A Vertically Integrated CMOS Microsystem for Time-Resolved Fluorescence Analysis

Abstract

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.

Noise analysis and measurement of integrator-based sensor interface circuits for fluorescence detection in lab-on-a-chip applications

“…There are disadvantages, however, mainly associated with the near isotropic light emission pattern. Rae et al showed LEDs deposited on an ASIC and used in conjunction with a single-photon avalanche diode (SPAD) array to measure fluorescent dye [28]. Chediak et al provided a more compact implementation where a small LED was deposited on a PIN photodiode below a microfluidic channel [37].…”

“…With suitably fast electronics it is possible to shutter the light source and record the decay of the fluorescence [28,54,55].…”

“…The absence of an optical filter is suspected for this omission. Later publications by the same group demonstrated optical detection using a two-chip solution, with the light-source chip placed down on the detection chip with the sample and high-quality optical filter placed in between [28]. A hypothetical hybrid ASIC/microfluidic LOC device for FD detection is shown in Figure 1.1.…”

Ultra-portable explosives sensor based on a CMOS fluorescence lifetime analysis micro-system

“…3 In this work, we demonstrate PL lifetime detection of low pressure explosive vapours of 1,4-dinitrobenzene (DNB) using thin films of a fluorescent conjugated copolymer combined with a very compact CMOS time-resolved fluorescence lifetime micro-system. 6 The fluorescent conjugated copolymer is a fluorene based copolymer "CDT Green (CDTG)" supplied by Cambridge Display Technology Limited (CDT Ltd). In addition to standard TCSPC measurements, we also use a two-gate rapid-lifetime determination (RLD) algorithm 7 to compute the PL lifetime in real time.…”

Modulation bandwidth studies of recombination processes in blue and green InGaN quantum well micro-light-emitting diodes

“…Fast modulation speeds would also be advantageous for the use of these devices in time-resolved fluorescence measurements. 4 There is also great interest because of the importance of these processes in the effect known as "droop," where--except at very low current densities below a few tens of A cm À2 --the quantum efficiency of GaN LEDs decreases with applied current. 5 There is much controversy over the physical mechanisms causing droop.…”