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用于时间分辨荧光分析的垂直集成 CMOS 微系统。

A Vertically Integrated CMOS Microsystem for Time-Resolved Fluorescence Analysis.

出版信息

IEEE Trans Biomed Circuits Syst. 2010 Dec;4(6):437-44. doi: 10.1109/TBCAS.2010.2077290.

DOI:10.1109/TBCAS.2010.2077290
PMID:23853381
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.

摘要

我们描述了一种集成激发、检测和滤波功能的两芯片微尺度时间分辨荧光分析仪。一个新的 8x8 阵列的驱动器采用标准的低压 0.35-μm 互补金属氧化物半导体制造,与 AlInGaN 蓝色微像素发光二极管 (micro-LED) 凸点键合。该阵列能够产生宽度为 777 ps(半峰全宽)的样品激发脉冲,从而能够研究短寿命荧光团。荧光发射由第二个垂直相对的 16x4 阵列的单光子雪崩二极管 (SPAD) 检测,该阵列采用 0.35-μm 高压 CMOS 技术制造,具有像素内时间门控光子计数电路。捕获的芯片数据被传输到 PC 进行进一步处理,包括直方图、寿命提取、校准和背景/噪声补偿。这构成了最小的固态微系统荧光衰减分析报告,取代了激光器、光电倍增管、体光学和离散电子器件。该系统通过对荧光胶体量子点和罗丹明样品的测量得到了验证。

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