Electro-osmosis modulated viscoelastic embryo transport in uterine hydrodynamics : mathematical modelling

Embryological transport features a very interesting and complex application of peristaltic fluid dynamics. Electro-osmotic phenomena are also known to arise in embryo transfer location. The fluid dynamic environment in embryological systems is also known to be non-Newtonian and exhibits strong viscoelastic properties. Motivated by these applications, the present article develops a new mathematical model for simulating two-dimensional peristaltic transport of a viscoelastic fluid in a tapered channel under the influence of electro-osmosis induced by asymmetric zeta potentials at the channel walls. The robust Jeffrey viscoelastic model is utilized. The finite Debye layer electro-kinetic approximation is deployed. The moving boundary problem is transformed to a steady boundary problem in the wave frame. The current study carries significant physiological relevance with an ever-increasing desire to study intrauterine fluid flow motion in an artificial uterus. The consequences of this model may introduce a new mechanical factor for embryo transport to a successful implantation site. Hydrodynamic characteristics are shown to be markedly influenced by the electro-osmosis, the channel taper angle and the phase shift between the channel walls. Furthermore it is demonstrated that volumetric flow rates and axial flow are both enhanced when the electro-osmotic force aids the axial flow for specific values of zeta potential ratio. Strong trapping of the bolus (representative of the embryo) is identified in the vicinity of the channel central line when the electro-osmosis opposes axial flow. The magnitude of the trapped bolus is observed to be significantly reduced with increasing tapered channel length whereas embryo axial motility is assisted with aligned electro-osmotic force

Metachronal propulsion of a magnetized particle-fluid suspension in a ciliated channel with heat and mass transfer

Biologically inspired pumping systems are of great interest in modern engineering since they achieve enhanced efficiency and circumvent the need for moving parts and maintenance. Industrial applications also often feature two-phase flows. In this article, motivated by these applications, the pumping of an electrically conducting particle-fluid suspension due to metachronal wave propulsion of beating cilia in a two-dimensional channel with heat and mass transfer under a transverse magnetic field is investigated theoretically. The governing equations for mass and momentum conservation for fluid- and particle-phases are formulated by ignoring the inertial forces and invoking the long wavelength approximation. The Jeffrey viscoelastic model is employed to simulate non-Newtonian characteristics. The normalized resulting differential equations are solved analytically. Symbolic software is employed to evaluate the results and simulate the influence of different parameters on flow characteristics. Results are visualized graphically with carefully selected and viable data

A survey of small bowel modelling and its applications for capsule endoscopy

This is the final version. Available on open access from Elsevier via the DOI in this recordThe small intestine, an anatomical site previously considered inaccessible to clinicians due to its small diameter and length, is the part of the gastrointestinal tract between the stomach and the colon. Since its introduction into clinical practice two decades ago, capsule endoscopy has become established as the primary modality for examining the surface lining of the small intestine. Today, researchers continue to develop ground-breaking technologies for novel miniature devices aiming for tissue biopsy, drug delivery and therapy. The purpose of this paper is to provide researchers and engineers in this area a comprehensive review of the progress in understanding the anatomy and physiology of the small intestine and how this understanding was translated to virtual and physical test platforms for assessing the performance of these intestinal devices. This review will cover both theoretical and practical studies on intestinal motor activities and the work on mathematical modelling and experimental investigation of capsule endoscope in the small intestine. In the end, the requirements for improving the current work are drawn, and the expectations on future research in this field are provided.Engineering and Physical Sciences Research Council (EPSRC)China Scholarship Counci

Fluid-Induced Propulsion of Rigid Particles in Wormlike Micellar Solutions

In the absence of inertia, a reciprocal swimmer achieves no net motion in a viscous Newtonian fluid. Here, we investigate the ability of a reciprocally actuated particle to translate through a complex fluid that possesses a network using tracking methods and birefringence imaging. A geometrically polar particle, a rod with a bead on one end, is reciprocally rotated using magnetic fields. The particle is immersed in a wormlike micellar (WLM) solution that is known to be susceptible to the formation of shear bands and other localized structures due to shear-induced remodeling of its microstructure. Results show that the nonlinearities present in this WLM solution break time-reversal symmetry under certain conditions, and enable propulsion of an artificial "swimmer." We find three regimes dependent on the Deborah number (De): net motion towards the bead-end of the particle at low De, net motion towards the rod-end of the particle at intermediate De, and no appreciable propulsion at high De. At low De, where the particle time-scale is longer then the fluid relaxation time, we believe that propulsion is caused by an imbalance in the fluid first normal stress differences between the two ends of the particle (bead and rod). At De~1, however, we observe the emergence of a region of network anisotropy near the rod using birefringence imaging. This anisotropy suggests alignment of the micellar network, which is "locked in" due to the shorter time-scale of the particle relative to the fluid

