A MEMS intracranial pressure device for monitoring brain injuries and disorders

描述（由申请人提供）：颅内压（ICP）监测是有效治疗脑损伤（如创伤性脑损伤（TBIs））和脑脊液流出障碍（如脑积水）患者必不可少的诊断工具。临床试验表明，ICP监测可降低死亡率，并最大限度地减少继发性损伤。到目前为止，各种ICP监测系统已经成功地准确监测ICP，但是：(a)它们有很高的感染概率（高达15%），(b)它们不允许长期监测ICP， (c)它们不兼容MRI（磁共振成像）。利用微机电系统（MEMS）领域的最新发展，我们提出了一种克服上述限制的“颅内压微棒”（IP<S）技术。该技术基于完全可植入（无电缆）的光学MEMS器件，该器件对ICP变化进行“颜色”编码：ICP转换为近红外（NIR）波长的比率光信号。该装置由一个可调微透镜组成，可将光聚焦到量子点双分子层中。两层中的每一层都包含独特波长的近红外量子点。当ICP变化时，微透镜的焦距发生变化，导致两个波长的比强度发生变化。一种非植入式的便携式光学装置用于激发微透镜/量子点组件并收集发射的近红外光谱。无电子（因此无需电源）IP<S设备可以长时间监测ICP，消除感染风险，允许患者舒适和活动，并与MRI兼容。我们提出了一个研究计划，具体目标如下：(a)可调微透镜/量子点双层组装优化：可调微透镜/量子点双层组装将从微透镜收集效率、微透镜内部压力分辨率、动态范围和量子点双层厚度等方面进行优化；(b)集成IP<S器件的微加工和测试：将微加工IP<S原型并确定其规格（ICP范围、分辨率、时间响应）；(c)体外研究：我们将通过将集成装置浸入含有脑脊液（CSF）的浴液中进行体外研究。将外部调整CSF的压力，以代表真实的ICP监测场景，并确定设备的长期耐用性和零漂移。提出的技术将有助于有效地管理和治疗脑损伤和脑脊液流出障碍，它将开创可用于各种压力监测生物医学应用的可植入和无电源的小型化设备的发展。

DESCRIPTION (provided by applicant): Intracranial pressure (ICP) monitoring is an essential diagnostic tool for the efficient treatment of patients with brain injuries (e.g. traumatic brain injuries (TBIs)) and cerebrospinal fluid outflow disorders (e.g. hydrocephalus). Clinical trials have shown that ICP monitoring decreases the mortality rate and minimizes secondary injuries. Various ICP monitoring systems have been successful so far in accurately monitoring ICP, but: (a) they have high probability of infection (up to 15%), (b) they do not allow long-term ICP monitoring and (c) they are not MRI (Magnetic Resonance Imaging) compatible. Taking advantage of recent developments in the MicroElectroMechanical Systems (MEMS) field, we propose an 'Intracranial Pressure Micro Stick' (IP<S) technology that overcomes the aforementioned limitations. The technology is based on a fully implantable (cable-free), optical, MEMS device that 'color' codes ICP changes: ICP is converted to a ratiometric optical signal in the near infrared (NIR) wavelength. The device consists of a tunable microlens that focuses light into a quantum-dot bilayer. Each of the two layers contains NIR quantum dots of a unique wavelength. The focal length of the microlens is altered when the ICP changes, resulting in a change in the ratiometric intensity of the two wavelengths. A non-implantable, portable optical unit is used to excite the microlens/quantum dot assembly and collect the emitted NIR spectrum. The electronic- free (and thus power-free) IP<S device enables prolonged ICP monitoring, eliminates the risk of infection, allows patient's comfort and mobility and it is MRI compatible. We propose a research plan with the following specific aims: (a) Optimization of the tunable microlens/quantum dot bilayer assembly: the tunable microlens/quantum dot bilayer assembly will be optimized with respect to the microlens collection efficiency, internal microlens pressure resolution, dynamic range, and quantum dot bilayer thickness; (b) Microfabrication and testing of the integrated IP<S device: an IP<S prototype will be microfabricated and its specifications will be established (ICP range, resolution, time response); (c) In-vitro Studies: We will perform in vitro studies by immersing the integrated device in a bath containing cerebrospinal fluid (CSF). The pressure of the CSF will be externally adjusted to represent a real ICP monitoring scenario and the long term durability and zero drift of the device will be determined. The proposed technology will help in efficiently managing and treating brain injuries and CSF outflow disorders, and it will inaugurate the development of implantable and power-free, miniaturized devices that can be used in a variety of pressure monitoring biomedical applications. PUBLIC HEALTH RELEVANCE: Intracranial pressure (ICP) monitoring is an important diagnostic tool for accessing the pathological condition of patients with traumatic brain injury (TBI), congenital or acquired hydrocephalus or mass lesions. This work aims to develop a new class of implantable ICP monitoring devices that will provide better management and efficient treatment of patients with elevated ICP.