INTEGRATED MICROFLUIDIC MICROELECTRONIC SYSTEMS: TOWARD ACCELERATED TWO DIMENSIONAL MAGNETIC RESONANCE SPECTROSCOPY

小型化始于微电子领域，与之相关的制造工艺彻底改变了我们沟通、处理信息和计算的方式。不久前，一种基于并行的新范式被提出，研究人员声称，小型化应该通过在单个芯片上进行大量生物分析和优化化学反应来实现生物学上的同样革命。因此，大规模并行生物分析在药物发现和化学/生物危害检测等各种应用中具有巨大的潜力。但是，只有当集成微流控微电子系统（IFES）的发展成为可能时，这种潜力才能发挥到最大程度。如今，IFES技术被用于从疾病诊断到DNA测序的各种应用中。的确，IFES技术提供了许多优势，比如；高通量筛选能力，低样品消耗和快速分析。因此，我们承担了用于药物发现应用和疾病管理所必需的新一代生命周期的开发。**在本研究计划中，我们将利用最新的微电子和微流体技术，加速特定的分子传感技术，即；磁共振波谱（MRS）。MRS广泛应用于药物发现研究，从天然衍生或合成的大量分子文库中筛选强效药物，可视化靶分子的三维结构，鉴定药物-靶结构的稳定性，以及阐明分子构象的快速时间尺度动态变化。尽管MRS在增强我们对生物分子结构的理解方面发挥了重要作用，但这种传感技术缺乏灵敏度。这是迄今为止用于实现药物发现目的所需的所谓二维MRS的经典设备的严重缺点。*该项目通过在单个芯片上集成大量小型化MRS探头，解决了2D MRS使用中的技术问题。微流体技术在这方面起着重要的作用。在微/纳升尺度上处理候选药物应该足够快，因为化学变化不会在MRS分析之前发生。此外，这项技术为发明新的MRS技术打开了大门，目的是首次监测生物分子的亚微秒动态变化。从经济角度来看，由于加拿大被认为是生物制药行业的国际资本之一（2011年制药行业对加拿大GDP的贡献为42亿美元），我们技术的利益相关者可能是在加拿大境内运营的所有制药公司。这项新技术为新成立的公司提供了巨大的机会，将药物发现研究和开发提升到一个全新的水平。这意味着加拿大人的生活质量得到了提高。

Miniaturization started in the field of microelectronics and the associated fabrication processes revolutionized the way we communicate, process information and compute. Not long ago, a new paradigm based on parallelism was formulated and researchers claimed that miniaturization should operate the same revolution in biology by accelerating bioassays and optimizing chemical reactions when performed in large numbers, on a single chip. Massively parallel biological analysis thus holds enormous potential for a variety of applications such as, drug discovery and detection of chemical/biological hazards. But this potential can only be unleashed to its fullest extent, when the development of Integrated Microfluidic Microelectronic Systems (IFES) is made possible. Nowadays, IFES technology is used in a variety of applications ranging from disease diagnosis to DNA sequencing. Indeed, IFES technology offers many advantages like; high throughput screening capabilities, low sample consumption and rapid analysis. Inasmuch, we undertake the development of the new generation of IFES used in drug discovery applications and necessary for disease management. **In this research program, we will exploit, state of the art, microelectronics and microfluidics, to achieve acceleration of a specific molecular sensing technique, namely; Magnetic Resonance Spectroscopy (MRS). MRS is widely used in drug discovery research for screening potent drugs selected from large libraries of naturally derived or synthesized molecules, visualization of the three dimensional structures of target molecules, identification of drug-target structure stability and last but not the least, elucidating fast time scale dynamic changes in molecular conformations. Despite the important role played by MRS in enhancing our understanding of biomolecular structures, this sensing technique lacks of sensitivity. This is a serious drawback of the classical devices used so far to implement the so-called two-dimensional MRS required for drug discovery purposes. *This project addresses the resolution of technical problems levied on the use of 2D MRS by integrating a large number of miniaturized MRS probes on a single chip. Microfluidics plays an important role in this endeavor. The handling of drug candidates at a micro/nano-liter scale should be fast enough, for chemical change not to take place before MRS analysis. **Moreover, this technology opens up doors for inventing new MRS techniques aiming at, and for the first time, monitoring sub-microsecond dynamic changes in biomolecules. From an economic point of view, and since Canada is considered one of the international capitals of bio-pharmaceutical industries (with $4.2 billion contribution from pharmaceutical sector to Canadian GDP in 2011), the stakeholders for our technology are, potentially, all of the pharmaceutical companies operating on the Canadian territory. This new technology offers great opportunities for new start up companies to take the drug discovery research and development to a whole new level. This translates into an improved quality of life for Canadians.