Microfluidic synthesis of ultra-small magnetic nanohybrids for enhanced magnetic resonance imaging

Abstract

We have developed a core alloying and shell gradient doping strategy for the controlled surface modification of nanoparticles, realized by a coupled competitive reducing-nucleation and precipitation reaction controlled in microfluidic channels. Here it is extended in surface modification of Fe and CoFe nanoparticles by doping zinc oxide and aluminum oxide to form well-dispersed stable ultra-small Fe_(1−x)Zn_x@Zn_(1−y)Fe_yO–(OH)_z and (CoFe)_(1−x)Al_x@Al_(1−y)(CoFe)_yO–(OH)_z nanohybrids as contrast agents for magnetic resonance imaging (MRI). They exhibit greatly enhanced T₁ weighted spin echo imaging and T₂ weighted spin echo imaging effects. Particularly, (CoFe)_(1−x)Al_x@Al_(1−y)(CoFe)_yO–(OH)_z nanohybrids give a T₁ relaxation rate (R₁) of 0.156 (μg-CoFe mL⁻¹)⁻¹ s⁻¹ and a T₂ relaxation rate (R₂) of 0.486 (μg-CoFe mL⁻¹)⁻¹ s⁻¹, much higher than the commercial gadopentetate dimeglumine (R₁ = 0.022 (μg-Gd mL⁻¹)⁻¹ s⁻¹; R₂ = 0.025 (μg-Gd mL⁻¹)⁻¹ s⁻¹). The R₁ of (CoFe)_(1−x)Al_x@Al_(1−y)(CoFe)_yO–(OH)_z nanohybrids is also higher than superparamagnetic iron oxide (SPIO) nanoparticles (R₁ = 0.121 (μg-Fe mL⁻¹)⁻¹ s⁻¹). SPIO nanoparticles of 7.1 ± 1.2 nm still show an excellent negative MRI contrast agent by the highest R₂ (5.07 (μg-Fe mL⁻¹)⁻¹ s⁻¹) and R₂/R₁ ratio (42) among these reagents.