Abstract

Organic fluorophores and quantum dots are ubiquitous as contrast agents for bio-imaging and as labels in bioassays to enable the detection of biological targets and processes. Upconversion nanoparticles (UCNPs) offer a different set of opportunities as labels in bioassays and for bioimaging. UCNPs are excited at near-infrared (NIR) wavelengths where biological molecules are optically transparent, and their luminesce in the visible and ultraviolet (UV) wavelength range is suitable for detection using complementary metal-oxide-semiconductor (CMOS) technology. These nanoparticles provide multiple sharp emission bands, long lifetimes, tunable emission, high photostability, and low cytotoxicity, which render them particularly useful for bio-imaging applications and multiplexed bioassays. This paper surveys several key concepts surrounding upconversion nanoparticles and the systems that detect and process the corresponding luminescence signals. The principle of photon upconversion, tuning of emission wavelengths, UCNP bioassays, and UCNP time-resolved techniques are described. Electronic readout systems for signal detection and processing suitable for UCNP luminescence using CMOS technology are discussed. This includes recent progress in miniaturized detectors, integrated spectral sensing, and high-precision time-domain circuits. Emphasis is placed on the physical attributes of UCNPs that map strongly to the technical features that CMOS devices excel in delivering, exploring the interoperability between the two technologies.

Highlights

  • Medical, environmental, and life science applications generate demands for low-cost small-size biochemical assay systems

  • Recent advances in single-photon avalanche diodes (SPADs) and on-chip to-digital converter (TDC) implemented in standard complementary metal-oxide-semiconductor (CMOS) processes have enabled time-correlated single photon counting (TCSPC) measurements to be performed by an imaging array, and with much higher time resolution [94]

  • Two characteristics are noteworthy when combining the use of Upconversion nanoparticles (UCNPs) with CMOS technology

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Summary

Introduction

Environmental, and life science applications generate demands for low-cost small-size biochemical assay systems. Intermittent emission limits their use for labeling individual biological molecules Both the organic fluorophores and quantum dots are generally excited with ultraviolet (UV) and visible light. UC nanoparticles, or UCNPs, exhibit anti-Stokes emission, and can be excited in the near-infrared (NIR) spectral region where biological molecules are generally optically transparent. These nanoparticles typically show sharp emission bands at a number of wavelengths, long lifetimes, tunable emission, high photostability, and low cytotoxicity, which render them useful for bio-imaging and bioassay applications [1]. This paper surveys several key concepts surrounding upconversion nanoparticles and the systems that detect and process the luminescence signal Throughout the paper, emphasis is placed on the physical attributes of UCNPs that map strongly to the technical features that CMOS devices excel in delivering, exploring the synergy between the two technologies

Upconversion Nanoparticles
Photon Upconversion
UCNP Structure and Optical Properties
UCNPs in Bioassays
Time Resolved Measurements
CMOS Microsystem
System Miniaturization
CMOS Spectral Detection
CMOS Time-Resolved Measurement
Findings
Conclusions
Full Text
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