Publications by authors named "Albert van den Berg"

248 Publications

When You Do Not Get the Whole Picture: Scene Perception After Occipital Cortex Lesions.

Front Neurosci 2021 13;15:716273. Epub 2021 Dec 13.

Donders Institute for Brain, Cognition and Behavior, Center for Cognitive Neuroscience, Radboud University Medical Center (RadboudUMC), Nijmegen, Netherlands.

Occipital cortex lesions (OCLs) typically result in visual field defects (VFDs) contralateral to the damage. VFDs are usually mapped with perimetry involving the detection of point targets. This, however, ignores the important role of integration of visual information across locations in many tasks of everyday life. Here, we ask whether standard perimetry can fully characterize the consequences of OCLs. We compare performance on a rapid scene discrimination task of OCL participants and healthy observers with simulated VFDs. While the healthy observers will only suffer the loss of part of the visual scene, the damage in the OCL participants may further compromise global visual processing. VFDs were mapped with Humphrey perimetry, and participants performed two rapid scene discrimination tasks. In healthy participants, the VFDs were simulated with hemi- and quadrant occlusions. Additionally, the GIST model, a computational model of scene recognition, was used to make individual predictions based on the VFDs. The GIST model was able to predict the performance of controls regarding the effects of the local occlusion. Using the individual predictions of the GIST model, we can determine that the variability between the OCL participants is much larger than the of the VFD could account for. The OCL participants can further be categorized as performing worse, the same, or better as their VFD would predict. While in healthy observers the extent of the simulated occlusion accounts for their performance loss, the OCL participants' performance is not fully determined by the or of their VFD as measured with Humphrey perimetry. While some OCL participants are indeed only limited by the local occlusion of the scene, for others, the lesions compromised the visual network in a more global and disruptive way. Yet one outperformed a healthy observer, suggesting a possible adaptation to the VFD. Preliminary analysis of neuroimaging data suggests that damage to the lateral geniculate nucleus and corpus callosum might be associated with the larger disruption of rapid scene discrimination. We believe our approach offers a useful behavioral tool for investigating why similar VFDs can produce widely differing limitations in everyday life.
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http://dx.doi.org/10.3389/fnins.2021.716273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710569PMC
December 2021

Self-Propelled Detachment upon Coalescence of Surface Bubbles.

Phys Rev Lett 2021 Dec;127(23):235501

Physics of Fluids group, Faculty of Science and Technology, Max Planck-University of Twente Center for Complex Fluid Dynamics, MESA+Institute, and J. M. Burgers Centre for Fluid Dynamics, University of Twente, P.O. Box 217, 7500 AE Enschede, Netherlands.

The removal of microbubbles from substrates is crucial for the efficiency of many catalytic and electrochemical gas evolution reactions in liquids. The current work investigates the coalescence and detachment of bubbles generated from catalytic decomposition of hydrogen peroxide. Self-propelled detachment, induced by the coalescence of two bubbles, is observed at sizes much smaller than those determined by buoyancy. Upon coalescence, the released surface energy is partly dissipated by the bubble oscillations, working against viscous drag. The remaining energy is converted to the kinetic energy of the out-of-plane jumping motion of the merged bubble. The critical ratio of the parent bubble sizes for the jumping to occur is theoretically derived from an energy balance argument and found to be in agreement with the experimental results. The present results provide both physical insight for the bubble interactions and practical strategies for applications in chemical engineering and renewable energy technologies like electrolysis.
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http://dx.doi.org/10.1103/PhysRevLett.127.235501DOI Listing
December 2021

Nanotechnology for a Sustainable Future: Addressing Global Challenges with the International Network4Sustainable Nanotechnology.

ACS Nano 2021 12 15;15(12):18608-18623. Epub 2021 Dec 15.

Waterloo Institute for Nanotechnology, University of Waterloo, Mike & Ophelia Lazaridis Quantum Nano Centre, 200 University Avenue W, Waterloo, Ontario N2L 3G1, Canada.

Nanotechnology has important roles to play in international efforts in sustainability. We discuss how current and future capabilities in nanotechnology align with and support the United Nations' Sustainable Development Goals. We argue that, as a field, we can accelerate the progress toward these goals both directly through technological solutions and through our special interdisciplinary skills in communication and tackling difficult challenges. We discuss the roles of targeting solutions, technology translation, the circular economy, and a number of examples from national efforts around the world in reaching these goals. We have formed a network of leading nanocenters to address these challenges globally and seek to recruit others to join us.
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http://dx.doi.org/10.1021/acsnano.1c10919DOI Listing
December 2021

Determining Particle Size and Position in a Coplanar Electrode Setup Using Measured Opacity for Microfluidic Cytometry.

Biosensors (Basel) 2021 Sep 23;11(10). Epub 2021 Sep 23.

BIOS Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, Max Planck Center for Complex Fluid Dynamics, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.

Microfluidic impedance flow cytometers enable high-throughput, non-invasive, and label-free detection of single-cells. Cytometers with coplanar electrodes are easy and cheap to fabricate, but are sensitive to positional differences of passing particles, owing to the inhomogeneous electric field. We present a novel particle height compensation method, which employs the dependence of measured electrical opacity on particle height. The measured electrical opacity correlates with the particle height as a result of the constant electrical double layer series capacitance of the electrodes. As an alternative to existing compensation methods, we use only two coplanar electrodes and multi-frequency analysis to determine the particle size of a mixture of 5, 6, and 7 µm polystyrene beads with an accuracy (CV) of 5.8%, 4.0%, and 2.9%, respectively. Additionally, we can predict the bead height with an accuracy of 1.5 µm (8% of channel height) using the measured opacity and we demonstrate its application in flow cytometry with yeast. The use of only two electrodes is of special interest for simplified, easy-to-use chips with a minimum amount of instrumentation and of limited size.
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http://dx.doi.org/10.3390/bios11100353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533872PMC
September 2021

Facilitating implementation of organs-on-chips by open platform technology.

