37 research outputs found
Miniature sensorized platform for engineered heart tissues
No full textThe high death toll of cardiovascular diseases worldwide and the lack of effective treatments for them are the main motivation for developing alternative and more efficient models for cardiac drug development and disease research. The missing link between current laboratory research on static in vitro and animal models and the clinical stage research on human patients could be created using the rapidly emerging Organ-on-Chip (OoC) technology. Themicrophysiological models developed within OoC research combine devices made of biocompatible, soft materials and human-origin organ-specific cell types, which are then exposed to flow, chemical, electrical or biomechanical stimuli.Modeling a human cardiac in vivo environment in an artificial model represents quite a challenge from several aspects. First, cardiac tissue in vivo is exposed to a strong coupling between different biomechanical and electrical stimuli that need to be faithfully captured by an in vitro model. Furthermore, such an in vitro model should recapitulate the complexity of cell-cell and cell-extracellular matrix (ECM) interactions between different cardiac cell types, while obtaining physiologically relevant responses. This thesis addresses the first challenge, in an attempt to engineer a dynamic, artificial microenvironment, suitable for the growth, monitoring, and stimulation of hiPSC-based engineered cardiac tissues (EHTs)....
JNP Zbor and Serbian orthodoxy
No full textIn this article the author researches the relationship between the Yugoslav National Movement Zbor and Serbian Orthodoxy. In the first part of the article he gives a short historical review of Ljoic's biography and history of the JNP Zbor. Thus, the theme is situated in historical context. In the second part of the article the author treats the Ljotic's relations, as a founder, president, leader and main ideologist of Zbor, with Serbian Orthodoxy and institution of the Serbian Orthodox Church. Special emphasis is on Ljotic's personal religiousness. In the last part the author researches influence of Orthodoxy upon JNP Zbor as an organization and ties between Zbor and the Serbian Orthodox Church.</jats:p
Some Estimations Of Positive And Negative Eigenvalues For An Inhomogeneous Membrane
No full text. In this paper we give some simple estimates of positive and negative eigenvalues for the inhomogeneous membrane boundary problem \Gamma\Deltau = mu; u j @D=0 if D ae R 2 is a simple connected domain and m is a real bounded function (possibly changing the sign). Introduction There exist lower bounds [1] for the smallest eigenvalue 1 for an inhomogeneous membrane problem \Gamma\Deltau = mu; u j @D=0 (1) where m is a bounded postive function on D and D ae R N is a simple connected domain. They are expressed in terms of the smallest positive zero of the Bessel function JN 2 \Gamma1 and the maximum of the function m. In some cases it is possible to deduce more precise estimates. Namely, if N = 2 and log m is a subharmonic function, Nehari [5] proved that 1 ? ßj 2 0 = R D m dx dy (j 0 is the smallest zero of the Bessel function J 0 ). This result is a generalization of the well known Faber-Krahn inequality [1]. In the case when D ae R 2 and when log m is not a subharmo..
Towards a read-out for capacitive displacement sensor in an engineered heart tissue device
No full textEngineered Heart Tissues (EHTs) are a valuable approach enabled by Organ-on-Chip (OoC) technology to model human cardiac tissue. These small microfluidic devices allow the culture and development of living cardiac cells in 3D structures, to reproduce tissue dynamics and functionality in-vitro, thus fostering the development of new and more precise models for human diseases and organs’ physiological response.One of the most important gaps in this recent technology is the lack of integration of electronic devices in the platforms, such as electrodes for tissue stimulation or sensors for real-time monitoring of the tissue.To cover this gap, a polymer-based platform with microwell and micropillars for culturing EHTs and measuring their contractile properties was developed in ECTM group at TU Delft. The contraction force exerted by the beating cardiac tissue, self-assembled around the micropillars, is quantified by measuring the displacement of the micropillars with spiral capacitive sensors embedded in the substrate. The force generated by the tissue corresponds to a capacitance change which is simulated to be in the aF range, requiring a high-precision, sensitive, and portable read-out circuitry.The investigation and development of this readout electronics is the final goal of this Master Thesis. A literature survey about possible capacitive readout techniques was conducted to identify suitable architectures for measuring such small dynamic changes in capacitance. Two solutions available on the market (Smartec UTI and Analog Devices AD7746) implementing two of these architectures were chosen, tested, and characterised. Benchmark measurements with accurate laboratory instrumentation were performed, and noise figures of the two solutions were evaluated.To allow the readout, EHT platforms with embedded sensors need to be transferred and assembled on a custom Printed Circuit Board (PCB): the viability of this challenging assembly process was evaluated. The multiple constraints deriving from such a complex project determined the development of a non-standard assembly process, which proved to be delicate and gave origin to multiple failure modes. Those were documented and analysed, to identify alternative or improved assembly procedures which need to be developed to fabricate reliable samples, since these weaknesses were identified as the most critical aspect at this point of the project.The results obtained showed how the two solutions for the readout provided results in good agreement with more precise non-portable laboratory instrumentation, and promising noise figures. The platforms with embedded sensors were successfully transferred to the developed PCBs, and measurements showed good agreement with the simulated static behaviour of the sensors, thus providing a valuable proof-of-concept for the whole project.The dynamic behaviour of the sensors was preliminarily investigated and characterized using nanoindentation tests, indicating the possibility to measure a linear relationship between the force applied and the difference in the sensed capacitance. Despite this good result, further tests need to be performed to verify it and to address some criticalities that were identified.Cardiac tissue was cultured on platforms with integrated sensors and the biocompatibility of the entire system was proved. The behaviour of the sensors during biological measurement with cardiac cells is left to future investigation
