Edwin van der Pol

Edwin van der Pol
University of Amsterdam | UVA · Amsterdam University Medical Centers

Doctor of Engineering

About

68
Publications
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6,243
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Introduction
Rapid detection and characterization of single extracellular vesicles as biomarker for disease

Publications

Publications (68)
Article
Background: Blood plasma is commonly used for biomarker research of extracellular vesicles (EVs). Removing all cells prior to analysis of EVs is essential. Objectives: We therefore studied the efficacy of the most commonly used centrifugation protocol to prepare cell-free plasma. Methods: Plasma was prepared according the double centrifugation...
Article
Full-text available
The refractive index of a solid depends on the illumination wavelength, temperature and material properties, such as the chemical composition, crystal structure, and isotropy. Refractive index measurements, however, also depend on environmental conditions, such as the temperature, pressure, CO2 concentration and humidity of the surrounding air. As...
Article
Full-text available
Extracellular vesicles (EVs) are tissue-specific particles released by cells containing valuable diagnostic information in the form of various biomolecules. To rule out selection bias or introduction of artefacts caused by EV isolation techniques, we present a clinically feasible, imaging flow cytometry (IFCM)–based methodology to phenotype and det...
Article
Extracellular vesicles (EVs) are an upcoming biomarker for disease. However, the measured concentrations of EVs by flow cytometry are incomparable due to analytical variables. This study aimed to investigate how the choice of fluorophore, and thereby brightness, affects the measured concentration of EVs. Four commonly used fluorophores allophycocya...
Article
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Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extrac...
Chapter
Extracellular vesicles (EVs) are lipid membrane enclosed particles that are released from cells into body fluids, such as blood. EVs offer potential new biomarkers of diseases, because the cellular origin, composition, concentration, and function of EVs change in health and disease. The concentration of EVs from specific cell types in blood can be...
Article
Citrate is the recommended anticoagulant for studies on plasma extracellular vesicles (EVs). Because citrate incompletely blocks platelet activation and the release of platelet-derived EVs, we compared EDTA and citrate in that regard. Blood from healthy individuals (n = 7) was collected and incubated with thrombin receptor-activating peptide-6 (TRA...
Article
The Extracellular Vesicle Flow Cytometry Working Group (http://www.evflowcytometry.org) is formed by members of the International Society for Extracellular Vesicles (ISEV), the International Society on Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH). This working group of flow cytometry experts de...
Article
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The particle size distribution (PSD) of extracellular vesicles (EVs) and other submicron particles in biofluids is commonly measured by nanoparticle tracking analysis (NTA) and tunable resistive pulse sensing (TRPS). A new technique for measuring the PSD is microfluidic resistive pulse sensing (MRPS). Because specific guidelines for measuring EVs t...
Article
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(1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was c...
Article
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Background, the mechanisms underlying left ventricular remodelling (LVR) after acute myocardial infarction (AMI) remain obscure. In the course of AMI, blood cells and endothelial cells release extracellular vesicles (EVs). We hypothesized that changes in EV concentrations after AMI may underlie LVR. Methods, plasma concentrations of EVs from endoth...
Article
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Knowledge of the sensitivity of a flow cytometer is essential for data interpretation and comparison. However, light scatter sensitivity currently cannot be quantified due to a lack of a standardized unit. Analogous to the QB approach for fluorescence, we show that it is possible to derive the detection efficiency Q and background B for light scatt...
Article
Full-text available
Accurate characterization of extracellular vesicles (EVs) is critical to explore their diagnostic and therapeutic applications. As the EV research field has developed, so too have the techniques used to characterize them. The development of reference materials are required for the standardization of these techniques. This work, initiated from the I...
Article
Full-text available
Extracellular vesicles (EVs) are cell-derived particles with a phospholipid membrane present in all body fluids. Because EV properties change in health and disease, EVs have excellent potential to become biomarkers for diagnosis, prognosis or monitoring of disease. The only technique capable of detecting, sizing, and phenotyping a million of EVs wi...
Article
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Extracellular vesicles (EVs) have great potential as biomarkers since their composition and concentration in biofluids are disease state dependent and their cargo can contain disease-related information. Large tumor-derived EVs (tdEVs, >1 μm) in blood from cancer patients are associated with poor outcome, and changes in their number can be used to...
Preprint
Full-text available
Accurate characterization of extracellular vesicles (EVs) is critical to explore their diagnostic and therapeutic applications. As the EV research field has developed, so too have the techniques used to characterize them. The development of reference materials is required for the standardization of these techniques. This work, initiated from the IS...
Article
Full-text available
Extracellular vesicles (EVs) present in blood originate from cells of different origins such as red blood cells (RBCs), platelets and leukocytes. In patients with cancer, a small portion of EVs originate from tumour cells and their load is associated with poor clinical outcome. Identification of these tumour-derived extracellular vesicles (tdEVs) i...
