Lab-On-A-Chip: A Mechanistic Approach for Biological Screening

摘要

Micro fabrication techniques have wide range of applications in the field of life science. Microfluidic devices are now playing vital roles in drug discovery, cell biology, neurobiology, pharmacology and tissue engineering. These micromechanical devices are capable of manipulating even single component/object like cells. Lab-on-a- chip (LOC) uses electrical, magnetic, and mechanical phenomena for cell trapping, sorting, analysis and fusion. By far, several approaches have been attempted to fabricate these microfluidic devices but generally two approaches, like in-plane and out-of-plane have been found to be practically workable, and out of these two the in-plane is considered to be the most convenient approach to fabricate such device with state-of-the-art planar technology [1]. This comprises of surface micromachining and different techniques of silicon etching that provides higher degree of flexibility. Microfluidic techniques are now used in various pharmacological screening studies to understand cell-cell interactions, homotypic and heterotypic intercellular cross talks in fundamental processes, such as tissue morphogenesis, and also provides cell-based and organ-based platforms for preclinical drug and toxicity testing [2,3]. In addition to these, LOCs are also used to assess contractility of muscles (Muscle-on-chips). A device was developed using muscular thin film (MTF) technology that made it possible to evaluate the contractility of both striated and smooth muscle simultaneously on the same chip [4]. The micro-total analysis systems complemented with optical and impedimetric readouts were used in quantitative characterization of changes in cell metabolism and morphology as a response to toxin exposure [5]. This principle is used in designing a biosensor as an alternative for skin irritation studies. Hydrogel-based diffusion chip with electric cell-substrate impedance sensing (ECIS) was also developed for cell viability assay and drug toxicity screening [6]. This model was used to simulate the drug diffusion system that involved a hydrogel-based tissue-mimicking structure with microfluidic channel having high stability. Consistently IC,, values were obtained by using this method [6]. Microfluidic systems consisting of micro analytical hybrid system are also used to screen the cytotoxic effects of chemotherapeutic agents (5-fluorouracil) on cancer cells [7]. A three-dimensional (3D) tumor spheroid chip was developed to evaluate pharmacokinetic (PK) aspects by balanced droplet dispensing system [8].