A Chemigenetic Fluorescence Lifetime Biosensor for Dopamine Sensing

dHaloLife635, a chemigenetic fluorescence-lifetime dopamine sensor in live HEK293T cells, shows a 0.21 ns fluorescence lifetime decrease upon dopamine binding.

• Why it matters: Intensity-based neurochemical sensors struggle with artifacts from sensor expression changes and rapid photobleaching, limiting reliable multi-neurochemical dynamics tracking in live neurons.
• What they did: The sensor combines hDRD1, a circularly permuted HaloTag, and JF635-HTL; dopamine-induced conformational changes shift the dye’s fluorescence lifetime, enabling binding readout.
• The result: In live HEK293T cells it responds to dopamine but not serotonin, L-DOPA, or GABA, and only marginally to norepinephrine; primary neurons confirm dopamine selectivity, supporting multiplexable lifetime sensing over extended timescales.

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