Multiplexed surface plasmon imaging of serum biomolecules: Fe3O4@Au Core/shell nanoparticles with plasmonic simulation insights

Abstract

Nano-biosensors that are not only sensitive and selective, but also enable multiplex detection of ultra-low levels of both large and small biomolecules in clinical sample matrices are essential for in vitro diagnostics. We present herein a multiplex surface plasmon microarray design that employs citrate-stabilized Fe3O4@Au core/shell nanoparticles (NPs) as the plasmon signal amplification label for combined detection of serum proteins and nucleotide markers. The multiplex sensing is demonstrated using two interleukins (IL-6 and IL-8) and two microRNAs (miRNA-21 and miRNA-155) in 10% serum, which is clinically relevant than simple buffer solution based biosensors. We observed that the surface plasmon signal change for larger proteins even at higher concentrations was less than the relatively smaller miRNA molecules. We draw two conclusions from this result: (i) the number of selectively bound analytes onto the sensor (i.e., antigen for an antibody or miRNA for a capture nucleotide) influences the signal change, and (ii) the extent of interaction of the detection probe carrying core/shell NP labels with the sensor surface plasmons influences the amount of signal change. Results indicate that both factors, (i) and (ii), are greater for small oligonucleotide hybridization assembly than a large sandwich protein immunoassembly. The core/shell NPs offered several fold enhanced sensitivity and wider dynamic range of detection over assays without using them. With recently growing attention on in vitro diagnostics for painless/minimally-invasive detection of diseases and abnormalities, findings presented herein are important for designing novel multiplex biosensors for real sample analysis in complex matrices.