Bacterial Cell Cultures in a Lab-on-a-Disc: A Simple and Versatile Tool for Quantification of Antibiotic Treatment Efficacy.

Pathogenic bacterial biofilms can be life-threatening, greatly decrease patient's quality of life, and are a substantial burden on the healthcare system. Current methods for evaluation of antibacterial treatments in clinics and systems used in drug development and screening either do not facilitate biofilm formation or are cumbersome to operate, need large reagent volumes, and are costly, limiting their usability. To address these issues, this work presents the development of a robust cell culture platform compatible with confocal microscopy.

An Ingestible Self-Polymerizing System for Targeted Sampling of Gut Microbiota and Biomarkers.

A proof-of-concept for the fabrication of a self-polymerizing system for sampling of gut microbiome in the upper gastrointestinal (GI) tract is presented. An orally ingestible microdevice is loaded with the self-polymerizing reaction mixture to entrap gut microbiota and biomarkers. This polymerization reaction is activated in the aqueous environment, like fluids in the intestinal lumen, and causes site-specific microsampling in the gastrointestinal tract.

Large-scale spontaneous self-organization and maturation of skeletal muscle tissues on ultra-compliant gelatin hydrogel substrates.

Cellular self-organization is the fundamental driving force behind the complex architectures of native tissue. Yet, attempts at replicating native tissue architectures in vitro often involve complex micro-fabrication methods and materials. While impressive progress has been made within engineered models of striated muscle, the wide adaptation of these models is held back by the need for specific tools and knowhow.

Polymeric carriers for enhanced delivery of probiotics.

Probiotics are live microorganisms (usually bacteria), which are defined by their ability to confer health benefits to the host, if administered adequately. Probiotics are not only used as health supplements but have also been applied in various attempts to prevent and treat gastrointestinal (GI) and non-gastrointestinal diseases such as diarrhea, colon cancer, obesity, diabetes, and inflammation. One of the challenges in the use of probiotics is putative loss of viability by the time of administration.

Customized fast-separable microneedles prepared with the aid of 3D printing for nanoparticle delivery.

3D printing of master molds for soft lithography-based fabrication of microneedles (MNs) is a cost effective, easy and fast method for producing MNs with variable designs. Deviating from the classical geometries of MNs, 'tanto blade'-inspired MNs showed effective skin penetration, acting as sharp structures with low insertion force of 10.6 N, which is sufficient for manual insertion.

Quantifying Optical Absorption of Single Plasmonic Nanoparticles and Nanoparticle Dimers Using Microstring Resonators.

The wide and ever-increasing applications of thermoplasmonics demand the need for sensitive and reliable tools to probe optical absorptions of individual nanoparticles. However, most of the currently available techniques focus only on measuring the surface temperature of nanostructures in a particular medium and are either invasive or suffer from low sensitivity, lengthy calibration, or the inability to probe single structures with nanogaps. Here, we present for the first time the use of micromechanical SiN string resonators for quantifying optical absorption cross sections of individual plasmonic nanostructures.

Monitoring cell endocytosis of liposomes by real-time electrical impedance spectroscopy.

Evaluation and understanding the effect of drug delivery in in vitro systems is fundamental in drug discovery. We present an assay based on real-time electrical impedance spectroscopy (EIS) measurements that can be used to follow the internalisation and cytotoxic effect of a matrix metalloproteinase (MMP)-sensitive liposome formulation loaded with oxaliplatin (OxPt) on colorectal cancer cells. The EIS response identified two different cellular processes: (i) a negative peak in the cell index (CI) within the first 5 h, due to onset of liposome endocytosis, followed by (ii) a subsequent CI increase, due to the reattachment of cells until the onset of cytotoxicity with a decrease in CI.

Development and characterization of a PDMS-based masking method for microfabricated Oral drug delivery devices.

With the growing popularity and application of microfabricated devices in oral drug delivery (ODD), masking technologies for drug loading and surface modification become highly relevant. Considering the speed of design and fabrication processes and the necessity for continuous alterations of e.g.

Orally ingestible medical devices for gut engineering.

Orally ingestible medical devices provide significant advancement for diagnosis and treatment of gastrointestinal (GI) tract-related conditions. From micro- to macroscale devices, with designs ranging from very simple to complex, these medical devices can be used for site-directed drug delivery in the GI tract, real-time imaging and sensing of gut biomarkers. Equipped with uni-direction release, or self-propulsion, or origami design, these microdevices are breaking the barriers associated with drug delivery, including biologics, across the GI tract.

3D Printed Stackable Titer Plate Inserts Supporting Three Interconnected Tissue Models for Drug Transport Studies.

Current in vitro drug screening methods often rely on single-cell models and are therefore imprecise in predicting drug absorption, distribution, metabolism, excretion, and toxicity. This study presents a method to fabricate 3D printed inserts that are compatible with commercially available titer plates. Hydrogels can be casted into the inserts and cells can be cultured either in or on the hydrogels.

Microcontainer Delivery of Antibiotic Improves Treatment of Pseudomonas aeruginosa Biofilms.

Biofilm-associated infections are difficult to treat effectively with antibiotics despite repeated treatments. Polymeric microdevices (microcontainers) have previously been shown to engulf in mucus layers and to provide tunable release. Such devices may overcome the challenge of delivering antibiotics into the biofilm, increasing the local drug concentration and hence improve local bacterial killing.

Single particles as resonators for thermomechanical analysis.

Thermal methods are indispensable for the characterization of most materials. However, the existing methods require bulk amounts for analysis and give an averaged response of a material. This can be especially challenging in a biomedical setting, where only very limited amounts of material are initially available.

