Biology subjects

Day, S. W.

Publications and source records attributed to Day, S. W..

7 recordsLinked to original sources

bioRxiv2026

Modular Integration of Impedance Sensing for Real-Time Assessment of Barrier Integrity

Microphysiological systems (MPS) are essential for modeling tissue barriers, yet integrating electrical readouts often requires permanently sealed microfluidic architectures that limit access to open-well (direct-access) workflows used in bioscience laboratories. To resolve this issue, we present a modular approach in which functional components are added and removed from a standard MPS core using a magnetic interface. This design preserves compatibility with established open-well protocols for seeding and downstream analysis, while microfluidic perfusion or electrical sensing capabilities are added only when needed. We demonstrate this approach with an impedance-sensing module that enables continuous impedance measurements to assess barrier function. By fitting spectra to an equivalent circuit model, we quantify junctional and non-junctional electrical contributions to barrier integrity over time, alongside conventional single-frequency TEER, and complementary permeability and imaging readouts. We apply this platform across three representative use cases, including LPS-induced disruption, shear stress-mediated strengthening, and compatibility with barrier models formed above a 3D hydrogel matrix.

bioengineering↗

bioRxiv2025

Oxygen Transport in Nanoporous SiN Membrane Compared to PDMS and Polypropylene for Microfluidic ECMO

Extracorporeal Membrane Oxygenation (ECMO) serves as a crucial intervention for patients with severe pulmonary dysfunction by facilitating oxygenation and carbon dioxide removal. While traditional ECMO systems are effective, their large priming volumes and significant blood-contacting surface areas can lead to complications, particularly in neonates and pediatric patients. Microfluidic ECMO systems offer a promising alternative by miniaturizing the ECMO technology, reducing blood volume requirements, and minimizing device surface area to improve safety and efficiency. This study investigates the oxygen transport performance of three membrane types-- polydimethylsiloxane (PDMS), polypropylene, and a novel nanoporous silicon nitride (SiN) membrane--in a microfluidic ECMO platform. While nanoporous membranes rely on pore-mediated diffusion and PDMS on polymer lattice diffusion, results show no significant differences in device oxygenation efficiency (p > 0.05). Blood-side factors, including the diffusion rate of oxygen through the red blood cell (RBC) membrane, RBC residence time, and hemoglobin binding kinetics, were identified as primary bottlenecks. Even computational models of a hypothetical infinitely permeable membrane corroborate the limited impact of membrane material. These findings suggest a shift in ECMO design priorities from membrane material to blood-side enhancements. This research provides a foundation for optimizing ECMO systems.

bioengineering↗

bioRxiv2022

The Modular μSiM Reconfigured: Integration of Microfluidic Capabilities to Study in vitro Barrier Tissue Models under Flow

Microfluidic approaches to study tissue barriers have emerged to address the lack of fluid flow in conventional "open-well" Transwell-like devices. However, microfluidic techniques have not achieved widespread usage in bioscience laboratories because they are not fully compatible with traditional, tried-and-true experimental protocols. To advance barrier tissue research, there is a need for a platform that combines the advantages of both conventional open-well and microfluidic systems. Here, we develop a plug-and-play flow module to add on-demand microfluidic capabilities to a modular microfluidic system featuring a silicon membrane "m-SiM" as an open-well device with live-cell imaging capabilities. The magnetic latching assembly of our design enables bi-directional reconfiguration between open-well and fluidic modes. This design feature allows users to conduct an experiment in an open-well format with established protocols and then add or remove microfluidic capabilities as desired. Our work also provides an experimentally-validated flow model to help select desired flow conditions based on the experimental needs. As a proof-of-concept, we demonstrate flow-induced alignment of endothelial cells and visualize different phases of neutrophil transmigration across an endothelial monolayer under flow. We anticipate that our reconfigurable design will be adopted by both engineering and bioscience laboratories due to the compatibility with standard open-well protocols and the simple flow addition capabilities.

bioengineering↗

bioRxiv2022

Local extensional flows promote long-range fiber alignment in 3D collagen hydrogels

Randomly oriented type I collagen (COL1) fibers in the extracellular matrix (ECM) are reorganized by biophysical forces into aligned domains extending several millimeters and with varying degrees of fiber alignment. These aligned fibers can transmit traction forces, guide tumor cell migration, facilitate angiogenesis, and influence tissue morphogenesis. To create aligned COL1 domains in microfluidic cell culture models, shear flows have been used to align thin COL1 matrices (<50m in height) in a microchannel. However, there has been limited investigation into the role of shear flows in aligning 3D hydrogels (>130m). Here, we show that pure shear flows do not induce fiber alignment in 3D atelo COL1 hydrogels, but the simple addition of local extensional flow promotes alignment that is maintained across several millimeters, with a degree of alignment directly related to the extensional strain rate. We further advance experimental capabilities by addressing the practical challenge of accessing a 3D hydrogel formed within a microchannel by introducing a magnetically coupled modular platform that can be released to expose the microengineered hydrogel. We demonstrate the platforms capability to pattern cells and fabricate multi-layered COL1 matrices using layer-by-layer fabrication and specialized modules. Our approach provides an easy-to-use fabrication method to achieve advanced hydrogel microengineering capabilities that combine fiber alignment with biofabrication capabilities.

