Quantification methods comparing in vitro and in vivo percutaneous permeation by microneedles and passive diffusion.

Microneedles (MNs) are needles with a tip diameter ranging from 10 to 100 um and a length ranging up to 1 mm. The first patent for drug delivery device for percutaneous administration filed by Alza corporation dates back to 1976 (Gerstel and Place, 1976), and in between 1989 and 2021 the filed patents for MNs are >4500 [1]. These devices can potential overcome some drawbacks of traditional needles, such as the pain generated during insertion, requirement for trained personnel to manipulate syringes, and difficulty of performing injections in elderly and obese patients. MNs and MN arrays are emerging as a convenient method to deliver compounds and extract blood without causing any pain. A promising application is the use of MNs as alternative solution to topical creams (TC) and transdermal patches (TP) for transdermal drug delivery. The external layer of human skin, the epidermis, offers a major barrier to transdermal drug delivery, thanks to the stratum corneum (SC). Exposed to the external environment, SC ultimately protects the human body from UV light radiation, heat, water loss, bacteria, fungi and viruses, and it is the barrier that controls diffusion rate for almost all compounds. TC and TP applications are limited by the skin permeability to lipophilic compounds and small molecules, and by the slow delivery rate of some compounds. MNs have been around for >35 year now, and it is a general opinion that MNs increase delivery compared to passive diffusion, thanks to the feature of penetrating the SC and reaching the dermis. This review recollects the existing studies that compare MN delivery of drugs with passive diffusion of the same drugs in alive organisms, giving an overview of what are the type of MNs, the chemical delivered and the methods employed to quantify drug delivery into skin and/or in the bloodstream. The final aim is to quantify the enhancement factor of MNs with respect to passive diffusion, and establish a possible standard on how tests can be performed in order to compare different data.

A precise relationship among Buller's drop, ballistospore, and gill morphologies enables maximum packing of spores within gilled mushrooms.

Basidiomycete fungi eject basidiospores using a surface tension catapult. A fluid drop forms at the base of each spore and, after reaching a critical size, coalesces with the spore and launches it from the gill surface. It has long been hypothesized that basidiomycete fungi pack the maximum number of spores into a minimal investment of biomass. Building on a nascent understanding of the physics underpinning the surface tension catapult, we modeled a spore's trajectory away from a basidium and demonstrated that to achieve maximum packing the size of the fluid drop, the size of the spore, and the distance between gills must be finely coordinated. To compare the model with data, we measured spore and gill morphologies from wild mushrooms and compared measurements with the model. The empirical data suggest that in order to pack the maximum number of spores into the least amount of biomass, the size of Buller's drop should be smaller but comparable to the spore size. Previously published data of Buller's drop and spore sizes support our hypothesis and also suggest a linear scaling between spore radius and Buller's drop radius. Morphological features of the surface tension catapult appear tightly regulated to enable maximum packing of spores. If mushrooms are maximally packed and Buller's drop radii scale linearly with spore radii, we predict that intergill distance should be proportional to spore radius to the power 3/2.

Switching mechanism and reverse engineering of low-power Cu-based resistive switching devices.

In the recent past, filamentary-based resistive switching devices have emerged as predominant candidates for future non-volatile memory storage. Most of the striking characteristics of these devices are still limited by the high power consumption and poor understanding of the intimate resistive switching mechanism. In this study, we present an atomic scale study of the filament formation in CuTe-Al2O3 by using a conductive scanning probe tip to analyse the shape and dimensions of the filament. Filaments studied were either created within a normal device or locally formed while using the tip as the top electrode. We demonstrate that it is possible to create with C-AFM a filament with a signature identical to a device (i.e. two orders of magnitude resistance window, 10(4) s retention operating at 5 µA). This is obtained by a dedicated material and resistance selection for the conductive tip. The filamentary mechanism of fully processed devices is demonstrated and observed by C-AFM. Filaments created with C-AFM can be repeatedly cycled and the ON state presents a 20 nm highly conductive spot which can be repeatedly turned into a poorly conductive path in the OFF state.