A point-of-care device for phenylalanine determination

用于苯丙氨酸测定的即时检测设备

• 批准号: 10210405
• 负责人: Robert Harper
• 金额: $ 100.21万
• 依托单位: ANALYTICAL DIAGNOSTIC SOLUTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10210405
• 关键词: Affect; Aging; Amino Acids; Automation; Biological; Blood; Blood specimen; Classical phenylketonuria; Clinic; Clinical Laboratory Improvement Amendments; Collection; Color; Country; Data; Developed Countries; Developing Countries; Development; Devices; Diagnostic; Diagnostic tests; Disease; Excipients; FDA approved; Feedback; Fingers; Formulation; Freezing; Glucose; Goals; Guidelines; Hand; Harvest; Health; Health Care Costs; Heel; Hematocrit procedure; Heparin; Hereditary Disease; Home; Institutional Review Boards; Intellectual functioning disability; Intervention; Joints; Laboratories; Letters; Measurement; Measures; Medical; Membrane; Mental disorders; Methods; Modeling; Monitor; Neonatal Screening; Neurologic; Oxidoreductase; Patients; Personal Satisfaction; Phase; Phenylalanine; Phenylketonurias; Plasma; Polymers; Problem behavior; Process; Quality of life; Reagent; Sampling; Seizures; Sensitivity and Specificity; Sodium Azide; Specificity; Spottings; System; Temperature; Testing; Time; Training; Tube; Tyrosine; Venous; Vial device; Whole Blood; amino acid metabolism; assay development; blind; dietary; dihydrolipoamide dehydrogenase; improved; in-vitro diagnostics; medical specialties; meter; monitoring device; non-compliance; phase 1 study; point of care; point of care testing; point-of-care diagnostics; self testing; stability testing; temporal measurement; test strip; tool; waiver

Abstract In Vitro Diagnostic Solutions (IVDS) proposes to develop the first and only FDA-approved point-of-care test (POCT) for the determination of L-phenylalanine (Phe) from a finger or heel-stick sample. The PKU Now will serve as a lifelong home monitoring device for PKU patients as well as a diagnostic testing device in lesser- developed regions. It will provide immediate feedback on blood Phe levels, which will enable stricter dietary compliance, substantially improve the quality of life for PKU patients and reduce healthcare costs. In Phase I studies, we successfully resolved three critical issues. We eliminated tyrosine interference that could obscure the measurement of Phe (Aim-1), eliminated hematocrit bias in the range of 32% to 60% (Aim-2) and established concordance between the “PKU Now” and a laboratory reference method, Amino Acid Analysis (AAA), in terms of accuracy and precision (Aim-3). PKU is the most common amino acid disorder, affecting 1 in 10,000 people. Most cases of PKU are detected by newborn screening in developed countries. PKU patients must monitor and control their Phe levels throughout their lives to avoid severe neurological complications, permanent intellectual disabilities and delayed development. Currently, Phe levels are measured at laboratories via blood collection or blood spotted onto Dried Blood Spot Cards and sent for mass spec analysis. This complicated process for monitoring Phe makes real time measurements impossible resulting in non-compliance. “Currently, results from DBS testing can take days to weeks. This situation endangers the health and well-being of tens of thousands of people with PKU. Such a device will open the way for newborn screening of PKU in developing countries. Of all babies born around the world, more than 2/3 won’t be tested for PKU” (PKU.org). IVDS’s proposed POCT, the “PKU Now”, will provide real-time blood Phe levels, thereby enabling immediate intervention and improving the quality of life of thousands of people. To complete development of the PKU Now, we will: Aim-1: Finalize assay development by evaluating bioactive components; Aim-2: Transition from hand assembly to semi-automated assembly of test strips; Aim-3: Develop and test synthetic controls; Aim-4: Validate the PKU Now using spiked blood samples (following potential changes from Aim-1); and Aim-5: In two Blind Studies, we will establish concordance between the data obtained from the PKU NowTM and data obtained from AAA using PKU patient samples. These studies will be conducted under approved IRBs’ and will follow all HIPPA guidelines. Once commercialized, the PKU NowTM will be the first POC diagnostic tool and home monitoring device for PKU patients, enabling real-time intervention and treatment.

摘要 体外诊断解决方案（IVDS）提出开发第一个也是唯一一个FDA批准的床旁检测 （POCT）用于测定来自手指或足跟棒样品的L-苯丙氨酸（Phe）。北京大学现在将 作为PKU患者的终身家庭监测设备，以及在较小的诊断测试设备- 发达地区它将提供血液Phe水平的即时反馈，这将使更严格的饮食控制成为可能。 合规性，大大提高了PKU患者的生活质量，降低了医疗成本。一期 通过研究，我们成功地解决了三个关键问题。我们排除了酪氨酸干扰 Phe（Aim-1）的测量消除了32%至60%（Aim-2）范围内的红细胞压积偏倚， 建立了“PKU Now”和实验室参考方法氨基酸分析之间的一致性 (AAA)在准确度和精密度方面（Aim-3）。PKU是最常见的氨基酸紊乱， 一万人在发达国家，大多数PKU病例是通过新生儿筛查发现的。PKU患者 必须在一生中监测和控制他们的苯丙氨酸水平，以避免严重的神经系统并发症， 永久性智力残疾和发育迟缓。目前，Phe水平的测量值为 实验室通过血液采集或将血液点在干血斑卡上并送去进行质谱分析 分析.这种用于监测Phe的复杂过程使得不可能进行真实的时间测量， 不遵守。“目前，DBS测试的结果可能需要几天到几周的时间。这种情况危及 成千上万的PKU患者的健康和福祉。这样的设备将为新生儿 在发展中国家筛查苯丙酮尿症。在世界各地出生的所有婴儿中，超过三分之二的人不会接受测试 for PKU”（PKU.org）. IVDS提出的POCT，即“PKU Now”，将提供实时血液Phe水平，从而 从而能够立即采取干预措施，并改善成千上万人的生活质量。完成 现在，我们将：目标-1：通过评估生物活性，完成测定开发 组件; Aim-2：从手动组装过渡到半自动组装试纸条; Aim-3： 开发和测试合成对照品;目标-4：使用加标血样检测PKU Now （根据目标-1的潜在变化）;和目标-5：在两项盲法研究中，我们将确定 从PKU NowTM获得的数据与使用PKU从AAA获得的数据之间的一致性 患者样本。这些研究将在经批准的IRB指导下进行，并将遵循所有HIPPA指南。 一旦商业化，PKU NowTM将成为第一个POC诊断工具和家庭监测设备， PKU患者，实现实时干预和治疗。