Miniaturized therapeutic systems for ultrasound-modulated drug delivery to the central and peripheral nervous system.

Ultrasound is a promising technology to address challenges in drug delivery, including limited drug penetration across physiological barriers and ineffective targeting. Here we provide an overview of the significant advances made in recent years in overcoming technical and pharmacological barriers using ultrasound-assisted drug delivery to the central and peripheral nervous system. We commence by exploring the fundamental principles of ultrasound physics and its interaction with tissue. The mechanisms of ultrasonic-enhanced drug delivery are examined, as well as the relevant tissue barriers. We highlight drug transport through such tissue barriers utilizing insonation alone, in combination with ultrasound contrast agents (e.g., microbubbles), and through innovative particulate drug delivery systems. Furthermore, we review advances in systems and devices for providing therapeutic ultrasound, as their practicality and accessibility are crucial for clinical application.

Decentralized ORP Measurements for Gut Redox Status Monitoring: Toward Personalized Gut Microbiota Balance.

Gut microbiome targeting has emerged as a new generation of personalized medicine and a potential wellness and disease driver. Specifically, the gut redox balance plays a key role in shaping the gut microbiota and its link with the host, immune system, and disease evolution. In this sense, precise and personalized nutrition has proven synergy and capability to modulate the gut microbiome environment through the formulation of dietary interventions, such as vitamin support. Accordingly, there are urgent demands for simple and effective analytical platforms for understanding the relationship between the tailored vitamin administration and the gut microbiota balance by rapid noninvasive on-the-spot oxidation/reduction potential monitoring for frequent and close surveillance of the gut redox status and targeting by personalized nutrition interventions. Herein, we present a disposable potentiometric sensor chip and a homemade multiwell potentiometric array to address the interplay of vitamin levels with the oxidation/reduction potential in human feces and saliva. The potentiometric ORP sensing platforms have been successfully validated and scaled up for the setup of a multiapplication prototype for cross-talk-free simple screening of many specimens. The interpersonal variability of the gut microbiota environment illustrates the potential of feces and saliva samples for noninvasive, frequent, and decentralized monitoring of the gut redox status to support timely human microbiota surveillance and guide precise dietary intervention toward restoring and promoting personalized gut redox balance.

Effect of Additives on the Surface Morphology, Energetics, and Contact Resistance of PEDOT:PSS.

For a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) film employed in a device stack, charge must pass through both the bulk of the film and interfaces between adjacent layers. Thus, charge transport is governed by both bulk and contact resistances. However, for ultrathin films (e.g., flexible devices, thin-film transistors, printed electronics, solar cells), interfacial properties can dominate over the bulk properties, making contact resistance a significant determinant of device performance. For most device applications, the bulk conductivity of PEDOT:PSS is typically improved by blending additives into the solid film. Doping PEDOT:PSS with secondary dopants (e.g., polar small molecules), in particular, increases the bulk conductivity by inducing a more favorable solid morphology. However, the effects of these morphological changes on the contact resistance (which play a bigger role at smaller length scales) are relatively unstudied. In this work, we use transfer length method (TLM) measurements to decouple the bulk resistance from the contact resistance of PEDOT:PSS films incorporating several common additives. These additives include secondary dopants, a silane crosslinker (typically used to stabilize the PEDOT:PSS film), and multi-walled carbon nanotubes (conductive fillers). Using conductive atomic force microscopy, Kelvin probe force microscopy, Raman spectroscopy, and photoelectron spectroscopy, we connect changes in the contact resistance to changes in the surface morphology and energetics as governed by the blended additives. We find that the contact resistance at the PEDOT:PSS/silver interface can be reduced by (1) increasing the ratio of PEDOT to PSS chains, (2) decreasing the work function, (3) decreasing the benzoid-to-quinoid ratio at the surface of the solid film, (4) increasing the film uniformity and contact area, and (5) increasing the phase-segregated morphology of the solid film.