Publications by authors named "Cees Otto"

Article Synopsis
  • Raman spectroscopy is introduced as an advanced method for identifying specific crystals (monosodium urate and calcium pyrophosphate) in synovial fluid, but its interpretation typically requires expertise that clinicians may lack.
  • A machine learning approach was developed to automate the classification of Raman spectra from synovial fluid samples collected from 446 patients, using training and validation datasets to improve accuracy.
  • The trained model achieved high classification accuracies (up to 96% for CPP and 92.5% for MSU), demonstrating its effectiveness in distinguishing pathological crystals from other particles, thus providing a more objective diagnostic tool for clinicians.
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  • Leukemia is a group of bone marrow tumors characterized by rapid cell growth, and current diagnosis methods rely on slow visual inspection of blood samples to identify subtypes.
  • The study presents a novel approach using Raman hyperspectral imaging to analyze bone marrow samples from 19 patients with different leukemia subtypes, capturing over 1.3 million cell spectra.
  • The automated analysis revealed distinct cellular components and created high-quality images at the single-cell level, demonstrating Raman imaging's potential in enhancing leukemia research despite some challenges with the clustering process.
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  • The objective of the study was to analyze calcium-containing crystals in synovial fluid from knee osteoarthritis patients using Raman spectroscopy and assess the effects of calcite crystals on biological responses.
  • The research involved collecting synovial fluid samples from 32 patients, identifying various crystals, and examining the immune responses of different cells exposed to calcite crystals.
  • Findings revealed calcite crystals in the majority of samples, with distinct pro-inflammatory responses observed in immune cells and other joint cells, suggesting that understanding these crystals could lead to new treatment strategies for osteoarthritis.
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  • The study evaluated the effectiveness of integrated Raman polarized light microscopy (iRPolM) in diagnosing calcium pyrophosphate (CPP)-associated arthritis using 400 samples from a hospital in the Netherlands.
  • Results showed strong agreement between iRPolM and the 2023 ACR/EULAR criteria, with high sensitivity (86.0%) and specificity (99.1%).
  • The findings suggest that iRPolM offers a reliable diagnosis for CPP crystals and could improve outcomes for patients compared to traditional polarized light microscopy.
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Extracellular vesicles (EVs) released from cells attract interest for their possible role in health and diseases. The detection and characterization of EVs is challenging due to the lack of specialized methodologies. Raman spectroscopy, however, has been suggested as a novel approach for biochemical analysis of EVs.

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Article Synopsis
  • Extracellular vesicles (EVs) found in blood plasma are emerging as promising disease biomarkers, but analyzing them individually is complicated due to the presence of numerous lipoprotein particles (LPPs) that can interfere with their isolation and characterization.
  • The study employed various advanced techniques, including atomic force microscopy and flow cytometry, to investigate the formation of EV-LPP complexes in biological samples and assess how these complexes affect EV analysis.
  • Findings indicate that LPPs can significantly influence EV measurements, impacting both the identification and quantification of biomarkers, and that the surrounding biological fluid can alter the properties of EVs, which is crucial for accurate profiling.
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Objectives: We studied the performance of Raman spectroscopy integrated with polarized light microscopy (iRPolM) as a next-generation technique for synovial fluid analysis in gout.

Methods: This is a prospective study, including consecutive synovial fluid samples drawn from any peripheral swollen joint. Diagnostic accuracy was compared to the 2015 ACR/EULAR Gout classification criteria as a reference test and to polarized light microscopy (PLM) analysis by a rheumatologist.

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Virtually every cell in the body releases extracellular vesicles (EVs), the contents of which can provide a "fingerprint" of their cellular origin. EVs are present in all bodily fluids and can be obtained using minimally invasive techniques. Thus, EVs can provide a promising source of diagnostic, prognostic, and predictive biomarkers, particularly in the context of cancer.

