In this review article, we focus on the various types of materials used in biomedical implantable devices, including the polymeric materials used as substrates and for the packaging of such devices. ...Polymeric materials are used because of the ease of fabrication, flexibility, and their biocompatible nature as well as their wide range of mechanical, electrical, chemical, and thermal behaviors when combined with different materials as composites. Biocompatible and biostable polymers are extensively used to package implanted devices, with the main criteria that include gas permeability and water permeability of the packaging polymer to protect the electronic circuit of the device from moisture and ions inside the human body. Polymeric materials must also have considerable tensile strength and should be able to contain the device over the envisioned lifetime of the implant. For substrates, structural properties and, at times, electrical properties would be of greater concern. Section gives an introduction of some medical devices and implants along with the material requirements and properties needed. Different synthetic polymeric materials such as polyvinylidene fluoride, polyethylene, polypropylene, polydimethylsiloxane, parylene, polyamide, polytetrafluoroethylene, poly(methyl methacrylate), polyimide, and polyurethane have been examined, and liquid crystalline polymers and nanocomposites have been evaluated as biomaterials that are suitable for biomedical packaging (section ). A summary and glimpse of the future trend in this area has also been given (section ). Materials and information used in this manuscript are adapted from papers published between 2010 and 2015 representing the most updated information available on each material.
Focusing and separation of particles such as cells at high throughput is extremely attractive for biomedical applications. Particle manipulation based on inertial effects requires a high flow speed ...and thus is well-suited to high-throughput applications. Recently, inertial focusing and separation using curvilinear microchannels has been attracting a great amount of interest because of the linear structure for parallelization, small device footprint, superior particle-focusing performance, and easy implementation of particle separation. However, the curvature directions of these microchannels alternate, leading to variations in both the magnitude and direction of the induced secondary flow. Accumulation of this variation along the channel causes unpredictable behaviors of particles. This paper systematically investigates the inertial-focusing phenomenon in low-aspect-ratio symmetric sinusoidal channels. First, we comprehensively studied the effects of parameters such as viscosity, flow conditions, particle size, and geometric dimensions of the microchannel on differential particle focusing. We found that particle inertial focusing is generally independent of fluid kinematic viscosity but highly dependent on particle size, flow conditions, and channel dimensions. Next, we derived an explicit scaling factor and included all four dimensionless parameters (particle-blockage ratio, curvature ratio, Dean number, and channel aspect ratio) in a single operational map to illustrate the particle-focusing patterns. Finally, we proposed a rational guideline to intuitively instruct the design of channel dimensions for separation of a given particle mixture.
We introduce a unique system to achieve on-demand droplet merging and splitting using a perpendicular AC electric field. The working mechanism involves a micropillar to split droplets, followed by ...electrocoalescence using an AC electric field. Adjusting the parameters of the AC signal and conductivity of the fluid result in different merging regimes. We observed a minimum threshold voltage and a strong influence of the surfactant. We hypothesize that the merging process is caused by dipole–dipole coalescence between the daughter droplets. At the same time, adjustment of the conductivity reveals a shift in the merging regimes and can be explained with an electric circuit diagram. Size-based sorting using this merging phenomenon is subsequently demonstrated, where alternate, single, double, and triple droplets sorting were achieved. The concept presented in this paper is potentially useful for drug dispensing or multivolume digital polymerase chain reaction, as droplets of multiple sizes can be generated simultaneously.
We introduce an effective method to actively induce droplet generation using negative pressure. Droplets can be generated on demand using a series of periodic negative pressure pulses. Fluidic ...network models were developed using the analogy to electric networks to relate the pressure conditions for different flow regimes. Experimental results show that the droplet volume is correlated to the pressure ratio with a power law of 1.3. Using a pulsed negative pressure at the outlet, we are able to produce droplets in demand and with a volume proportional to the pulse width.
Existing therapies for type 2 diabetes mellitus (T2DM) show limited efficacy or have adverse effects. Numerous genetic variants associated with T2DM have been identified, but progress in translating ...these findings into potential drug targets has been limited. Here, we describe the tools and platforms available to identify effector genes from T2DM-associated coding and non-coding variants and prioritize them for functional studies. We discuss QSER1 and SLC12A8 as examples of genes that have been identified as possible T2DM candidate genes using these tools and platforms. We suggest further approaches, including the use of sequencing data with increased sample size and ethnic diversity, single-cell omics data for analyses, glycaemic trait associations to predict gene function and, potentially, human induced pluripotent stem cell 'village' cultures, to strengthen current gene functionalization workflows. Effective prioritization of T2DM-associated genes for experimental validation could expedite our understanding of the genetic mechanisms responsible for T2DM to facilitate the use of precision medicine in its treatment.
