For over the last decade, researchers at the National Center for Microscopy and Imaging Research (NCMIR, http://ncrrdr.ucsd.edu) have been developing and implementing novel technologies to propel collaborative research. NCMIR has built flexible high throughput, cyber infrastructure environments which connect researchers to advanced imaging instruments datagrids and computational grids. Through the integration of pioneering research in remote instrumentation research (known as Telemicroscopytrade) and grid based distributed computing and data management, this group demonstrated this vision in the context of The Telescience Project (https://telescience.ucsd.edu). Telescience provides an end-to-end, single sign-on solution for biomedical image analysis and structure-function correlation that integrates users with resources and applications with unified security and without prohibitive complexity. Here, we describe the flattening and generalization of the layers of software that make up the Grid-based system architecture of the project. In particular, we focus on the maturation and generalization of the architecture, including the development of an Application to middleware interaction component (ATOMIC) services fabric that streamlines application integration with core grid middleware. This broadening of the overall grid service architecture is the product of over 6 years of user-developer iterative software refinement cycles which have resulted in a suite of Telescience Tools that provide generalized solutions for increasing the interoperability of user interfaces (Web portals and applications) and externally addressable grid resources (instruments and computers)