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

总结/摘要 先兆子痫是一种妊娠并发症，其特征是血压升高，蛋白尿， 涉及多个器官系统的内皮功能障碍。在世界范围内，先兆子痫是胎儿死亡的最大原因。 和孕产妇发病率和死亡率，并占近16%的孕产妇死亡，每年在美国 只有国家。在美国，非裔美国妇女不成比例地受到先兆子痫的影响， 发生率比白色或西班牙裔妇女高1.5至2倍。令人惊讶的是， 先兆子痫相关的死亡在非洲裔美国妇女中高达4倍。有几个因素 归因于这种差异，包括合并症的发生率较高，症状检测延迟， 误诊，以及社会经济和保险状况的差异。此外，60%的先兆子痫相关 死亡是可以预防的。目前，还没有批准的诊断测试来预测 患者将发展为先兆子痫。先兆子痫患者需要住院治疗和持续监测 因此，迫切需要一种诊断测试，可以识别那些 有先兆子痫风险的患者。 正在进行重大努力，以在疾病发作前检测先兆子痫。最近，它被证明是 肾小球内脏上皮细胞（即足细胞）脱落到先兆子痫患者的尿液中， 在妊娠中期，在先兆子痫诊断之前检测，具有高灵敏度和特异性。方法 目前检测足细胞依赖于过夜培养和细胞沉降到胶原蛋白包被的载玻片上， 该方法耗时且易受污染，或者Cytospin技术，该方法易于产生高浓度的 由于污染红细胞（RBC）或管型（粘蛋白分泌物）导致的假阳性率。 在足细胞检测方法中的干扰，以及长时间的过夜孵育， 免疫荧光减弱了足细胞作为先兆子痫快速诊断标志物的效用。为此目的， Affinergy正在开发一种即时设备，该设备将捕获，分离并允许快速定量诊断 足细胞这种技术将提高足细胞捕获的质量，并导致显著的成本节约 通过最大限度地减少时间和对昂贵设备的需求。在第一阶段的申请中，我们将专注于开发 用于分离足细胞的最佳肽修饰磁珠。

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.