## 1 Introduction  
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. In fact, 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]. 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. Several examples of microfluidics applied to biomedical field are present in the literature [3; 4; 5], from the identification of cancer biomarkers such as circulating tumor cells, circulating tumor DNA and extracellular vesicles [6; 7] to single cell analysis [8] and organ-on-a-chip technology [7; 9], to nucleic acid diagnostics [10; 11; 12].  
Among different materials suitable for microsystem fabrication, polydimethylsiloxane (PDMS) has been widely used in a variety of microfluidic applications, including for manufacturing lab-on-a-chip and micro total analysis systems [13]. PDMS, a silicone-based organic elastomer, is indeed a low-cost, flexible, optically transparent, and easily processing material [14]. This polymer is greatly employed for microfluidics and flexible affinity sensing platform [15], due to many advantages, such as miniaturization aimed at reducing the amount of samples and reagents, minimize time and cost, improve reproducibility, automate separations and detections. Different microfluidic platforms based on PDMS have been proposed to provide microchannels or microchambers for purification, processing and sensing of analytes, to achieve separation and detection with high resolution and sensitivity [15]. Moreover, PDMS is recognized as a highly biocompatible material [16; 17], which has the intrinsic capacity of spontaneously and strongly adsorb nucleic acids [18; 19]. This effect becomes more evident when PDMS surfaces are endowed with positive charges [20], a modification easily performed due to the capability of this material to undergo functionalization with silane groups [21]. Not only the functionalization of PDMS is easily obtained, but also PDMS itself can be used to introduce novel properties on other polymeric materials [22].  
Our group already demonstrated the huge potentialities of PDMS-based microdevices for the purification and analysis of biomarkers [11; 19]. Here, two configurations of spiral-shaped microdevices are presented. The two configurations have different geometries, which display different surface to volume (S/V) ratios. This aspect is particularly important since a microfluidic device with higher S/V could adsorb higher amounts of biomarkers and, possibly, capture a higher amount of rare microRNAs. The capture of microRNAs occurs on the microdevice surfaces, which are functionalized with positive charges able to attract the negative charges present on the phosphate groups of the microRNA backbones. After an extensive study of PDMS properties in adsorbing/eluting microRNAs, the best conditions were transferred to two types of microfluidic devices, which were deeply characterized. The best working conditions were then validated via real-time PCR for the detection of a pool of microRNAs related to non-small cell lung cancer (NSCLC), selected as proof-of-principle of a biological application.