Biomicrofluidics 2021 Sep 12;15(5):051301. Epub 2021 Oct 12.

BIOS Lab on a Chip Group, MESA+ Institute for Nanotechnology, Max Planck Institute for Complex Fluid Dynamics, University of Twente, Enschede, the Netherlands.

Organ-on-chip (OoC) and multi-organs-on-chip (MOoC) systems have the potential to play an important role in drug discovery, disease modeling, and personalized medicine. However, most devices developed in academic labs remain at a proof-of-concept level and do not yet offer the ease-of-use, manufacturability, and throughput that are needed for widespread application. Commercially available OoC are easier to use but often lack the level of complexity of the latest devices in academia. Furthermore, researchers who want to combine different chips into MOoC systems are limited to one supplier, since commercial systems are not compatible with each other. Given these limitations, the implementation of standards in the design and operation of OoCs would strongly facilitate their acceptance by users. Importantly, the implementation of such standards must be carried out by many participants from both industry and academia to ensure a widespread acceptance and adoption. This means that standards must also leave room for proprietary technology development next to promoting interchangeability. An open platform with standardized interfacing and user-friendly operation can fulfill these requirements. In this Perspective article, the concept of an open platform for OoCs is defined from a technical perspective. Moreover, we discuss the importance of involving different stakeholders in the development, manufacturing, and application of such an open platform.
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http://dx.doi.org/10.1063/5.0063428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514251PMC
September 2021

Fabrication of freestanding Pt nanowires for use as thermal anemometry probes in turbulence measurements.

Microsyst Nanoeng 2021 2;7:28. Epub 2021 Apr 2.

Physics of Fluids Group, MESA+ Institute, University of Twente, 7522 NB Enschede, The Netherlands.

We report a robust fabrication method for patterning freestanding Pt nanowires for use as thermal anemometry probes for small-scale turbulence measurements. Using e-beam lithography, high aspect ratio Pt nanowires (~300 nm width, ~70 µm length, ~100 nm thickness) were patterned on the surface of oxidized silicon (Si) wafers. Combining wet etching processes with dry etching processes, these Pt nanowires were successfully released, rendering them freestanding between two silicon dioxide (SiO) beams supported on Si cantilevers. Moreover, the unique design of the bridge holding the device allowed gentle release of the device without damaging the Pt nanowires. The total fabrication time was minimized by restricting the use of e-beam lithography to the patterning of the Pt nanowires, while standard photolithography was employed for other parts of the devices. We demonstrate that the fabricated sensors are suitable for turbulence measurements when operated in constant-current mode. A robust calibration between the output voltage and the fluid velocity was established over the velocity range from 0.5 to 5 m s in a SF atmosphere at a pressure of 2 bar and a temperature of 21 °C. The sensing signal from the nanowires showed negligible drift over a period of several hours. Moreover, we confirmed that the nanowires can withstand high dynamic pressures by testing them in air at room temperature for velocities up to 55 m s.
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http://dx.doi.org/10.1038/s41378-021-00255-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433353PMC
April 2021

Highly parallelized human embryonic stem cell differentiation to cardiac mesoderm in nanoliter chambers on a microfluidic chip.

Biomed Microdevices 2021 05 31;23(2):30. Epub 2021 May 31.

BIOS Lab On a Chip Group, MESA+ Institute for Nanotechnology, Max Planck - University of Twente Center for Complex Fluid Dynamics, University of Twente, Enschede, The Netherlands.

Human stem cell-derived cells and tissues hold considerable potential for applications in regenerative medicine, disease modeling and drug discovery. The generation, culture and differentiation of stem cells in low-volume, automated and parallelized microfluidic chips hold great promise to accelerate the research in this domain. Here, we show that we can differentiate human embryonic stem cells (hESCs) to early cardiac mesodermal cells in microfluidic chambers that have a volume of only 30 nanoliters, using discontinuous medium perfusion. 64 of these chambers were parallelized on a chip which contained integrated valves to spatiotemporally isolate the chambers and automate cell culture medium exchanges. To confirm cell pluripotency, we tracked hESC proliferation and immunostained the cells for pluripotency markers SOX2 and OCT3/4. During differentiation, we investigated the effect of different medium perfusion frequencies on cell reorganization and the expression of the early cardiac mesoderm reporter MESP1 by live-cell imaging. Our study demonstrates that microfluidic technology can be used to automatically culture, differentiate and study hESC in very low-volume culture chambers even without continuous medium perfusion. This result is an important step towards further automation and parallelization in stem cell technology.
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http://dx.doi.org/10.1007/s10544-021-00556-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166733PMC
May 2021

Mimicking and surpassing the xenograft model with cancer-on-chip technology.

EBioMedicine 2021 Apr 25;66:103303. Epub 2021 Mar 25.

Applied Stem Cell Technologies, TechMed Centre, University of Twente, P. O. Box 217, 7500 AE Enschede, the Netherlands.

Organs-on-chips are in vitro models in which human tissues are cultured in microfluidic compartments with a controlled, dynamic micro-environment. Specific organs-on-chips are being developed to mimic human tumors, but the validation of such 'cancer-on-chip' models for use in drug development is hampered by the complexity and variability of human tumors. An important step towards validation of cancer-on-chip technology could be to first mimic cancer xenograft models, which share multiple characteristics with human cancers but are significantly less complex. Here we review the relevant biological characteristics of a xenograft tumor and show that organ-on-chip technology is capable of mimicking many of these aspects. Actual comparisons between on-chip tumor growth and xenografts are promising but also demonstrate that further development and empirical validation is still needed. Validation of cancer-on-chip models to xenografts would not only represent an important milestone towards acceptance of cancer-on-chip technology, but could also improve drug discovery, personalized cancer medicine, and reduce animal testing.
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http://dx.doi.org/10.1016/j.ebiom.2021.103303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024912PMC
April 2021

Monitoring Contractile Cardiomyocytes via Impedance Using Multipurpose Thin Film Ruthenium Oxide Electrodes.

