A new smart neonatal incubator for real-time detection of sepsis

描述（由申请人提供）：Isomark LLC开发了一种基于呼吸的早期检测技术（由生物标志物和检测仪器组成），可以精确定位急性全身性炎症的发作。Isomark的呼吸生物标志物可以提供新生儿健康的指标。该技术将1）改善新生儿护理结果并挽救生命，以及2）通过减少感染来降低与新生儿重症监护室（NICU）患者的“过度”管理相关的成本，从而缩短住院时间-这是新生儿护理的主要费用来源。Isomark的目标是提供一种新的“智能”新生儿培养箱产品，用于实时评估NICU中的新生儿健康。问题：由于缺乏早期和特异性感染标志物，超过90%的婴儿在绒毛膜炎的脓毒症评估期间接受不必要的治疗。绒毛膜羊膜炎是由于感染引起的绒毛膜羊膜的炎症反应。绒毛膜炎是早产前胎膜早破（PPROM）的主要原因，也是早产（<35周）的主要原因。虽然在确诊的绒毛膜炎病例中，只有约3 - 10%的新生儿发生先天性败血症，但作为预防措施，应开始预防性抗生素治疗。预防性抗生素治疗持续长达72小时，同时对婴儿进行评估，并允许培养物生长，以确认是否存在感染。在NICU接受抗生素治疗时，婴儿经常与母亲分开。因此，高达97%的病例会发生长达三天的不必要治疗，这给医疗保健系统带来了巨大的成本。Isomark的技术：Isomark开发了一种非侵入性且易于识别的生物标志物，用于实时监测疑似全身炎症或感染的患者。在临床前研究中，Isomark的技术通过呼吸δ值（即13 C/12 C比率）有效地检测感染的发生，早在诱导内毒素血症发生后2小时，比感染性休克的临床体征早14至18小时。在来自机械通气儿科患者的初步临床数据中，呼吸δ值成功区分了全身炎症反应综合征（SIRS）和非SIRS。基于这些临床前数据，我们相信Isomark的无创呼吸分析将为新生儿临床医生提供一种筛查患者急性全身炎症和潜在感染的新方法。这种新工具可用于筛查患有绒毛膜炎的新生儿，以消除不必要的抗生素治疗和NICU停留的需要。Isomark团队：在第一阶段，由Isomark工作人员、威斯康星州大学新生儿研究人员和GE全球研究工程师组成的团队将解决重症监护孵化器中婴儿无创呼吸生物标志物测量的技术问题，并确定碳增量值用于检测患有绒毛膜羊膜炎的母亲所生新生儿的急性炎症/感染。申报产品：该项目的成功完成将产生一种新的“智能”新生儿培养箱，能够实时检测急性全身炎症。I期项目将产生令人信服的数据，证明呼吸δ值的变化是新生儿急性全身性炎症的生物标志物。在第二阶段，我们将为新生儿培养箱配备Isomark的实时呼吸检测系统，并将现场部署这些培养箱，以证明新生儿急性全身性炎症的有效隔离。在第三阶段，Isomark将为FDA进行临床试验 批准新的培养箱用于早期发现败血症，然后开始销售该设备。

DESCRIPTION (provided by applicant): Isomark LLC has developed a breath-based early detection technology (comprised of biomarkers and instruments for detection) that can pinpoint the onset of acute systemic inflammation. Isomark's breath biomarkers may provide an indicator of neonatal health. This technology will 1) improve neonatal care outcomes and save lives, and 2) reduce costs associated with "excessive" management of the neonatal intensive care unit (NICU) patient by reducing infections, thus leading to shorter hospital stays - a major source of expense in neonatal care. Isomark's goal for this project is to provide a new 'smart' neonatal incubator product for real-time assessment of neonatal health in the NICU. The Problem: More than 90% of infants undergo unnecessary treatment during sepsis evaluations in cases of chorioamnionitis due to a lack of an early and specific marker for infection. Chorioamnionitis is an inflammatory response of the chorioamnion due to infection. Chorioamnionitis is a leading cause of prelabor preterm rupture of membranes (PPROM) and a leading cause of premature birth (<35 weeks). Although only about 3 to 10% of neonates develop congenital sepsis in confirmed cases of chorioamnionitis, prophylactic antibiotic treatment is initiated as a precautionary measure. Prophylactic antibiotic treatment continues for up to 72 hours while infants are evaluated and cultures are allowed to grow in order to confirm the presence or absence of infection. The infant is frequently separated from the mother while in the NICU for antibiotic treatment. Thus up to three days of unnecessary treatment occurs in up to 97% of cases, at a significant cost to the health care system. Isomark's technology: Isomark has developed a non-invasive and easily identifiable biomarker for real-time monitoring of patients suspected of having systemic inflammation or infection. In preclinical studies, Isomark's technology effectively detected the onset of infection via breath delta values (i.e. 13C/12C ratio) as early as 2 hours after onset of induced endotoxemia and 14 to 18 hours earlier than clinical signs of septic shock. The breath delta value successfully discriminated systemic inflammatory response syndrome (SIRS) from no-SIRS in preliminary clinical data from mechanically ventilated pediatric patients. Based on these preclinical data, we believe that Isomark's noninvasive breath analysis will provide neonatal clinicians with a new means of screening patients for acute systemic inflammation and potential infections. This new tool can be used to screen neonates with chorioamnionitis to eliminate the need for unnecessary antibiotic treatment and NICU stays. Isomark's Team: In phase I, a team consisting of Isomark staff, University of Wisconsin's Neonatal researchers and GE Global Research engineers will address technical aspects of non-invasive breath biomarker measurements in infants in critical care incubators, and determine the carbon delta value for detecting acute inflammation/infection in neonates born to mothers with chorioamnionitis. Proposed Product: The successful completion of this project will result in a new 'smart' neonatal incubator capable of real-time detection of acute systemic inflammation. The Phase I project will generate convincing data that demonstrate changes in breath delta value are a biomarker for acute systemic inflammation in neonates. In phase II, we will equip neonatal incubators with Isomark's real-time breath detection system and will field deploy these incubators to demonstrate effective segregation of acute systemic inflammation in neonates. In phase III, Isomark will perform clinical trials for FDA clearance of the new incubator for early detection of sepsis, and then begin marketing the device.