Microfluidic Channel System Research Articles

Effects of Panax notoginseng saponins on alleviating low shear induced endothelial inflammation and thrombosis via Piezo1 signalling

Ethnopharmacological relevancePanax notoginseng saponins (PNS) are the major effective components of Panax notoginseng (burk) F.H.Chen which is one of the classic promoting blood circulation herbs in traditional Chinese medicine. PNS is widely used in China for the treatment of cerebral ischemic stroke. Pathological low shear stress is a causal factor in endothelial inflammation and thrombosis. However, the mechanism of PNS against low shear related endothelial inflammation is still unclear. Aim to the studyThis study aims to investigate the effects of PNS against endothelial inflammation induced by low shear stress and to explore the underlying mechanical and biological mechanisms. Materials and methodsMouse model of carotid partial ligation for inducing low endothelial shear stress was established, the pharmacodynamic effect and mechanism of PNS against endothelial inflammation induced by low shear stress through Piezo1 were explored. Yoda1-evoked Piezo1 activation and expression in human umbilical vein endothelial cells (HUVECs) were determined at static condition. Microfluidic channel systems were used to apply shear stress on HUVECs and Piezo1 siRNA HUVECs to determine PECAM-1, p-YAP and VCAM-1 expression. And platelet rich plasma (PRP) was introduced to low shear treated endothelial cells surface to observe the adhesion and activation by fluorescence imaging and flowcytometry. ResultsPNS attenuated endothelial inflammation and improved blood flow in a reasonable dose response pattern in carotid partial ligation mouse model by influencing Piezo1 and PECAM-1 expression, while suppressing yes-associated protein (YAP) nuclear translocation. We found Piezo1 sensed abnormal shear stress and transduced these mechanical signals by different pathways in HUVECs, and PNS relieved endothelial inflammation induced by low shear stress through Piezo1. We also found Piezo1 signalling has interaction with PECAM-1 under low shear stress, which were involved in platelets adhesion to endothelial cells. Low shear stress increased YAP nuclear translocation and increased VCAM-1 expression in HUVECs which might activate platelets. PNS inhibited low shear induced Piezo1 and PECAM-1 expression and YAP nuclear translocation in HUVECs, furthermore inhibited platelet adhesion and activation on dysfunctional endothelial cells induced by low shear stress. ConclusionPNS ameliorated endothelial inflammation and thrombosis induced by low shear stress through modulation of the Piezo1 channel, PECAM-1 expression, and YAP nuclear translocation. PNS might serve as a potential therapeutic candidate for ameliorating endothelial inflammation induced by abnormal blood shear stress.

Dynamic Characteristics of λ-DNA Molecules Translocating through Tapered Microfluidic Channel System Driven by Electric Field Force

The dynamic characteristics of single DNA molecules translocating within micro/nano-channels are fundamental for a wide range of applications such as stretching, separating, mapping, and even sequencing of DNA molecules. In this study, a type of tapered microchannel chip with uniform height for all configurations was fabricated, with the major tapered structure having a length of 13 μm and a width that tapers from 5 μm to 20 μm. The dynamic characteristics such as the trajectories and velocities of λ-DNA molecules translocating from different positions driven by an external DC electric field force were systematically investigated by single-molecule fluorescence imaging technology. Some dynamic characteristics of DNA molecules translocation were found. Considering simply the effects of electrophoretic force and electro-osmotic force on the DNA molecules, the dynamic characteristics of DNA molecules are well understood. For example, the velocity of the DNA molecule is inversely proportional to the diameter of the tapered channel and the turning phenomena of the trajectory of the DNA molecules translocating through microchannels. This study is helpful and proposes new ideas for the design and development of microfluidic chips for the quantitative manipulation of DNA molecules.

In–human testing of a non-invasive continuous low–energy microwave glucose sensor with advanced machine learning capabilities

Continuous glucose monitoring schemes that avoid finger pricking are of utmost importance to enhance the comfort and lifestyle of diabetic patients. To this aim, we propose a microwave planar sensing platform as a potent sensing technology that extends its applications to biomedical analytes. In this paper, a compact planar resonator-based sensor is introduced for noncontact sensing of glucose. Furthermore, in vivo and in-vitro tests using a microfluidic channel system and in clinical trial settings demonstrate its reliable operation. The proposed sensor offers real-time response and a high linear correlation (R2 ∼ 0.913) between the measured sensor response and the blood glucose level (GL). The sensor is also enhanced with machine learning to predict the variation of body glucose levels for non-diabetic and diabetic patients. This addition is instrumental in triggering preemptive measures in cases of unusual glucose level trends. In addition, it allows for the detection of common artifacts of the sensor as anomalies so that they can be removed from the measured data. The proposed system is designed to noninvasively monitor interstitial glucose levels in humans, introducing the opportunity to create a customized wearable apparatus with the ability to learn.

