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System or component prognosis can be accomplished by integrating a combination of technologies into an overall processing architecture. Key elements of this include sensed data inputs, understanding of failure physics, and variability-based life prediction techniques. Future prognosis systems can take advantage of newly developed probabilistic microstructural-based material simulation modeling for prediction of crack initiation and small crack growth of significantly smaller size than allowed by present day sensor technology. This work presents an overview of ongoing prognosis development and how material-based modeling fits within processing architectural plans.