CS

C. Silvestri

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Organ-on-chip (OOC) is becoming the alternative tool to conventional in vitro screening. Heart-on-chip devices including microstructures for mechanical and electrical stimulation have been demonstrated to be advantageous to study structural organization and maturation of heart cells. This paper presents the development of metal and polymeric strain gauges for in situ monitoring of mechanical strain in the Cytostretch platform for heart-on-chip application. Specifically, the optimization of the fabrication process of metal titanium (Ti) strain gauges and the investigation on an alternative material to improve the robustness and performance of the devices are presented. The transduction behavior and functionality of the devices are successfully proven using a custom-made set-up. The devices showed resistance changes for the pressure range (0-3 kPa) used to stretch the membranes on which heart cells can be cultured. Relative resistance changes of approximately 0.008% and 1.2% for titanium and polymeric strain gauges are respectively reported for membrane deformations up to 5%. The results demonstrate that both conventional IC metals and polymeric materials can be implemented for sensing mechanical strain using robust microfabricated organ-on-chip devices. ...
The high aspect ratio and the porous nature of spatially oriented forest-like carbon nanotube (CNT) structures represent a unique opportunity to engineer a novel class of nanoscale assemblies. By combining CNTs and conformal coatings, a 3D lightweight scaffold with tailored behavior can be achieved. The effect of nanoscale coatings, aluminum oxide (Al2O3) and nonstoichiometric amorphous silicon carbide (a-SiC), on the thermal transport efficiency of high aspect ratio vertically aligned CNTs, is reported herein. The thermal performance of the CNT-based nanostructure strongly depends on the achieved porosity, the coating material and its infiltration within the nanotube network. An unprecedented enhancement in terms of effective thermal conductivity in a-SiC coated CNTs has been obtained: 181% compared to the as-grown CNTs and Al2O3 coated CNTs. Furthermore, the integration of coated high aspect ratio CNTs in an epoxy molding compound demonstrates that, next to the required thermal conductivity, the mechanical compliance for thermal interface applications can also be achieved through coating infiltration into foam-like CNT forests. ...
Conference paper (2018) - W.F. Quiros-Solano, N. Gaio, C. Silvestri, Y.B. Arik, O.M.J.A. Stassen, A.D. van der Meer, C.V.C. Bouten, A. van den Berg, R. Dekker, P.M. Sarro
We present a novel method to easily and reliably transfer highly porous, large area, thin microfabricated Polydimethylsiloxane (PDMS) porous membranes on Lab-on-Chip (LOC) and Organ-on-Chip (OOC) devices. The use of silicon as carrier substrate and a water-soluble sacrificial layer allows a simple and reproducible transfer of the membranes to any PDMS-based OOC and LOC device. The use of IC and MEMS compatible techniques reduces significantly the fabrication time and the need of manual handling. Our method is suitable for automatic assembling systems, such as pick-and-place, crucial to significantly increase the throughput of OOC and LOC devices assembling. Membranes with 8 μm pore size and as thin as 4 μm are successfully transferred. The viability and biocompatibility of the transfer was assessed by culturing two different cell lines on an OOC with transferred porous PDMS membranes. ...
Conference paper (2018) - J.A. Alfaro, P.M. Sberna, C. Silvestri, M. Mastrangeli, R. Ishihara, P.M. Sarro
A novel, simple, low-cost method for the void-free filling of high aspect ratio (HAR) through-silicon-vias (TSVs) is presented. For the first-time pure indium, a type-I superconductor metal, is used to fill HAR vias, 300 to 500 μm in depth and 50 to 100 μm in diameter. The low electrical resistivity achieved without sintering, its reproducibility and straightforward processing steps, and the short time required to fill large arrays of vias at wafer scale - all make this method one of the simplest and quickest options for filling HAR TSVs for MEMS 3D integration. Moreover, the low melting point (∼ 150 °C), malleability and superconductivity at 3.41 K make indium an interesting option in 3D interconnects for connecting quantum devices operating below 4 K. ...
Journal article (2018) - W. F. Quirós-Solano, N. Gaio, A. van den Berg, R. Dekker, P.M. Sarro, O.M.J.A. Stassen, Y.B. Arik, C. Silvestri, N.C.A. Van Engeland, A. Van der Meer, R. Passier, C.M. Sahlgren, C.V.C. Bouten
We present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 μm in diameter and a wide porosity range (2–65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 μm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs. ...
Polymeric (PEDOT:PSS) strain gauges embedded in PDMS membranes fabricated using a full wafer-scale fabrication process capable of realizing reproducible small features, are reported. The devices are characterized using a customized setup, which provides mechanical stretch while dynamically reading the electrical resistance. Measurements show relative resistance changes of approximately 11% for applied pressure up to 4 kPa. The process described is tailored to fabricate pressure sensors and microelectrodes for a flexible substrate-based Organ-on-Chip platform. ...
An unprecedented enhancement in electrical conductivity of horizontally aligned carbon nanotube (HA-CNT) structures using a 10 nm conformal coating of alumina (Al2O3) or amorphous silicon carbide (a-SiC) is presented. By combining the capability to grow long vertically aligned CNTs (VA-CNTs) with a liquid-assisted flattening technique, dense arrays of HA-CNTs exhibiting a high degree of alignment are realized and integrated at wafer-scale. Suspended structures, ranging from large area membranes to narrow beams, can be fabricated. The impressive enhancement in electrical conductivity, approximately 209% for the Al2O3 coated HA-CNTs (Al2O3/HA-CNTs) and 2276% for the a-SiC ones (a-SiC/HA-CNTs), demonstrates the potential of CNT-based scaffolds as scalable and functional building blocks for suspended interconnects, heat spreaders and novel chemical and optical sensors. ...
Doctoral thesis (2017) - Cinzia Silvestri, Lina Sarro, Guo Qi Zhang
The performances of microelectronic and optoelectronic devices are often severely limited by high temperatures and insufficient heat management. Therefore, when considering device fabrication and packaging, it is important to select materials based on their thermal performance. The increasing demand for more integrated functionality and miniaturization of microelectronic systems is pushing the limits of traditional cooling and packaging approaches. In fact, thermal management may well be the major bottleneck of the next electronics revolution. Efficient thermal management solutions are required at chip level as well as at system level. For example, heat dissipation is fundamental in microprocessor and integrated circuits (ICs) as in current mobile electronic or in server farms. Moreover, self-heating in applications like high power light-emitting diodes and solar cells affects their long-termstability. Therefore, novel cooling solutions are being developed based on nanotechnologies and functional nanomaterials. In particular, nanomaterials aremainly used as localized on-chip cooling solutions. They span from harvesting thermal energy, by using piezoelectric nanowires and super-lattice thin films, to heat spreading through graphene layers or nanocrystalline diamond, towards carbon nanotubes (CNTs) as thermal interface material (TIM) and heat sinks... ...
Thermal material properties play a fundamental role in the thermal management of microelectronic systems. The porous nature of carbon nanotube (CNT) arrays results in a very high surface area to volume ratio, which makes the material attractive for surface driven heat transfer mechanisms. Here, we report on the heat transfer performance of lithographically defined micropins made of carbon nanotube (CNT) nanofoam, directly grown on microhotplates (MHPs). The MHP is used as an in situ characterization platform with controllable hot-spot and integrated temperature sensor. Under natural convection, and equivalent power supplied, we measured a significant reduction in hot-spot temperature when augmenting the MHP surface with CNT micropins. In particular, a strong enhancement of convective and radiative heat transfer towards the surrounding environment is recorded, due to the high aspect ratio and the foam-like morphology of the patterned CNTs. By combining electrical characterizations with high-resolution thermographic microscopy analysis, we quantified the heat losses induced by the integrated CNT nanofoams and we found a unique temperature dependency of the equivalent convective heat transfer coefficient, Hc. The obtained results with the proposed non-destructive characterization method demonstrate that significant improvements can be achieved in microelectronic thermal management and hierarchical structured porous material characterization. ...

