Point-of-care device to identify patients at risk for preeclampsia

摘要/摘要 先兆子痫是妊娠的一种并发症，其特征是血压升高、蛋白尿和 涉及多个器官系统的内皮功能障碍。在世界范围内，先兆子痫是胎儿的最大原因 和孕产妇发病率和死亡率，每年占美国孕产妇死亡的近16% 只有一个州。在美国，非裔美国女性受到子痫前期的影响不成比例， 与白人或西班牙裔女性相比，发病率增加了1.5到2倍。令人惊讶的是，美国的死亡率 在非裔美国女性中，与子痫前期相关的死亡率高出4倍。有几个因素是 可归因于这种差异，包括更高的合并症发生率，症状的延迟检测， 误诊，以及社会经济和保险地位的差异。此外，60%的先兆子痫与 死亡被发现是可以预防的。目前，还没有得到批准的诊断测试来预测 患者会患上先兆子痫。先兆子痫患者需要住院治疗和持续监测 因此，迫切需要一种能够识别这些疾病的诊断测试。 有先兆子痫风险的患者。 目前正在作出重大努力，以便在发病前发现先兆子痫。最近，它被证明是 肾小球内脏上皮细胞(即足细胞)被排入先兆子痫患者的尿液中，并且可以 在诊断先兆子痫之前的第二个三个月检测，具有很高的敏感性和特异性。方法 为了检测目前依赖于过夜培养和细胞在胶原蛋白涂层玻片上沉淀的足细胞， 这是耗时且容易受到污染的技术，或者细胞旋体技术，它容易产生高 由于污染红细胞(RBC)或管型(粘蛋白分泌物)而导致的假阳性率。 足细胞检测方法不一致，以及随后漫长的过夜孵化 免疫荧光削弱了足细胞作为子痫前期快速诊断标记物的作用。为此， AffinEnergy正在开发一种护理点设备，该设备将捕获、隔离并允许快速量化诊断 足细胞。这种技术将提高足细胞捕获的质量，并带来显著的成本节约 通过最大限度地减少时间和对昂贵设备的需求。在这个第一阶段的应用程序中，我们将重点开发 分离足细胞的最佳多肽修饰磁珠。

SUMMARY/ABSTRACT Preeclampsia is a complication of pregnancy characterized by elevated blood pressure, proteinuria, and endothelial dysfunction involving multiple organ systems. Worldwide, preeclampsia is the largest cause of fetal and maternal morbidity and mortality, and accounts for nearly 16% annually of maternal deaths in the United States alone. African American women are disproportionately affected by preeclampsia in the United States, with a 1.5 to 2 fold increase in incidence over white or Hispanic women. Strikingly, the mortality rate for preeclampsia-associated deaths is up to 4-fold higher in African American women. Several factors have been attributed to this disparity, including higher incidence of comorbidities, delayed detection of symptoms, misdiagnosis, and differences in socioeconomic and insurance status. Moreover, 60% of preeclampsia-related deaths were found to have been preventable. Currently, there is no approved diagnostic test to predict which patients will develop preeclampsia. Patients with preeclampsia require hospitalization and continuous monitoring of the mother and fetus, thus, there is an urgent and unmet need for a diagnostic test that can identify those patients at risk for preeclampsia. Significant efforts are underway to detect preeclampsia prior to disease onset. Recently, it was demonstrated that glomerular visceral epithelial cells (i.e. podocytes) are shed into the urine of preeclamptic patients and can be detected in the second trimester, prior to preeclampsia diagnosis, with high sensitivity and specificity. Methods to detect podocytes currently rely on overnight culture and sedimentation of cells onto collagen-coated slides, which is time consuming and susceptible to contamination, or the Cytospin technique, which is prone to high false-positive rates due to contaminating red blood cells (RBCs) or casts (mucoprotein secretions). Inconsistencies in the method of podocyte detection, and lengthy overnight incubations followed by immunofluorescence weaken the utility of podocytes as a rapid diagnostic marker of preeclampsia. To this end, Affinergy is developing a point-of-care device that will capture, isolate, and allow rapid quantification of diagnostic podocytes. Such a technology will improve the quality of podocyte capture and lead to significant cost savings by minimizing time and need for expensive equipment. In this Phase I application, we will focus on developing optimal peptide-modified magnetic beads for isolating podocytes.