3D printed microfluidic valve on PCB for flow control applications using liquid metal.

Direct 3D printing of active microfluidic elements on PCB substrates enables high-speed fabrication of stand-alone microdevices for a variety of health and energy applications. Microvalves are key components of microfluidic devices and liquid metal (LM) microvalves exhibit promising flow control in microsystems integrated with PCBs. In this paper, we demonstrate LM microvalves directly 3D printed on PCB using advanced digital light processing (DLP). Electrodes on PCB are coated by carbon ink to prevent alloying between gallium-based LM plug and copper electrodes. We used DLP 3D printers with in-house developed acrylic-based resins, Isobornyl Acrylate, and Diurethane Dimethacrylate (DUDMA) and functionalized PCB surface with acrylic-based resin for strong bonding. Valving seats are printed in a 3D caterpillar geometry with chamber diameter of 700 µm. We successfully printed channels and nozzles down to 90 µm. Aiming for microvalves for low-power applications, we applied square-wave voltage of 2 Vpp at a range of frequencies between 5 to 35 Hz. The results show precise control of the bistable valving mechanism based on electrochemical actuation of LMs.

Tungsten Oxide Coated Liquid Metal Electrodes via Galvanic Replacement as Heavy Metal Ion Sensors.

Gallium liquid metals (LMs) like Galinstan and eutectic Gallium-Indium (EGaIn) have seen increasing applications in heavy metal ion (HMI) sensing, because of their ability to amalgamate with HMIs like lead, their high hydrogen potential, and their stable electrochemical window. Furthermore, coating LM droplets with nanopowders of tungsten oxide (WO) has shown enhancement in HMI sensing owing to intense electrical fields at the nanopowder-liquid-metal interface. However, most LM HMI sensors are droplet based, which show limitations in scalability and the homogeneity of the surface. A scalable approach that can be extended to LM electrodes is therefore highly desirable. In this work, we present, for the first time, WO-Galinstan HMI sensors fabricated via photolithography of a negative cavity, Galinstan brushing inside the cavity, lift-off, and galvanic replacement (GR) in a tungsten salt solution. Successful GR of Galinstan was verified using optical microscopy, SEM, EDX, XPS, and surface roughness measurements of the Galinstan electrodes. The fabricated WO-Galinstan electrodes demonstrated enhanced sensitivity in comparison with electrodes structured from pure Galinstan and detected lead at concentrations down to 0.1 mmol·L-1. This work paves the way for a new class of HMI sensors using GR of WO-Galinstan electrodes, with applications in microfluidics and MEMS for a toxic-free environment.

Two-Photon Direct Laser Writing of 3D Scaffolds through C, H-Insertion Crosslinking in a One-Component Material System.

The popularity of two-photon direct laser writing in biological research is remarkable as this technique is capable of 3D fabrication of microstructures with unprecedented control, flexibility and precision. Nevertheless, potential impurities such as residual monomers and photoinitiators remaining unnoticed from the photopolymerization in the structures pose strong challenges for biological applications. Here, the first use of high-precision 3D microstructures fabricated from a one-component material system (without monomers and photoinitiators) as a 3D cell culture platform is demonstrated. The material system consists of prepolymers with built- in crosslinker motieties, requiring only aliphatic C, H units as reaction partners following two-photon excitation. The material is written by direct laser writing using two-photon processes in a solvent-free state, which enables the generation of structures at a rapid scan speed of up to 500 mm s-1 with feature sizes scaling down to few micrometers. The generated structures possess stiffnesses close to those of common tissue and demonstrate excellent biocompatibility and cellular adhesion without any additional modification. The demonstrated approach holds great promise for fabricating high-precision complex 3D cell culture scaffolds that are safe in biological environments.

Three-dimensional printing of transparent fused silica glass.

Glass is one of the most important high-performance materials used for scientific research, in industry and in society, mainly owing to its unmatched optical transparency, outstanding mechanical, chemical and thermal resistance as well as its thermal and electrical insulating properties. However, glasses and especially high-purity glasses such as fused silica glass are notoriously difficult to shape, requiring high-temperature melting and casting processes for macroscopic objects or hazardous chemicals for microscopic features. These drawbacks have made glasses inaccessible to modern manufacturing technologies such as three-dimensional printing (3D printing). Using a casting nanocomposite, here we create transparent fused silica glass components using stereolithography 3D printers at resolutions of a few tens of micrometres. The process uses a photocurable silica nanocomposite that is 3D printed and converted to high-quality fused silica glass via heat treatment. The printed fused silica glass is non-porous, with the optical transparency of commercial fused silica glass, and has a smooth surface with a roughness of a few nanometres. By doping with metal salts, coloured glasses can be created. This work widens the choice of materials for 3D printing, enabling the creation of arbitrary macro- and microstructures in fused silica glass for many applications in both industry and academia.

