Absorbable cyst brushes.

Cytobrushes are used for low-invasive sample collection and screening in multiple diseases, with a significant impact on early detection, prevention, and diagnosis. This study focuses on improving the safety of cell brushing in hard-to-reach locations by exploring brush construction from absorbable materials. We investigated the efficacy of loop brushes made of absorbable suture wires of Chirlac, Chirasorb, Monocryl, PDS II, Vicryl Rapid, Glycolon, and Catgut during their operation in conjunction with fine-needle aspiration in an artificial cyst model. PDS II brushes demonstrated the highest efficiency, while Monocryl and Catgut also provided a significant brushing effect. Efficient brushes portrayed higher flexural rigidity than their counterparts, and their efficiency was inversely proportional to their plastic deformation by the needle. Our results open avenues for safer cell biopsies in hard-to-reach locations by utilizing brushes composed of absorbable materials.

Droplet Impact on Asymmetric Hydrophobic Microstructures.

Textured hydrophobic surfaces that repel liquid droplets unidirectionally are found in nature such as butterfly wings and ryegrass leaves and are also essential in technological processes such as self-cleaning and anti-icing. In many occasions, surface textures are oriented to direct rebounding droplets. Surface macrostructures (>100 µm) have often been explored to induce directional rebound. However, the influence of impact speed and detailed surface geometry on rebound is vaguely understood, particularly for small microstructures. Here, we study, using a high-speed camera, droplet impact on surfaces with inclined micropillars. We observed directional rebound at high impact speeds on surfaces with dense arrays of pillars. We attribute this asymmetry to the difference in wetting behavior of the structure sidewalls, causing slower retraction of the contact line in the direction against the inclination compared to with the inclination. The experimental observations are complemented with numerical simulations to elucidate the detailed movement of the drops over the pillars. These insights improve our understanding of droplet impact on hydrophobic microstructures and may be useful for designing structured surfaces for controlling droplet mobility.

Droplet Impact on Surfaces with Asymmetric Microscopic Features.

The impact of liquid drops on a rigid surface is central in cleaning, cooling, and coating processes in both nature and industrial applications. However, it is not clear how details of pores, roughness, and texture on the solid surface influence the initial stages of the impact dynamics. Here, we experimentally study drops impacting at low velocities onto surfaces textured with asymmetric (tilted) ridges. We found that the difference between impact velocity and the capillary speed on a solid surface is a key factor of spreading asymmetry, where the capillary speed is determined by the friction at a moving three-phase contact line. The line-friction capillary number Caf = µfV0/σ (where µf,V0, and σ are the line friction, impact velocity, and surface tension, respectively) is defined as a measure of the importance of the topology of surface textures for the dynamics of droplet impact. We show that when Caf ≪ 1, the droplet impact is asymmetric; the contact line speed in the direction against the inclination of the ridges is set by line friction, whereas in the direction with inclination, the contact line is pinned at acute corners of the ridges. When Caf ≫ 1, the geometric details of nonsmooth surfaces play little role.

Synthetic Paper Separates Plasma from Whole Blood with Low Protein Loss.

The separation of plasma from whole blood is the first step in many diagnostic tests. Point-of-care tests often rely on integrated plasma filters, but protein retention in such filters limits their performance. Here, we investigate plasma separation on interlocked micropillar scaffolds ("synthetic paper") by the local agglutination of blood cells coupled with the capillary separation of the plasma. We separated clinically relevant volumes of plasma with high efficiency in a separation time on par with that of state of the art techniques. We investigated different covalent and noncovalent surface treatments (PEGMA, HEMA, BSA, O2 plasma) on our blood filter and their effect on protein recovery and identified O2 plasma treatment and 7.9 µg/cm2 agglutination antibody as most suitable treatments. Using these treatments, we recovered at least 82% of the blood plasma proteins, more than with state-of-the-art filters. The simplicity of our device and the performance of our approach could enable better point-of-care tests.

Droplet leaping governs microstructured surface wetting.

