Development of Flexible Microsystems for Bacterial Biofilm Management

开发用于细菌生物膜管理的灵活微系统

• 批准号: 1809436
• 负责人: Reza Ghodssi
• 金额: $ 33万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1809436&HistoricalAwards=false
• 关键词: Development; Flexible; Microsystems; Bacterial; Biofilm

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.

细菌生物膜是感染和环境生物污染的主要原因，难以去除，并导致抗生素耐药菌株的迅速增加。它们经常在一系列具有复杂弯曲几何形状的难以进入的环境中引发灾难性后果，最终导致持续感染、植入失败和全身污染。需要可行的方法来检测、预防和去除导尿管、假体植入物和供水系统等场所的生物膜，而目前这些场所尚不存在检测和根除生物膜的有效方法。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运行提供了机会。目标是开发一种范例，使动态灵活的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南。成功监测和去除生物膜将产生巨大影响，改善所有人群的生活质量。这些系统有潜力减少抗生素耐药性和医疗保健获得性感染的传播，对于解决资源匮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）优化微系统在复杂的 3D 环境中传感和抑制生物膜：将选择薄膜电极作为简单而灵敏的电化学阻抗传感器，在微流体系统中通过生物电效应作为传感器和生物膜抑制剂进行测试。此外，该设备将通过计算模型针对生物膜检测进行优化。该模型将检查相关几何形状的传​​感器电场的变化。 2）生物膜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，特别是柔性基板，例如聚酰亚胺，并以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接合。 3）使用具有数据传输和反馈控制的环境模型进行设备测试：导尿管将作为测试用例。这将考虑到独特的几何、细菌和流体条件而开发。 3D 打印结构精确地再现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）电子系统来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，考虑与生物膜生物量相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治疗，实时指示生物膜的形成。该项目解决了预防、识别和去除复杂表面上生物膜的挑战。需要采用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。将探索柔性传感器、细菌生物膜和生物电治疗之间的复杂相互作用。生物膜的电减少使得易受攻击的系统能够进行远程编程。将清楚地列举关键参数（包括细菌种类、表面几何形状和流体条件）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急需领域的生物膜监测和去除问题。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Flexible Platform for In Situ Impedimetric Detection and Bioelectric Effect Treatment of Escherichia Coli Biofilms

用于大肠杆菌生物膜原位阻抗检测和生物电效应处理的灵活平台

• DOI: 10.1109/tbme.2018.2872896
• 发表时间: 2019-05
• 期刊: IEEE Transactions on Biomedical Engineering
• 影响因子: 4.6
• 作者: Huiszoon, Ryan C.;Subramanian, Sowmya;Ramiah Rajasekaran, Pradeep;Beardslee, Luke A.;Bentley, William E.;Ghodssi, Reza
• 通讯作者: Ghodssi, Reza

Integrated System for Bacterial Detection and Biofilm Treatment On Indwelling Urinary Catheters

留置导尿管细菌检测和生物膜处理集成系统

• DOI: 10.1109/tbme.2021.3066995
• 发表时间: 2021-03
• 期刊: IEEE Transactions on Biomedical Engineering
• 影响因子: 4.6
• 作者: Huiszoon, Ryan Cornelis;Han, Jinjing;Chu, Sangwook;Stine, Justin Matthew;Beardslee, Luke;Ghodssi, Reza
• 通讯作者: Ghodssi, Reza

A Coculture Based Tyrosine-Tyrosinase Electrochemical Gene Circuit for Connecting Cellular Communication with Electronic Networks

基于共培养的酪氨酸-酪氨酸酶电化学基因电路，用于连接细胞通信与电子网络

• DOI: 10.1021/acssynbio.9b00469
• 发表时间: 2020-05
• 期刊: ACS Synthetic Biology
• 影响因子: 4.7
• 作者: VanArsdale, Eric;Hörnström, David;Sjöberg, Gustav;Järbur, Ida;Pitzer, Juliana;Payne, Gregory F.;van Maris, Antonius J.;Bentley, William E.
• 通讯作者: Bentley, William E.

BIONANOSCAFFOLDS-ENABLED NON-WETTING SURFACES FOR ANTIBIOFOULING APPLICATIONS

用于防污应用的 BIONANOS支架非润湿表面

• 发表时间: 2019-01
• 期刊: Actuators and Microsystems
• 作者: Sangwook Chu; Ishita Shahi
• 通讯作者: Ishita Shahi

IN SITU SENSOR ELECTRODE PATTERNING ON URINARY CATHETERS TOWARDS INFECTION PREVENTION

导尿管上的原位传感器电极图案可预防感染

• 发表时间: 2019-01
• 期刊: Actuators and Microsystems (Transducers 2019
• 作者: Ryan C. Huiszoon; Sangwook Chu
• 通讯作者: Sangwook Chu