Publications by authors named "Jaap M J Den Toonder"

Sweat is a biomarker-rich fluid with potential for continuous patient monitoring via wearable devices. However, biomarker concentrations vary with the sweat rate per gland, posing a challenge for sweat sensing. To address this, we propose an algorithm to compute both the number of active sweat glands and their individual sweat rates.

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Using sweat instead of blood for monitoring chemical biomarker concentrations of hospitalised patients offers several advantages for both the patients and healthcare workers. Unlike blood, sweat can be noninvasively and continuously sampled without direct involvement of a professional, and sweat contains a rich composition of biomarkers. However, patients in resting state have extremely low sweat rates and they produce correspondingly small sweat volumes, which makes sweat sensing of hospitalised patients highly challenging.

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Hypothesis: Nonpolar solvents with added charge control agents are widely used in various applications, such as E-paper displays. In spite of previous work, the mechanisms governing charge generation in nonpolar liquids, particularly those induced by electrochemical reactions at the liquid-solid interface, are not completely understood. We hypothesize that a physics-based model, according to the modified Butler-Volmer equation, can be used to quantitatively predict the injection of charges and the corresponding currents, in nonpolar solvents with surfactants.

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Cilia are hair-like organelles present on cell surfaces. They often exhibit a collective wave-like motion that can enhance fluid or particle transportation function, known as metachronal motion. Inspired by nature, researchers have developed artificial cilia capable of inducing metachronal motion, especially magnetic actuation.

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Organ-on-a-chip (OOC) models based on microfluidic technology are increasingly used to obtain mechanistic insight into (patho)physiological processes in humans, and they hold great promise for application in drug development and regenerative medicine. Despite significant progress in OOC development, several limitations of conventional microfluidic devices pose challenges. First, most microfluidic systems have rectangular cross sections and flat walls, and therefore tubular/ curved structures, like blood vessels and nephrons, are not well represented.

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Biological systems interact directly with the environment and learn by receiving multimodal feedback via sensory stimuli that shape the formation of internal neuronal representations. Drawing inspiration from biological concepts such as exploration and sensory processing that eventually lead to behavioral conditioning, we present a robotic system handling objects through multimodal learning. A small-scale organic neuromorphic circuit locally integrates and adaptively processes multimodal sensory stimuli, enabling the robot to interact intelligently with its surroundings.

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Cilia are slender, hair-like cell protrusions that are present ubiquitously in the natural world. They perform essential functions, such as generating fluid flow, propulsion, and feeding, in organisms ranging from protozoa to the human body. The coordinated beating of cilia, which results in wavelike motions known as metachrony, has fascinated researchers for decades for its role in functions such as flow generation and mucus transport.

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4D microstructured actuators are micro-objects made of stimuli-responsive materials capable of induced shape deformations, with applications ranging from microrobotics to smart micropatterned haptic surfaces. The novel technology dual-wavelength volumetric microlithography (DWVML) realizes rapid printing of high-resolution 3D microstructures and so has the potential to pave the way to feasible manufacturing of 4D microdevices. In this work, DWVML is applied for the first time to printing stimuli-responsive materials, namely, liquid crystal networks (LCNs).

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Hypothesis: Electronic paper displays rely on electrokinetic effects in nonpolar solvents to drive the displacement of colloidal particles within a fluidic cell. While Electrophoresis (EP) is a well-established and frequently employed phenomenon, electro-osmosis (EO), which drives fluid flow along charged solid surfaces, has not been studied as extensively. We hypothesize that by exploiting the interplay between these effects, an enhanced particle transport can be achieved.

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Despite recent advances in artificial cilia technologies, the application of metachrony, which is the collective wavelike motion by cilia moving out-of-phase, has been severely hampered by difficulties in controlling closely packed artificial cilia at micrometer length scales. Moreover, there has been no direct experimental proof yet that a metachronal wave in combination with fully reciprocal ciliary motion can generate significant microfluidic flow on a micrometer scale as theoretically predicted. In this study, using an in-house developed precise micro-molding technique, we have fabricated closely packed magnetic artificial cilia that can generate well-controlled metachronal waves.

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Metastasis is a multi-step process that is critically affected by cues from the tumor micro-environment (TME), such as from the extracellular matrix (ECM). The role of the ECM in the onset of metastasis, invasion, is not yet fully understood. A further complicating factor is that the ECM in the TME is mostly heterogeneous, in particular presenting a basement membrane (BM) directly enveloping the tumor, which acts as a barrier to invasion into the surrounding stromal ECM.

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Cancer-on-chip (CoC) models, based on microfluidic chips harboring chambers for 3D tumor-cell culture, enable us to create a controlled tumor microenvironment (TME). CoC models are therefore increasingly used to systematically study effects of the TME on the various steps in cancer metastasis. Moreover, CoC models have great potential for developing novel cancer therapies and for predicting patient-specific response to cancer treatments.

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Biological cilia, hairlike organelles on cell surfaces, often exhibit collective wavelike motion known as metachrony, which helps generating fluid flow. Inspired by nature, researchers have developed artificial cilia as microfluidic actuators, exploring several methods to mimic the metachrony. However, reported methods are difficult to miniaturize because they require either control of individual cilia properties or the generation of a complex external magnetic field.

