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

点击翻译按钮获取中文摘要

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.