Cinzia Silvestri

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies.Significance:The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies.Significance:The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies. Significance: The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

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.

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.

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.