Synthesis of Uniform NaLnF4 (Ln: Sm to Ho) Nanoparticles for Mass Cytometry

Over the past decade, there have been extensive developments in the field of lanthanide-based nanoparticles (NPs). Most studies have focused on the application of upconverting NaYF4-based NPs for deep tissue imaging and paramagnetic NaGdF4 NPs for MRI. Current applications for the remaining members of the lanthanide series are rather limited. Recently, a novel bioanalytical technique known as mass cytometry (MC) has been developed which can benefit from the entire lanthanide series of NPs. MC is a high throughput multiparametric cell-by-cell analysis technique based on atomic mass spectrometry that uses antibodies labeled with metal isotopes for biomarker detection. NaLnF(4) NPs offer the promise of high sensitivity coupled with multiparameter detection, provided that NPs can, be synthesized with a narrow size distribution. Here we describe the synthesis of six members of this NP family (NaSmF4) NaEuF4, NaGdF4, NaTbF4, NaDyF4, NaHoF4) with the appropriate size (5-30 nm) and size distribution (CV < 5%) for MC. We employed the coprecipitation method developed by Li and Zhang [Nanotechnology 2008, 19, 345606], and for each member of this series, we examined the heating rate, final reaction temperature, and composition of the reaction mixture in an attempt to optimize the synthesis. For each of the six NaLnF(4), in the range of the target sizes, we were able to identify "sweet spots" in the reaction conditions to obtain NPs with a narrow size distribution. In addition, we investigated the oleate surface coverage of the NPs and the effect of long-term storage (2 years) on the colloidal stability of the NPs. Finally, NaTbF4 NPs were rendered hydrophilic via lipid encapsulation and tested for nonspecific binding with KG1a and Ramos cells by mass cytometry.