Development of Flexible Microsystems for Bacterial Biofilm Management

细菌生物膜是感染和环境生物污损的主要原因，很难去除，并导致抗生素耐药细菌菌株的快速增加。它们通常在一系列具有复杂弯曲几何形状的不可接近环境中引发灾难性后果，最终导致持续感染、植入物失效和全身污染。需要可行的方法来检测、预防和去除包括导尿管、假体植入物和水系统在内的场所中的生物膜，其中目前不存在检测和消除生物膜的有效方法。柔性设备技术的进步为反馈驱动的生物膜管理系统在这些脆弱地区的运行提供了机会。我们的目标是开发一个范例，使动态灵活的传感器微系统检测，监测和抑制生物膜的多维表面，特别是圆柱形环境的导尿管。表面细菌种类，流体条件和几何形状是这种方法的基础，为确定生物膜检测和预防方法提供了指南。生物膜的成功监测和去除将产生巨大的影响，提高所有人口统计数据的人的生活质量。这些系统有可能减少耐药性和医疗获得性感染的传播，对于应对资源贫乏地区的这些挑战特别有吸引力。此外，这些设备的低成本制造潜力将使高中教师能够将其纳入实验室STEM课程。为了系统地开发这种方法，本提案的目标分为三个任务：1）优化用于在复杂的3D环境中感测和抑制生物膜的微系统：选择薄膜电极作为一种简单、灵敏的电化学阻抗传感器，在微流控系统中作为传感器和生物膜抑制剂通过生物电效应进行测试。此外，该装置将通过计算模型优化生物膜检测。该模型将检查相关几何结构的传感器电场的变化。2)用于生物膜的集成柔性装置的制造：适当的材料和制造工艺由每种应用的特定几何形状和环境要求确定，特别是柔性基底，例如聚酰亚胺，用金作为惰性电极材料。柔性基板将使设备能够根据需要折叠和缩放，以与脆弱的复杂曲面对接。3)使用具有数据传输和反馈控制的环境模型进行器械测试：导尿管将作为测试用例。这将考虑到独特的几何形状，细菌和流体条件。3D打印结构精确地重建了与生物膜的几何相互作用，其中传感器响应和生物电治疗将同时进行评估。将开发无线控制（使用蓝牙或Wifi）电子系统以操作阻抗传感器并使用电极控制生物膜去除。将开发反馈驱动的动态生物膜控制，考虑对应于生物膜生物量的阈值阻抗感测值。该系统将基于实时指示生物膜形成的阻抗传感器数据引入生物电效应治疗。该项目解决了在复杂表面上预防、识别和去除生物膜的挑战。为了克服这些问题，需要一种将应用微生物学和工程学科相结合的跨学科方法。柔性传感器，细菌生物膜和生物电治疗之间的复杂相互作用将被探讨。生物膜的电还原使易受攻击的系统中的远程可编程性成为可能。系统设计的关键参数，包括细菌种类，表面几何形状和流体条件的影响将被清楚地枚举。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Bacterial biofilms, a major cause of infection and environmental biofouling, are difficult to remove and contribute to the rapid increase in antibiotic-resistant bacterial strains. They often induce catastrophic consequences in an array of inaccessible environments with complex curved geometries, ultimately leading to persistent infections, implant failure, and systemic contamination. There is demand for viable methods to detect, prevent, and remove biofilms in locales including urinary catheters, prosthetic implants, and water systems, where currently effective methods do not exist to detect and eradicate biofilms. Advances in flexible device technology yield opportunities for feedback-driven biofilm management systems for operation in these vulnerable areas. The objective is to develop a paradigm enabling dynamic flexible sensor microsystems for detecting, monitoring, and inhibiting biofilms on multidimensional surfaces, in particular the cylindrical environment of a urinary catheter. The surface bacterial species, fluid conditions, and geometry are the basis for this approach, creating a guide for identifying methods of biofilm detection and prevention on demand. Successful monitoring and removal of biofilm will have a dramatic impact, improving quality of life for people of all demographics. These systems have the potential to reduce the spread of antibiotic-resistant and healthcare-acquired infections, and are particularly attractive for addressing these challenges in resource-poor regions. Moreover, the potential for low-cost manufacturing of these devices will enable their inclusion by high school teachers into laboratory-based STEM curricula.To systematically develop this methodology, the objective of this proposal is divided into three tasks: 1) Optimization of microsystems for sensing and inhibiting biofilms in complex, 3D environments: Thin film electrodes will be selected as a simple and sensitive electrochemical impedance sensor, tested in a microfluidic system as a sensor and biofilm inhibitor via the bioelectric effect. Furthermore, the device will be optimized for biofilm detection via a computational model. The model will examine changes in the electric field of the sensor for the relevant geometry. 2) Manufacturing of integrated flexible devices for biofilms: appropriate materials and fabrication processes are determined by specific geometric and environmental requirements of each application, notably flexible substrates, such as polyimide, with gold as an inert electrode material. The flexible substrates will enable folding and scaling of the device as required to interface with the vulnerable complex curved surface. 3) Device testing using environmental model with data transmission and feedback control: A urinary catheter will serve as a test case. This will be developed considering the unique geometric, bacterial, and fluidic conditions. 3D-printed structures precisely recreate geometry interactions with biofilm, where sensor response and bioelectric treatment will be evaluated simultaneously. A wireless controlled (using Bluetooth or Wifi) electronic system will be developed to operate the impedance sensor and control the biofilm removal using the electrodes will be developed. Feedback-driven dynamic biofilm control will be developed, considering threshold impedance sensing values corresponding to biofilm biomass. The system will introduce a bioelectric effect treatment based on impedance sensor data indicating the formation of a biofilm in real-time. This project addresses the challenge of preventing, identifying, and removing biofilms on a complex surface. An interdisciplinary approach combining applied microbiology and engineering disciplines is required to overcome these problems. Complex interactions between flexible sensors, bacterial biofilms, and bioelectric treatment will be explored. Electrical reduction of biofilm enables remote programmability in vulnerable systems. The impact on system design of key parameters including bacterial species, surface geometry, and fluidic conditions will be clearly enumerated. The fundamental methodology developed here will enable further research to address biofilm monitoring and removal in areas of dire need.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.