On-chip optical biosensing methods for quantitative measurement of antibiotic resistance

本项目将研究与医疗器械相关的耐抗生素细菌感染问题。目标是开发改进的方法，用于在医疗设备环境中对这一问题进行定量评估。该项目将建立一个廉价、可重复和定量的基础，以比较减少耐药细菌出现的创新治疗策略。在这项工作中获得的知识将有助于监管科学领域的研究人员提高对新型抗生素评估的预测能力。这项工作还将有助于提高评估使用现有抗生素或现有抗生素组合的新疗法的预测能力。研究生和本科生将有机会发展他们的沟通和领导能力。该团队将每月在GWU或FDA举行互动会议。GWU-FDA合作团队将开发一种基于微流体和片上光学传感的体外耐药性进化模型，以评估生物膜在2周内对导尿管的抗生素耐药性如何产生，以响应临床实际的药代动力学/药效学。该模型将导管上的生物膜暴露于与体内相似的2周浓度-时间曲线。该模型旨在使用芯片实验室技术来提高测试的吞吐量。该项目将带来新的见解，并提高对与留置和植入医疗设备相关的生物膜所带来的特殊感染挑战的机制理解。PI将使用光学诊断和微流体技术的最新发展。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。

This project will study the problem of antibiotic-resistant bacterial infection associated with medical devices. The goal is to develop improved methodologies for quantitative assessment of this problem in the medical device context. This project will develop an inexpensive, reproducible and quantitative basis for comparing innovative therapeutic strategies to reduce the emergence of drug resistant bacteria. The knowledge gained in this work will help researchers in the area of regulatory science to improve predictive capability for the assessment of novel antibiotics. This work will also help to improve predictive capability for assessment of new therapies using existing antibiotics or combinations of existing antibiotics. Graduate and undergraduate students will have opportunities to develop their communication and leadership skills. The team will hold monthly interactive meetings at GWU or FDA. The GWU-FDA collaborative team will develop an in vitro resistance evolution model based on microfluidics and on-chip optical sensing to assess how antibiotic resistance emerges in biofilm over 2 weeks on urinary catheters in response to clinically realistic pharmacokinetics/pharmacodynamics. This model will expose biofilm on catheters to 2-week concentration-time profiles similar to those experienced in vivo. The model aims to use lab-on-a-chip technology to increase the throughput of testing. This project will lead to new insight and improved mechanistic understanding of the special infection challenges that are posed by biofilms that are associated with indwelling and implanted medical devices. The PI will use recent developments in optical diagnostics and microfluidics technology.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.