David N Ku

David N Ku
Georgia Institute of Technology | GT · School of Mechanical Engineering and Scheller School of Business

PhD, MD

About

291
Publications
27,568
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Introduction

Publications

Publications (291)
Article
Full-text available
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. pharmacies, drive-thru sites, schools). While stakeholders often express the de...
Article
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 succes...
Article
The structure of occlusive arterial thrombi is described in this paper. Macroscopic thrombi are made from whole blood in a collagen-coated, large-scale stenosis with high shear flow conditions similar to an atherosclerotic artery. The millimeter-sized thrombi are harvested for histology and scanning electron microscopy. Histological images showed 3...
Article
Full-text available
Shear-Induced Platelet Aggregation (SIPA) occurs under elevated shear rates (~10000 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 (GPIb)-A1 binding. This proces...
Article
Full-text available
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 bl...
Article
Full-text available
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 coa...
Article
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-le...
Article
Full-text available
Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the “RADx <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SM</sup> Tech Test Verification Core” and its...
Article
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. Theo...
Article
Full-text available
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 t...
Preprint
Full-text available
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-le...
Article
Full-text available
The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compare...
Article
The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compare...
Article
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 agg...
Article
Full-text available
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 no...
Preprint
Full-text available
Background: Current prevalence of COVID-19 drives many policy decisions, but is hampered by ambiguities in testing and reporting. We propose an alternative method for estimating community prevalence that is inexpensive and timely. We test the Hypothesis that the survey sampling provides a quantitative prevalence that is similar to widespread genomi...
Article
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...
Preprint
Full-text available
Background Current prevalence of COVID-19 drives many policy decisions, but is hampered by ambiguities in testing and reporting. We propose an alternative method for estimating community prevalence that is inexpensive and timely. We test the Hypothesis that the survey sampling provides a quantitative prevalence that is similar to widespread genomic...
Article
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. It is hypothesized that...
Article
Full-text available
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 K o n values in biochemistry. During occlusive thrombosis in arteries, the growth rate of the thrombus explodes to capture a billi...
Article
Full-text available
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 (× 10-6 s)".
Article
Full-text available
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...
Article
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...
Conference Paper
Von Willebrand Factor (VWF) captures platelets under high shear by unfolding to elongated form under hydrodynamic stress exposing binding sites. Recent studies (Fu et al, Nature Comm. 2017) show that subsequent to elongation of VWF, there is a second step local-tension-dependent transition to a high affinity state with GPIbα. High-affinity sites de...
Article
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. (United States) medical device sector, our analysis reveals that research grants contribute to create a greater lev...
Article
Full-text available
Platelet accumulation under high shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. Current antiplatelet therapies remain ineffective within a large percentage of the population, while presenting significant risks for bleeding. We explore a novel way to inhibit arterial thrombus formation by biophys...
Preprint
Full-text available
The transition from globular to elongated states of biopolymers in shear flow occurs at a distinct critical shear rate, $\dot{\gamma }^{*}$. The magnitude of $\dot{\gamma }^{*}$ depends on the internal potential and the polymer length. For example, the critical shear is much larger for von Willebrand Factor (vWF) compared to DNA. Furthermore, it is...
Article
Introduction: Funding for scientific advancement comes from two dominant sources: public funds used to generate knowledge, and private sector funds in the pursuit of commercial products. It is unclear how to compare the outputs of these two financial mechanisms because both sectors are motivated by common goods but are also governed by divergent fo...
Article
The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein vo...
Article
Full-text available
Recently, it has been shown that constructs of poly(vinyl alcohol) (PVA) hydrogel fibers reproduce closely the tensile behavior of ligaments. However, the biological response to these systems has not been explored yet. Here, we report the first in vivo evaluation of these implants and focus on the integration in bone, using a rabbit model of bone t...
Article
Understanding of the hemodynamics of Type B aortic dissection may improve outcomes by informing upon patient selection, device design, and deployment strategies. This project characterized changes to aortic hemodynamics as the result of dissection. We hypothesized that dissection would lead to elevated flow reversal and disrupted pulsatile flow pat...
Article
Platelets contribute to thrombus formation in a variety of ways. Platelet adhesion, activation, and thrombus growth depend greatly on the type of hemodynamic environment surrounding an inciting event. Microfluidic systems may be used to explore these relationships. In this review, we describe some important considerations required in the design of...
Article
Background: Endovascular aneurysm repair (EVAR) with a modular endograft has become the preferred treatment for abdominal aortic aneurysms. A novel concept is endovascular aneurysm sealing (EVAS), consisting of dual endoframes surrounded by polymer-filled endobags. This dual-lumen configuration is different from a bifurcation with a tapered trajec...
Article
Intravascular thrombosis can lead to heart attacks and strokes that together are the leading causes of death in the US (Kochanek, K.D., Murphy, S.L., Xu, J.Q., 2014). The ability to identify the offending biofluid mechanical conditions and predict the timescale of thrombotic occlusion in vessels and devices may improve patient outcomes. A computati...
