Development of a Colorimetric Sensor for Detection of Cerebrospinal Fluid Leaks

项目总结 Chemeleon，Inc.是一家总部位于纽约的初创公司，正在开发一种新型的比色生物传感器，可以快速诊断 脑脊液(CSF)在护理点(POC)泄漏，例如由医生诊断创伤性脑 急诊科(ED)的受伤(TBI)患者或急救医务人员(EMT) 在救护车上，或在脊柱和耳鼻喉科手术的术中和术后护理期间。脑脊液 当缓冲大脑和脊椎的液体通过周围的破裂漏出时，就会发生泄漏 膜。这些渗漏主要是由颅脑损伤引起的，但在脊柱手术、耳鼻咽喉科也是一种风险。 手术、腰椎穿刺术和硬膜外麻醉，也可以是自发的。脑脊液漏与脑脊液漏 对于急诊医生、急救医生和外科医生来说，其他体液是一个众所周知的问题，因为泄漏通常表现为 单侧鼻漏或耳漏，从鼻子或耳朵流出的清澈的水样分泌物，或与血液和 脊椎手术期间的其他液体。目前还没有针对脑脊液泄漏的PoC诊断和现有方法 要求将患者样本发送到第三方实验室，以获得可能需要4-7天的结果。治疗延误 或误诊会显著增加危及生命的脑膜炎、感染和中风的风险。患有疾病的患者 发生脑膜炎的脑脊液鼻漏的发病率也要高得多。此外，为期一周的 停留不仅会给患者带来严重的痛苦和不适，而且还会导致极高的 医疗保健成本。在这项直接到第二阶段的计划中，Chemeleon的目标是通过以下方式推进脑脊液泄漏诊断 开发一种新型的、廉价的生物传感器，不需要额外的设备或人员培训，可以 在几分钟内提供结果，使医疗专业人员能够做出时间敏感的决定。Chemeleon有 已经成功开发了结合诱导纳米结构动态表面(BINDS)分析的原型 这结合了脑脊液蛋白生物标记物--β-2-转铁蛋白(B2tr)。这绑定了平台技术集成 纳米光子报告表面有b2tr特异的适体受体，其中b2tr与传感器结合。 表面改变表面能量，产生肉眼可见的鲜艳的颜色变化。证明- 概念实验显示，Chemeleon的结合脑脊液检测方法可以在10分钟内检测到1微克/毫升的b2tr， 高于脑脊液中发现的4-5微克/毫升。对于直接到第二阶段的研究，脑脊液传感器将进一步 开发用于实现临床和临床使用所需的高特异性、高灵敏度和低读出时间 字段设置。Chemeleon将专注于(1)优化传感器性能，以快速区分脑脊液和鼻腔 体液和血液样本，(2)最终确定制造工艺，以实现高效放大，以及(3)设计和 测试商业体外诊断原型。Chemeleon的脑脊液传感器将在 头部创伤、脊柱和耳鼻喉科手术病例的决策和提出一个模块化平台 用于其他医疗诊断的发展。

PROJECT SUMMARY Chemeleon, Inc. is a NYC-based startup that is developing a novel colorimetric biosensor that rapidly diagnoses cerebrospinal fluid (CSF) leaks at the Point-of-Care (POC), such as by doctors to diagnose Traumatic Brain Injury (TBI) patients in the Emergency Department (ED), or the Emergency Medical Technician (EMT) in the ambulance, or during intraoperative and post-operative care for spinal and otolaryngological surgeries. CSF leaks occur when the fluid that cushions the brain and spine escapes through ruptures in the surrounding membranes. These leaks are largely caused by TBIs but are also a risk during spinal surgeries, otolaryngological surgeries, lumbar punctures and epidurals and they can also be spontaneous. Distinguishing CSF leaks from other bodily fluids is a well-known problem for ED doctors, EMTs and surgeons as the leaks often present as unilateral rhinorrhea or otorrhea, a clear watery discharge from the nose or ear, or as a mixture with blood and other fluids during spinal surgery. Currently there are no POC diagnostics for CSF leaks and existing methods require patient samples to be sent to third-party laboratories for results that can take 4-7 days. Treatment delays or misdiagnoses significantly increase the risk for life-threatening meningitis, infections and stroke. Patients with CSF rhinorrhea that develop meningitis have also have much higher morbidity rates. Additionally, the weeklong stay not only causes significant distress and discomfort for the patient, but also leads to radically higher healthcare costs. In this Direct-to-Phase II proposal, Chemeleon aims to advance CSF leak diagnosis by developing a novel, inexpensive biosensor that requires no additional equipment or personnel training that can provide results in minutes, enabling medical professionals to make time-sensitive decisions. Chemeleon has already successfully developed a prototype Binding-Induced Nanostructured Dynamic Surface (BINDS) Assay that binds the CSF protein biomarker, beta-2-transferrin (b2TR). This BINDS platform technology integrates nanophotonic reporter surfaces with b2TR-specific aptamer receptors, where binding of b2TR to the sensor surface alters the surface energy producing a vibrant color change that is visible to the naked eye. Proof-of- concept experiments revealed that Chemeleon’s BINDS CSF assay could detect 1 µg/ml of b2TR in 10 minutes, which is higher than the 4-5 µg/ml found in CSF. For Direct-to-Phase II studies, the CSF sensor will be further developed to achieve the high specificity, high sensitivity and low readout time required for use in clinical and field settings. Chemeleon will focus on (1) optimizing sensor performance to rapidly distinguish CSF from nasal fluid and blood samples, (2) finalizing manufacturing processes for efficient scale-up, and (3) designing and testing a commercial in vitro diagnostic prototype. Chemeleon’s CSF sensor will provide advancements in decision-making for head trauma, spinal and otolaryngological surgical cases and present a modular platform for the development of other healthcare diagnostics.