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

小型化始于微电子领域，相关的制造工艺彻底改变了我们交流、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，微型化应该通过在单个芯片上大量执行时加速生物检测和优化化学反应，来进行同样的生物学革命。因此，大规模并行生物分析在药物发现和检测化学/生物危害等各种应用方面具有巨大的潜力。但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、低样本消耗和快速分析。因此，我们承担了用于药物发现应用和疾病管理所需的新一代IFES的开发。**在这项研究计划中，我们将利用最先进的微电子学和微流体技术，实现特定分子传感技术的加速，即磁共振光谱(MRS)。MRS被广泛应用于药物发现研究，用于从天然或合成的大分子文库中筛选有效药物，可视化靶分子的三维结构，鉴定药物靶结构的稳定性，最后但不是最不重要的，阐明分子构象的快时间尺度动态变化。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敏感性。这是迄今为止用于实现药物发现所需的所谓二维MRS的经典设备的一个严重缺陷。*这项计划通过将大量微型MRS探头集成到一个芯片上，解决了使用2D MRS所带来的技术问题。微流体学在这一努力中发挥着重要作用。在微纳升规模上处理候选药物的速度应该足够快，以便在MRS分析之前不会发生化学变化。**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中亚微秒的动态变化。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首都之一(2011年，制药行业为加拿大GDP贡献了42亿美元)，我们技术的利益相关者可能是在加拿大领土上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，使药物发现和研究开发达到一个全新的水平。这转化为加拿大人生活质量的提高。

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.