Innovative Fabrication of Hollow Microneedle Arrays Enabling Blood Sampling with a Self-Powered Microfluidic Patch.

Microneedles are gaining a lot of attention in the context of sampling cutaneous biofluids such as capillary blood. Their minimal invasiveness and user-friendliness make them a prominent substitute for venous puncture or finger-pricking. Although the latter is suitable for self-sampling, the impracticality of manual handling and the difficulty of obtaining enough qualitative sample is driving the search for better solutions. In this context, hollow microneedle arrays (HMNAs) are particularly interesting for completely integrating sample-to-answer solutions as they create a duct between the skin and the sampling device. However, the fabrication of sharp-tipped HMNAs with a high aspect ratio (AR) is challenging, especially since a length of ≥1500 µm is desired to reach the blood capillaries. In this paper, we first described a novel two-step fabrication protocol for HMNAs in stainless steel by percussion laser drilling and subsequent micro-milling. The HMNAs were then integrated into a self-powered microfluidic sampling patch, containing a capillary pump which was optimized to generate negative pressure differences up to 40.9 ± 1.8 kPa. The sampling patch was validated in vitro, showing the feasibility of sampling 40 µL of liquid. It is anticipated that our proof-of-concept is a starting point for more sophisticated all-in-one biofluid sampling and point-of-care testing systems.

Microstructural changes enhance oxygen transport in tomato (Solanum lycopersicum) fruit during maturation and ripening.

Climacteric ripening of tomato fruit is initiated by a characteristic surge of the production rate of ethylene, accompanied by an increase in respiration rate. As both activities consume O2 and produce CO2 , gas concentration gradients develop in the fruit that cause diffusive transport. This may, in turn, affect respiration and ethylene biosynthesis. Gas diffusion in fruit depends on the amount and connectivity of cells and intercellular spaces in 3D. We investigated micromorphological changes in different tomato tissues during development and ripening by visualizing cells and pores based on high-resolution micro-computed tomography, and computed effective O2 diffusivity coefficients based on microstructural features of the tissues. We demonstrated that mesocarp and septa tissues have larger cells but small and more disconnected pores than the placenta and columella, resulting in relatively lower effective O2 diffusivity coefficients. Cell disintegration occurred in the mesocarp and septa during ripening, indicating lysigenous air pore formation and resulting in a gradual increase of the effective O2 diffusivity. The results suggest that hypoxic conditions caused by the increasing size and, hence, diffusion resistance of the growing fruit may induce an increase of tissue porosity that results in a greatly enhanced O2 diffusivity and, thus, helps to alleviate them.

X-ray computed tomography for 3D plant imaging.

X-ray computed tomography (CT) is a valuable tool for 3D imaging of plant tissues and organs. Applications include the study of plant development and organ morphogenesis, as well as modeling of transport processes in plants. Some challenges remain, however, including attaining higher contrast for easier quantification, increasing the resolution for imaging subcellular features, and decreasing image acquisition and processing time for high-throughput phenotyping. In addition, phase contrast, multispectral, dark-field, soft X-ray, and time-resolved imaging are emerging. At the same time, a large amount of 3D image data are becoming available, posing challenges for data management. We review recent advances in the area of X-ray CT for plant imaging, and describe opportunities for using such images for studying transport processes in plants.

3D Printing of Monolithic Capillarity-Driven Microfluidic Devices for Diagnostics.

Rapid diagnostic testing at the site of the patient is essential when a fully equipped laboratory is not accessible. To maximize the impact of this approach, low-cost, disposable tests that require minimal user-interference and external equipment are desired. Fluid transport by capillary wicking removes the need for bulky ancillary equipment to actuate and control fluid flow. Nevertheless, current microfluidic paper-based analytical devices based on this principle struggle with the implementation of multistep diagnostic protocols because of fabrication-related issues. Here, 3D-printed microfluidic devices are demonstrated in a proof-of-concept enzyme-linked immunosorbent assay in which a multistep assay timeline is completed by precisely engineering capillary wetting within printed porous bodies. 3D printing provides a scalable route to low-cost microfluidic devices and obviates the assembly of discrete components. The resulting rapid and seamless transition between digital data and physical objects allows for rapid design iterations, and opens up perspectives on distributed manufacturing.

Designing Mechanical Properties of 3D Printed Cookies through Computer Aided Engineering.

Additive manufacturing or 3D printing can be applied in the food sector to create food products with personalized properties such as shape, texture, and composition. In this article, we introduce a computer aided engineering (CAE) methodology to design 3D printed food products with tunable mechanical properties. The focus was on the Young modulus as a proxy of texture. Finite element modelling was used to establish the relationship between the Young modulus of 3D printed cookies with a honeycomb structure and their structure parameters. Wall thickness, cell size, and overall porosity were found to influence the Young modulus of the cookies and were, therefore, identified as tunable design parameters. Next, in experimental tests, it was observed that geometry deformations arose during and after 3D printing, affecting cookie structure and texture. The 3D printed cookie porosity was found to be lower than the designed one, strongly influencing the Young modulus. After identifying the changes in porosity through X-ray micro-computed tomography, a good match was observed between computational and experimental Young's modulus values. These results showed that changes in the geometry have to be quantified and considered to obtain a reliable prediction of the Young modulus of the 3D printed cookies.

