A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood

The flux of platelet agonists into flowing blood is a critical event in thrombosis and hemostasis. However, few in vitro methods exist for examining and controlling the role of platelet agonists on clot formation and stability under hemodynamic conditions. In this paper, we describe a membrane-based method for introducing a solute into flowing blood at a defined flux. The device consisted of a track-etched polycarbonate membrane reversibly sealed between two microfluidic channels; one channel contained blood flowing at a physiologically relevant shear rate, and the other channel contained the agonist(s). An analytical model described the solute flux as a function of the membrane permeability and transmembrane pressure. The model was validated using luciferase as a model solute for transmembrane pressures of 50–400 Pa. As a proof-of-concept, the weak platelet agonist ADP was introduced into whole blood flowing at 250 s-1 at three fluxes (1.5, 2.4, and 4.4 × 10-18 mol µm-2 s-1). Platelet aggregation was monitored by fluorescence microscopy during the experiment and the morphology of aggregates was determined by post hoc confocal and electron microscopy. At the lowest flux (1.5 × 10-18 mol µm-2 s-1), we observed little to no aggregation. At the higher fluxes, we observed monolayer (2.4 × 10-18 mol µm-2 s-1) and multilayer (4.4 × 10-18 mol µm-2 s-1) aggregates of platelets and found that the platelet density within an aggregate increased with increasing ADP flux. We expect this device to be a useful tool in unraveling the role of platelet agonists on clot formation and stability

Flow chamber and microfluidic approaches for measuring thrombus formation in genetic bleeding disorders

Platelet adhesion and aggregation, coagulation, fibrin formation, and fibrinolysis are regulated by the forces and flows imposed by blood at the site of a vascular injury. Flow chambers designed to observe these events are an indispensable part of doing hemostasis and thrombosis research, especially with human blood. Microfluidic methods have provided the flexibility to design flow chambers with complex geometries and features that more closely mimic the anatomy and physiology of blood vessels. Additionally, microfluidic systems with integrated optics and/or pressure sensors and on-board signal processing could transform what have been primarily research tools into clinical assays. Here, we describe a historical review of how flow-based approaches have informed biophysical mechanisms in genetic bleeding disorders, challenges and potential solutions for developing models of bleeding in vitro, and outstanding issues that need to be addressed prior to their use in clinical settings

Optic Imaging of Two-Phase-Flow Behavior in 1D Nanoscale Channels

Gas in tight sand and shale exists in underground reservoirs with microdarcy (µd) or even nanodarcy (nd) permeability ranges; these reservoirs are characterized by small pore throats and crack-like interconnections between pores. The size of the pore throats in shale may differ from the size of the saturating-fluid molecules by only slightly more than one order of magnitude. The physics of fluid flow in these rocks, with measured permeability in the nanodarcy range, is poorly understood. Knowing the fluid-flow behavior in the nanorange channels is of major importance for stimulation design, gas-production optimization, and calculations of the relative permeability of gas in tight shale-gas systems. In this work, a laboratory-on-chip approach for direct visualization of the fluid-flow behavior in nanochannels was developed with an advanced epi-fluorescence microscopy method combined with a nanofluidic chip. Displacements of two-phase flow in 100-nmdepth slit-like channels were reported. Specifically, the two-phase gas-slip effect was investigated. Under experimental conditions, the gas-slippage factor increased as the water saturation increased. The two-phase flow mechanism in 1D nanoscale slit-like channels was proposed and proved by the flow-pattern images. The results are crucial for permeability measurement and understanding fluidflow behavior for unconventional shale-gas systems with nanoscale pores

Optic Imaging of Two-Phase Flow Behavior in Nano-Scale Fractures

Gas in tight sand and shale exists in underground reservoirs with microdarcy (uD) or even nanodarcy permeability ranges; these reservoirs are characterized by small pore throats and crack-like interconnections between pores. The size of the pore throats in shale may differ from the size of the saturating fluid molecules by only slightly more than one order of magnitude. The physics of fluid flow in these rocks, with measured permeability in the nanodarcy range, is poorly understood. Knowing the fluid flow behavior in the nano-range channels is of major importance for both simulation studies and calculations of the relative permeability of gas in tight shale gas systems. In this work, a lab-on-chip approach for direct visualization of the fluid flow behavior in nanochannels was developed using an advanced single-molecule imaging system combined with a nano-fluidic chip. Displacements of two-phase flow in 100 nm depth channels were characterized. Specifically, the two-phase gas slippage effect was investigated. Under experimental conditions, the gas slippage factor increased as the water saturation increased. The two-phase flow mechanism in nano-scale channels was proposed and proved by the flow pattern images. The results are crucial for permeability measurement and gas slippage factor determination for unconventional shale gas systems with nano-scale pores

Coupling Magnetic Torque and Force for Colloidal Microbot Assembly and Manipulation

For targeted transport in the body, biomedical microbots (μbots) must move effectively in three‐dimensional (3D) microenvironments. Swimming μbots translate via asymmetric or screw‐like motions while rolling ones use friction with available surfaces to generate propulsive forces. Previously the authors have shown that planar rotating magnetic fields assemble μm‐scale superparamagnetic beads into circular μbots that roll along surfaces. In this, gravity is required to pull μbots near the surface; however, this is not necessarily practical in complex geometries. Here, the authors show that rotating magnetic fields, in tandem with directional magnetic gradient forces, can be used to roll μbots on surfaces regardless of orientation. Simplifying implementation, a spinning permanent magnet is used to generate differing ratios of rotating and gradient fields, optimizing control for different environments. This use of a single magnetic actuator sidesteps the need for complex electromagnet or tandem field setups, removes requisite gravitational load forces, and enables μbot targeting in complex 3D biomimetic microenvironments