A novel laser-based spectrophotometer for real-time analysis of doubly labeled wa

描述(由申请人提供)：在这个小型企业创新研究第二阶段项目中，洛斯加托斯研究公司(LGR)建议(与KineMed和代谢解决方案公司合作)开发和测试一种新型的基于激光的分光光度计(水同位素分析仪)，用于测量葡萄糖代谢和能量消耗。该仪器将基于LGR的专利离轴ICOS技术。水同位素分析仪将能够实时监测人类和动物生物样本(血液、尿液、唾液)中的氧和氢同位素，而不需要蒸馏。在这项工作中，LGR正在与KineMed Inc.和新陈代谢解决方案公司合作，开发和部署这种廉价、便携式和快速的仪器，直接(不经蒸馏)测量生物样品中的2H/1H(或D/H)和18O/16O，目标精度为D/H优于1/mil，18O/16O为0.4/mil。系统性能将首先在重量法制备的水样中展示，然后在水生物(人和动物)样品中展示。所有结果将通过与对相同样品进行的同位素比质谱仪(IRMS)测量的直接比较来验证。LGR将开发仪器，MSI和LGR将开发直接注射策略，MSI和KineMed将提供测试样品并使用IRMS进行测量。在第二阶段结束时，将向美国农业部、NIA或CALERIE指定的实验室(减少能量摄入的长期影响综合评估)提供一个系统进行评估。公共卫生相关性：LGR拟议的水同位素分析仪将在临床环境中自主运行，并报告对人类和动物生物样本(血液、尿液、唾液)中D/H和18O/16O的实时测量。这些新的和独特的仪器将成为能量消耗的双标记水测试的标准方法，以及用于测量包括人类在内的生命系统中代谢动力学的代谢测试的标准方法，用于新陈代谢紊乱、癌症以及炎症和神经退化疾病。KineMed最初将与LGR的水同位素分析仪(第二阶段仪器)一起部署氢化葡萄糖处置测试(KineMed获得专利)，该测试涉及葡萄糖代谢的测量，因此可作为胰岛素抵抗的指标。

DESCRIPTION (provided by applicant): In this Small Business Innovative Research Phase II project, Los Gatos Research (LGR) proposes to develop and test (with collaborators KineMed and Metabolic Solutions) a novel laser-based spectrophotometer (Water Isotope Analyzer) for measurements of glucose metabolism and of energy expenditure. The instrument will be based on LGR's patented Off-Axis ICOS technology. The Water Isotope Analyzer will be capable of real-time monitoring of oxygen and hydrogen isotopes in human and animal biological samples (blood, urine, saliva) directly and without distillation. In this effort, LGR is collaborating with KineMed Inc. and Metabolic Solutions Inc. to develop and deploy this inexpensive, portable and fast instrument for measurements of 2H/1H (or D/H) and 18O/16O in biological samples directly (without distillation) with a target precision of better than 1 per mil for D/H and 0.4 per mil for 18O/16O. System performance will be demonstrated first in gravimetrically prepared water samples and subsequently in aqueous biological (human and animal) samples. All results will be validated by direct comparison with Isotope Ratio Mass Spectrometry (IRMS) measurements made on the same samples. LGR will develop the instrument, MSI and LGR will develop the direct injection strategy, and MSI and KineMed will provide the test samples and measure them using IRMS. At the end of Phase II, a system will be made available to a USDA, NIA- or CALERIE-designated (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) laboratory for evaluation. PUBLIC HEALTH RELEVANCE: LGR's proposed Water Isotope Analyzer will operate autonomously in a clinical setting and report real-time measurements of D/H and 18O/16O in human and animal biological samples (blood, urine, saliva). These new and unique instruments will become the standard methodology for the Doubly-Labeled-Water test for energy expenditure, and for metabolic tests for measuring molecular kinetics in living systems, including humans, for metabolic disorders, cancer, and diseases of inflammation and neurodegeneration. The Deuterated Glucose Disposal Test (patented by KineMed) that KineMed will initially deploy with LGR's Water Isotope Analyzer (Phase II instrument) involves measurement of glucose metabolism and thus serves as an indicator of insulin resistance.