Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell–cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.United States. Army Research Office. Institute for Soldier NanotechnologiesNational Institutes of Health (U.S.) (HL092836)National Institutes of Health (U.S.) (EB02597)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL099073)National Science Foundation (U.S.) (DMR0847287)United States. Office of Naval Research (ONR PECASE Award)United States. Office of Naval Research (Young Investigator award)National Research Foundation of Korea (grant (NRF-2010-220-D00014)

A Microfluidic Platform Containing Sidewall Microgrooves for Cell Positioning and Trapping

Microfluidic channels enable the control of cell positioning and the capturing of cells for high-throughput screening and other cellular applications. In this paper, a simple microfluidic platform is proposed for capturing small volumes of cells using sidewall microgrooves. The cell docking patterns in the channels containing sidewall microgroove are also studied. Both numerical and experimental investigations are performed within channels containing sidewall microgrooves of three different widths (i.e., 50, 100 and 200 µm). It is observed that channels containing sidewall microgrooves play an important role in regulating cell positioning and patterning. The obtained results revealed that 10 to 14 cells were positioned inside the sidewall channels of 200 µm width, two to five cells were positioned within the channels of 100 µm width, and one to two individual cells were docked within the sidewall channel of 50 µm width. Particle modelling shows the prediction of cell positioning within sidewall microgrooves. The positions of cells docked within microgroove-containing channels were also quantified. Furthermore, the shear stress variation and cell positioning in the sidewall microgrooves were correlated. Therefore, these sidewall microgroove-containing channels could be potentially useful for regulating cell positioning and patterning on two-dimensional surfaces, three-dimensional microenvironments and high-throughput screening. Cell patterning and positioning are of great importance in many biological applications, such as drug screening and cell-based biosensing

High-throughput size-based rare cell enrichment using microscale vortices

Cell isolation in designated regions or from heterogeneous samples is often required for many microfluidic cell-based assays. However, current techniques have either limited throughput or are incapable of viable off-chip collection. We present an innovative approach, allowing high-throughput and label-free cell isolation and enrichment from heterogeneous solution using cell size as a biomarker. The approach utilizes the irreversible migration of particles into microscale vortices, developed in parallel expansion-contraction trapping reservoirs, as the cell isolation mechanism. We empirically determined the critical particle∕cell diameter Dcrt and the operational flow rate above which trapping of cells∕particles in microvortices is initiated. Using this approach we successfully separated larger cancer cells spiked in blood from the smaller blood cells with processing rates as high as 7.5×106 cells∕s. Viable long-term culture was established using cells collected off-chip, suggesting that the proposed technique would be useful for clinical and research applications in which in vitro culture is often desired. The presented technology improves on current technology by enriching cells based on size without clogging mechanical filters, employing only a simple single-layered microfluidic device and processing cell solutions at the ml∕min scale