Sensors (Basel) 2021 Feb 18;21(4). Epub 2021 Feb 18.

BIOS Lab on a Chip Group, Max Planck Centre for Complex Fluid Dynamics and Technical Medical Centre, MESA+ Institute for Nanotechnology, University of Twente, 7500 AE Enschede, The Netherlands.

A ruthenium oxide (RuOx) electrode was used to monitor contractile events of human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) through electrical impedance spectroscopy (EIS). Using RuOx electrodes presents an advantage over standard thin film Pt electrodes because the RuOx electrodes can also be used as electrochemical sensor for pH, O, and nitric oxide, providing multisensory functionality with the same electrode. First, the EIS signal was validated in an optically transparent well-plate setup using Pt wire electrodes. This way, visual data could be recorded simultaneously. Frequency analyses of both EIS and the visual data revealed almost identical frequency components. This suggests both the EIS and visual data captured the similar events of the beating of (an area of) hPSC-CMs. Similar EIS measurement was then performed using the RuOx electrode, which yielded comparable signal and periodicity. This mode of operation adds to the versatility of the RuOx electrode's use in in vitro studies.
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http://dx.doi.org/10.3390/s21041433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923073PMC
February 2021

Single catalyst particle diagnostics in a microreactor for performing multiphase hydrogenation reactions.

Faraday Discuss 2021 May 5;229:267-280. Epub 2021 Mar 5.

Inorganic Chemistry and Catalysis, Debye Institute for Nanomaterials Science, Utrecht University, The Netherlands.

Since inter- and intra-particle heterogeneities in catalyst particles are more the rule than the exception, it is advantageous to perform high-throughput screening for the activity of single catalyst particles. A multiphase system (gas/liquid/solid) is developed, where droplet-based microfluidics and optical detection are combined for the analysis of single catalyst particles by safely performing a hydrogenation study on in-house synthesized hollow Pd/SiO catalyst microparticles, in a polydimethylsiloxane (PDMS) microreactor. A two-phase segmented flow system of particle-containing droplets is combined with a parallel gas-reactant channel separated from the flow channel by a 50 μm thick gas permeable PDMS wall. In this paper, the developed microreactor system is showcased by monitoring the Pd-catalyzed hydrogenation of methylene blue. A discoloration of blue to brown visualizes the hydrogenation activity happening in a high-throughput fashion on the single Pd/SiO spherical catalyst microparticles, which are encapsulated in 50 nL-sized droplets. By measuring the reagent concentration at various spots along the length of the channel the reaction time can be determined, which is proportional to the residence time in the channel. The developed experimental platform opens new possibilities for single catalyst particle diagnostics in a multiphase environment.
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http://dx.doi.org/10.1039/d0fd00006jDOI Listing
May 2021

Collagen I Based Enzymatically Degradable Membranes for Organ-on-a-Chip Barrier Models.

ACS Biomater Sci Eng 2021 07 24;7(7):2998-3005. Epub 2021 Feb 24.

Applied Stem Cell Technologies, Technical Medical Centre, University of Twente, PO Box 217, Enschede 7500 AE, The Netherlands.

Organs-on-chips are microphysiological in vitro models of human organs and tissues that rely on culturing cells in a well-controlled microenvironment that has been engineered to include key physical and biochemical parameters. Some systems contain a single perfused microfluidic channel or a patterned hydrogel, whereas more complex devices typically employ two or more microchannels that are separated by a porous membrane, simulating the tissue interface found in many organ subunits. The membranes are typically made of synthetic and biologically inert materials that are then coated with extracellular matrix (ECM) molecules to enhance cell attachment. However, the majority of the material remains foreign and fails to recapitulate the native microenvironment of the barrier tissue. Here, we study microfluidic devices that integrate a vitrified membrane made of collagen-I hydrogel (VC). The biocompatibility of this membrane was confirmed by growing a healthy population of stem cell derived endothelial cells (iPSC-EC) and immortalized retinal pigment epithelium (ARPE-19) on it and assessing morphology by fluorescence microscopy. Moreover, VC membranes were subjected to biochemical degradation using collagenase II. The effects of this biochemical degradation were characterized by the permeability changes to fluorescein. Topographical changes on the VC membrane after enzymatic degradation were also analyzed using scanning electron microscopy. Altogether, we present a dynamically bioresponsive membrane integrated in an organ-on-chip device with which disease-related ECM remodeling can be studied.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278385PMC
July 2021

Measuring Both pH and O with a Single On-Chip Sensor in Cultures of Human Pluripotent Stem Cell-Derived Cardiomyocytes to Track Induced Changes in Cellular Metabolism.

ACS Sens 2021 01 29;6(1):267-274. Epub 2020 Dec 29.

BIOS Lab on a Chip group, MESA+ Institute for Nanotechnology, Max Planck Centre for Complex Fluid Dynamics and Technical Medical Centre, University of Twente, Enschede 7500 AE, The Netherlands.

studies which focus on cellular metabolism can benefit from time-resolved readouts from the living cells. pH and O concentration are fundamental parameters upon which cellular metabolism is often inferred. This work demonstrates a novel use of a ruthenium oxide (RuO) electrode for studies. The RuO electrode was characterized to measure both pH and O using two different modes. When operated potentiometrically, continuous pH reading can be obtained, and O concentration can be measured chronoamperometrically. In this work, we demonstrate the use of the RuO electrodes in inferring two different types of metabolism of human pluripotent stem cell-derived cardiomyocytes. We also show and discuss the interpretation of the measurements into meaningful extracellular acidification rates and oxygen consumption rates of the cells. Overall, we present the RuO electrode as a versatile and powerful tool in cell metabolism studies, especially in comparative settings.
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http://dx.doi.org/10.1021/acssensors.0c02282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836059PMC
January 2021

Microfluidic organ-on-a-chip model of the outer blood-retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure.

