Development of on-chip ultra high-throughput whole-animal assay technologies

片上超高通量全动物检测技术的开发

• 批准号: 7431027
• 负责人: Mehmet Fatih Yanik
• 金额: $ 251.75万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7431027
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In recent years, the advantages of using the nematode Caenorhabditis elegans as a model system for human disease have become increasingly apparent, culminating in two Nobel Prizes in Physiology and Medicine within the last five years. Existing vertebrate animal models, and the instrumentation incorporated to study them, cannot be utilized for high throughput assays for rapid identification of novel genes, and drug leads. The model organism C. elegans allows in vivo genome-wide assays and high- throughput screens due to the availability of unmatched genetic techniques, its transparency, and the ability to grow it in minute volumes. Yet, since the first publications in early 1960s, little has changed how scientists manipulate this tiny organism manually, as a result of which even simple large-scale assays still take months to years to complete. Importantly, due to the lack of key technologies, several assays either cannot be performed at all or have to be dramatically simplified for high-throughput screens. We propose (1) development of the first on-chip ultra high-throughput whole- animal manipulation technologies for in vivo drug screens and genome-wide discovery of gene functions and interactions by complex on-chip behavioral and biochemical assay strategies; and (2) the first large-scale in vivo study of mechanisms of neural degeneration and regeneration following reproducible injuries using the proposed techniques. The proposed technologies and high-throughput assay strategies can significantly impact discovery of many molecular mechanisms using disease models of small animals.

近年来，利用秀丽隐杆线虫的优势 作为人类疾病的模型系统已经变得越来越明显， 在过去的五年里，他两次获得诺贝尔生理学和医学奖。现有 脊椎动物模型，以及用于研究它们的仪器，不能 用于快速鉴定新基因和药物的高通量测定 线索.模式生物C. elegans允许在体内进行全基因组测定， 由于无与伦比的遗传技术的可用性， 透明度，以及在微小体积中生长的能力。然而，自从第一次出版以来， 在20世纪60年代早期，科学家们手动操纵这种微小生物方式几乎没有改变， 结果，即使是简单的大规模测定仍然需要数月至数年来 完成.重要的是，由于缺乏关键技术，几种检测方法要么不能 或者必须显著简化以用于高通量筛选。 我们建议（1）开发第一个片上超高通量全- 用于体内药物筛选和全基因组发现的动物操作技术 通过复杂的芯片上行为和生物化学测定的基因功能和相互作用 策略;（2）第一次大规模的神经机制的体内研究 退化和再生后，可再生的损伤，使用建议的 技术.所提出的技术和高通量测定策略可以 使用疾病模型发现许多分子机制， 小动物。

项目成果

High-throughput in vivo genetic and drug screening using femtosecond laser nano-surgery, and microfluidics.

使用飞秒激光纳米手术和微流体进行高通量体内遗传和药物筛选。

• DOI: 10.1109/iembs.2008.4649743
• 发表时间: 2008
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
• 作者: Rohde,Christopher;Gilleland,Cody;Samara,Chrysanthi;Zeng,Fei;Yanik,MehmetFatih
• 通讯作者: Yanik,MehmetFatih

Organ-targeted high-throughput in vivo biologics screen identifies materials for RNA delivery.

• DOI: 10.1039/c4ib00150h
• 发表时间: 2014-10
• 期刊: Integrative biology : quantitative biosciences from nano to macro
• 作者: Chang TY;Shi P;Steinmeyer JD;Chatnuntawech I;Tillberg P;Love KT;Eimon PM;Anderson DG;Yanik MF
• 通讯作者: Yanik MF

Microfluidic in vivo screen identifies compounds enhancing neuronal regeneration.

微流体体内筛选识别增强神经元再生的化合物。

• DOI: 10.1109/iembs.2009.5334771
• 发表时间: 2009
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
• 作者: Rohde,ChristopherB;Gilleland,Cody;Samara,Chrysanthi;Norton,Stephanie;Haggarty,Stephen;Yanik,MehmetFatih
• 通讯作者: Yanik,MehmetFatih

Fully automated cellular-resolution vertebrate screening platform with parallel animal processing.

• DOI: 10.1039/c1lc20849g
• 发表时间: 2012-02-21
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Chang TY;Pardo-Martin C;Allalou A;Wählby C;Yanik MF
• 通讯作者: Yanik MF

Large-scale analysis of neurite growth dynamics on micropatterned substrates.

微图案基底上神经突生长动力学的大规模分析。

• DOI: 10.1039/c0ib00058b
• 发表时间: 2011
• 期刊: Integrative biology : quantitative biosciences from nano to macro
• 作者: Wissner-Gross,ZacharyD;Scott,MarkA;Ku,David;Ramaswamy,Priya;FatihYanik,Mehmet
• 通讯作者: FatihYanik,Mehmet