bioengineering↗

bioRxiv2021

The Effect of Blood Viscosity on Shear-Induced Hemolysis using a Magnetically Levitated Shearing Device

IntroductionBlood contacting medical devices, including rotary blood pumps, can cause shear-induced blood damage that may lead to adverse effects in patients. Due in part to an inadequate understanding of how cell-scale fluid mechanics impact red blood cell membrane deformation and damage, there is currently not a uniformly accepted engineering model for predicting blood damage caused by complex flow fields within ventricular assist devices (VADs). MethodsWe empirically investigated hemolysis in an axial Couette flow device typical of a rotary VAD to expand our current understanding of shear-induced blood damage in two ways. First, we used a magnetically levitated device to accurately control the shear rate and exposure time experienced by blood and to minimize the effects of other uncharacterized stresses. Second, we explored the effects of both hematocrit and plasma viscosity on shear-induced hemolysis to characterize blood damage based on the viscosity-independent shear rate, rather than on shear stress. ResultsOver a shear rate range of 20,000-80,000 1/s, the Index of Hemolysis was found to be largely independent of hematocrit, bulk viscosity, or the suspension media viscosity. ConclusionIt is recommended that future investigations of shear-induced blood damage report findings with respect to the viscosity-neutral term of shear rate, in addition to the bulk whole blood viscosity measured at an appropriate shear rate relevant to the flow conditions of the device.

bioengineering↗

bioRxiv2020

A power amplification dyad in seahorses

Ubiquitous constraints derived from the muscles structure limit the power capacity of fast contracting muscles. Correspondingly, organisms evolved elastic elements that store energy which, when released, can be used to rapidly accelerate appendages. Such latch-mediated spring actuation (LaMSA) systems comprise of a single elastic element and are used to actuate a single mass. Here we reveal a dual LaMSA system in seahorses, in which two elastic elements actuate two masses: the head as they rapidly swing it towards the prey, and the water mass sucked into the mouth to prevent the prey from escaping. This power-amplified system enhances the speeds of both head rotation and suction flows by x10 compared to similarly-sized fish. Furthermore, the dual system provides temporal coordination between head rotation and suction flows, a novel function for LaMSA. These findings extend the known function, capacity and design of LaMSA systems.

biophysics↗

bioRxiv2020

Numerical Model to Predict Hemolysis and Transport in a Membrane-Based Microfluidic Device

Microfluidic devices promise to overcome the limitations of conventional hemodialysis and oxygenation technologies by incorporating novel membranes with ultrahigh permeability into portable devices with low blood volume. However, the characteristically small dimensions of these devices contribute to both non-physiologic shear that could damage blood components and laminar flow that inhibits transport. While many studies have applied empirical and computational models of hemolysis to medical devices, such as valves and blood pumps, little is known about blood damage in the microfluidic flow regime. In this study, four design variants of a microfluidic membrane-based oxygenator and two controls (positive and negative) are introduced and modeled using a Computational Fluid Dynamics (CFD) model to predict hemolysis. The simulations were performed in ANSYS Fluent for nine shear stress-based Power Law hemolysis model variants. Empirical testing of the devices in a recirculating loop revealed levels of hemolysis significantly lower (3 ppm hemolysis for pump, tube, and device combined) than the hemolysis ranges (>10 ppm) observed in conventional oxygenators. We found that most of the nine tested hemolysis models overpredict (5x to 10x) hemolysis compared to empirical experiments. However, two models demonstrated higher predictive accuracy for hemolysis values in devices characterized by low shear conditions, while another set of three models exhibited better performance for devices operating under higher shear conditions. Our study highlights the limitations of combining hemolysis models with computational fluid dynamics models for a priori in silico device-induced hemolysis. Nevertheless, with a judicious selection of hemolysis models based on the shear ranges of the test device, we propose that computational modeling can complement empirical testing in the development of novel micro-dialyzers or oxygenators, allowing for a more efficient iterative design process. Furthermore, the low device-induced hemolysis (< 2 ppm) measured in our study at physiologically relevant flow rates is promising for the future development of microfluidic dialyzers and oxygenators.

bioengineering↗