Lab Chip 2021 01 21;21(2):272-283. Epub 2020 Dec 21.

Applied Stem Cell Technologies, Technical Medical Centre, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands.

The outer blood-retinal barrier (oBRB) tightly controls the transport processes between the neural tissue of the retina and the underlying blood vessel network. The barrier is formed by the retinal pigment epithelium (RPE), its basal membrane and the underlying choroidal capillary bed. Realistic three-dimensional cell culture based models of the oBRB are needed to study mechanisms and potential treatments of visual disorders such as age-related macular degeneration that result from dysfunction of the barrier tissue. Ideally, such models should also include clinically relevant read-outs to enable translation of experimental findings in the context of pathophysiology. Here, we report a microfluidic organ-on-a-chip model of the oBRB that contains a monolayer of human immortalized RPE and a microvessel of human endothelial cells, separated by a semi-permeable membrane. Confluent monolayers of both cell types were confirmed by fluorescence microscopy. The three-dimensional vascular structures within the chip were imaged by optical coherence tomography: a medical imaging technique, which is routinely applied in ophthalmology. Differences in diameters and vessel density could be readily detected. Upon inducing oxidative stress by treating with hydrogen peroxide (HO), a dose dependent increase in barrier permeability was observed by using a dynamic assay for fluorescence tracing, analogous to the clinically used fluorescence angiography. This organ-on-a-chip of the oBRB will allow future studies of complex disease mechanisms and treatments for visual disorders using clinically relevant endpoints in vitro.
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http://dx.doi.org/10.1039/d0lc00639dDOI Listing
January 2021

Patterning Biological Gels for 3D Cell Culture inside Microfluidic Devices by Local Surface Modification through Laminar Flow Patterning.

Micromachines (Basel) 2020 Dec 16;11(12). Epub 2020 Dec 16.

Applied Stem Cell Technologies, University of Twente, 7500-AE Enschede, The Netherlands.

Microfluidic devices are used extensively in the development of new in vitro cell culture models like organs-on-chips. A typical feature of such devices is the patterning of biological hydrogels to offer cultured cells and tissues a controlled three-dimensional microenvironment. A key challenge of hydrogel patterning is ensuring geometrical confinement of the gel, which is generally solved by inclusion of micropillars or phaseguides in the channels. Both of these methods often require costly cleanroom fabrication, which needs to be repeated even when only small changes need be made to the gel geometry, and inadvertently expose cultured cells to non-physiological and mechanically stiff structures. Here, we present a technique for facile patterning of hydrogel geometries in microfluidic chips, but without the need for any confining geometry built into the channel. Core to the technique is the use of laminar flow patterning to create a hydrophilic path through an otherwise hydrophobic microfluidic channel. When a liquid hydrogel is injected into the hydrophilic region, it is confined to this path by the surrounding hydrophobic regions. The various surface patterns that are enabled by laminar flow patterning can thereby be rendered into three-dimensional hydrogel structures. We demonstrate that the technique can be used in many different channel geometries while still giving the user control of key geometric parameters of the final hydrogel. Moreover, we show that human umbilical vein endothelial cells can be cultured for multiple days inside the devices with the patterned hydrogels and that they can be stimulated to migrate into the gel under the influence of trans-gel flows. Finally, we demonstrate that the patterned gels can withstand trans-gel flow velocities in excess of physiological interstitial flow velocities without rupturing or detaching. This novel hydrogel-patterning technique addresses fundamental challenges of existing methods for hydrogel patterning inside microfluidic chips, and can therefore be applied to improve design time and the physiological realism of microfluidic cell culture assays and organs-on-chips.
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http://dx.doi.org/10.3390/mi11121112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765499PMC
December 2020

Coccolithophore calcification studied by single-cell impedance cytometry: Towards single-cell PIC:POC measurements.

Biosens Bioelectron 2020 Nov 10;173:112808. Epub 2020 Nov 10.

BIOS Lab-on-a-Chip Group, MESA+ Institute, Max Planck Center for Complex Fluid Dynamics, University of Twente, P.O. Box 217, AE Enschede, 7500, the Netherlands.

Since the industrial revolution 30% of the anthropogenic CO is absorbed by oceans, resulting in ocean acidification, which is a threat to calcifying algae. As a result, there has been profound interest in the study of calcifying algae, because of their important role in the global carbon cycle. The coccolithophore Emiliania huxleyi is considered to be globally the most dominant calcifying algal species, which creates a unique exoskeleton from inorganic calcium carbonate platelets. The PIC (particulate inorganic carbon): POC (particulate organic carbon) ratio describes the relative amount of inorganic carbon in the algae and is a critical parameter in the ocean carbon cycle. In this research we explore the use of microfluidic single-cell impedance spectroscopy in the field of calcifying algae. Microfluidic impedance spectroscopy enables us to characterize single-cell electrical properties in a non-invasive and label-free way. We use the ratio of the impedance at high frequency vs. low frequency, known as opacity, to discriminate between calcified coccolithophores and coccolithophores with a calcite exoskeleton dissolved by acidification (decalcified). We have demonstrated that using opacity we can discriminate between calcified and decalcified coccolithophores with an accuracy of 94.1%. We have observed a correlation between the measured opacity and the cell height in the channel, which is supported by FEM simulations. The difference in cell density between calcified and decalcified cells can explain the difference in cell height and therefore the measured opacity.
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http://dx.doi.org/10.1016/j.bios.2020.112808DOI Listing
November 2020

Modular microreactor with integrated reflection element for online reaction monitoring using infrared spectroscopy.

