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

 描述（由申请人提供）：新生儿高胆红素血症发生在几乎所有新生儿中，如果及时识别、监测和预防或管理其进展为极端高胆红素血症，则可能是良性的。由于胆红素在中枢神经系统中的沉积，新生儿黄疸具有神经毒性的风险。血浆中的大部分胆红素与血浆蛋白（主要是血清白蛋白）结合。胆红素结合能力（BBC）定义了婴儿未结合或“游离”胆红素水平与他/她“耐受”胆红素负荷增加的能力之间的动态关系。BBC与白蛋白（Alb）水平不是同义词，因为胆红素的Alb结合受到多种分子、生物和代谢因素的混淆。虽然存在各种方法来测量BBC，但没有一种成功地商业化。其中，血液荧光测定法是最有希望的设备，可以在护理点使用，并提供快速和准确的BBC测量。SBIR第一阶段的资助证明了这种设备是可能的。第二阶段赠款向新生儿医院提供了改进的设备。已发表的关于这些设备的临床研究不仅与先前的知识合作，而且提出了BBC测量可以改善现有新生儿护理的方法。该项目的目的是将第一阶段和第二阶段开发的现代化血液荧光计转换为适合在新生儿保育室、NICU和新生儿门诊的护理点环境中操作的最终产品。在第一年，Aviv的目标是开发和评估“单”位置血液荧光计，以提高先前设计的准确性;开发和评估试剂盒设计，提高易用性;改进内部参考的使用;开发校准的主要标准;开发验证检查。从第1年开始并持续到第2年，Aviv将：执行有效期测试;确定操作的环境限制;集成条形码阅读器和实验室信息管理软件支持;对器械和软件进行内部质量检查;调查对测量的潜在干扰;并将使用指南纳入文件和软件。在第二年，Aviv将：具有可商业化的实施例;开发方法和文档;确定制造、营销、销售和分销的合作伙伴。在开展这些活动的同时，斯坦福大学的露西尔·帕卡德儿童医院将进行临床研究，以评估BBC测量在临床环境中的有用性。将咨询新生儿护理管理领域经验丰富的顾问、临床实验室主任以及具有新生儿重症监护病房和临床实验室实践经验的人员，以确定器械和试剂盒的适用性。目的是获得使用BBC测定的专家建议，以告知血液荧光计系统的其他临床有用的修改。

 DESCRIPTION (provided by applicant): Neonatal hyperbilirubinemia occurs in almost all newborns, and may be benign if its progression to extreme hyperbilirubinemia is recognized, monitored, and prevented or managed in a timely manner. Neonatal jaundice carries the risk of neurotoxicity, due to the deposition of bilirubin in the central nervous system. Most of the bilirubin in plasma is bound to plasma proteins (mainly serum albumin). Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors. While various methods exist to measure BBC, none have been successfully commercialized. Of these, hematofluorometry holds the greatest promise of a device that can be used at the point of care, and give rapid and accurate BBC measurements. A SBIR Phase I grant demonstrated that such a device is possible. A Phase II grant delivered improved devices to neonatal hospitals. Published clinical studies with these devices not only collaborated prior knowledge, but suggested ways in which BBC measurements may improve existing neonatal care. The aims of this project are to transform the modernized hematofluorometers developed in Phases I and II into a final product suitable for operation in a point-of-care environment in the newborn nursery, NICU, and neonatal outpatient clinic. In year one, Aviv's goals are to develop and evaluate a "single" position hematofluorometer in terms of increased accuracy over prior designs; develop and evaluate kit designs that increase the ease of use; improve the use of the internal reference; develop primary standards for calibration; develop validation checks. Beginning in year 1 and continuing into year 2, Aviv will: perform shelf-life tests; determine environmental limits of operation; integrate a bar code reader and laboratory information management software support; internal quality checks into the device and software; investigate potential interferences to measurements; and incorporate guidance for use into documentation and software. During year 2 Aviv will: have a commercializable embodiment; develop methods and documentation; identify partners for manufacturing, marketing, sales, and distribution. Concurrent with these activities, Stanford University's Lucile Packard Children's Hospital will conduct clinical studies to evaluate the usefulness of BBC measurements in a clinical setting. Experienced consultants in the fields of neonatal care management, clinical lab directors, and those with hands-on experience neonatal intensive care units and clinical labs will be consulted on the suitability of the device and reagent kit. The goal is to obtain expert recommendations for the use of the BBC assay to inform additional clinically useful modifications of the hematofluorometer system.