Evaluation Of The Clinical Results Of Using Microfluidic Channel System For Sperm Selection In IVF Cycles In Patients With Low Sperm Concentration

Objective: Microfluidic channel system (MAC), a new generation method, gives the chance to select better quality spermatozoa with lower DNA fragmentation indices. This study evaluated the treatment results in patients who underwent ICSI-ET due to the MAC technique's male factors. Methods: Sakarya University ART Center carried out this retrospective study. Patients with 35 male factor indications were included in our study. In these patients, swim-up (SU) was used in the first of two consecutive IVF cycles, and the MAC sperm preparation technique was used in the second. Our study compared fertilization, quality embryo counts, implantation after fresh embryo transfer, pregnancy rates, fifth-day embryo, and frozen embryo numbers. Results: Fertilization rate was higher in the MAC group than in the SU group (P=0.009). The number of 3rd and 5th Day Grade 1 embryo in the MAC group was statistically higher than in the SU group (p=0.000 for both parameters). The number of quality embryos frozen on day 5 was higher in the MAC group than in the SU group (P=0.000). Conclusions: It is thought that MAC application does not make a statistically significant contribution on implantation and pregnancy in IVF cycles performed due to the malefactor. However, it may positively affect fertilization rate and embryo quality. In addition, we think that it increases the number of embryos frozen at the end of the cycle, and for this reason, the MAC technique may provide positive benefits to IVF treatments.

Comparison of Random and Site-Directed Immobilization of Antibody for α-Fetoprotein Direct Immunoassay by Protein Chip

For immunoassay, immobilization of antibody is the most important technique in bioengineering for maintaining its intrinsic activity of antigen binding. The sugar chain in the Fc region carried by antibody can be oxidized into aldehyde group by sodium m-periodate, which can couple with the amino-group on chemistry modified substrate surface through covalent linking. Thereby, in situ site-directed immobilization of the oxidized antibody for only one-step reaction can be performed. Here we propose a facile method that oxidized anti-human α-fetoprotein antibody (anti-AFP) was in situ site-directed immobilized on APTES treated silicon substrate utilizing microfluidic channel system for AFP immunoassay. The shape of the immobilized anti-AFP was observed by AFM and imaged by imaging ellipsometry of self-developed protein system. Results shown that the amount of antibody immobilization amount and capacity of antigen binding of random immobilization and site-directed immobilization were separately enhanced 16.0% and 7.0%. the suggested strategy has the advantages of simple, environment-friend and convenient-operation.

Numerical analysis on the effects of microfluidic-based bioprinting parameters on the microfiber geometrical outcomes

The application of microfluidics technology in additive manufacturing is an emerging approach that makes possible the fabrication of functional three-dimensional cell-laden structured biomaterials. A key challenge that needs to be addressed using a microfluidic-based printhead (MBP) is increasing the controllability over the properties of the fabricated microtissue. Herein, an MBP platform is numerically simulated for the fabrication of solid and hollow microfibers using a microfluidic channel system with high level of controllability over the microfiber geometrical outcomes. Specifically, the generation of microfibers is enabled by studying the effects of microfluidic-based bioprinting parameters that capture the different range of design, bioink material, and process parameter dependencies as numerically modeled as a multiphysics problem. Furthermore, the numerical model is verified and validated, exhibiting good agreement with literature-derived experimental data in terms of microfiber geometrical outcomes. Additionally, a predictive mathematical formula that correlates the dimensionless process parameters with dimensionless geometrical outcomes is presented to calculate the geometrical outcomes of the microfibers. This formula is expected to be applicable for bioinks within a prescribed range of the density and viscosity value. The MBP applications are highlighted towards precision fabrication of heterogeneous microstructures with functionally graded properties to be used in organ generation, disease modeling, and drug testing studies.

Advance of microfluidic constriction channel system of measuring single-cell cortical tension/specific capacitance of membrane and conductivity of cytoplasm.