Lab Chip 2020 11;20(22):4166-4174

BIOS Lab on a Chip Group, MESA+ Institute for Nanotechnology, University of Twente, Drienerlolaan 5, Enschede, The Netherlands.

We report on the fabrication of an internal reflection element (IRE) combined with a modular polymer microfluidic chip that can be used for attenuated total reflection (ATR) infrared spectroscopy. The IRE is fabricated from a silicon wafer. Two different polymers are used for the fabrication of the two types of modular microfluidic chips, namely polydimethylsiloxane (PDMS) and cyclic olefin copolymer (COC). The microfluidic chip is modular in the sense that several layers of mixing channels, using the herringbone mixer principle, and reactions chambers, can be stacked to facilitate the study of the desired reaction. A model Paal-Knorr reaction is carried out to prove that the chip works as intended. Furthermore, we highlight the strength of IR spectroscopy as a tool for reaction monitoring by identifying the peaks and showing the different reaction orders at the different steps of the Paal-Knorr reaction. The reduction of the aldehyde groups indicates a (pseudo) first order reaction whereas the vibrational modes associated with the ring formation indicate a zero order reaction. This zero order reaction can be explained with literature, where it is suggested that water acts as a catalyst during the dehydration step, which is the final step in the pyrrole ring formation.
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http://dx.doi.org/10.1039/d0lc00704hDOI Listing
November 2020

Plasmonic Nanocrystal Arrays on Photonic Crystals with Tailored Optical Resonances.

ACS Appl Mater Interfaces 2020 Aug 5;12(33):37657-37669. Epub 2020 Aug 5.

BIOS Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, Technical Medical Centre & Max Planck Center for Complex Fluid Dynamics, University of Twente, 7522 NB Enschede, the Netherlands.

Hierarchical plasmonic-photonic microspheres (PPMs) with high controllability in their structures and optical properties have been explored toward surface-enhanced Raman spectroscopy. The PPMs consist of gold nanocrystal (AuNC) arrays (3rd-tier) anchored on a hexagonal nanopattern (2nd-tier) assembled from silica nanoparticles (SiONPs) where the uniform microsphere backbone is termed the 1st-tier. The PPMs sustain both photonic stop band (PSB) properties, resulting from periodic SiONP arrangements of the 2nd-tier, and a surface plasmon resonance (SPR), resulting from AuNC arrays of the 3rd-tier. Thanks to the synergistic effects of the photonic crystal (PC) structure and the AuNC array, the electromagnetic (EM) field in such a multiscale composite structure can tremendously be enhanced at certain wavelengths. These effects are demonstrated by experimentally evaluating the Raman enhancement of benzenethiol (BT) as a probe molecule and are confirmed via numerical simulations. We achieve a maximum SERS enhancement factor of up to ∼10 when the resonances are tailored to coincide with the excitation wavelength by suitable structural modifications.
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http://dx.doi.org/10.1021/acsami.0c05596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441488PMC
August 2020

Controlled pharmacokinetic anti-cancer drug concentration profiles lead to growth inhibition of colorectal cancer cells in a microfluidic device.

Lab Chip 2020 08;20(17):3167-3178

Applied Stem Cell Technology, TechMed Centre, University of Twente, P. O. Box 217, 7500 AE Enschede, The Netherlands.

We present a microfluidic device to expose cancer cells to a dynamic, in vivo-like concentration profile of a drug, and quantify efficacy on-chip. About 30% of cancer patients receive drug therapy. In conventional cell culture experiments drug efficacy is tested under static concentrations, e.g. 1 μM for 48 hours, whereas in vivo, drug concentration follows a pharmacokinetic profile with an initial peak and a decline over time. With the rise of microfluidic cell culture models, including organs-on-chips, there are opportunities to more realistically mimic in vivo-like concentrations. Our microfluidic device contains a cell culture chamber and a drug-dosing channel separated by a transparent membrane, to allow for shear stress-free drug exposure and label-free growth quantification. Dynamic drug concentration profiles in the cell culture chamber were controlled by continuously flowing controlled concentrations of drug in the dosing channel. The control over drug concentrations in the cell culture chambers was validated with fluorescence experiments and numerical simulations. Exposure of HCT116 colorectal cancer cells to static concentrations of the clinically used drug oxaliplatin resulted in a sensible dose-effect curve. Dynamic, in vivo-like drug exposure also led to statistically significant lower growth compared to untreated control. Continuous exposure to the average concentration of the in vivo-like exposure seems more effective than exposure to the peak concentration (Cmax) only. We expect that our microfluidic system will improve efficacy prediction of in vitro models, including organs-on-chips, and may lead to future clinical optimization of drug administration schedules.
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http://dx.doi.org/10.1039/d0lc00419gDOI Listing
August 2020

Functional connectivity of the Precuneus reflects effectiveness of visual restitution training in chronic hemianopia.

Neuroimage Clin 2020 26;27:102292. Epub 2020 May 26.

Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.

Visual field defects in chronic hemianopia can improve through visual restitution training, yet not all patients benefit equally from this long and exhaustive procedure. Here, we asked if resting-state functional connectivity prior to visual restitution could predict training success. In two training sessions of eight weeks each, 20 patients with chronic hemianopia performed a visual discrimination task by directing spatial selective attention towards stimuli presented in either hemifield, while suppressing eye movements. We examined two effects: a sensitivity change in the attended (trained) minus the unattended (control) hemifield (i.e., a training-specific improvement), and an overall improvement (i.e., a total change in sensitivity after both sessions). We then identified five visual resting-state networks and evaluated their functional connectivity in relation to both training effects. We found that the functional connectivity strength between the anterior Precuneus and the Occipital Pole Network was positively related to the attention modulated (i.e., training-specific) improvement. No such relationship was found for the overall improvement or for the other visual networks of interest. Our finding suggests that the anterior Precuneus plays a role in attention-modulated visual field improvements. The resting-state functional connectivity between the anterior Precuneus and the Occipital Pole Network may thus serve as an imaging-based biomarker that quantifies a patient's potential capacity to direct spatial attention. This may help to identify hemianopia patients that are most likely to benefit from visual restitution training.
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http://dx.doi.org/10.1016/j.nicl.2020.102292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303670PMC
March 2021

Useful Field of View Performance in the Intact Visual Field of Hemianopia Patients.

