Deconvolution volumetric additive manufacturing.

Volumetric additive manufacturing techniques are a promising pathway to ultra-rapid light-based 3D fabrication. Their widespread adoption, however, demands significant improvement in print fidelity. Currently, volumetric additive manufacturing prints suffer from systematic undercuring of fine features, making it impossible to print objects containing a wide range of feature sizes, precluding effective adoption in many applications. Here, we uncover the reason for this limitation: light dose spread in the resin due to chemical diffusion and optical blurring, which becomes significant for features ⪅0.5 mm. We develop a model that quantitatively predicts the variation of print time with feature size and demonstrate a deconvolution method to correct for this error. This enables prints previously beyond the capabilities of volumetric additive manufacturing, such as a complex gyroid structure with variable thickness and a fine-toothed gear. These results position volumetric additive manufacturing as a mature 3D printing method, all but eliminating the gap to industry-standard print fidelity.

Volumetric Printing of Thiol-Ene Photo-Cross-Linkable Poly(ε-caprolactone): A Tunable Material Platform Serving Biomedical Applications.

Current thoroughly described biodegradable and cross-linkable polymers mainly rely on acrylate cross-linking. However, despite the swift cross-linking kinetics of acrylates, the concomitant brittleness of the resulting materials limits their applicability. Here, photo-cross-linkable poly(ε-caprolactone) networks through orthogonal thiol-ene chemistry are introduced. The step-growth polymerized networks are tunable, predictable by means of the rubber elasticity theory and it is shown that their mechanical properties are significantly improved over their acrylate cross-linked counterparts. Tunability is introduced to the materials, by altering Mc (or the molar mass between cross-links), and its effect on the thermal properties, mechanical strength and degradability of the materials is evaluated. Moreover, excellent volumetric printability is illustrated and the smallest features obtained via volumetric 3D-printing to date are reported, for thiol-ene systems. Finally, by means of in vitro and in vivo characterization of 3D-printed constructs, it is illustrated that the volumetrically 3D-printed materials are biocompatible. This combination of mechanical stability, tunability, biocompatibility, and rapid fabrication by volumetric 3D-printing charts a new path toward bedside manufacturing of biodegradable patient-specific implants.

Optical reflectance imaging reveals interlayer coupling in mechanically stacked MoS2 and WS2 bilayers.

Optical reflectance imaging is a popular technique for characterizing 2D materials, thanks to its simplicity and speed of data acquisition. The use of this method for studying interlayer phenomena in stacked 2D layers has, however, remained limited. Here we demonstrate that optical imaging can reveal the nature of interlayer coupling in stacked MoS2 and WS2 bilayers through their observed reflectance contrast versus the substrate. Successful determination of interlayer coupling requires co-optimization of the illumination wavelength and the thickness of an underlying SiO2 film. Our observations are supported by multilayer optical calculations together with an analysis of the effect of any interlayer gap. This approach promises quick characterization of constructed 2D material systems.

Ethyl Cellulose-Based Thermoreversible Organogel Photoresist for Sedimentation-Free Volumetric Additive Manufacturing.

Liquid photoresists are abundant in the field of light-based additive manufacturing (AM). However, printing unsupported directly into a vat of material in emerging volumetric AM technologies-typically a benefit due to fewer geometric constraints and less material waste-can be a limitation when printing low-viscosity liquid monomers and multimaterial constructs due to part drift or sedimentation. With ethyl cellulose (EC), a thermoplastic soluble in organic liquids, a simple three-component transparent thermoreversible gel photoresist with melting temperature of ≈64 °C is formulated. The physically crosslinked network of the gel leads to storage moduli in the range of 0.1-10 kPa and maximum yield stress of 2.7 kPa for a 10 wt% EC gel photoresist. Nonzero yield stress enables sedimentation-free tomographic volumetric patterning in low-viscosity monomer without additional hardware or modification of apparatus. In addition, objects inserted into the print container can be suspended in the gel material which enables overprinting of multimaterial devices without anchors connecting the object to the printing container. Flexural strength is also improved by 100% compared to the neat monomer for a formulation with 7 wt% EC.

