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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.

Through the process of photon upconversion, trivalent lanthanide doped nanocrystals convert long-wavelength excitation radiation in the infrared or near infrared region to higher energy emission radiation from ultraviolet to infrared. Such materials offer potential for numerous advantages in analytical applications in comparison to molecular fluorophores and quantum dots. The use of IR radiation as an excitation source reduces autofluorescence and scattering of excitation radiation, which leads to a reduction of background in optical experiments. The upconverting nanocrystals offer excellent photostability and are composed of materials that are not particularly toxic to biological organisms. Excitation at long wavelengths also minimizes damage to biological materials. In this review, the different mechanisms responsible for the upconversion process, and methods that are used to synthesize and decorate upconverting nanoparticles are presented to indicate how absorption and emission can be tuned. Examples of recent applications of upconverting nanoparticles in bioassays for the detection of proteins, nucleic acids, metabolites and metal ions offer indications of analytical advantages in the development of methods of analysis. Examples include multi-color and multi-modal imaging, and the use of upconverting nanoparticles in theranostics., (Copyright © 2014. Published by Elsevier B.V.)

A complementary approach to published synthetic methods for tetrazinanones, precursors to verdazyl radicals, is described herein. This approach uses carbohydrazide, a commercially available reagent, as a common starting material. Unlike previous methods described in the literature, this synthetic scheme does not rely on phosgene, phosgene substitutes, or the limited pool of commercially available monosubstituted hydrazines for its execution. A large variety of alkyl substitution patterns at the N-1 and N-5 positions of verdazyl radicals are possible, including both symmetrically and unsymmetrically substituted products. An initial condensation reaction of carbohydrazide with a specific aldehyde introduces the desired C-3 substituent in the final verdazyl radical product and protects the NH(2) groups during the subsequent N-1 and N-5 alkylation reactions. A succeeding methanolysis and concomitant ring-closing reaction gives the tetrazinanone. A number of known oxidation methods can then be employed to form the final verdazyl radical product.