Invest Ophthalmol Vis Sci 2020 05;61(5):43

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Purpose: Postchiasmatic brain damage commonly results in an area of reduced visual sensitivity or blindness in the contralesional hemifield. Previous studies have shown that the ipsilesional visual field can be impaired too. Here, we examine whether assessing visual functioning of the "intact" ipsilesional visual field can be useful to understand difficulties experienced by patients with visual field defects.

Methods: We compared the performance of 14 patients on a customized version of the useful field of view test that presents stimuli in both hemifields but only assesses functioning of their intact visual half-field (iUFOV) with that of equivalent hemifield assessments in 17 age-matched healthy control participants. In addition, we mapped visual field sensitivity with the Humphrey Field Analyzer. Last, we used an adapted version of the National Eye Institute Visual Quality of Life-25 to measure their experienced visual quality of life.

Results: We found that patients performed worse on the second and third iUFOV subtests, but not on the first subtest. Furthermore, patients scored significantly worse on almost every subscale, except ocular pain. Summed iUFOV scores (assessing the intact hemifield only) and Humphrey field analyzer scores (assessing both hemifields combined) showed almost similar correlations with the subscale scores of the adapted National Eye Institute Visual Quality of Life-25.

Conclusions: The iUFOV test is sensitive to deficits in the visual field that are not picked up by traditional perimetry. We therefore believe this task is of interest for patients with postchiasmatic brain lesions and should be investigated further.
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http://dx.doi.org/10.1167/iovs.61.5.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405799PMC
May 2020

Mass Transport Determined Silica Nanowires Growth on Spherical Photonic Crystals with Nanostructure-Enabled Functionalities.

Small 2020 Jun 13;16(24):e2001026. Epub 2020 May 13.

BIOS Lab on a Chip Group, Technical Medical Centre, MESA+ Institute for Nanotechnology & Max Planck Centre for Complex Fluid Dynamics, University of Twente, Enschede, 7500 AE, the Netherlands.

A robust and facile method has been developed to obtain directional growth of silica nanowires (SiO NWs) by regulating mass transport of silicon monoxide (SiO) vapor. SiO NWs are grown by vapor-liquid-solid (VLS) process on a surface of gold-covered spherical photonic crystals (SPCs) annealed at high temperature in an inert gas atmosphere in the vicinity of a SiO source. The SPCs are prepared from droplet confined colloidal self-assembly. SiO NW morphology is governed by diffusion-reaction process of SiO vapor, whereby directional growth of SiO NWs toward the low SiO concentration is obtained at locations with a high SiO concentration gradient, while random growth is observed at locations with a low SiO concentration gradient. Growth of NWs parallel to the supporting substrate surface is of great importance for various applications, and this is the first demonstration of surface-parallel growth by controlling mass transport. This controllable NW morphology enables production of SPCs covered with a large number of NWs, showing multilevel micro-nano feature and high specific surface area for potential applications in superwetting surfaces, oil/water separation, microreactors, and scaffolds. In addition, the controllable photonic stop band properties of this hybrid structure of SPCs enable the potential applications in photocatalysis, sensing, and light harvesting.
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http://dx.doi.org/10.1002/smll.202001026DOI Listing
June 2020

Dimension-reconfigurable bubble film nanochannel for wetting based sensing.

Nat Commun 2020 02 10;11(1):814. Epub 2020 Feb 10.

International Joint Laboratory of Nanofluidics and Interfaces, School of Physical Science and Technology, Northwestern Polytechnical University, 710100, Xi'an, China.

Dimensions and surface properties are the predominant factors for the applications of nanofluidic devices. Here we use a thin liquid film as a nanochannel by inserting a gas bubble in a glass capillary, a technique we name bubble-based film nanofluidics. The height of the film nanochannel can be regulated by the Debye length and wettability, while the length independently changed by applied pressure. The film nanochannel behaves functionally identically to classical solid state nanochannels, as ion concentration polarizations. Furthermore, the film nanochannels can be used for label-free immunosensing, by principle of wettability change at the solid interface. The optimal sensitivity for the biotin-streptavidin reaction is two orders of magnitude higher than for the solid state nanochannel, suitable for a full range of electrolyte concentrations. We believe that the film nanochannel represents a class of nanofluidic devices that is of interest for fundamental studies and also can be widely applied, due to its reconfigurable dimensions, low cost, ease of fabrication and multiphase interfaces.
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http://dx.doi.org/10.1038/s41467-020-14580-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010761PMC
February 2020

Automated Analysis of Platelet Aggregation on Cultured Endothelium in a Microfluidic Chip Perfused with Human Whole Blood.

Micromachines (Basel) 2019 Nov 14;10(11). Epub 2019 Nov 14.

Applied Stem Cell Technologies group, University of Twente, 7522 NB Enschede, The Netherlands.

Organ-on-a-chip models with incorporated vasculature are becoming more popular to study platelet biology. A large variety of image analysis techniques are currently used to determine platelet coverage, ranging from manually setting thresholds to scoring platelet aggregates. In this communication, an automated methodology is introduced, which corrects misalignment of a microfluidic channel, automatically defines regions of interest and utilizes a triangle threshold to determine platelet coverages and platelet aggregate size distributions. A comparison between the automated methodology and manual identification of platelet aggregates shows a high accuracy of the triangle methodology. Furthermore, the image analysis methodology can determine platelet coverages and platelet size distributions in microfluidic channels lined with either untreated or activated endothelium used for whole blood perfusion, proving the robustness of the method.
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http://dx.doi.org/10.3390/mi10110781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915557PMC
November 2019

Ion Concentration Polarization for Microparticle Mesoporosity Differentiation.

