A point-of-care device for phenylalanine determination

摘要 体外诊断解决方案(IVDS)建议开发第一个也是唯一一个FDA批准的护理点测试 用于测定手指或鞋跟样本中的L苯丙氨酸(Phe)。北大现在将 可作为PKU患者的终生家庭监护设备，也可作为较小患者的诊断测试设备 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 合规，大幅提高北大患者的生活质量，降低医疗成本。在第一阶段 通过研究，我们成功地解决了三个关键问题。我们消除了可能模糊的酪氨酸干扰 Phe(Aim-1)的测定消除了32%至60%(Aim-2)的红细胞压积偏差和 建立了“北大NOW”和实验室参考方法氨基酸分析之间的一致性 (AAA)，在准确度和精确度方面(AIM-3)。PKU是最常见的氨基酸紊乱，影响1/4 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。北卡罗来纳大学患者 必须在他们的一生中监测和控制他们的Phe水平，以避免严重的神经并发症， 永久性智力残疾和发育迟缓。目前，Phe水平的测量标准为 实验室通过采集血液或将血液斑点在干血斑卡片上并送去进行质检 分析。这种监控PHE的复杂过程使实时测量变得不可能，从而导致 不合规。目前，星展银行的检测结果可能需要几天到几周的时间。这种情况危及到 数万名北京大学学生的健康和福祉。这样的设备将为新生儿开辟道路 在发展中国家对北京大学进行筛查。在全世界出生的所有婴儿中，超过三分之二不会接受检测 供北大使用“(PKU.org)。IVDS提出的POCT，即“PKU Now”，将提供实时的血液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。要完成 北京大学的发展现在，我们将：目标-1：通过评估生物活性来完成测试发展 部件.AIM-2：从手工组装向半自动组装试条过渡.AIM-3： 开发和测试合成对照；目标-4：现在使用添加的血液样本验证PKU (遵循AIM-1的潜在变化)；和AIM-5：在两项盲法研究中，我们将建立 从PKU NoowTM获得的数据与使用PKU从AAA获得的数据之间的一致性 病人样本。这些研究将在经批准的IRBs下进行，并将遵循HIPPA的所有指南。 一旦商业化，北大NowTM将成为第一个PoC诊断工具和家庭监控设备，用于 北大患者，实现实时干预和治疗。

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.