Advancing microfluidic point-of-care platelet function tests: opportunities and challenges from bench to market.

Platelets are critical for blood clotting, with shear-induced platelet aggregation (SIPA) playing a key role in hemostasis and the prevention of excessive bleeding. SIPA function potentially leads to life-threatening diseases such as hemorrhage and myocardial infarction, which are leading causes of death globally. Point-of-care platelet function tests (POC PFTs) are developed to assess platelet dysfunction and distinguish between normal and abnormal platelet activity.

PneumoniaCheck, a novel aerosol collection device, permits capture of airborne Mycobacterium tuberculosis and characterisation of the cough aeromicrobiome in people with tuberculosis.

Background: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than Mycobacterium tuberculosis complex (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB.

Detection of pathogenic bacteria and biomarkers in lung specimens from cystic fibrosis patients.

Diagnosing lung infections is often challenging because of the lack of a high-quality specimen from the diseased lung. Since persons with cystic fibrosis are subject to chronic lung infection, there is frequently a need for a lung specimen. In this small, proof of principle study, we determined that PneumoniaCheck, a non-invasive device that captures coughed droplets from the lung on a filter, might help meet this need.

Material strengths of shear-induced platelet aggregation clots and coagulation clots.

Arterial occlusion by thrombosis is the immediate cause of some strokes, heart attacks, and peripheral artery disease. Most prior studies assume that coagulation creates the thrombus. However, a contradiction arises as whole blood (WB) clots from coagulation are too weak to stop arterial blood pressures (> 150 mmHg).

Novel tubing connectors reduce ECMO circuit thrombosis.

Background: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions.

Methods: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi.

N-Acetyl Cysteine Prevents Arterial Thrombosis in a Dose-Dependent Manner In Vitro and in Mice.

Background: Platelet-rich thrombi occlude arteries causing fatal infarcts like heart attacks and strokes. Prevention of thrombi by current antiplatelet agents can cause major bleeding. Instead, we propose using N-acetyl cysteine (NAC) to act against the protein VWF (von Willebrand factor), and not platelets, to prevent arterial thrombi from forming.

Don't forget about human factors: Lessons learned from COVID-19 point-of-care testing.

During the COVID-19 pandemic, the development of point-of-care (POC) diagnostic testing accelerated in an unparalleled fashion. As a result, there has been an increased need for accurate, robust, and easy-to-use POC testing in a variety of non-traditional settings (i.e.

Designing for simplicity: lessons from Mesa Biotech for microfluidic entrepreneurs and early-stage companies.

The COVID-19 pandemic has proven the need for point-of-care diagnosis of respiratory diseases and microfluidic technology has risen to the occasion. Mesa Biotech (San Diego, CA) originally developed the Accula platform for the diagnosis of influenza A and B and then extended the platform to SARS-CoV-2. Mesa Biotech has experienced tremendous success, culminating in acquisition by Thermo Fisher for up to $550m USD.

Structure of shear-induced platelet aggregated clot formed in an in vitro arterial thrombosis model.

The structure of occlusive arterial thrombi is described herein. Macroscopic thrombi were made from whole blood in a collagen-coated, large-scale stenosis model with high shear flow similar to an atherosclerotic artery. The millimeter-sized thrombi were harvested for histology and scanning electron microscopy.

SIPA in 10 milliseconds: VWF tentacles agglomerate and capture platelets under high shear.

Shear-induced platelet aggregation (SIPA) occurs under elevated shear rates (10 000 s-1) found in stenotic coronary and carotid arteries. The pathologically high shear environment can lead to occlusive thrombosis by SIPA from the interaction of nonactivated platelets and von Willebrand factor (VWF) via glycoprotein Ib-A1 binding. This process under high shear rates is difficult to visualize experimentally with concurrent molecular- and cellular-resolutions.

Thrombogenicity of biomaterials depends on hemodynamic shear rate.

Background: While it is well recognized that different biomaterials induce thrombosis at low shear rates, the effect of high shear rates may be quite different. We hypothesize that the amount of thrombus formation on a given material can be greatly influenced by the local shear rate.

Methods: We tested this hypothesis with two different whole blood perfusion loop assays to quantify biomaterial thrombogenicity as a function of shear stress.

Global Thrombosis Test: Occlusion by Coagulation or SIPA?

