From Cleanroom to Desktop: Emerging Micro-Nanofabrication Technology for Biomedical Applications

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities

A novel dynamic multicellular co-culture system for studying individual blood-brain barrier cell types in brain diseases and cytotoxicity testing

Blood brain barrier (BBB) cells play key roles in the physiology and pathology of the central nervous system (CNS). BBB dysfunction is implicated in many neurodegenerative diseases, including Alzheimer’s disease (AD). The BBB consists of capillary endothelial cells, pericytes encircling the endothelium and surrounding astrocytes extending their processes towards it. Although there have been many attempts to develop in vitro BBB models, the complex interaction between these celltypes makes it extremely difficult to determine their individual contribution to neurotoxicity in vivo. Thus, we developed and optimised an in vitro multicellular co-culture model within the Kirkstall Quasi Vivo System. The main aim was to determine the optimal environment to culture human brain primary endothelial cells, pericytes and astrocytes whilst maintaining cellular communication without formation of a barrier in order to assess the contribution of each cell type to the overall response. As a proof of concept for the present system, the effects of amyloid-beta 25-35 peptide (Aβ25-35), a hall mark of AD, were explored. This multicellular system will be a valuable tool for future studies on the specific roles of individual BBB cell type (while making connection with each other through medium) in CNS disorders as well as in cytotoxicity tests

Compartmentalized Microfluidics for In Vitro Alzheimer’s Disease Studies

Compartmentalized microfluidic devices are designed to engineer the cellular environment for cell cultures. The practical use of the compartmentalized chambers can be expanded to induce co-pathological cell cultures, where one cell population expresses a specific disease state, while being in direct-cell or metabolic contact to a second or third unaffected cell population. A typical example for co-pathological cell states in the brain is the well-known neurodegenerative Alzheimer’s disease (AD), which still lacks effective treatment approaches. In the brain, AD shows specific disease progression patterns from one functional brain region to another. However, in normal dissociated neuron cultures using petri dishes, the extraction of the progression patterns is very difficult. In this chapter, we describe the methodology to design and fabricate a compartmentalized microfluidic device and apply it to an in vitro AD model to mimic the key pathological hallmarks of AD, allowing us to study disease progression patterns from a “diseased” towards a “healthy” cell population. This derived co-pathological model of AD provides the ability to monitor time-variant changes in cell network morphology and electrophysiology during disease progression and may potentially be used for pharmaceutical tests

Hysteresis in multiphase microfluidics at a T-junction

Multiphase microfluidics offer a wide range of functionalities in the fields of fluid dynamics, biology, particle synthesis, and, more recently, also in logical computation. In this article, we describe the hysteresis of immiscible, multiphase flow obtained in hydrophilic, microfluidic systems at a T-junction. Stable and unstable state behaviors, in the form of segmented and parallel flow patterns of oil and water, were reliably produced, depending upon the history of the flow rates applied to the phases. The transition mechanisms between the two states were analyzed both experimentally and using numerical simulations, describing how the physical and fluid dynamic parameters influenced the hysteretic behavior of the flow. The characteristics of these multiphase systems render them suitable to be used as pressure comparators and also for the implementation of microfluidic logic operations