This paper reported a microfluidic platform which realized the characterization of inherent single-cell biomechanical and bioelectrical parameters simultaneously. Individual cells traveled through a constriction channel with deformation images and impedance variations captured and processed into cortical tension Tc , specific membrane capacitance Csm , and cytoplasmic conductivity σcy based on an equivalent biophysical model. These properties of thousands of individual cells of K562, Jurkat, HL-60, HL-60 treated with paraformaldehyde (PA)/cytochalasin D (CD)/concanavalin A (ConA), granulocytes of Donor 1, Donor 2, and Donor 3 were quantified for the first time. Leveraging Tc , Csm , and σcy , (1) high accuracies of classifying wild-type and processed HL-60 cells (e.g., 93.5% of PA treated vs. CD treated HL-60 cells) were realized, revealing the effectiveness of using these three biophysical parameters in cell-type classification; (2) low accuracies of classifying normal granulocytes from three donors (e.g., 56.4% of Donor 1 vs. 2), indicating comparable parameters for normal granulocytes. In conclusion, this platform can characterize single-cell Tc , Csm , and σcy concurrently and quantify multiple parameters in single-cell analysis.

Substrate-Independent Laser-Induced Graphene Electrodes for Microfluidic Electroanalytical Systems

Laser-induced graphene’s (LIG) inherent graphene-like and highly porous characteristics and its simple, scalable, and inexpensive fabrication render it a desirable electrode material for bio- and chemosensors. The best LIG electrodes are made in polyimide foils using a CO2 laser scriber, which unfortunately limits their integration into more sophisticated analytical devices due to polyimide’s inertness. The transfer of LIG electrodes onto standard polymer substrates used in microfluidic systems and their use in microfluidic assays were therefore studied and the resulting electrodes characterized morphologically, chemically, and electroanalytically. It was found that a direct pressure-driven transfer produces highly functional transfer-LIG (tLIG) electrodes. tLIG differed from LIG electrodes with respect to a much smoother surface and hence a lower active surface area, a loss of the graphene characteristic Raman 2D peak, and a slight decrease in electron transfer rates. However, their performance in amperometric detection strategies were comparable also when used in adhesive-tape-enabled microfluidic channels for the detection of p-aminophenol. tLIG outperformed LIG electrodes in their ability to be integrated into more advanced microfluidic channel systems made of an all-polymethyl methacrylate (PMMA) substrate for the biosensing detection of alkaline phosphatase, commonly used as a biomarker and as a biosensor amplification system. LIG and tLIG have hence the potential to change electroanalytical sensing in diagnostic systems as their fabrication requires minimal resources, is highly scalable, and allows their integration into simple and, as tLIG, also sophisticated analytical systems.

Abstract 314: Micropatterning supported method for cancer spheroid assays under flow and high throughput CAR-T cell potency assay with single cell resolution

Abstract Tumor spheroids, organoids, and cell culture models demand defined cell-cell and cell-matrix interactions, ideally with specific cell attachment on adhesion sites for multicellular spheroids or single cells. Our bioinert based micropatterning technology allows for the creation of adhesion spots while the surrounding passivated area is biologically inert, not interfering with the assay.We use this micro-patterning of adhesion ligands on highly passivated surfaces to generate homogenously distributed spheroids within a microfluidic channel system which can be perfused. Spheroids can either be directly generated by a simple injection of a large number of cells and a self-sorting process or by the addition of pre-formed spheroids, which will bind to the patterned adhesion sites. Perfusion of the spheroid chip enables the homogenous supply of all spheroids with nutrients and oxygen, and also the application of a defined shear stress, metabolite analysis together with toxicological screenings or even co-culture of multiple spheroid types. Applying a flow increases the overall spheroid growth, but condenses the cell aggregate, as well as influences the drug triggered protein expression response towards a more in vivo-like reaction.We also use this technique to generate arrays of homogenously distributed single cancer cells to evaluate cytotoxic T cell activity on a single cell level. By optical analysis combined with machine-learning based image processing of cell / spheroid arrays we obtained efficient label-free analysis of each cancer cell - T cell interaction over time. Citation Format: Elias Horn, Miriam Balles, Angelika J. Fischbeck, Jan Schwarz, Dane A. Thyssen, David W. Drell, Elfriede Noessner, Roman Zantl. Micropatterning supported method for cancer spheroid assays under flow and high throughput CAR-T cell potency assay with single cell resolution [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 314.

