A Novel Device for Determination of GFR Markers

一种测定 GFR 标志物的新型装置

• 批准号: 7405479
• 负责人: BIKAS VAIDYA
• 金额: $ 48.61万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7405479
• 关键词: Acetic Acid; Acetic Acids; American; Analytical Chemistry; Appearance; Automation; Biological Assay; Bismuth; Blood; Capillary Electrophoresis; Chemicals; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Trials; Complex; Computer software; Contrast Media; Creatinine; Data; Detection; Development; Devices; Diabetes Mellitus; Diagnostic; Dialysis procedure; Dissociation; Doctor of Medicine; Doctor of Philosophy; Edetic Acid; Electrochemistry; Electrodes; End stage renal failure; Engineering; Evaluation; Fluorescence; Functional disorder; Funding; Glomerular Filtration Rate; Goals; Government; Health Personnel; Health Professional; High Pressure Liquid Chromatography; Human Resources; Hypertension; I125 isotope; Impaired Renal Function; In Vitro; Indiana; Inulin; Iodides; Iodine; Iohexol; Iothalamate; Kidney; Kidney Diseases; Kidney Failure; Kidney Function Tests; Kidney Transplantation; Label; Laboratories; Lupus Erythematosus; Maintenance; Measurement; Measures; Membrane; Methods; Microfluidics; Monitor; Numbers; Patients; Performance; Persons; Phase; Physical Dialysis; Plasma; Povidone; Povidone-Iodine; Process; Purpose; Radiation; Radio; Radioactive; Radioactive Iodine; Radioactivity; Radioisotopes; Radiolabeled; Reaction; Renal function; Research; Research Personnel; Risk; Roentgen Rays; Sampling; Scientist; Serum; Services; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Staging; Standards of Weights and Measures; System; Technology; Testing; Therapeutic Intervention; Training; United States Food and Drug Administration; United States National Institutes of Health; Universities; Urine; Work; analytical method; base; cancer immunotherapy; commercialization; data management; design; experience; indexing; innovation; instrumentation; medical schools; novel; oxidation; pre-clinical; prevent; radiotracer; rapid technique

DESCRIPTION (provided by applicant): About 20 million Americans have chronic kidney disease while an additional 20 million are at risk. Over the next 10 years, the number of patients in the U.S. with end stage renal disease is expected to double. Some major causes of kidney dysfunction include hypertension, diabetes, lupus erythematosus, chemotherapy and immuno-suppression therapy. In all these instances, it is essential to have an accurate test of kidney function to determine the most appropriate therapeutic intervention. Preventing or slowing the progression of renal disease through early recognition of impaired renal function will reduce the number of patients with end stage renal disease and also prevent or reduce the need for dialysis and kidney transplantation. Glomerular Filtration Rate (GFR) is one of the best indexes of kidney function and it is determined by measuring the disappearance of certain agents from the blood and their appearance in urine. Although commonly used, the accurate estimation of GFR from serum creatinine is unreliable and insensitive as a marker of chronic kidney disease. Conversely, Inulin and radiolabeled Iothalamate provide an accurate measurement of GFR but Inulin is too expensive for common use and Iothalamate is difficult to assay because it requires either iodine-125 radiolabeling or expensive and cumbersome HPLC analysis. This Phase II SBIR proposal describes the development of a small bench-top device that can accurately, rapidly (5 minutes), and conveniently measure "cold" (non-radioactively labeled) Iothalamate in blood and urine samples that will render the usage of radioactively labeled Iothalamate and burdensome HPLC assays obsolete. During the Phase I project, Lynntech designed, fabricated, assembled, and tested a breadboard Iothalamate detection system from commercially available, off-the-shelf components. The system demonstrated sufficient sensitivity (< 20 ppm) in plasma and urine and sample analysis was complete in 5 minutes with minimal sample manipulation. The Phase II workplan describes the optimization of the detection method and the design, assembly, and testing of a fully-integrated bench-top device. The performance of the bench-top device will be compared to an HPLC method developed by our collaborator at the Indiana School of Medicine. The Phase II research also includes the identification of disposable components and process automation in the bench-top system. Glomerular Filtration Rate (GFR) is one of the best indexes of kidney function and it is determined by measuring the disappearance of certain agents from the blood and their appearance in urine. Currently available methods for determination of GFR markers are either too expensive, difficult to assay or require the use of radio-labeled markers. Lynntech's inexpensive and easy to use system can accurately detect non- radiolabeled GFR markers in plasma and urine which will enable the rapid and convenient determination of GFR.

描述（由申请人提供）：大约有2000万美国人患有慢性肾脏疾病，另有2000万人处于危险之中。在接下来的10年里，美国终末期肾病患者的数量预计将翻一番。肾功能不全的一些主要原因包括高血压、糖尿病、红斑狼疮、化疗和免疫抑制治疗。在所有这些情况下，必须进行准确的肾功能测试，以确定最合适的治疗干预。通过早期识别肾功能受损来预防或减缓肾脏疾病的进展，将减少终末期肾脏疾病患者的数量，并预防或减少对透析和肾移植的需求。肾小球滤过率（GFR）是肾功能的最佳指标之一，它是通过测量某些药剂从血液中消失及其在尿液中出现来确定的。虽然常用，但从血清肌酐准确估计GFR作为慢性肾脏疾病的标志物是不可靠和不敏感的。相反，菊粉和放射性标记的碘酞酸盐提供GFR的准确测量，但是菊粉对于常用来说太昂贵，并且碘酞酸盐难以测定，因为它需要碘-125放射性标记或昂贵且繁琐的HPLC分析。本II期SBIR提案描述了小型台式装置的开发，该装置可准确、快速（5分钟）且方便地测量血液和尿液样本中的“冷”（非放射性标记）碘酞酸盐，这将使放射性标记碘酞酸盐和繁琐的HPLC测定法的使用过时。在第一阶段项目中，Lynntech设计、制造、组装和测试了一个由市售现成组件制成的试验板碘酞酸盐检测系统。该系统在血浆和尿液中表现出足够的灵敏度（< 20 ppm），并且样品分析在5分钟内完成，样品操作最少。第二阶段工作计划描述了检测方法的优化以及完全集成的台式设备的设计、组装和测试。将台式装置的性能与我们在印第安纳州医学院的合作者开发的HPLC方法进行比较。第二阶段的研究还包括确定一次性组件和台式系统中的过程自动化。肾小球滤过率（GFR）是肾功能的最佳指标之一，它是通过测量某些药剂从血液中消失及其在尿液中出现来确定的。目前可用的用于测定GFR标志物的方法要么太昂贵，难以测定，要么需要使用放射性标记的标志物。Lynntech的廉价且易于使用的系统可以准确地检测血浆和尿液中的非放射性标记的GFR标志物，这将使得能够快速且方便地测定GFR。