Interfacial gas enrichment (IGE) of dissolved gases in water is shown to govern the strong attraction between solid hydrophobic surfaces of an atomic force microscopy (AFM) colloidal probe and solid ...substrate. However, the role of IGE in controlling the attraction between fluid–fluid interfaces of foam films and emulsion films is difficult to establish by AFM techniques because of the extremely fast coalescence. Here, we applied droplet-based microfluidics to capture the fast coalescence event under the creeping flow condition and quantify the effect of IGE on the drainage and stability of water films between coalescing oil droplets. The amount of dissolved gases is controlled by partially degassing the oil phase. When the amount of dissolved gases (oxygen) in oil decreases (from 7.89 to 4.59 mg/L), the average drainage time of coalescence significantly increases (from 19 to 50 ms). Our theoretical quantification of the coalescence by incorporating IGE into the multilayer van der Waals attraction theory confirms the acceleration of film drainage dynamics by the van der Waals attractive force generated by IGE. The thickness of the IGE layer decreases from 5.5 to 4.9 nm when the amount of dissolved gas decreases from 7.89 to 4.59 mg/L. All these results establish the universal role of dissolved gases in governing the strong attraction between particulate hydrophobic interfaces.
The hepatocyte nuclear factors (HNFs) namely HNF1α/β, FOXA1/2/3, HNF4α/γ and ONECUT1/2 are expressed in a variety of tissues and organs, including the liver, pancreas and kidney. The spatial and ...temporal manner of HNF expression regulates embryonic development and subsequently the development of multiple tissues during adulthood. Though the HNFs were initially identified individually based on their roles in the liver, numerous studies have now revealed that the HNFs cross-regulate one another and exhibit synergistic relationships in the regulation of tissue development and function. The complex HNF transcriptional regulatory networks have largely been elucidated in rodent models, but less so in human biological systems. Several heterozygous mutations in these HNFs were found to cause diseases in humans but not in rodents, suggesting clear species-specific differences in mutational mechanisms that remain to be uncovered. In this review, we compare and contrast the expression patterns of the HNFs, the HNF cross-regulatory networks and how these liver-enriched transcription factors serve multiple functions in the liver and beyond, extending our focus to the pancreas and kidney. We also summarise the insights gained from both human and rodent studies of mutations in several HNFs that are known to lead to different disease conditions.
Stem cells represent a unique opportunity for regenerative medicine to cure a broad number of diseases for which current treatment only alleviates symptoms or retards further disease progression. ...However, the number of stem cells available has speedily increased these past 10 years and their diversity presents new challenges to clinicians and basic scientists who intend to use them in clinics or to study their unique properties. In addition, the recent possibility to derive pluripotent stem cells from somatic cells using epigenetic reprogramming has further increased the clinical interest of stem cells since induced pluripotent stem cells could render personalized cell-based therapy possible. The present review will attempt to summarize the advantages and challenges of each type of stem cell for current and future clinical applications using specific examples.
Core–shell microparticles containing an aqueous core have demonstrated their value for microencapsulation and drug delivery systems. The most important step in generating these uniquely structured ...microparticles is the formation of droplets and double emulsion. The droplet generator must meet the performance and reliability requirements, including accurate size control with tunability and monodispersity. Herein, we present a facile technique to generate surfactant-free core–shell droplets with an aqueous core in a microfluidic device. We demonstrate that the geometry of the core–shell droplets can be precisely adjusted by the flow rates of the droplet components. As the shell is polymerized after the formation of the core–shell droplets, the resulting solid microparticles ensure the encapsulation of the aqueous core and prevent undesired release. We then study experimentally and theoretically the behaviour of resultant microparticles under heating and compression. The microparticles demonstrate excellent stability under both thermal and mechanical loads. We show that the rupture force can be quantitatively predicted from the shell thickness relative to the outer shell radius. Experimental results and theoretical predictions confirm that the rupture force scales directly with the shell thickness.
Graphical abstract
Current complexities in human pluripotent stem cell (hPSC)‐based studies. hPSC studies begin with the recruitment of patients harboring disease‐associated gene variant(s) that may increase ...susceptibility to disease development. Somatic reprogramming is then performed to derive patient‐specific human induced pluripotent stem cells (hiPSCs), followed by step‐wise directed differentiation to a relevant cell type before qualitative/quantitative assays are performed to assess for phenotypic or gene expression differences between the healthy and diseased hiPSCs.
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