Microstructured surfaces that control the direction of liquid transport are not only ubiquitous in nature, but they are also central to technological processes such as fog/water harvesting, oil-water separation, and surface lubrication. However, a fundamental understanding of the initial wetting dynamics of liquids spreading on such surfaces is lacking. Here, we show that three regimes govern microstructured surface wetting on short time scales: spread, stick, and contact line leaping. The latter involves establishing a new contact line downstream of the wetting front as the liquid leaps over specific sections of the solid surface. Experimental and numerical investigations reveal how different regimes emerge in different flow directions during wetting of periodic asymmetrically microstructured surfaces. These insights improve our understanding of rapid wetting in droplet impact, splashing, and wetting of vibrating surfaces and may contribute to advances in designing structured surfaces for the mentioned applications.

Capillary Pumping Independent of Liquid Sample Viscosity.

Capillary flow is a dominating liquid transport phenomenon on the micro- and nanoscale. As described at the beginning of the 20th century, the flow rate during imbibition of a horizontal capillary tube follows the Washburn equation, i.e., decreases over time and depends on the viscosity of the sample. This poses a problem for capillary driven systems that rely on a predictable flow rate and where the liquid viscosity is not precisely known. Here we introduce and successfully experimentally verify the first compact capillary pump design with a flow rate constant in time and independent of the liquid viscosity that can operate over an extended period of time. We also present a detailed theoretical model for gravitation-independent capillary filling, which predicts the novel pump performance to within measurement error margins, and in which we, for the first time, explicitly identify gas inertia dominated flow as a fourth distinct flow regime in capillary pumping. These results are of potential interest for a multitude of applications and we expect our results to find most immediate applications within lab-on-a-chip systems and diagnostic devices.

Performance of an innovative culture-based digital dipstick for detection of bacteriuria.

IMPORTANCE: In this study, we explore the transformative potential of UTI-lizer, an emerging technology not yet commercially available. Our manuscript shows that UTI-lizer is a promising alternative for detecting the five main pathogens that cause urinary tract infections (UTIs). The results also indicate that digital dipsticks have the potential to uniquely provide UTI diagnostic quality on par with that of gold-standard testing, with the added benefits of ease of testing, rapid test handling time, and simple test equipment. This technology can be helpful in quickly ruling out bacterial infections and reducing the unnecessary use of antibiotics, especially in primary care settings or at the point of care. Moreover, the UTI-lizer test can reduce the number of negative urine samples sent to central laboratories, thus easing the burden of UTI diagnostics on the healthcare system. We believe our study, as well as current and upcoming research based on this technology, is highly relevant for clinical microbiologists, microbiology scientists, general practitioners, and urologists.

3D-Printed Biohybrid Microstructures Enable Transplantation and Vascularization of Microtissues in the Anterior Chamber of the Eye.

Hybridizing biological cells with man-made sensors enable the detection of a wide range of weak physiological responses with high specificity. The anterior chamber of the eye (ACE) is an ideal transplantation site due to its ocular immune privilege and optical transparency, which enable superior noninvasive longitudinal analyses of cells and microtissues. Engraftment of biohybrid microstructures in the ACE may, however, be affected by the pupillary response and dynamics. Here, sutureless transplantation of biohybrid microstructures, 3D printed in IP-Visio photoresin, containing a precisely localized pancreatic islet to the ACE of mice is presented. The biohybrid microstructures allow mechanical fixation in the ACE, independent of iris dynamics. After transplantation, islets in the microstructures successfully sustain their functionality for over 20 weeks and become vascularized despite physical separation from the vessel source (iris) and immersion in a low-viscous liquid (aqueous humor) with continuous circulation and clearance. This approach opens new perspectives in biohybrid microtissue transplantation in the ACE, advancing monitoring of microtissue-host interactions, disease modeling, treatment outcomes, and vascularization in engineered tissues.

Integration of microfluidics with grating coupled silicon photonic sensors by one-step combined photopatterning and molding of OSTE.