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The key risk factor for glaucoma is increased intraocular pressure (IOP). Glaucoma drainage devices implanted in the eye can reduce IOP and thus stop disease progression. However, most devices currently used in clinical practice are passive and do not allow for postsurgical IOP control, which may result in serious complications such as hypotony (i.

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Evolution has produced natural systems that generate motion and sense external stimuli at the micro- and nanoscales. At extremely small scales, the intricate motions and large deformations shown by these biosystems are due to a tipping balance between their structural compliance and the actuating force generated in them. Artificially mimicking such ingenious systems for scientific and engineering applications has been approached through the development and use of different smart materials mostly limited to microscale dimensions.

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In cardiac fibrosis, in response to stress or injury, cardiac fibroblasts deposit excessive amounts of collagens which contribute to the development of heart failure. The biochemical stimuli in this process have been extensively studied, but the influence of cyclic deformation on the fibrogenic behavior of cardiac fibroblasts in the ever-beating heart is not fully understood. In fact, most investigated mechanotransduction pathways in cardiac fibroblasts seem to ultimately have profibrotic effects, which leaves an important question in cardiac fibrosis research unanswered: how do cardiac fibroblasts stay quiescent in the ever-beating human heart? In this study, we developed a human cardiac fibrosis-on-a-chip platform and utilized it to investigate if and how cyclic strain affects fibrogenic signaling.

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Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal.

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Research targeting the development of on-body sensors has been significantly growing in recent years - an example is on-skin sweat sensing. However, the wide inter and intra person variability of skin characteristics make testing of these sensors and included materials such as skin adhesives difficult, which hampers especially the initial development phase of such wearables. Besides the development of wearable sweat sensors, companies developing deodorants, cosmetics, medical adhesives and wearable textiles now need to perform expensive human subjects testing with little control over the exact sweat mechanisms.

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Hydrogels can exhibit a remarkably complex response to external stimuli and show rich mechanical behavior. Previous studies of the mechanics of hydrogel particles have generally focused on their static, rather than dynamic, response, as traditional methods for measuring single particle response at the microscopic scale cannot readily measure time-dependent mechanics. Here, we study both the static and the time-dependent response of a single batch of polyacrylamide (PAAm) particles by combining direct contact forces, applied by using Capillary Micromechanics, a method where particles are deformed in a tapered capillary, and osmotic forces are applied by a high molecular weight dextran solution.

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Optical transparency is highly desirable in bioelectronic sensors because it enables multimodal optical assessment during electronic sensing. Ultrathin (<5 µm) organic electrochemical transistors (OECTs) can be potentially used as a highly efficient bioelectronic transducer because they demonstrate high transconductance during low-voltage operation and close conformability to biological tissues. However, the fabrication of fully transparent ultrathin OECTs remains a challenge owing to the harsh etching processes of nanomaterials.

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Glaucoma is a group of eye conditions that damage the optic nerve, the health of which is vital for vision. The key risk factor for the development and progression of this disease is increased intraocular pressure (IOP). Implantable glaucoma drainage devices have been developed to divert aqueous humor from the glaucomatous eye as a means of reducing IOP.

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Article Synopsis
  • The study introduces a new microfluidic chip, the MPA-Chip, designed to efficiently isolate circulating tumor cells (CTCs) from the blood of cancer patients, aiming to improve cancer treatment monitoring.
  • The chip utilizes various micropillar geometries, with the lozenge design proving to be the most effective, achieving over 85% capture efficiency and over 90% purity in isolating CTCs.
  • Validation on breast cancer patients demonstrated that the MPA-Chip could indicate disease state and treatment response, showing a correlation between chemotherapy duration and a decrease in captured CTCs.
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Chemical monitoring communicates diverse environmental information from industrial and biological processes. However, promising and sustainable systems and associated inspection devices that dynamically enable on-site quality monitoring of target chemicals confined inside transformable and opaque channels are yet to be investigated. This paper designs stretchable photo-sensor patch sheets for nonsampling, source-free, and label-free on-site dynamic chemical monitoring of liquids flowing inside soft tubes via simple deformable surface wrapping.

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Cilia are microscopic hair-like external cell organelles that are ubiquitously present in nature, also within the human body. They fulfill crucial biological functions: motile cilia provide transportation of fluids and cells, and immotile cilia sense shear stress and concentrations of chemical species. Inspired by nature, scientists have developed artificial cilia mimicking the functions of biological cilia, aiming at application in microfluidic devices like lab-on-chip or organ-on-chip.

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This work presents a prototype system based on a multichannel receiving (RX) integrated circuit (IC) for contrast-enhanced ultrasound (CEUS) imaging. The RX IC is implemented in a 40-nm low-voltage CMOS technology and is designed to interface to a capacitive micromachined ultrasonic transducer array. To enable a direct connection of the RX electronics to the transducer, an analog multiplexer with on-chip protection circuitry is developed.

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