Surface-enhanced Raman scattering (SERS) spectroscopy stands out due to its sensitivity, selectivity, and multiplex ability. The development of ready-to-use, simple, and low-cost SERS substrates is one of the main challenges of the field. In this paper, the intrinsic reproducibility of microfluidics technology was used for the fabrication of self-assembled nanoparticle structures over a paper film. The paper SERS substrates were fabricated by assembling anisotropic particles, gold nanostars (GNSs), and nanorods (NRs) onto paper to offer an extra enhancement to reach ultra-sensitive detection limits. A polydimethylsiloxane PDMS-paper hybrid device was used to control the drying kinetics of the nanoparticles over the paper substrate. This method allowed a high reproducibility and homogeneity of the fabrication of SERS substrates that reach limits of detection down to the picomolar range. This simple and low-cost fabrication of a paper-based sensing device was tested for the discrimination of different cell lineages.

3D printing technology is a tremendously powerful technology to fabricate electrochemical sensing devices. However, current conductive filaments are not aimed at electrochemical applications and therefore require intense activation protocols to unleash a suitable electrochemical performance. Current activation methods based on (electro)chemical activation (using strong alkaline solutions and organic solvents and/or electrochemical treatments) or combined approaches are time-consuming and require hazardous chemicals and dedicated operator intervention. Here, pioneering spark-discharge-activated 3D-printed electrodes were developed and characterized, and it was demonstrated that their electrochemical performance was greatly improved by the effective removal of the thermoplastic support polylactic acid (PLA) as well as the formation of sponge-like and low-dimensional carbon nanostructures. This reagent-free approach consists of a direct, fast, and automatized spark discharge between the 3D-electrode and the respective graphite pencil electrode tip using a high-voltage power supply. Activated electrodes were challenged toward the simultaneous voltammetric determination of dopamine (DP) and serotonin (5-HT) in cell culture media. Spark discharge has been demonstrated as a promising approach for conductive filament activation as it is a fast, green (0.94 GREEnness Metric Approach), and automatized procedure that can be integrated into the 3D printing pipeline.

Organ on-a-chip (OoC) is a promising technology that aims to recapitulate human body pathophysiology in a more precise way to advance in drug development and complex disease understanding. However, the presence of OoC in biological laboratories is still limited and mainly restricted to laboratories with access to cleanroom facilities. Besides, the current analytical methods employed to extract information from the organ models are endpoint and post facto assays which makes it difficult to ensure that during the biological experiment the cell microenvironment, cellular functionality and behaviour are controlled. Hence, the integration of real-time biosensors is highly needed and requested by the OoC end-user community to provide insight into organ function and responses to stimuli. In this context, electrochemical sensors stand out due to their advantageous features like miniaturization capabilities, ease of use, automatization and high sensitivity and selectivity. Electrochemical sensors have been already successfully miniaturized and employed in other fields such as wearables and point-of-care devices. We have identified that the explanation for this issue may be, to a large extent, the accessibility to microfabrication technologies. These fields employ preferably digital manufacturing (DM), which is a more accessible microfabrication approach regardless of funding and facilities. Therefore, we envision that a paradigm shift in microfabrication that adopts DM instead of the dominating soft lithography for the in-lab microfabrication of OoC devices will contribute to the dissemination of the field and integration of the promising real-time sensing.