We present a novel integration method for packaging silicon photonic sensors with polymer microfluidics, designed to be suitable for wafer-level production methods. The method addresses the previously unmet manufacturing challenges of matching the microfluidic footprint area to that of the photonics, and of robust bonding of microfluidic layers to biofunctionalized surfaces. We demonstrate the fabrication, in a single step, of a microfluidic layer in the recently introduced OSTE polymer, and the subsequent unassisted dry bonding of the microfluidic layer to a grating coupled silicon photonic ring resonator sensor chip. The microfluidic layer features photopatterned through holes (vias) for optical fiber probing and fluid connections, as well as molded microchannels and tube connectors, and is manufactured and subsequently bonded to a silicon sensor chip in less than 10 minutes. Combining this new microfluidic packaging method with photonic waveguide surface gratings for light coupling allows matching the size scale of microfluidics to that of current silicon photonic biosensors. To demonstrate the new method, we performed successful refractive index measurements of liquid ethanol and methanol samples, using the fabricated device. The minimum required sample volume for refractive index measurement is below one nanoliter.

Pt-Al2O3 dual layer atomic layer deposition coating in high aspect ratio nanopores.

Functional nanoporous materials are promising for a number of applications ranging from selective biofiltration to fuel cell electrodes. This work reports the functionalization of nanoporous membranes using atomic layer deposition (ALD). ALD is used to conformally deposit platinum (Pt) and aluminum oxide (Al(2)O(3)) on Pt in nanopores to form a metal-insulator stack inside the nanopore. Deposition of these materials inside nanopores allows the addition of extra functionalities to nanoporous materials such as anodic aluminum oxide (AAO) membranes. Conformal deposition of Pt on such materials enables increased performances for electrochemical sensing applications or fuel cell electrodes. An additional conformal Al(2)O(3) layer on such a Pt film forms a metal-insulator-electrolyte system, enabling field effect control of the nanofluidic properties of the membrane. This opens novel possibilities in electrically controlled biofiltration. In this work, the deposition of these two materials on AAO membranes is investigated theoretically and experimentally. Successful process parameters are proposed for a reliable and cost-effective conformal deposition on high aspect ratio three-dimensional nanostructures. A device consisting of a silicon chip supporting an AAO membrane of 6 mm diameter and 1.3 µm thickness with 80 nm diameter pores is fabricated. The pore diameter is reduced to 40 nm by a conformal deposition of 11 nm Pt and 9 nm Al(2)O(3) using ALD.

Efficient filter-in-centrifuge separation of low-concentration bacteria from blood.

Separating bacteria from infected blood is an important step in preparing samples for downstream bacteria detection and analysis. However, the extremely low bacteria concentration and extremely high blood cell count make efficient separation challenging. In this study, we introduce a method for separating bacteria from blood in a single centrifugation step, which involves sedimentation velocity-based differentiation followed by size-based cross-flow filtration over an inclined filter. Starting from 1 mL spiked whole blood, we recovered 32 ± 4% of the bacteria (Escherichia coli, Klebsiella pneumonia, or Staphylococcus aureus) within one hour while removing 99.4 ± 0.1% of the red blood cells, 98.4 ± 1.4% of the white blood cells, and 90.0 ± 2.6% of the platelets. Changing the device material could further increase bacteria recovery to >50%. We demonstrated bacterial recovery from blood spiked with 10 CFU mL-1. Our simple hands-off efficient separation of low-abundant bacteria approaches clinical expectations, making the new method a promising candidate for future clinical use.

Copper-mediated synthesis of temperature-responsive poly(N-acryloyl glycinamide) polymers: a step towards greener and simple polymerisation.

Stimuli-responsive materials with reversible supramolecular networks controlled by a change in temperature are of interest in medicine, biomedicine and analytical chemistry. For these materials to become more impactful, the development of greener synthetic practices with more sustainable solvents, lower energy consumption and a reduction in metallic catalysts is needed. In this work, we investigate the polymerisation of N-acryloyl glycinamide monomer by single-electron transfer reversible-deactivation radical polymerisation and its effect on the cloud point of the resulting PNAGA polymers. We accomplished 80% conversion within 5 min in water media using a copper wire catalyst. The material exhibited a sharp upper critical solution temperature (UCST) phase transition (10-80% transition within 6 K). These results indicate that UCST-exhibiting PNAGA can be synthesized at ambient temperatures and under non-inert conditions, eliminating the cost- and energy-consuming deoxygenation step. The choice of copper wire as the catalyst allows the possibility of catalyst recycling. Furthermore, we show that the reaction is feasible in a simple vial which would facilitate upscaling.

Scalable Production of Monodisperse Bioactive Spider Silk Nanowires.

