Development of Flexible Microsystems for Bacterial Biofilm Management

细菌生物膜是感染和环境生物污染的主要原因，难以去除，并导致耐抗生素细菌菌株迅速增加。它们通常会在一系列具有复杂弯曲几何形状的难以接近的环境中引起灾难性的后果，最终导致持续感染、植入物失败和全身污染。目前还没有有效的方法来检测和根除生物膜，因此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地方的生物膜。灵活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区域的操作提供了机会。目标是开发一种范例，使动态柔性传感器微系统能够检测、监测和抑制多维表面上的生物膜，特别是导尿管的圆柱形环境。表面细菌种类、流体条件和几何形状是该方法的基础，为根据需要确定生物膜检测和预防方法提供了指导。成功地监测和去除生物膜将产生巨大的影响，提高所有人口统计数据的生活质量。这些系统有可能减少抗生素耐药性和卫生保健获得性感染的传播，对于解决资源贫乏地区的这些挑战尤其具有吸引力。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基于实验室的STEM课程。为了系统地发展这一方法，本提案的目标分为三个任务：1)优化在复杂的3D环境中传感和抑制生物膜的微系统：薄膜电极将被选择作为一种简单而敏感的电化学阻抗传感器，通过生物电效应在微流体系统中作为传感器和生物膜抑制剂进行测试。此外，该装置将通过计算模型对生物膜检测进行优化。该模型将检查传感器电场的变化，以获得相关的几何形状。2)用于生物膜的集成柔性器件的制造：适当的材料和制造工艺取决于每种应用的特定几何和环境要求，特别是柔性衬底，如聚酰亚胺，以金作为惰性电极材料。柔性基板将使设备能够折叠和缩放，以与脆弱的复杂曲面接口。3)采用具有数据传输和反馈控制的环境模型进行设备测试：以导尿管为测试用例。这将发展考虑到独特的几何，细菌和流体条件。3d打印结构精确地再现了与生物膜的几何相互作用，传感器响应和生物电处理将同时进行评估。将开发一种无线控制（使用蓝牙或Wifi）电子系统来操作阻抗传感器，并使用电极控制生物膜的去除。将开发反馈驱动的动态生物膜控制，考虑生物膜生物量对应的阈值阻抗传感值。该系统将引入基于阻抗传感器数据的生物电效应处理，实时指示生物膜的形成。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。需要应用微生物学和工程学科相结合的跨学科方法来克服这些问题。将探讨柔性传感器、细菌生物膜和生物电处理之间复杂的相互作用。生物膜的电还原使脆弱系统的远程可编程性成为可能。包括细菌种类、表面几何形状和流体条件在内的关键参数对系统设计的影响将被清楚地列举。这里开发的基本方法将使进一步的研究能够解决迫切需要的地区的生物膜监测和去除问题。该奖项反映了美国国家科学基金会的法定使命，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.