Nanodiamond Landmarks for Subcellular Multimodal Optical and Electron Imaging

TL;DR

This paper introduces a multimodal imaging technique using functionalized nanodiamonds as biolabels for subcellular structures, enabling precise localization in both optical and electron microscopy without cytotoxicity or photobleaching.

Contribution

The study demonstrates a versatile method for targeting nanodiamonds to subcellular structures and imaging them with both microscopy types, enhancing nanoscale biological investigations.

Findings

Nanodiamonds can be targeted to specific subcellular structures.

The method allows rapid localization in electron microscopy.

Nanodiamonds are observable in optical microscopy for tracking.

Abstract

There is a growing need for biolabels that can be used in both optical and electron microscopies, are non-cytotoxic, and do not photobleach. Such biolabels could enable targeted nanoscale imaging of sub-cellular structures, and help to establish correlations between conjugation-delivered biomolecules and function. Here we demonstrate a subcellular multi-modal imaging methodology that enables localization of inert particulate probes, consisting of nanodiamonds having fluorescent nitrogen-vacancy centers. These are functionalized to target specific structures, and are observable by both optical and electron microscopies. Nanodiamonds targeted to the nuclear pore complex are rapidly localized in electron-microscopy diffraction mode to enable "zooming-in" to regions of interest for detailed structural investigations. Optical microscopies reveal nanodiamonds for in-vitro tracking or uptake-confirmation. The approach is general, works down to the single nanodiamond level, and can leverage the unique capabilities of nanodiamonds, such as biocompatibility, sensitive magnetometry, and gene and drug delivery.