Lung-on-a-chip: the future of respiratory disease models and pharmacological studies.

Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs; and in the case of this review, the lung. Lung-on-a-chip models result in a more accurate reflection compared to conventional in vitro models. Pharmaceutical drug testing methods traditionally use animal models in order to evaluate pharmacological and toxicological responses to a new agent. However, these responses do not directly reflect human physiological responses. In this review, current and future applications of the lung-on-a-chip in the respiratory system will be discussed. Furthermore, the limitations of current conventional in vitro models used for respiratory disease modeling and drug development will be addressed. Highlights of additional translational aspects of the lung-on-a-chip will be discussed in order to demonstrate the importance of this subject for medical research.

CMOS-Compatible Silicon Nanowire Field-Effect Transistor Biosensor: Technology Development toward Commercialization.

Owing to their two-dimensional confinements, silicon nanowires display remarkable optical, magnetic, and electronic properties. Of special interest has been the development of advanced biosensing approaches based on the field effect associated with silicon nanowires (SiNWs). Recent advancements in top-down fabrication technologies have paved the way to large scale production of high density and quality arrays of SiNW field effect transistor (FETs), a critical step towards their integration in real-life biosensing applications. A key requirement toward the fulfilment of SiNW FETs' promises in the bioanalytical field is their efficient integration within functional devices. Aiming to provide a comprehensive roadmap for the development of SiNW FET based sensing platforms, we critically review and discuss the key design and fabrication aspects relevant to their development and integration within complementary metal-oxide-semiconductor (CMOS) technology.

Complementary metal oxide semiconductor compatible silicon nanowires-on-a-chip: fabrication and preclinical validation for the detection of a cancer prognostic protein marker in serum.

An integrated translational biosensing technology based on arrays of silicon nanowire field-effect transistors (SiNW FETs) is described and has been preclinically validated for the ultrasensitive detection of the cancer biomarker ALCAM in serum. High-quality SiNW arrays have been rationally designed toward their implementation as molecular biosensors. The FET sensing platform has been fabricated using a complementary metal oxide semiconductor (CMOS)-compatible process. Reliable and reproducible electrical performance has been demonstrated via electrical characterization using a custom-designed portable readout device. Using this platform, the cancer prognostic marker ALCAM could be detected in serum with a detection limit of 15.5 pg/mL. Importantly, the detection could be completed in less than 30 min and span a wide dynamic detection range (∼10(5)). The SiNW-on-a-chip biosensing technology paves the way to the translational clinical application of FET in the detection of cancer protein markers.

Quasi-spherical microwells on superhydrophobic substrates for long term culture of multicellular spheroids and high throughput assays.

Multicellular tumour spheroids closely recapitulate the physiological environment of tumour tissues. However, their implementation in drug screening assays remains limited due to the technological challenges of forming large numbers of high quality spheroids in platforms compatible with high throughput screening. A simple bench-top microfabrication strategy is demonstrated here based on the principle of ice lithography carried out on superhydrophobic substrates to fabricate quasi-spherical microwells (spheriwells). The microwells shapes and dimensions are directly controlled by the hydrophobicity of the substrate and the volume of the water droplets. The prepared concave microwells enable the formation of dense and homogeneous multicellular tumour spheroids. Spheroids formed within spheriwells are trapped within the microwells, which eliminate loss during media manipulation and facilitate long-term on-chip culture. Morphological and phenotypical changes associated with the growth of MCF-7 adenocarcinoma cells in spheriwells were characterised using imaging flow cytometry and revealed the appearance of heterogeneous populations with loss of E-Cadherin expression. The compatibility of the spheriwells with an on-chip MTT assay is demonstrated. The very unusual shape of the spheriwells, prepared using materials and methods routinely used in most research laboratories, provides a straightforward and scalable platform to prepare high quality multicellular tumour spheroids compatible with high throughput biological screening assays.