Heart on a chip: Micro-nanofabrication and microfluidics steering the future of cardiac tissue engineering

The evolution of micro and nanofabrication approaches significantly spurred the advancements of cardiac tissue engineering over the last decades. Engineering in the micro and nanoscale allows for the rebuilding of heart tissues using cardiomyocytes. The breakthrough of human induced pluripotent stem cells expanded this field rendering the development of human tissues from adult cells possible, thus avoiding the ethical issues of the usage of embryonic stem cells but also creating patient-specific human engineered tissues. In the case of the heart, the combination of cardiomyocytes derived from human induced pluripotent stem cells and micro/nano engineering devices gave rise to new therapeutic approaches of cardiac diseases. In this review, we survey the micro and nanofabrication methods used for cardiac tissue engineering, ranging from clean room-based patterning (such as photolithography and plasma etching) to electrospinning and additive manufacturing. Subsequently, we report on the main approaches of microfluidics for cardiac culture systems, the so-called “Heart on a Chip”, and we assess their efficacy for future development of cardiac disease modeling and drug screening platforms

Hydrophilic polymeric coatings for enhanced, serial-siphon based flow control on centrifugal lab-on-disc platforms

In this paper, we implement rotational flow control on a polymeric microfluidic “lab-on-a-disc” device by combining serial siphoning and capillary valving for sequential release of on-board stored liquid reagents. The functionality of this integrated, multi-step centrifugal assay platform is tightly linked by the capability to establish reproducible, capillary-driven priming of the innately hydrophobic siphon microchannels. We here demonstrate for the first time that spin-coated hydrophilic polymeric films of poly(vinyl alcohol) and (hydroxylpropyl)methylcellulose provide stable contact angles

Rapid prototyping of electrochemical lateral flow devices: stencilled electrodes

A straightforward and very cost effective method is proposed to prototype electrodes using pressure sensitive adhesives (PSA) and a simple cutting technique. Two cutting methods, namely blade cutting and CO2 laser ablation, are compared and their respective merits are discussed. The proposed method consists of turning the protective liner on the adhesive into a stencil to apply screen-printing pastes. After the electrodes have been printed, the liner is removed and the PSA can be used as a backing material for standard lateral flow membranes. We present the fabrication of band electrodes down to 250 μm wide, and their characterization using microscopy techniques and cyclic voltammetry. The prototyping approach presented here facilitates the development of new electrochemical devices even if very limited fabrication resources are available. Here we demonstrate the fabrication of a simple lateral-flow device capable of determining glucose in blood. The prototyping approach presented here is highly suitable for the development of novel electroanalytical tools.This work has been funded by the Spanish Ministry of Economy through the DADDi2 project (Grant TEC2013-48506). MK acknowledges funding through the Beatriu de Pinós program (BP-DGR-2013), supported by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the Cofund programme of the Marie Curie Actions of the 7th R&D Framework Programme of the European Union. We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)Peer reviewe

Near future climate change projections with implications for the agricultural sector of three major Mediterranean islands

AbstractThe paper presents the analysis of a sub-set of high-resolution bias-adjusted simulations from the EURO-CORDEX initiative, in order to examine the changes in the mean climate and the extremes in three Mediterranean islands, namely, Sicily, Crete and Cyprus, in the near future (2031–2060) compared to the present climate (1971–2000), under two future scenarios, i.e. RCP4.5 and RCP8.5. The analysis entails commonly used climatic indices of interest related to the islands' agricultural sector. The results indicate robust increases for both the mean maximum and minimum temperatures on a seasonal basis, as well as for the temperature related extremes under both climate scenarios. On the contrary, the changes in precipitation are less pronounced as the changes in the seasonal precipitation are not found statistically significant for the three islands under both scenarios. The projected warming combined with the projected unchanged precipitation pattern in the future, especially in spring and summer, might expose the crops to conditions with a negative impact on the plants' phenology, leading to implications on crop production and quality. The results presented here might be the basis for the development of an adaptation strategy specifically targeted on the three islands but also replicable to other Mediterranean islands

Emerging technologies and their potential for generating new assistive technologies

Limited access to assistive technology (AT) is a well-recognized global challenge. Emerging technologies have potential to develop new assistive products and bridge some of the gaps in access to AT. However, limited analyses exist on the potential of these technologies in the AT field. This paper describes a study that aimed to provide an overview of emerging technological developments and their potential for the AT field. It involved conducting a gray literature review and patent analysis to create an overview of the emerging enabling technologies that may foster the development of new AT products and services and identify emerging AT applications. The analysis identified seven enabling technologies that are relevant to the AT field. These are artificial intelligence, emerging human-computer interfaces, sensor technology, robotics, advances in connectivity and computing, additive manufacturing and new materials. Whilst there are over 3.7 million patents related to these enabling technologies, only a fraction of them–11,000 patents were identified in the analysis specifically related to AT (0.3%). The paper presents some of the promising examples. Overall, the results indicate that there is an enormous potential for new AT solutions that capitalize on emerging technological advances

Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering

Cardiac cell therapy holds a real promise for improving heart function and especially of the chronically failing myocardium. Embedding cells into 3D biodegradable scaffolds may better preserve cell survival and enhance cell engraftment after transplantation, consequently improving cardiac cell therapy compared with direct intramyocardial injection of isolated cells. The primary objective of a scaffold used in tissue engineering is the recreation of the natural 3D environment most suitable for an adequate tissue growth. An important aspect of this commitment is to mimic the fibrillar structure of the extracellular matrix, which provides essential guidance for cell organization, survival, and function. Recent advances in nanotechnology have significantly improved our capacities to mimic the extracellular matrix. Among them, electrospinning is well known for being easy to process and cost effective. Consequently, it is becoming increasingly popular for biomedical applications and it is most definitely the cutting edge technique to make scaffolds that mimic the extracellular matrix for industrial applications. Here, the desirable physico-chemical properties of the electrospun scaffolds for cardiac therapy are described, and polymers are categorized to natural and synthetic.Moreover, the methods used for improving functionalities by providing cells with the necessary chemical cues and a more in vivo- like environment are reported