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We demonstrate how algorithm-improved confocal Raman microscopy (ai-CRM), in combination with chemical enhancement by two-dimensional substrates, can be used as an ultrasensitive detection method for rhodamine (R6G) molecules adsorbed from aqueous solutions. After developing a protocol for laser-induced reduction of graphene oxide, followed by noninvasive Raman imaging, a limit of detection (LOD) of 5 × 10 M R6G was achieved using ai-CRM. An equivalent subnanomolar LOD was also achieved on another graphene oxide analogue -UV/ozone-oxidized graphene.

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Human milk fat forms the main energy source for breastfed infants, and is highly variable in terms of concentration and composition. Understanding the changes in human milk lipid composition and conformational state during a breastfeed can provide insight into lipid synthesis and secretion in the mammary gland. Therefore, the aim of this study was to evaluate human milk fatty acid length, degree of unsaturation (lipid composition) and lipid phase (lipid conformational state) at different stages during a single breastfeed (fore-, bulk- and hindmilk).

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Organosilicon compounds are ubiquitous in everyday use. Application of some of these compounds in food, cosmetics and pharmaceuticals is widespread on the assumption that these materials are not systemically absorbed. Here the interactions of various organosilicon compounds (simeticone, hexamethyldisilazane and polydimethylsiloxane) with cell membranes and models thereof were characterized with a range of analytical techniques, demonstrating that these compounds were retained in or on the cell membrane.

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Three-dimensional (3D)-printing techniques such as stereolithography (SLA) are currently gaining momentum for the production of miniaturized analytical devices and molds for soft lithography. However, most commercially available SLA resins inhibit polydimethylsiloxane (PDMS) curing, impeding reliable replication of the 3D-printed structures in this elastomeric material. Here, we report a systematic study, using 16 commercial resins, to identify a fast and straightforward treatment of 3D-printed structures and to support accurate PDMS replication using UV and/or thermal post-curing.

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Hypothesis: The wettability of complex fluids on surfaces usually depends on the adsorption of solutes to any of the constituting interfaces. Controlling such interfacial processes by varying the composition of a phase enables the design of smart responsive systems. Our goal is to demonstrate that 3D Confocal Raman Microscopy (CRM) can reveal the mechanistic details of such processes by allowing to simultaneously monitor the contact angle variation and redistribution of the chemical species involved.

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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) is difficult as they are outnumbered by EVs of different tissue of origin as well a large number of lipoproteins (LPs) that are in the same size range.

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Confocal Raman microscopy is important for characterizing 2D materials, but its low throughput significantly hinders its applications. For metastable materials such as graphene oxide (GO), the low throughput is aggravated by the requirement of extremely low laser dose to avoid sample damage. Here we introduce algorithm-improved confocal Raman microscopy (ai-CRM), which increases the Raman scanning rate by one to two orders of magnitude with respect to state-of-the-art works for a variety of 2D materials.

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Plasmonic sensitization of semiconductors is an attractive approach to increase light-induced photocatalytic performance; one method is to use plasmonic nanostructures in core@shell geometry. The occurrence and mechanism of synergetic effects in photocatalysis of such geometries are under intense debate and proposed to occur either through light-induced charge transfer (CT) or through thermal effects. This study focuses on the relation between the dimensions of Ag@CeO nanocubes, the wavelength-dependent efficiency, and the mechanism of light-induced direct CT.

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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 here a new method based on synchronized Rayleigh and Raman light scattering from a single laser beam, which optically traps single EVs.

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Tumor-derived extracellular vesicles (tdEVs) are promising blood biomarkers for cancer disease management. However, blood is a highly complex fluid that contains multiple objects in the same size range as tdEVs (30 nm-1 μm), which obscures an unimpeded analysis of tdEVs. Here, we report a multi-modal analysis platform for the specific capture of tdEVs on antibody-functionalized stainless steel substrates, followed by their analysis using SEM, Raman spectroscopy and AFM, at the single EV level in terms of size and size distribution, and chemical fingerprint.

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Mammalian cells release extracellular vesicles (EVs) into their microenvironment that travel the entire body along the stream of bodily fluids. EVs contain a wide range of biomolecules. The transported cargo varies depending on the EV origin.

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