Nanodiamonds with silicon vacancy defects for nontoxic photostable fluorescent labeling of neural precursor cells

Abstract

Nanodiamonds (NDs) containing silicon vacancy (SiV) defects were evaluated as a potential biomarker for the labeling and fluorescent imaging of neural precursor cells (NPCsFluorescent biomarkers for labeling cellular and molecular targets are emerging as increasingly important tools in biomedical research and medicine. The range of potential applications is diverse, from monitoring drug or tumor localization within the body [1], to assessing the migration of transplanted stem cells used in cell based therapies [2]. A major goal is to develop improved fluorescent labeling reagents that achieve optimal fluorescence intensity without photo-bleaching or blinking. These latter properties are observed with most currently used fluorescent proteins, quantum dots, metallic and dielectric beads and hinders their use for long-term repeated imaging applications [3]. An additional goal is to generate fluorescent biomarkers that can be specifically targeted to distinct cellular or molecular targets via the conjugation of antibodies, growth factors, organic chemicals or drugs. In these respects, nanodiamonds (NDs) offer several advantages. First, atomic changes in ND structure produces bright optical defects that possess unrivalled photostability, even for the smallest NDs (~5-10 nm) [4,5]. Second, being made of carbon, they are biocompatible, non-toxic and highly amenable to surface functionalization, enabling the conjugation of biomolecules such as DNA and proteins [6][7][8]. Despite these promising features, further improvement of the optical properties of NDs could enhance their utility as fluorescent biomarkers. The most common optical defect that can be "naturally" incorporated into the NDs is a nitrogen vacancy center (NV), a nitrogen atom close to a vacancy in the diamond lattice [9]. NV emits over a broad range of wavelengths (575 -800 nm), and has been explored as a potential candidate for atomic resolution magnetic resonance imaging [10]. However despite its promising properties for magnetic sensing, the optical properties of NV centers are not ideal. Specifically, its peak absorption at 532 nm overlaps with wavelengths that excite cellular auto-fluorescence and the

Diamond Nanophotonics

“…Moreover, the ZPL fluorescence of the SiV center is almost fully linearly polarized at room temperature [48,50,54] , a property highly useful in quantum cryptography where the polarization is often used to encode information. The SiV center's narrow emission bandwidth, the possibility to excite its fluorescence using red laser light or an electron beam (cathodoluminescence) [55] as well as the availability of colloidal nanodiamonds in water [56,57] , have recently triggered investigations to use nanodiamonds containing SiV centers as fluorescent labels for bioimaging of cells and living organisms [58] . Here, excitation and emission in the red or near-infrared spectral range allow for deep tissue imaging and aid in avoiding tissue autofluorescence.…”

Determination of temperature dependent parameters of zero-phonon line in photo-luminescence spectrum of silicon-vacancy centre in CVD diamond thin films

“…Diamond shows a unique combination of physical and chemical properties such as high hardness, thermal conductivity, chemical stability, wide band gap (∼ 5.5 eV) [1,2] and biocompatibility, which make it advantageous for optoelectronics [3,4] and biotechnology [5]. These applications are determined not only by the intrinsic properties of diamond but also by crystallographic defects and impurities.…”

Novel imaging tools for investigating the role of immune signalling in the brain

“…Imaging whole organs require long exposure times owing to repeated z-stacking and are thus readily susceptible to bleaching with traditional fluorophore tagged probes or antibodies. Nanodiamonds are additionally non-toxic, emit beyond the range of cellular autofluorescence (with nitrogen or silicon vacancy centres) and have the ability to be utilised as efficient drug carriers (Merson et al 2013) making them an ideal particle to incorporate into RNA based ISH techniques for whole organ imaging. Alternatively, the conjugation of improved fluorescent lanthanides such as the europium chelate BHHST (4,-4'-bis-(1",1",1",2",2",3",3"-heptafluoro-4",6"-hexanedion-6"-yl) sulfonylamino-propyl-ester-N-succinimide-ester-o-terphenyl) to RNA probes would also be advantageous compared to conventional fluorophores.…”