Correction: 4D synchrotron microtomography and pore-network modelling for direct in situ capillary flow visualization in 3D printed microfluidic channels.

Correction for '4D synchrotron microtomography and pore-network modelling for direct in situ capillary flow visualization in 3D printed microfluidic channels' by Agnese Piovesan et al., Lab Chip, 2020, 20, 2403-2411, DOI: .

4D synchrotron microtomography and pore-network modelling for direct in situ capillary flow visualization in 3D printed microfluidic channels.

Powder-based 3D printing was employed to produce porous, capillarity-based devices suitable for passive microfluidics. Capillary imbibition in such devices was visualized in situ through dynamic synchrotron X-ray microtomography performed at the European Synchrotron Radiation Facility (ESRF) with sub-second time resolution. The obtained reconstructed images were segmented to observe imbibition dynamics, as well as to compute the system effective contact angle and to generate a pore-network to model capillary imbibition. A contact angle gradient was observed resulting in a preferential wicking direction, with the central portion of the microfluidic channel filling faster than the edge areas. The contact angle analysis and the pore-network model results suggest that this is due to spatial variations in the material surface properties arising from both the 3D printing and the subsequent drying processes.

Pore network model for permeability characterization of three-dimensionally-printed porous materials for passive microfluidics.

Stand-alone and portable lab-on-chips (LOC) can be obtained by exploiting capillary flow in porous media. Polymethylmethacrylate (PMMA) platforms obtained through powder-based three-dimensional (3D) printing are appropriate for capillarity-driven LOCs. However, fluid flow in such platforms needs to be characterized well. For this purpose, a 3D pore network (PN) was extracted from high-resolution µCT images of printed PMMA through a watershed algorithm and a PN model was developed with the final goal of characterizing material permeability. The effect of all parameters involved in the PN extraction and modeling was investigated. The study focused in particular on the effect of the number of seeds for the watershed segmentation, pore sphericity, and pore-to-pore channel shape that was modeled as a bicylindrical or biconical object. The results proved that all PN extraction and modeling parameters influenced the permeability, which was found to be lower the higher the number of seeds and when using sphericity and biconical channels. Eventually, the Calinski-Harabasz index value was used to identify the optimal number of watershed seeds.

Computational and Experimental Fatigue Analysis of Contoured Spinal Rods.

Posterior fixation with contoured rods is an established methodology for the treatment of spinal deformities. Both uniform industrial preforming and intraoperative contouring introduce tensile and compressive plastic deformations, respectively, at the concave and at the convex sides of the rod. The purpose of this study is to develop a validated numerical framework capable of predicting how the fatigue behavior of contoured spinal rods is affected by residual stresses when loaded in lordotic and kyphotic configurations. Established finite element models (FEM) describing static contouring were implemented as a preliminary simulation step and were followed by subsequent cyclical loading steps. The equivalent Sines stress distribution predicted in each configuration was compared to that in straight rods (SR) and related to the corresponding experimental number of cycles to failure. In the straight configuration, the maximum equivalent stress (441 MPa) exceeds the limit curve, as confirmed by experimental rod breakage after around 1.9 × 105 loading cycles. The stresses further increased in the lordotic configuration, where failure was reached within 2.4 × 104 cycles. The maximum equivalent stress was below the limit curve for the kyphotic configuration (640 MPa), for which a run-out of 106 cycles was reached. Microscopy inspection confirmed agreement between numerical predictions and experimental fatigue crack location. The contouring technique (uniform contouring (UC) or French bender (FB)) was not related to any statistically significant difference. Our study demonstrates the key role of residual stresses in altering the mean stress component, superposing to the tensile cyclic load, potentially explaining the higher failure rate of lordotic rods compared to kyphotic ones.

Residual Stresses in Titanium Spinal Rods: Effects of Two Contouring Methods and Material Plastic Properties.

Posterior spinal fixation based on long spinal rods is the clinical gold standard for the treatment of severe deformities. Rods need to be contoured prior to implantation to fit the natural curvature of the spine. The contouring processes is known to introduce residual stresses and strains which affect the static and fatigue mechanical response of the implant, as determined through time- and cost-consuming experimental tests. Finite element (FE) models promise to provide an immediate understanding on residual stresses and strains within a contoured spinal rods and a further insight on their complex distribution. This study aims at investigating two rod contouring strategies, French bender (FB) contouring (clinical gold standard), and uniform contouring, through validated FE models. A careful characterization of the elastoplastic material response of commercial implants is led. Compared to uniform contouring, FB induces highly localized plasticizations in compression under the contouring pin with extensive lateral sections undergoing tensile residual stresses. The sensitivity analysis highlighted that the assumed postyielding properties significantly affect the numerical predictions; therefore, an accurate material characterization is recommended.