Comparison of biocompatibility and adsorption properties of different plastics for advanced microfluidic cell and tissue culture models

Microfluidic technology is providing new routes toward advanced cell and tissue culture models to better understand human biology and disease. Many advanced devices have been made from poly(dimethylsiloxane) (PDMS) to enable experiments, for example, to study drug metabolism by use of precision-cut liver slices, that are not possible with conventional systems. However, PDMS, a silicone rubber material, is very hydrophobic and tends to exhibit significant adsorption and absorption of hydrophobic drugs and their metabolites. Although glass could be used as an alternative, thermoplastics are better from a cost and fabrication perspective. Thermoplastic polymers (plastics) allow easy surface treatment and are generally transparent and biocompatible. This study focuses on the fabrication of biocompatible microfluidic devices with low adsorption properties from the thermoplastics poly(methyl methacrylate) (PMMA), polystyrene (PS), polycarbonate (PC), and cyclic olefin copolymer (COC) as alternatives for PDMS devices. Thermoplastic surfaces were oxidized using UV-generated ozone or oxygen plasma to reduce adsorption of hydrophobic compounds. Surface hydrophilicity was assessed over 4 weeks by measuring the contact angle of water on the surface. The adsorption of 7-ethoxycoumarin, testosterone, and their metabolites was also determined after UV-ozone treatment. Biocompatibility was assessed by culturing human hepatoma (HepG2) cells on treated surfaces. Comparison of the adsorption properties and biocompatibility of devices in different plastics revealed that only UV-ozone-treated PC and COC devices satisfied both criteria. This paper lays an important foundation that will help researchers make informed decisions with respect to the materials they select for microfluidic cell-based culture experiments.     

A new parallel plate shear cell for in situ real-space measurements of complex fluids under shear flow

We developed and tested a parallel plate shear cell that can be mounted on top of an inverted microscope to perform confocal real-space measurements on complex fluids under shear. To follow structural changes in time, a plane of zero velocity is created by letting the plates move in opposite directions. The location of this plane is varied by changing the relative velocities of the plates. The gap width is variable between 20 and 200 microm with parallelism better than 1 microm. Such a small gap width enables us to examine the total sample thickness using high numerical aperture objective lenses. The achieved shear rates cover the range of 0.02-10(3) s(-1). This shear cell can apply an oscillatory shear with adjustable amplitude and frequency. The maximum travel of each plate equals 1 cm, so that strains up to 500 can be applied. For most complex fluids, an oscillatory shear with such a large amplitude can be regarded as a continuous shear. We measured the flow profile of a suspension of silica colloids in this shear cell. It was linear except for a small deviation caused by sedimentation. To demonstrate the excellent performance and capabilities of this new setup we examined shear induced crystallization and melting of concentrated suspensions of 1 microm diameter silica colloids.     

Biomarker-Oriented Therapy in Bladder and Renal Cancer

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials. Currently, patients with metastatic UC (mUC) are usually treated with second-line ICI, while cisplatin-ineligible patients with programmed death-ligand 1 (PD-L1) positive tumors can benefit from first-line ICI. Platinum-relapsed UC patients harboring FGFR2/3 mutations can be treated with erdafitinib, while enfortumab vedotin has emerged as a novel third-line treatment option for mUC. In metastatic (clear cell) renal cell carcinoma (RCC), ICI was first introduced as second-line treatment after vascular endothelial growth factor receptor—tyrosine kinase inhibition (VEGFR-TKI). Currently, ICIs have also been introduced as first-line treatment in metastatic RCC. Although there is no evidence up to now for beneficial adjuvant treatment after surgery with VEGFR-TKIs in high-risk non-metastatic RCC, several trials are underway investigating the potential beneficial effect of ICIs in this setting.     

Analysis of a transparent organic photoconductive sensor

The electro-optical performance of transparent photoconductive sensors based on stacks of organic layers is investigated. The photoconductive sensors are composed of interdigitated electrodes covered with a stack of two transparent organic compounds: a hole transport layer 1,3,5-tris[(3-methylphenyl)phenylamino]benzene (m-MTDAB) and an exciton generation layer 3,4,9,10-perylenetetracarboxylic bis-benzimidazole (PTCBI). The photocurrent through the device is measured as a function of the voltage across the electrodes for different illumination levels. Based on the measurements we can explain the working principle of the photoconductive sensor and compare the performance of four different stacks. In order to study the optical sensitivity in more detail, a photoconductive device with two parallel electrodes is manufactured and illuminated by a line-shaped laser beam that covers only a fraction of the gap between the electrodes. The current through the photoconductive sensor is measured as a function of the position of the local illumination for a set of voltages. The experimental results confirm that there is a high-field space charge region near the cathode.     

