Microfabricated Implantable Flowmeter for CSF Shunts Phase II

描述（由申请人提供）： 一种植入式无线流量传感器系统正在开发中，该系统将能够测量通过脑室腹膜（VP）分流管的脑脊液（CSF）流量，目前用于治疗脑积水患者。CSF流量是分流功能的关键指标，目前无法原位测量，导致缺乏直接评估分流功能或预测其失败的临床方法。使用MEMS微加工方法，所提出的流量传感器将被制造成足够小的尺寸，以便与植入的VP分流器集成。流量计中的关键元件是电容结构，其随着CSF流量的变化而改变属性。内部无源电路和外部手持电路之间的电磁耦合允许在不需要植入电池或经皮导线的情况下植入流量传感器。拟议的第二阶段项目将建立在第一阶段令人鼓舞的结果的基础上，第一阶段展示了概念验证MEMS传感器的无线询问，以及流量与传感器谐振之间存在可轻松测量的关系。在第二阶段，将制造全功能的流量传感MEMS芯片，以及一个修改后的手持单元，将显示和输出流量，基于流量和谐振之间的已知关系。体外测试将建立传感器植入物的校准，并将证明在CSF流量的整个生理范围内、长时间内以及使用适当的体模模型时的测量准确度。同时，将制备慢性绵羊脑积水模型，沿着在传感器植入物原型中实施适当的包装、生物相容性和灭菌性，并考虑MR兼容性。动物试验方案的性能应评价传感器在以下方面的性能：（1）检测血流阻塞的灵敏度和特异性，（2）CSF流量测量准确度，以及（3）对分流通畅性的影响。 公共卫生相关性： 每年在美国大约有23,000例分流翻修手术，以纠正用于治疗脑积水患者的脑室腹膜（VP）分流的相对常见的失败。然而，儿童仍然死于分流失败，研究表明，早期发现将挽救这些儿童中的很大一部分。植入式无线CSF流量计将使临床医生能够在常规门诊访视期间监测分流功能（而不是等待脑积水症状的再次出现），从而检测即将发生的分流失败，避免紧急救生治疗，并降低VP分流失败相关的死亡率。

DESCRIPTION (provided by applicant): An implantable wireless flow sensor system has been under development that would enable measurement of the flow of cerebrospinal fluid (CSF) through the ventriculoperitoneal (VP) shunt, currently used to treat hydrocephalus patients. CSF flow is a key indicator of shunt function, and there is currently no way to measure it in situ, resulting in the absence of clinical methods to directly assess shunt function or to predict its failure. Using MEMS microfabrication methods, the proposed flow sensor will be manufactured at a size small enough to be integrable with implanted VP shunts. The key elements in the flow meter are capacitive structures that change properties with change in CSF flow. Electromagnetic coupling between the internal passive circuitry and an external handheld circuit allows implantation of the flow sensor without the need for implanted batteries or transcutaneous wires. The proposed Phase II project will build on the encouraging results of Phase I, which demonstrated the wireless interrogation of proof-of-concept MEMS sensors and the presence of a readily measurable relationship of flow to the resonance of the sensor. In Phase II, fully-function flow-sensing MEMS chips will be manufactured, as well as a revised handheld unit that will display and output flow, based on the known relationship between flow rate and resonance. In vitro testing will establish calibration for the sensor implants, and will demonstrate measurement accuracy over the full physiological range of CSF flow, over long periods of time, and with appropriate phantom models. In parallel, a chronic sheep hydrocephalus model will be in preparation, along with implementation of appropriate packaging, biocompatibility, and sterilizability into the sensor implant prototypes, as well as consideration of MR compatibility. Performance of an animal test protocol shall evaluate the sensor in regard to (1) sensitivity and specificity with regard to detection of flow obstruction, (2) CSF flow measurement accuracy, and (3) effect on shunt patency. PUBLIC HEALTH RELEVANCE: Every year there are approximately 23,000 shunt revisions performed in the U.S., in order to correct the relatively common failure of ventriculoperitoneal (VP) shunts used to treat hydrocephalus patients. However, children are still dying from shunt failure, and studies indicate that earlier detection would save a large fraction of these children. An implantable, wireless CSF flow meter would enable the clinician to monitor shunt function during routine office visits (rather than waiting for the re-appearance of hydrocephalus symptoms), allowing detection of impending shunt failure, avoidance of lifesaving treatment on an emergency basis, and reduction of mortality associated with VP shunt failure.