This project develops a portfolio of molecular tags that emit strong signals when stimulated by mid-infrared (MIR) light. These molecular MIR tags are designed to light up selected parts in the cell when illuminated with an MIR microscope. The MIR tags developed by the investigators enable the visualization of molecular diffusion and chemical conversion, including numerous metabolic processes in cells and tissues, processes that have hitherto remained out of reach for MIR microscopy. This development transforms the MIR microscope from an instrument for inspecting static images of cells and tissue to a technology for studying dynamic processes such as cellular cholesterol uptake, protein synthesis and lipogenesis. This capability opens up new opportunities for investigating cellular processes that are difficult to study with standard optical microscopy methods. The investigators are committed to broaden the participation of a diverse pool of students by providing summer research training to students from HBCUs through the Access to Careers in Engineering and Sciences (ACES) program.
MIR imaging, typically in the form of Fourier transform infrared (FTIR) microscopy, is a label-free imaging tool based on molecular vibrational contrast. MIR labels or tags can significantly improve the specificity of MIR imaging, yet MIR labels have so far not been used for imaging purposes. The use of MIR labels would expand the complementary vibrational palette in IR microscopy, opening up a new catalogue of biorthogonal molecular probes based on IR transitions, and offering strategies for super-multiplex imaging. In this project, the PI and co-PI develop a portfolio of chemical motifs that exhibit an exceptionally strong IR-response. They will use these motifs as vibrational tags of small molecules, including cholesterol, glucose, nucleic acids, amino acids and other metabolites. In addition, the team will design probes suitable for fluorescence encoded infrared (FEIR) excitation and detection, enabling multiplex labeling studies in the MIR microscope with sensitivities that reach the single molecule limit.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
