Paper-based electrochemical aptasensor using Ti₃C₂ MXene for sensitive detection of Mammaglobin-A biomarker

Breast cancer is one of the most prevalent cancers worldwide and a leading cause of cancer-related mortality. However, early detection of the disease can significantly reduce the mortality rate of cancer patients. The current detection methods of breast cancer are expensive, time consuming, invasive and require professional assistance. To overcome these challenges, a minimally invasive low-cost paper-based point-of-care (POC) electrochemical sensing platform has been developed for early-stage detection of breast cancer. The proposed sensor is fabricated using a screen-printing technique, incorporating two-dimensional Ti₃C₂ (MXene) nanosheets onto the working electrode. These nanosheets provide enhanced electrochemical performance, enabling an exceptionally low limit of detection (LOD) ∼ 4 cells mL^-1) attributed to their high conductivity and large surface area. The electrode surface is further functionalized with specific aptamers, facilitating selective target recognition. The proof-of-concept study was validated using multiple cell lines, including A549 (lung cancer cells), NIH3T3 (fibroblast), and HEK293 (kidney cells), and MDA-MB-231(breast cancer cell line), to evaluate the specificity of the developed aptasensor. The sensing mechanism relies on the selective binding of aptamers to Mammaglobin A proteins expressed on circulating tumor cells (CTCs). This interaction induces conformational changes in the aptamer, resulting in measurable alterations in the electrochemical properties at the electrode interface. The conjugation of the biomarker with the aptamer upon aptamer-protein interaction, results in a change in current, which is sensed by cyclic voltammogram (CV). The resulting signal is used to plot a calibration curve for quantitative analysis. Further, these sensing experiments are validated using in vitro experiments with human blood serum as a proof of concept. Overall, the developed paper-based electrochemical POC device offers significant advantages, including affordability, ease of use, rapid response, and quantitative detection capability.