The evaluation of proteins on bio-devices is one of the most important issues in biotechnology fields. In particular, evaluation of the changes in orientation and partial changes in structure of immobilized proteins are required for the development of sophisticated bio-devices. There are various methods being developed for protein evaluation. In this chapter, time-of-flight secondary ion mass spectrometry (TOF-SIMS), one of the most sensitive surface analysis methods, is described in terms of protein measurement. TOF-SIMS is useful for the evaluation of bio-device surfaces because it provides a submicron-scale mapping, orientation, and conformation of immobilized proteins on devices. In addition, TOF-SIMS requires no pretreatment of samples, such as labeling with a fluorescent probe or coating with metallic thin films, to prepare the samples. In the near future, conformation change of proteins after reactions or environmental change, such as changes in pH and orientation of binding sites of immobilized protein, will be measured with TOF-SIMS based on the analysis of partial chemical structures.
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