Additive Manufacturing of Electrically Conductive Multi-Layered Nanocopper in an Air Environment.

The additive manufacturing (AM) of functional copper (Cu) parts is a major goal for many industries, from aerospace to automotive to electronics, because Cu has a high thermal and electrical conductivity as well as being ~10× cheaper than silver. Previous studies on AM of Cu have concentrated mainly on high-energy manufacturing processes such as Laser Powder Bed Fusion, Electron Beam Melting, and Binder Jetting. These processes all require high-temperature heat treatment in an oxygen-free environment. This paper shows an AM route to multi-layered microparts from novel nanoparticle (NP) Cu feedstocks, performed in an air environment, employing a low-power (<10 W) laser sintering process. Cu NP ink was deposited using two mechanisms, inkjet printing, and bar coating, followed by low-power laser exposure to induce particle consolidation. Initial parts were manufactured to a height of approximately 100 µm, which was achieved by multi-layer printing of 15 (bar-coated) to 300 (inkjetted) layers. There was no evidence of oxidised copper in the sintered material, but they were found to be low-density, porous structures. Nonetheless, electrical resistivity of ~28 × 10-8 Ω m was achieved. Overall, the aim of this study is to offer foundational knowledge for upscaling the process to additively manufacture Cu 3D parts of significant size via sequential nanometal ink deposition and low-power laser processing.

Quantum Nature of Charge Transport in Inkjet-Printed Graphene Revealed in High Magnetic Fields up to 60T.

Inkjet-printing of graphene, iGr, provides an alternative route for the fabrication of highly conductive and flexible graphene films for use in devices. However, the contribution of quantum phenomena associated with 2D single layer graphene, SLG, to the charge transport in iGr is yet to be explored. Here, the first magneto-transport study of iGr in high magnetic fields up to 60 T is presented. The observed quantum phenomena, such as weak localization and negative magnetoresistance, are strongly affected by the thickness of the iGr film and can be explained by a combination of intra- and inter-flake classical and quantum charge transport. The quantum nature of carrier transport in iGr is revealed using temperature, electric field, and magnetic field dependences of the iGr conductivity. These results are relevant for the exploitation of inkjet deposition of graphene, which is of particular interest for additive manufacturing and 3D printing of flexible and wearable electronics. It is shown that printed nanostructures enable ensemble averaging of quantum interference phenomena within a single device, thereby facilitating comparison between experiment and underlying statistical models of electron transport.

Photosensitisation of inkjet printed graphene with stable all-inorganic perovskite nanocrystals.

All-inorganic perovskite nanocrystals (NCs) with enhanced environmental stability are of particular interest for optoelectronic applications. Here we report on the formulation of CsPbX3 (X is Br or I) inks for inkjet deposition and utilise these NCs as photosensitive layers in graphene photodetectors, including those based on single layer graphene (SLG) as well as inkjet-printed graphene (iGr) devices. The performance of these photodetectors strongly depends on the device structure, geometry and the fabrication process. We achieve a high photoresponsivity, R > 106 A W-1 in the visible wavelength range and a spectral response controlled by the halide content of the perovskite NC ink. By utilising perovskite NCs, iGr and gold nanoparticle inks, we demonstrate a fully inkjet-printed photodetector with R ≈ 20 A W-1, which is the highest value reported to date for this type of device. The performance of the perovskite/graphene photodetectors is explained by transfer of photo-generated charge carriers from the perovskite NCs into graphene and charge transport through the iGr network. The perovskite ink developed here enabled realisation of stable and sensitive graphene-based photon detectors. Compatibility of inkjet deposition with conventional Si-technologies and with flexible substrates combined with high degree of design freedom provided by inkjet deposition offers opportunities for partially and fully printed optoelectronic devices for applications ranging from electronics to environmental sciences.

Printing biohybrid materials for bioelectronic cardio-3D-cellular constructs.

Conductive hydrogels are emerging as promising materials for bioelectronic applications as they minimize the mismatch between biological and electronic systems. We propose a strategy to bioprint biohybrid conductive bioinks based on decellularized extracellular matrix (dECM) and multiwalled carbon nanotubes. These inks contained conductive features and morphology of the dECM fibers. Electrical stimulation (ES) was applied to bioprinted structures containing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). It was observed that in the absence of external ES, the conductive properties of the materials can improve the contractile behavior of the hPSC-CMs, and this effect is enhanced under the application of external ES. Genetic markers indicated a trend toward a more mature state of the cells with upregulated calcium handling proteins and downregulation of calcium channels involved in the generation of pacemaking currents. These results demonstrate the potential of our strategy to manufacture conductive hydrogels in complex geometries for actuating purposes.

