Development of a novel 3D microfluidic assay platform for the assessment of human stem-cell derived epithelial function.

为了解决这个问题，我们将开发一种芯片上实验室的设备，它可以由廉价的塑料制成，并在一块不到一平方厘米大小的单一芯片上集成几种实验室功能。这种使用方便的微型设备将被用来培养肺细胞，这些细胞可以从成人干细胞中几乎无限地获得。这些细胞将在芯片中生长，在那里它们形成一个上皮屏障，并为一侧是空气、另一侧是液体的呼吸道组织提供一个模型。它还提供组织周围的持续流动，旨在提供营养并清除体内产生的废物；它还允许在不同的时间点收集组织周围液体的小样本，以监测上皮细胞的行为。我们还将监测芯片中肺组织形成的上皮屏障的电学特性，以便跟踪环境触发因素的影响。通过这种方式，我们将创建一个智能生物芯片，提供一个可持续和可访问的呼吸道上皮屏障模型，它可以受到环境诱因(如室内灰尘、花粉或病毒)的影响，并用于研究潜在的新药疗法与已有的抗炎疗法(如类固醇)的效果。该项目的目标是：-设计、制造和测试不同版本的芯片，以提供最接近肺组织的最佳组织结构和功能。-开发辅助硬件和软件以控制液体流动，收集样本并测量屏障。-开发从成人干细胞制造肺细胞的简化方法。-使用智能生物芯片测试药物合作者提供的药物。这项新技术有可能更准确地预测肺组织对药物治疗的反应，缩短药物开发从药物发现到人体试验的时间，并确定新的药物靶点。这个系统将使新的实验成为可能，这将导致对呼吸道疾病的更好的理解。该平台还将提供一种简单、快速的方式，对我们在日常生活中吸入或接触到的新的和现有的药物和化合物(如气雾剂)进行毒理学和药理学筛选。

To solve this problem we will develop a lab-on-a-chip device that can be made from inexpensive plastics and integratesseveral laboratory functions on a single chip of less than a square centimetre in size. This user-friendly miniaturised devicewill be used to grow lung cells that can be derived in almost limitless supply from adult human stem cells. The cells will begrown in the chip where they make an epithelial barrier and provide a model for airway tissue with air on one side and liquidon the other. It also provides constant flow around the tissue and is designed to provide nutrients and remove wasteproducts as occurs in the body; it also enables small samples of the liquid surrounding the tissue to be collected at differenttime points to monitor the behaviour of the epithelial cells. We will also monitor the electrical properties of the epithelialbarrier formed by the lung tissue in the chip so that the effect of environmental triggers can be followed. In this way we willcreate a 'Smart biochip' that provides a sustainable and accessible model of the airway epithelial barrier which can bechallenged with environmental triggers (such as house dust, pollen or viruses) and used to investigate the effects ofpotential new drug therapies in comparison with established anti-inflammatory therapies such as steroids.The objectives of the project are:-design, fabricate and test different versions of chip to give the optimum tissue structure and function that most closelyresembles the lung tissue.-develop the supporting hardware and software to control fluid flow, sample collection and measure the barrier.-develop simplified methods to make lung cells from adult human stem cells.-use the Smart Biochip to test drugs provided by pharmaceutical collaborators.This new technology has the potential to more accurately predict responses of lung tissue to drug therapies, shorten thelength of time of drug development from drug discovery to trials in humans and identify new drug targets. This system willenable new experiments which will lead to an improved understanding of diseases of the airways. The platform will alsoprovide a simple, fast way to perform toxicology and pharmacology screens of new and existing drugs and compoundssuch as aerosols that we inhale or exposed to in our daily life.