A theoretical and experimental study of the mechanism of axoplasmic convection in nerve fibers driven by peristaltic surface waves

In the study of cell biology, investigators have found that substances which are produced within the cell nucleus are sometimes found throughout the cell at points distant from the site of production. In the case of nerve cells (neurons), this is particularly dramatic because of the unusual elongated geometry of these cells. A neuron possesses a cylindrical tubular extension called an axon or axis cylinder which is characterized by a large length-to-diameter ratio (103-106). The existence of a continuous proximo-distal flow of axoplasm within these cylindrical axons has now been demonstrated by numerous investigators. In this study, engineering techniques are employed to explore the role of microperistalsis as a possible driving mechanism for this axoplasmic flow. An experimental technique for injecting axons (5-10 microns-diameter) with micropipettes under visual microscopic control has been perfected. A new technique for microcapillary tube viscometric measurements applicable to micro samples of biological materials is presented. Using these techniques, a flow curve has been obtained for the axoplasmic substance. The results of these experiments indicate that axoplasin behaves as a highly viscous, pseudo-plastic material. No evidence of significant time-dependent thixotropic or viscoelastic effects was apparent. A theoretical analysis of the peristaltic pumping of pseudoplastic fluids at low Reynolds numbers by means of an infinite train of sinusoidal peristaltic waves is. presented. Results are shown as a series of pump characteristic curves involving the geometrical properties of tlie wave and the flow properties of the pseudo-plastic fluid as parameters. Data obtained from experiments performed on a plane, two-dimensional model are used to confirm the theoretical results. Cinemicrographic evidence reported in the literature describing waves traveling over the surface of axons in culture is discussed. A study of the geometrical properties of the peristaltic waves taken from these motion picture data is presented. The viscometric data obtained from axoplasm are used to establish system resistance curves for axons idealized as uniform cylindrical tubes. These data are correlated with the theoretical pump characteristic curves to determine an expected flow rate. A comparison between the theoretical flow rates and the observed axonal flow rates gives quantitative support to the hypothesis that peristalsis is the mechanism for axoplasmic flow. In addition, it is shown that the peristaltic pumping of a pseudoplastic fluid depends only on the geometrical properties of the peristaltic waves and the flow behavior index of the fluid. For this case of axoplasm, this indicates that the theoretical flow speed of axoplasm is independent both of the consistency of the axoplasmic material and the diameter of the axon

Implantable Microsystem Technologies For Nanoliter-Resolution Inner Ear Drug Delivery

Advances in protective and restorative biotherapies have created new opportunities to use site-directed, programmable drug delivery systems to treat auditory and vestibular disorders. Successful therapy development that leverages the transgenic, knock-in, and knock-out variants of mouse models of human disease requires advanced microsystems specifically designed to function with nanoliter precision and with system volumes suitable for implantation. The present work demonstrates a novel biocompatible, implantable, and scalable microsystem consisted of a thermal phase-change peristaltic micropump with wireless control and a refillable reservoir. The micropump is fabricated around a catheter microtubing (250 μm OD, 125 μm ID) that provided a biocompatible leak-free flow path while avoiding complicated microfluidic interconnects. Direct-write micro-scale printing technology was used to build the mechanical components of the pump around the microtubing directly on the back of a printed circuit board assembly. In vitro characterization results indicated nanoliter resolution control over the desired flow rates of 10–100 nL/min by changing the actuation frequency, with negligible deviations in presence of up to 10× greater than physiological backpressures and ±3°C ambient temperature variation. A biocompatibility study was performed to evaluate material suitability for chronic subcutaneous implantation and clinical translational development. A stand-alone, refillable, in-plane, scalable, and fully implantable microreservoir platform was designed and fabricated to be integrated with the micropump. The microreservoir consists two main components: a cavity for storing the drug and a septum for refilling. The cavity membrane is fabricated with thin Parylene-C layers, using a polyethylene glycol (PEG) sacrificial layer. The septum thickness is minimized by pre-compression down to 1 mm. The results of in vitro characterization indicated negligible restoring force for the optimized cavity membrane and thousands of punctures through the septum without leakage. The micropump and microreservoir were integrated into microsystems which were implanted in mice. The microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion. The results match with syringe pump gold standard. For the first time a miniature and yet scalable microsystem for inner ear drug delivery was developed, enabling drug discovery opportunities and translation to human

