In broad segments of the bio-pharmaceutical and medical device markets, the industry leaders are transitioning their technology development strategy from internal innovation to third party acquisition. At the same time the R&D budgets in these organizations continue to grow. The net result is most internal developments are being directed to incremental projects even though these organizations have the unique prerequisites (funding, problem statements, domain expertise, etc.) to conduct transformative research. The widespread adoption of this R&D strategy has broken the connection between the most scientifically intractable industrial problems, and the technical teams who are closest to these difficulties. At the same time academic funding has aggressively taken on grand challenges, and focused on translational research, but the nature of this focus can create inefficiency in identifying critical scientific problems outside the specific funding focus. In this talk I will review my journey in & out of academics and industry in an attempt to motivate an approach for identifying new high impact scientific problems. As examples, I will discuss the research and development I led as part of the maturation of the atomic force microscope, and how fundamental advances were applied to obtain high spatial resolution (sub-nanometer), high force sensitivity (