Drug Evaluation Based on a Multi-Channel Cell Chip with a Horizontal Co-Culture

We developed a multi-channel cell chip containing a three-dimensional (3D) scaffold for horizontal co-culture and drug toxicity screening in multi-organ culture (human glioblastoma, cervical cancer, normal liver cells, and normal lung cells). The polydimethylsiloxane (PDMS) multi-channel cell chip (PMCCC) was based on fused deposition modeling (FDM) technology. The architecture of the PMCCC was an open-type cell chip and did not require a pump or syringe. We investigated cell proliferation and cytotoxicity by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and analysis of oleanolic acid (OA)-treated multi-channel cell chips. The results of the MTT and LDH assays showed that OA treatment in the multi-channel cell chip of four cell lines enhanced chemoresistance of cells compared with that in the 2D culture. Furthermore, we demonstrated the feasibility of the application of our multi-channel cell chip in various analysis methods through Annexin V-fluorescein isothiocyanate/propidium iodide staining, which is not used for conventional cell chips. Taken together, the results demonstrated that the PMCCC may be used as a new 3D platform because it enables simultaneous drug screening in multiple cells by single point injection and allows analysis of various biological processes.

Metallic Nanoparticle-Based Optical Cell Chip for Nondestructive Monitoring of Intra/Extracellular Signals

The biosensing platform is noteworthy for high sensitivity and precise detection of target analytes, which are related to the status of cells or specific diseases. The modification of the transducers with metallic nanoparticles (MNPs) has attracted attention owing to excellent features such as improved sensitivity and selectivity. Moreover, the incorporation of MNPs into biosensing systems may increase the speed and the capability of the biosensors. In this review, we introduce the current progress of the developed cell-based biosensors, cell chip, based on the unique physiochemical features of MNPs. Mainly, we focus on optical intra/extracellular biosensing methods, including fluorescence, localized surface plasmon resonance (LSPR), and surface-enhanced Raman spectroscopy (SERS) based on the coupling of MNPs. We believe that the topics discussed here are useful and able to provide a guideline in the development of new MNP-based cell chip platforms for pharmaceutical applications such as drug screening and toxicological tests in the near future.

Gold Nanowires/Fibrin Nanostructure as Microfluidics Platforms for Enhancing Stem Cell Differentiation: Bio-AFM Study

Organ-on-a-chip technology has gained great interest in recent years given its ability to control the spatio-temporal microenvironments of cells and tissues precisely. While physical parameters of the respective niche such as microchannel network sizes, geometric features, flow rates, and shear forces, as well as oxygen tension and concentration gradients, have been optimized for stem cell cultures, little has been done to improve cell-matrix interactions in microphysiological systems. Specifically, detailed research on the effect of matrix elasticity and extracellular matrix (ECM) nanotopography on stem cell differentiation are still in its infancy, an aspect that is known to alter a stem cell’s fate. Although a wide range of hydrogels such as gelatin, collagen, fibrin, and others are available for stem cell chip cultivations, only a limited number of elasticities are generally employed. Matrix elasticity and the corresponding nanotopography are key factors that guide stem cell differentiation. Given this, we investigated the addition of gold nanowires into hydrogels to create a tunable biointerface that could be readily integrated into any organ-on-a-chip and cell chip system. In the presented work, we investigated the matrix elasticity (Young’s modulus, stiffness, adhesive force, and roughness) and nanotopography of gold nanowire loaded onto fibrin hydrogels using the bio-AFM (atomic force microscopy) method. Additionally, we investigated the capacity of human amniotic mesenchymal stem cells (hAMSCs) to differentiate into osteo- and chondrogenic lineages. Our results demonstrated that nanogold structured-hydrogels promoted differentiation of hAMSCs as shown by a significant increase in Collagen I and II production. Additionally, there was enhanced calcium mineralization activity and proteoglycans formation after a cultivation period of two weeks within microfluidic devices.

Single-cell ChIP-seq imputation with SIMPA by leveraging bulk ENCODE data

Single-cell ChIP-seq analysis is challenging due to data sparsity. We present SIMPA (https://github.com/salbrec/SIMPA), a single-cell ChIP-seq data imputation method leveraging predictive information within bulk ENCODE data to impute missing protein-DNA interacting regions of target histone marks or transcription factors. Machine learning models trained for each single cell, each target, and each genomic region enable drastic improvement in cell types clustering and genes identification.