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In this review, we overview designs and applications of microfluidics-based human mini-brains for reconstituting CNS disorders and expanded model systems ranging from the CNS to CNS-connecting organ axes with future perspectives.

Drug-induced skin sensitization is prevalent worldwide and can trigger life-threatening health conditions, such as Stevens Johnson Syndrome. However, existing in vitro skin models cannot adequately predict the skin sensitization effects of drugs administered into the systemic circulation because dermal inflammation and injury are preceded by conversion of parent drugs into antigenic reactive metabolites in the liver and subsequent activation of the immune system. Here, we demonstrate that recapitulation of these early tandem cellular processes in a compartmentalized liver-immune coculture array is sufficient to predict the skin sensitization potential of systemic drugs. Human progenitor cell (HepaRG)-derived hepatocyte spheroids and U937 myeloid cells, a representative antigen presenting cell (APC), can maintain their respective functions in 2 concentric micro-chambers, which are connected by a diffusion microchannel network. Paradigm drugs that are reported to cause severe cutaneous drug reactions (i.e. carbamazepine, phenytoin and allopurinol) can be metabolized into their reactive metabolites, which diffuse efficiently into the adjoining immune compartment within a 48 hour period. By measuring the extent of U937 activation as indicated by IL8, IL1β and CD86 upregulation upon drug administration, we show that the liver-immune coculture array more consistently and reliably distinguish all 3-paradigm skin sensitizing drugs from a non-skin sensitizer than conventional bulk Transwell coculture. Given its miniaturized format, design simplicity and prediction capability, this novel in vitro system can be readily scaled into a screenable platform to identify the skin sensitization potential of systemically-administered drugs.

In this paper, we present a method combining surface-enhanced Raman scattering (SERS) spectroscopy to detect biomolecules in a label-free way with an electrokinetic preconcentration technique (electrophoresis) to amplify biomolecular signals at low concentrations. A constant electric field is applied to charged biomolecules in solution, attracting them to an oppositely charged electrode, which is also used as a SERS substrate. Within 5 min, we observed that the SERS signal of 10 fM adenine was amplified to the level of the signal of non-preconcentrated 1 microM adenine (sensitivity improvement by 8 orders of magnitude) and the method was effective over a wide range of concentrations (10 fM to 1 microM). The signals were further amplified under stronger electric field and longer application: The increase of the signal intensity was observed to be 51 times at -0.6 V cm(-1) after 25 min. The effectiveness of this method allows the creation of label-free, target-specific, and highly sensitive monitoring applications.