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它们的速度显著提高，成本显著降低，促进了它们在各种应用中的爆炸性使用。例如，基因组测序现在的成本是1万美元，而十年前是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，这些将赋予现有方法相同的速度、成本、准确性和规模优势。这些可扩展的技术在理解疾病过程和药物发现方面至关重要，在药物发现中，正在使用果蝇(Fly)、线虫(Celegans)等模式生物和模拟器官细胞自然组织的人造组织结构。例如，最近宣布的通过推进创新神经技术(大脑)倡议进行的大脑研究，以开发技术来彻底改变我们对人脑组织原理的理解，在最初的5年中针对果蝇和线虫进行工具开发。*我的实验室最近出现在这个新领域的前沿，这是因为我们在线虫电刺激行为方面的既定工作，以及我们在果蝇幼虫对听觉刺激的神经元反应方面的最新发现。此外，我们最近在应用快速崛起的3D打印技术打印凝胶中的血管网络方面所做的努力，提供了一种在3D特定图案中定位细胞的新方法，以设计类似于生物实验的组织结构。*以我们已有的工作和最近的成功为基础，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(如线虫和果蝇幼虫)相互作用背后的基础科学。利用这一理解，我们将设计和设计创新的芯片上实验室设备，用于涉及这些微生物的生物和药物发现分析。我们还将开发混合微制造技术，用于制造人造组织，如具有集成血管网络的结构，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，提高产量，并针对药物发现或生物研究中的特定应用，使这些分析自动化。通过降低研究成本和增强能力，这些系统可以显著提高生物和生物医学研究人员的生产率。**

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.**