Langmuir 2019 Jul 16;35(30):9704-9712. Epub 2019 Jul 16.

BIOS-Lab on a chip group, MESA+ Institute for Nanotechnology , Max Planck-University of Twente Center for Complex Fluid Dynamics University of Twente , Drienerlolaan 5 , Enschede , The Netherlands.

Microparticle porosity is normally determined in bulk manner providing an ensemble average that hinders establishing the individual role of each microparticle. On the other hand, single particle characterization implies expensive technology. We propose to use ion concentration polarization to measure differences in mesoporosity at the single particle level. Ion concentration polarization occurs at the interface between an electrolyte and a porous particle when an electric field is applied. The extent of ion concentration polarization depends, among others, on the mesopore size and density. By using a fluorescence marker, we could measure differences in concentration polarization between particles with 3 and 13 nm average mesopore diameters. A qualitative model was developed in order to understand and interpret the phenomena. We believe that this inexpensive method could be used to measure differences in mesoporous particle materials such as catalysts.
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http://dx.doi.org/10.1021/acs.langmuir.9b00802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671885PMC
July 2019

Scalable microphysiological system to model three-dimensional blood vessels.

APL Bioeng 2019 Jun 21;3(2):026105. Epub 2019 Jun 21.

Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.

Blood vessel models are increasingly recognized to have value in understanding disease and drug discovery. However, continued improvements are required to more accurately reflect human vessel physiology. Realistic three-dimensional (3D) cultures of human vascular cells inside microfluidic chips, or vessels-on-chips (VoC), could contribute to this since they can recapitulate aspects of the microenvironment by including mechanical stimuli such as shear stress. Here, we used human induced pluripotent stem cells as a source of endothelial cells (hiPSC-ECs), in combination with a technique called viscous finger patterning (VFP) toward this goal. We optimized VFP to create hollow structures in collagen I extracellular-matrix inside microfluidic chips. The lumen formation success rate was over 90% and the resulting cellularized lumens had a consistent diameter over their full length, averaging 336 ± 15 m. Importantly, hiPSC-ECs cultured in these 3D microphysiological systems formed stable and viable vascular structures within 48 h. Furthermore, this system could support coculture of hiPSC-ECs with primary human brain vascular pericytes, demonstrating their ability to accommodate biologically relevant combinations of multiple vascular cell types. Our protocol for VFP is more robust than previously published methods with respect to success rates and reproducibility of the diameter between- and within channels. This, in combination with the ease of preparation, makes hiPSC-EC based VoC a low-cost platform for future studies in personalized disease modeling.
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http://dx.doi.org/10.1063/1.5090986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588522PMC
June 2019

Wafer-scale fabrication of high-quality tunable gold nanogap arrays for surface-enhanced Raman scattering.

Nanoscale 2019 Jul 13;11(25):12152-12160. Epub 2019 Jun 13.

BIOS Lab-on-a-Chip Group, MESA+ Institute, Max Planck Center for Complex Fluid Dynamics, University of Twente, 7522 NB Enschede, The Netherlands.

We report a robust and high-yield fabrication method for wafer-scale patterning of high-quality arrays of dense gold nanogaps, combining displacement Talbot lithography based shrink-etching with dry etching, wet etching, and thin film deposition techniques. By using the self-sharpening of <111>-oriented silicon crystal planes during the wet etching process, silicon structures with extremely smooth nanogaps are obtained. Subsequent conformal deposition of a silicon nitride layer and a gold layer results in dense arrays of narrow gold nanogaps. Using this method, we successfully fabricate high-quality Au nanogaps down to 10 nm over full wafer areas. Moreover, the gap spacing can be tuned by changing the thickness of deposited Au layers. Since the roughness of the template is minimized by the crystallographic etching of silicon, the roughness of the gold nanogaps depends almost exclusively on the roughness of the sputtered gold layers. Additionally, our fabricated Au nanogaps show a significant enhancement of surface-enhanced Raman scattering (SERS) signals of benzenethiol molecules chemisorbed on the structure surface, at an average enhancement factor up to 1.5 × 10.
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http://dx.doi.org/10.1039/c9nr02215eDOI Listing
July 2019

Postdeposition UV-Ozone Treatment: An Enabling Technique to Enhance the Direct Adhesion of Gold Thin Films to Oxidized Silicon.

ACS Nano 2019 Jun 13;13(6):6782-6789. Epub 2019 Jun 13.

BIOS Lab-on-a-Chip Group, MESA+ Institute & Max Planck Center for Complex Fluid Dynamics , University of Twente , 7522 NB Enschede , The Netherlands.

We found that continuous films of gold (Au) on oxidized silicon (SiO) substrates, upon treatment with ultraviolet (UV)-ozone, exhibit strong adhesion to the SiO support. Importantly, the enhancement is independent of micro- or nanostructuring of such nanometer-thick films. Deposition of a second Au layer on top of the pretreated Au layer makes the adhesion stable for at least 5 months in environmental air. Using this treatment method enables us to large-scale fabricate various SiO-supported Au structures at various thicknesses with dimensions spanning from a few hundreds of nanometers to a few micrometers, without the use of additional adhesion layers. We explain the observed adhesion improvement as polarization-induced increased strength of AuSi bonds at the Au-SiO interface due to the formation of a gold oxide monolayer on the Au surface by the UV-ozone treatment. Our simple and enabling method thus provides opportunities for patterning Au micro/nanostructures on SiO substrates without an intermediate metallic adhesion layer, which is critical for biosensing and nanophotonic applications.
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http://dx.doi.org/10.1021/acsnano.9b01403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595434PMC
June 2019

Large-scale fabrication of highly ordered sub-20 nm noble metal nanoparticles on silica substrates without metallic adhesion layers.

