Medical Device Enabled by Portable Fluorescence Microscopy and Microfluidics for Monitoring Surgical Inflammation Biomarkers

监测患者对感染的个体反应不仅对早期诊断至关重要，而且对确定患者的有效治疗也至关重要。在美国，大约有1400万例手术是在住院医院进行的，超过10万人随后发生手术部位感染（SSI）。其管理和治疗每年额外花费100亿美元。此外，77%的手术患者死亡可归因于SSI。新不伦瑞克罗格斯大学将开发一个生物医学平台，以快速准确地执行规定的诊断测试。与目前用于这些测试的仪器相比，该合同将取得重大进展，这些仪器体积庞大，价格昂贵，需要经过技术培训的工作人员进行手工样品处理才能进行这些测试。未来，提议的平台可以在多个医疗保健环境中进行转换，包括初级保健办公室、紧急护理环境、重症监护病房和测试实验室。该奖项产生的生物医学平台将具有极大的潜力，有利于人类的健康和福祉。该项目将培养生物传感器、微流体、微加工、光学和机器学习领域的本科生和研究生。该项目还将使拟议的研究纳入调查人员的教育工作。此外，该奖项将促进研究人员开展各种外展活动，包括让K-12学生参与研究，通过教育讲座吸引公众参与，并在网上广泛传播知识。患者对感染的个性化免疫反应监测不仅对早期诊断至关重要，而且对确定有效的治疗也至关重要，从而对患者的预后产生重大影响。SSI是术后患者面临的常见情况。SSI的早期视觉表现包括伤口部位的炎症和脓肿、疼痛、发烧和不适。随后进行微生物培养，需要数天才能得到结果，这在治疗途径中留下了巨大的诊断空白。高风险患者术后频繁定量临床批准的生物标志物（如c反应蛋白（CRP）、降钙素原（PCT））可以提供SSI的早期指征，然而，他们的检测需要集中的实验室设施、训练有素的专业人员和较长的等待时间才能得到结果。在这项工作中，研究人员设想了一个仅使用一滴全血就能定量炎症蛋白的生物医学平台。提出的创新是基于光子学，微流体，智能手机支持的光学传感和3-D多层微流体架构在单个生物芯片上的交叉集成，具有自动化全血处理，以提供患者样本的临床测试结果。传感器将配备实时测量能力和机器学习模型，以训练传感器数据并提供测试结果。传感器将以从罗伯特伍德约翰逊医院收集的患者样本为基准。研究人员设想提议的生物传感器平台是通用的，预功能化的墨盒可以交换用于不同的传染病生物标志物测试。这种变革性的研究还将开辟新的教育计划，以培养下一代工程师和科学家。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。

Monitoring patients’ individual response to infections is vital not only for early diagnosis but also to determine effective treatment for the patients. In United States, around 14 million operative procedures are performed in inpatient hospital settings with more than hundred thousand people subsequently developing surgical site infections (SSI). Its management and treatment cost another US $10 billion yearly in excess costs. Further, 77% of the deaths of surgical patients are attributed to SSI. This award which is being made to Rutgers University New Brunswick will develop a biomedical platform to perform prescribed diagnostics tests rapidly and accurately. The award will enable a significant advance compared to currently employed instruments used for these tests which are bulky, costly, and requires manual sample processing by technically trained staff to perform these tests. In future, proposed platform can translated in multiple healthcare settings including primary care offices, emergency care settings, intensive care units and testing laboratories. Biomedical platform resulting from this award will have a great potential to benefit human health and welfare. This project will train undergraduate and graduate students in the fields of biosensors, microfluidics, microfabrication, optics, and machine learning. The project will also enable the integration of proposed research into investigators educational efforts. Further, the award will facilitate the investigators to implement various outreach activities including engaging K-12 students in research, and the public through educational lectures and making them available online for broad dissemination of knowledge.Personalized immune response monitoring of patients to infections is critical not only for early diagnosis but also for determining effective therapy, thereby having a significant impact in patients’ outcome. SSI is a common condition faced by patients’ post-surgical procedures. Early visual indications of SSI include inflammation and puss at the site of the wound, pain, fever, and discomfort. This is followed by a microbial culture which takes multiple days to get the results, leaving huge diagnostic gaps in the treatment pathway. Post-operative frequent quantification of clinically approved biomarkers (e.g., C-reactive protein (CRP), procalcitonin (PCT)) on high-risk patients could provide an early indication of an SSI, however, their testing requires centralized lab facility, trained professionals and longer wait times to get the results. In this work, investigators envision a biomedical platform for inflammatory proteins quantification using only a drop of whole blood. The proposed innovation is based on a cross-cut integration of photonics, microfluidics, smartphone enabled optical sensing, and 3-D multi-layer microfluidic architectures on a single biochip with automated whole blood processing to provide clinical test results from patient samples. Sensors will be equipped with real-time measurement capability and machine learning models to train the sensors data and provide test results. Sensors will be benchmarked with patient samples collected from Robert Wood Johnson Medical Hospital. Investigators envisions proposed biosensor platform to be generic and the pre-functionalized cartridges can be swapped out for different infectious diseases biomarkers testing. This transformative research will also open new educational initiatives to train the next generation of engineers and scientists.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.