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Self-assembling density gradients for sickle cell diagnosis in low resource areas

用于资源匮乏地区镰状细胞诊断的自组装密度梯度

基本信息

批准号：
8916826
负责人：
Betsy Wonderly Trainor
金额：
$ 22.38万
依托单位：
DAKTARI DIAGNOSTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-25 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8916826
关键词：
Africa Africa South of the Sahara Anemia Area Back Biological Assay Blood Blood capillaries Blood specimen Businesses Case-Control Studies Centrifugation Characteristics Child Childhood Clinic Clinical Coagulation Process Collection Comorbidity Complex Country Custom Detection Developed Countries Developing Countries Development Devices Diagnosis Diagnostic Diagnostic tests Disease Duct (organ) structure Electrophoresis Engineering Environment Erythrocytes Evaluation Fingers Genotype Health Health Technology Heel Hemoglobinopathies Humidity Individual Infant Infection Laboratories Lead Life Location Low income Malaria Materials Testing Medical Methods Microspheres Molds Names Neonatal Screening Newborn Infant Pain Parasitemia Penicillins Performance Persons Phase Pilot Projects Platelet aggregation Polymers Primary Health Care Property Quality Control Reading Reagent Recruitment Activity Reference Standards Reporting Research Infrastructure Resources Respiratory distress Running Rural Sampling Sensitivity and Specificity Sickle Cell Sickle Cell Anemia Sickle Cell Trait Side Small Business Innovation Research Grant Source South Carolina Specificity Specimen System Teaching Hospitals Technology Temperature Testing Tube United States Universities Venous Venous blood sampling Visual Work World Health Organization Zambia abstracting acronyms base capillary cost cross reactivity density design diagnostic accuracy disease diagnosis effective intervention expectation global health improved infancy innovation innovative technologies instrument instrumentation meetings novel nutrition operation performance tests point of care programs prototype screening sickle cell crisis sickling success trait

项目摘要

DESCRIPTION (provided by applicant): The World Health Organization has recently recognized sickle cell disease as a major global health concern. The highest rates of sickle cell disease and sickle cell trait are seen in malaria-endemic developing countries, which also have the most severe resource constraints, especially on clinical laboratory infrastructure. Daktari Diagnostics, a 50-person, venture-backed start-up company focused on the pressing needs for innovative global health technologies is partnering with the Whitesides laboratory at Harvard University and the University Teaching Hospital in Lusaka, Zambia, to develop a novel polymer system into a low-cost, rapid, and simple-to-use assay for the screening and diagnosis of sickle cell disease in resource-limited settings. The sickle cell assay-named Mpana, an acronym for MultiPhase ANAlyzer, and also a Swahili word meaning "a broad, wide, open channel"-is based on self-assembling polymer technology developed by the Whitesides group for industrial and medical applications, and recently shown in preliminary studies in Zambia to be useful for the identification of sickle cells in blood with high sensitivity and high specificity. Moreover, by design these polymer systems are robust and have strong material properties that immediately suggest a path to a commercial product that can meet the difficult constraints necessary for success in resource-limited settings- long shelf-life in environmental extremes, minimal power requirements enabling battery operation, simplicity of use, and, importantly, low cost. The Mpana project described here will transition the promising prototype from the academic setting into a commercial manufacturing environment. For the operator, the final Mpana assay will involve loading capillary blood from a heel stick or finger prick into a small microhematocrit tube pre-filled with multiphase polymers that form step-gradients based on density-and inserting the loaded tube into a small battery-operated centrifugation instrument with a simple user interface. Inside the tube, under centrifugation, dense sickle cells settle to a specific location in the densty gradient, forming a band that can be easily read visually or optically. After approximately 12 minutes, the Mpana system will report out the presence of sickle cell disease, sickle cell trait, o a normal red blood cell profile, and will differentiate HbSS from HbSC disease. Results will be reported either automatically, or by a visual readout, and will be quality controlled through QC reagents included within the microhematocrit tube. To develop the final Mpana assay, we will optimize the current multi-phase polymers developed by the Whiteside group for stability and manufacturability. We will also develop a robust anti-coagulation tube coating and final tube material that will enable easy blood collection for the operator, as well as improve the sensitivit and specificity of the system through the elimination of RBC and platelet aggregation, which can confound the density-based assay performance. In addition, we will develop control microbeads of a fixed, narrow density as on-board QC material, used to confirm the stability of the density gradient. On the instrument side, we will convert what has been an expensive, table-top centrifuge used in the preliminary Harvard studies in Zambia, into a low-cost, portable, battery-operated centrifuge system, a core Daktari expertise for developing simple instrumentation that has been applied previously by the Daktari engineering team to the development of a handheld, battery-operated CD4 system. As a final set of preliminary studies, we will evaluate the performance of the commercial prototype in the context of difficult sample specimens, including specimens containing interfering substances, severe anemia, and a variety of hemoglobinopathies, first in de-identified samples obtained from the Medical University of South Carolina, and finally in an initial pilot study at the University Teaching Hospital in Zambia. We expect the final deliverable from this two-year Phase I SBIR program will be a simple, low-cost instrument and assay tube capable of being used at the primary care level to rapidly and inexpensively identify children with sickle cell disease and sickle trait, at a level of accuracy demonstrably matching or exceeding the expectations of the RFA.

