Cathal D O'Connell

Liquid Deposition Patterning of Conducting Polymer Ink onto Hard and Soft Flexible Substrates via Dip-Pen Nanolithography

Ink formulations and protocols that enable the deposition and patterning of a conducting polymer (PEDOT:PSS) in the nanodomain have been developed. Significantly, we demonstrated the ability to pattern onto soft substrates such as silicone gum and polyethylene terephthalate (PET), which are materials of interest for low cost, flexible electronics. The deposition process and dimensions of the polymer patterns are found to be critically dependent on a number of parameters, including the pen design, ink properties, time after inking the pen, dwell time of the pen on the surface, and the nature of material substrate. By assessing these different parameters, an improved understanding of the ability to control the dimensions of individual PEDOT:PSS structures down to 600 nm in width and 10-80 nm in height within patterned arrays was obtained. This applicability of DPN for simple and nonreactive liquid deposition patterning of conducting polymers can lead to the fabrication of organic nanoelectronics or biosensors and complement the efforts of existing printing techniques such as inkjet and extrusion printing by scaling down conductive components to submicrometer and nanoscale dimensions.

Liquid ink deposition from an atomic force microscope tip: Deposition monitoring and control of feature size

The controlled deposition of attoliter volumes of liquid inks may engender novel applications such as targeted drug delivery to single cells and localized delivery of chemical reagents at nanoscale dimensions. Although the deposition of small organic molecules from an atomic force microscope tip, known as dip-pen nanolithography (DPN), has been extensively studied, the deposition of liquid inks is little understood. In this work, we have used a set of model ink-substrate systems to develop an understanding of the deposition of viscous liquids using an unmodified AFM tip. First, the growth of dot size with increasing dwell time is characterized. The dynamics of deposition are found to vary for different ink-substrate systems, and the change in deposition rate over the course of an experiment limits our ability to quantify the ink-transfer dynamics in terms of liquid properties and substrate wettability. We find that the most critical parameter affecting the deposition rate is the volume of ink on the cantilever, an effect resulting in a 10-fold decrease in deposition rate (aL/s) over 2 h of printing time. We suggest that a driving force for deposition arises from the gradient in Laplace pressure set up when the tip touches the substrate. Second, the forces acting upon the AFM cantilever during ink deposition were measured in order to gain insight into the underlying ink-transfer mechanism. The force curve data and simple geometrical arguments were used to elucidate the shape of the ink meniscus at the instant of deposition, a methodology that may be used as an accurate and real-time means of monitoring the volume of deposited dots. Taken together, our results illustrate that liquid deposition involves a very different transfer mechanism than traditionally ascribed to DPN molecular transport.

Ink‐on‐Probe Hydrodynamics in Atomic Force Microscope Deposition of Liquid Inks

The controlled deposition of attolitre volumes of liquids may engender novel applications such as soft, nano-tailored cell-material interfaces, multi-plexed nano-arrays for high throughput screening of biomolecular interactions, and localized delivery of reagents to reactions confined at the nano-scale. Although the deposition of small organic molecules from an AFM tip, known as dip-pen nanolithography (DPN), is being continually refined, AFM deposition of liquid inks is not well understood, and is often fraught with inconsistent deposition rates. In this work, the variation in feature-size over long term printing experiments for four model inks of varying viscosity is examined. A hierarchy of recurring phenomena is uncovered and there are attributed to ink movement and reorganisation along the cantilever itself. Simple analytical approaches to model these effects, as well as a method to gauge the degree of ink loading using the cantilever resonance frequency, are described. In light of the conclusions, the various parameters which need to be controlled in order to achieve uniform printing are dicussed. This work has implications for the nanopatterning of viscous liquids and hydrogels, encompassing ink development, the design of probes and printing protocols.

In situ handheld three-dimensional bioprinting for cartilage regeneration

Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three‐dimensional (3D) printing is an exciting and innovative biofabrication technology that enables the surgeon to deliver tissue‐engineering techniques at the time and location of need. We have created a hand‐held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single‐session surgery. This pilot study assessed the ability of the biopen to repair a full‐thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical‐sized full‐thickness chondral defect was created in the weight‐bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand‐held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench‐based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra‐ or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real‐time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.

