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

我们的目标是通过开发一种护理点数字技术来彻底改变传统的新生儿筛查模式 用于脂肪酸氧化紊乱(FAO)和半乳糖血症生化筛查的微流控平台。 这些疾病是先天的代谢错误，在以下情况下会产生深远的神经和降血糖影响 没有及早发现。虽然这些疾病包括在传统的新生儿筛查中，但需要多天时间 转身，婴儿仍然死于运输干血斑点的系统所固有的“致命延迟” 送到一个中心实验室。通过酶或分子分析确认常见FAO的诊断可以 需要几个月的时间，让家庭处于充满压力和不确定的境地。通过酶活性进行的护理点测试是 对解决这些问题至关重要。到目前为止，还没有一种单一的新生儿筛查技术 可用于生化筛查或诊断确认。 Baebies的数字微流体平台是公认的创新、实惠、自动化的基于微滴的平台 可配置的液体处理系统，以应对这一挑战。数字微流控技术 实现了分析的小型化，显著减少了试剂和样本量，同时及时提供 指导临床干预的数据。Baebies的指导理念是，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了两年多 这是美国首次对多发性溶酶体储存障碍进行新生儿筛查的先导性研究。 拟议的出生地点(POB)新生儿筛查平台使用相同的底层数字微流体 技术和目标是15分钟的结果时间，以便通过控制喂养迅速进行治疗 可以启动计划。 该项目的目标是论证使用数字微流控检测中链的技术可行性 酰辅酶A脱氢酶(MCAD)缺乏症、超长链酰辅酶A脱氢酶(VLCAD)缺乏症 以及全血样本中的半乳糖血症，以改进出生时的新生儿筛查。第一阶段 具体目标包括全血样本分析的生化发展，整合和 多重面板的分析验证，以及使用来自中国的血液样本的初步方法比较 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，完成自给式药筒的开发，并对方法进行初步研究 比较一下。出生点平台将能够扩展到 未来。

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.