Grant: Collaborative Health Research Projects

Antibodies are molecules made by the immune system to fight off infections. The immune system is capable of making animmense 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 tobind to a specific target molecule. In addition to their natural role in fighting off infections, this lock-and-key relationship iswhat makes antibodies extremely effective as targeted drugs. Unlike more conventional small molecule drugs, the specificbinding 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 billionsproduced in an animal. Due to limits in sensitivity, current approaches to this problem require that the cells that produceantibodies be grown in culture. This process is extremely inefficient, allowing for the sampling of less than 0.1% of allantibodies, and is also time-consuming and expensive. An exciting alternative is to develop more sensitive technologies thatallow for the direct analysis of millions of antibodies generated from single cells. In this project we will enable this approachusing miniaturized devices, called microfluidics, that consist of tens of thousands of channels, chambers, and valves, whichare integrated on a compact lab- on-a-chip format. The small volumes of these systems greatly increase measurementsensitivity and will be used to identify antibodies from single cells at much higher speed and precision than is currentlypossible. This will be applied to identify antibodies that can influence stem cells involved in wound healing and fibrosis. Theoutcomes of this project will be a new and validated platform technology for the improved discovery of antibody-basedtherapeutics.