Point-of-birth newborn screening for MCAD/VLCAD and galactosemia to eliminate deadly delays for time critical conditions

对 MCAD/VLCAD 和半乳糖血症进行出生点新生儿筛查，以消除时间紧迫情况下的致命延误

• 批准号: 9545038
• 负责人: Ramakrishna Sista
• 金额: $ 69.66万
• 依托单位: BAEBIES, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9545038
• 关键词: Address; Advisory Committees; Bedside Testings; Biochemical; Biochemistry; Biological Assay; Birth; Blood; Blood specimen; Clinical; Data; Development; Devices; Diagnosis; Diagnostic; Diet; Disease; Elderly; Family Leave; Funding; Future; Galactosemias; Geographic Locations; Hypoglycemia; Inborn Errors of Metabolism; Incidence; Individual; Infant; Intake; Intervention; Laboratories; Life Expectancy; Liquid substance; Long-Chain-Acyl-CoA Dehydrogenase; Metabolic; Methods; Microfluidics; Miniaturization; Missouri; Molecular Analysis; Neonatal Screening; Neurologic; Neurologic Deficit; Newborn Infant; Nurseries; Outcome; Patients; Performance; Phase; Pilot Projects; Positioning Attribute; Reagent; Reference Standards; Sampling; Sensitivity and Specificity; Socioeconomic Status; Spottings; Survivors; System; Technology; Testing; Time; Uncertainty; United States; Universities; Validation; Vision; Whole Blood; acyl-CoA dehydrogenase; assay development; base; clinical Diagnosis; cost effective; design; digital; enzyme activity; fatty acid oxidation; feeding schedule; improved; improved outcome; infant death; innovation; instrument; microfluidic technology; novel; point of care; screening

We aim to revolutionize the traditional newborn screening paradigm by developing a point-of-care digital microfluidic platform for biochemical screening of fatty acid oxidation disorders (FAOs) and galactosemia. These disorders are inborn errors of metabolism that have profound neurological and hypoglycemic effects if not detected early. Although these disorders are included in traditional newborn screening with a multi-day turnaround, infants still die due to the “deadly delays” inherent to the system of transporting dried blood spots to a central laboratory. Confirmation of a diagnosis of common FAOs by enzymatic or molecular analysis can take months, leaving families in a stressful position of uncertainty. Point-of-care testing by enzyme activity is critical to address these issues. As of yet there is not a single point-of-care newborn screening technology available for biochemical screening or diagnostic confirmation. Baebies’ digital microfluidic platform is a recognized innovative, affordable, automated microdroplet-based liquid handling system that can be configured to address this challenge. The digital microfluidic technology enables miniaturization of assays and significantly reduces reagent and sample volumes while providing timely data to guide clinical intervention. Baebies is guided by a vision that every newborn deserves a healthy start. Baebies’ current product is for a laboratory setting and has been in use for over 2 years in the state of Missouri for the first ever newborn screening pilot study of multiple lysosomal storage disorders in the United States. The proposed point-of-birth (POB) newborn screening platform utilizes the same underlying digital microfluidic technology and aims for a time-to-result of 15 minutes so that prompt treatment through a controlled feeding schedule can be initiated. The project objective is to demonstrate technical feasibility of using digital microfluidics to detect medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and galactosemia in whole blood samples for improved newborn screening at the point-of-birth. The Phase I specific aims include biochemistry development of the assays on whole blood samples, integration and analytical validation of the multiplexed panel, and preliminary method comparison using blood samples from newborns at the University of Pittsburgh. In Phase II, we will complete hardware development of the point-ofbirth platform, complete development of a self-contained cartridge, and perform a pilot study for method comparison. The point-of-birth platform will have the ability to expand to other time-critical conditions in the future.

我们的目标是通过开发一种即时数字化的新生儿筛查模式， 微流控平台用于脂肪酸氧化障碍（FAOs）和半乳糖血症的生化筛选。 这些疾病是先天性的代谢缺陷，具有深刻的神经和低血糖的影响，如果 没有及早发现。尽管这些疾病包括在传统的新生儿筛查中， 即使在这种情况下，由于运输干血斑系统固有的“致命延误”，婴儿仍然会死亡 一个中心实验室通过酶或分子分析确认常见FAOs的诊断， 需要几个月的时间，让家庭处于不确定的紧张境地。通过酶活性进行即时检测是 解决这些问题至关重要。到目前为止，还没有一种单一的护理点新生儿筛查技术 可用于生化筛查或诊断确认。 Baebies的数字微流体平台是一个公认的创新，负担得起的，自动化的微滴为基础的 液体处理系统，可以配置为解决这一挑战。数字微流控技术 能够实现测定的小型化，并显著减少试剂和样品体积，同时提供及时的 指导临床干预的数据。Baebies的愿景是每个新生儿都应该有一个健康的开始。 Baebies目前的产品是用于实验室环境，并已在密苏里州使用超过2年 在美国进行的第一次新生儿筛查试验性研究中发现了多发性溶酶体贮积症。 所提出的出生点（POB）新生儿筛查平台利用相同的底层数字微流体 技术和目标的时间为15分钟的结果，使及时治疗，通过控制喂养 时间表可以启动。 该项目的目标是证明使用数字微流体检测中链的技术可行性 酰基辅酶A脱氢酶（MCAD）缺乏、极长链酰基辅酶A脱氢酶（VLCAD）缺乏 和半乳糖血症的全血样本，以改善新生儿筛查在出生点。I期 具体目标包括全血样品分析的生物化学开发，整合和 多重组的分析验证，以及使用来自 匹兹堡大学的新生儿。在第二阶段，我们将完成出生点的硬件开发 平台，完成了独立检测盒的开发，并对方法进行了初步研究 对比出生点平台将有能力扩展到其他时间紧迫的条件， 未来