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

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

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

A lithographic polymer process sequence for chemical sensing arrays

A novel process for the deposition of four different patternable polymers to be used as sensing layers in chemical sensors, on the same substrate, using lithographic techniques is described. The process is combined with the engineering of the swelling properties of two of the polymeric materials upon exposure to DUV irradiation to expand the array to six or eight elements. The use of lithographic processes allows the deposition of polymeric films at the desired pattern and for a wide film thickness range. The sensing properties of the deposited and engineered films in the array were characterized by monitoring volume expansion upon exposure to volatile organic compounds. The process is particularly useful in the fabrication of chemical sensor arrays where polymers with varying sensitivities and selectivities are required. © 2006 Elsevier B.V. All rights reserved

Entropic nanothermodynamic potential from molecular trapping within photon induced nano-voids in photon processed PDMS layers

In any thermodynamic system, including nanosystems, the free energy change during sorption is related to its internal stressing. However, experimental evidence of energy flow between thermodynamic states before and after sorption of a small number of molecules in nanosystems is rare, due to the minute energy flow and sub-nm strain variation. In this work, it is shown that the entropic variation during isothermal and isobaric sorption of gaseous (water or methanol) molecules in an ensemble of photon induced nano-voids within a PDMS matrix is proportional to the number of nano-voids and the entropic nanothermodynamic potential is the outcome of the confinement of translational motion of the adsorbed molecules within the nano-voids. Following irradiation of PDMS with a molecular fluorine laser at 157 nm, white light reflectance spectroscopy establishes the relation between the entropic variation, via the sub-nm strain field, and the external parameters (number of photons and adsorbed molecules). Moreover, the contribution of entropic, internal, chemical and surface energy components in the stressing field is analyzed by nanoindentation and atomic force microscopy. The methodology allows the identification of nanothermodynamic potentials and strain field variations in thin polymeric layers at pJ and sub-nm levels. \ua9 2012 The Royal Society of Chemistry

Biomolecular layer thickness evaluation using White Light Reflectance Spectroscopy

A White Light Reflectance Spectroscopy (WLRS) methodology is applied in the evaluation of the effectiveness of biomolecules immobilization onto solid surfaces as well as their subsequent reaction with counterpart biomolecules via measuring the respective layers thickness. In particular we investigated the adsorption of rabbit and mouse gamma-globulins as well as their reaction with complementary antibodies. The results obtained with the proposed methodology were compared with those received by atomic force microscopy analysis of the same samples. It was found that the developed method provides a simple, very fast and accurate approach for thin biomolecular layers thickness determination