Screening aptamers targeting the cell membranes of clinical cancer tissues on an integrated microfluidic system

Clinical tests of liquid and tissue biopsies are critical for cancer diagnosis and prognostic monitoring. Our previous studies have established an integrated microfluidic system capable of automatically screening aptamer biomarkers through a tissue-based systematic evolution of ligands by exponential enrichment (tissue-SELEX) process, and the screened aptamer candidates specifically bind ovarian cancer tissues. However, using pathological tissue sections for tissue-SELEX may inadvertently screen aptamers that randomly target intracellular molecules; only cell membrane ligands, in contrast, are useful for designing probes that can capture circulating tumor cells in blood. In this work, we therefore screened aptamers that were able to recognize cell membranes in clinical tissue sections via a two-step SELEX process carried out on an integrated microfluidic system that featured a 1) membrane pre-screen SELEX to screen a single-strained DNA library against cell membranes in 5 h and 2) tissue-SELEX in 15 h. Among the screened aptamer candidates, we identified one aptamer (namely mcTx-17), which bound to cell membranes of ovarian cancer tissues with high specificity and sensitivity, which could be used as a biosensing probe for detection of ovarian cancer. We therefore advocate this approach for the future identification of cancer biomarkers from liquid and tissue biopsies.