Automated Manufacturing of High Performance Nanofluidic Separation Devices

高性能纳流分离装置的自动化制造

• 批准号: 7667530
• 负责人: Colleen K Van Pelt
• 金额: $ 37.98万
• 依托单位: CORSOLUTIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-26 至 2011-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7667530
• 关键词: Address; Affect; Area; Arts; Beds; Binding; Biological; Biological Sciences; Blood capillaries; Charge; Chemicals; Chromatography; Clinical; Complex; Complex Mixtures; Computer software; Coupled; Data; Data Analyses; Data Quality; Databases; Defect; Devices; Diagnostic; Dimensions; Feedback; Genomics; Goals; Ions; Kinetics; Laboratories; Laboratory Study; Length; Light; Liquid Chromatography; Mass Spectrum Analysis; Monitor; Optics; Pattern Recognition; Performance; Phase; Play; Polysaccharides; Post-Translational Protein Processing; Process; Proteins; Proteomics; Quality Control; Reproducibility; Research Personnel; Robotics; Sample Size; Sampling; Site; Small Business Innovation Research Grant; Solvents; Source; Structure; System; Techniques; Technology; Testing; Time; Variant; Work; capillary; complex biological systems; cost; cost effective; detector; improved; innovation; interest; ionization; light transmission; liquid chromatography mass spectrometry; manufacturing process; mass spectrometer; nano; nanofluidic; novel strategies; particle; prevent; prototype; public health relevance; sensor; technology development; time use; user-friendly

DESCRIPTION (provided by applicant): Nano-liquid chromatography (nanoLC) can resolve highly complex, otherwise intractable biological mixtures, and offer high sensitivity due to its enhanced resolving power. As a result when coupled to mass spectrometry, nanoLC can address complex proteomic problems such as molecular interactions, ion structures, quantitation, and kinetics. Consequently nanoLC is a necessity for biological laboratories. But unfortunately the technique is alarmingly underutilized as it suffers from limitations including reproducibility issues created by column bed inconsistencies, difficulty making nano-fluidic connections, difficulty troubleshooting system malfunctions, and the technique is labor intensive. CorSolutions is developing a robust, user-friendly, "plug- and-play" nano-LC electrospray device that will address all of the limitations of the nanoLC technique, except for the irreproducible column performance issues. These column-to-column inconsistencies arise from particle packing variations within the packed beds introduced during manufacturing, which result in performance variations and therefore limit the technology from pervasive use in the biological and clinical diagnostic fields. CorSolutions will develop automated column packing and automated, optical packed-bed inspection technology for manufacturing packed columns for nanofluidic applications. This technology will allow for both automated manufacture and subsequent inspection of the columns produced. The inspection technology will monitor light transmission through a column bed, detecting any inconsistencies in particle packing such as voids. This approach will offer consistently packed columns with reproducible column performance. Furthermore this manufacturing approach will reduce the cost of nanoLC columns, as extensive quality control testing will no longer be required. Reproducible column performance and lower column cost, together with the "plug-and-play" nanoLC system CorSolutions is developing, will dramatically reduce the complexity of nanoLC, allowing pervasive use of the technology. Also, this manufacturing approach, which could offer inexpensive, one-time use columns, may allow for nanoLC to enter the field of clinical diagnostics. The goals of the Phase I SBIR will be to first construct an automated column packing prototype, which will create columns with reproducibly packed beds and will contain an integrated photoelectric sensor to terminate the packing process when the column bed reaches a desired length. The second goal will be to construct an automated optical packed bed inspection prototype with pattern recognition software to identify bed defects. The final goal is to evaluate the prototypes by assessing column quality. This will include manufacturing 30 columns, assessing inter- and intra-column performance variables, and comparing the data to that of commercial columns. Our long term objective is to provide a novel approach for the manufacture of reproducibly performing, low cost nanofluidic columns. This will allow nanoLC to become an integral part of biological laboratories, and allow biologists to benefit from its highly informative data. PUBLIC HEALTH RELEVANCE: Nano-liquid chromatography mass spectrometry (nanoLC/MS) is a powerful technique for proteomic and glycomic studies which is able to not only identify proteins and glycans from very complex mixtures, but is also able to structurally characterize differences between the components, which is particularly important for post-translational modifications. However, nanofluidic technologies have been slow to commercialize due to lack of advanced and cost effective manufacturing approaches. Furthermore the existing manufacturing processes have not allowed for consistent column-to-column performance in conventional nanoLC, which is serving as a barrier to widespread acceptance of the technique. Therefore technology development allowing for the manufacture of columns with enhanced, reproducible performance as well as reduced column cost, will permit the powerful nanoLC technique to infiltrate all biological laboratories, which could enable scientific discoveries and greater understanding of complex biological systems.

