A High-Throughput Time-Resolved Mini-Silicon Photomultiplier With Embedded Fluorescence Lifetime Estimation in 0.13 <formula formulatype="inline"> <tex Notation="TeX">$\mu$</tex></formula>m CMOS

Abstract

We describe a miniaturized, high-throughput, time-resolved fluorescence lifetime sensor implemented in a 0.13 m CMOS process, combining single photon detection, multiple channel timing and embedded pre-processing of fluorescence lifetime estimations on a single device. Detection is achieved using an array of single photon avalanche diodes (SPADs) arranged in a digital silicon photomultiplier (SiPM) architecture with 400 ps output pulses and a 10% fill-factor. An array of time-to-digital converters (TDCs) with ≈50 ps resolution records up to 8 photon events during each excitation period. Data from the TDC array is then processed using a centre-of-mass method (CMM) pre-calculation to produce fluorescence lifetime estimations in real-time. The sensor is believed to be the first reported implementation of embedded fluorescence lifetime estimation. The system is demonstrated in a practical laboratory environment with measurements of a variety of fluorescent dyes with different single exponential lifetimes, successfully showing the sensor's ability to overcome the classic pile-up limitation of time-correlated single photon counting (TCSPC) by over an order of magnitude.

A Low-Power Gateable Vernier Ring Oscillator Time-to-Digital Converter for Biomedical Imaging Applications

“…3(a), there are eight differential delay elements in each RO, so we can have 16 phase pairs, which are PS(1) to PS (16) and PF (1) to PF (16). The triggers the sampling operation of its corresponding , where .…”

“…Then, the conversion is completed and the ROs will be turned off. In order to cover a large dynamic range with the gateable Vernier ring oscillator TDC, a loop counter, being triggered by the phase PF (16), is implemented to record the circulation number of the fast RO during the conversion.…”

“…The output of the sampling circuits is recorded and updated at the rising edge of every phase clock in the fast RO, i.e., PF(1) to PF (16). The output of the loop counter has an increment every period of PF (16).…”

“…Since the fluorescence lifetime is extremely sensitive to the local environmental condition, then the fluorescence lifetime spectrum using the timecorrelated single-photon counting (TCSPC) method reveals a number of important biological and chemical information. Such a principle has been widely used in time-resolved fluorescence imaging [16]- [18].…”

Improving the counting efficiency in time-correlated single photon counting experiments by dead-time optimization

“…The idea of routing a signal coming from a single detector to multiple converters is known in the literature. 24 The main idea of the F-TAC is presented in Figure 6. Several time-to-amplitude converters are put in parallel, sharing the same stop signal provided by the external sync source, e.g., the excitation laser.…”