Keywords
genetically encoded probes
fluorescence
luminescence
live-cell measurement
activity-based sensing
Abstract
What evidence is needed to determine how an activity-based amino-acid reaction can convert intracellular formaldehyde into fluorescent or luminescent signal? This review answers by treating activity-based intracellular sensing as a property of a sociotechnical workflow rather than a feature that can be read from average accuracy. The focal setting is live-cell measurement of formaldehyde using genetically encoded optical reporters, where valid structures or bright signals can be mistaken for useful molecules or specific biological mechanisms without independent controls. Evidence from the assigned publications is synthesized with foundational studies of calibration, distribution shift, causal structure, and responsible deployment. Four requirements follow: preserve the lineage of molecular structures, spectra, protein constructs, illumination conditions, cellular readouts, and assay controls; measure stability across relevant perturbations; connect confidence to a specific action; and maintain a route for human challenge and correction. The framework distinguishes descriptive performance from decision utility and separates uncertainty about the world from uncertainty created by the model and its evaluator. It also shows why faster inference or richer reasoning is valuable only when it improves a defined decision under a transparent resource budget. The article is a literature review and research agenda, not a report of a newly completed trial.
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