Long-Term Stability of Polymer-Coated Surface Transverse Wave Sensors for the Detection of Organic Solvent Vapors.

Arrays with polymer-coated acoustic sensors, such as surface acoustic wave (SAW) and surface transverse wave (STW) sensors, have successfully been applied for a variety of gas sensing applications. However, the stability of the sensors' polymer coatings over a longer period of use has hardly been investigated. We used an array of eight STW resonator sensors coated with different polymers. This sensor array was used at semi-annual intervals for a three-year period to detect organic solvent vapors of three different chemical classes: a halogenated hydrocarbon (chloroform), an aliphatic hydrocarbon (octane), and an aromatic hydrocarbon (xylene). The sensor signals were evaluated with regard to absolute signal shifts and normalized signal shifts leading to signal patterns characteristic of the respective solvent vapors. No significant time-related changes of sensor signals or signal patterns were observed, i.e., the polymer coatings kept their performance during the course of the study. Therefore, the polymer-coated STW sensors proved to be robust devices which can be used for detecting organic solvent vapors both qualitatively and quantitatively for several years.

Numerics made easy: solving the Navier-Stokes equation for arbitrary channel cross-sections using Microsoft Excel.

The fluid mechanics of microfluidics is distinctively simpler than the fluid mechanics of macroscopic systems. In macroscopic systems effects such as non-laminar flow, convection, gravity etc. need to be accounted for all of which can usually be neglected in microfluidic systems. Still, there exists only a very limited selection of channel cross-sections for which the Navier-Stokes equation for pressure-driven Poiseuille flow can be solved analytically. From these equations, velocity profiles as well as flow rates can be calculated. However, whenever a cross-section is not highly symmetric (rectangular, elliptical or circular) the Navier-Stokes equation can usually not be solved analytically. In all of these cases, numerical methods are required. However, in many instances it is not necessary to turn to complex numerical solver packages for deriving, e.g., the velocity profile of a more complex microfluidic channel cross-section. In this paper, a simple spreadsheet analysis tool (here: Microsoft Excel) will be used to implement a simple numerical scheme which allows solving the Navier-Stokes equation for arbitrary channel cross-sections.

Surface Acoustic Wave Resonator Chip Setup for the Elimination of Interfering Conductivity Responses.

A surface acoustic wave (SAW) resonator chip setup is presented that eliminates interfering signal responses caused by changes in the electrical environment of the surrounding media. When using a two-port resonator, applying electrically shielding layers between the interdigital transducers (IDTs) can be challenging due to the limited dimensions. Therefore, a layered setup consisting of an insulating polymer layer and a conductive gold layer was preferred. The SAW resonators were provided with polycarbonate housings, resulting in SAW resonator chips. This setup enables easy application of a wide range of coatings to the active part of the resonator surface, while ensuring subsequent electrical and fluidic integration of the resonator chips into a microfluidic array for measurements. The signal responses of uncoated SAW resonators and those with polymer coatings with and without a gold layer were tested with aqueous potassium chloride (KCl) solutions up to 3 mol/L, corresponding to conductivities up to 308 mS/cm. The use of a polymer coating at the thickness of the first Love mode resonance and a conductive gold layer completely reduced the electrical impact on the SAW resonator signal response, making small signals resulting from changes in viscosity and density of the KCl solutions visible.

Generation of precision microstructures based on reconfigurable photoresponsive hydrogels for high-resolution polymer replication and microoptics.

Microstructured molds are essential for fabricating various components ranging from precision optics and microstructured surfaces to microfluidics. However, conventional fabrication technology such as photolithography requires expensive equipment and a large number of processing steps. Here, we report a facile method to fabricate micromolds based on a reusable photoresponsive hydrogel: Uniform micropatterns are engraved into the hydrogel surface using photo masks under UV irradiation within a few minutes. Patterns are replicated using polydimethylsiloxane with minimum feature size of 40 µm and smoothness of Rq ~ 3.4 nm. After replication, the patterns can be fully erased by light thus allowing for reuse as a new mold without notable loss in performance. Utilizing greyscale lithography, patterns with different height levels can be produced within the same exposure step. We demonstrate the versatility of this method by fabricating diffractive optical elements devices and a microlens array and microfluidic device with 100 µm wide channels.

