Potentio-tunable FET sensor having a redox-polarizable single electrode for the implementation of a wearable, continuous multi-analyte monitoring device.

The emerging field of wearable devices for monitoring bioanalytes calls for the miniaturization of biochemical sensors. The only commercially available electrochemical wearable monitoring medical devices for bioanalytes are the amperometric continuous glucose monitoring (CGM) systems. The use of such amperometric methods to monitor glucose levels requires a relatively large electrode surface area for sufficient redox species collection, allowing accurate measurements to be made. Consequently, miniaturization of such sensors bearing large electrodes is challenging. Furthermore, it is difficult to introduce and deploy more than one electrode-based sensor per device, thereby limiting the number of analytes that can be monitored in parallel. To address these limitations, we have employed a non-referenced, single polarizable electrode coupled to a fin-shaped field-effect transistor (Fin-FET). We have discovered that by passivating the FET area by a relatively thick oxide and/or polytetrafluoroethylene (PTFE) polymer, leaving only the polarizable working electrode (WE) exposed, we can monitor redox analytes at the micromolar to millimolar concentration range. We attribute this effect to the WE polarization by the solution redox species. We have exploited the superior sensitivity of the adjacent silicon-based Fin-FET to detect changes in sensor electrode potentials induced by the redox species. Furthermore, we demonstrated the correlation between a specific analyte and the biasing WE potential on the accumulation/depletion of the coupled Fin-FET channel as manifested by the transistor source-drain current. Moreover, we utilized the analyte-electrode potential interaction, which is analyte-specific, to tune the specificity of the sensor towards an analyte of choice. In addition, we demonstrated the use of a single-electrode potentiometric sweep to assist in identifying the accumulation/depletion as a result of analyte-WE state. Collectively, the tiny potentio-tunable electrochemical sensor (PTEchem sensor) area is ~50 × 50 µm, and dedicated wireless transducer facilitates the use of this sensor for wearable continuous, multi-metabolite monitoring.

The tumor suppressor maspin mediates E2F1-induced sensitivity of cancer cells to chemotherapy.

The E2F1 transcription factor is a critical downstream target of the tumor suppressor RB. When activated, E2F1 can induce cell proliferation and/or apoptosis. In addition, E2F1 overexpression sensitizes cancer cells to chemotherapeutic drugs. In a screen for genes that are regulated synergistically by E2F1 and chemotherapy in cancer cells, we identified the proapoptotic tumor suppressor gene maspin (mammary serine protease inhibitor) as a novel E2F1-regulated gene. In line with being an E2F-regulated gene, maspin expression is inhibited by short hairpin RNA directed against E2F1 and increases upon activation of endogenous E2F. Furthermore, maspin mRNA and protein levels are elevated upon activation of exogenous E2F1. Importantly, we show that E2F1-mediated upregulation of maspin is enhanced by chemotherapeutic drugs, and inhibition of maspin expression significantly impairs the ability of E2F1 to promote chemotherapy-induced apoptosis. Summarily, our data indicate that maspin is an important effector of E2F1-induced chemosensitization.