Microfluidic Platforms for Biological Investigations

微制造芯片实验室（LOC）设备正广泛应用于细胞、组织、器官和整个生物系统的生物学研究，例如蠕虫（秀丽隐杆线虫）和果蝇（果蝇）。由于其诸多优势，整个生物系统为研究感知和响应各种刺激信号的神经行为机制提供了经济有效且相关的手段。然而，它们的小尺寸（微米到毫米）给它们在细胞和行为分析中的操作带来了挑战。因此，目前的人工研究不仅缓慢而费力，而且在研究整个生物系统时有时也不准确和不一致。本研究计划建议开发创新的LOC技术，以改进生物有机体的分析方法，以回答基本和复杂的神经行为问题。

Microfabricated Lab-On-a-Chip (LOC) devices are being applied to a wide range of biological studies on cells, tissues, organs and whole biological systems, e.g. the worm (C. elegans) and the fruit fly (Drosophila). Due to their many advantages, whole biological systems offer cost-effective and relevant means to study the neurobehavioral mechanisms of sensing and responding to various stimulating signals. However, their small sizes (micrometers to millimeters) impose challenges for their manipulation in cellular and behavioral assays. Hence, current manual efforts are not only slow and laborious, but also sometimes inaccurate and inconsistent in studying whole biological systems. This research program proposes developing innovative LOC techniques that will improve the ways bio-organisms are assayed to answer fundamental and complex neurobehavioral questions. The overall goal of this research program is to develop various LOC techniques (by conducting two innovative research themes) to accurately manipulate and measure the response of biological specimens to relevant stimuli (e.g. chemical and electrical) at neuronal and behavioural levels. These LOCs will make it possible to screen chemicals on Drosophila and C. elegans in automated, high-throughput, quantitative and repeatable manners. In research theme 1, we will develop LOCs that enable automated measurements of the toxic effects of different chemicals on Drosophila larvae. To be able to accomplish this, we will develop fundamental understanding of the effects of surface properties on stimulating spatial preference of egg-laying in adult Drosophila. We will use the knowledge and expertise acquired to develop sorting and compartmentalization modules to parallelize eggs into microchambers where they will be exposed controllably to chemicals. It is important to investigate the effects of flow characteristics on the survival and development of eggs into larvae. Techniques to stimulate and parametrically study the movement and neuronal activities of larvae will then be investigated. In research theme 2, we will develop unique manipulation (e.g. immobilization and orientation) and surgical (e.g. dissection) micro-tools and integrate them inside chips that can enable even non-expert researchers access the internal environment of small biological substances (e.g. worm and fruit fly) in a timely automated manner. We need to fundamentally investigate the mechanical properties of the outer body shelves of these organisms and the use of various forces (e.g. dielectrophoretic and acoustic) to manipulate them in order to be able to design and develop the abovementioned tools. Knowledge and techniques to be developed are directly applicable to many studies such as organ/egg extraction and/or inner-body recording of neuromuscular activities in bio-specimens. Six graduate and five undergraduate students will be trained in this research program and will gain technical, scientific, interdisciplinary and soft skills. The developed knowledge and techniques can be applied in drug discovery, toxicology, neurosciences and systems biology. By automation, quantitative data from these specimens in higher throughputs can be obtained in easy manners as compared to existing techniques. In the long term, the research will benefit Canada by accelerating and lowering the cost of toxicity tests, preclinical drug discovery, neuronal mapping and fundamental investigation of bio-processes.