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，很难清除，并导致抗药性细菌菌株的迅速增加。它们经常在一系列复杂的曲线型环境中导致灾难性的后果，最终导致持续性感染、植入物失败和系统性污染。需要可行的方法来检测、预防和去除现场的生物膜，包括导尿管、假体植入物和水系统，在这些地方，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作创造了机会。其目的是开发一种范例，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这种方法的基础，创建了按需识别生物膜检测和预防方法的指南。成功地监测和清除生物膜将产生巨大的影响，改善所有人口结构的人的生活质量。这些系统有可能减少抗生素耐药性和医疗保健获得性感染的传播，在应对资源匮乏地区的这些挑战方面特别有吸引力。此外，这些设备的低成本制造潜力将使它们能够被高中教师纳入基于实验室的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)优化在复杂的3D环境中感知和抑制生物膜的微系统：将选择薄膜电极作为简单而灵敏的电化学阻抗传感器，在微流控系统中通过生物电效应作为传感器和生物膜抑制器进行测试。此外，该设备将通过计算模型对生物膜检测进行优化。该模型将检测相关几何形状的传感器电场的变化。2)生物膜综合柔性装置的制造：合适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，特别是以金为惰性电极材料的聚酰亚胺等柔性衬底。灵活的衬底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)利用数据传输和反馈控制的环境模型进行设备测试：以一根导尿管为测试案例。这将考虑到独特的几何、细菌和流体条件而开发。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。考虑与生物膜生物量相对应的阈值阻抗敏感值，开发反馈驱动的动态生物膜控制。该系统将引入基于阻抗传感器数据的生物电效应治疗，该数据实时指示生物膜的形成。该项目解决了防止、识别和清除复杂表面上的生物膜的挑战。为了克服这些问题，需要一种结合应用微生物学和工程学科的跨学科方法。将探索柔性传感器、细菌生物膜和生物电处理之间的复杂相互作用。生物膜的电减少使脆弱系统中的远程可编程性成为可能。将清楚地列举包括细菌种类、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。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。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.