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.

Reconstruction of the ovary microenvironment utilizing macroporous scaffold with affinity-bound growth factors.

Implementing ovarian tissue engineering for the maturation of primordial follicles, the most abundant follicle population in the ovary, holds great potential for women fertility preservation. Here, we evaluated whether macroporous alginate scaffolds with affinity-bound bone morphogenetic protein-4 (BMP-4) could mimic the ovary microenvironment and support the culture and growth of primordial follicles seeded with supporting ovarian cells. Porcine primordial follicles developed in the alginate scaffolds up to the pre-antral stage within 21 days. Affinity-bound BMP-4 significantly contributed to follicular maturation, as evident by the 5-fold increase in the number of developing follicles and enhanced estradiol secretion in these cultures compared to when BMP-4 was added to cultures with no affinity binding. After 21 days in culture, an increase in GDF-9/AMH gene expression, which is correlated with follicular development, was statistically significant when BMP-4 was affinity bound, compared to all other scaffold groups. When developed in-vivo, after xeno-transplantation of the follicle devices supplemented with additional angiogenic factors, the follicles reached antral size and secreted hormones at levels leading to restoration of ovarian function in ovariectomized severe combined immunodeficiency (SCID) mice. Altogether, our results provide first affirmation for the applicability of macroporous alginate scaffolds as a suitable platform for promoting follicle maturation in-vitro and in-vivo, and lay the foundations for the advantageous use of affinity binding presentation of growth factors to cultured follicles.