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.

摘要 本申请是关于国家中心推进转化科学SBIR/STTR 综合征集。体外诊断解决方案有限责任公司（IVDS）建议开发一种即时检测（POCT） 快速测定血液肌酸磷酸激酶（CPK）活性，以改善长链 脂肪酸氧化障碍（LCFAODs）。FAODs是常染色体遗传的先天性代谢缺陷， 隐性模式导致线粒体内能量产生不足， 方面的影响.婴儿或婴儿期发作的FAOD与肝功能障碍、低酮性低血糖、 脑病和并发症，严重者导致猝死。晚发型或成人型 FAOD通常与肌无力、肌痛和横纹肌溶解有关。之时尚 FAODs在全球约为1/10，000的新生儿，据估计，FAOD患者需要17.55个住院日 包括对患者、护理人员和医疗保健的显著时间、成本和努力负担 系统CPK是横纹肌溶解症和代谢失代偿的重要生物标志物， LCFAODs长期表现患者的经常监测的生物标志物。有一个紧急的， 对CPK测定的简单易用和准确的家庭监测的未满足需求，以帮助患者管理 他们的水合作用，饮食，活动水平和药物（Ultragenyx）。IVDS开创了通用POCT平台 基于用于确定分析物的精确浓度的成本有效的、便携式的和易于使用的装置 从手指针刺、脚跟针刺或微量采血管抽取全血。该平台基于比色检测 通过嵌入有LED面板的反射计，所述LED面板被选择为覆盖目前超过85%的比色指示器 市场上测试条提供血液成分与血浆的原位分离，并利用化学物质 具有超出常见干扰物范围的最大吸光度的指示剂，例如，血红蛋白和胆红素， 精确检测CPK活性。CPK Now是一个简单、准确、快速的POCT， 只有20微升的血液。移动的应用程序显示并存储血液CPK水平的结果， 传播给护理提供者，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。成功地执行这一建议将对这些国家产生持久的积极影响。 患有LCFAODs，并改变了复发性横纹肌溶解症的临床模式。具体 本提案的目的是：1）最终确定CPK检测制剂，2）膜的分析验证 制剂，3）消除30%至52%范围内的红细胞压积偏倚，4）立即建立CPK的一致性 使用患者样本与参比品进行比较，以及5）编制最终报告。