Rapid, Multiscale Sensing Using Acoustic Detection Mechanisms

使用声学检测机制进行快速、多尺度传感

• 批准号: 8755187
• 负责人: Andrew P Goodwin
• 金额: $ 219.29万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8755187
• 关键词: Acoustics; Benchmarking; Biochemical; Biological; Biological Markers; Biosensor; Bypass; Chemicals; Clinical; Complex; Contrast Media; Detection; Development; Diagnostic; Diagnostic Imaging; Emulsions; Environment; Epitopes; Error Sources; Generations; Goals; Heating; In Vitro; Lead; Liquid substance; Measures; Methods; Microbubbles; Microfluidics; Modality; Noise; Oligonucleotides; Peptides; Process; Reagent; Research; Sampling; Signal Transduction; Solutions; System; Technology; Testing; Time; Ultrasonography; base; design; in vivo; in vivo imaging; point-of-care diagnostics; public health relevance; response; sensor; sound; success

DESCRIPTION (provided by applicant): The goal of the proposed research is to design a new class of in vitro and in vivo biosensors in which rapid, analyte-triggered droplet fusion creates a uniquely detectable acoustic signal. Development of a technology that could provide a convenient, inexpensive, and portable method for detecting biomolecules without sample manipulation would provide new avenues for measuring both systemic and localized biomolecular levels in many different environments and media. For in vitro detection, an in-solution sensor would obviate the need for sample processing and washing steps that may lead to added time, expense, and sources of error. In addition, droplets can be utilized to almost any scale, from microfluidic chips to batch processing. Finally, the almost nonexistent acoustic background in controlled in vitro environments allows this method to bypass problems with background noise, such as autofluorescence, that greatly complicate and mitigate signals arising from typical biomarker detection modalities. For in vivo imaging, there are few technologies that can respond to levels of specific biomarkers in a localized environment, and those that can typically possess only modest on-off ratios. Building from our previous success with biochemically-responsive ultrasound contrast agents, the proposed sensors will create specifically detectable ultrasound signals for in vivo imaging that we expect will exceed our previous benchmark of 20 dB (100-fold) on-off ratios. The proposed research will mark the first example of sound as a chemical detection modality, which would facilitate the construction of an entirely new class of sensors, diagnostics, and imaging agents. We propose to perform single and multiplexed sound sensing by employing biomarker-driven generation of microbubbles, which scatter sound in a unique way that cannot be found in any biological medium. Because of the small expense associated with both the proposed detection reagents and system, the proposed technology is expected to be useful for both routine clinical analyses and point-of-care diagnostics. To generate microbubbles only in response to biomolecular analytes, we propose to create emulsions that are poorly visible to ultrasound under normal conditions but transform into bubbles upon sensing a specific biomolecule. The emulsions will be formulated with oligonucleotides and peptide epitopes that will promote fusion through biochemical recognition. Once the emulsions reach a critical size they may be specifically vaporized into bubbles by sound or controlled heating, even in the presence of unactivated emulsions. By employing a mechanism by which sensing analytes either block or permit the formation of detectable droplets, this technology can be applied to both in vitro diagnostics and in vivo imaging.

描述(申请人提供)：拟议研究的目标是设计一类新的体外和体内生物传感器，其中快速的分析物触发的液滴融合创建 独特的可检测声学信号。一种技术的发展可以提供一种方便、廉价和便携的方法来检测生物分子，而不需要处理样品，这将为在许多不同的环境和介质中测量系统和局部生物分子水平提供新的途径。对于体外检测，溶液中传感器将消除样品处理和洗涤步骤的需要，这些步骤可能导致额外的时间、费用和误差来源。此外，从微流控芯片到批量处理，液滴几乎可以用于任何规模。最后，受控体外环境中几乎不存在的声学背景允许该方法绕过背景噪声问题，如自发荧光，这些背景噪声极大地复杂化和缓解了典型生物标记物检测模式产生的信号。对于活体成像，很少有技术可以对局部环境中特定生物标志物的水平做出反应，而且那些技术通常只能具有适度的开关比。基于我们之前在生物化学响应型超声造影剂方面的成功，建议的传感器将为活体成像创建专门可检测的超声信号，我们预计将超过我们之前的基准20分贝(100倍)开关比。这项拟议的研究将标志着声音作为一种化学检测方式的第一个例子，这将有助于构建一种全新的传感器、诊断和成像试剂。我们建议通过使用生物标记物驱动的微气泡来执行单一和多路声音传感，微气泡以一种在任何生物介质中都找不到的独特方式散射声音。由于建议的检测试剂和系统的相关费用很小，建议的技术预计将对常规临床分析和护理点诊断都有用。为了仅响应生物分子分析物而产生微泡，我们建议创建在正常情况下超声波很难看到的乳状液，但在检测到特定生物分子时会转化为气泡。这些乳剂将由寡核苷酸和多肽表位组成，这些表位将通过生化识别促进融合。一旦乳状液达到临界尺寸，即使在未活化的乳状液存在的情况下，也可以通过声音或受控加热将其专门汽化成气泡。通过采用传感分析物阻止或允许形成可检测液滴的机制，这项技术既可以应用于体外诊断，也可以应用于体内成像。