Introduction: Development of molecular probes that bind specifically and with high affinity to cancer biomarkers is one of the most important objectives in the early diagnosis and therapy of cancer. HER2, a very well-known breast cancer biomarker, overexpressed in roughly 18% to 22% of breast cancer cases It has been shown that blockade of HER2 signaling by using HER2 receptor inhibitors leads to a reversal of most HER2 tumorigenic features. Aptamer targeting HER2 seems to be an invaluable tool can be used instead of Herceptin which has been used as a well-tolerated and active first-line treatment in women with HER2 positive breast cancer. Aptamers are single stranded oligonucleic acid molecules that bind their targets with high affinity and specificity. The attractive features of aptamers make them very good candidates for clinical applications and ideal alternatives for antibodies in numerous applications. Aptamers are typically selected from large libraries of random DNA sequences by a procedure termed systematic evolution of ligands by exponential enrichment (SELEX). In this study, cell based strategy called Cell SELEX was employed to enrich DNA aptamers that are able to identify HER2 positive cells and HER2 protein in its natural conformation. In this paper we have addressed main challenges for the cell SELEX technique. We have also developed a new method, cell enzyme-linked aptamer based assay, we named it “Cell ELABA”, as an alternative to flow cytometry to monitor the enrichment of aptamers in different rounds of cell SELEX.

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