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Advanced Packaging enables heterogeneous integration of chiplets with die-embedding and die-stacking techniques, and provides maximum device performance with a much faster product development cycle. However, as the 2.5D and 3D packages are getting more and more complicated, it is very challenging to ramp the yield and assure the reliability of new products within this short timeline using conventional methods. Artificial Intelligence (AI)-assisted design co-optimization, manufacturing process simulation and monitoring, yield enhancement, reliability assurance, and failure mode prediction, which were developed for Si fabrication, could be employed to shorten the advanced packaging development cycle. This presentation summarizes the current status for the various applications of simulation and AI in advanced packaging. Further development trends are highlighted with the goal of providing a holistic and robust virtual representation, or digital twin, for advanced packaging.