The chemistry of cyborgs--interfacing technical devices with organisms.

The term "cyborg" refers to a cybernetic organism, which characterizes the chimera of a living organism and a machine. Owing to the widespread application of intracorporeal medical devices, cyborgs are no longer exclusively a subject of science fiction novels, but technically they already exist in our society. In this review, we briefly summarize the development of modern prosthetics and the evolution of brain-machine interfaces, and discuss the latest technical developments of implantable devices, in particular, biocompatible integrated electronics and microfluidics used for communication and control of living organisms. Recent examples of animal cyborgs and their relevance to fundamental and applied biomedical research and bioethics in this novel and exciting field at the crossroads of chemistry, biomedicine, and the engineering sciences are presented.

Fabrication of Multi-Material Pneumatic Actuators and Microactuators Using Stereolithography.

Pneumatic actuators are of great interest for device miniaturization, microactuators, soft robots, biomedical engineering, and complex control systems. Recently, multi-material actuators have become of high interest to researchers due to their comprehensive range of suitable applications. Three-dimensional (3D) printing of multi-material pneumatic actuators would be the ideal way to fabricate customized actuators, but so far, this is mostly limited to deposition-based methodologies, such as fused deposition modeling (FDM) or Polyjetting. Vat-based stereolithography is one of the most relevant high-resolution 3D printing methods but is only rarely utilized in the multi-material 3D printing of materials. This study demonstrated multi-material stereolithography using combinations of materials with different Young's moduli, i.e., 0.5 MPa and 1.1 GPa, for manufacturing pneumatic actuators and microactuators with a resolution as small as 200 µm. These multi-material actuators have advantages over single-material actuators in terms of their deformation controllability and ease of assembly.

Influence of Parylene F Coatings on the Wetting Properties of Soft Polydimethylsiloxane (PDMS).

Understanding the wettability of soft surfaces is of key importance for the development of protective and repellent coatings and controlling droplet dynamics when required. There are many factors that affect the wetting and dynamic dewetting behavior of soft surfaces, such as the formation of wetting ridges, the adaptive behavior of the surface caused by the interaction of the fluid with the surface, or the presence of free oligomers that are washed out of the soft surface. In this work, we report the fabrication and characterization of three soft polydimethylsiloxane (PDMS) surfaces with elastic moduli ranging from 7 kPa to 56 kPa. The dynamic dewetting behavior of liquids with different surface tensions was studied on these surfaces, and the data show soft and adaptive wetting behavior of the soft PDMS, as well as the presence of free oligomers. Thin layers of Parylene F (PF) were introduced to the surfaces and their influence on the wetting properties was studied. We show that the thin layers of PF prevent adaptive wetting by preventing the diffusion of liquids into the soft PDMS surfaces and by causing the loss of the soft wetting state. The dewetting properties of the soft PDMS are enhanced, leading to low sliding angles of ≤10° for water, ethylene glycol, and diiodomethane. Therefore, the introduction of a thin PF layer can be used to control wetting states and to increase the dewetting behavior of soft PDMS surfaces.

In Situ Actuators with Gallium Liquid Metal Alloys and Polypyrrole-Coated Electrodes.

Gallium liquid metal alloys (GLMAs) such as Galinstan and gallium-indium eutectic (EGaIn) are interesting materials due to their high surface tensions, low viscosities, and electrical conductivities comparable to classical solid metals. They have been used for applications in microelectromechanical systems (MEMS) and, more recently, liquid metal microfluidics (LMMF) for setting up devices like actuators. However, their high tendency to alloy with the most common metals used for electrodes such as gold (Au), platinum (Pt), titanium (Ti), nickel (Ni), and tungsten-titanium (WTi) is a major problem limiting the scaleup and applicability, e.g., liquid metal actuators. Stable electrodes are key elements for many applications and thus, the lack of an electrode material compatible with GLMAs is detrimental for many potential application scenarios. In this work, we study the effect of actuating Galinstan on various solid metal electrodes and present an electrode protection methodology that, first, prevents alloying and, second, prevents electrode corrosion. We demonstrate reproducible actuation of GLMA segments in LMMF, showcasing the stability of the proposed protective coating. We investigated a range of electrode materials including Au, Pt, Ti, Ni, and WTi, all in aqueous environments, and present the resulting corrosion/alloying effects by studying the interface morphology. Our proposed protective coating is based on a simple method to electrodeposit electrically conductive polypyrrole (PPy) on the electrodes to provide a conductive alloying-barrier layer for applications involving direct contact between GLMAs and electrodes. We demonstrate the versatility of this approach by direct three-dimensional (3D) printing of a 500 µm microfluidic chip on a set of electrodes onto which PPy is electrodeposited in situ for actuation of Galinstan plugs. The developed protection protocol will provide a generic, widely applicable strategy to protect a wide range of electrodes from alloying and corrosion and thus form a key element in future applications of GLMAs.

