The Next Big Thing is: There is no Next Big Thing.
"The Next Big Thing does exist...it just doesn't look BIG to IBM. That is a common problem with large companies. When you have revenues of $40B to $100B no one thing will move the needle. Nothing looks big or interesting. Innovative or disruptive technologies are viewed as a threat to the core revenue stream, rather than promising new opportunities. This is the premise of The Innovators Dilemma by Clayton Christensen."
Don works at Microsoft. He's 100% working with companies that could become the next big thing, and lists 32 of them. I've personally only heard of three that he mentions: Akimbo, Newsgator and Onfolio (Don - didn't we just buy them??). I need to find out more about Adesso Systems ('WinFS today'), Digipede (gridware) and Fractal Edge (data visualization).
(Don - check out RSSLabs (in Boston too...) - they're using .NET to do some interesting stuff in the RSS and OPML space: OPMLSearch.com, OPMLWorkstation.com and TopTensources.com. Bela, Jim and John are the people there.)
If you're a startup and wanting to get in touch with someone at Microsoft, here are some people that could help you out.