Low-cost luminescence lifetime imaging

A method for frequency-domain luminescence lifetime measurements of a sample, the method comprising:

• generating excitation light that is intensity-modulated at a first modulation frequency;
• directing at least a first portion of the excitation light at the sample to thereby cause an intensity-modulated luminescent emission from the sample;
• combining the intensity-modulated luminescent emission with a second portion of the intensity-modulated excitation light that has not contributed to luminescence of the sample to produce combined light;
• further intensity-modulating the combined light at a second modulation frequency to generate a doubly intensity-modulated optical signal that depends on a lifetime-induced phase shift between the intensity-modulated excitation light and the intensity-modulated luminescent emission;
• obtaining at least one intensity measurement that depends on the lifetime-induced phase shift by temporally integrating the doubly intensity-modulated optical signal with a detector;
• and
• processing the at least one intensity measurement to determine a lifetime value associated with the sample, using a machine-learned regression model.

A method for calibrating a frequency-domain luminescence lifetime measurement system for use with a sample, the method comprising:

• generating excitation light that is intensity-modulated at a first modulation frequency;
• imparting controlled optical path-length differences between first and second portions of the intensity-modulated excitation light to simulate respective luminescence lifetime-induced phase shifts;
• for each of the optical path-length differences:
• combining the first and second portions of the intensity-modulated excitation light to produce combined light,
• further intensity-modulating the combined light at a second modulation frequency to produce a doubly intensity-modulated optical signal,
• obtaining at least one intensity measurement corresponding to the controlled optical path-length difference by temporally integrating the doubly intensity-modulated optical signal with a detector;
• computing ground-truth lifetime values from the controlled optical path-length differences;
• and
• training a machine-learning regression model based on training data comprising the intensity measurements paired with the ground-truth lifetime values.