Design principles for molecular Raman sensors: A sea of opportunities

Molecular Raman sensors come with an unprecedented opportunity and promise of allowing simultaneous imaging and tracking of multiple bioanalytes in living cells. How can we achieve this dream goal for molecular imaging? Careful and strategic design of Raman sensors will be key. While we can utilize insights from foundational principles underlying molecular fluorescence sensor design to acheive selective detection, handling the inherent low sensitivity of Raman scattering is vital. Along with instrumentation, basic organic chemistry and molecular spectroscopy concepts can be leveraged to improve the sensitivity of Raman sensors to achieve live-cell imaging of endogenous levels of bioanalytes. In this Current Opinion paper, we attempt a 'Molecular Raman sensor design 101' for the chemical biologist, highlighting lessons from recent exciting examples of responsive Raman sensors.