A key bidirectional switching issue in optogenetics emulated with laser dyes to illustrate its mitigation using nonlinear optical tools

Conventionally, bidirectional optogenetic switches are controlled with linear excitation (e.g., monochromatic CW light), which has serious limitations when there is a spectral overlap between the “on” and “off” states of switch. The crosstalk lowers selectivity photoactivation step, resulting in moderate photoequilibrium value poor dynamic range for Using stimulated depletion quenching (SDQ), nonlinear optical strategy similar to STED, we demonstrate enhanced on one side switch, thus shifting beyond what achievable light. discussion built around Cph8 as prototypical switch lacking complete photoreversibility upon because crosstalk. We use two fluorescent dyes analogues emulate key feature off Cph8; this way, focus initial step abstract from complicated subsequent dynamics. By applying SDQ mixture dyes, enhance regime. Increased via techniques should translate into an improved broad variety switches. These experiments provide basis further expand foundations non-conventional control methods biological switching.