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

用于测定新生儿胆红素容量的护理点系统

• 批准号: 8249700
• 负责人: Glen D Ramsay
• 金额: $ 66.11万
• 依托单位: AVIV BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8249700
• 关键词: Accounting; Albumins; Athetoid cerebral palsy; Bar Codes; Bilirubin; Binding; Biological Assay; Birth; Birth Weight; Blood; Blood capillaries; Blood specimen; Calibration; Cessation of life; Clinic; Clinical; Clinical Research; Computer software; Computers; Contracts; Data; Development; Documentation; Electronics; Environment; Evaluation Studies; Fluorescence; Gestational Age; Glass; Goals; Heating; Hospitals; Hyperbilirubinemia; Icterus; Information Management; Informed Consent; Inpatients; Institutional Review Boards; Intensive Care; Internet; Laboratories; Lead; Life; Marketing; Measures; Memory; Methods; Mind; Molds; Monitor; Neonatal; Neurologic; Neurologic Dysfunctions; Noise; Nurseries; Optics; Pediatric Hospitals; Performance; Phase; Phototherapy; Plastics; Point-of-Care Systems; Population; Privacy; Production; Protocols documentation; Reader; Reading; Reagent; Risk; Sampling; Serum; Serum Albumin; Signal Transduction; Slide; Solid; Specific qualifier value; Speech; Staging; System; Technology; Temperature; Testing; Transfusion; Tube; Universities; Whole Blood; Work; Writing; base; capillary; cost; design; effective therapy; experience; hearing impairment; improved; instrument; medical schools; meetings; miniaturize; neonate; new technology; operation; pediatrician; point of care; prototype; research and development; response; scale up; trend; user-friendly

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.

描述（由申请人提供）：众所周知，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型脑瘫，伴有言语、眼部和听力障碍，甚至死亡。现代管理基于监测血清总胆红素（TBS），考虑其他临床参数，例如出生体重和胎龄，并根据需要进行有效治疗（光疗和/或罕见的换血）。不幸的是，表面上健康的新生儿出生后很快就出院的趋势使得该人群随后黄疸的治疗变得更加困难。长期以来，人们建议但未使用的更好的预测新生儿因胆红素升高而导致神经系统后遗症的风险的指标是衡量血液室中胆红素通过与血清白蛋白结合而螯合的能力。未结合胆红素的浓度（胆红素从脉管系统逃逸的驱动因素）可以根据 TBS 和结合能力计算出来。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，所有这些参数都可以通过特殊用途的荧光计（血液荧光计）在非常少量的全血中直接测量，该荧光计多年前首次描述，利用与白蛋白结合的胆红素的天然荧光。该技术适合现场护理使用。 该项目的目标是将一期开发的现代化、小型化血液荧光计改造成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的接口。这 第二个目标是开发一种易于使用且价格低廉的试剂盒。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，然后将该设计扩展到可以批量生产的产品。第三个目标是在临床环境中用新生儿血液样本测试该仪器，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新技术。通过这些拟议的改进，该仪器将为下一阶段做好准备：将其投放市场用于立即研发用途和临床研究，并最终获得 FDA 批准用于一般用途。 公共健康相关性：长期以来建议但未使用的新生儿因胆红素升高而发生神经系统后遗症风险的更好预测指标是衡量胆红素通过与血清白蛋白结合而在血液隔室中隔离的能力。未结合胆红素的浓度（胆红素从脉管系统逃逸的驱动因素）可以根据 TBS 和结合能力计算出来。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，所有这些参数都可以通过特殊用途的荧光计（血液荧光计）在非常少量的全血中直接测量，该荧光计多年前首次描述，利用与白蛋白结合的胆红素的天然荧光。该技术适合床旁使用。该项目的目标是将一期开发的现代化小型化血液荧光计改造为适合在各种床旁环境下操作的产品，完成易于使用的一次性样本处理耗材的开发，并验证系统对特定新生儿人群样本的性能。