High throughput liquid handling platform using open-space microfluidics

混合、取样或输送精确体积的液体是学术界和工业界大量实验室实验的核心。它的范围从分析土壤含量到精确测量鼻拭子中的病毒载量。对于需要精确或自动化的应用，机器人液体处理机已经取代了手动添加或移除液体的步骤。然而，这些机器人液体处理机只不过是移动吸管的机器人，具有与标准吸管相同的局限性。微流体学是一个在微尺度上控制精确和少量流体的研究领域，它准备在高通量实验中克服这种“移液专制”。标准的微流控装置利用通道来引导流体。微流体学的一个新兴分支，称为开放空间微流体学，利用开放通道的几何形状来限制和控制液体，而不需要“墙”。在这个项目中，我们计划在我们团队之前的技术开发的基础上，利用开放式微流控技术组装一个液体处理平台。通过使用这一独特的系统，将在高通量细胞处理和基因转染领域探索新的应用和新的发现领域，例如研究动态刺激细胞信号通路的作用，以及通过执行高通量芯片上器官和体外组织对芯片的灌流和治疗来研究在肿瘤学领域的作用。能够组装这个液体处理平台对于支持蒙特利尔理工学院、协和大学和蒙大略省L医院(CHUM，蒙特利尔)现有的开放空间微流控和高通量筛查研究人员以及其他医疗保健和工业合作伙伴(MISO芯片公司)至关重要。为了组装这个平台，需要一个具有大视场和荧光能力的倒置显微镜，以及一个可以安装在显微镜上的孵化室。这个小室将用于需要精确环境控制的长期多路生物实验。最后，该平台将需要一个基于压力的双通道微流控控制器和流量传感器来控制和监测开放空间微流控设备的运行。该平台每年将培训超过5名高素质的专业人员，将促进与癌症生物学家和医学肿瘤学家的合作，每年将有48名本科生使用该平台作为蒙特利尔理工学院生物微机械研究课程的一部分。

Mixing, sampling, or delivering precise volumes of liquid is at the core of a profusion of laboratory experiments in academia and industry. It can range from analyzing soil content to precisely measuring the virus load in a nasal swab. For applications where precision or automatization is required, robotic liquid handlers have been adopted to replace the manual steps of adding or removing liquids. However, these robotic liquid handlers are nothing more than robots moving pipettes around and have the same limitations of standard pipettes. Microfluidics, a field of study where precise and small volumes of fluids are controlled at the microscale, is poised to overcome this "tyranny of pipetting" in high throughput experiments. Standard microfluidic devices utilize channels to guide fluids. An emerging subfield of microfluidics, named open-space microfluidics, takes advantage of open channel geometries to confine and control liquids without "walls". In this project, we propose to assemble a liquid handling platform using open-space microfluidics based upon previous technological developments made by our team. By using this unique system, new applications and new areas of discovery will be explored in the field of high throughput cell processing and gene transfection, such as studying the effect of dynamically stimulating cell signaling pathways as well as in the field on oncology by performing high throughput organ-on-chip and ex vivo tissue on chip perfusion and treatment. Being able to assemble this liquid handling platform will be essential to support current researchers in open-space microfluidics and high throughput screening at Polytechnique Montreal, Concordia University and the Centre de recherche du Centre Hospitalier de l'Université de Montréal (CHUM, Montreal), and other health care and industrial partners through a fee for service (MISO Chip Inc.). To assemble this platform, an inverted microscope with a large field of view and fluorescence capabilities will be required, as well as an incubation chamber that can be installed on the microscope. This chamber will be used for long-term multiplexed biological experiments where precise environmental control is required. Finally, the platform will require a 2-channel pressure-based microfluidic controller and flow rate sensors to control and monitor the operation of the open-space microfluidic devices. The platform will train over 5 highly qualified professionals a year, will stimulate collaboration with cancer biologists and medical oncologists, and will be used by 48 undergraduate students per year as part of a research-based course on bioMEMS at Polytechnique Montreal.