Techniques, devices and systems are disclosed for characterizing particles in a fluid sample by optical space-time coding. In one aspect, a microfluidic device for optical detection of particles includes a substrate, a microfluidic channel formed on the substrate and structured to carry a fluid sample containing particles, in which the microfluidic channel is structured to transmit a probe light, and a mask formed on one side of the microfluidic channel and structured to include a pattern of openings along the microfluidic channel, in which at least two of the openings have varying dimensions across the microfluidic channel, and in which the pattern of openings encodes a waveform on the probe light that transmits through the microfluidic channel to allow optical detection of a position of a particle in the microfluidic channel.