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

微型化始于微电子领域，相关的制造工艺彻底改变了我们通信、处理信息和计算的方式。不久前，一种基于并行性的新范式被制定出来，研究人员声称，小型化应该通过在单个芯片上大量进行时加速生物测定和优化化学反应来实现生物学中的相同革命。因此，大规模并行生物分析具有巨大的潜力，用于各种应用，如药物发现和化学/生物危害的检测。但是，只有当集成微流控微电子系统（IFES）的发展成为可能时，这种潜力才能得到最大程度的释放。如今，IFES技术被用于从疾病诊断到DNA测序的各种应用。事实上，IFES技术提供了许多优势，如高通量筛选能力，低样品消耗和快速分析。因此，我们致力于开发用于药物发现应用和疾病管理所需的新一代IFES。** 在这项研究计划中，我们将利用最先进的微电子和微流体技术，实现特定分子传感技术的加速，即;磁共振光谱（MRS）。MRS被广泛用于药物发现研究，用于从天然衍生或合成的分子的大型文库中筛选有效药物，靶分子的三维结构的可视化，药物-靶结构稳定性的鉴定，以及最后但并非最不重要的是，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。* 本项目旨在通过将大量微型MRS探头集成在一个芯片上，解决使用2D MRS所带来的技术问题。微流体在这奋进发挥着重要作用。在微/纳升尺度下处理候选药物应该足够快，以便在MRS分析之前不发生化学变化。** 此外，这项技术为发明新的MRS技术打开了大门，旨在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），因此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，使药物发现研究和开发达到一个全新的水平。这意味着加拿大人的生活质量得到改善。

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.