Optimizing the screening process for inhibitory aptamers specific to folate receptor alpha on an integrated, shear force-controlling microfluidic system

• Inhibitory aptamers that specifically targeted and blocked folate receptor alpha (FRα) for ovarian cancer (OvCa) therapy was reported. • A new integrated microfluidic system (IMS) was designed to automate the entire systematic evolution of ligands by exponential enrichment (SELEX), precisely controlling the washing shear force that gradually washed away low-affinity aptamers, allowing high-affinity, high-specificity, single-stranded DNA aptamers to be screened within 15 h. • Screened aptamers inhibited OvCa progression significantly in wound-healing tests when compared with an anti-cancer drug targeting FRα. Folate receptor alpha (FRα) has been regarded as a promising target for ovarian cancer (OvCa) therapy. This work focused on improving the identification of inhibitory aptamers that specifically target and block FRα. A new integrated microfluidic system (IMS) was designed to automate the entire systematic evolution of ligands by exponential enrichment (SELEX), precisely controlling the washing shear force from 62.7 nN to 451.7 nN that gradually washed away low-affinity aptamers, allowing high-affinity, high-specificity, single-stranded DNA aptamers to be screened within 15 h, which is significantly shorter than conventional process (weeks to months) while consuming 50 % less samples and reagents. Furthermore, screened aptamers significantly inhibited OvCa progression, achieving 20 % higher wound recovery in wound-healing tests when compared with an anti-cancer drug targeting FRα. In summary, precisely controlled shear force by IMS could optimize aptamers screening with high affinity/specificity towards FRα, which inhibited OvCa cell growth, suggesting their applicability as promising candidates for onco-therapy.