4D Printed Shape-Memory Elastomer for Thermally Programmable Soft Actuators.

Polymeric shape-memory elastomers can recover to a permeant shape from any programmed deformation under external stimuli. They are mostly cross-linked polymeric materials and can be shaped by three-dimensional (3D) printing. However, 3D printed shape-memory polymers so far only exhibit elasticity above their transition temperature, which results in their programmed shape being inelastic or brittle at lower temperatures. To date, 3D printed shape-memory elastomers with elasticity both below and above their transition temperature remain an elusive goal, which limits the application of shape-memory materials as elastic materials at low temperatures. In this paper, we printed, for the first time, a custom-developed shape-memory elastomer based on polyethylene glycol using digital light processing, which possesses elasticity and stretchability in a wide temperature range, below and above the transition temperature. Young's modulus in these two states can vary significantly, with a difference of up to 2 orders of magnitude. This marked difference in Young's modulus imparts excellent shape-memory properties to the material. The difference in Young's modulus at different temperatures allows for the programming of the pneumatic actuators by heating and softening specific areas. Consequently, a single actuator can exhibit distinct movement modes based on the programming process it undergoes.

Maskless projection lithography for the fast and flexible generation of grayscale protein patterns.

Protein patterns of different shapes and densities are useful tools for studies of cell behavior and to create biomaterials that induce specific cellular responses. Up to now the dominant techniques for creating protein patterns are mostly based on serial writing processes or require templates such as photomasks or elastomer stamps. Only a few of these techniques permit the creation of grayscale patterns. Herein, the development of a lithography system using a digital mirror device which allows fast patterning of proteins by immobilizing fluorescently labeled molecules via photobleaching is reported. Grayscale patterns of biotin with pixel sizes in the range of 2.5 µm are generated within 10 s of exposure on an area of about 5 mm(2) . This maskless projection lithography method permits the rapid and inexpensive generation of protein patterns definable by any user-defined grayscale digital image on substrate areas in the mm(2) to cm(2) range.

Emerging Technologies and Materials for High-Resolution 3D Printing of Microfluidic Chips.

In recent years, 3D printing has had a huge impact on the field of biotechnology: from 3D-printed pharmaceuticals to tissue engineering and microfluidic chips. Microfluidic chips are of particular interest and importance for the field of biotechnology, since they allow for the analysis and screening of a wide range of biomolecules - including single cells, proteins, and DNA. The fabrication of microfluidic chips has historically been time-consuming, however, and is typically limited to 2.5 dimensional structures and a restricted palette of well-known materials. Due to the high surface-to-volume ratios in microfluidic chips, the nature of the chip material is of paramount importance to the final system behavior. With the emergence of 3D printing, however, a wide range of microfluidic systems are now being printed for the first time in a manner that facilitates flexibility while minimizing time and cost. Nevertheless, resolution and material choices still remain challenges and in the focus of current research, aiming for (1) 3D printing with high resolutions in the range of tens of micrometers and (2) a wider range of available materials for these high-resolution prints. The first part of this chapter highlights recent emerging technologies in the field of high-resolution printing via stereolithography (SL) and 2-photon polymerization (2PP) and seeks to identify particularly interesting emerging technologies which could have a major impact on the field in the near future. The second part of this chapter highlights current developments in the field of materials that are used for these high-resolution 3D printing technologies.

Enhanced PTC Effect in Polyamide/Carbon Black Composites.

