SBIR Phase II: Novel Multi-Wavelength Time-Resolved Laser Induced Fluorescence Detector

SBIR 第二阶段：新型多波长时间分辨激光诱导荧光探测器

• 批准号: 0091507
• 负责人: Daniel Engebretson
• 金额: $ 50万
• 依托单位: DAKOTA TECHNOLOGIES INC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0091507&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Novel; Multi

This Small Business Innovation Research (SBIR) Phase II project will lead to a breakthrough in the use of laser-induced fluorescence (LIF) for chromatographic detection. Commercial standalone LIF detectors are based on CW lasers and collect data at a fixed wavelength. Consequently, they add minimal capability for resolving complex mixtures beyond that inherent in the chromatographic separation itself. On-the-fly fluorescence lifetime measurements at a single emission wavelength have been proposed as a better way to resolve the signals of co-eluting species. Our approach is far more powerful because it provides lifetimes on-the-fly and at several wavelengths simultaneously. A new prism flow cell fiber optically coupled to the emission spectrograph was introduced in Phase I. In addition, two different algorithms strategies for analyzing the multi-dimensional fluorescence data were developed and demonstrated. In Phase II a diode-pumped laser will replace the flashlamp pumped excitation laser, thereby providing 100 times higher pulse repetition frequency, 10 times shorter pulse duration, and 10 times better shot-to-shot stability. New digitizer technology will be incorporated to accommodate the laser's high repetition frequency. Important Phase II activities include fluorescence methods development to extend the range of applications to drugs and drug metabolites and elaboration of the chemometric algorithms.The instrumental approach to be realized through the Phase II research will have a profound impact on QA/QC assessments of drug purity, bioequivalence and pharmacokinetic studies, and research investigations in humans and animals. Sales of several hundred units per year to pharmaceutical manufacturers, contract research organizations, and universities are anticipated. The technology will later be adapted for faster and more accurate DNA sequencing.

这个小型企业创新研究 (SBIR) 第二阶段项目将在激光诱导荧光 (LIF) 色谱检测的使用方面取得突破。商用独立 LIF 探测器基于 CW 激光器，并以固定波长收集数据。因此，除了色谱分离本身固有的功能之外，它们还增加了最小限度的解析复杂混合物的能力。单个发射波长下的动态荧光寿命测量已被提议作为解析共洗脱物质信号的更好方法。我们的方法要强大得多，因为它可以同时在多个波长上动态提供寿命。第一阶段引入了一种与发射光谱仪光学耦合的新型棱镜流动池光纤。此外，还开发并演示了两种用于分析多维荧光数据的不同算法策略。在第二阶段，二极管泵浦激光器将取代闪光灯泵浦激发激光器，从而提供高出 100 倍的脉冲重复频率、缩短 10 倍的脉冲持续时间以及提高 10 倍的逐次稳定性。将采用新的数字化仪技术来适应激光器的高重复频率。重要的第二阶段活动包括荧光方法开发，以扩大药物和药物代谢物的应用范围，以及化学计量算法的阐述。通过第二阶段研究实现的仪器方法将对药物纯度的 QA/QC 评估、生物等效性和药代动力学研究以及人类和动物的研究调查产生深远的影响。预计每年向药品制造商、合同研究组织和大学销售数百件。 该技术随后将进行调整，以实现更快、更准确的 DNA 测序。