This Funding Opportunity Announcement (FOA) encourages Small Business Innovation Research (SBIR) research grant applications to develop next-generation tools that distinguish heterogeneous states among cells and have commercial potential. Applications should define the current state of technology as a benchmark against which the new tool(s) will be measured. Applications should also propose proof-of-concept testing of the tool(s) in a complex biological tissue or living organism. The new tools should provide substantially increased sensitivity, selectivity, spatiotemporal resolution, scalability or non-destructive analysis of multiple global or functional measures of single cells. These novel technologies will aid in obtaining a fine-grained, integrative and dynamic view of heterogeneous cellular states/classes and will provide innovative platforms to transform research into the cellular basis of diseases.