Self-heating nanocomposites with a positive temperature coefficient (PTC) provide outstanding potential for a broad range of engineering applications in automobile, spacecraft, or smart building. Therefore, extensive studies have been carried out to understand thermo-electrical behavior. However, some controversies remain, especially on the material composition, to clarify influencing factors on the PTC performance. In this study, the thermo-electrical behaviors of injection molded carbon black (CB)/polyamide (PA) nanocomposites have been investigated. Three types of CB with well-defined specific surface area and polyamides with high and low crystallinity were selected to provide a guideline for self-heating devices including PTC-Effects. Significantly reduced specific resistances up to 2.7 Ω·cm were achieved by incorporating CB with a high specific surface area into a highly crystalline PA. Noticeable PTC-Effects of ~53% and average surface temperatures up to 147 °C have been observed due to self-heating, which confirms a promising material performance as a heating device.

Deterministic Lateral Displacement Microfluidic Chip for Minicell Purification.

Deterministic lateral displacement (DLD) is a well-known microfluidic technique for particle separation with high potential for integration into bioreactors for therapeutic applications. Separation is based on the interaction of suspended particles in a liquid flowing through an array of microposts under low Reynolds conditions. This technique has been used previously to separate living cells of different sizes but similar shapes. Here, we present a DLD microchip to separate rod-shaped bacterial cells up to 10 µm from submicron spherical minicells. We designed two microchips with 50 and 25 µm cylindrical posts and spacing of 15 and 2.5 µm, respectively. Soft lithography was used to fabricate polydimethylsiloxane (PDMS) chips, which were assessed at different flow rates for their separation potential. The results showed negligible shear effect on the separation efficiency for both designs. However, the higher flow rates resulted in faster separation. We optimized the geometrical parameters including the shape, size, angle and critical radii of the posts and the width and depth of the channel as well as the number of arrays to achieve separation efficiency as high as 75.5% on a single-stage separation. These results pave the way for high-throughput separation and purification modules with the potential of direct integration into bioreactors.

A parallelized, perfused 3D triculture model of leukemia forin vitrodrug testing of chemotherapeutics.

Leukemia patients undergo chemotherapy to combat the leukemic cells (LCs) in the bone marrow. During therapy not only the LCs, but also the blood-producing hematopoietic stem and progenitor cells (HSPCs) may be destroyed. Chemotherapeutics targeting only the LCs are urgently needed to overcome this problem and minimize life-threatening side-effects. Predictivein vitrodrug testing systems allowing simultaneous comparison of various experimental settings would enhance the efficiency of drug development. Here, we present a three-dimensional (3D) human leukemic bone marrow model perfused using a magnetic, parallelized culture system to ensure media exchange. Chemotherapeutic treatment of the acute myeloid leukemia cell line KG-1a in 3D magnetic hydrogels seeded with mesenchymal stem/stromal cells (MSCs) revealed a greater resistance of KG-1a compared to 2D culture. In 3D tricultures with HSPCs, MSCs and KG-1a, imitating leukemic bone marrow, HSPC proliferation decreased while KG-1a cells remained unaffected post treatment. Non-invasive metabolic profiling enabled continuous monitoring of the system. Our results highlight the importance of using biomimetic 3D platforms with proper media exchange and co-cultures for creatingin vivo-like conditions to enablein vitrodrug testing. This system is a step towards drug testing in biomimetic, parallelizedin vitroapproaches, facilitating the discovery of new anti-leukemic drugs.

Application of Micro/Nanoporous Fluoropolymers with Reduced Bioadhesion in Digital Microfluidics.

Digital microfluidics (DMF) is a versatile platform for conducting a variety of biological and chemical assays. The most commonly used set-up for the actuation of microliter droplets is electrowetting on dielectric (EWOD), where the liquid is moved by an electrostatic force on a dielectric layer. Superhydrophobic materials are promising materials for dielectric layers, especially since the minimum contact between droplet and surface is key for low adhesion of biomolecules, as it causes droplet pinning and cross contamination. However, superhydrophobic surfaces show limitations, such as full wetting transition between Cassie and Wenzel under applied voltage, expensive and complex fabrication and difficult integration into already existing devices. Here we present Fluoropor, a superhydrophobic fluorinated polymer foam with pores on the micro/nanoscale as a dielectric layer in DMF. Fluoropor shows stable wetting properties with no significant changes in the wetting behavior, or full wetting transition, until potentials of 400 V. Furthermore, Fluoropor shows low attachment of biomolecules to the surface upon droplet movement. Due to its simple fabrication process, its resistance to adhesion of biomolecules and the fact it is capable of being integrated and exchanged as thin films into commercial DMF devices, Fluoropor is a promising material for wide application in DMF.