Functionalized Gold Nanoparticles with a Cohesion Enhancer for Robust Flexible Electrodes.

The development of conductive inks is required to enable additive manufacturing of electronic components and devices. A gold nanoparticle (AuNP) ink is of particular interest due to its high electrical conductivity, chemical stability, and biocompatibility. However, a printed AuNP film suffers from thermally induced microcracks and pores that lead to the poor integrity of a printed electronic component and electrical failure under external mechanical deformation, hence limiting its application for flexible electronics. Here, we employ a multifunctional thiol as a cohesion enhancer in the AuNP ink to prevent the formation of microcracks and pores by mediating the cohesion of AuNPs via strong interaction between the thiol groups and the gold surface. The inkjet-printed AuNP electrode exhibits an electrical conductivity of 3.0 × 106 S/m and stable electrical properties under repeated cycles (>1000) of mechanical deformation even for a single printed layer and in a salt-rich phosphate-buffered saline solution, offering exciting potential for applications in flexible and 3D electronics as well as in bioelectronics and healthcare devices.

Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices.

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.

Impedimetric Characterization of Bipolar Nanoelectrodes with Cancer Cells.

Merging of electronics with biology, defined as bioelectronics, at the nanoscale holds considerable promise for sensing and modulating cellular behavior. Advancing our understanding of nanobioelectronics will facilitate development and enable applications in biosensing, tissue engineering, and bioelectronic medicine. However, studies investigating the electrical effects when merging wireless conductive nanoelectrodes with biology are lacking. Consequently, a tool is required to develop a greater understanding of merging conductive nanoparticles with cells. Herein, this challenge is addressed by developing an impedimetric method to evaluate bipolar electrode (BPE) systems that could report on electrical input. A theoretical framework is provided, using impedance to determine if conductive nanoparticles can be polarized and used to drive current. It is then demonstrated that 125 nm of gold nanoparticle (AuNP) bipolar electrodes (BPEs) could be sensed in the presence of cells when incorporated intracellularly at 500 µg/mL using water and phosphate-buffered saline (PBS) as electrolytes. These results highlight how nanoscale BPEs act within biological systems. This research will impact the rational design of using BPE systems in cells for both sensing and actuating applications.

Bespoke 3D-Printed Polydrug Implants Created via Microstructural Control of Oligomers.

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up" without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.

Exploiting Generative Design for 3D Printing of Bacterial Biofilm Resistant Composite Devices.

As the understanding of disease grows, so does the opportunity for personalization of therapies targeted to the needs of the individual. To bring about a step change in the personalization of medical devices it is shown that multi-material inkjet-based 3D printing can meet this demand by combining functional materials, voxelated manufacturing, and algorithmic design. In this paper composite structures designed with both controlled deformation and reduced biofilm formation are manufactured using two formulations that are deposited selectively and separately. The bacterial biofilm coverage of the resulting composites is reduced by up to 75% compared to commonly used silicone rubbers, without the need for incorporating bioactives. Meanwhile, the composites can be tuned to meet user defined mechanical performance with ±10% deviation. Device manufacture is coupled to finite element modelling and a genetic algorithm that takes the user-specified mechanical deformation and computes the distribution of materials needed to meet this under given load constraints through a generative design process. Manufactured products are assessed against the mechanical and bacterial cell-instructive specifications and illustrate how multifunctional personalization can be achieved using generative design driven multi-material inkjet based 3D printing.

Development of Conductive Gelatine-Methacrylate Inks for Two-Photon Polymerisation.

Conductive hydrogel-based materials are attracting considerable interest for bioelectronic applications due to their ability to act as more compatible soft interfaces between biological and electrical systems. Despite significant advances that are being achieved in the manufacture of hydrogels, precise control over the topographies and architectures remains challenging. In this work, we present for the first time a strategy to manufacture structures with resolutions in the micro-/nanoscale based on hydrogels with enhanced electrical properties. Gelatine methacrylate (GelMa)-based inks were formulated for two-photon polymerisation (2PP). The electrical properties of this material were improved, compared to pristine GelMa, by dispersion of multi-walled carbon nanotubes (MWCNTs) acting as conductive nanofillers, which was confirmed by electrochemical impedance spectroscopy and cyclic voltammetry. This material was also confirmed to support human induced pluripotent stem cell-derived cardiomyocyte (hPSC-CMs) viability and growth. Ultra-thin film structures of 10 µm thickness and scaffolds were manufactured by 2PP, demonstrating the potential of this method in areas spanning tissue engineering and bioelectronics. Though further developments in the instrumentation are required to manufacture more complex structures, this work presents an innovative approach to the manufacture of conductive hydrogels in extremely low resolution.