Elongated protein-based micro- and nanostructures are of great interest for a wide range of biomedical applications, where they can serve as a backbone for surface functionalization and as vehicles for drug delivery. Current production methods for protein constructs lack precise control of either shape and dimensions or render structures fixed to substrates. This work demonstrates production of recombinant spider silk nanowires suspended in solution, starting with liquid bridge induced assembly (LBIA) on a substrate, followed by release using ultrasonication, and concentration by centrifugation. The significance of this method lies in that it provides i) reproducability (standard deviation of length <13% and of diameter <38%), ii) scalability of fabrication, iii) compatibility with autoclavation with retained shape and function, iv) retention of bioactivity, and v) easy functionalization both pre- and post-formation. This work demonstrates how altering the function and nanotopography of a surface by nanowire coating supports the attachment and growth of human mesenchymal stem cells (hMSCs). Cell compatibility is further studied through integration of nanowires during aggregate formation of hMSCs and the breast cancer cell line MCF7. The herein-presented industrial-compatible process enables silk nanowires for use as functionalizing agents in a variety of cell culture applications and medical research.

Soft metamaterial with programmable ferromagnetism.

Magnetopolymers are of interest in smart material applications; however, changing their magnetic properties post synthesis is complicated. In this study, we introduce easily programmable polymer magnetic composites comprising 2D lattices of droplets of solid-liquid phase change material, with each droplet containing a single magnetic dipole particle. These composites are ferromagnetic with a Curie temperature defined by the rotational freedom of the particles above the droplet melting point. We demonstrate magnetopolymers combining high remanence characteristics with Curie temperatures below the composite degradation temperature. We easily reprogram the material between four states: (1) a superparamagnetic state above the melting point which, in the absence of an external magnetic field, spontaneously collapses to; (2) an artificial spin ice state, which after cooling forms either; (3) a spin glass state with low bulk remanence, or; (4) a ferromagnetic state with high bulk remanence when cooled in the presence of an external magnetic field. We observe the spontaneous emergence of 2D magnetic vortices in the spin ice and elucidate the correlation of these vortex structures with the external bulk remanence. We also demonstrate the easy programming of magnetically latching structures.

Semi-automated preparation of fine-needle aspiration samples for rapid on-site evaluation.

Rapid on-site evaluation (ROSE) significantly improves the diagnostic yield of fine needle aspiration (FNA) samples but critically depends on the skills and availability of cytopathologists. Here, we introduce a portable device for semi-automated sample preparation for ROSE. In a single platform, the device combines a smearing tool and a capillary-driven chamber for staining FNA samples. Using a human pancreatic cancer cell line (PANC-1) and liver, lymph node, and thyroid FNA model samples, we demonstrate the capability of the device to prepare samples for ROSE. By minimizing the equipment needed in the operating room, the device may simplify the performance of FNA sample preparation and lead to a wider implementation of ROSE.

Bioengineered Pancreas-Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia.

Aberrant glucose homeostasis is the most common metabolic disturbance affecting one in ten adults worldwide. Prediabetic hyperglycemia due to dysfunctional interactions between different human tissues, including pancreas and liver, constitutes the largest risk factor for the development of type 2 diabetes. However, this early stage of metabolic disease has received relatively little attention. Microphysiological tissue models that emulate tissue crosstalk offer emerging opportunities to study metabolic interactions. Here, a novel modular multitissue organ-on-a-chip device is presented that allows for integrated and reciprocal communication between different 3D primary human tissue cultures. Precisely controlled heterologous perfusion of each tissue chamber is achieved through a microfluidic single "synthetic heart" pneumatic actuation unit connected to multiple tissue chambers via specific configuration of microchannel resistances. On-chip coculture experiments of organotypic primary human liver spheroids and intact primary human islets demonstrate insulin secretion and hepatic insulin response dynamics at physiological timescales upon glucose challenge. Integration of transcriptomic analyses with promoter motif activity data of 503 transcription factors reveals tissue-specific interacting molecular networks that underlie ß-cell stress in prediabetic hyperglycemia. Interestingly, liver and islet cultures show surprising counter-regulation of transcriptional programs, emphasizing the power of microphysiological coculture to elucidate the systems biology of metabolic crosstalk.

