Commercial Development of a Novel Microfluidic Platform for Real-Time Biopharmaceutical Analysis

用于实时生物制药分析的新型微流体平台的商业开发

• 批准号: 9622234
• 负责人: Erik Gentalen
• 金额: $ 32.45万
• 依托单位: INTABIO, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-10 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9622234
• 关键词: Address; Advanced Development; Affect; Back; Biological Products; Blood capillaries; Cells; ChIP-on-chip; Charge; Chromatography; Complex; Computer software; Data; Data Display; Detection; Development; Device or Instrument Development; Electrodes; Generations; Heterogeneity; Image; Ions; Isoelectric Focusing; Lasers; Mass Spectrum Analysis; Measures; Methodology; Microfluidic Microchips; Microfluidics; Modification; Molecular Weight; Monoclonal Antibodies; Nature; Optics; Patients; Performance; Pharmaceutical Preparations; Phase; Positioning Attribute; Post-Translational Protein Processing; Preparation; Process; Production; Productivity; Protein Isoforms; Proteins; Reagent; Real-Time Systems; Research Infrastructure; Research Project Grants; Risk; Sampling; Science; Small Business Innovation Research Grant; System; Systems Integration; Techniques; Testing; Time; Toxic effect; Translating; Vertebral column; absorption; base; commercialization; cost; design; drug development; drug quality; effective therapy; graphical user interface; improved; innovation; instrument; instrumentation; lens; manufacturing process; mass spectrometer; microfluidic technology; novel; pressure; prevent; prototype; rapid detection; software development; tool

Project Summary   Biopharmaceuticals are complex molecules manufactured in living cells, and as a result, frequent quality testing is required for development, regulatory approval, and manufacturing. Capillary isoelectric focusing (cIEF) is a widely used analytical technique that provides rapid detection of most protein modifications. Mass spectrometry (MS) measures intrinsic molecular weight, and has the unique capability of identifying the specific nature of a given protein modification. Combining cIEF and MS is a powerful and highly effective approach to determining compositional differences between protein isoforms. However, current methodologies require labor intensive preparative chromatography to isolate sufficient material for the combined cIEF and MS analysis, and so are severely limited in capacity and throughput. To address this issue, Intabio has developed the Blaze™ system, a proprietary protein analytics platform that will be the first commercially available system to seamlessly integrate cIEF with MS analysis. The Blaze system utilizes a novel microfluidic chip design to integrate (1) separation of protein isoforms by isoelectric focusing, (2) imaging of protein isoforms by 280nm absorption for detection and quantitation, and (3) MS sample preparation and delivery by electrospray into an adjacent mass spectrometer to detect and identify each isoform. The Blaze system's integration of these steps drastically reduces the analysis time to only minutes per sample. This SBIR project will advance the development of the Blaze instrument, software and consumable kit, and will establish a consumable manufacturing process to prepare for commercial launch. Phase 1 will focus on advancing the core innovation - the chip and clamshell. The clamshell holds the microfluidic chip in the instrument and acts as the world-to-chip-interface, providing inputs for reagents, samples, pressure and electrodes. In Phase 1, the laser bonding process for the three-layer chip will be optimized to improve yield and chip performance by exploring multiple combinations of bonding parameters. Additionally, prototype designs to integrate the chip and clamshell into a single “cartridge” for improved ease-of-use will be designed and tested. Phase 2 will advance the prototype cartridge to a commercial, disposable version and set up the commercial manufacturing process for the chip cartridge. Commercial instrument and software development will also be completed in Phase 2. Instrument development will address strategies to reduce material cost and integrate an internal autosampler function; software development will refine integration and display of cIEF and MS data, as well as complete cfr21part11 compliance. The innovation and research from this project will advance the fields of protein separation science and expand the microfluidic technology field. This project will also transform biopharmaceutical drug development and manufacturing by enabling more frequent, comprehensive testing. This will result in profound productivity gains, translating into a greater number of higher quality drugs developed in less time and with less cost.

项目摘要   生物药物是在活细胞中生产的复杂分子，结果，频率 开发，监管批准和制造需要质量测试。毛细管等电 聚焦（CIEF）是一种广泛的分析技术，可快速检测大多数蛋白质 修改。质谱（MS）测量固有分子量，并具有独特的能力 确定给定蛋白质修饰的特定性质。结合CIEF和MS是一个强大而高度的 确定蛋白质同工型之间复合差异的有效方法。但是，当前 方法学需要劳动密集型制备的色谱法，以隔离足够的材料 结合CIEF和MS分析，因此容量和吞吐量受到严重限制。为了解决这个问题， Intabio开发了Blaze™系统，这是一个专有的蛋白质分析平台，将成为第一个 可商购的系统，无缝将CIEF与MS分析整合在一起。大火系统利用 新型微流体芯片设计以整合（1）通过等电聚焦分离蛋白质同工型，（2）成像 蛋白质同工型的检测和定量遭受280nm的受苦，（3）MS样品制备和 通过电喷雾传递到相邻的质谱仪中，以检测和识别每种同工型。大火 系统对这些步骤的集成大大减少了分析时间，每个样本只有几分钟。 这个SBIR项目将推动开发Blaze工具，软件和消耗套件的开发， 并将建立一个易于制造的工艺来准备商业发布。第1阶段将集中 在推进核心创新 - 芯片和翻盖。翻盖将微流体芯片固定在 仪器并充当世界到片段的面，为试剂，样品，压力和压力提供输入 电极。在阶段1中，将优化三层芯片的激光键合过程，以提高产量和 通过探索键合参数的多种组合来芯片性能。此外，原型设计 将设计和测试将芯片和翻盖板整合到单个“墨盒”中，以提高使用的易用性。 第2阶段将将原型墨盒推向商业，一次性版本并设置广告 芯片盒的制造过程。商业仪器和软件开发也将是 在第2阶段完成。仪器开发将解决降低材料成本的策略，并整合 内部自动采样器功能；软件开发将完善CIEF和MS数据的集成和显示， 以及完整的CFR21PART11合规性。 该项目的创新和研究将推进蛋白质分离科学领域和 扩展微流体技术领域。该项目还将改变生物制药药物开发 并通过更频繁地进行全面测试来制造。这将带来深远的生产力 收益，转化为更少的时间和成本更低的更高质量的药物。