Abstract

The isolation and analysis of circulating biomarkers, the main concern of liquid biopsy, could greatly benefit from microfluidics. Microfluidics has indeed the huge potentiality to bring liquid biopsy into the clinical practice. Here, two polydimethylsiloxane (PDMS)-based microdevices are presented as valid tools for capturing microRNAs biomarkers from clinically-relevant samples. After an extensive study of functionalized polydimethylsiloxane (PDMS) properties in adsorbing/eluting microRNAs, the best conditions were transferred to the microdevices, which were thoroughly characterized. The channels morphology and chemical composition were measured, and parameters for the automation of measures were setup. The best working conditions were then used with microdevices, which were proven to capture microRNAs on all channel surfaces. Finally, microfluidic devices were successfully validated via real-time PCR for the detection of a pool of microRNAs related to non-small cell lung cancer, selected as proof-of-principle. The microfluidic approach described here will allow a step forward towards the realization of an efficient microdevice, possibly automated and integrated into a microfluidic lab-on-a-chip with high analytical potentialities.

Highlights

  • In recent years, the concept of a non-invasive but specific diagnostic analysis, able to detect minimal amount of biomarkers at the early stages of a pathology, has grown enormously

  • The direct adsorption of microRNAs on a PDMS microdevice was already demonstrated by our group [19,20]

  • Considering the potential use of this microdevice aimed at biomarker detection, the synthetic miR-1246 was selected because of its suggested potential role as biomarker for several cancer types [28,29], including the non-small cell lung cancer (NSCLC) [30]

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Summary

Introduction

The concept of a non-invasive but specific diagnostic analysis, able to detect minimal amount of biomarkers at the early stages of a pathology, has grown enormously. The ability to tailor medical care to an individual patient is connected to the possibility of collecting information on that individual, starting from low amount of biological samples, to be collected throughout time. To this regard, liquid biopsy is gaining significant attention for biomarker analysis and discovery, especially for pathologies like cancer [1,2]. Liquid biopsy is gaining significant attention for biomarker analysis and discovery, especially for pathologies like cancer [1,2] In this context, microfluidic technologies offer great potential to revolutionize the way for sampling, sample separation, mixing, chemical reaction, and detection of biomarkers in clinical settings.

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