Swimming dynamics of a micro-organism in a couple stress fluid : a rheological model of embryological hydrodynamic propulsion

Mathematical simulations of embryological fluid dynamics are fundamental to improving clinical understanding of the intricate mechanisms underlying sperm locomotion. The strongly rheological nature of reproductive fluids has been established for a number of decades. Complimentary to clinical studies, mathematical models of reproductive hydrodynamics provide a deeper understanding of the intricate mechanisms involved in spermatozoa locomotion which can be of immense benefit in clarifying fertilization processes. Although numerous non-Newtonian studies of spermatozoa swimming dynamics in non-Newtonian media have been communicated, very few have addressed the micro-structural characteristics of embryological media. This family of micro-continuum models include Eringen’s micro-stretch theory, Eringen’s microfluid and micropolar constructs and V.K. Stokes’ couple-stress fluid model, all developed in the 1960s. In the present paper we implement the last of these models to examine the problem of micro-organism (spermatozoa) swimming at low Reynolds number in a homogenous embryological fluid medium with couple stress effects. The micro-organism is modeled as with Taylor’s classical approach, as an infinite flexible sheet on whose surface waves of lateral displacement are propagated. The swimming speed of the sheet and rate of work done by it are determined as function of the parameters of orbit and the couple stress fluid parameter (α). The perturbation solutions are validated with a Nakamura finite difference algorithm. The perturbation solutions reveal that the normal beat pattern is effective for both couple stress and Newtonian fluids only when the amplitude of stretching wave is small. The swimming speed is observed to decrease with couple stress fluid parameter tending to its Newtonian limit as alpha tends to infinity. However the rate of work done by the sheet decreases with α and approaches asymptotically to its Newtonian value. The present solutions also provide a good benchmark for more advanced numerical simulations of micro-organism swimming in couple-stress rheological biofluids

Bioengineering approaches to simulate human colon microbiome ecosystem

Background Several diseases associated to colon microbial imbalance (dysbiosis), such as obesity, diabetes, inflammatory bowel disease, cardiovascular disease and cancer, are being reverted by modulation of gut microbiota composition through treatment with prebiotics and probiotics. Multiple in vitro models have been developed over the past three decades, with several experimental configurations, as they provide a quick, easy, and cost-effective approach to study the gut microbiome, as compared to troublesome and time-consuming in vivo studies. Scope and approach This review aims to provide an overview of the most relevant available in vitro models used to mimic the human colon microbiome dynamics, including macro-scale and microfluidic-based models. Main characteristics, functionalities, current applications and advantages or disadvantages of the models are discussed in order to provide useful information for end users (namely food and pharmaceutical researchers), when selecting the most appropriated model for assessing health claims and safety of novel functional food and drugs. Finally, the use of these colon models as a tool to study prebiotic and probiotic response in host-microbiota interaction is reviewed. Key findings and conclusions A wide range of in vitro models representing specific colon parts have been developed. However, none of these models can simultaneously cover all the key conditions found in the human colon (namely anatomical, physical, biochemical, and biological characteristics), as well as the complex microbiome-host interaction. Thus, there is a significant opportunity for further improvement of the models experimental setups towards more realistic operating systems, including mucosal surfaces, intestinal cells and tissues allowing microbiomehost crosstalk representation.SFRH/BD/139884/2018 from the Portuguese Foundation for Science and Technology (FCT). This study was supported by the FCT under the scope of the strategic funding of UIDB/04469/2020 unit and the Project ColOsH PTDC/BTM–SAL/30071/2017 (POCI–01–0145–FEDER–030071)info:eu-repo/semantics/publishedVersio

Complex High-Content Phenotypic Screening

There has been a renewed interest in cell-based phenotypic screening in drug discovery with the goal of improving the success and decreasing the clinical failure rate of new therapeutics. This has increasingly led to the development of biomimetic cellular models that more faithfully replicate human disease biology. Human tumour models have advanced to include relevant cell types such as primary patient tumour cells and grown using organotypic and 3D methods. Tissue organoids, which are 3D organ buds displaying realistic microanatomy, are becoming more commonly used in drug discovery to advance in vitro assays which predict drug toxicity and pharmacokinetics. Emerging technologies and cell culture methods are constantly improving the quality of tissue modelling that can be employed during primary phenotypic screening, and this has resulted in the identification of more efficacious and patient-relevant therapeutics