Adaptive time modulation technique for multiplexed on-chip particle detection across scales

Integrated optofluidic biosensors have demonstrated ultrasensitivity down to single particle detection and attomolar target concentrations. However, a wide dynamic range is highly desirable in practice and can usually only be achieved by using multiple detection modalities or sacrificing linearity. Here, we demonstrate an analysis technique that uses temporal excitation at two different time scales to simultaneously enable digital and analog detection of fluorescent targets. We demonstrated the seamless detection of nanobeads across eight orders of magnitude from attomolar to nanomolar concentration. Furthermore, a combination of spectrally varying modulation frequencies and a closed-loop feedback system that provides rapid adjustment of excitation laser powers enables multiplex analysis in the presence of vastly different concentrations. We demonstrated this ability to detect across scales via an analysis of a mixture of fluorescent nanobeads at femtomolar and picomolar concentrations. This technique advances the performance and versatility of integrated biosensors, especially toward point-of-use applications.