A Conductive and Flexible Polymer for Sensor Integration in Organ-on-Chip Platforms

Sensing and stimulating microstructures are necessary to develop more specialized and highly accurate Organ-on-Chip (OOC) platforms. In this paper, we present the integration of a conductive polymer, poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), on a stretchable membrane, core element of an Heart-on-Chip. The electrical conductivity along with its biocompatibility, high transparency (≈88%) and mechanical elasticity (≈1.2 GPa) make this material a candidate to develop novel microstructures for electrical monitoring and stimulation of cells in flexible-substrate based OOCs. Microstructures with different shapes and geometries of PEDOT:PSS embedded in a 9 μm-thick Polydimethylsiloxane (PDMS) membrane are developed following a wafer-level fabrication approach. PEDOT:PSS layers between 120 nm and 300 nm are obtained by varying the deposition conditions. The layers are successfully patterned and microstructures with lateral dimensions down to 2 μm. The obtained results indicate that this polymer is a suitable material for microfabrication of sensing and stimulating elements in OOC platforms. ...
We present a silicon carbide (SiC) based surface micromachined nanoreactor for in-situ characterization of reactions between solid nanostructured materials and gasses in transmission electron microscopes (TEMs). For the first time SiC is used as construction material for this device and a novel design of gas-microchannel with a two-level height is implemented. The use of SiC compared to the standard construction materials allows for easier and more reliable fabrication of the complete microsystem and for improved performance in terms of temperature. Additionally, the two-level height channel eases the loading of the specimens without affecting the sensitivity in the gas analysis. ...
Journal article (2016) - Nikolas Gaio, Cinzia Silvestri, Berend van Meer, Sten Vollebregt, CL Mummery, Ronald Dekker
Microelectrode arrays (MEAs) are widely used in biological application to locally stimulate and record the electrical activity of living cells. Here, a novel fabrication process for a carbon nanotube (CNT)-based MEA integrated on the backside of a free standing stretchable membrane is reported. The new process flow overcomes the manually intensive procedures used in the previous works. The microfabricated upside-down CNT MEA consists of microelectrodes with an area of 110 μm2 covered with cobalt-grown CNTs. The surface area enhancement and the foamlike morphology of the CNTs allow an increase of the charge injection per unit area at the electrode–electrolyte interface, resulting in a significantly lower electrochemical impedance of the electrodes. In particular, at 1 kHz, the fabricated CNT-MEA electrodes show a reduction of the overall impedance up to 96% in comparison with benchmark TiN electrodes. The obtained results confirm the effectiveness of the proposed surface texturing through CNT integration. Moreover, the quality and the morphology as well as the biocompatibility of the fabricated CNT-based electrodes were assessed. The obtained results demonstrate that significant improvement can be achieved by integrating structured nanoporous material on MEAs. ...