A point of care-device for the determination of creatinine phosphokinase (CPK), the CPK Now

用于测定肌酸酐磷酸激酶 (CPK) 的护理点设备，CPK Now

• 批准号: 10822139
• 负责人: Robert Harper
• 金额: $ 29.59万
• 依托单位: ANALYTICAL DIAGNOSTIC SOLUTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10822139
• 关键词: Accident and Emergency department; Address; Adolescent; Adult; Attenuated; Australia; Bilirubin; Biological Assay; Biological Markers; Birth; Blood; Blood specimen; Caregivers; Chemicals; Child; Clinical; Clinical Management; Clinics and Hospitals; Consent Forms; Creatine Kinase; Creatinine; Defect; Detection; Development; Devices; Diagnosis; Diagnostic Equipment; Diet; Disease; Dose; Encephalopathies; Enzymes; Fingers; Formulation; Functional disorder; Germany; Glucosephosphate Dehydrogenase Deficiency; Health; Healthcare Systems; Heel; Hematocrit procedure; Hemoglobin; Hepatic; Home; Hydration status; Hypoglycemia; In Situ; Inborn Errors of Metabolism; Incidence; Inherited; Institutional Review Boards; Length of Stay; Letters; Live Birth; Marketing; Medical Genetics; Membrane; Metabolic; Mitochondria; Monitor; Muscle Weakness; Myalgia; National Center for Advancing Translational Sciences; Newborn Infant; Outcome; Patient Monitoring; Patients; Pattern; Pharmaceutical Preparations; Phase; Plasma; Prevalence; Production; Protocols documentation; Rare Diseases; Reagent; Recurrence; Reporting; Research Priority; Rhabdomyolysis; Sampling; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Sudden Death; Technology; Testing; Time; United States; Universities; Utah; Validation; Whole Blood; adenylate kinase; autosome; care providers; cost; cost effective; detection limit; enzyme activity; experience; fatty acid oxidation; fatty acid transport; home test; improved; in-vitro diagnostics; infancy; inhibitor; long chain fatty acid; meter; mobile application; oxidation; patient biomarkers; personalized management; point of care; point of care testing; portability; rapid diagnosis; remote grading; remote monitoring; response; screening; self testing; test strip; tool; treatment strategy

Abstract This application is in regard to the National Center for Advancing Translational Sciences SBIR/STTR Omnibus Solicitation. In Vitro Diagnostic Solutions, LLC (IVDS) proposes to develop a point-of-care test (POCT) to rapidly determine blood creatine phosphokinase (CPK) activity for the improved management of long-chain fatty acid oxidation disorders (LCFAODs). FAODs are inborn errors of metabolism inherited in an autosomal recessive pattern that result in deficient energy production within the mitochondria and severe downstream effects. Infantile or adolescent-onset FAODs are associated with hepatic dysfunction, hypoketotic hypoglycemia, encephalopathy, and intercurrent illness, with severe cases resulting in sudden death. Later or adult-onset FAODs are typically associated with muscle weakness, myalgias, and rhabdomyolysis. The prevalence of FAODs is about 1 in 10,000 births globally, and it is estimated that FAOD patients require 17.55 hospital days per year comprising a significant time, cost, and effort burden on the patients, caregivers, and the healthcare system. CPK is an important biomarker for rhabdomyolysis and metabolic decompensation and is the most frequently monitored biomarker for patients with long-term manifestations of LCFAODs. There is an urgent, unmet need for simple-to-use and accurate home monitoring for CPK determination to help patients manage their hydration, diet, activity levels, and medication (Ultragenyx). IVDS has pioneered a universal POCT platform based on a cost-effective, portable, and simple-to-use device for determining accurate concentrations of analytes in whole blood from a finger-stick, heel-stick, or microtainer draw. The platform is based on colorimetric detection via a reflectometer embedded with a panel of LEDs chosen to cover over 85% of colorimetric indicators currently on the market. Test strips provide in situ separation of blood components from plasma and utilize a chemical indicator with absorbance maximum outside the range of common interferents, e.g., hemoglobin and bilirubin, to provide precise detection of CPK activity. The CPK Now is a single step, accurate, and rapid POCT requiring only 20 µL of blood. A mobile app displays and stores results of blood CPK levels which can be remotely disseminated to the care provider to make essential decisions on whether the patient should go to the emergency room or manage from home. Successful execution of this proposal will have a lasting, positive impact on those suffering from LCFAODs and shift the clinical paradigms surrounding recurrent rhabdomyolysis. The specific aims of this proposal are: 1) Finalize CPK Detection Formulation, 2) Analytical Validation of Membrane Formulations, 3) Eliminate Hematocrit Bias in the Range of 30% to 52%, 4) Establish Concordance of CPK Now to the Reference Using Patient Samples, and 5) Prepare Final Report.

抽象的 本申请涉及国家转化科学促进中心 SBIR/STTR 综合征集。体外诊断解决方案有限责任公司 (IVDS) 提议开发即时检测 (POCT) 快速测定血液肌酸磷酸激酶 (CPK) 活性，以改善长链的管理 脂肪酸氧化障碍（LCFAOD）。 FAOD 是常染色体遗传的先天性代谢错误 导致线粒体内能量产生不足和严重下游的隐性模式 影响。婴儿或青少年发病的FAOD与肝功能障碍、低酮性低血糖、 脑病，并发疾病，严重者导致猝死。较晚或成人发病 FAOD 通常与肌肉无力、肌痛和横纹肌溶解症有关。患病率 全球大约有万分之一的新生儿患有FAOD，估计FAOD患者需要住院17.55天 每年给患者、护理人员和医疗保健人员带来大量的时间、成本和精力负担 系统。 CPK是横纹肌溶解和代谢失代偿的重要生物标志物，也是最重要的生物标志物。 经常监测具有长期 LCFAOD 表现的患者的生物标志物。有紧急情况， 对简单易用且准确的家庭监测 CPK 测定以帮助患者进行管理的需求尚未得到满足 他们的水分、饮食、活动水平和药物 (Ultragenyx)。 IVDS 开创了通用 POCT 平台 基于经济高效、便携式且易于使用的设备，用于确定分析物的准确浓度 指尖采血、足跟采血或微量采血器抽取的全血。该平台基于比色检测 通过嵌入 LED 面板的反射计，选择覆盖目前超过 85% 的比色指示器 在市场上。测试条可将血液成分与血浆原位分离，并利用化学物质 最大吸光度超出常见干扰物（例如血红蛋白和胆红素）范围的指示剂，以 提供CPK活性的精确检测。 CPK Now 是一步、准确、快速的 POCT，需要 仅 20 µL 血液。移动应用程序显示并存储血液 CPK 水平结果，可以远程查看 分发给护理人员以做出关于患者是否应该去急诊室的重要决定 房间或在家管理。该提案的成功执行将对相关人员产生持久、积极的影响 患有 LCFAOD 并改变了复发性横纹肌溶解症的临床范式。具体的 该提案的目标是：1) 最终确定 CPK 检测配方，2) 膜的分析验证 配方，3) 消除 30% 至 52% 范围内的血细胞比容偏差，4) 立即建立 CPK 一致性 使用患者样本参考，以及 5) 准备最终报告。