Event-triggered logical flow control for comprehensive process integration of multi-step assays on centrifugal microfluidic platforms

Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.The centrifugal "lab-on-a-disc" concept has proven to have great potential for process integration of bioanalytical assays, in particular where ease-of-use, ruggedness, portability, fast turn-around time and cost efficiency are of paramount importance. Yet, as all liquids residing on the disc are exposed to the same centrifugal field, an inherent challenge of these systems remains the automation of multi-step, multi-liquid sample processing and subsequent detection. In order to orchestrate the underlying bioanalytical protocols, an ample palette of rotationally and externally actuated valving schemes has been developed. While excelling with the level of flow control, externally actuated valves require interaction with peripheral instrumentation, thus compromising the conceptual simplicity of the centrifugal platform. In turn, for rotationally controlled schemes, such as common capillary burst valves, typical manufacturing tolerances tend to limit the number of consecutive laboratory unit operations (LUOs) that can be automated on a single disc. In this paper, a major advancement on recently established dissolvable film (DF) valving is presented; for the very first time, a liquid handling sequence can be controlled in response to completion of preceding liquid transfer event, i.e. completely independent of external stimulus or changes in speed of disc rotation. The basic, event-triggered valve configuration is further adapted to leverage conditional, large-scale process integration. First, we demonstrate a fluidic network on a disc encompassing 10 discrete valving steps including logical relationships such as an AND-conditional as well as serial and parallel flow control. Then we present a disc which is capable of implementing common laboratory unit operations such as metering and selective routing of flows. Finally, as a pilot study, these functions are integrated on a single disc to automate a common, multi-step lab protocol for the extraction of total RNA from mammalian cell homogenate.Peer reviewe

Paper imbibition for timing of multi-step liquid handling protocols on event-triggered centrifugal microfluidic lab-on-a-disc platforms

This document is the Accepted Manuscript version of the following article: David J. Kinahan, Sinéad M. Kearney, Olivier P. Faneuil, Macdara T. Glynn, Nikolay Dimov, and Jens Ducrée, ‘Paper imbibition for timing of multi-step liquid handling protocols on event-triggered centrifugal microfluidic lab-on-a-disc platforms’, RSC Advances, Vol. 5 (3): 1818-1826, 2015, doi: https://doi.org/10.1039/C4RA14887H, published by the Royal Society of Chemistry.Rotational microfluidic platforms have attracted swiftly growing interest over the last decade due to their suitability for integration and automation of sample preparation and detection. Valving is of pivotal importance on these compact "Lab-on-a-Disc" (LoaD) platforms as all liquids are exposed to the same centrifugal field. A number of valving technologies have been developed to coordinate timing of serial and/or parallel multi-step/multi-liquid assay protocols comprising of laboratory unit operations (LUOs) such as the release, metering and mixing of sample and reagents. So far these valving techniques could be broadly categorised into rotationally controlled or externally actuated schemes. Only recently a new, "event-triggered" flow control has been introduced. In this approach, a valve is opened upon arrival of a liquid at a defined destination on the disc; this innovative mechanism for the first time permits the cascading of LUOs independent of the spin rate. In one technology, dissolvable films (DFs) are configured with a pneumatic chamber to offer function akin to an electrical relay. Dissolving one DF, termed the control film (CF), results in the release of liquid at a distal location through a so-called load film (LF). In this paper, a new method for temporal control of actuating DF-based, event-triggered CFs which are serially aligned at defined distances along a paper strip is introduced. Liquids are transported through the paper strip at a given velocity, thus setting well-defined intervals between subsequent LUOs, e.g. incubation steps. As a proof-of-concept, we present a disc with integrated metering and mixing which can perform a prototypical, 4-fold serial dilution; a common function in bioanalytical protocols. Imbibition of the paper strip sequentially opens five valves for serial dilution and mixing. To illustrate an unprecedented level of on-disc automation, this is followed by a branched cascade of 17 event-triggered valves (for a total of 22 liquid handling steps) which completes the serial dilution protocol.Peer reviewedFinal Accepted Versio

Highly sensitive label-free in vitro detection of aflatoxin B1 in an aptamer assay using optical planar waveguide operating as a polarization interferometer

This work reports on further development of an optical biosensor for the in vitro detection of mycotoxins (in particular, aflatoxin B1) using a highly sensitive planar waveguide transducer in combination with a highly specific aptamer bioreceptor. This sensor is built on a SiO2–Si3N4–SiO2 optical planar waveguide (OPW) operating as a polarization interferometer (PI), which detects a phase shift between p- and s-components of polarized light propagating through the waveguide caused by the molecular adsorption. The refractive index sensitivity (RIS) of the recently upgraded PI experimental setup has been improved and reached values of around 9600 rad per refractive index unity (RIU), the highest RIS values reported, which enables the detection of low molecular weight analytes such as mycotoxins in very low concentrations. The biosensing tests yielded remarkable results for the detection of aflatoxin B1 in a wide range of concentrations from 1 pg/mL to 1 μg/mL in direct assay with specific DNA-based aptamers