Performance Prediction of Compact Fin-and-Tube Heat Exchangers in Maldistributed Airflow

An experimental study of a fin-and-tube heat exchanger was performed in two different configurations (single and three-screen mode). To this end, a test rig was constructed to evaluate the heat transfer capacity on the air side and water side. A wide range of Reynolds numbers on the air side was investigated. A series of measurements was performed with uniform inlet flow conditions. These served to determine the heat transfer correlation for the fin type using the Wilson plot method. No correlation was available, as the fin is an adapted inclined louvered type. To validate these results, a thorough uncertainty analysis was performed. Parallel to the experiments, a simulation program was written, designed to take non-uniform flow into account. The program is based on a local (section by section) analysis scheme. To validate the program, a series of non-uniform measurements was performed. Results showed that the program is able to predict the impact of non-uniform inlet flow conditions. The numerical code can be used as a design tool to develop more efficient heat exchangers.     

Spatial distribution of polybrominated diphenyl ethers in southern Ontario as measured in indoor and outdoor window organic films

Organic films were collected from indoor and outdoor window surfaces, along an urban-rural transect extending northward from Toronto, Ontario, Canada, and analyzed for 41 polybrominated diphenyl ether congeners (PBDE). For exterior films, urban sigmaPBDE concentrations were approximately 10x greater than rural concentrations, indicating an urban-rural gradient and greater PBDE sources in urban areas. Urban films ranged from 2.5 to 14.5 ng/m2 (mean = 9.0 ng/ m2), excluding the regional "hotspot" Electronics Recycling Facility, compared to 1.1 and 0.56 ng/m2 at the Suburban and Rural sites. Interior urban films (mean = 34.4 ng/m2) were 3 times greater than rural films (10.3 ng/m2) and were representative of variations in building characteristics. Indoor films were 1.5-20 times greater than outdoor films, consistent with indoor sources of PBDEs and enhanced degradation in outdoor films. Congener profiles were dominated by BDE-209 (51.1%), consistent with deca-BDE as the main source mixture, followed by congeners from the penta-BDE mixture (BDE-99:13.6% and -47:9.4%) and some octa-BDE (BDE-183:1.5%). Congener patterns suggest a degradative loss of lower brominated compounds in outdoor films versus indoor films. Gas-phase air concentrations were back-calculated from film concentrations using the film-air partition coefficient (K(FA)). Mean calculated air concentrations were 4.8 pg/m3 for outdoor and 42.1 pg/m3 for indoor urban sites, indicating that urban indoor air is a source of PBDEs to urban outdoor air and the outdoor regional environment.     

Multitargeted Approach for the Optimization of Morphogenesis and Barrier Formation in Human Skin Equivalents

In vitro skin tissue engineering is challenging due to the manifold differences between the in vivo and in vitro conditions. Yet, three-dimensional (3D) human skin equivalents (HSEs) are able to mimic native human skin in many fundamental aspects. However, the epidermal lipid barrier formation, which is essential for the functionality of the skin barrier, remains compromised. Recently, HSEs with an improved lipid barrier formation were generated by (i) incorporating chitosan in the dermal collagen matrix, (ii) reducing the external oxygen level to 3%, and (iii) inhibiting the liver X receptor (LXR). In this study, we aimed to determine the synergic effects in full-thickness models (FTMs) with combinations of these factors as single-, double-, and triple-targeted optimization approaches. The collagen–chitosan FTM supplemented with the LXR inhibitor showed improved epidermal morphogenesis, an enhanced lipid composition, and a better lipid organization. Importantly, barrier functionality was improved in the corresponding approach. In conclusion, our leading optimization approach substantially improved the epidermal morphogenesis, barrier formation, and functionality in the FTM, which therefore better resembled native human skin.     

Front glass thickness requirements for high resolution polarized stereoscopic displays: A simulation platform

The tendency of the display market is towards displays with higher resolutions. Therefore, patterned retarder‐based stereoscopic displays require smaller front glass thickness to maintain good vertical viewing angle and limited crosstalk. To properly design these stereoscopic displays and quantify these requirements, we developed a simulation platform to predict radiance, polarization profile, and crosstalk over viewing angles and over wavelengths. Tunable parameters such as the distance between the pixels and the patterned retarder, and the optical properties of the patterned retarder are included. The simulation platform has been validated by comparing outcomes of simulations with measurements. We predict crosstalk accounting for both the human eye field of view and the diameter of the pupil. We found that to obtain a vertical viewing angle of at least ± 30° and crosstalk of at most 0.11 for a display with a pixel pitch beyond 0.27 mm, the display should include black absorbers, and the thickness of the front glass should be at most 0.5 mm. For higher resolution displays (pixel pitch no more than 0.21 mm), a front glass thickness at most 0.15 mm is required to produce a vertical viewing angle beyond ± 14° and a minimum viewing distance of 0.3 m.