Improved Cancer Biomarker Detection Using Novel Air Amplifier Designs in ESI-MS

在 ESI-MS 中使用新型空气放大器设计改进癌症生物标志物检测

• 批准号: 7497257
• 负责人: THOMAS A DOW
• 金额: $ 15.49万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-04 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497257
• 关键词: Air; Amplifiers; Biological Markers; Classification; Collaborations; Complex Mixtures; Computers; Detection; Devices; Diagnosis; Disease; Early Diagnosis; Elements; Engineering; Evaluation; Feedback; Health Systems Agencies; Injection of therapeutic agent; Instruction; Internet; Iodine-131 Human Serum Albumin; Laboratories; Malignant Neoplasms; Mass Spectrum Analysis; Methodology; Methods; Metric; Monitor; Ovarian; Patient Care; Patients; Peptides; Performance; Pliability; Prostate; Proteins; Proteomics; Protocols documentation; Range; Reaction; Recovery; Reproducibility; Research; Sampling; Site; Spectrometry, Mass, Electrospray Ionization; Staging; System; Technology; Time; base; clinically relevant; design; improved; ionization; liquid chromatography mass spectrometry; models and simulation; novel; numb protein; outcome forecast; response; tool; Air; Amplifiers; Biological Markers; Classification; Collaborations; Complex Mixtures; Computers; Detection; Devices; Diagnosis; Disease; Early Diagnosis; Elements; Engineering; Evaluation; Feedback; Health Systems Agencies; Injection of therapeutic agent; Instruction; Internet; Iodine-131 Human Serum Albumin; Laboratories; Malignant Neoplasms; Mass Spectrum Analysis; Methodology; Methods; Metric; Monitor; Ovarian; Patient Care; Patients; Peptides; Performance; Pliability; Prostate; Proteins; Proteomics; Protocols documentation; Range; Reaction; Recovery; Reproducibility; Research; Sampling; Site; Spectrometry, Mass, Electrospray Ionization; Staging; System; Technology; Time; base; clinically relevant; design; improved; ionization; liquid chromatography mass spectrometry; models and simulation; novel; numb protein; outcome forecast; response; tool

DESCRIPTION (provided by applicant): The identification and quantification of candidate biomarkers specific for a given cancer (e.g., ovarian, prostate) using tools such as liquid chromatography-mass spectrometry (LC-MS) is necessary for the diagnosis and treatment of the disease. Improved limits of detection for LC-MS and LC-tandem MS (LC-MS/MS) by implementation of devices such as the air amplifier proposed here will further these efforts enabling better patient care. Design using computer modeling and simulation, and fabrication using precision engineering methodologies will result in a stable, low tolerance air amplifier. The improved limits of detection by a well-designed and implemented air amplifier device will result in detection and quantification of low abundance candidate biomarkers in biofluids for both discovery-based and targeted proteomic applications. Systematic evaluation of the new air amplifier designs will utilize electrospray ionization mass spectrometry (ESI-MS). This will compare the original air amplifier design to the newly designed air amplifier based on the metrics of ionization time (MS analysis), limits of detection, and number of protein identifications from LC-MS/MS. After establishing a reproducible protocol for the air amplifier, it will be directly applicable for biomarker discovery and target based analysis. Multi-site evaluation of the improved air amplifier is proposed to determine inter-laboratory reproducibility. As a final element of this proposed research, the air amplifier design and application instructions will be disseminated on the internet for open access.

描述（由申请人提供）：使用诸如液相色谱 - 质谱法（LC-MS）等工具的特定于给定癌症（例如卵巢，前列腺）的候选生物标志物的识别和量化对于诊断和治疗是必要的。通过实施诸如空气放大器等设备（例如，LC-MS/MS）的LC-MS和LC-TANDEM MS（LC-MS/MS）的检测限制，此处提出的设备将进一步进一步实现这些努力，从而实现更好的患者护理。使用计算机建模和仿真设计，并使用精确工程方法制造将产生稳定的低公差空气放大器。设计良好的空气放大器设备的检测限制的提高将导致生物流体中低丰度候选生物标志物的检测和量化，用于基于发现的基于发现和靶向蛋白质组学的应用。新的空气放大器设计的系统评估将利用电喷雾电离质谱法（ESI-MS）。这将根据电离时间的指标（MS分析），检测限和来自LC-MS/MS的蛋白质鉴定数量，将原始空气放大器设计与新设计的空气放大器进行比较。在为空气放大器建立可重现协议后，它将直接适用于生物标志物发现和基于目标的分析。提出了改进的空气放大器的多站点评估，以确定实验室间的可重复性。作为这项拟议研究的最终元素，空中放大器的设计和应用说明将在Internet上传播以进行开放访问。