Sectorization of Macromolecular Single Crystals Unveiled by Probing Shear Anisotropy.

Polymer single crystals continue to infiltrate emerging technologies such as flexible organic field-effect transistors because of their excellent translational symmetry and chemical purity. However, owing to the methodological challenges, direct imaging of the polymer chains folding direction resulting in sectorization of single crystals has rarely been investigated. Herein, we directly image the sectorization of polymer single crystals through anisotropic elastic deformation on the surface of macromolecular single crystals. A variant of friction force microscopy, in which the scanning direction of the probe tip is parallel with the cantilever axis, allows for high contrast imaging of the sectorization in polymer single crystals. The lateral deflection of the cantilever resulting from shear forces transverse to the scan direction shows a close connection with the in-plane components of the elastic tensor of the polymer single crystals, which is of a fundamentally different origin than the friction forces. This allows for fast, facile, and nondestructive characterization of the microstructure and in-plane elastic anisotropy of compliant crystalline materials such as polymers.

Volumetric additive manufacturing of silica glass with microscale computed axial lithography.

Glass is increasingly desired as a material for manufacturing complex microscopic geometries, from the micro-optics in compact consumer products to microfluidic systems for chemical synthesis and biological analyses. As the size, geometric, surface roughness, and mechanical strength requirements of glass evolve, conventional processing methods are challenged. We introduce microscale computed axial lithography (micro-CAL) of fused silica components, by tomographically illuminating a photopolymer-silica nanocomposite that is then sintered. We fabricated three-dimensional microfluidics with internal diameters of 150 micrometers, free-form micro-optical elements with a surface roughness of 6 nanometers, and complex high-strength trusses and lattice structures with minimum feature sizes of 50 micrometers. As a high-speed, layer-free digital light manufacturing process, micro-CAL can process nanocomposites with high solids content and high geometric freedom, enabling new device structures and applications.

Friction of Ti3C2Tx MXenes.

2D materials are well-known for their low-friction behavior by modifying the interfacial forces at atomic surfaces. Of the wide range of 2D materials, MXenes represent an emerging material class but their lubricating behavior has been scarcely investigated. Herein, the friction mechanisms of 2D Ti3C2Tx MXenes are demonstrated which are attributed to their surface terminations. We find that Ti3C2Tx MXenes do not exhibit the well-known frictional layer dependence of other 2D materials. Instead, the nanoscale lubricity of 2D MXenes is governed by the termination species resulting from synthesis. Annealing the MXenes demonstrate a 7% reduction in OH termination which translates to a 16-57% reduction of friction in agreement with DFT calculations. Finally, the stability of MXene flakes is demonstrated upon isolation from their aqueous environment. This work indicates that MXenes can provide sustainable lubricity at any thickness which makes them uniquely positioned among 2D material lubricants.

Latent image volumetric additive manufacturing.

Volumetric additive manufacturing (VAM) enables rapid printing into a wide range of materials, offering significant advantages over other printing technologies, with a lack of inherent layering of particular note. However, VAM suffers from striations, similar in appearance to layers, and similarly limiting applications due to mechanical and refractive index inhomogeneity, surface roughness, etc. We hypothesize that these striations are caused by a self-written waveguide effect, driven by the gelation material nonlinearity upon which VAM relies, and that they are not a direct recording of non-uniform patterning beams. We demonstrate a simple and effective method of mitigating striations via a uniform optical exposure added to the end of any VAM printing process. We show this step to additionally shorten the period from initial gelation to print completion, mitigating the problem of partially gelled parts sinking before print completion, and expanding the range of resins printable in any VAM printer.

Object-Space Optimization of Tomographic Reconstructions for Additive Manufacturing.

