Nanoscale electrochemical 3D deposition of cobalt with nanosecond voltage pulses in an STM

To explore a minimal feature size of <100 nm with electrochemical additive manufacturing, we use a strategy originally applied to microscale electrochemical machining for the nanoscale deposition of Co on Au. The concept's essence is the localization of electrochemical reactions below a probe during polarization with ns-long voltage pulses. As shown, a confinement that exceeds that predicted by a simple model based on the time constant for one-dimensional double layer charging enables a feature size of <100 nm for 2D patterning. We further indirectly verify the potential for out-of-plane deposition by tracking growth curves of high-aspect-ratio deposits. Importantly, we report a lack of anodic stability of Au tips used for patterning. As an inert probe is the prerequisite for controlled structuring, we experimentally verify an increased resistance of Pt probes against degradation. Consequently, the developed setup and processes show a path towards reproducible direct 2D and 3D patterning of metals at the nanoscale.ISSN:2040-3364ISSN:2040-337

Microscale additive manufacturing of metal – mechanical properties

Additive manufacturing (AM) is transforming the way we design and fabricate structures on many scales. A main driving force of this movement is the ability of AM to overcome geometrical constraints imposed by subtractive manufacturing techniques. Because such design restrictions become increasingly limiting at small length scales, microscale AM has the potential to significantly expand the capabilities of microfabrication. Yet, for AM to become a beneficial addition to current microfabrication techniques, the properties of materials fabricated by AM have to be determined and quality standards have to be established. Thus, a comparison was performed of the mechanical properties of metals deposited with most of the currently suggested microscale metal AM techniques [1]. The range of techniques studied includes well established approaches, e.g., focused electron beam induced deposition and laser forward transfer, as well as more novel methods, e.g., electrohydrodynamic printing and electrochemical deposition. The mechanical performance of structures deposited with these methods was evaluated using nanoindentation and microcompression (Fig. 1b), and the materials’ microstructure was analyzed using cross-sectional electron microscopy. Please click Additional Files below to see the full abstract

Multi-metal electrohydrodynamic redox 3d printing at the submicron scale: Microstructure – geometrical gradients – chemical gradients and the resulting mechanical properties

An extensive range of metals can be dissolved and re-deposited in liquid solvents using electrochemistry. We harness this concept for additive manufacturing, demonstrating the focused electrohydrodynamic ejection of metal ions dissolved from sacrificial anodes and their subsequent reduction to elemental metals on the substrate. This technique, termed electrohydrodynamic redox printing (EHD-RP), enables the direct, ink-free fabrication of polycrystalline multi-metal 3D structures without the need for post-print processing. On- the-fly switching and mixing of two or more metals printed from a single multichannel nozzle facilitates a chemical feature size of \u3c400 nm with a spatial resolution of 250 nm at printing speeds of up to 10 voxels per second. The additive control of the chemical architecture of materials provided by EHD-RP unlocks the synthesis of 3D bi-metal structures with programmed local properties and opens new avenues for the direct fabrication of chemically architected materials and devices. Mechanical properties can be locally controlled by alloying, dealloying (resulting in controlled porosity) and grain-size tuning via process control. The properties of EHD-RP are put into perspective by comparing with the most prominent current technologies for metal 3D printing at the nanoscale (Fig. 1). Please click Additional Files below to see the full abstract

Additive manufacturing of multi-metals and multi-materials by electrohydrodynamic redox printing – towards 3D gradient materials with submicrometer resolution

Many emerging applications in microscale engineering require the fabrication of three-dimensional architectures in inorganic materials. Small-scale additive manufacturing (AM) aspires to provide access to these geometries with feature sizes in the micro- and submicrometer range. Yet, the synthesis of device-grade inorganic materials is still a challenge for AM – a major handicap for its incorporation in advanced micro- and nanofabrication processes [1,2]. Please click Additional Files below to see the full abstract

Direct in- and out-of-plane writing of metals on insulators by electron-beam-enabled, confined electrodeposition with submicrometer feature size