Sustained superhydrophobic friction reduction at high liquid pressures and large flows.

This Article introduces and experimentally explores a novel self-regulating method for reducing the friction losses in large microchannels at high liquid pressures and large liquid flows, overcoming previous limitations with regard to sustainable liquid pressure on a superhydrophobic surface. Our design of the superhydrophobic channel automatically adjusts the gas pressure in the lubricating air layer to the local liquid pressure in the channel. This is achieved by pneumatically connecting the liquid in the microchannel to the gas-pockets trapped at the channel wall through a pressure feedback channel. When liquid enters the feedback channel, it compresses the air and increases the pressure in the gas-pocket. This reduces the pressure drop over the gas-liquid interface and increases the maximum sustainable liquid pressure. We define a dimensionless figure of merit for superhydropbic flows, W(F) = P(L)D/γ cos(θ(c)), which expresses the fluidic energy carrying capacity of a superhydrophobic microchannel. We experimentally verify that our geometry can sustain three times higher liquid pressure before collapsing, and we measured better friction-reducing properties at higher W(F) values than in previous works. The design is ultimately limited in time by the gas-exchange over the gas-liquid interface at pressures exceeding the Laplace pressure. This method could be applicable for reducing near-wall laminar friction in both micro and macro scale flows.

Fibrillar Nanomembranes of Recombinant Spider Silk Protein Support Cell Co-culture in an In Vitro Blood Vessel Wall Model.

Basement membrane is a thin but dense network of self-assembled extracellular matrix (ECM) protein fibrils that anchors and physically separates epithelial/endothelial cells from the underlying connective tissue. Current replicas of the basement membrane utilize either synthetic or biological polymers but have not yet recapitulated its geometric and functional complexity highly enough to yield representative in vitro co-culture tissue models. In an attempt to model the vessel wall, we seeded endothelial and smooth muscle cells on either side of 470 ± 110 nm thin, mechanically robust, and nanofibrillar membranes of recombinant spider silk protein. On the apical side, a confluent endothelium formed within 4 days, with the ability to regulate the permeation of representative molecules (3 and 10 kDa dextran and IgG). On the basolateral side, smooth muscle cells produced a thicker ECM with enhanced barrier properties compared to conventional tissue culture inserts. The membranes withstood 520 ± 80 Pa pressure difference, which is of the same magnitude as capillary blood pressure in vivo. This use of protein nanomembranes with relevant properties for co-culture opens up for developing advanced in vitro tissue models for drug screening and potent substrates in organ-on-a-chip systems.

On-chip temperature compensation in an integrated slot-waveguide ring resonator refractive index sensor array.

We present an experimental study of an integrated slot-waveguide refractive index sensor array fabricated in silicon nitride on silica. We study the temperature dependence of the slot-waveguide ring resonator sensors and find that they show a low temperature dependence of -16.6 pm/K, while at the same time a large refractive index sensitivity of 240 nm per refractive index unit. Furthermore, by using on-chip temperature referencing, a differential temperature sensitivity of only 0.3 pm/K is obtained, without individual sensor calibration. This low value indicates good sensor-to-sensor repeatability, thus enabling use in highly parallel chemical assays. We demonstrate refractive index measurements during temperature drift and show a detection limit of 8.8 x 10-6 refractive index units in a 7 K temperature operating window, without external temperature control. Finally, we suggest the possibility of athermal slot-waveguide sensor design.

Digital dipstick: miniaturized bacteria detection and digital quantification for the point-of-care.

Established digital bioassay formats, digital PCR and digital ELISA, show extreme limits of detection, absolute quantification and high multiplexing capabilities. However, they often require complex instrumentation, and extensive off-chip sample preparation. In this study, we present a dipstick-format digital biosensor (digital dipstick) that detects bacteria directly from the sample liquid with a minimal number of steps: dip, culture, and count. We demonstrate the quantitative detection of Escherichia coli (E. coli) in urine in the clinically relevant range of 102-105 CFU ml-1 for urinary tract infections. Our format shows 89% sensitivity to detect E. coli in clinical urine samples (n = 28) when it is compared to plate culturing (gold standard). The significance and uniqueness of this diagnostic test format is that it allows a non-trained operator to detect urinary tract infections in the clinically relevant range in the home setting.