Modulating the biological function of protein by tailoring the adsorption orientation on nanoparticles.

Protein orientation in nanoparticle-protein conjugates plays a crucial role in binding to cell receptors and ultimately, defines their targeting efficiency. Therefore, understanding fundamental aspects of the role of protein orientation upon adsorption on the surface of nanoparticles (NPs) is vital for the development of clinically important protein-based nanomedicines. In this work, new insights on the effect of the different orientation of cytochrome c (cyt c) bound to gold nanoparticles (GNPs) using various ligands on its apoptotic activity is reported. Time-of-Flight Secondary-Ion Mass Spectrometry (ToF-SIMS), electrochemical and circular dichroism (CD) analyses are used to investigate the characteristics of cyt c orientation and structure on functionalized GNPs. These studies indicate that the orientation and position of the heme ring inside the cyt c structure can be altered by changing the surface chemistry on the GNPs. A difference in the apoptosis inducing capability because of different orientation of cyt c bound to the GNPs is observed. These findings indicate that the biological activity of a protein can be modulated on the surface of NPs by varying its adsorption orientation. This study will impact on the rational design of new nanoscale biosensors, bioelectronics, and nanoparticle-protein based drugs.

Recommended Personal Protective Equipment for Cochlear Implant and Other Mastoid Surgery During the COVID-19 Era.

OBJECTIVES/HYPOTHESIS: The overall aim of this study was to evaluate personal protective equipment (PPE) that may facilitate the safe recommencement of cochlear implantation in the COVID-19 era, with the broader goal of minimizing the period of auditory deprivation in prelingually deaf children and reducing the risk of cochlear ossification in individuals following meningitis. METHODS: The study design comprised 1) an objective assessment of mastoid drilling-induced droplet spread conducted during simulated cochlear implant (CI) surgery and its mitigation via the use of a protective drape tent and 2) an evaluation of three PPE configurations by otologists while performing mastoid drilling on ex vivo temporal bones. The various PPE solutions were assessed in terms of their impact on communication, vital physiological parameters, visual acuity and fields, and acceptability to surgeons using a systematic risk-based approach. RESULTS: Droplet spread during simulated CI surgery extended over 2 m, a distance greater than previously reported. A drape tent significantly reduced droplet spread. The ensemble of a half-face mask and safety spoggles (foam lined safety goggles) had consistently superior performance across all aspects of clinical usability. All other PPE options were found to substantially restrict the visual field, making them unsafe for microsurgery. CONCLUSIONS: The results of this preclinical study indicate that the most viable solution to enable the safe conduct of CI and other mastoid surgery is a combination of a filtering facepiece (FFP3) mask or half-face respirator with safety spoggles as PPE. Prescription spoggles are an option for surgeons who need to wear corrective glasses to operate. A drape tent reduces droplet spread. A multicenter clinical trial to evaluate the effectiveness of PPE should be the next step toward safely performing CI surgery during the COVID-19 era. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2693-2699, 2020.

Processability of Atypical WC-Co Composite Feedstock by Laser Powder-Bed Fusion.

Processing of tool materials for cutting applications presents challenges in additive manufacturing (AM). Processes must be carefully managed in order to promote the formation of favourable high-integrity 'builds'. In this study, for the first time, a satelliting process is used to prepare a WCM-Co (12 wt.% Co) composite. Melting trials were undertaken to evaluate the consolidation behaviour of single tracks within a single layer. Tracks with continuous and relatively uniform surface morphology were obtained. These features are essential for high-quality AM builds in order to encourage good bonding between subsequent tracks within a layer which may reduce porosity within a 3D deposition. This study elucidates the formation of track irregularities, melting modes, crack sensitivity, and balling as a function of laser scanning speed and provides guidelines for future production of WCM-Co by laser powder-bed fusion.

Remotely Controlled in Situ Growth of Silver Microwires Forming Bioelectronic Interfaces.

There is a pressing need to advance our ability to construct three-dimensional (3D) functional bioelectronic interfaces. Additionally, to ease the transition to building cellular electronic systems, a remote approach to merge electrical components with biology is desirable. By combining 3D digital inkjet printing with bipolar electrochemistry, we remotely control and fabricate conductive wires, forming a first of its kind contactless bionic manufacturing procedure. It enables controlled fabrication of conductive wires in a three-dimensional configuration. Moreover, we demonstrate that this technology could be used to grow and interface conductive conduits in situ with mammalian cells, offering a new strategy to engineering bioelectronic interfaces. This represents a step change in the production of functional complex circuitry and considerably increases the manufacturing capabilities of merging cells with electronics. This approach provides a platform to construct bioelectronics in situ offering a potential paradigm shift in the methods for building bioelectronics with potential applications in biosensing and bioelectronic medicine.

