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

摘要 本申请是关于国家高级翻译科学中心SBIR/STTR的 综合征集。在体外诊断解决方案，有限责任公司(IVDS)建议开发一种护理点测试(POCT) 快速检测血肌酸磷酸酶(CPK)活性以改进长链管理 脂肪酸氧化紊乱(LCFAOD)。FAOD是常染色体遗传的先天新陈代谢错误 导致线粒体内能量生产不足和严重下游的隐性模式 效果。婴儿或青少年发病的FAOD与肝功能障碍、低酮症低血糖、 脑病和并发疾病，严重者会导致猝死。晚发或成年型 FAOD通常与肌肉无力、肌痛和横纹肌溶解有关。疾病的流行 全球FAOD的发生率约为万分之一，据估计，FAOD患者需要17.55天的住院日 每年给患者、护理人员和医疗保健人员带来巨大的时间、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，是最重要的 长期表现为慢性脂肪肝的患者的频繁监测的生物标志物。有一个紧急的， 对简单易用和准确的家庭监护的需求未得到满足，以确定帮助患者管理CPK的决心 他们的水分、饮食、活动水平和药物(Ultragenyx)。IVDS开创了一个通用的POCT平台 基于一种经济高效、便携且简单易用的设备，用于确定分析物的准确浓度 从指棒、鞋跟棒或微容器抽出的全血。该平台是基于比色检测的 通过嵌入LED面板的反射计，选择覆盖目前85%以上的色度指示器 在市场上。试纸提供血液成分与血浆的原位分离，并利用一种化学物质 最大吸光度超出常见干扰物(如血红蛋白和胆红素)范围的指示剂 提供CPK活性的精确检测。CPK现在是一个简单、准确、快速的POCT要求 只有20微克L的血。一款移动应用程序可以远程显示和存储血液CPK水平的结果 传播给护理提供者，以便就患者是否应该去急诊做出必要的决定 在家住宿或管理。这项提议的成功执行将对以下方面产生持久的积极影响 患有LcFAOD并改变围绕复发性横纹肌溶解症的临床模式。具体的 这项建议的目的是：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%范围内的红细胞压积偏差，4)现在建立CPK的一致性 使用患者样本作为参考，5)准备最终报告。

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.