Characterization and Processing of Elastomers for Organ-on-Chip Applications
No full textThe current standard for organ-on-chip substrate materials is polydimethylsiloxane (PDMS). PDMS has many beneficial properties such as biocompatibility, transparency, elasticity, and easy prototyping. The main disadvantages of PDMS are its hydrophobicity (reducing cell attachment and cell proliferation), quick hydrophobic recovery (within a few hours) after surface modification, and unselective absorption of small molecules, altering drug concentration during testing or causing cross-contamination between channels. To overcome these shortcomings, an alternative material lacking the disadvantages and retaining the advantages of PDMS is needed in the field. Ostemer 324, Ostemer 220 and a variation of PDMS (PDMS+) were characterized to determine whether they would be a suitable alternative to PDMS as substrate material. The materials were compared to PDMS and characterized for spin-coating and curing on silicon wafers, moulding, etching, surface wettability before and after surface modification (plasma treatment), stiffness, optical transparency, biocompatibility and absorption of small molecules. The results of this work show that Ostemer 324 appears to be a promising alternative, with similar characteristics to PDMS. The main advantage is its hydrophilic surface, which becomes even more hydrophilic after plasma treatment, and slow hydrophobic recovery rate. However, its curing time is longer, the material is stiffer and not easy to mould. Ostemer 220 shows very poor adhesion on Teflon coated silicon wafers, is hard to mould, and shows inconsistent results during biocompatibility testing. PDMS+ is very similar to PDMS, and improves upon the latter in terms of surface wettability after surface modification, hydrophobic recovery and small molecule absorption.Biomedical Engineerin
Highly reproducible tissue positioning with tapered pillar design in engineered heart tissue platforms
No full textWe present a novel design of elastic micropillars for tissue self-assembly in engineered heart tissue (EHT) platforms. The innovative tapered profile confines reproducibly the tissue position along the main micropillar axis, increasing the accuracy of tissue contraction force measurement. Polydimethylsiloxane-based pillars were designed and fabricated by wafer-level molding in an hourglass shape, with symmetric tapering producing a restriction for tissue movement in the middle of the pillars’ length. Confinement efficacy of the new geometry was validated by comparing the tissue performance in straight versus tapered (75° or 80° tapering angle) micropillars. While in all three cases compact tissues formed successfully, for both tapered designs the functionality assays evidenced yield increase from 15% to 100%, higher spatial tissue confinement, and correspondingly higher accuracy and smaller dispersion in measurements of tissue contraction force.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.MicroelectronicsElectronic Components, Technology and Material
FET-based integrated charge sensor for organ-on-chip applications
No full textWe present an extremely compact field effect transistor (FET)-based electrochemical sensor for in situ real-time and label-free measurement of ion concentrations in the cell culture area of organs-on-chip (OoCs) devices. This sensor replaces the functionality of an external reference electrode, crucial in standard electrochemical sensing, by controlling the FET threshold voltage via a capacitive control gate. The silicon- and polymer-based charge sensor can be integrated in OoC platforms by means of a wafer-scale and CMOS-compatible microfabrication process. This fabrication approach inherently allows a superior level of accuracy, repeatability and scalability compared to common OoC manufacturing methods. The sensor combines in a single device the complementary benefits of silicon-based electronics and of flexible polymer membranes with integrated microelectrodes – congenial substrates to sustain dynamic stimuli and mimic physiological tissue microenvironments. The integration of the polymer membrane in the sensing region makes this miniature sensor a preferable option for high sensitivity biochemical measurements in OoC applications, including monitoring the pH of cell culture media and of tissue culturing microenvironments, quantification of ion displacement in cells, and complementary research on disease modeling.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic Components, Technology and MaterialsElectronic Instrumentatio
Spectral properties of an operator of Riesz potential type and its product with the Bergman projection on a bounded domain
No full textMicroelectromechanical Organs-on-Chip
No full textStemming from the convergence of tissue engineering and microfluidics, organ-on-chip (OoC) technology can reproduce in vivo-like dynamic microphysiological environments for tissues in vitro. The possibility afforded by OoC devices of realistic recapitulation of tissue and organ (patho)physiology may hold the key to bridge the current translational gap in drug development, and possibly foster personalized medicine. Here we underline the biotechnological convergence at the root of OoC technology, and outline research tracks under development in our group at TU Delft along two main directions: fabrication of innovative microelectromechanical OoC devices, integrating stimulation and sensing of tissue activity, and their embedding within advanced platforms for pre-clinical research. We conclude with remarks on the role of open technology platforms for the broader establishment of OoC technology in pre-clinical research and drug development.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic Components, Technology and Material
Sensor applications for organ-on-chip platforms
No full textMonitoring cell conditions and microenvironment in real time is crucial for Organ-on-Chip (OoC) functionality. In particular, biological cues such as ions, including metals and metabolites, play a critical role in physiology and homeostasis in the human body. • Real-time monitoring of ions without optical systems is an unmet need for OOCs [1]. • Electrochemical sensors, such as organic electrochemical [2] and thin-film transistors [3], may address this need. Most of these sensors however rely on reference electrodes.greenElectronic Components, Technology and Material
