Microfluidic Platforms to Unravel Mysteries of Alzheimer's Disease: How Far Have We Come?

Abstract

Alzheimer's disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells such as microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms.

Keywords: 3D culture; Alzheimer’s disease; lab-on-chip; microfluidics; organ-on-chip.

Figure 1

The pathophysiology of Alzheimer’s disease is very complex. Major pathological hallmarks of Alzheimer’s disease are provided. Among all the hallmarks, Aβ accumulation is considered the major cause of neurodegeneration in Alzheimer’s disease. It has been found that all other causes such as tau pathology and/or neuroinflammation ultimately converge to Aβ accumulation. For instance, microglia, the innate immune system of the nervous system, mediates neuroinflammation by the production of cytokines such as IL33, IL-8 and IL-1β. Microglial activation initiates inflammation of the neural tissues. The cytokines (IL-33) produced in the due process help in Aβ clearance whereas IL-8 and IL-1β cause synaptic dysfunction. This molecular mechanism reflects the complex.

Figure 2

Timeline of the progress of microfluidics in biomedical research. Abbreviations: GC, gas chromatography; µTAS, micro total analysis system; PDMS, Polydimethylsiloxane.

Figure 3

Schematic representation of the materials used for the fabrication of microfluidic chips. Hydrogels made up of natural materials, i.e., alginate, serve as matrices for culturing of cells in microfluidic chips. Thermoplastics such as polyvinyl chloride, polystyrene and high-density polyethylene are commonly used in fabrication. Moreover, the typical white color of paper makes it well suited for color-based detection methods in most assays and used for multiple bioassays in the form of origami-inspired folding devices. Elastomer is generally made up of PDMS. The glass-based microfluidic channel is made by the laser direct writing method. Thermoset, polyester-based, is a droplet-based device that can be used at different flow rates with three different oils.