描述(申请人提供)：世界卫生组织最近承认镰状细胞疾病是一个主要的全球健康问题。在疟疾流行的发展中国家，镰状细胞疾病和镰状细胞特征的发病率最高，这些国家也有最严重的资源限制，特别是在临床实验室基础设施方面。达科塔里诊断公司是一家由50人组成的创业公司，专注于创新的全球卫生技术的迫切需求。该公司正与哈佛大学的怀特赛兹实验室和赞比亚卢萨卡的大学教学医院合作，开发一种新的聚合物系统，成为一种低成本、快速和简单易用的检测方法，用于在资源有限的环境中筛查和诊断镰状细胞疾病。镰状细胞分析名为Mpana，是多相分析仪的首字母缩写，也是斯瓦希里语的意思，意思是“广泛、宽广、开放的通道”，基于Whiteside集团为工业和医疗应用开发的自组装聚合物技术，最近在赞比亚进行的初步研究表明，该技术有助于鉴定血液中的镰状细胞，具有高灵敏度和高特异性。此外，通过设计，这些聚合物系统非常坚固，具有强大的材料特性，可以立即提供一条通往商业产品的道路，可以满足在资源有限的环境中取得成功所需的困难限制-在极端环境下的长保质期，支持电池操作的最低电力需求，使用简单，以及重要的是，低成本。这里描述的Mpana项目将把前景看好的原型从学术环境转变为商业制造环境。对于操作员来说，最终的mpana检测将包括将脚跟棒或手指刺中的毛细血管血液加载到一个小的微量红细胞压积试管中。预先填充多相聚合物，形成基于密度的阶梯梯度-并将加载的管插入小型电池供电的离心仪，具有简单的用户界面。在试管内，在离心机的作用下，密集的镰状细胞聚集在密度梯度中的特定位置，形成一条易于视觉或光学阅读的条带。大约12分钟后，MPANA系统将报告存在镰状细胞病、镰状细胞特征或正常的红细胞图谱，并将区分HbSS和HBSC疾病。结果将自动报告，或通过视觉读数报告，并将通过微量红细胞压积管内包括的QC试剂进行质量控制。为了开发最终的Mpana测试，我们将优化怀特赛德集团开发的当前多相聚合物的稳定性和可制造性。我们还将开发一种坚固的抗凝管涂层和最终管材料，使操作员能够轻松采集血液，并通过消除红细胞和血小板聚集来提高系统的敏感性和特异性，这可能会扰乱基于密度的分析性能。此外，我们将开发固定、窄密度的可控微珠作为车载质控材料，用于确认密度梯度的稳定性。在仪器方面，我们将把哈佛大学在赞比亚的初步研究中使用的昂贵的台式离心机改造成低成本、便携式、电池供电的离心机系统，这是达克塔里开发简单仪器的核心专业知识，达克塔里的工程团队以前曾将其应用于手持电池供电的CD4系统的开发。作为最后一组初步研究，我们将在困难的样本样本的背景下评估商业原型的性能，包括含有干扰物质、严重贫血和各种血红蛋白疾病的样本，首先是从南卡罗来纳医科大学获得的未确认样本，最后是在赞比亚大学教学医院进行的初步试点研究。我们预计，这项为期两年的SBIR计划的最终成果将是一种简单、低成本的仪器和分析管，能够用于初级保健水平，以快速、廉价的方式识别患有镰状细胞疾病和镰状特征的儿童，其准确度明显符合或超过RFA的预期。