Microsystem Development for Clozapine Monitoring in Schizophrenia

描述（由申请人提供）：氯氮平是治疗精神分裂症最有效的抗精神病药，精神分裂症是一种终身衰弱和破坏性疾病。它也是唯一一种具有临床实践指南的抗精神病药物，建议通过血液水平测量指导剂量，以获得最佳疗效。然而，氯氮平仍然未得到充分利用，因为其频繁抽血监测血液水平和白色血细胞计数。事实上，氯氮平可能是精神健康中最未充分利用的循证治疗方法之一。通过治疗性血浆范围对疗效和安全性进行真实的实时监测，并最终监测副作用（特别是白色血细胞计数），将实现个性化药物和铅 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费用减少。芯片实验室（Lab-on-a-Chip，缩写为ICSI）设备是一种平移微系统，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，该生物传感器基于阵列电化学传感器，结合基于壳聚糖的选择性探针，用于真实的实时低容量分析氯氮平血液浓度。该装置将进行优化，用于敏感和特异性的原位检测。 氯氮平检测我们将在高度控制的住院患者中，参考标准实验室方法，通过血液样本分析验证氯氮平治疗患者的可持续性 敏感性和选择性。这项工作是第一步的future研究建议的发展和整合的白色血细胞监测和引发用户的要求到血液。这种带有样本处理和自动化微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，并彻底改变氯氮平治疗精神分裂症的方法。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