CMOS imagers for low-level light and high-speed biomedical applications.

摘要

Abstract Fluorescence optical imaging is becoming a very important technique for in vivo imaging and characterization of biological tissues. In order to add more contrast to the fluorescence image, fluorescence life-time imaging (FLIM) can be used, making it possible to differentiate between molecules with overlapping spectra, such as cancerous and noncancerous cells. However, designing FLIM imaging systems in a compact, complete camera-on-chip solution is a very challenging task and has led to significant research efforts in designing high-speed and high sensitivity imagers.;The sensitivity was further improved using avalanche photodiode single-photon counters that were implemented in a standard digital 130 nm CMOS technology. The circuit achieves deadtimes as low as 200 ps, which is at least an order of magnitude less than previous work. The circuit also has a higher fill-factor of 25%, compared to 1-5% in previous work. A novel deadtime reduction technique design for active quench and reset circuits is also discussed.;The dynamic range of the imager was also improved using a novel design that relies on single-photon counting in time-domain. The design can achieve high sensitivity and high dynamic range, while maintaining a speed that is around 1000 times faster than conventional time-domain imagers. In order to further improve the frame rate, an imager that allows for simultaneous pixel counting and threshold detection in time-domain was also designed. The pixel also includes a novel analog counting technique that al10ws for an increased fill-factor.;This work focuses on designing low-light level imagers in CMOS technology for biomedical applications that can be suitable for extremely high-speed imaging applications, such as FLIM. A fully integrated, 256-pixel CMOS camera-on-chip, was fabricated in a standard CMOS 0.18 mum technology. The imager was tested by controlling it with an Altera FPGA board. When clocking the ADC at a frequency of 1 MHz, images were obtained at about 60 frames/so The design was next improved to achieve ultrahigh-speed imaging using a CMOS imager that can capture 8 frames with a frame capture rate that is higher than 1.25 billion frames per second.