*Article* **Silicon Nanofluidic Membrane for Electrostatic Control of Drugs and Analytes Elution**

**Nicola Di Trani 1,2, Antonia Silvestri 1,3, Yu Wang 1, Danilo Demarchi 3, Xuewu Liu 1 and Alessandro Grattoni 1,4,5,\***


danilo.demarchi@polito.it


Received: 8 June 2020; Accepted: 15 July 2020; Published: 19 July 2020

**Abstract:** Individualized long-term managemen<sup>t</sup> of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal managemen<sup>t</sup> of pathologies, such as diabetes, hypertension, rheumatoid arthritis. Several triggered systems for drug delivery have been demonstrated. However, they mostly rely on continuous external stimuli, which hinder their application for long-term treatments. In this work, we investigated a silicon nanofluidic technology that incorporates a gate electrode and examined its ability to achieve reproducible control of drug release. Silicon carbide (SiC) was used to coat the membrane surface, including nanochannels, ensuring biocompatibility and chemical inertness for long-term stability for in vivo deployment. With the application of a small voltage (≤ 3 V DC) to the buried polysilicon electrode, we showed in vitro repeatable modulation of membrane permeability of two model analytes—methotrexate and quantum dots. Methotrexate is a first-line therapeutic approach for rheumatoid arthritis; quantum dots represent multi-functional nanoparticles with broad applicability from bio-labeling to targeted drug delivery. Importantly, SiC coating demonstrated optimal properties as a gate dielectric, which rendered our membrane relevant for multiple applications beyond drug delivery, such as lab on a chip and micro total analysis systems (μTAS).

**Keywords:** electrostatic gating; nanofluidic diffusion; controlled drug release; silicon membrane; smart drug delivery
