Carbon Nanotube Thin Film Biosensors for Sensitive and Reproducible Whole Virus Detection

Here, we report the label-free, sensitive, and real-time electrical detection of whole viruses using carbon nanotube thin film (CNT-TF) field effect devices. Selective detection of approximately 550 model viruses, M13-bacteriophage, is demonstrated using a simple two-terminal (no gate electrode) configuration. Chemical gating through specific antibody-virus binding on CNT surface is proposed to be the sensing mechanism. Compared to electrical impedance sensors with identical microelectrode dimensions (no CNT), the CNT-TF sensors exhibit sensitivity 5 orders higher. We believe the reported approach could lead to a reproducible and cost-effective solution for rapid viral identification

3D bioprinting of liver-mimetic construct with alginate/cellulose nanocrystal hybrid bioink

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.bprint.2017.12.001 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/3D bioprinting is a novel platform for engineering complex, three-dimensional (3D) tissues that mimic real ones. The development of hybrid bioinks is a viable strategy that integrates the desirable properties of the constituents. In this work, we present a hybrid bioink composed of alginate and cellulose nanocrystals (CNCs) and explore its suitability for extrusion-based bioprinting. This bioink possesses excellent shear-thinning property, can be easily extruded through the nozzle, and provides good initial shape fidelity. It has been demonstrated that the viscosities during extrusion were at least two orders of magnitude lower than those at small shear rates, enabling the bioinks to be extruded through the nozzle (100µm inner diameter) readily without clogging. This bioink was then used to print a liver-mimetic honeycomb 3D structure containing fibroblast and hepatoma cells. The structures were crosslinked with CaCl2 and incubated and cultured for 3 days. It was found that the bioprinting process resulted in minimal cell damage making the alginate/CNC hybrid bioink an attractive bioprinting material.Natural Sciences and Engineering Research Council (NSERC) of Canada (grant no. RGPIN-2016-04398

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)

Recent advances and challenges: Translational research of minimally invasive wearable biochemical sensors

Wearable diagnostic devices that continuously monitor biomarkers of interest can significantly improve disease outcome. However, there is currently a lack of commercially available wearable biochemical health devices. Many of the commercially available devices are limited to monitoring the body's physical parameters. Even though there has been progress in the development of minimally invasive wearable biochemical sensors (WBS), many challenges hinder their real-life implementation. In this review, we focus on studies that have evaluated the sensor's performance in vivo, classified as level 4 of the technology readiness level (TRL), to identify and understand the important technological factors and strategies towards the actualization of wearable biosensors. We first discuss recent progresses of WBS categorized by the transducers and target biofluid. Through comparative analysis, we show that sensor performance depends highly on the sensing element design such that the choice of bioreceptor, incorporation of nanomaterial, and surface area modifications have a profound effect on sensitivity, linear range, and stability. We observed that correctional analysis may be required to account the effect of external factors that can influence the sensor performance. Furthermore, translating in vitro sensor characterization is successful when monitoring simple biofluids, but personalized calibration that correlates the sensor response to a reference technique was observed to be the best method to accurately determine biomarker concentrations. By focusing on studies with validated in vivo experiments (compared to standard techniques), we assess how various design strategies influence the WBS’ in vivo performance

Carbon Nanotube Thin Film Biosensors for Sensitive and Reproducible Whole Virus Detection

Here, we report the label-free, sensitive, and real-time electrical detection of whole viruses using carbon nanotube thin film (CNT-TF) field effect devices. Selective detection of approximately 550 model viruses, M13-bacteriophage, is demonstrated using a simple two-terminal (no gate electrode) configuration. Chemical gating through specific antibody-virus binding on CNT surface is proposed to be the sensing mechanism. Compared to electrical impedance sensors with identical microelectrode dimensions (no CNT), the CNT-TF sensors exhibit sensitivity 5 orders higher. We believe the reported approach could lead to a reproducible and cost-effective solution for rapid viral identification.</p

Reversible gating of ion transport through DNA-functionalized carbon nanotube membranes

Carbon nanotubes (CNTs) can be used to create unique fluidic systems for studying ion transport in nanochannels due to their well-defined geometry, atomically smooth and chemically inert surface, and similarity to transmembrane protein pores. Here, we report the reversible molecular gating of ion transport across DNA-functionalized CNT membranes. The diffusive transport rates of ferricyanide ions through membranes, each with an array of aligned transmembrane CNT channels, were monitored. Single-stranded DNA (T15) gate molecules were covalently linked to CNT channel entrances, and reversible opening and closing of CNT channels were achieved by the addition and removal of complementary DNAs (A15) with a remarkable open/close flux ratio of > 1000, which is substantially higher than the protein-gated CNT systems reported previously. Furthermore, at least two-orders of magnitude difference in ion fluxes was observed when single base-pair mismatched DNAs were used in place of the complementary DNAs. Comprehensive theoretical analysis is also presented. The experimental results can be explained by steric hindrance, ion partitioning, and electrostatic repulsion at the CNT entrances, as well as the thermodynamics of DNA binding.This research is financially supported by a Discovery grant from the Natural Sciences and Engineering Research Council of Canada (NSERC)

Carbon Nanotube-Based Supercapacitors with Excellent ac Line Filtering and Rate Capability <i>via</i> Improved Interfacial Impedance

We report the fabrication of high-performance, self-standing composite sp²-carbon supercapacitor electrodes using single-walled carbon nanotubes (CNTs) as conductive binder. The 3-D mesoporous mesh architecture of CNT-based composite electrodes grants unimpaired ionic transport throughout relatively thick films and allows superior performance compared to graphene-based devices at an ac line frequency of 120 Hz. Metrics of 601 μF/cm² with a −81° phase angle and a rate capability (RC) time constant of 199 μs are obtained for thin carbon films. The free-standing carbon films were obtained from a chlorosulfonic acid dispersion and interfaced to stainless steel current collectors with various surface treatments. CNT electrodes were able to cycle at 200 V/s and beyond, still showing a characteristic parallelepipedic cyclic votammetry shape at 1 kV/s. Current densities are measured in excess of 6400 A/g, and the electrodes retain more than 98% capacity after 1 million cycles. These promising results are attributed to a reduction of series resistance in the film through the CNT conductive network and especially to the surface treatment of the stainless steel current collector