Chemical Imaging of Buried Interfaces in Organic-Inorganic Devices Using Focused Ion Beam-Time-of-Flight-Secondary-Ion Mass Spectrometry.

Organic-inorganic hybrid materials enable the design and fabrication of new materials with enhanced properties. The interface between the organic and inorganic materials is often critical to the device's performance; therefore, chemical characterization is of significant interest. Because the interfaces are often buried, milling by focused ion beams (FIBs) to expose the interface is becoming increasingly popular. Chemical imaging can subsequently be obtained using secondary-ion mass spectrometry (SIMS). However, the FIB milling process damages the organic material. In this study, we make an organic-inorganic test structure to develop a detailed understanding of the processes involved in FIB milling and SIMS imaging. We provide an analysis methodology that involves a "clean-up" process using sputtering with an argon gas cluster ion source to remove the FIB-induced damage. The methodology is evaluated for two additive manufactured devices, an encapsulated strain sensor containing silver tracks embedded in a polymeric material and a copper track on a flexible polymeric substrate created using a novel nanoparticle sintering technique.

Optimisation of Substrate Angles for Multi-material and Multi-functional Inkjet Printing.

Three dimensional inkjet printing of multiple materials for electronics applications are challenging due to the limited material availability, inconsistencies in layer thickness between dissimilar materials and the need to expose the printed tracks of metal nanoparticles to temperature above 100 °C for sintering. It is envisaged that instead of printing a dielectric and a conductive material on the same plane, by printing conductive tracks on an angled dielectric surface, the required number of silver layers and consequently, the exposure of the polymer to high temperature and the build time of the component can be significantly reduced. Conductive tracks printed with a fixed print height (FH) showed significantly better resolution for all angles than the fixed slope (FS) sample where the print height varied to maintain the slope length. The electrical resistance of the tracks remained under 10Ω up to 60° for FH; whereas for the FS samples, the resistance remained under 10Ω for samples up to 45°. Thus by fixing the print height to 4 mm, precise tracks with low resistance can be printed at substrate angles up to 60°. By adopting this approach, the build height "Z" can be quickly attained with less exposure of the polymer to high temperature.

Author Correction: Additive manufacture of complex 3D Au-containing nanocomposites by simultaneous two-photon polymerisation and photoreduction.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Identification of Novel "Inks" for 3D Printing Using High-Throughput Screening: Bioresorbable Photocurable Polymers for Controlled Drug Delivery.

A robust methodology is presented to identify novel biomaterials suitable for three-dimensional (3D) printing. Currently, the application of additive manufacturing is limited by the availability of functional inks, especially in the area of biomaterials; this is the first time when this method is used to tackle this problem, allowing hundreds of formulations to be readily assessed. Several functional properties, including the release of an antidepressive drug (paroxetine), cytotoxicity, and printability, are screened for 253 new ink formulations in a high-throughput format as well as mechanical properties. The selected candidates with the desirable properties are successfully scaled up using 3D printing into a range of object architectures. A full drug release study and degradability and tensile modulus experiments are presented on a simple architecture to validating the suitability of this methodology to identify printable inks for 3D printing devices with bespoke properties.

Electrochemically stimulating developments in bioelectronic medicine.

Cellular homeostasis is in part controlled by biological generated electrical activity. By interfacing biology with electronic devices this electrical activity can be modulated to actuate cellular behaviour. There are current limitations in merging electronics with biology sufficiently well to target and sense specific electrically active components of cells. By addressing this limitation, researchers give rise to new capabilities for facilitating the two-way transduction signalling mechanisms between the electronic and cellular components. This is required to allow significant advancement of bioelectronic technology which offers new ways of treating and diagnosing diseases. Most of the progress that has been achieved to date in developing bioelectronic therapeutics stimulate neural communication, which ultimately orchestrates organ function back to a healthy state. Some devices used in therapeutics include cochlear and retinal implants and vagus nerve stimulators. However, all cells can be impacted by electrical inputs which gives rise to the opportunity to broaden the use of bioelectronic medicine for treating disease. Electronic actuation of non-excitable cells has been shown to lead to 'programmed' cell behaviour via application of electronic input which alter key biological processes. A neglected form of cellular electrical communication which has not yet been considered when developing bioelectronic therapeutics is faradaic currents. These are generated during redox reactions. A precedent of electrochemical technology being used to modulate these reactions, thereby controlling cell behaviour, has already been set. In this mini review we highlight the current state of the art of electronic routes to modulating cell behaviour and identify new ways in which electrochemistry could be used to contribute to the new field of bioelectronic medicine.