Article
Extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support of critically ill patients is used frequently in the pediatric population. ECMO is burdened by complications, including thrombosis and hemorrhage. Here we demonstrate the focused location of clots, their histological composition, and the relationship of in situ thrombus to local...
Article
Full-text available
Background: Identifying lung pathogens and acute spikes in lung counts remain a challenge in the treatment of patients with cystic fibrosis (CF). Bacteria from the deep lung may be sampled from aerosols produced during coughing. Methods: A new device was used to collect and measure bacteria levels from cough aerosols of patients with CF. Sputum and...
Article
Purpose: Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary mechanical life support for critically ill patients. ECMO is burdened by both thrombotic and hemorrhagic complications. Recently there has been a clinical shift from roller pumps to centrifugal pumps. In this study, we report on bulk thrombus formation within pumps re...
Article
Objectives: Aortic remodeling after dissection is poorly understood. Thus, optimal patient-specific recommendations for treatment are lacking. An in vitro aortic model of Type B dissection was used to interrogate local aortic hemodynamic parameters implicated in thrombosis and aneurysm formation. We hypothesize that dissections with multiple reentr...
Article
The effects of flow and particle properties on margination of particles in red blood cell (RBC) suspensions is investigated using direct numerical simulation (DNS) of cellar blood flow. We focus on margination of particles in the flow of moderately dense suspensions of RBCs. We hypothesize that margination rate in nondilute suspensions is mainly dr...
Article
The ability to predict the timescale of thrombotic occlusion in stenotic vessels may improve patient risk assessment for thrombotic events. In blood contacting devices, thrombosis predictions can lead to improved designs to minimize thrombotic risks. We have developed and validated a model of high shear thrombosis based on empirical correlations be...
Article
Flow chambers are increasingly used to model thrombus formation in (patho)physiologically inspired geometries and conditions. The flexible design enabled by microfluidics and the variety of commercially available devices makes comparisons between flow chambers challenging [1]. There is also a need to make faithful comparisons between these in vitro...
Article
Acute arterial occlusions occur in high shear rate hemodynamic conditions. Arterial thrombi are platelet-rich when examined histologically compared with red blood cells in venous thrombi. Prior studies of platelet biology were not capable of accounting for the rapid kinetics and bond strengths necessary to produce occlusive thrombus under these con...
Patent
Full-text available
Implantable biomaterials, particularly hydrogel substrates with porous surfaces, and methods for enhancing the compatibility of biomaterials with living tissue, and for causing physical attachment between biomaterials and living tissues are provided. Also provided are implants suitable for load-bearing surfaces in hard tissue repair, replacement, o...
Article
Computational modeling of arterial thrombus formation based on patient-specific data holds promise as a non-invasive tool for preventive diagnosis of atherosclerotic lesions. Platelet transport to the surface of a growing thrombus may be a rate limiting step in rapid thrombus formation, so accurate modeling of platelet transport may be essential fo...
Patent
Full-text available
A device for collecting material from lung aerosols. The device functions by collecting aerosols from the lower airway separated from material in the by collecting air from the upper airway in a chamber that when full causes the remaining exhaled aerosols from the lungs to be captured by a filter. The filter collects sample of material from the sep...
Article
The Respiratory Syncytial Virus (RSV) is the most common cause of serious lower respiratory tract infections in infants and young children. RSV often causes increased airway resistance, clinically detected as wheezing by chest auscultation. In this disease, expiratory flows are significantly reduced due to the high resistance in patient's airway pa...
Article
Most previous studies have investigated in vitro thrombus formation under steady flow conditions at physiological shear rates, though occlusive thrombosis leading to myocardial infarction and stroke forms under elevated shear rates and pulsatile flow. Two reports of pulsatile flow on thrombosis have yielded conflicting results. In the present study...
Article
Background: In chronic venous insufficiency, incompetent valves prevent effective blood return and lead to varicose veins, lower extremity edema, and stasis ulcers. Several surgical interventions have been described, including valve transplantation, but these extensive procedures are only moderately effective and require inpatient hospitalization....
Article
Full-text available
Insufficient bone anchoring is a major limitation of artificial substitutes for connective osteoarticular tissues. The use of coatings containing osseoconductive ceramic particles is one of the actively explored strategies to improve osseointegration and strengthen the bone-implant interface for general tissue engineering. Our hypothesis is that hy...
Article
Tendon or ligament with an elongated body comprising a flexible median part and at least one end part showing a different tensile stiffness from that of the median part, said body having a fibrous structure formed from biocompatible fibers having a diameter superior to 0.1 μm, said fibers forming the body of the device wherein the median part compr...
Article
Full-text available
The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but in...
Article
While the emphasis on venture capital and governmental funding as essential financing sources for enhancing entrepreneurial activities expands, little research has focused on the distinct roles of these two types of financial capital in the entrepreneurship literature. This study provides a theoretical framework that suggests that governmental rese...
Article
Arterial, platelet-rich thrombosis depends on shear rates and integrin binding to either a collagen surface or to the growing thrombus, which are mechanistically different. In general, small microfluidic test sections may favor platelet-surface adhesion without testing for the primary mode of intra-arterial thrombosis, i.e. platelet-platelet bondin...
Article
Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used to compute shear rates in stenoses with growing b...
Conference Paper
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal