Microfluidic technologies for high-throughput monocIonal antibody selection from single cells

该项目将把两个具有互补专业知识的研究小组聚集在一起，一个是受过医学培训的国际公认的免疫学家约翰·施雷德博士，另一个是卡尔·汉森博士，他是物理学家和工程师，在新的微流体科学创新方面处于领先地位。这些跨学科团队将共同开发一种新颖而创新的设备，以解决基础和应用医学研究中的一个关键问题--快速而廉价地产生高价值单抗。单抗与血液中的抗体相对应，这些抗体通过与病毒或毒素结合来保护我们免受感染，并负责对我们以前遇到的疾病产生免疫力。抗体具有独特的性质，它们有数百万种不同的形状。“单抗”是一种具有特定形状的抗体的纯制备，可以选择不同的单抗来对抗病毒或靶向癌症。单抗是增长最快的一类新型治疗药物，正在为乳腺癌、结肠癌、淋巴组织和其他癌症(赫赛汀、艾比妥、利妥昔单抗、阿瓦斯丁)以及关节炎和克罗恩病(Remicade、Humira)提供突破性治疗。在疾病诊断和生物医学研究中，找到选择性地与几乎任何物质结合的单抗的能力也具有巨大的医学和商业重要性。尽管有这种巨大的潜力，但通过传统手段发现和生产高质量抗体仍然是一个主要瓶颈。目前的技术昂贵，需要数月或数年的开发，而且与生产容易用于人类的抗体不兼容。该项目将融合微工程、免疫学和生物光子学的最新技术，使邮票大小的设备能够对数千个单细胞产生的抗体进行灵敏的测量，并复制具有有用特征的抗体的遗传配方，以便无限量地制造人或兔的单抗，用于治疗或用作试剂。研究的结果应该会带来令人兴奋的商业机会。

This project will bring together two research groups with complementary expertise led by Dr. John Schrader, a medically-trained, internationally recognized immunologist, and Dr. Carl Hansen a physicist and engineer who is a leader in innovation in the new science of microfluidics. Together these interdisciplinary teams will develop a novel and innovative device that will address a pivotal problem in basic and applied medical research - the rapid and inexpensive generation of high-value monoclonal antibodies. Monoclonal antibodies are counterparts of the antibodies in our blood that protect us from infections by binding to viruses or toxins and are responsible for immunity to diseases we have encountered before. Antibodies have the unique property thai they come in millions of different shapes. A "monoclonal antibody " is a pure preparation of one antibody with its one particular shape and different monoclonal antibodies can be selected to fight a virus or target a cancer. Monoclonal antibodies are the fastest growing class of new therapeutic agents and are providing breakthrough treatments e.g for cancers of the breast, colon, lymphatic tissues and others (Herceptin, Erbitux, Rituximab, Avastin) and arthritis and Crohn's disease (Remicade, Humira). The ability to find a monoclonal antibody that selectively binds to virtually any substance is also of enormous medical and commercial importance in the diagnosis of disease and in biomedical research. Despite this enormous potential, the discovery and production of high-quality antibodies by conventional means is a major bottleneck. Current techniques are expensive, require months or years of development, and are not compatible with the production of antibodies that can be easily used in humans. This project will merge state-of-the-art techniques in microengineering, immunology, and biophotonics to enable a postage stamp-size device to make sensitive measurements on the antibodies made by thousands of single cells and copy the genetic recipes for antibodies with useful characteristics, so that they can be made in unlimited quantities as human or rabbit monoclonal antibodies for use as therapies or as reagents. The results of the research should lead to exciting commercial opportunities.