Mimicking the kidney: A key role in organ-on-chip development

Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal models. In this regard, promising advances have recently been made by the so-called "organ-on-chip"(OOC) technology. By combining cell culture with microfluidics, biomedical researchers have started to develop microengineered models of the functional units of human organs. With the capacity to mimic physiological microenvironments and vascular perfusion, OOC devices allow the reproduction of tissue- and organ-level functions. When considering drug testing, nephrotoxicity is a major cause of attrition during pre-clinical, clinical, and post-approval stages. Renal toxicity accounts for 19% of total dropouts during phase III drug evaluation more than half the drugs abandoned because of safety concerns. Mimicking the functional unit of the kidney, namely the nephron, is therefore a crucial objective. Here we provide an extensive review of the studies focused on the development of a nephron-on-chip device

Efectos de la implantación iónica de boro sobre el aislamiento eléctrico entre MESFET's en circuitos integrados de GaAs

[spa] Al principio de los años 60, aparecieron los primeros transistores FET en Arseniuro de Galio. En el instante en que el silicio se imponía de forma definitiva al germanio, la aparición de este nuevo material venía justificada por múltiples razones: a) El material GaAs de tipo N presenta unas propiedades de transporte muy buenas; b) Se pueden conseguir alturas de barrera Schottky elevadas, con diversidad de metales (Al,Pt,Ti,...), obteniéndose diodos con un factor de calidad excelente y un valor de la corriente en inverso baja; c) La estructura de bandas del GaAs que presenta un gap directo, favorece las transiciones ópticas entre las bandas. Este hecho, ha determinado que el GaAs sea el material base, sobre el que se ha desarrollado la Optoelectrónica; d) La posibilidad de obtener un substrato semi-aislante, es una importante ventaja para simplificar la tecnología de circuitos integrados en GaAs, al permitir utilizar el substrato para realizar el aislamiento entre dispositivos. Las diferentes propiedades que hemos enunciado, hacen del GaAs, además de su aplicación generalizada en optoelectrónica, el candidato idóneo para aplicaciones de alta velocidad como amplificadores hiperfrecuencia (Gigahertz) y circuitos integrados lógicos de gran velocidad (Gigabits). En esta memoria, analizaremos el aislamiento entre dispositivos MESFET obtenido mediante la implantación iónica de boro en comparación con otros métodos de aislamiento. La evaluación de los resultados obtenidos, se realizará en función de la corriente de fugas existente entre dispositivos - capítulo III- y el mayor o menor grado de backgating que presenten los mismos-capítulo IV-. No es posible lograr una comprensión de los efectos tecnológicos de un proceso como la implantación iónica, sin estudiar en primer lugar aspectos propios de la física de semiconductores como es los defectos producidos por la irradiación, en particular los eléctricamente activos. Así, en el capítulo I, se estudia las características de los defectos producidos por la implantación iónica de boro, mediante espectroscopía de emisión térmica (DLTS). Este análisis no sería completo sin el estudio de los parámetros ópticos asociados a los mismos. Por ello, en el capítulo II, se analizan los espectros de fotocapacidad, mediante la aplicación de una nueva técnica (Optical Isothermal Transient Spectroscopy), cuyos resultados nos han permitido confirmar la existencia de interacción entre los defectos producidos

Gas identification with tin oxide sensor array and self-organizing maps: adaptive correction of sensor drifts

Low-cost tin oxide gas sensors are inherently nonspecific. In addition, they have several undesirable characteristics such as slow response, nonlinearities, and long-term drifts. This paper shows that the combination of a gas-sensor array together with self-organizing maps (SOM's) permit success in gas classification problems. The system is able to determine the gas present in an atmosphere with error rates lower than 3%. Correction of the sensor's drift with an adaptive SOM has also been investigate

Surface-Bound Molecular Gradients for the High-Throughput Screening of Cell Responses

Chemical gradient surfaces are described as surfaces with a gradually varying composition along their length. Continuous chemical gradients have recently been proposed as an alternative to discrete microarrays for the high-throughput screening of the effects of ligand concentration in cells. Here, we review some of the most recent examples in which gradients have been used to evaluate the effect of a varying ligand concentration in cell adhesion, morphology, growth, and differentiation of cells, including some of our recent findings. They show the importance of the organization of ligands at the nanoscale, which is highlighted by abrupt changes in cell behavior at critical concentration thresholds