Volumetric 3D printing motivated by computed axial lithography enables rapid printing of homogeneous parts but requires a high dimensionality gradient-descent optimization to calculate image sets. Here we introduce a new, simpler approach to image-computation that algebraically optimizes a model of the printed object, significantly improving print accuracy of complex parts under imperfect material and optical precision by improving optical dose contrast between the target and surrounding regions. Quality metrics for volumetric printing are defined and shown to be significantly improved by the new algorithm. The approach is extended beyond binary printing to grayscale control of conversion to enable functionally graded materials. The flexibility of the technique is digitally demonstrated with realistic projector point spread functions, printing around occluding structures, printing with restricted angular range, and incorporation of materials chemistry such as inhibition. Finally, simulations show that the method facilitates new printing modalities such as printing into flat, rather than cylindrical packages to extend the applications of volumetric printing.

Recent advances in microfluidic methods in cancer liquid biopsy.

Early cancer detection, its monitoring, and therapeutical prediction are highly valuable, though extremely challenging targets in oncology. Significant progress has been made recently, resulting in a group of devices and techniques that are now capable of successfully detecting, interpreting, and monitoring cancer biomarkers in body fluids. Precise information about malignancies can be obtained from liquid biopsies by isolating and analyzing circulating tumor cells (CTCs) or nucleic acids, tumor-derived vesicles or proteins, and metabolites. The current work provides a general overview of the latest on-chip technological developments for cancer liquid biopsy. Current challenges for their translation and their application in various clinical settings are discussed. Microfluidic solutions for each set of biomarkers are compared, and a global overview of the major trends and ongoing research challenges is given. A detailed analysis of the microfluidic isolation of CTCs with recent efforts that aimed at increasing purity and capture efficiency is provided as well. Although CTCs have been the focus of a vast microfluidic research effort as the key element for obtaining relevant information, important clinical insights can also be achieved from alternative biomarkers, such as classical protein biomarkers, exosomes, or circulating-free nucleic acids. Finally, while most work has been devoted to the analysis of blood-based biomarkers, we highlight the less explored potential of urine as an ideal source of molecular cancer biomarkers for point-of-care lab-on-chip devices.

Volumetric additive manufacturing via tomographic reconstruction.

Additive manufacturing promises enormous geometrical freedom and the potential to combine materials for complex functions. The speed, geometry, and surface quality limitations of additive processes are linked to their reliance on material layering. We demonstrated concurrent printing of all points within a three-dimensional object by illuminating a rotating volume of photosensitive material with a dynamically evolving light pattern. We printed features as small as 0.3 millimeters in engineering acrylate polymers and printed soft structures with exceptionally smooth surfaces into a gelatin methacrylate hydrogel. Our process enables us to construct components that encase other preexisting solid objects, allowing for multimaterial fabrication. We developed models to describe speed and spatial resolution capabilities and demonstrated printing times of 30 to 120 seconds for diverse centimeter-scale objects.

Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells.

Circulating tumor cells (CTCs) play an essential role in the metastasis of tumors, and thus can serve as a valuable prognostic factor for malignant diseases. As a result, the ability to isolate and characterize CTCs is essential. This review underlines the potential of dielectrophoresis for CTCs enrichment. It begins by summarizing the key performance parameters and challenges of CTCs isolation using microfluidics. The two main categories of CTCs enrichment-affinity-based and label-free methods-are analysed, emphasising the advantages and disadvantages of each as well as their clinical potential. While the main argument in favour of affinity-based methods is the strong specificity of CTCs isolation, the major advantage of the label-free technologies is in preserving the integrity of the cellular membrane, an essential requirement for downstream characterization. Moving forward, we try to answer the main question: "What makes dielectrophoresis a method of choice in CTCs isolation?" The uniqueness of dielectrophoretic CTCs enrichment resides in coupling the specificity of the isolation process with the conservation of the membrane surface. The specificity of the dielectrophoretic method stems from the differences in the dielectric properties between CTCs and other cells in the blood: the capacitances of the malignantly transformed cellular membranes of CTCs differ from those of other cells. Examples of dielectrophoretic devices are described and their performance evaluated. Critical requirements for using dielectrophoresis to isolate CTCs are highlighted. Finally, we consider that DEP has the potential of becoming a cytometric method for large-scale sorting and characterization of cells.