描述（由申请人提供）：纳米液相色谱法（nanoLC）可以解析高度复杂的，否则难以处理的生物混合物，并由于其增强的分辨率而提供高灵敏度。因此，当与质谱联用时，nanoLC可以解决复杂的蛋白质组学问题，如分子相互作用、离子结构、定量和动力学。因此，nanoLC是生物实验室的必需品。但不幸的是，该技术的利用率令人担忧，因为它受到限制，包括由柱床不一致性产生的再现性问题，难以进行纳米流体连接，难以排除系统故障，并且该技术是劳动密集型的。CorSolutions正在开发一种强大的、用户友好的“即插即用”纳米LC电喷雾装置，该装置将解决纳米LC技术的所有限制，除了不可重现的柱性能问题。这些柱与柱之间的不一致性是由制造过程中引入的填充床内的颗粒填充变化引起的，这导致性能变化，因此限制了该技术在生物和临床诊断领域的广泛使用。CorSolutions将开发自动化柱填充和自动化光学填充床检测技术，用于制造纳米流体应用的填充柱。该技术将允许自动化制造和随后对所生产的柱进行检查。该检测技术将监测通过柱床的光传输，检测颗粒填充中的任何不一致性，如空隙。这种方法将提供具有可重现柱性能的一致填充柱。此外，这种制造方法将降低nanoLC柱的成本，因为不再需要广泛的质量控制测试。可再生的色谱柱性能和较低的色谱柱成本，以及CorSolutions正在开发的“即插即用”nanoLC系统，将大大降低nanoLC的复杂性，从而使该技术得到广泛应用。此外，这种制造方法可以提供廉价的一次性柱，可以使nanoLC进入临床诊断领域。第一阶段SBIR的目标是首先构建一个自动化柱填充原型，该原型将创建具有可重复填充床的柱，并将包含一个集成的光电传感器，以在柱床达到所需长度时终止填充过程。第二个目标将是构建一个自动化的光学填充床检测原型与模式识别软件，以确定床的缺陷。最终目标是通过评估色谱柱质量来评估原型。这将包括生产30个色谱柱，评估色谱柱间和色谱柱内性能变量，并将数据与商业色谱柱的数据进行比较。我们的长期目标是提供一种新的方法，用于制造可再现的性能，低成本的纳米流体柱。这将使nanoLC成为生物实验室不可或缺的一部分，并使生物学家从其高度信息化的数据中受益。 公共卫生相关性：纳米液相色谱质谱（nanoLC/MS）是一种用于蛋白质组学和糖组学研究的强大技术，不仅能够从非常复杂的混合物中识别蛋白质和聚糖，而且还能够在结构上表征组分之间的差异，这对于翻译后修饰特别重要。然而，由于缺乏先进的和具有成本效益的制造方法，纳米流体技术商业化缓慢。此外，现有的制造工艺不允许在常规纳米LC中具有一致的柱到柱性能，这是该技术被广泛接受的障碍。因此，允许制造具有增强的、可再现的性能以及降低的柱成本的柱的技术开发将允许强大的nanoLC技术渗透到所有生物实验室，这可以使科学发现和对复杂生物系统的更好理解成为可能。