Additive microfabrication processes based on localized electroplating enable the one-step deposition of micro-scale metal structures with outstanding performance, e.g. high electrical conductivity and mechanical strength. They are therefore evaluated as an exciting and enabling addition to the existing repertoire of microfabrication technologies. Yet, electrochemical processes are generally restricted to conductive or semiconductive substrates, precluding their application in the manufacturing of functional electric devices where direct deposition onto insulators is often required. Here, we demonstrate the direct, localized electrodeposition of copper on a variety of insulating substrates, namely Al2O3, glass and flexible polyethylene, enabled by electron-beam-induced reduction in a highly confined liquid electrolyte reservoir. The nanometer-size of the electrolyte reservoir, fed by electrohydrodynamic ejection, enables a minimal feature size on the order of 200 nm. The fact that the transient reservoir is established and stabilized by electrohydrodynamic ejection rather than specialized liquid cells could offer greater flexibility towards deposition on arbitrary substrate geometries and materials. Installed in a low-vacuum scanning electron microscope, the setup further allows for operando, nanoscale observation and analysis of the manufacturing process

Dubious effects of methadone as an "anticancer" drug on ovarian cancer cell-lines and patient-derived tumor-spheroids

Background. The opioid agonist D, L-methadone exerts analgesic effects via the mu opioid receptor, encoded by OPRM1 and therefore plays a role in chronic pain management. In preclinical tumor-models D,L-methadone shows apoptotic and chemo-sensitizing effects and was therefore hyped as an off-label "anticancer" drug without substantiation from clinical trials. Its effects in ovarian cancer (OC) are completely unexplored. Methods. We analyzed OPRM1-mRNA expression in six cisplatin-sensitive, two cisplatin-resistant OC cell-lines, 170 OC tissue samples and 12 non-neoplastic control tissues. Pro-angiogenetic, cytotoxic and apoptotic effects of D,L-methadone were evaluated in OC cell-lines and four patient-derived tumor-spheroid models. Results. OPRM1 was transcriptionally expressed in 69% of OC-tissues and in three of eight OC cell-lines. D, L-methadone exposure significantly reduced cell-viability in five OC cell-lines irrespective of OPRM1 expression. D, L-methadone, applied alone or combined with cisplatin, showed no significant effects on apoptosis or VEGF secretion in cell-lines. Notably, in two of the four sphero id models, treatment with D, L-methadone significantly enhanced cell growth (by up to 121%), especially after long-term exposure. This is consistent with the observed attenuation of the inhibitory effects of cisplatin in three spheroid models when adding D, L-methadone. The effect of methadone treatment on VEGF secretion in tumor-spheroids was inconclusive. Conclusions. Our study demonstrates that certain OC samples express OPRM1, which, however, is not a prerequisite for D, L-methadone function. As such, D,L-methadone may exert also detrimental effects by stimulating the growth of certain OC-cells and abrogating cisplatin's therapeutic effect. (C) 2022 The Authors. Published by Elsevier Inc.Peer reviewe

Dubious effects of methadone as an “anticancer” drug on ovarian cancer cell-lines and patient-derived tumor-spheroids

BackgroundThe opioid agonist D,L-methadone exerts analgesic effects via the mu opioid receptor, encoded by OPRM1 and therefore plays a role in chronic pain management. In preclinical tumor-models D,L-methadone shows apoptotic and chemo-sensitizing effects and was therefore hyped as an off-label “anticancer” drug without substantiation from clinical trials. Its effects in ovarian cancer (OC) are completely unexplored.MethodsWe analyzed OPRM1-mRNA expression in six cisplatin-sensitive, two cisplatin-resistant OC cell-lines, 170 OC tissue samples and 12 non-neoplastic control tissues. Pro-angiogenetic, cytotoxic and apoptotic effects of D,L-methadone were evaluated in OC cell-lines and four patient-derived tumor-spheroid models.ResultsOPRM1 was transcriptionally expressed in 69% of OC-tissues and in three of eight OC cell-lines. D,L-methadone exposure significantly reduced cell-viability in five OC cell-lines irrespective of OPRM1 expression. D,L-methadone, applied alone or combined with cisplatin, showed no significant effects on apoptosis or VEGF secretion in cell-lines. Notably, in two of the four spheroid models, treatment with D,L-methadone significantly enhanced cell growth (by up to 121%), especially after long-term exposure. This is consistent with the observed attenuation of the inhibitory effects of cisplatin in three spheroid models when adding D,L-methadone. The effect of methadone treatment on VEGF secretion in tumor-spheroids was inconclusive.ConclusionsOur study demonstrates that certain OC samples express OPRM1, which, however, is not a prerequisite for D,L-methadone function. As such, D,L-methadone may exert also detrimental effects by stimulating the growth of certain OC-cells and abrogating cisplatin's therapeutic effect.</p

Additive manufacturing of metals at small length scales – microstructure, properties and novel multi-metal electrochemical concepts

