EFRI-BioFlex: Rapid Identification of Blood, Urine, and Saliva Toxins and Bacterial Infections with a SERS/LSS Flexible System

拟议活动的知识价值：将通过结合表面增强拉曼光谱学和光散射光谱学，开发一种便携式混合传感系统，用于快速检测和鉴定血液、尿液和唾液中的毒素和细菌。用于毒素检测的拉曼的独特化学灵敏度和用于在便宜的便携式系统中鉴定细菌的光散射灵敏度将提供适合于紧急情况、流动或家庭使用的强大且快速的诊断工具。 在美国，意外药物过量死亡每年造成25，000多人死亡。同样，细菌感染导致更多的死亡。毒素中毒和细菌感染都可能导致脓毒症和脓毒性休克，是急诊医学中严重的健康问题，影响着数百万人。在危及生命的中毒和菌血症病例中，患者的存活率与识别致病因子的速度高度相关。将该系统与智能手机等便携式数据传输设备对接，以个性化的远程医疗方式将结果快速传输给医疗保健提供者，这将在最需要的情况下实现最快的治疗时间。毒素和细菌鉴定在一个系统中的组合有可能减少或消除对几个主要的耗时的诊断测试的需要，这些测试需要大型昂贵的仪器和先进的设施。该系统将允许快速、可靠和廉价地鉴定几乎所有生物危险化合物，并将超过目前大型和昂贵的临床仪器所能检测的有限数量的毒素。同样，用于识别感染中细菌种类的血液培养技术需要几天时间，有些菌株需要长达五天才能被检测到，或者根本无法完全培养。在严重脓毒症的情况下，这种缓慢的过程导致患者存活率约为40%。此外，细菌感染的快速分类有可能减少具有抗生素抗性的细菌菌株的出现。拟议的灵活的系统将是变革性的性质，将有一个直接的影响，在危及生命的情况下的死亡率，也可能有一个深远的影响，对未来的医疗服务。拟议活动的影响更广泛：开发的仪器将作为一个研究和教育工具，专门从事急诊和实验室医学在贝斯以色列女执事医疗中心的临床研究员和哈佛生物和生物医学科学计划的研究生在他们的论文研究项目。它还将提供给其他教育机构，供合作项目使用。该项目还涉及暑期本科生和高中生在研究和开发相关的设备的子课题工作。与用拟议的系统快速鉴定化学毒素和血流感染有关的材料将纳入哈佛的两门课程。这项工作的结果还将通过同行评审的期刊出版物和国际会议介绍广泛传播。先进生物医学成像和光子学中心致力于整合代表性不足的群体的成员。一个关键目标是让妇女和少数民族成为所有研究小组中活跃的博士后和/或研究生。 这种灵活的组合系统将从三个方面造福社会。首先，诊断测试操作的成本和复杂性的大幅降低将降低医疗保健的成本。第二，毒素和细菌鉴定的快速测试将挽救成千上万人的生命。 第三，拟议的系统将减少耐药性细菌菌株的出现，这将有助于缓解最大和最昂贵的新兴医疗保健问题之一。

Intellectual Merit of Proposed Activity:A portable hybrid sensing system for the rapid detection and identification of toxins and bacteria in blood, urine, and saliva will be developed by combining surface enhanced Raman spectroscopy and light scattering spectroscopy. The unique chemical sensitivity of Raman for toxin detection and the sensitivity of light scattering for bacterial identification in an inexpensive, portable system would provide a powerful and rapid diagnostic tool suitable for emergency, ambulatory or home use. Unintentional drug overdose deaths account for more than 25,000 annual fatalities in the United States. Similarly, bacterial infection results in an even larger number of deaths. Both toxin poisoning and bacterial infection, which can cause sepsis and septic shock, are serious health problems in emergency medicine, affecting millions of people. In life threatening cases of poisoning and bacteremia, the patient survival rate is highly correlated with the speed of identifying the offending agent. Interfacing the system with a portable data transfer device such as a smartphone to quickly transmit results to healthcare providers in a personalized telemedicine manner will allow for the fastest possible treatment times in situations that need them most. The combination of toxin and bacterial identification in a single system has the potential to decrease or eliminate the need for several major time-consuming diagnostic tests that require large expensive instruments and advanced facilities. This system will allow rapid, reliable, and inexpensive identification of virtually all biologically dangerous compounds and will surpass the limited number of toxins which current large and expensive clinical instruments can detect. Similarly, blood culture technology for identifying the bacterial species in an infection takes several days, with some strains taking up to five days to be detected, or simply failing to culture entirely. In cases of severe sepsis, this slow procedure results in a patient survival of approximately 40%. Additionally, the rapid classification of bacterial infections has a likelihood of reducing the emergence of bacterial strains with antibiotic resistance. The proposed flexible system will be transformative in nature, will have an immediate impact on the mortality rates in life-threatening circumstances, and could also have a profound influence on the future of healthcare delivery.Broader Impact of Proposed Activity:The developed instrumentation will serve as a research and educational tool for clinical fellows specializing in emergency and laboratory medicine at Beth Israel Deaconess Medical Center and by Harvard Biological and Biomedical Science Program graduate students in their thesis research projects. It will also be made available to other educational institutions for use in collaborative projects. The project also involves summer undergraduate and high school students to work on sub-topics in the research and development related to the device. Material related to the rapid identification of chemical toxins and blood stream infections with the proposed system will be incorporated in two courses at Harvard. The results of this work will also be disseminated broadly through peer-reviewed journal publications and international conference presentations. The Center for Advanced Biomedical Imaging and Photonics is dedicated to the integration of members of under-represented groups. One key goal is to have women and minorities as active postdocs and/or graduate students in all research groups. The combined flexible system will benefit society in three ways. First, a substantial decrease in the cost and complexity of operation of the diagnostic tests will reduce the cost of healthcare. Second, the presence of fast tests for toxin and bacterial identification will save tens of thousands of lives. Third, the proposed system will reduce the emergence of antibiotic-resistant bacterial strains, which would help alleviate one of the largest and most expensive emerging healthcare issues.