Microsystem Development for Clozapine Monitoring in Schizophrenia

描述(申请人提供)：氯氮平是治疗精神分裂症最有效的抗精神病药物，精神分裂症是一种终生衰弱和毁灭性的疾病。它也是唯一一种临床实践指南建议根据血液水平测量指导剂量以获得最佳疗效的抗精神病药物。然而，氯氮平仍然没有得到充分利用，因为它经常抽血监测血液水平和白细胞计数。事实上，氯氮平可能是精神健康中最未得到充分利用的循证治疗方法之一。通过治疗性血浆范围实时监测疗效和安全性，并最终监测副作用(特别是白细胞计数)，将使个性化药物和铅成为可能 为了更好地利用这种药物，提高治疗成功率，并可能导致数百万美元的住院和治疗成本下降。芯片实验室(LOC)设备是一种可转换的微系统，在临床诊断中提供了许多优势，将台式方法带入了护理点。该创新研究项目将开发一种新型的高通量生物传感器，该传感器基于阵列电化学LOC，与壳聚糖为基础的选择性探针集成在一起，用于氯氮平血药浓度的实时低容量分析。该设备将针对灵敏和特定的现场测试进行优化 氯氮平检测。我们将参照标准的实验室方法，在高度受控的住院环境中，通过氯氮平治疗患者的血液样本分析来验证LOC。 对于敏感性，以及在门诊环境中的选择性。这项工作是为开发和整合白细胞监测和引出用户需求到LOC的未来研究建议而迈出的第一步。这种具有样本处理和自动化微型系统的未来设备将允许治疗团队在现场进行血液分析，从而提高使用率和接受度，降低成本，并使氯氮平治疗精神分裂症发生革命性变化。1

DESCRIPTION (provided by applicant): Clozapine is the most effective antipsychotic for schizophrenia treatment, a lifelong debilitating and devastating disorder. It is also the only antipsychotic with clinical practice guidelines recommending to have dosage guided by blood level measurements for optimum efficacy. Yet, clozapine remains underutilized because of its frequent blood draws for monitoring blood levels and white blood cell counts. In fact, clozapine may be one of the most underutilized evidence based treatments in mental health. Real time monitoring of efficacy and safety through therapeutic plasma ranges, and eventually monitoring for side effects (particularly white blood cell counts), will enable personalized medicine and lead to better utilization of this medication, improve treatment success rates and potentially lead to millions of dollars in decreased hospitalization and treatment costs. Lab-on-a-Chip (LOC) devices are translational microsystems that provide numerous advantages in clinical diagnostics, bringing bench top methods into the point of care. The proposed innovative research project will develop a novel and high throughput biosensor based on an arrayed electrochemical LOC, integrated with chitosan-based selective probes for real time low volume analysis of clozapine blood levels. The device will be optimized for sensitive and specific in-situ clozapine detection. We will validate the LOC with blood sample analysis in clozapine-treated patients with reference to standard laboratory means, both in a highly controlled inpatient setting for sensitivity and in an outpatient setting for selectivity. This work is the first step towards fture research proposals for the development and integration of white blood cell monitoring and elicited user requirements into the LOC. Such future devices with sample handling and automation micro-systems will allow treatment teams to do blood analysis on-site, thus improving use and acceptance, decreasing costs and revolutionizing schizophrenia treatment with clozapine. 1