Novel laser spectrophotometer for real-time analysis of doubly labeled water

描述（由申请人提供）：在这个小型企业创新研究I期项目中，洛斯加托斯研究（LGR）提出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血液样本中的H2O同位素。在这项工作中，LGR正在与Kinemed Inc.合作。开发和部署这种廉价、便携和快速的仪器，用于测量血液样品中的2 H/1H（或D/H）和18（O）/16（O），目标精度优于D/H的1/mil和18（O）/16（O）的0.4/mil。系统性能将首先在重量法制备的水样中得到证明，随后在含水生物样品中得到证明。所有结果将通过与相同样品的同位素比质谱（IRMS）测量结果直接比较进行验证。LGR将开发仪器，KineMed将提供测试样品并使用IRMS进行测量。在第一阶段结束时，将向NIA或CALERIE指定的（减少能量摄入长期影响的综合评估）实验室提供原型系统进行评估。 项目叙述：LGR提出的水同位素分析仪将在临床环境中自动运行，并报告人体血液样本中D/H和18（O）/16（O）的实时测量结果。这些新仪器将成为能量消耗的双标记水测试的标准方法，以及Kinemed用于测量包括人类在内的生命系统中的分子动力学的测试，用于代谢紊乱，癌症以及炎症和神经退行性疾病。Kinemed最初将与LGR的水同位素分析仪一起部署的氘代葡萄糖处置测试（Kinemed的专利）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 I project, Los Gatos Research (LGR) proposes to develop and test 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 H2O isotopes in human and animal blood samples. In this effort, LGR is collaborating with Kinemed Inc. to develop and deploy this inexpensive, portable and fast instrument for measurements of 2H/1H (or D/H) and 18(O)/16(O) in blood samples with a target precision of better than 1 per mil for D/H and 0.4 per mil for 18(O)/16(O). System performance will be demonstrated first in gravimetrically prepared water samples and subsequently in aqueous biological 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 and KineMed will provide the test samples and measure them using the IRMS. At the end of Phase I, a prototype system will be made available to a NIA- or CALERIE-designated (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) laboratory for evaluation. Project Narrative: LGR's proposed Water Isotope Analyzer will operate autonomously in a clinical setting and report real-time measurements of D/H and 18(O)/16(O) in human blood samples. These new instruments will become the standard methodology for the Doubly-Labeled-Water test for energy expenditure, and for Kinemed's 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 involves measurement of glucose metabolism and thus serves as an indicator of insulin resistance.