Measuring ultra-low levels of nucleotide biomarkers using quartz crystal microbalance and {SPR} microarray imaging methods: A comparative analysis

By Premaratne, Gayan; Mubarak, Zainab H. Al; Senavirathna, Lakmini; Liu, Lin; Krishnan, Sadagopan
Published in Sensors and Actuators B: Chemical NULL 2017

Abstract

Abstract Circulating serum nucleotide biomarkers are useful indicators for early diagnosis of cancer, respiratory illnesses, and other deadly diseases. In this work, we compared detection performances of a quartz crystal microbalance (QCM), which is a mass sensor, with that of a surface plasmon resonance (SPR) microarray for an oligonucleotide mimic of a microRNA-21 biomarker. A surface immobilized capture oligonucleotide probe was used to hybridize with the target oligonucleotide (i.e., the microRNA-21 mimic) to facilitate selective detection. To obtain ultra-low femtomolar (fM) detection sensitivity, gold nanoparticles (50 nm) were conjugated with the target oligonucleotide. We achieved detection limits of 28 and 47 fM for the target oligonucleotide by the {QCM} and {SPRi} microarray, respectively. We also conducted sample recovery studies and performed matrix effect analysis. Although the {QCM} had a lower detection limit, the microarray approach offered better throughput for analysis of up to 16 samples. We confirmed that the designed assay was selective for the target oligonucleotide and did not show signals for the control oligonucleotide with five mismatch sites relative to the target sequence. Combination of the {QCM} and microarray methods that utilize the same assay chemistry on gold are useful for overcoming clinical sample matrix effects and achieving ultra-low detection of small nucleotide biomarkers with quantitative insights.

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