Temperature-Modulated Micromechanical Thermal Analysis with Microstring Resonators Detects Multiple Coherent Features of Small Molecule Glass Transition.

Micromechanical Thermal Analysis utilizes microstring resonators to analyze a minimum amount of sample to obtain both the thermal and mechanical responses of the sample during a heating ramp. We introduce a modulated setup by superimposing a sinusoidal heating on the linear heating and implementing a post-measurement data deconvolution process. This setup is utilized to take a closer look at the glass transition as an important fundamental feature of amorphous matter with relations to the processing and physical stability of small molecule drugs.

Quantitative SERS Assay on a Single Chip Enabled by Electrochemically Assisted Regeneration: A Method for Detection of Melamine in Milk.

Reusability of sensors is relevant when aiming to decrease variation between measurements, as well as cost and time of analysis. We present an electrochemically assisted surface-enhanced Raman spectroscopy (SERS) platform with the capability to reverse the analyte-surface interaction, without damaging the SERS substrate, allowing for efficient sensor reuse. The platform was used in combination with a sample pretreatment step, when detecting melamine from milk.

In Vitro, Ex Vivo and In Vivo Evaluation of Microcontainers for Oral Delivery of Insulin.

Enhancing the oral bioavailability of peptides has received a lot of attention for decades but remains challenging, partly due to low intestinal membrane permeability. Combining a permeation enhancer (PE) with unidirectionally releasing microcontainers (MCs) has previously been shown to increase insulin permeation across Caco-2 cell monolayers. In the present work, this setup was further employed to compare three common PEs-sodium caprate (C), sodium dodecyl sulfate (SDS), and lauroyl carnitine.

Development of an automated flow-based spectrophotometric immunoassay for continuous detection of zearalenone.

Considering the widespread contaminations of food products with mycotoxins, it is important to develop, robust, time- and cost-effective detection methods. We developed and optimized an immunoassay using a continuous flow system for the detection of zearalenone (ZEN). The assay was performed in a flow mode using an automated sequential injection system.

Determining Thermal Conductivity of Small Molecule Amorphous Drugs with Modulated Differential Scanning Calorimetry and Vacuum Molding Sample Preparation.

Thermal conductivity is a material specific property, which influences many aspects of pharmaceutical development, such as processing, modelling, analysis, and the development of novel formulation approaches. We have presented a method to measure thermal conductivity of small molecule organic glasses, based on a vacuum molding sample preparation technique combined with modulated differential scanning calorimetry. The method is applied to the two amorphous model compounds indomethacin and celecoxib.

Investigation of Mucoadhesion and Degradation of PCL and PLGA Microcontainers for Oral Drug Delivery.

Microfabricated devices have been introduced as a promising approach to overcome some of the challenges related to oral administration of drugs and, thereby, improve their oral bioavailability. In this study, we fabricate biodegradable microcontainers with different polymers, namely poly-ɛ-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) 50:50 and PLGA 75:25 by hot punching. The mucoadhesion of the microcontainers is assessed with an retention model on porcine intestinal tissue.

Pyrolytic carbon resonators for micromechanical thermal analysis.

Thermal analysis is essential for the characterization of polymers and drugs. However, the currently established methods require a large amount of sample. Here, we present pyrolytic carbon resonators as promising tools for micromechanical thermal analysis (MTA) of nanograms of polymers.

Present and Future of Surface-Enhanced Raman Scattering.

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products.

Microcontainers for oral insulin delivery - In vitro studies of permeation enhancement.

Oral delivery of peptides is challenging due to their low uptake through the small intestinal epithelium. Tight junctions, connecting the enterocytes, impede permeability, often necessitating the use of permeation enhancers in the formulation. Loading of peptide and permeation enhancer into micro-scale devices, such as microcontainers, can potentially confine the effective absorptive area through unidirectional release and thereby enhance absorption.

Biodegradable microcontainers - towards real life applications of microfabricated systems for oral drug delivery.

Microfabrication techniques have been applied to develop micron-scale devices for oral drug delivery with a high degree of control over size, shape and material composition. Recently, microcontainers have been introduced as a novel approach to obtain unidirectional release to avoid luminal drug loss, enhance drug permeation, protect drug payload from the harsh environment of the stomach, and explore the ability for targeted drug delivery. However, in order to eventually pave the way for real life applications of these microfabricated drug delivery systems, it is necessary to fabricate them in biodegradable materials approved for similar applications and with strategies that potentially allow for large scale production.

Modular, Lightweight, Wireless Potentiostat-on-a-Disc for Electrochemical Detection in Centrifugal Microfluidics.

Interfacing electrochemical sensors in a lab-on-a-disc (LoD) system with a potentiostat is often tedious and challenging. We here present the first multichannel, modular, lightweight, and wirelessly powered, custom-built potentiostat-on-a-disc (PoD) for centrifugal microfluidic applications. The developed potentiostat is in the form factor of a typical digital video disc (DVD) and weighs only 127 g.

Where Is the Drug? Quantitative 3D Distribution Analyses of Confined Drug-Loaded Polymer Matrices.

To enhance oral bioavailability of poorly soluble drugs, microfabricated devices can be utilized. One example of such devices is microcontainers. These are cylindrical in shape with an inner cavity for drug loading and with only the top side open for release.

Thread-Like Radical-Polymerization via Autonomously Propelled (TRAP) Bots.

Micromotor-mediated synthesis of thread-like hydrogel microstructures in an aqueous environment is presented. The study utilizes a catalytic micromotor assembly (owing to the presence of a Pt layer), with an on-board chemical reservoir (i.e.