On-Chip Neural Induction Boosts Neural Stem Cell Commitment: Toward a Pipeline for iPSC-Based Therapies.

The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast markers, on par with those reprogrammed in standard well-conditions. The NSCs differentiated in microfluidic chips show upregulation of neuroectodermal markers (ZIC1, PAX6, SOX1), highlighting their propensity for nervous system development. Cells obtained on conventional well plates and microfluidic chips are compared for reprogramming and neural induction by bulk RNA sequencing. Pathway enrichment analysis of NSCs from chip showed neural stem cell development enrichment and boosted commitment to neural stem cell lineage in initial phases of neural induction, attributed to a confined environment in a microfluidic chip. This method provides a cost-effective pipeline to reprogram and differentiate iPSCs for therapeutics compliant with current good manufacturing practices.

Mixing Insulating Commodity Polymers with Semiconducting n-type Polymers Enables High-Performance Electrochemical Transistors.

Diluting organic semiconductors with a host insulating polymer is used to increase the electronic mobility in organic electronic devices, such as thin film transistors, while considerably reducing material costs. In contrast to organic electronics, bioelectronic devices such as the organic electrochemical transistor (OECT) rely on both electronic and ionic mobility for efficient operation, making it challenging to integrate hydrophobic polymers as the predominant blend component. This work shows that diluting the n-type conjugated polymer p(N-T) with high molecular weight polystyrene (10 KDa) leads to OECTs with over three times better mobility-volumetric capacitance product (µC*) with respect to the pristine p(N-T) (from 4.3 to 13.4 F V-1 cm-1 s-1) while drastically decreasing the amount of conjugated polymer (six times less). This improvement in µC* is due to a dramatic increase in electronic mobility by two orders of magnitude, from 0.059 to 1.3 cm2 V-1 s-1 for p(N-T):Polystyrene 10 KDa 1:6. Moreover, devices made with this polymer blend show better stability, retaining 77% of the initial drain current after 60 minutes operation in contrast to 12% for pristine p(N-T). These results open a new generation of low-cost organic mixed ionic-electronic conductors where the bulk of the film is made by a commodity polymer.

Bimetallic Hollow Nanostructures for Colorimetric Detection of Picomolar Level of Mercury.

In this paper, we report the use of bimetallic hollow nanostructures (BHNS), consisting of gold and silver metals, for colorimetric detection of mercury. The sodium dodecyl sulphate (SDS)-capped BHNS were prepared by galvanic etching of silver nanoparticles (AgNPs) using gold chloride resulting in a partially hollow AgNPs with the gold layer at its surface. These BHNS were interacted with an aqueous solution of mercury ions (Hg2+) in the concentration range of 10 pM-10 mM. Interestingly, at higher concentration range (10 µM-10 mM), a noticeable change in the solution color was observed with a prominent decrease in the absorption intensity and blue-shift in the peak plasmonic wavelength. This could be attributed to (i) complexation reaction between the anionic BHNS (due to the negatively charged SDS capping) and cationic Hg2+ and (ii) oxidative etching of silver from BHNS causing its depletion and resulting into Ag-Hg amalgam and/or aggregation of the nanostructures. In contrast, at lower concentration range (i.e., 10 pM-10 nM), an increase in the absorption intensity was observed, which was possibly due to the oxidative etching of silver from BHNS without aggregation of the nanostructures. The low amount of Hg2+ was not sufficient enough to interact with SDS capping layer present on the BHNS surface, unlike the higher concentrations of mercury and therefore, did not cause any aggregation. The developed colorimetric sensor showed high sensitivity and selectivity towards Hg2+ detection with a limit of detection of 10 pM and good linearity (R² = 0.97) in the concentration range of 10 pM-10 nM.

Dendrimer as a multifunctional capping agent for metal nanoparticles for use in bioimaging, drug delivery and sensor applications.

Advances in nanoparticle research, particularly in the domain of surface-engineered, function-oriented nanoparticles, have had a profound effect in many areas of scientific research and aided in bringing unprecedented developments forward, particularly in the biomedical field. Surface modifiers/capping agents have a direct bearing on the major properties of metal nanoparticles (MNPs), ranging from their physico-chemical properties to their stability and functional applications. Among the different classes of capping agents, dendrimers have gained traction as effective multifunctional capping agents for MNPs due to their unique structural qualities, dendritic effect and polydentate nature. Dendrimer-coated metal nanoparticles (DC-MNPs) are typically produced by both (i) a one-pot strategy, where metal ions are reduced in the presence of dendrimer molecules and (ii) a multi-pot strategy, where a sequence of reactions involving the reduction of metal ions, activation, conjugation and purification steps are involved. These DC-MNPs have shown remarkable ability to stabilize MNPs by means of electrostatic interactions, coordination chemistry or covalent attachment, due to them entailing a large number of sites at which further molecular moieties can be conjugated. This review article is an attempt to consolidate the on-going work, particularly over the last five years, in the field of the synthesis of dendrimer-coated MNPs and their potential applications in bioimaging, drug delivery and biochemical sensors.