Microsyst Nanoeng 2018 23;4. Epub 2018 Apr 23.

1BIOS Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, MIRA Institute for Biomedical Technology and Technical Medicine, Max Planck Center for Complex Fluid Dynamics, University of Twente, Enschede, 7522 NB The Netherlands.

Periodic noble metal nanoparticles offer a wide spectrum of applications including chemical and biological sensors, optical devices, and model catalysts due to their extraordinary properties. For sensing purposes and catalytic studies, substrates made of glass or fused-silica are normally required as supports, without the use of metallic adhesion layers. However, precise patterning of such uniform arrays of silica-supported noble metal nanoparticles, especially at sub-100 nm in diameter, is challenging without adhesion layers. In this paper, we report a robust method to large-scale fabricate highly ordered sub-20 nm noble metal nanoparticles, i.e., gold and platinum, supported on silica substrates without adhesion layers, combining displacement Talbot lithography (DTL) with dry-etching techniques. Periodic photoresist nanocolumns at diameters of ~110 nm are patterned on metal-coated oxidized silicon wafers using DTL, and subsequently transferred at a 1:1 ratio into anti-reflection layer coating (BARC) nanocolumns with the formation of nano-sharp tips, using nitrogen plasma etching. These BARC nanocolumns are then used as a mask for etching the deposited metal layer using inclined argon ion-beam etching. We find that increasing the etching time results in cone-shaped silica features with metal nanoparticles on the tips at diameters ranging from 100 nm to sub-30 nm, over large areas of 3×3 cm. Moreover, subsequent annealing these sub-30 nm metal nanoparticle arrays at high-temperature results in sub-20 nm metal nanoparticle arrays with ~10 uniform particles.
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http://dx.doi.org/10.1038/s41378-017-0001-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161447PMC
April 2018

In-Channel Responsive Surface Wettability for Reversible and Multiform Emulsion Droplet Preparation and Applications.

ACS Appl Mater Interfaces 2019 May 24;11(18):16934-16943. Epub 2019 Apr 24.

BIOS/Lab on a Chip Group, MESA+ Institute for Nanotechnology , University of Twente , Enschede 7500AE , The Netherlands.

We report on a simple approach for in-channel functionalization of a polydimethylsiloxane (PDMS) surface to obtain a switchable and reversible wettability change between hydrophilic and hydrophobic states. The thermally responsive polymer, poly( N-Isopropylacrylamide) (PNIPAAm), was grafted on the surface of PDMS channels by UV-induced surface grafting. PNIPAAm-grafted PDMS (PNIPAAm-g-PDMS) surface wettability can be thermally tuned to obtain water contact angles varying in the range of 24.3 to 106.1° by varying temperature at 25-38 °C. By selectively modifying the functionalized area in the microfluidic channels, multiform emulsion droplets of oil-in-water (O/W), water-in-oil (W/O), oil-in-water-in-oil (O/W/O), and water-in-oil-in-water (W/O/W) could be created on-demand. Combining solid surface wettability and liquid-liquid interfacial properties, tunable generation of O/W and W/O droplet and stratified flows were enabled in the same microfluidic device with either different or the same two-phase fluidic systems, by properly heating/cooling thermal-responsive microfluidic channels and choosing suitable surfactants. Controllable creation of O/W/O and W/O/W droplets was also achieved in the same microfluidic device, by locally heating or cooling the droplet generation areas with integrated electric heaters to achieve opposite surface wettability. Hollow microcapsules were prepared using double emulsion droplets as templates in the microfluidic device with sequential hydrophobic and hydrophilic channel segments, demonstrating the strength of the proposed approach in practical applications.
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http://dx.doi.org/10.1021/acsami.9b03160DOI Listing
May 2019

Microfluidics Assisted Fabrication of Three-Tier Hierarchical Microparticles for Constructing Bioinspired Surfaces.

ACS Nano 2019 03 15;13(3):3638-3648. Epub 2019 Mar 15.

BIOS Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, Technical Medical Centre and Max Planck Center for Complex Fluid Dynamics , University of Twente , Enschede 7522NB , The Netherlands.

Construction of textured bioinspired surfaces with refined structures that exhibit superior wetting properties is of great importance for many applications ranging from self-cleaning, antibiofouling, anti-icing, oil/water separation, smart membrane, and microfluidic devices. Previously, the preparation of artificial surfaces generally relies on the combination of different approaches together, which is a lack of flexibility to control over the individual architecture unit, the surface topology, as well as the complex procedure needed. In this work, we report a method for rapid fabrication of three-tier hierarchical microunits (structures consisting of multiple levels) using a facile droplet microfluidics approach. These units include the first-tier microspheres consisting of the second-tier close-packed polystyrene (PS) nanoparticles decorated with the third-tier elegant polymer nanowrinkles. These nanowrinkles on the PS nanoparticles are formed according to the interfacial instability induced by gradient photopolymerization of N-isopropylacrylamide (NIPAM) monomers. The formation process and topologies of nanowrinkles can be regulated by the photopolymerization process and the fraction of carboxylic groups on the PS nanoparticle surface. Such a hierarchical microsphere mimics individual units of bioinspired surfaces. Therefore, the surfaces from self-assembly of these fabricated two-tier and three-tier hierarchical microunits collectively exhibit "gecko" and "rose petal" wetting states, with the micro- and nanoscale structures amplifying the initial hydrophobicity but still being highly adhesive to water. This approach offers promising advantages of high-yield fabrication, precise control over the size and component of the microspheres, and integration of microfluidic droplet generation, colloidal nanoparticle self-assembly, and interfacial polymerization-induced nanowrinkles in a straightforward manner.
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http://dx.doi.org/10.1021/acsnano.9b00245DOI Listing
March 2019
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