A user-friendly scalable microfluidic platform for enhanced neuron-cell culture

DESCRIPTION (provided by applicant): Cardiac arrhythmias affect more than 5 million people nationwide, resulting in more than 1.2 million hospitalizations and 400,000 deaths yearly. The development of cardiac ablation has significantly improved treatment outcomes. Ablation traditionally has relied on electroanatomic mapping which can be tedious and often requires the use of complex navigation systems. Even so, the spatiotemporal resolution of current mapping modalities remains low. These limitations cause ablation to be a highly specialized and costly procedure offered only at select centers. In addition, the effectiveness of ablation is difficult t evaluate during the procedure due to limitations of traditional mapping technologies. The inability to accurately predict ultimate success at the time of initial procedure leads to recurren arrhythmia and repeat ablations. Direct visualization catheters offer simplicity compared to traditional electroanatomic mapping tools in that cardiac anatomy can be directlyvisualized without the need for complex mapping systems. However, a major limitation of direct visualization catheters is that electrophysiology cannot be directly mapped. For example, in pulmonary vein isolation for atrial fibrillation, although this is largely an anatomically based procedure, direct visualization alone cannot readily facilitate physiologically directed ablation (e.g. ablation based on complex atrial fractionated electrograms or identification of focal rotors) Likewise, when performing substrate modification ablation for ventricular tachycardia, identification of ablation targets visually is problematic at best. Furthermore, as is the case for traditional mapping/ablation systems, ablation efficacy cannot be directly verified, and relies on surrogate endpoints such as electrical block which can be confounded intra-procedurally by tissue edema. Here we propose to combine the simpler approach of a direct visualization catheter with novel, inexpensive, and scalable electrophysiological mapping technology, using voltage sensitive fluorescent dyes to intuitively visualize both anatomy and electrophysiology. In particular, photostable dyes with emissions in the near-infrared spectrum can be optimized for safe in vivo imaging. This system will beapplicable to all forms of arrhythmia, including atrial fibrillation, and promises to reduce costs by reducing procedural complexity, procedure time, and arrhythmia recurrence rates. During Phase I the following three specific aims will be addressed: 1. Demonstrate technical feasibility of fluorescence imaging using an affordable light-emitting- diode/single camera system. 2. [Establish preliminary deliverability and safety of optimized near-infrared voltage sensitive dye(s) for clinical use.] 3. Demonstrate the feasibility f a balloon-tipped endovascular visualization catheter to minimally invasively optically map ratiometric voltage in a live animal. In subsequent work, the device and dye designs will be further optimized, dye safety profile will be characterized in more detail, we will refine a clinicl procedural approach in animal models, and the software analysis approach will be expanded, all while pushing toward the ultimate goal of a commercial product. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Over five million people in the U.S. suffer from abnormal heart rhythms. At present, only a small fraction of people are offered curative ablation therapy because these procedures are complex and resource intensive. This project takes initialsteps to develop a system that allows physicians to directly visualize abnormal heart rhythms and thereby more easily and effectively treat them.