Dependence of impedance of embedded single cells on cellular behaviour

Non-invasive single cell analyses are increasingly required for the medicaldiagnostics of test substances or the development of drugs and therapies on the single celllevel. For the non-invasive characterisation of cells, impedance spectroscopy whichprovides the frequency dependent electrical properties has been used. Recently,microfludic systems have been investigated to manipulate the single cells and tocharacterise the electrical properties of embedded cells. In this article, the impedance ofpartially embedded single cells dependent on the cellular behaviour was investigated byusing the microcapillary. An analytical equation was derived to relate the impedance ofembedded cells with respect to the morphological and physiological change ofextracellular interface. The capillary system with impedance measurement showed afeasibility to monitor the impedance change of embedded single cells caused bymorphological and physiological change of cell during the addition of DMSO. By fittingthe derived equation to the measured impedance of cell embedded at different negativepressure levels, it was able to extrapolate the equivalent gap and gap conductivity betweenthe cell and capillary wall representing the cellular behaviour

Design and fabrication of a microsystem to handle biological objects

Biological particle microhandling is a common operation in medicine and microbiology, and a lot of research work has been addressed to develop faster, cheaper and more efficient manipulation techniques. In this way, microsystem technologies play an important role because they can be used to fabricate microparticle manipulators. This paper describes the design and fabrication of a microsystem to handle biological objects, based on the dielectrophoretic effects. The development of the right technological option among the possibilities at disposal is also discussed. The proposed design, a whole microsystem including electrical, optical and fluidic interfaces, was developed employing gold and platinum metals, silicon micromachining, and photoresin patterning techniques. Furthermore, the structure of the utilized microelectrode arrays, as well as the resulting microchip are also reported

Simple and fast method for fabrication of endoscopic implantable sensor arrays

Here we have developed a simple method for the fabrication of disposable implantable all-solid-state ion-selective electrodes (ISE) in an array format without using complex fabrication equipment or clean room facilities. The electrodes were designed in a needle shape instead of planar electrodes for a full contact with the tissue. The needle-shape platform comprises 12 metallic pins which were functionalized with conductive inks and ISE membranes. The modified microelectrodes were characterized with cyclic voltammetry, scanning electron microscope (SEM), and optical interferometry. The surface area and roughness factor of each microelectrode were determined and reproducible values were obtained for all the microelectrodes on the array. In this work, the microelectrodes were modified with membranes for the detection of pH and nitrate ions to prove the reliability of the fabricated sensor array platform adapted to an endoscope

Motion in microfluidic ratchets

The ubiquitous random motion of mesoscopic active particles, such as cells, can be "rectified" or directed by embedding the particles in systems containing local and periodic asymmetric cues. Incorporated on lab-on-a-chip devices, these microratchet-like structures can be used to self-propel fluids, transport particles, and direct cell motion in the absence of external power sources. In this Focus article we discuss recent advances in the use of ratchet-like geometries in microfluidics which could open new avenues in biomedicine for applications in diagnosis, cancer biology, and bioengineering

Miniaturizable ion-selective arrays based on highly stable polymer membranes for biomedical applications

Poly(vinylchloride) (PVC) is the most common polymer matrix used in the fabrication of ion-selective electrodes (ISEs). However, the surfaces of PVC-based sensors have been reported to show membrane instability. In an attempt to overcome this limitation, here we developed two alternative methods for the preparation of highly stable and robust ion-selective sensors. These platforms are based on the selective electropolymerization of poly(3,4-ethylenedioxythiophene) (PEDOT), where the sulfur atoms contained in the polymer covalently interact with the gold electrode, also permitting controlled selective attachment on a miniaturized electrode in an array format. This platform sensor was improved with the crosslinking of the membrane compounds with poly(ethyleneglycol) diglycidyl ether (PEG), thus also increasing the biocompatibility of the sensor. The resulting ISE membranes showed faster signal stabilization of the sensor response compared with that of the PVC matrix and also better reproducibility and stability, thus making these platforms highly suitable candidates for the manufacture of robust implantable sensors. Keywords: ion-selective electrode (ISE) sensor, pH detection, ischemia, electrochemistry, implantable device, biomedicine, endoscop