ABSTRACT

Fluorescent biomarkers such as uorescent proteins (FPs) [1], organic dyes [2], and quantum dots (QDs) [3] have been widely used for biological and biomedical imaging due to their fair brightness and biocompatibility [4,5]. However, these common uorescent biomarkers will photobleach, blink, or unfortunately exhibit both. erefore, recent eorts have been directed toward development of a biocompatible luminescent/uorescent labels that neither photobleach nor blink. In addition, higher molecular brightness in such ideal uorescent probes would allow deeper and more sensitive uorescence tomography. Fluorescent nanodiamonds (FNDs) present a good candidate for such ideal uorescent probe since they are 5-100 nm large [6], biocompatible particles with excellent photostability and have surface that can be easily functionalized [7]. ese features have directed their use toward numerous demanding uorescent imagining modalities such as

11.1 Introduction 11.2 General Properties of

FNDs as Biomarkers and Biosensors

11.3 Nanoscale Imaging of Biological Systems with NV Centers Hosted in Nanodiamonds

11.4 Super-Resolution Microscopy with FNDs

11.5 Nanoscale Sensing of Biological Systems with NV Centers Hosted in Nanodiamonds

11.6 Manipulation Techniques

11.7 Conclusion 11.8 List of Acronyms References

uorescence lifetime imaging microscopy (FLIM) [8], FNDs are used as donors in uorescence resonance energy transfer experiments (FRETs) [9], as probes in long-term in vivo tracking [10] together with in vivo single particle tracking [11], as well as in both super-resolution microscopy modalities such as localizationbased [12], and by using stimulated emission depletion (STED) microscopy [13] which in turn is scanning-based. Moreover, the nitrogen vacancy (NV) centers in FNDs can act as optically readable sensors that could measure with very high precision variety of physical quantities including ultrasensitive magnetometry [14], sensing of the electrical elds [15], ion concentrations [16], and thermometry  [17]. From a point of view of biological applications, it is extremely exciting to employ these nanoscale sensors in living cells as demonstrated by Kucsko et al. [17]. On the other hand, recent demonstration of the electron spin resonance (ESR) signal detection from a single protein using as a sensor single NV center in bulk diamond paved the way for the future experiments in the cells where the bulk diamond should be replaced by a nanodiamond with similar NV magnetic sensitivity [18].