Development of a Colorimetric Sensor for Detection of Cerebrospinal Fluid Leaks

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.