Microfluidic technology platform for selection of functional monoclonal antibodies with application to fibrosis

抗体是由免疫系统产生的分子，用于对抗感染。免疫系统有能力 各种各样的不同抗体，每一种抗体都可能是对外来物质和病原体作出反应而产生的， 包括病毒和细菌。就像一把钥匙只能开一把锁一样，身体选择每一种抗体的能力是， 与特定的靶分子结合。除了它们在抵抗感染方面的自然作用外，这种锁和钥匙的关系 抗体作为靶向药物极其有效的原因与传统的小分子药物不同， 抗体仅与某些分子结合可大大提高治疗的有效性并使副作用最小化。 然而，开发这些精确药物的一个未解决的挑战是从数十亿中找到最好的抗体 在动物身上产生的。由于灵敏度的限制，目前解决这个问题的方法要求产生的细胞 抗体在培养物中生长。这一过程效率极低，只允许抽样不到所有样本的0.1%。 抗体，并且也是耗时且昂贵的。一个令人兴奋的替代方案是开发更敏感的技术， 允许直接分析从单细胞产生的数百万种抗体。在本项目中，我们将启用这种方法 使用小型化的设备，称为微流体，由成千上万的通道，腔室和阀门组成， 都集成在一个紧凑的芯片实验室中。这些系统体积小，大大增加了测量 灵敏度，并将用于识别抗体从单细胞在更高的速度和精度比目前 可能这将被应用于识别可以影响伤口愈合和纤维化干细胞的抗体。的 该项目的成果将是一个新的和经过验证的平台技术，用于改进基于抗体的发现。 治疗学

Antibodies are molecules made by the immune system to fight off infections. The immune system is capable of making an immense variety of different antibodies, each of which may be produced in response to foreign agents and pathogens, including viruses, and bacteria. In analogy to how a key fits into only one lock, the body selects each antibody for its ability to bind to a specific target molecule. In addition to their natural role in fighting off infections, this lock-and-key relationship is what makes antibodies extremely effective as targeted drugs. Unlike more conventional small molecule drugs, the specific binding of antibodies to only certain molecules can greatly improve the effectiveness of therapies and minimize side effects. However, an unmet challenge in developing these precision drugs is finding the best antibodies out of the many billions produced in an animal. Due to limits in sensitivity, current approaches to this problem require that the cells that produce antibodies be grown in culture. This process is extremely inefficient, allowing for the sampling of less than 0.1% of all antibodies, and is also time-consuming and expensive. An exciting alternative is to develop more sensitive technologies that allow for the direct analysis of millions of antibodies generated from single cells. In this project we will enable this approach using miniaturized devices, called microfluidics, that consist of tens of thousands of channels, chambers, and valves, which are integrated on a compact lab- on-a-chip format. The small volumes of these systems greatly increase measurement sensitivity and will be used to identify antibodies from single cells at much higher speed and precision than is currently possible. This will be applied to identify antibodies that can influence stem cells involved in wound healing and fibrosis. The outcomes of this project will be a new and validated platform technology for the improved discovery of antibody-based therapeutics.