Personalized antibiotherapy: development and evaluation of a microfluidic biosensor platform for non-invasive, multianalyte on-site diagnostics

个性化抗生物治疗：用于非侵入性多分析物现场诊断的微流体生物传感器平台的开发和评估

• 批准号: 404478562
• 负责人: Dr.-Ing. Can Dincer
• 金额: --
• 依托单位: Leibniz-Institut für Neue Materialien gGmbH (INM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404478562?language=en
• 关键词: Personalized; antibiotherapy; development; evaluation; microfluidic

Antibiotherapy achieves constantly increasing importance in human medicine. Herein, an individualized antibiotherapy, comprising the antibiotic dose and the dosing interval as well as the duration, plays a decisive role in the efficacy of the anti-infective therapy. However, due to the lack of the methods for bedside concentration monitoring, antibiotic dosages are, if at all, adapted only to the body weight of the patients. In this context, a major problem is the in-hospital development of multidrug resistance as a consequence of suboptimal antibiotic use.A non-invasive approach, enabling such diagnostics in non-invasively collected body fluids such as exhaled breath condensate (EBC), urine and saliva, would be highly desirable for a personalized antibiotherapy. In this respect, microfluidic lab-on-a-chip (LOC) platforms provide an acceleration of the specific and sensitive quantification of various analytes along with a low sample consumption, faster sample-to-result times and an easy integration of complex laboratory functions. Therefore, the goal of the proposed project is the implementation and pre-clinical evaluation of a microfluidic multiplexed biosensor platform for the non-invasive, on-site quantification of a panel of parameters, comprising various ß-lactam antibiotics, as well as renal and inflammation biomarkers, in order to allow a personalized antibiotherapy.In this project, various endogenous biomarkers including creatinine and cystatin C for renal function, and interleukin-6 and acute phase proteins (e.g., serum amyloid A, C-reactive protein and procalcitonin) for bacterial inflammation will be evaluated regarding their sensitivity and selectivity. Furthermore, in large animal experiments, investigating various antibiotic dosages, the quasi real-time surveillance of inflammation markers and antibiotic pharmacokinetics will be carried out in blood, tissue and non-invasively collected EBC samples. Hence, this project includes the realization of an EBC sampling device for rapid and non-invasive specimen collection.A successful implementation of the planned microfluidic LOC device in combination with a performant biomolecular sensing system could be a game-changer in the antibiotherapy. Since it would enable the (non-invasive) profiling of the inflammation progress and the antibiotic pharmacokinetics and thus, could pave the way for a personalized antibiotherapy. Furthermore, this could be a significant landmark on the global combat against the antibiotic resistance.

抗生素治疗在人类医学中日益重要。在此，个体化抗生素治疗，包括抗生素剂量和给药间隔以及持续时间，在抗感染治疗的疗效中起决定性作用。然而，由于缺乏床边浓度监测的方法，抗生素的剂量，如果有的话，只适应患者的体重。在这种情况下，一个主要问题是由于使用不理想的抗生素而在医院内产生多药耐药。一种非侵入性的方法，能够在非侵入性收集的体液中进行诊断，如呼出液（EBC）、尿液和唾液，这对于个性化抗生素治疗是非常可取的。在这方面，微流控芯片实验室（LOC）平台加速了各种分析物的特异性和敏感性定量，同时降低了样品消耗，加快了样品到结果的时间，并易于集成复杂的实验室功能。因此，拟议项目的目标是实施和临床前评估微流控多路生物传感器平台，用于非侵入性，现场量化一组参数，包括各种ß-内酰胺类抗生素，以及肾脏和炎症生物标志物，以便进行个性化的抗生素治疗。在这个项目中，各种内源性生物标志物，包括用于肾功能的肌酐和胱抑素C，以及用于细菌性炎症的白介素-6和急性期蛋白（如血清淀粉样蛋白A、C反应蛋白和降钙素原），将被评估其敏感性和选择性。此外，在大型动物实验中，研究各种抗生素剂量，将在血液、组织和无创采集的EBC样本中进行炎症标志物和抗生素药代动力学的准实时监测。因此，本项目包括实现一种快速无创标本采集的EBC采样装置。计划中的微流体LOC装置与高性能生物分子传感系统的成功实施可能会改变抗生素治疗的游戏规则。因为它可以（非侵入性）分析炎症进展和抗生素药代动力学，因此可以为个性化抗生素治疗铺平道路。此外，这可能是全球对抗抗生素耐药性的一个重要里程碑。