A comparative study on EpCAM antibody immobilization on gold surfaces and microfluidic channels for the detection of circulating tumor cells

Detection of circulating tumor cells (CTCs) from the bloodstream holds great importance to diagnose cancer at early stages. However, CTCs being extremely rare in blood makes them difficult to reach. In this paper, we introduced different surface modification techniques for the enrichment and detection of MCF-7 in microfluidic biosensor applications using gold surface and EpCAM antibody. Mainly, two different mechanisms were employed to immobilize the antibodies; covalent bonding and bioaffinity interaction. Self-assembled monolayers (SAMs) formed on the gold surfaces were treated further for the immobilization of the antibody. The bioaffinity-based studies were performed with streptavidin and biotinylated EpCAM over the SAM coated surfaces. The cell attachment events were monitored using fluorescent microscope. Comparisons were made considering the length and functional end of alkanethiols and the positioning of the antibody. Then, these methods were integrated into a microfluidic channel system. Surface characterizations were performed with X-ray Photoelectron Spectroscopy, Atomic Force Microscopy, and contact angle measurements. The selectivity studies were carried out with EpCAM negative K562 leukaemia cell lines and the experiments were repeated for different types of surfaces, such as glass and polymer. Studies showed that long (n>10) and aromatic ring containing alkanethiols lead to better cell capture events compared to shorter ones. Results obtained from the comparisons are of importance for the gold surface-based microfluidic biosensor designs aimed for CTC detection.

VasQchip: A Novel Microfluidic, Artificial Blood Vessel Scaffold for Vascularized 3D Tissues

AbstractTo date, tissue engineering and organ‐on‐a‐chip devices become more powerful as replacements for animal testings in high throughput drug screenings. However, the majority of the devices are either based on static 2D or 3D cell cultures or on microfluidic channel systems that are usually rectangular and do not fit to the geometry of natural blood vessels. Therefore, a semicircular microfluidic blood vessel scaffold (vasQchip) with a surrounding microfluidic compartment for vascularized 3D cell culture was developed, which resembles the curvature of natural blood vessels. vasQchip is composed of a porous microchannel which is produced by micro‐thermoforming of polycarbonate membranes. The pores generated by ion track technology allow for the support of nutrients and gases as well as for the exchange of growth factors or immune cells with the surrounding compartment. Eventually the surrounding compartment can be used for the establishment of 3D cell cultures in order to reconstruct vascularized tissues. Here, the vasQchip for its biocompatibility is characterized to somatic primary cells, the diffusion of molecules through the artificial blood vessels and its suitability for 3D cell culture. In addition, shear stress and flow regimes are simulated in order to mimic the natural environment of vascularized tissues.

Mode conversion enables optical pulling force in photonic crystal waveguides

We propose a robust scheme to achieve optical pulling force using the guiding modes supported in a hollow core double-mode photonic crystal waveguide instead of the structured optical beams in free space investigated earlier. The waveguide under consideration supports both the 0th order mode with a larger forward momentum and the 1st order mode with a smaller forward momentum. When the 1st order mode is launched, the scattering by the object inside the waveguide results in the conversion from the 1st order mode to the 0th order mode, thus creating the optical pulling force according to the conservation of linear momentum. We present the quantitative agreement between the results derived from the mode conversion analysis and those from rigorous simulation using the finite-difference in the time-domain numerical method. Importantly, the optical pulling scheme presented here is robust and broadband with naturally occurred lateral equilibriums and has a long manipulation range. Flexibilities of the current configuration make it valuable for the optical force tailoring and optical manipulation operation, especially in microfluidic channel systems.

Optofluidic refractive index sensor based on air-suspended SU‐8 grating couplers

This work presents the design, numerical simulation, fabrication and characterization of a label-free optofluidic refractive index sensor that is based on air-suspended SU‐8 grating couplers. By exploiting a polymer-onto-polymer lamination method for thin structured SU‐8 films, waveguide grating couplers can be fabricated in a film on top of a microfluidic channel system. A capillary force valve, integrated into the microchannels, precisely positions the employed test analytes, which are different DI water based sugar solutions, below the sensing grating coupler. By performing numerical simulations, the sensing grating coupler is optimized to a center wavelength of 1550nm in the case that pure DI water (n=1.33) is applied to the microfluidic channel. When a supported mode, guided in the waveguide, reaches the sensing grating region, it is exposed to the test solution resulting in a change of the effective refractive index of the mode. Similar to the simulation results, the experimental characterization of the sensor structure demonstrates a refractive index sensitivity of approximately 400nm per refractive index unit (RIU) with respect to the wavelength shift of the grating coupler response, and 17dBRIU‐1 with respect to the intensity decrease at the individual center wavelengths for refractive index variations between n=1.33 and n=1.36. Due to the combination of microfluidic channels and air-suspended grating couplers, analytes can directly be probed in-line in an integrated microfluidic channel making the presented principle suitable for low-cost, in-line polymer optofluidic and photonic sensing applications.

