Submillimeter Technology for Molecular Biomarkers

描述(由申请人提供)： 这项研究项目的最终目标将是开发一种低成本、可靠和广泛可用的护理点测试设备并将其商业化，用于对人类患者的疾病进行筛查、诊断和管理。这项拟议的技术名为人体呼吸的亚毫米光声光谱，最初将用于识别和量化分子生物标记谱，这些分子生物标记谱模拟了具有少数选定疾病症状的患者对代谢产物的识别，这些疾病包括哮喘、支气管扩张和间质性肺部疾病。提出的技术的一个主要优点是它是非侵入性的，并且基于对特定疾病特征的分子指纹图谱的状态特定检测而具有高度选择性。这将通过应用最近可用的高强度和高度单色的反向波振荡器光谱源(10-100毫瓦功率，3x10/-8厘米/-1线宽)来实现。这些功能将被整合到我们的设备设计中，并被用来识别和测量选定的分子标记的特征频率特征，包括一氧化氮、一氧化碳和具有ppb或更高灵敏度的氨，这是有效医疗应用所必需的。拟议的工作将证明拟议的技术用于诊断和管理选定的疾病的可行性和实用性。我们建议在第一阶段STTR期间执行以下任务：1)组装初始台架规模的组装和设置。2)建立分子标记的校准和验证程序。3)制定在装置的样品室中制备和传递特定浓度的标记分子的程序。4)展示单个特定生物标志物分子的ppb检测水平。5)演示了不同生物标志物模拟混合物的同时ppb检测。6)从概念上设计小尺寸二期样机。商业化：拟议的研究将为第二阶段和第三阶段的初始仪器设计的简化和小型化铺平道路。在这一开发过程中，我们将与医疗器械制造商合作，协助制造、FDA批准和营销。将进一步探索商业化的细分市场，以实现其更广泛和更一般的医疗用途。

DESCRIPTION (provided by applicant): The ultimate objective of this research project will be the development and commercialization of a low cost, reliable and widely available point-of-care testing device for screening, diagnosis and management of disease in human patients. The proposed technique, submillimeter photoacoustic spectrometry of human breath, will initially be used to identify and quantify molecular bio-marker profiles that simulate the discrimination of metabolic products in patients with symptoms for a small number of selected diseases including asthma, bronchiectasis, interstitial lung disease. A major advantage of the proposed technique is that it is non-invasive, and highly selective based on state-specific detection of molecular finger print profiles characteristic of the specific diseases. This will be achieved by application of recently availability of intense and highly monochromatic backward-wave oscillators spectroscopic sources (10-100 mWatt power, 3x10/-8 cm/-1 linewidth). Such capabilities will be incorporated in our device design, and exploited to identify and measure the characteristic frequency signatures of selected molecular markers including nitric oxide, carbon monoxide, and ammonia with ppb or better sensitivity necessary for effective medical application. The proposed work will demonstrate the feasibility and practicability of the proposed technique for the diagnosis and management of the selected diseases. We propose to carry out the following tasks during this Phase I STTR: 1) Assemble initial bench scale assembly and setup. 2) Establish procedures for calibration and verification of molecular markers. 3) Develop procedures for preparation and delivery of specified concentrations of marker molecules in sample chamber of device. 4) Demonstrate ppb detection levels for single specific biomarker molecules. 5) Demonstrate simultaneous ppb detection of simulant mixtures of different bio-markers. 6) Conceptually design small footprint Phase II prototype. Commercialization: The proposed studies will prepare the way for the subsequent simplification and miniaturization of the initial instrumental design in Phases II and III. During this development, we will work with medical device manufacturers to assist in manufacturing, FDA approval, and marketing. Further market segments for commercialization will be explored for its wider and more general medical use.