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.

项目摘要 Chemeleon，Inc。是一家基于纽约市的初创公司，正在开发一种新型的比色生物传感器 脑脊液（CSF）在护理点（POC）上泄漏，例如医生诊断大脑创伤性大脑 急诊科（ED）的伤害（TBI）患者或急诊医疗技术员（EMT） 救护车，或在术中和术后护理期间，用于脊柱和耳鼻喉科手术。 CSF 当在周围破裂的大脑和脊柱逸出时，会泄漏 膜。这些泄漏主要是由TBI引起的，但在脊柱手术期间也是一种风险 手术，腰椎穿刺和硬膜外术，也可能是赞助的。区分CSF泄漏与 对于ED医生，EMT和外科医生来说，其他身体流体是一个众所周知的问题，因为泄漏通常是 单侧鼻露或耳露，从鼻子或耳朵上清除水状的排出，或作为血液和血液的混合物 脊柱手术期间的其他烟。目前没有CSF泄漏和现有方法的POC诊断 要求将患者样本发送到第三方实验室，以获取可能需要4-7天的结果。治疗延迟 或误诊大大增加了威胁生命的脑膜炎，感染和中风的风险。患者 发展脑膜炎的CSF鼻漏也具有更高的发病率。此外，为期一周 留下不仅会给患者带来严重的困扰和不适，还会导致更高 医疗保健费用。在这个直接到相的II提案中，Chemeleon旨在通过 开发一种小说，廉价的生物传感器，不需要其他设备或人员培训 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。 Chemeleon具有 已经成功开发了一种原型结合诱导的纳米结构动态表面（结合）测定 结合CSF蛋白生物标志物Beta-2-转铁蛋白（B2TR）。这绑定了平台技术集成 具有B2TR特异性apptamer接收器的纳米光子记者表面，其中B2TR与传感器结合 表面改变了肉眼可见的充满活力的颜色变化的表面能。证明 概念实验表明，Chemeleon的结合CSF分析可以在10分钟内检测1 µg/ml的B2TR， 高于CSF中发现的4-5 µg/ml。对于直接到期II研究，CSF传感器将进一步 开发为实现高特异性，高灵敏度和较低的读数时间，用于临床和 现场设置。 Chemeleon将重点介绍（1）优化传感器性能以迅速将CSF与鼻腔区分开 流体和血液样本，（2）最终确定制造过程，以进行有效的扩大，（3）设计和设计和 测试商业体外诊断原型。 Chemeleon的CSF传感器将提供进步 头部创伤，脊柱和耳鼻喉科手术病例的决策，并呈现模块化平台 用于开发其他医疗诊断。