Many emerging applications in microscale engineering demand the fabrication of threedimensional architectures in inorganic materials. Small-scale additive manufacturing (AM) aspires to provide access to these geometries with feature sizes in the micro- and submicrometer range. Yet, the synthesis of device-grade inorganic materials is still a challenge for AM, and the properties of additively manufactured materials are typically inferior to those of materials deposited via traditional, subtractive 2D fabrication routes – a major handicap for incorporating AM in advanced micro- and nanofabrication processes. Materials engineering is thus necessary to improve the quality of printed inorganic materials. This thesis revolves around the materials science of small-scale AM of metals, focusing on both, contemporary techniques and novel concepts introduced in this thesis. The work covers two major topics: first, it establishes a comprehensive overview of the microstructure and properties of metals synthesized by modern additive methods. Second, it explores new techniques that enable facile electrochemical AM of high-quality metals and unlock multi-metal printing of chemically architected geometries with spatially modulated properties at the submicron-scale. In combination, these studies present a further step towards the integration of AM into modern microfabrication routines. The first part of the thesis defines the state of the art of small-scale metal AM, providing a detailed literature review of current techniques and an experimental survey of their materials’ properties. Note that the thesis in general concentrates on the study and development of methods that enable direct additive deposition of metals. Thus, it considers indirect concepts based on the fabrication of organic templates by two-photon lithography in combination with subsequent metallization procedures in little detail only. Today, almost a dozen different methods are available for the direct deposition of metal 3D geometries with a resolution better than 10 μm. As these approaches build on different physico-chemical principles, their characteristics such as feature size, speed and complexity of printable geometries, as well as the synthesized metals and their microstructure, vary greatly. A discussion of the individual principles and capabilities puts the concepts in perspective to each other and projects their potentials. The thesis then presents an experimental study on the "quality" of metals deposited by these methods. In collaboration with most of the groups active in the field of small-scale metal AM, the thesis explores the microstructure and resulting mechanical properties of today’s materials. On one hand, we show that metals with a wide range of microstructures and elastic and plastic properties are synthesized. Especially electrochemical methods deposit dense and crystalline metals with excellent mechanical properties that compare well to those of thin-film nanocrystalline materials. On the other hand, the results reveal large variations in materials performance that can be related to the microstructure of the individual materials. Thus, the study provides practical guidelines for users of small-scale additive methods and establishes a baseline for the necessary optimization of printed metals. The second part of the thesis presents novel electrochemical AM methods that offer a spatial resolution 1 μm. First, two chapters introduce electrohydrodynamic redox printing (EHD-RP). This technique enables the direct, ink-free fabrication of polycrystalline multi-metal 3D structures with a resolution of 250 nm and a feature size of 100 nm. The electrochemical concept enables outstanding as-printed materials properties (for example a strength of copper that competes with highest values reported for nanocrystalline copper) printed at speeds that outperform current electrochemical techniques by one order of magnitude. Although neither its speed, its resolution nor its overall materials properties are unrivaled by competing methods, EHD-RP excels in an advantageous combination of these characteristics, readily permitting applications in microfabrication. Additionally, as a most unique feature, EHD-RP enables multi-metal printing with unprecedented detail. As shown, the additive control of the chemical architecture of metals with a chemical feature size <400 nm unlocks the synthesis of 3D bi-metal structures with spatially varying microstructure and thus locally modified properties. The last chapter discusses the potential of tip-induced deposition in the electrochemical scanning tunneling microscope (STM) for nanoscale AM. A strong confinement of deposition below the nanometer-sized probe enables 2D patterning of cobalt with a feature size of 50 nm. The potential for 3D printing is demonstrated, but reliable 3D fabrication is hampered by unsatisfactory stability of employed gold STM probes. Consequently, the chapter concludes with the development of more stable Pt and Pt-20at.%Ir probes, readying the designed setup for true 3D deposition. Nevertheless, a low deposition speed, a narrow processing window and a comparably complex instrumentation are identified as significant challenges for the proposed concept. In conclusion, the thesis experimentally identifies materials challenges for contemporary smallscale AM of metals but at the same time presents a potential solution by introducing EHD-RP – an electrochemical concept that offers ink-free printing of high-quality metals. Additionally, the demonstrated multi-metal printing with submicrometer resolution sketches a route towards the bottom-up fabrication of chemically designed 3D devices and materials with properties tuned at single-voxel level – staking out a niche for small-scale AM as an enabling technology for chemically architected, inorganic materials that could spark the development of novel materials for e.g. catalysis, active chemical devices, sensors, or metamaterials that combine architected geometry and chemistry