Nano-bioelectronics via dip-pen nanolithography

The emerging field of nano-biology is borne from advances in our ability to control the structure of materials on finer and finer length-scales, coupled with an increased appreciation of the sensitivity of living cells to nanoscale topographical, chemical and mechanical cues. As we envisage and prototype nanostructured bioelectronic devices there is a crucial need to understand how cells feel and respond to nanoscale materials, particularly as material properties (surface energy, conductivity etc.) can be very different at the nanoscale than at the bulk. However, the patterning of organic bioelectronic materials is often not achievable using conventional fabrication techniques, especially on soft, biocompatible substrates. Nonconventional nanofabrication strategies are required. Dip-pen nanolithography is a nanofabrication technique which uses the nanoscale tip of an atomic force microscope to direct-write functional inks. Over the past decade, the technique has evolved as uniquely capable in the realm of bio-nanofabrication, with the capability to deposit both biomolecules and electrode materials. This review highlights this new tool for fabricating nanoscale bioelectronic devices, and for enabling heretofore unrealised experiments in the response of living cells to tailored nano-environments. We firstly introduce bioelectronics, followed by a survey of different lithography methods and their use to achieve paradigmic bioelectronic architectures. We then focus on dip-pen nanolithography, highlighting the range of bioelectronic materials and biomolecules which can be deposited using the technique, as well as its demonstrated use as a lithography tool in nano-biology. We discuss the progress made towards upscaling the DPN technology towards larger areas, in particular via the polymer pen approach.

Print Me an Organ? Ethical and Regulatory Issues Emerging from 3D Bioprinting in Medicine

Recent developments of three-dimensional printing of biomaterials (3D bioprinting) in medicine have been portrayed as demonstrating the potential to transform some medical treatments, including providing new responses to organ damage or organ failure. However, beyond the hype and before 3D bioprinted organs are ready to be transplanted into humans, several important ethical concerns and regulatory questions need to be addressed. This article starts by raising general ethical concerns associated with the use of bioprinting in medicine, then it focuses on more particular ethical issues related to experimental testing on humans, and the lack of current international regulatory directives to guide these experiments. Accordingly, this article (1) considers whether there is a limit as to what should be bioprinted in medicine; (2) examines key risks of significant harm associated with testing 3D bioprinting for humans; (3) investigates the clinical trial paradigm used to test 3D bioprinting; (4) analyses ethical questions of irreversibility, loss of treatment opportunity and replicability; (5) explores the current lack of a specific framework for the regulation and testing of 3D bioprinting treatments.

Nanoscale platinum printing on insulating substrates.

The deposition of noble metals on soft and/or flexible substrates is vital for several emerging applications including flexible electronics and the fabrication of soft bionic implants. In this paper, we describe a new strategy for the deposition of platinum electrodes on a range of materials, including insulators and flexible polymers. The strategy is enabled by two principle advances: (1) the introduction of a novel, low temperature strategy for reducing chloroplatinic acid to platinum using nitrogen plasma; (2) the development of a chloroplatinic acid based liquid ink formulation, utilizing ethylene glycol as both ink carrier and reducing agent, for versatile printing at nanoscale resolution using dip-pen nanolithography (DPN). The ink formulation has been printed and reduced upon Si, glass, ITO, Ge, PDMS, and Parylene C. The plasma treatment effects reduction of the precursor patterns in situ without subjecting the substrate to destructively high temperatures. Feature size is controlled via dwell time and degree of ink loading, and platinum features with 60 nm dimensions could be routinely achieved on Si. Reduction of the ink to platinum was confirmed by energy dispersive x-ray spectroscopy (EDS) elemental analysis and x-ray diffraction (XRD) measurements. Feature morphology was characterized by optical microscopy, SEM and AFM. The high electrochemical activity of individually printed Pt features was characterized using scanning electrochemical microscopy (SECM).

Three-dimensional neural cultures produce networks that mimic native brain activity

Development of brain function is critically dependent on neuronal networks organized through three dimensions. Culture of central nervous system neurons has traditionally been limited to two dimensions, restricting growth patterns and network formation to a single plane. Here, with the use of multichannel extracellular microelectrode arrays, we demonstrate that neurons cultured in a true three‐dimensional environment recapitulate native neuronal network formation and produce functional outcomes more akin to in vivo neuronal network activity.

Enthusiastic portrayal of 3D bioprinting in the media: Ethical side effects

There has been a surge in mass media reports extolling the potential for using three-dimensional printing of biomaterials (3D bioprinting) to treat a wide range of clinical conditions. Given that mass media is recognized as one of the most important sources of health and medical information for the general public, especially prospective patients, we report and discuss the ethical consequences of coverage of 3D bioprinting in the media. First, we illustrate how positive mass media narratives of a similar biofabricated technology, namely the Macchiarini scaffold tracheas, which was involved in lethal experimental human trials, influenced potential patient perceptions. Second, we report and analyze the positively biased and enthusiastic portrayal of 3D bioprinting in mass media. Third, we examine the lack of regulation and absence of discussion about risks associated with bioprinting technology. Fourth, we explore how media misunderstanding is dangerously misleading the narrative about the technology.