Single‐Nanoparticle Cell Barcoding by Tunable FRET from Lanthanides to Quantum Dots

Abstract

Fluorescence barcoding based on nanoparticles provides many advantages for multiparameter imaging. However, creating different concentration-independent codes without mixing various nanoparticles and by using single-wavelength excitation and emission for multiplexed cellular imaging is extremely challenging. Herein, we report the development of quantum dots (QDs) with two different SiO shell thicknesses (6 and 12 nm) that are coated with two different lanthanide complexes (Tb and Eu). FRET from the Tb or Eu donors to the QD acceptors resulted in four distinct photoluminescence (PL) decays, which were encoded by simple time-gated (TG) PL intensity detection in three individual temporal detection windows. The well-defined single-nanoparticle codes were used for live cell imaging and a one-measurement distinction of four different cells in a single field of view. This single-color barcoding strategy opens new opportunities for multiplexed labeling and tracking of cells.

Optical Multiplexed Bioassays for Improved Biomedical Diagnostics

“…[32] These color codes can be transferred from the parent cells to the daughter cells without signs of color mixing for weeks,s uggesting ap romising candidate for long-term monitoring of cell division. In comparison, concentration-independent lifetime-multiplexing with individual nanoparticles would also achieve the same goal and may generate al arger encoding capacity.Chen et al [33] developed atype of barcode consisting of QDs and two different lanthanide complexes (Tb and Eu) with aSiO 2 shell in between (left in Figure 5b). Four barcodes with unique lifetimes were obtained by FRET from Tb or Eu donors to the QD acceptors using two different thicknesses of SiO 2 shell.…”

A clinical role for Förster resonance energy transfer in molecular diagnostics of disease

“…Another promising application of FRET in microarrays is to create different barcodes for probing distinct binding events. Due to the innumerable available luminophores (e.g., organic dyes, NPs, lanthanide complexes) and the different properties of luminescence, namely color, lifetime, intensity, and polarization, FRET between luminophores with different emission spectra, lifetimes, and brightness placed at defined distances to each other has the potential to provide extremely high numbers of barcodes for higher-order multiplexed microarray application in diagnostics [24,25]. Theoretically, the combination of only five colors, five lifetimes, and five intensities can result in 5 5 × 5 = 5 25 = 298 × 10 15 (~300 quadrillion) distinguishable codes, if these codes can be spatially separated.…”

Optical Multiplexed Bioassays for Improved Biomedical Diagnostics

“…In comparison, concentration‐independent lifetime‐multiplexing with individual nanoparticles would also achieve the same goal and may generate a larger encoding capacity. Chen et al . developed a type of barcode consisting of QDs and two different lanthanide complexes (Tb and Eu) with a SiO 2 shell in between (left in Figure b).…”