Nitric Oxide Microfluidic Sensor

一氧化氮微流控传感器

• 批准号: 8713067
• 负责人: Mark H Schoenfisch
• 金额: $ 30万
• 依托单位: CLINICAL SENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8713067
• 关键词: Affect; Aliquot; Animal Model; Animals; Antibiotics; Bacteria; Biological Markers; Blood; Blood Volume; Blood specimen; Calibration; Cause of Death; Clinic; Clinical; Clinical Management; Clinical Research; Complex; Critical Illness; Detection; Devices; Diagnosis; Early Diagnosis; Evaluation; Exclusion Criteria; Family suidae; Fever; Goals; Healthcare; Healthcare Systems; Heart Rate; Hospital Costs; In Vitro; Incidence; Indium; Infection; Intensive Care Units; Intervention; Length of Stay; Licensing; Ligation; Literature; Lung; Measurement; Measures; Membrane; Methods; Microfluidic Microchips; Microfluidics; Modality; Modeling; Monitor; Morbidity - disease rate; Mus; Nitric Oxide; North Carolina; Nosocomial Infections; Nosocomial pneumonia; Outcome; Pain management; Pathogen detection; Patient Care; Patients; Perforated Appendicitis; Performance; Phase; Physiological; Play; Pneumonia; Pre-Clinical Model; Predictive Value; Production; Protocols documentation; Puncture procedure; Quality Control; Relative (related person); Reporting; Reproducibility; Risk; Risk Assessment; Sampling; Sepsis; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Symptoms; Systemic infection; Technology; Testing; Therapeutic Uses; Time; Translations; Treatment Effectiveness; Treatment outcome; United States; Universities; Validation; Work; base; catheter related infection; clinically significant; commercialization; cost; data management; design; improved; in vivo; macrophage; meetings; micro-total analysis system; microbial; miniaturize; mortality; novel; pathogen; phase 2 study; physical conditioning; point of care; pre-clinical; prototype; public health relevance; rapid detection; rapid diagnosis; response; screening; sensor

DESCRIPTION (provided by applicant): This Small Business Innovation Research (SBIR) Phase I project aims to develop a microfluidic-based nitric oxide (NO) sensor as an early sepsis risk assessment device. Sepsis causes significant strain on the U.S. healthcare system, consuming over $17 billion annually due to extended hospital stays, and significant morbidity and mortality. Rapid diagnosis and intervention are critical to improve patient outcomes. Unfortunately, current methods of diagnosing sepsis rely on the detection of symptoms (e.g., fever and irregular heart rate) that only become evident after the infection has progressed to dangerous levels (advanced sepsis). The goals of this project are to: 1) manufacture prototype miniaturized microfluidic sensors for the measurement of NO levels in drawn blood; and, 2) determine the potential clinical utility of NO determination in preclinical, monomicrobial models of pulmonary sepsis. Using indirect analysis methods, literature studies have found significant elevations (>10x basal) in blood nitric oxide due to sepsis. However, the lack of a rapid and direct sensor for NO has frustrated the translation of these findings to the clinic. Initial studie in a porcine model of polymicrobial sepsis have shown that this microfluidic NO sensor can represents a new paradigm for diagnosing early sepsis and saving lives. This finding is supported by in vitro studies showing that macrophages release NO in response to bacteria, with increasing magnitude according to bacteria load. Through the proposed studies we will develop a novel, miniaturized NO sensing platform to enable the rapid measurement of this biomarker in small aliquots of blood. After meeting specific analytical performance requirements for this device (sensitivity and selectivity for NO, linear response range, reproducibility, etc.),we will determine the predictive value of NO measurement in established preclinical models of pulmonary sepsis. Most in vivo studies of NO in sepsis have been performed in polymicrobial models such as cecal ligation and puncture (CLP). While this model faithfully recapitulates ruptured appendicitis, the microbiological milieu is more complex than most hospital-acquired infections (i.e., most catheter-related infections and cases of hospital-acquired pneumonia have a single etiologic agent). Both clinical pneumonia and the preclinical, murine models of pneumonia share common immunoinflammatory elements and, in contrast to CLP, are highly reproducible and titratable. These models will allow testing of several clinically significant parameters, including: 1) differentiating the blood nitric oxide response in Gram- positive and Gram-negative infections, 2) determining whether the in vivo nitric oxide response is proportional to microbial burden, and 3) screening commonly used therapeutic modalities (for example, pain management and antibiotics) to assess their affects on the blood nitric oxide response to infection. These studies will establish key parameters for the evaluation of the blood nitric oxide sensor in clinical subjects.

描述（由申请人提供）：这个小企业创新研究（SBIR）一期项目旨在开发一种基于微流体的一氧化氮（NO）传感器，作为早期败血症风险评估设备。败血症给美国医疗保健系统带来了巨大的压力，由于住院时间延长，每年消耗超过170亿美元，发病率和死亡率也很高。快速诊断和干预对改善患者预后至关重要。不幸的是，目前诊断败血症的方法依赖于检测症状（例如，发烧和心率不规律），这些症状只有在感染进展到危险水平（晚期败血症）后才会变得明显。本项目的目标是：1)制造用于测量抽取血液中NO水平的微型微流体传感器原型；2)确定NO检测在肺脓毒症临床前单菌模型中的潜在临床应用价值。使用间接分析方法，文献研究发现脓毒症导致血一氧化氮显著升高（bbb10倍基础）。然而，缺乏一种快速和直接的一氧化氮传感器阻碍了将这些发现转化为临床。在猪多微生物脓毒症模型中的初步研究表明，这种微流控NO传感器可以代表一种诊断早期脓毒症和挽救生命的新范式。这一发现得到了体外研究的支持，研究表明巨噬细胞释放NO作为对细菌的反应，并根据细菌负荷的增加而增加。通过提出的研究，我们将开发一种新型的，小型化的NO传感平台，以便在小比例的血液中快速测量这种生物标志物。在满足该设备特定的分析性能要求（对NO的灵敏度和选择性、线性响应范围、重现性等）后，我们将确定NO测量在已建立的肺脓毒症临床前模型中的预测价值。大多数一氧化氮在脓毒症中的体内研究都是在多微生物模型中进行的，如盲肠结扎和穿刺（CLP）。虽然该模型忠实地概括了阑尾炎破裂，但微生物环境比大多数医院获得性感染更复杂（即，大多数导管相关感染和医院获得性肺炎病例具有单一病原）。临床肺炎和临床前小鼠肺炎模型都有共同的免疫炎症因子，与CLP相反，具有高度可重复性和可滴定性。这些模型将允许测试几个具有临床意义的参数，包括：1)区分革兰氏阳性和革兰氏阴性感染时的血液一氧化氮反应，2)确定体内一氧化氮反应是否与微生物负担成正比，以及3)筛选常用的治疗方式（例如疼痛管理和抗生素）以评估其对感染时血液一氧化氮反应的影响。这些研究将为临床受试者评估血液一氧化氮传感器建立关键参数。