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: 10080660
• 负责人: Robert Harper
• 金额: $ 94.49万
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080660
• 关键词: Affect; Aging; Amino Acids; Automation; Bedside Testings; Biological; Blood; Blood specimen; Classical phenylketonuria; Clinic; Clinical Laboratory Improvement Amendments; Collection; Color; Country; Data; Developed Countries; Developing Countries; Development; Devices; Diagnostic; Diagnostic tests; Diet; Disease; Excipients; FDA approved; Feedback; Fingers; Formulation; Freezing; Glucose; Goals; Guidelines; Hand; Harvest; Health; Health Care Costs; Heel; Hematocrit procedure; Heparin; Hereditary Disease; Home environment; In Vitro; 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; dihydrolipoamide dehydrogenase; improved; medical specialties; meter; monitoring device; non-compliance; phase 1 study; point of care; point-of-care diagnostics; stability testing; temporal measurement; 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.

抽象的 体外诊断解决方案 (IVDS) 提议开发第一个也是唯一一个经 FDA 批准的即时检测 (POCT) 用于测定手指或脚后跟样本中的 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，从而实现更严格的饮食 合规性，大幅改善 PKU 患者的生活质量并降低医疗成本。第一阶段 研究中，我们成功解决了三个关键问题。我们消除了可能掩盖的酪氨酸干扰 Phe 的测量 (Aim-1)，消除了 32% 至 60% 范围内的血细胞比容偏差 (Aim-2) 和 建立了“PKU Now”与实验室参考方法（氨基酸分析）之间的一致性 (AAA)，在准确性和精密度方面 (Aim-3)。 PKU 是最常见的氨基酸紊乱，影响 1 % 10,000 人。在发达国家，大多数 PKU 病例是通过新生儿筛查发现的。北大患者 必须在一生中监测和控制他们的 Phe 水平，以避免严重的神经系统并发症， 永久性智力障碍和发育迟缓。目前，Phe 水平测量为 实验室通过血液采集或将血液点在干血点卡上并送去进行质谱分析 分析。这种复杂的 Phe 监测过程使得实时测量变得不可能，从而导致 不遵守规定。 “目前，DBS 测试结果可能需要几天到几周的时间。这种情况危及到 数万名 PKU 患者的健康和福祉。这样的设备将为新生儿开辟道路 发展中国家的 PKU 筛查。世界各地出生的所有婴儿中，超过 2/3 不会接受检测 for PKU”（PKU.org）。IVDS 提议的 POCT，即“PKU Now”，将提供实时血液 Phe 水平，从而 能够立即进行干预并改善成千上万人的生活质量。完成 现在，我们将： 目标 1：通过评估生物活性来完成检测开发 成分; Aim-2：试纸条从手工组装过渡到半自动组装；目标3： 开发和测试综合控制； Aim-4：使用加标血液样本验证 PKU Now （遵循 Aim-1 的潜在变化）；目标 5：在两项盲研究中，我们将建立 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。这些研究将在批准的 IRB 下进行，并将遵循所有 HIPPA 指南。 一旦商业化，PKU NowTM 将成为首个 POC 诊断工具和家庭监控设备。 PKU 患者，实现实时干预和治疗。