The global thrombosis test (GTT) is a point of care device that tests thrombotic and thrombolytic status. The device exposes whole blood flow to a combination of both high and low shear stress past and between ball bearings potentially causing thrombin and fibrin formation. The question arises as to whether thrombosis in the GTT is dominated by coagulation-triggered red clot or high shear-induced white clot.

Negatively charged nanoparticles of multiple materials inhibit shear-induced platelet accumulation.

Platelet accumulation by VWF under high shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. Current anti-platelet therapies remain ineffective for a large percentage of the population, while presenting significant risks for bleeding. We explore a novel way to inhibit arterial thrombus formation.

Mechanobiology of shear-induced platelet aggregation leading to occlusive arterial thrombosis: A multiscale in silico analysis.

Occlusive thrombosis in arteries causes heart attacks and strokes. The rapid growth of thrombus at elevated shear rates (~10,000 1/s) relies on shear-induced platelet aggregation (SIPA) thought to come about from the entanglement of von Willebrand factor (VWF) molecules. The mechanism for SIPA is not yet understood in terms of cell- and molecule-level dynamics in fast flowing bloodstreams.

Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC).

The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi.

Clot Permeability, Agonist Transport, and Platelet Binding Kinetics in Arterial Thrombosis.

The formation of wall-adherent platelet aggregates is a critical process in arterial thrombosis. A growing aggregate experiences frictional drag forces exerted on it by fluid moving over or through the aggregate. The magnitude of these forces is strongly influenced by the permeability of the developing aggregate; the permeability depends on the aggregate's porosity.

Biorheology of occlusive thrombi formation under high shear: in vitro growth and shrinkage.

Occlusive thrombi formed under high flow shear rates develop very rapidly in arteries and may lead to myocardial infarction or stroke. Rapid platelet accumulation (RPA) and occlusion of platelet-rich thrombi and clot shrinkage have been studied after flow arrest. However, the influence of margination and shear rate on occlusive clot formation is not fully understood yet.

Platelet α-granules are required for occlusive high-shear-rate thrombosis.

von Willebrand factor (VWF) is essential for the induction of arterial thrombosis. In this study, we investigated the critical role of platelet VWF in occlusive thrombosis formation at high shear in mice that do not express platelet VWF (Nbeal2-/-). Using in silico modeling, in vitro high-shear microfluidics, and an in vivo Folts model of arterial thrombosis we reproduced the platelet dynamics that occur under pathological flow in a stenosed vessel.

Endograft exclusion of the false lumen restores local hemodynamics in a model of type B aortic dissection.

Objective: Endovascular intervention in uncomplicated type B dissection has not been shown conclusively to confer benefit on patients. The hemodynamic effect of primary entry tear coverage is not known. Endovascular stent grafts were deployed in a model of aortic dissection with multiple fenestrations to study these effects.

Occlusive thrombosis in arteries.

Thrombus formation in major arteries is life threatening. In this review article, we discuss how an arterial thrombus can form under pathologically high shear stresses, with bonding rates estimated to be the fastest values in biochemistry. During occlusive thrombosis in arteries, the growth rate of the thrombus explodes to capture a billion platelets in about 10 min.

Correction to: A Predictive Model of High Shear Thrombus Growth.

This erratum is to correct the heading of column 2 (titled "b") in Table 1, which was missing proper units. The heading for that column was revised to include proper units, reading "b (× 10 s)".

Shear-induced platelet aggregation: 3D-grayscale microfluidics for repeatable and localized occlusive thrombosis.

Atherothrombosis leads to complications of myocardial infarction and stroke as a result of shear-induced platelet aggregation (SIPA). Clinicians and researchers may benefit from diagnostic and benchtop microfluidic assays that assess the thrombotic activity of an individual. Currently, there are several different proposed point-of-care diagnostics and microfluidic thrombosis assays with different design parameters and end points.

Who Create Jobs? Venture Capital, Research Grants, and Regional Employment in the U.S.

We build on the exploratory and exploitative learning literature that suggests that venture capital and governmental research grants may impact regional employment in a different manner. Using a regional employment dataset in the U.S.

Intermediate fenestrations reduce flow reversal in a silicone model of Stanford Type B aortic dissection.

Pulsatile, three-dimensional hemodynamic forces influence thrombosis, and may dictate progression of aortic dissection. Intimal flap fenestration and blood pressure are clinically relevant variables in this pathology, yet their effects on dissection hemodynamics are poorly understood. The goal of this study was to characterize these effects on flow in dissection models to better guide interventions to prevent aneurysm formation and false lumen flow.