Point-of Care System for Determination of Bilirubin Capacity in Neonates

描述（由申请人提供）：长期以来，已知新生儿不受控制的高胆红素血症（黄疸）会导致神经功能障碍，包括不可逆的手足徐动样脑瘫伴语言、视力和听力障碍，甚至死亡。现代管理是基于监测血清总胆红素（TBS），考虑到其他临床参数，如出生体重和胎龄，并给予有效的治疗（光疗和/或罕见的交换输血），如果需要的话。不幸的是，新生儿出生后很快就出院的趋势使这一人群中随后的黄疸管理更加困难。一个长期建议，但没有使用，更好的预测新生儿的神经系统后遗症的风险，由于胆红素升高是一个衡量的能力，螯合胆红素在血液室结合血清白蛋白。未结合胆红素的浓度（胆红素从脉管系统逃逸的驱动因素）可以从TBS和结合能力计算。目前现有的用于测定结合能力和未结合胆红素的方法并不容易。然而，所有这些参数可以直接测量简单地在一个非常小的体积的全血与一个特殊用途的荧光计，血液荧光计，第一次描述年前，通过利用天然荧光胆红素结合到白蛋白。该技术适用于床旁使用。 该项目的目的是将第一阶段开发的现代化和小型化血液荧光计改造为适合在各种护理点环境中操作的产品，包括重症监护和健康婴儿托儿所，新生儿住院诊所和儿科医生办公室。第一个目标是优化基本的光学和电子设计：重新设计电子设备以支持医院信息管理要求，例如条形码阅读器，打印机以及直接或通过本地互联网与计算机接口。的 第二个目的是开发一种易于使用和廉价的试剂盒。第一阶段的工作表明，需要做更多的工作来设计满足这些要求的套件，然后将这种设计扩展到可以大规模生产的产品。第三个目标是在临床环境中用新生儿血液样本测试仪器，以证明它非常适合满足需求。考虑到这一目标，斯坦福大学医学院和儿童医院已同意作为分包商参与评估这项新技术。有了这些改进建议，该仪器将准备进入下一阶段：立即将其投放市场进行研发和临床研究，并最终获得FDA的批准用于一般用途。 公共卫生相关性：一个长期建议，但没有使用，更好的预测新生儿的神经系统后遗症的风险，由于胆红素升高是一个衡量的能力，螯合胆红素在血液室结合血清白蛋白。未结合胆红素的浓度（胆红素从脉管系统逃逸的驱动因素）可以从TBS和结合能力计算。目前现有的用于测定结合能力和未结合胆红素的方法并不容易。 然而，所有这些参数可以直接测量简单地在一个非常小的体积的全血与一个特殊用途的荧光计，血液荧光计，第一次描述年前，通过利用天然荧光胆红素结合到白蛋白。本项目的目的是将第一阶段开发的现代化和小型化血液荧光计转换为适用于各种护理点环境的产品，完成易于使用的样本处理一次性用品的开发，并验证系统对特定新生儿人群样本的性能。

DESCRIPTION (provided by applicant): Uncontrolled hyperbilirubinemia (jaundice) in neonates has long been known to lead to neurological dysfunction including irreversible athetoid cerebral palsy with speech, ocular and hearing impairments, and even death. Contemporary management is based upon monitoring the total serum bilirubin (TBS), taking into account other clinical parameters such as birth weight and gestational age, and administering effective treatment (phototherapy and/or the rare exchange transfusion), if dictated. Unfortunately, the trend towards discharge of apparently healthy neonates from the hospital very soon after birth has made the management of subsequent jaundice more difficult in that population. A long suggested, but not used, better predictor of the neonate's risk for neurological sequelae due to elevated bilirubin is a measure of the capacity to sequester bilirubin in the blood compartment by its binding to serum albumin. The concentration of unbound bilirubin, the driver for bilirubin escaping from the vasculature, can be calculated from the TBS and binding capacitl. Presently existing methods for assaying binding capacity and unbound bilirubin are not facile. However, all these parameters can be directly measured simply in a very small volume of whole blood with a special purpose fluorometer, the hematofluorometer, first described years ago, by making use of the natural fluorescence of bilirubin bound to albumin. This technology is amenable to point-of-care use. The aims of this project are to transform the modernized and miniaturized hematofluorometer developed in Phase I into a product suitable for operation in various point-of-care environments, including the intensive care and healthy baby nurseries, the neonatal inpatient clinic, and the pediatrician's office. The first aim is to optimize the basic optical and electronic design: redesin the electronics to support the hospital information management requirements, such as a bar code reader, printer, and interface with a computer, either directly or via the local internet. The second aim is to develop a reagent kit that is easy to use and inexpensive. Phase I work demonstrated that significantly more work is needed to design a kit meeting these requirements, and then scaling this design up into a product that can be mass produced. The third aim is to test the instrument with neonate blood samples in a clinical environment to demonstrate that it well suited to meet the needs. With this goal in mind, Stanford University's Medical School and Children's Hospital has agreed to participate as a subcontractor to evaluate the new technology. With these proposed improvements, the instrument will be ready for the next stages: releasing it to the market for immediate R&D uses and clinical studies, and eventual approval by the FDA for general use. PUBLIC HEALTH RELEVANCE: A long suggested, but not used, better predictor of the neonate's risk for neurological sequelae due to elevated bilirubin is a measure of the capacity to sequester bilirubin in the blood compartment by its binding to serum albumin. The concentration of unbound bilirubin, the driver for bilirubin escaping from the vasculature, can be calculated from the TBS and binding capacitl. Presently existing methods for assaying binding capacity and unbound bilirubin are not facile. However, all these parameters can be directly measured simply in a very small volume of whole blood with a special purpose fluorometer, the hematofluorometer, first described years ago, by making use of the natural fluorescence of bilirubin bound to albumin. This technology is amenable to point-of-care use.The aims of this project are to transform the modernized and miniaturized hematofluorometer developed in Phase I into a product suitable for operation in various point-of-care environments, to complete development of easy-to-use sample handling disposables, and to verify the performance of the system for samples from a specified population of neonates.