Microsystems for drug discovery and biological studies

基因组学和蛋白质组学分析的小型化导致其速度显著提高，成本显著降低，促进了其在各种应用中的爆炸式使用。例如，基因组测序今天花费1万美元，而十年前花费1亿美元;这已经彻底改变了生物研究，药物发现和临床诊断的许多分支。实验室自动化技术小型化的下一个重大挑战是处理和操纵活的生物细胞、胚胎、幼虫和小生物体，这将在速度、成本、准确性和规模方面与现有方法具有相同的优势。这些可扩展的技术对于理解疾病过程和药物发现至关重要，其中使用了模型生物，如果蝇（苍蝇），秀丽隐杆线虫（蠕虫）和模拟器官中细胞自然组织的人工组织构建体。例如，最近宣布的通过推进创新神经技术进行脑研究（BRAIN）计划，旨在开发技术以彻底改变我们对人类大脑组织原理的理解，在头5年将果蝇和秀丽隐杆线虫作为工具开发的目标。* 我的实验室最近出现在这个新兴领域的最前沿，这是由于我们对秀丽隐杆蠕虫电刺激行为的既定工作，以及我们对果蝇幼虫对听觉刺激的神经元反应的最新发现。此外，我们最近在调整快速新兴的3D打印技术以在凝胶中打印血管网络方面的努力提供了一种新的方法，可以在3D中以特定模式定位细胞，以设计用于生物实验的组织样结构。基于我们的既定工作和最近的成功，该研究计划的短期目标是调查和了解外部刺激（如电场，声音或流动）与生物活体（如秀丽隐杆线虫蠕虫和果蝇幼虫）相互作用背后的基础科学。利用这种理解，我们将设计和工程师创新的芯片实验室设备，用于涉及这些生物体的生物和药物发现测定。 我们还将开发混合微制造技术，用于制造具有集成血管网络的人造组织，以模拟疾病过程并用于药物发现。从长远来看，我们将开发集成的微系统，以降低成本，提高吞吐量，并自动化这些针对药物发现或生物研究中特定应用的分析。通过降低研究成本和提高能力，这些系统可以显著提高生物和生物医学研究人员的生产力。

Miniaturization of assays in genomics and proteomics led to dramatic improvements in their speed at significantly lower cost, facilitating an explosion in their use in a wide variety of applications. For instance, sequencing a genome costs 10,000$ today as opposed to 100 million$ a decade ago; this has revolutionized many branches of biological research, drug discovery and clinical diagnostics.*** The next grand challenge in miniaturization of laboratory automation technologies is in handling and manipulating of living biological cells, embryos, larvae and small organisms that would confer the same advantages of speed, cost, accuracy and scale over existing methods. These scalable technologies are critically important in understanding disease process and in drug discovery where model organisms such as Drosophila (fly), C.elegans (worm) and artificial tissue constructs that mimic the natural organization of cells in an organ are being used. For instance, the recently announced Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, to develop technologies to revolutionize our understanding of the organizational principles of the human brain, targets Drosophila and C.elegans for tool developmnt in its first 5 years. *** My laboratory has recently emerged at the forefront of this nascent field due our established work on the electrically stimulated behavior of C.elegans worms and our more recent findings on the neuronal response of Drosophila larva to auditory stimulus. Also, our recent efforts at adapting the rapidly emerging 3D printing technology to print vascular networks in gels provides a novel way to position cells in specific patterns in 3D to engineer tissue like constructs for biological experimentation.*** Building on our established work and recent successes, the short-term aim of this research program, is to investigate and understand the fundamental science behind interaction of external stimuli such as electric field, sound or flow with biological living organisms such as C.elegans worms and Drosophila larva. Using that understanding, we will design and engineer innovative Lab-on-Chip devices for biological and drug discovery assays that involve these organisms. We will also develop hybrid microfabrication technologies for the manufacture of artificial tissue like constructs with integrated vascular networks to model disease processes and for use in drug discovery.*** Over the long term, we will develop integrated microsystems that lower the cost, increase throughput and automate these assays targeted towards specific applications in drug discovery or biological research. By lowering the cost of research and enhancing capability, these systems can significantly enhance the productivity of biological and biomedical researchers.**