two patents have been applied about this technology. 2) Physical adsorption is a kind of immobilization method mainly used in proteinchip. The biological activity of the immobilized protein is usually less than that of soluble state and the amount of immobilized protein was unstable due to the desorption and the competitive adsorption of other proteins. In order to overcome the problem, a kind of covalent immobilization method using aldehyde has been developed. This silicon surface modification is simple and in favor of the maintenance of protein activity. The modification method has been routinely used in the proteinchip preparation. 3) Another kind of surface modification with a mixed silanes layer to immobilize proteins has also been developed for silicon and gold surface. Using this method, not only the biomolecules can be immobilized but also the non-specific adsorption is effectively inhibited. This modification has the advantage of stability of the immobilized protein, less effect of protein conformation, and high biological activity. 4) CA153 is a kind of cancer marker in blood for the early detection of the breast cancer. The Optical ProteinChip has been successively used to detect CA153 in serum and the detection sensitivity is high enough for the clinic detection. Cooperating with the Chinese Academy of Medical Sciences, the group has detected 23 patient’s serum with different CA15-3 concentration. The detection result using Optical ProteinChip is highly consistent with that of the gold standard—ECLIA (electrochemiluminescence immunoassay), indicating that Optical ProteinChip can be used for quantitative detection with high sensitivity.