Development of a Colorimetric Sensor for Detection of Cerebrospinal Fluid Leaks

开发用于检测脑脊液泄漏的比色传感器

• 批准号: 10602859
• 负责人: Min Hu
• 金额: $ 84.04万
• 依托单位: DRINKSAVVY, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-02 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10602859
• 关键词: Accident and Emergency department; Ambulances; Bacterial Infections; Binding; Biological; Biological Assay; Biological Markers; Biosensor; Blood; Blood specimen; Body Fluids; Brain; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Cerebrospinal Fluid Rhinorrhea; Cessation of life; Chemistry; Clinical; Color; Craniocerebral Trauma; Decision Making; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Distress; Ear; Emergency Medical Technicians; Emergency medical service; Ensure; Equipment; Evaluation; Extravasation; Eye; Frequencies; Future; Health Care Costs; Healthcare; Hospitalization; Human Resources; In Transferrin; In Vitro; Infection; Instruction; Laboratories; Left; Life; Liquid substance; Medical; Membrane; Meningitis; Methods; Modification; Morbidity - disease rate; Nanostructures; Nose; Operative Surgical Procedures; Optical reporter; Optics; Otorhinolaryngologic Surgical Procedures; Otorrhea; Pathology; Patient risk; Patient-Focused Outcomes; Patients; Performance; Phase; Physicians; Postoperative Care; Process; Property; Proteins; Quality Control; Reporter; Reproducibility; Research; Risk; Rupture; Sampling; Sensitivity and Specificity; Specificity; Specimen; Spinal Puncture; Spine surgery; Stroke; Surface; Surgeon; Surgical complication; TBI Patients; Technology; Testing; Time; Training; Transferrin; Traumatic Brain Injury; Validation; Vendor; Vertebral column; Work; aptamer; commercial prototype; design; digital media; emergency settings; experimental study; improved; in-vitro diagnostics; infection risk; large scale production; manufacturing process; manufacturing scale-up; nanophotonic; novel; phase 2 study; point of care; point-of-care diagnostics; prevent; protein biomarkers; prototype; rapid diagnosis; receptor; scale up; sensor; skull base; standard of care; success; technology platform; trauma surgery; usability

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.

项目概要 Chemeleon, Inc. 是一家总部位于纽约的初创公司，正在开发一种新型比色生物传感器，可快速诊断 在护理点 (POC) 发生脑脊液 (CSF) 渗漏，例如医生诊断脑外伤时发生的脑脊液渗漏 急诊科 (ED) 的受伤 (TBI) 患者，或急救中心的紧急医疗技术员 (EMT) 救护车或脊柱和耳鼻喉科手术的术中和术后护理期间。 当缓冲大脑和脊柱的液体通过周围的破裂漏出时，就会发生泄漏 这些渗漏主要是由 TBI 引起的，但也是脊柱手术、耳鼻喉科手术中的风险。 手术、腰椎穿刺和硬膜外麻醉也可以区分脑脊液漏和自发性漏。 对于急诊医生、急救人员和外科医生来说，其他体液是一个众所周知的问题，因为渗漏通常表现为 单侧鼻漏或耳漏，从鼻子或耳朵流出清澈的水样分泌物，或与血液和液体混合 目前还没有针对脑脊液漏的 POC 诊断和现有方法。 要求将患者样本发送至第三方实验室才能获得结果，这可能会导致治疗延迟 4-7 天。 误诊或误诊会显着增加患者罹患危及生命的脑膜炎、感染和中风的风险。 发展为脑膜炎的脑脊液鼻漏的发病率也高得多。 住院不仅会给患者带来严重的痛苦和不适，还会导致患者的病情急剧恶化。 在这项直接进入第二阶段的提案中，Chemeleon 旨在通过以下方式推进脑脊液漏诊断： 开发一种新型、廉价的生物传感器，不需要额外的设备或人员培训 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策。 已经成功开发了结合诱导纳米结构动态表面 (BINDS) 测定的原型 该 BINDS 平台技术集成了结合 CSF 蛋白质生物标志物 β-2-转铁蛋白 (b2TR) 的技术。 纳米光子报告表面具有 b2TR 特异性适体受体，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颜色变化。 概念实验表明，Chemeleon 的 BINDS CSF 检测可以在 10 分钟内检测到 1 µg/ml 的 b2TR， 这比 CSF 中发现的 4-5 µg/ml 更高。对于直接进行 II 期研究，CSF 传感器将进一步提高。 开发用于实现临床和应用所需的高特异性、高灵敏度和短读出时间 Chemeleon 将专注于 (1) 优化传感器性能，以快速区分 CSF 和鼻腔。 液体和血液样本，(2) 最终确定生产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 CSF 传感器将带来以下方面的进步。 头部外伤、脊柱和耳鼻喉科手术病例的决策并提供模块化平台 用于开发其他医疗诊断。