A new microfluidic device design for a defined positioning of neurons in vitro.

A new triangle-shaped microfluidic channel system for defined cell trapping is presented. Different variants of the same basic geometry were produced to reveal the best fitting parameter combinations regarding efficiency and sensitivity. Variants with differences in the trap gap width and the inter-trap distance were analyzed in detail by Computational Fluid Dynamics simulations and in experiments with artificial beads of different sizes (30, 60, 80 μm). Simulation analysis of flow dynamics and pressure profiles revealed strongly reduced pressure conditions and balanced flow rates inside the microfluidic channels compared to commonly used systems with meandering channels. Quantitative experiments with beads showed very good trapping results in all channel types with slight variations due to geometrical differences. Highest efficiency in terms of fast trap filling and low particle loss was shown with channel types having a larger trap gap width (20 μm) and/or a larger inter-trap distance (400 μm). Here, experimental success was achieved in almost 85% to 100% of all cases. Particle loss appeared significantly more often with large beads than with small beads. A significantly reduced trapping efficiency of about 50% was determined by using narrow trap gaps and a small inter-trap distance in combination with large 80 μm beads. The combination of the same parameters with small and medium beads led to an only slight decrease in trapping efficiency (80%). All channel types were tested qualitatively with invertebrate neurons from the pond snail Lymnaea stagnalis. The systems were appropriate to trap those sensitive neurons and to keep their viability in the trapping area at the same time.

Single-Molecule Transcription Factor Dynamics in Saccharomyces Cerevisiæ Glucose Sensing

Metabolic processes underlie all forms of life. An organism's ability to utilise chemical energy to stay alive and eventually reproduce is a central feature of life, regardless of organism length scale. To achieve this, an organism must be able to adapt to varying surrounding environmental conditions. Cells respond to external stimuli by releasing kinase cascades along often intricate signalling pathways which regulate cellular function. These chemical signals eventually bring about some cell level response.Brewer's yeast, Saccharomyces cerevisiae is an extremely well characterised eukaryote model organism and many of its signal pathways have been studied extensively. The bulk behaviour of glucose sensing in yeast has recently been well characterised(1) but the dynamics and interaction of individual molecules in the pathway has not. We use several mutant yeast strains with fluorescent protein tags attached to the transcription factors Mig1 and Msn2 and the AMP kinase Snf1.We have developed a novel high speed fluorescence microscope system capable of imaging and tracking diffusing single or small clusters of fluorescent protein molecules. We have combined this with a bespoke microfluidic channel system allowing us to precisely change the extracellular glucose content and study the dynamics of signal transduction along the glucose sensing pathway in yeast. Our novel deconvolution method(2) let us count the total protein copy number by compartment and accurately follow a cascade interaction with transcription factors.1. Bendrioua L, Smedh M, Almquist J, Cvijovic M, Jirstrand M, Goksor M, et al. Yeast AMP-activated protein kinase monitors glucose concentration changes and absolute glucose levels. J Biol Chem. 2014;289(18):12863-75.2. Wollman AJM, Leake MC. Millisecond single-molecule localization microscopy combined with convolution analysis and automated image segmentation to determine protein concentrations in complexly structured, functional cells, one cell at a time. Faraday Discuss. 2015 Jan;184:401-24.

Microfluidic System Protocols for Integrated On-Chip Communications and Cooling

The advancements in multi-core central processing units have attracted new designs ranging from mechanisms of packing higher number of transistors into the small space, new techniques for communications (e.g., wireless network on chips), or new methodologies for cooling the chip. The latter two design aspects are the focus of this paper, where a microfluidic system is utilized for performing both functions. The miniaturization of microfluidic channels makes it attractive to embed them into the chips to transport fluids that can remove the heat from the processor cores. The extension of the cooling purpose of on-chip microfluidic channels is done by integrating communication feature. The communication process is achieved by transporting fluid through the channel and injecting information through air droplets. Protocols for microfluidic communications are applied, including physical layer functionalities and medium access protocols. The protocol design takes into considerations various properties of the microfludics. Based on the proposed system, the tradeoffs between the data rate and its impact on the amount of heat that can be removed from the processor are evaluated. This system provides new forms of condensed processor design of the future, in which integration of multiple functionalities of microfluidic channel system embedded into multi-core processors.

