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 tem- poral 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. (c) 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement

Automated summary

Integrated optofluidic biosensors have achieved ultrahigh sensitivity for single particle detection and attomolar target concentrations. However, a wide dynamic range is often needed in practical applications, which can only be achieved by using multiple detection modalities or sacrificing linearity. In this study, a novel analysis technique using temporal excitation at two different time scales is demonstrated to enable simultaneous digital and analog detection of fluorescent targets. The technique enables seamless detection of nanobeads across eight orders of magnitude of concentration and multiplex analysis of fluorescent nanobead mixtures with vastly different concentrations. This advancement significantly improves the performance and versatility of integrated biosensors, especially for point-of-use applications.