A vertically integrated CMOS microsystem for time-resolved fluorescence analysis

We describe a two-chip micro-scale time-resolved fluorescence analyzer integrating excitation, detection, and filtering. A new 8×8 array of drivers realized in standard low-voltage 0.35-μm complementary metal-oxide semiconductor is bump-bonded to AlInGaN blue micro-pixellated light-emitting diodes (micro-LEDs). The array is capable of producing sample excitation pulses with a width of 777 ps (FWHM), enabling short lifetime fluorophores to be investigated. The fluorescence emission is detected by a second, vertically-opposed 16 × 4 array of single-photon avalanche diodes (SPADs) fabricated in 0.35-μm high-voltage CMOS technology with in-pixel time-gated photon counting circuitry. Captured chip data are transferred to a PC for further processing, including histogramming, lifetime extraction, calibration and background/noise compensation. This constitutes the smallest reported solid-state microsystem for fluorescence decay analysis, replacing lasers, photomultiplier tubes, bulk optics, and discrete electronics. The system is demonstrated with measurements of fluorescent colloidal quantum dot and Rhodamine samples.