Patternable polymer microstructure for optical biosensing

Introduction: Applications of rapid sensing and detection of biological analytes are growing due to the significant environmental monitoring, health screening, cell growth and bio/chemical sensors. These factors influence the research and development on simple, cheap and sensitive functional biomolecular device. The interest in the label-free optical detection has been increased as the optical waveguide has a direct light interaction with surrounding analytes, easy integration with microfluidic system and the capability to provide specific interaction. Methods: In this work, we demonstrate the potential of microstructure as an optical biosensor. Visible wavelength is utilized because it is commonly used in biological and chemical sensing for both label and label-free sensing. The SU8 polymer microstructures waveguides were fabricated on 3.5 µm oxide. The microstructures are simulated using COMSOL Multiphysics. Simulation was recorded based on refractive index that mimic the bioanalytes solution and biological binding. Then the experimental setup is developed to control the optical component and manipulate the liquid samples. The fabricated devices were characterized by using the end-facet technique. Meanwhile, microfluidic channel system was also constructed in order to inject the liquid sample into the sensor surface. Results: The wavelength shift for microresonator structure approximately 41.2 nm for 0.1 increments of surrounding refractive index. The experiments demonstrate that the shift occurred approximately 22.5 nm. In other hand, simulated Bragg grating structure gained the shift at 63.2 nm. Meanwhile, the experimental results achieve approximately 20.3 nm. Conclusions: Thus, both simulation and experimental results strongly indicate that patternable polymer microstructure has a huge potential for optical biosensing applications at visible region.

Improved reproducibility and quality of GvHD biomarker assay: application of multiplex microfluidic channel system.

Improved reproducibility and quality of GvHD biomarker assay: application of multiplex microfluidic channel system

Design, fabrication and characterization of an arrayable all-polymer microfluidic valve employing highly magnetic rare-earth composite polymer

We present a new magnetically actuated microfluidic valve that employs a highly magnetic composite polymer (M-CP) containing rare-earth hard-magnetic powder for its actuating element and for its valve seat. The M-CP offers much higher magnetization compared to the soft-magnetic, ferrite-based composite polymers typically used in microfluidic applications. Each valve consists of a permanently magnetized M-CP flap and valve seat mounted on a microfluidic channel system fabricated in poly(dimethylsiloxane) (PDMS). Each valve is actuated under a relatively small external magnetic field of 80 mT provided by a small permanent magnet mounted on a miniature linear actuator. The performance of the valve with different flap thicknesses is characterized. In addition, the effect of the magnetic valve seat on the valve’s performance is also characterized. It is experimentally shown that a valve with a 2.3 mm flap thickness, actuated under an 80 mT magnetic field, is capable of completely blocking liquid flow at a flow rate of 1 ml min−1 for pressures up to 9.65 kPa in microfluidic channels 200 μm wide and 200 μm deep. The valve can also be fabricated into an array for flow switching between multiple microfluidic channels under continuous flow conditions. The performance of arrays of valves for flow routing is demonstrated for flow rates up to 5 ml min−1 with larger microfluidic channels of up to 1 mm wide and 500 μm deep. The design of the valves is compatible with other commonly used polymeric microfluidic components, as well as other components that use the same novel permanently magnetic composite polymer, such as our previously reported cilia-based mixing devices.

Microfluidic emulation of mechanical circulatory support device shear-mediated platelet activation.

Thrombosis of ventricular assist devices (VADs) compromises their performance, with associated risks of systemic embolization, stroke, pump stop and possible death. Anti-thrombotic (AT) drugs, utilized to limit thrombosis, are largely dosed empirically, with limited testing of their efficacy. Further, such testing, if performed, typically examines efficacy under static conditions, which is not reflective of actual shear-mediated flow. Here we adopted our previously developed Device Thrombogenicity Emulation methodology to design microfluidic platforms able to emulate representative shear stress profiles of mechanical circulatory support (MCS) devices. Our long-term goal is to utilize these systems for point-of-care (POC) personalized testing of AT efficacy under specific, individual shear profiles. First, we designed different types of microfluidic channels able to replicate sample shear stress patterns observed in MCS devices. Second, we explored the flexibility of microfluidic technology in generating dynamic shear stress profiles by modulating the geometrical features of the channels. Finally, we designed microfluidic channel systems able to emulate the shear stress profiles of two commercial VADs. From CFD analyses, the VAD-emulating microfluidic systems were able to replicate the main characteristics of the shear stress waveforms of the macroscale VADs (i.e., shear stress peaks and duration). Our results establish the basis for development of a lab-on-chip POC system able to perform device-specific and patient-specific platelet activation state assays.