Article
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Extracellular vesicles (EVs) are commonly studied by flow cytometry. Due to their small size and low refractive index, the scatter intensity of most EVs is below the detection limit of common flow cytometers. Here, we aim to improve forward scatter (FSC) and side scatter (SSC) sensitivity of a common flow cytometer to detect single 100 nm EVs. The...
Article
Full-text available
Extracellular vesicles (EVs) are small, heterogeneous and difficult to measure. Flow cytometry (FC) is a key technology for the measurement of individual particles, but its application to the analysis of EVs and other submicron particles has presented many challenges and has produced a number of controversial results, in part due to limitations of...
Article
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Extracellular vesicles (EVs) in plasma are commonly identified by staining with antibodies and generic dyes, but the specificity of antibodies and dyes to stain EVs is often unknown. Previously, we showed that platelet-depleted platelet concentrate contains two populations of particles >200 nm, one population with a refractive index (RI) < 1.42 tha...
Article
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Background: Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is...
Article
Introduction The platelet P2Y12 antagonist ticagrelor reduces all-cause and cardiovascular mortality in patients after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release prothrombotic extracellular vesicles (EVs) exposing P-selectin, fibrinogen and phosphatidylseri...
Article
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Extracellular Vesicles (EVs) can be used as biomarkers in diseases like cancer, as their lineage of origin and molecular composition depend on the presence of cancer cells. Recognition of tumor-derived EVs (tdEVs) from other particles and EVs in body fluids requires characterization of single EVs to exploit their biomarker potential. We present her...
Article
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Recent years have seen an increase of extracellular vesicle (EV) research geared towards biological understanding, diagnostics and therapy. However, EV data interpretation remains challenging owing to complexity of biofluids and technical variation introduced during sample preparation and analysis. To understand and mitigate these limitations, we g...
Article
Several proteomics studies have been conducted to identify new cerebrospinal fluid (CSF) biomarkers in Multiple Sclerosis (MuS). However, the complexity of CSF and its invasive collection, limits its use. Therefore, the goal of biomarker research in MuS is to identify novel distinctive targets in CSF or in easily accessible biofluids. Tears represe...
Preprint
Full-text available
Nanoscale flow cytometry (NFC) is becoming a method of choice for the phenotypic analysis of viruses and extracellular vesicles (EVs). However, many of these particles are smaller than 200 nm in diameter, which places them at the limit of detection for many commercial flow cytometers. The use of reference particles of size, fluorescence, and light-...
Article
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Activated platelets contribute to thrombosis and inflammation by the release of extracellular vesicles (EVs) exposing P-selectin, phosphatidylserine (PS) and fibrinogen. P2Y12 receptor antagonists are routinely administered to inhibit platelet activation in patients after acute myocardial infarction (AMI), being a combined antithrombotic and anti-i...
Article
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Biomarkers in the blood of cancer patients include circulating tumor cells (CTCs), tumor‐educated platelets (TEPs), tumor‐derived extracellular vesicles (tdEVs), EV‐associated miRNA (EV‐miRNA), and circulating cell‐free DNA (ccfDNA). Because the size and density of biomarkers differ, blood is centrifuged to isolate or concentrate the biomarker of i...
Article
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Flow cytometry is commonly used to investigate the potential for extracellular vesicles (EVs) to be biomarkers of disease. A typical flow cytometer detects fluorescence and scatter intensities of single EVs in arbitrary units. These arbitrary units complicate data interpretation and data comparison between different flow cytometers. For example, co...
Article
Full-text available
Background The concentration of extracellular vesicles (EVs) in body fluids is a promising biomarker for disease, and flow cytometry remains the clinically most applicable method to identify the cellular origin of single EVs in suspension. To compare concentration measurements of EVs between flow cytometers, solid polystyrene reference beads and EV...
Article
Full-text available
Background Detection of extracellular vesicles (EVs) by flow cytometry (FCM) has poor inter‐laboratory comparability due to differences in FCM sensitivity. Previous workshops distributed polystyrene beads to set a scatter‐based diameter gate to improve the comparability of EV concentration measurements. However, polystyrene beads provide limited in...
Article
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Background: Extracellular vesicles (EVs) in biofluids are potential biomarkers of disease. To explore the clinical relevance of EVs, a specific generic EV marker would be useful, one that does not require antibodies and binds to all EVs. Here we evaluated 5 commonly used generic markers for flow cytometry. Methods: Flow cytometry (A60-Micro, Apo...
Article
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Post-infarct left ventricle remodelling (LVR) is defined as the structural and functional changes of the myocardium occurring after acute myocardial infarction (AMI) and leading to the loss of contractile tissue and subsequently to post-infarct heart failure (HF). LVR affects 30% of patients after AMI, deteriorating the prognosis. At present, no cl...
Article
