Rapid, Multiscale Sensing Using Acoustic Detection Mechanisms

使用声学检测机制进行快速、多尺度传感

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：拟议研究的目标是设计一类新型体外和体内生物传感器，其中快速、分析物触发的液滴融合产生独特的可检测声音信号。开发一种能够提供一种方便、廉价且便携式的无需样品操作即可检测生物分子的方法的技术将为在许多不同环境和介质中测量全身和局部生物分子水平提供新的途径。对于体外检测，溶液内传感器将消除样品处理和清洗步骤的需要，这些步骤可能会导致时间、费用和错误来源的增加。此外，液滴几乎可以用于任何规模，从微流控芯片到批量处理。最后，受控体外环境中几乎不存在的声背景允许该方法绕过背景噪声问题，例如自发荧光，这些问题极大地复杂化并减轻了典型生物标志物检测方式产生的信号。对于体内成像，很少有技术可以响应局部环境中特定生物标志物的水平，并且通常只能具有适度的开关比。基于我们之前在生化响应超声造影剂方面取得的成功，所提出的传感器将为体内成像产生专门可检测的超声信号，我们预计该信号将超过我们之前 20 dB（100 倍）开关比的基准。拟议的研究将标志着声音作为化学检测方式的第一个例子，这将有助于构建全新类型的传感器、诊断和成像剂。我们建议通过采用生物标记驱动的微泡生成来执行单一和多重声音传感，微泡以任何生物介质中都找不到的独特方式散射声音。由于与所提出的检测试剂和系统相关的费用很小，因此所提出的技术预计可用于常规临床分析和护理点诊断。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条件下超声波很难看到的乳液，但在感测到特定生物分子时转变成气泡。该乳液将用寡核苷酸和肽表位配制，通过生化识别促进融合。一旦乳液达到临界尺寸，即使存在未活化的乳液，它们也可以通过声音或受控加热专门汽化成气泡。通过采用传感分析物阻止或允许可检测液滴形成的机制，该技术可应用于体外诊断和体内成像。