A digitally driven manufacturing process for high resolution patterning of cell formations.

This paper presents the engineering and validation of an enabling technology that facilitates new capabilities in in vitro cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells.

Optimization and fabrication of programmable domains for soft magnetic robots: A review.

Driven by the aim of realizing functional robotic systems at the milli- and submillimetre scale for biomedical applications, the area of magnetically driven soft devices has received significant recent attention. This has resulted in a new generation of magnetically controlled soft robots with patterns of embedded, programmable domains throughout their structures. This type of programmable magnetic profiling equips magnetic soft robots with shape programmable memory and can be achieved through the distribution of discrete domains (voxels) with variable magnetic densities and magnetization directions. This approach has produced highly compliant, and often bio-inspired structures that are well suited to biomedical applications at small scales, including microfluidic transport and shape-forming surgical catheters. However, to unlock the full potential of magnetic soft robots with improved designs and control, significant challenges remain in their compositional optimization and fabrication. This review considers recent advances and challenges in the interlinked optimization and fabrication aspects of programmable domains within magnetic soft robots. Through a combination of improvements in the computational capacity of novel optimization methods with advances in the resolution, material selection and automation of existing and novel fabrication methods, significant further developments in programmable magnetic soft robots may be realized.

Micro-scale aerosol jet printing of superparamagnetic Fe3O4 nanoparticle patterns.

The opportunity to create different patterns of magnetic nanoparticles on surfaces is highly desirable across many technological and biomedical applications. In this paper, this ability is demonstrated for the first time using a computer-controlled aerosol jet printing (AJP) technology. AJP is an emerging digitally driven, non-contact and mask-less printing process which has distinguishing advantages over other patterning technologies as it offers high-resolution and versatile direct-write deposition of a wide range of materials onto a variety of substrates. This research demonstrates the ability of AJP to reliably print large-area, fine-feature patterns of superparamagnetic iron oxide nanoparticles (SPIONs) onto both rigid material (glass) and soft and flexible materials (polydimethylsiloxane (PDMS) films and poly-L-lactic acid (PLLA) nanofilms). Investigation identified and controlled influential process variables which permitted feature sizes in the region of 20 µm to be realised. This method could be employed for a wide range of applications that require a flexible and responsive process that permits high yield and rapid patterning of magnetic material over large areas. As a first proof of concept, we present patterned magnetic nanofilms with enhanced manipulability under external magnetic field gradient control and which are capable of performing complex movements such as rotation and bending, with applicability to soft robotics and biomedical engineering applications.

Digitally Driven Aerosol Jet Printing to Enable Customisable Neuronal Guidance.

Digitally driven manufacturing technologies such as aerosol jet printing (AJP) can make a significant contribution to enabling new capabilities in the field of tissue engineering disease modeling and drug screening. AJP is an emerging non-contact and mask-less printing process which has distinct advantages over other patterning technologies as it offers versatile, high-resolution, direct-write deposition of a variety of materials on planar and non-planar surfaces. This research demonstrates the ability of AJP to print digitally controlled patterns that influence neuronal guidance. These consist of patterned poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) tracks on both glass and poly(potassium 3-sulfopropyl methacrylate) (PKSPMA) coated glass surfaces, promoting selective adhesion of SH-SY5Y neuroblastoma cells. The cell attractive patterns had a maximum height ≥0.2 µm, width and half height ≥15 µm, Ra = 3.5 nm, and RMS = 4.1. The developed biocompatible PEDOT:PSS ink was shown to promote adhesion, growth and differentiation of SH-SY5Y neuronal cells. SH-SY5Y cells cultured directly onto these features exhibited increased nuclei and neuronal alignment on both substrates. In addition, the cell adhesion to the substrate was selective when cultured onto the PKSPMA surfaces resulting in a highly organized neural pattern. This demonstrated the ability to rapidly and flexibly realize intricate and accurate cell patterns by a computer controlled process.

3D printed fluidics with embedded analytic functionality for automated reaction optimisation.

Additive manufacturing or '3D printing' is being developed as a novel manufacturing process for the production of bespoke micro- and milliscale fluidic devices. When coupled with online monitoring and optimisation software, this offers an advanced, customised method for performing automated chemical synthesis. This paper reports the use of two additive manufacturing processes, stereolithography and selective laser melting, to create multifunctional fluidic devices with embedded reaction monitoring capability. The selectively laser melted parts are the first published examples of multifunctional 3D printed metal fluidic devices. These devices allow high temperature and pressure chemistry to be performed in solvent systems destructive to the majority of devices manufactured via stereolithography, polymer jetting and fused deposition modelling processes previously utilised for this application. These devices were integrated with commercially available flow chemistry, chromatographic and spectroscopic analysis equipment, allowing automated online and inline optimisation of the reaction medium. This set-up allowed the optimisation of two reactions, a ketone functional group interconversion and a fused polycyclic heterocycle formation, via spectroscopic and chromatographic analysis.

Three-dimensional printing (3DP) of neonatal head phantom for ultrasound: thermocouple embedding and simulation of bone.

A neonatal head phantom, comprising of an ellipsoidal geometry and including a circular aperture for simulating the fontanel was designed and fabricated, in order to allow an objective assessment of thermal rise in tissues during trans-cranial ultrasonic scanning of pre-term neonates. The precise position of a series of thermocouples was determined on the basis of finite-element analysis, which identified crucial target points for the thermal monitoring within the phantom geometry. Three-Dimensional Printing (3DP) was employed for the manufacture of the skull phantom, which was subsequently filled with dedicated brain-mimic material. A novel 3DP material combination was found to be able to mimic the acoustic properties of neonatal skull bone. Similarly, variations of a standard recipe for tissue mimic were examined, until one was found to mimic the brain of an infant. A specific strategy was successfully pursued to embed a thermocouple within the 3DP skull phantom during the manufacturing process. An in-process machine vision system was used to assess the correct position of the deposited thermocouple inside the fabricated skull phantom. An external silicone-made skin-like covering completed the phantom and was manufactured through a Direct Rapid Tooling (DRT) technique.