Towards simultaneous electrical and optical investigation of BLMS using a novel microfluidic device

We firstly describe the influence of the phospholipid (PL) composition of bilayer lipid membrane on their electrical properties: (i) the more unsaturations in the tail, the earlier the BLM breakdown and (ii) the bulkier the head group, the less stable the membrane. Secondly, we design and fabricate novel devices that couple such electri-cal characterization to optical investigation and that enable the preparation of asym-metrical membranes: a “macro” device including a drilled PMMA plate as well as microfluidic device consisting of a glass-teflon foil-glass sandwich

Integrated Lithographic Molding for Microneedle-Based Devices

This paper presents a new fabrication method consisting of lithographically defining multiple layers of high aspect-ratio photoresist onto preprocessed silicon substrates and release of the polymer by the lost mold or sacrificial layer technique, coined by us as lithographic molding. The process methodology was demonstrated fabricating out-of-plane polymeric hollow microneedles. First, the fabrication of needle tips was demonstrated for polymeric microneedles with an outer diameter of 250 mum, through-hole capillaries of 75-mum diameter and a needle shaft length of 430 mum by lithographic processing of SU-8 onto simple v-grooves. Second, the technique was extended to gain more freedom in tip shape design, needle shaft length and use of filling materials. A novel combination of silicon dry and wet etching is introduced that allows highly accurate and repetitive lithographic molding of a complex shape. Both techniques consent to the lithographic integration of microfluidic back plates forming a patch-type device. These microneedle-integrated patches offer a feasible solution for medical applications that demand an easy to use point-of-care sample collector, for example, in blood diagnostics for lithium therapy. Although microchip capillary electrophoresis glass devices were addressed earlier, here, we show for the first time the complete diagnostic method based on microneedles made from SU-8

Modulation of Bile Acid Metabolism to Improve Plasma Lipid and Lipoprotein Profiles

New drugs targeting bile acid metabolism are currently being evaluated in clinical studies for their potential to treat cholestatic liver diseases, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Changes in bile acid metabolism, however, translate into an alteration of plasma cholesterol and triglyceride concentrations, which may also affect cardiovascular outcomes in such patients. This review attempts to gain insight into this matter and improve our understanding of the interactions between bile acid and lipid metabolism. Bile acid sequestrants (BAS), which bind bile acids in the intestine and promote their faecal excretion, have long been used in the clinic to reduce LDL cholesterol and, thereby, atherosclerotic cardiovascular disease (ASCVD) risk. However, BAS modestly but consistently increase plasma triglycerides, which is considered a causal risk factor for ASCVD. Like BAS, inhibitors of the apical sodium-dependent bile acid transporter (ASBTi’s) reduce intestinal bile acid absorption. ASBTi’s show effects that are quite similar to those obtained with BAS, which is anticipated when considering that accelerated faecal loss of bile acids is compensated by an increased hepatic synthesis of bile acids from cholesterol. Oppositely, treatment with farnesoid X receptor agonists, resulting in inhibition of bile acid synthesis, appears to be associated with increased LDL cholesterol. In conclusion, the increasing efforts to employ drugs that intervene in bile acid metabolism and signalling pathways for the treatment of metabolic diseases such as NAFLD warrants reinforcing interactions between the bile acid and lipid and lipoprotein research fields. This review may be considered as the first step in this process

Microstamped petri dishes for scanning electrochemical microscopy analysis of arrays of microtissues

While scanning electrochemical microscopy (SECM) is a powerful technique for non-invasive analysis of cells, SECM-based assays remain scarce and have been mainly limited so far to single cells, which is mostly due to the absence of suitable platform for experimentation on 3D cellular aggregates or microtissues. Here, we report stamping of a Petri dish with a microwell array for large-scale production of microtissues followed by their in situ analysis using SECM. The platform is realized by hot embossing arrays of microwells (200 mum depth; 400 mum diameter) in commercially available Petri dishes, using a PDMS stamp. Microtissues form spontaneously in the microwells, which is demonstrated here using various cell lines (e.g., HeLa, C2C12, HepG2 and MCF-7). Next, the respiratory activity of live HeLa microtissues is assessed by monitoring the oxygen reduction current in constant height mode and at various distances above the platform surface. Typically, at a 40 mum distance from the microtissue, a 30% decrease in the oxygen reduction current is measured, while above 250 mum, no influence of the presence of the microtissues is detected. After exposure to a model drug (50% ethanol), no such changes in oxygen concentration are found at any height in solution, which reflects that microtissues are not viable anymore. This is furthermore confirmed using conventional live/dead fluorescent stains. This live/dead assay demonstrates the capability of the proposed approach combining SECM and microtissue arrays formed in a stamped Petri dish for conducting cellular assays in a non-invasive way on 3D cellular models

Micromachining of buried micro channels in silicon

A new method for the fabrication of micro structures for fluidic applications, such as channels, cavities, and connector holes in the bulk of silicon wafers, called buried channel technology (BCT), is presented in this paper. The micro structures are constructed by trench etching, coating of the sidewalls of the trench, removal of the coating at the bottom of the trench, and etching into the bulk of the silicon substrate. The structures can be sealed by deposition of a suitable layer that closes the trench. BCT is a process that can be used to fabricate complete micro channels in a single wafer with only one lithographic mask and processing on one side of the wafer, without the need for assembly and bonding. The process leaves a substrate surface with little topography, which easily allows further processing, such as the integration of electronic circuits or solid-state sensors. The essential features of the technology, as well as design rules and feasible process schemes, will be demonstrated on examples from the field of ¿-fluidic