Review Article: Capturing the physiological complexity of the brain's neuro-vascular unit in vitro.

With the accelerating pace of brain research in recent years and the growing appreciation of the complexity of the brain and several brain-associated neurological diseases, the demand for powerful tools to enhance drug screening, diagnosis, and fundamental research is greater than ever. Highly representative models of the central nervous system (CNS) can play a critical role in meeting these needs. Unfortunately, in vivo animal models lack controllability, are difficult to monitor, and do not model human-specific brain behavior accurately. On the other hand, in silico computational models struggle to capture comprehensively the intertwined biological, chemical, electrical, and mechanical complexity of the brain. This leaves us with the promising domain of "organ-on-chip" in vitro models. In this review, we describe some of the most pioneering efforts in this expanding field, offering a perspective on the new possibilities as well as the limitations of each approach. We focus particularly on how the models reproduce the blood-brain barrier (BBB), which mediates mass transport to and from brain tissue. We also offer a brief commentary on strategies for evaluating the blood-brain barrier functionality of these in vitro models, including trans-endothelial electrical resistance (TEER), immunocytochemistry, and permeability analysis. From the early membrane-based models of the BBB that have grown into the Transwell® class of devices, to the era of microfluidic chips and a future of bio-printed tissue, we see enormous improvement in the reliability of in vitro models. More and more of the biological and structural complexity of the BBB is being captured by microfluidic chips, and the organ-specificity of bio-printed tissue is also significantly improved. Although we believe that the long-term solution will eventually take the form of automated and parallelized bio-printing systems, we find that valuable transport studies can already be accomplished with microfluidic platforms.

Controlled folding of graphene: GraFold printing.

We have used elastomeric stamps with periodically varying adhesive properties to introduce structure and print folded graphene films. The structure of the induced folds is investigated with scanning probe techniques, high-resolution electron-microscopy, and tip-enhanced Raman spectroscopy. Furthermore, a finite element model is developed to show the fold formation process. Terahertz spectroscopy reveals induced anisotropy of carrier mobility along, and perpendicular to, the graphene folds. Graphene fold printing is a new technique which allows for significant modification of the properties of 2D materials without damaging or chemically modifying them.

A practical guide for the fabrication of microfluidic devices using glass and silicon.

This paper describes the main protocols that are used for fabricating microfluidic devices from glass and silicon. Methods for micropatterning glass and silicon are surveyed, and their limitations are discussed. Bonding methods that can be used for joining these materials are summarized and key process parameters are indicated. The paper also outlines techniques for forming electrical connections between microfluidic devices and external circuits. A framework is proposed for the synthesis of a complete glass/silicon device fabrication flow.

Large-area and high-resolution distortion measurement based on Moiré fringe method for hot embossing process.

A Moiré fringe approach is developed to identify simultaneously the global and local distortions in hot-embossed polymeric samples. A square grid pattern with a pitch of 63.5 microm is hot-embossed on the polymer substrate. When a reference grid, a polymeric film with the same pattern, is placed on top of the sample, a Moiré fringe pattern is observed and recorded by a document scanner. The deviation of the intersections of the fringes from their ideal positions presents the residual distortion in the sample. With different sample-reference rotation angles eight images are acquired for the same sample to achieve the optimal result by a data fitting technique. The validity of this method is proved by the self-consistency of the results from the eight images. To the best of our knowledge, this is the first time distortion quantification has been achieved both in a large area up to that of a scanner and with a high resolution at the level of 1 microm. Furthermore, we do not use any expensive instrument, nor need to measure the sample-reference rotation angle or position the sample precisely, and the process is run automatically by a computer instead of manual operation.