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实验室设备，它可以由廉价的塑料制成，并在一个不到一平方厘米的芯片上集成几个实验室功能。这种用户友好的小型设备将用于培养肺细胞，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，在那里它们形成上皮屏障，并为一侧为空气另一侧为液体的气道组织提供模型。它还在组织周围提供恒定的流动，旨在提供营养物质并清除体内产生的废物;它还能够在不同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由肺组织形成的上皮屏障的电特性，以便可以跟踪环境触发因素的影响。通过这种方式，我们将创造一种“智能生物芯片”，它提供了一种可持续的和可访问的气道上皮屏障模型，可以通过环境触发器进行挑战（如室内灰尘、花粉或病毒），并用于研究潜在的新药物疗法与已建立的抗炎疗法（如类固醇）相比的效果。- 设计，制造和测试不同版本的芯片，以提供最佳的组织结构和功能，最接近肺组织。开发支持硬件和软件，以控制流体流动，样品收集和测量屏障。开发简化的方法，从成人干细胞中制造肺细胞。使用智能生物芯片测试制药合作者提供的药物。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。该系统将使新的实验，这将导致更好地了解疾病的气道。该平台还将提供一种简单，快速的方法来对新的和现有的药物和化合物进行毒理学和药理学筛选，例如我们在日常生活中吸入或暴露的气溶胶。

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.