Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data for in vivo tests. In this review, we discuss the characteristics of 3D cell culture systems in comparison to the two-dimensional (2D) monolayer culture, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles. The innovations and development in 3D culture systems for drug discovery over the past 5 years are also reviewed in the article, emphasizing the cellular response to different classes of anticancer drugs, focusing particularly on similarities and differences between 3D and 2D models across the field. The progression and advancement in the application of 3D cell cultures in cell-based biosensors is another focal point of this review.

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Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors

Research to develop alternative electrode materials with high energy densities in Li-ion batteries has been actively pursued to satisfy the power demands for electronic devices and hybrid electric vehicles. This critical review focuses on anode materials composed of Group IV and V elements with their composites including Ag and Mg metals as well as transition metal oxides which have been intensively investigated. This critical review is devoted mainly to their electrochemical performances and reaction mechanisms (313 references).

Li-alloy based anode materials for Li secondary batteries.

High energy-density lithium-ion batteries are in demand for portable electronic devices and electrical vehicles. Since the energy density of the batteries relies heavily on the cathode material used, major research efforts have been made to develop alternative cathode materials with a higher degree of lithium utilization and specific energy density. In particular, layered, Ni-rich, lithium transition-metal oxides can deliver higher capacity at lower cost than the conventional LiCoO2 . However, for these Ni-rich compounds there are still several problems associated with their cycle life, thermal stability, and safety. Herein the performance enhancement of Ni-rich cathode materials through structure tuning or interface engineering is summarized. The underlying mechanisms and remaining challenges will also be discussed.

Nickel‐Rich Layered Lithium Transition‐Metal Oxide for High‐Energy Lithium‐Ion Batteries

Over 7,000 peer reviewed articles have been published on electrochemical glucose assays and sensors over recent years. Their number makes a full review of the literature, or even of the most recent advances, impossible. Nevertheless, this chapter should acquaint the reader with the fundamentals of the electrochemistry of glucose and provide a perspective of the evolution of the electrochemical glucose assays and monitors helping diabetic people, who constitute about 5 % of the world’s population. Because of the large number of diabetic people, no assay is performed more frequently than that of glucose. Most of these assays are electrochemical. The reader interested also in nonelectrochemical assays used in, or proposed for, the management of diabetes is referred to a 2007 excellent review of Kondepati and Heise [1].

Electrochemical glucose sensors and their applications in diabetes management.

CMOS active pixel sensors (APS) have performance competitive with charge-coupled device (CCD) technology, and offer advantages in on-chip functionality, system power reduction, cost, and miniaturization. This paper discusses the requirements for CMOS image sensors and their historical development, CMOS devices and circuits for pixels, analog signal chain, and on-chip analog-to-digital conversion are reviewed and discussed.

CMOS image sensors: electronic camera-on-a-chip

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

Electroless plating of very thin metal films, such as copper, is accomplished with a spray processor. Atomized droplets or a continuous stream of an electroless plating solution are sprayed on a substrate. The electroless plating solution may be prepared by mixing a reducing solution and a metal stock solution immediately prior to the spraying. The deposition process may be carried out in an apparatus which includes metal stock solution and reducing reservoirs, a mixing chamber for forming the plating solution, optionally an inert gas or air (oxygen) source, a process chamber in which the solution is sprayed on the substrate and a control system for providing solutions to the mixing chamber and the process chamber in accordance with a predetermined program for automated mixing and spraying of the plating solution. The process can be used to form metal films as thin as 100 A and these films have low resistivity values approaching bulk values, low surface roughness, excellent electrical and thickness uniformity and mirror-like surface. Low temperature annealing may be used to further improve electrical characteristics of the deposited films. The thin metal films produced by the disclosed process can be used in semiconductor wafer fabrication and assembly, and in preparation of thin film discs, thin film heads, optical storage devices, sensor devices, microelectromachined sensors (MEMS) and actuators, and optical filters.

Electroless deposition of metal films with spray processor

Electroless copper deposition for ULSI

Electroless Cu thermodynamics, electrochemistry, mechanism, kinetics, and mass transport are reviewed. Electroless Cu deposition is a thermodynamically favorable and kinetically inhibited process, with two electrochemical reactions including anodic oxidation of a reducing agent and cathodic reduction of metal ions occurring simultaneously, with a multistep catalytic redox mechanism, an Arrhenius type of rate equation, and mass-transport limited reaction in narrow and deep features such as subhalf micron trenches and vias of high aspect ratios (>3). Selective and blanket electroless Cu deposition from formaldehyde-based solutions with ethylenediaminetetraacetic acid as a complexing agent was investigated for trench/via filling applications. A single-wafer electroless Cu deposition system with up to 8 in. wafer capability has been designed and manufactured. An electroless Cu deposition solution and operation conditions have been optimized to obtain electroless Cu films at high deposition rate (∼75 to 120 nm/min), with low resistivity (p < 2 μΩ cm), low surface roughness (R a ∼ 10 to 15 nm for ∼1.5 μm thick deposits) and good electrical uniformity (std dev <3% for 6 in. wafers and 5 to 7% for 8 in. wafers). A novel dry seeding method on sputtered Cu/Al bilayers has been developed to provide protection of Cu catalytic properties from passivation by using an Al sacrificial layer and to obtain uniform initiation and blanket growth of electroless Cu by in situ Al dissolution in the plating bath. Electroless Cu films blanket deposited on sputtered Cu/Al seed layer were conformal with 100% step coverage. A novel wet seeding method has been developed with Cu contact displacement deposition on a TiN diffusion barrier to provide selective and blanket electroless copper plating. Subhalf micron (down to 0.3 μm) trenches and vias of high aspect ratios (up to 5:1) were completely filled for both blanket and selective electroless deposition modes.

https://iopscience.iop.org/article/10.1149/1.1837505/pdf

Selective and Blanket Electroless Copper Deposition for Ultralarge Scale Integration

The transport of copper in silicon dioxide thermally grown on single crystalline silicon was studied by capacitance techniques, secondary ion mass spectroscopy (SIMS) analysis, and Rutherford backscattering spectrometry (RBS). Metal/oxide/silicon (MOS) capacitors were used to study the penetration of copper into the oxide as a function of temperature and applied electric field. The role of a titanium layer between the copper and the oxide was also studied. Bias‐thermal stress (BTS) studies of MOS structures were conducted at 150°C to 300°C with an electric field of 1 MV/cm for times ranging between 10 min and 168 h. It is shown that without bias a relatively small amount of copper reaches the silicon/silicon dioxide interface, with a maximum surface concentration of about 1017 cm−3 that drops exponentially with depth in the oxide. The high‐frequency (100 kHz) capacitance vs. voltage (CV) characteristics of the MOS devices changed drastically when a positive bias was applied to the gate and copper reached the silicon/silicon‐dioxide interface. The penetration time for copper through the oxide was characterized as a function of the temperature. The copper drift velocity, mobility and diffusivity in the oxide were determined and the copper profiles in the capacitors were characterized by SIMS. The activation energy for the diffusivity and mobility models was found to be . Devices without a barrier layer, which were stressed under a positive electric field, showed high copper concentration in the oxide, up to 1021 cm−3. At high temperatures and long stress times a significant amount of copper was also found in the silicon substrate. A titanium layer thicker than 5 nm acted as effective barrier even after 30 h of BTS at 300°C.

Yosi Shacham-Diamand

Papers

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

Electroless deposition of metal films with spray processor

Electroless copper deposition for ULSI

Selective and Blanket Electroless Copper Deposition for Ultralarge Scale Integration

Copper transport in thermal SiO2