Blood contains extracellular vesicles (EVs), which are biological nanoparticles with clinical applications. In blood plasma, EVs are outnumbered by similar-sized lipoprotein particles (LPs), leading to controversial data such as non-specific binding of antibodies to LPs. Flow cytometry is a clinically applicable technique to characterize single EVs...
Article
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Owing to the relationship between extracellular vesicles (EVs) and physiological and pathological conditions, the interest in EVs is exponentially growing. EVs hold high hopes for novel diagnostic and translational discoveries. This review provides an expert-based update of recent advances in the methods to study EVs and summarizes currently accept...
Article
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Extracellular vesicles (EVs) mediate normal physiological homeostasis and pathological processes by facilitating intercellular communication. Research of EVs in basic science and clinical settings requires both methodological standardization and development of reference materials (RM). Here, we show insights and results of biological RM development...
Conference Paper
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Background: Extracellular vesicles, such as exosomes, are abundantly present in human body fluids. Since the size, concentration and composition of these vesicles change during disease, vesicles have promising clinical applications, including cancer diagnosis. However, since ~70% of the vesicles have a diameter <70 nm, detection of single vesicles...
Conference Paper
Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, re...
Article
In future, measurements of extracellular vesicles in body fluids could become a standard diagnostic tool in medicine. For this purpose, reliable and traceable methods, which can be easily applied in hospitals, have to be established. Within the European Metrological Research Project (EMRP) 'Metrological characterization of micro-vesicles from body...
Article
The research field of extracellular vesicles (EV), such as microparticles and exosomes, is growing exponentially. The goal of this review is to provide an overview of recent developments relevant to the readers of the Journal of Thrombosis and Haemostasis. We will discuss nomenclature, the presence of EV in fluids, methods of isolation and detectio...
Article
Full-text available
Because procedures of handling and storage of body fluids affect numbers and composition of extracellular vesicles (EVs), standardization is important to ensure reliable and comparable measurements of EVs in a clinical environment. We aimed to develop standard protocols for handling and storage of human body fluids for EV analysis. Conditions such...
Article
Full-text available
Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, re...
Article
Full-text available
The size of extracellular vesicles (EVs) can be determined with a tunable resistive pulse sensor (TRPS). Because the sensing pore diameter varies from pore to pore, the minimum detectable diameter also varies. The aim of this study is to determine and improve the reproducibility of TRPS measurements. Experiments were performed with the qNano system...
Article
Full-text available
The refractive index (RI) dictates interaction between light and nanoparticles, and therefore is important to health, environmental and materials sciences. Using nanoparticle tracking analysis, we have determined the RI of heterogeneous particles < 500 nm in suspension. We demonstrate feasibility of distinguishing silica and polystyrene beads based...
Article
Full-text available
Background: Isolation of extracellular vesicles from plasma is a challenge due to the presence of proteins and lipoproteins. Isolation of vesicles using differential centrifugation or density-gradient ultracentrifugation results in co-isolation of contaminants such as protein aggregates and incomplete separation of vesicles from lipoproteins, resp...
Article
Enumeration of extracellular vesicles has clinical potential as a biomarker for disease. In biological samples, the smallest and largest vesicles typically differ 25-fold in size, 300,000-fold in concentration, 20,000-fold in volume, and 10,000,000-fold in scattered light. Due to this heterogeneity, currently employed techniques detect concentratio...
Article
Full-text available
Extracellular vesicles (EVs) have clinical importance due to their roles in a wide range of biological processes. The detection and characterization of EVs are challenging because of their small size, low refractive index, and heterogeneity. In this manuscript, the size distribution of an erythrocyte-derived EV sample is determined using state-of-t...
Article
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We use transmission and backscattering optical coherence tomography (OCT) to distinguish and quantify dependent and multiple scattering effects in turbid media. With transmission OCT the dependent scattering coefficients for a range of monodisperse silica particle suspensions are determined. An excellent agreement is observed between the measured d...
Conference Paper
Full-text available
Concentration dependent scattering coefficients are measured using transmission optical coherence tomography (OCT) and compared to a dependent scattering model. The backscattering OCT signal is fitted with the extended Huygens-Fresnel model. Both models give good results.
Article
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Cell-derived or extracellular vesicles, including microparticles and exosomes, are abundantly present in body fluids such as blood. Although such vesicles have gained strong clinical and scientific interest, their detection is difficult because many vesicles are extremely small with a diameter of less than 100 nm, and, moreover, these vesicles have...
Article
Full-text available
Background: Activated platelets release platelet extracellular vesicles (PEVs). Adenosine diphosphate (ADP) receptors P2Y1 and P2Y12 both play a role in platelet activation, The present hypothesis herein is that the inhibition of these receptors may affect the release of PEVs. Methods: Platelet-rich plasma from 10 healthy subjects was incubated...