Development of multimodal sensing devices for receptor-free molecular detection and quantification

利用便携式设备对痕量化学和生物分子进行检测、区分和定量，在能源、环境、执法和健康等领域具有重要的应用价值。基于微/纳机电系统(MEMS/NEMS)的化学和生物传感器具有灵敏度高、体积小、多检测、低功耗等优点。然而，使用化学选择性界面(例如，自组装单分子膜、聚合物涂层、受体等)在MEMS/NEMS传感器中获得化学选择性。一直是一个长期存在的挑战。尽管MEMS/NEMS器件具有许多优点，但依赖于化学选择性界面的MEMS/NEMS器件并没有足够的化学选择性。即使使用像电子鼻这样的阵列格式，基于弱分子相互作用的化学选择性也是部分特定的。另一方面，基于适体、抗体和多肽等受体的生物传感被认为具有很高的选择性，但存在非靶标背景分子的非特异性吸附、保存期有限以及缺乏可靠和可重复的受体固定方法等问题。因此，使用实时、微型传感器平台对化学和生物分子进行高灵敏度和选择性的检测、区分和量化仍然是一个关键的挑战。目前可用的技术，如离子迁移率光谱、气相色谱-质谱法和标记荧光光谱，通常体积大、耗时长、价格昂贵。因此，开发不依赖于化学选择界面而具有选择性和定量的新型微型多模式传感平台是非常有吸引力的。*将光热/光声光谱技术与MEMS/NEMS相结合可以在不牺牲微型传感器件的灵敏度的情况下提供化学选择性。例如，光热悬臂梁偏转光谱结合了双金属微悬臂梁的高热敏感度和中红外光谱的高选择性，能够获得极少量(数十皮克级)吸附分子的分子特征。传统的红外光谱学依赖于比尔-兰伯特定律，是基于使用低温冷却的红外探测器探测通过样品的透射光的微小强度变化。增加入射红外功率会增加固有的背景信号，而不会增加信噪比。相反，在MEMS/NEMS的光热/光声红外光谱中，红外吸收引起样品温度的变化，这些微小的温度变化由MEMS/NEMS传递，从而导致随着入射红外功率的增加而增强的信噪比。通过使用宽可调、高功率的量子级联激光器，申请人已经进行了概念验证实验并报告了这一实验。**这里提出了通过将光机械光谱组件集成到可以使用微/纳米制造技术制造的微/纳米器件中来开发新的多模式传感器件。这些新型微型传感器将作为一个高灵敏度的谐振器和温度计工作，可以提供至少两个正交信号，如吸附分子的质量和光谱信息。来自这些设备的信息的组合将提供化学和生物制剂检测、鉴别和定量所需的极高的灵敏度和选择性。这些多模式传感设备将立即应用于能源、环境、执法和健康，造福所有加拿大人。

Detection, differentiation, and quantification of trace amounts of chemical and biological molecules with a portable device are of great interest in many applications such as energy, environment, law-enforcement, and health. Chemical and biological sensors based on micro/nanoelectromechanical systems (MEMS/NEMS) offer many advantages such as high sensitivity, miniature size, multiple detection, and low-power consumption. However, obtaining chemical selectivity in MEMS/NEMS sensors using chemoselective interfaces (for example, self-assembled monolayer, polymer coating, receptors, etc.) has been a longstanding challenge. Despite their many advantages, MEMS/NEMS devices relying on chemoselective interfaces do not have sufficient chemical selectivity. Chemical selectivity based on weak molecular interactions is partially specific even when an array format like an electronic nose is used. On the other hand, biological sensing based on receptors such as aptamer, antibodies, and peptides is thought to be very selective, but suffers from non-specific adsorption of non-target background molecules, limited shelf-life, and lack of robust and reproducible receptor immobilization methods. Therefore, highly sensitive and selective detection, differentiation, and quantification of chemical and biological molecules using real-time, miniature sensor platforms still remains as a crucial challenge. Currently available technologies, such as ion mobility spectrometry, gas chromatography-mass spectrometry, and labeled fluorescence spectroscopy are usually bulky, time-consuming, and expensive. Therefore, the development of new miniature multimodal sensing platforms which are not relying on chemoselective interfaces but being selective and quantitative is very attractive.**Incorporating photothermal/photoacoustic spectroscopic techniques with MEMS/NEMS can provide the chemical selectivity without sacrificing the sensitivity of miniaturized sensing devices. For example, photothermal cantilever deflection spectroscopy, which combines the high thermal sensitivity of a bimetallic microcantilever with the high selectivity of mid infrared (IR) spectroscopy, is capable of obtaining molecular signatures of extremely small quantities of adsorbed molecules (tens of picogram level). Conventional IR spectroscopy, which relies on Beer-Lambert's law, is based on detecting small intensity changes in transmitted light through a sample using a cryogenically cooled IR detector. Increasing the incident IR power increases the inherent background signal without enhancing the signal-to-noise ratio (SNR). In contrast, in photothermal/photoacoustic IR spectroscopy with MEMS/NEMS, IR absorption induces changes in the sample temperature and these minute temperature changes are transduced by MEMS/NEMS, which results in an enhanced SNR with increased incident IR power. By employing a broadly tunable, high power quantum cascade laser, the proof-of-concept experiments were already performed and reported by the applicant.**Here the development of new multimodal sensing devices by integrating opto-mechanical spectroscopy components into micro/nano-devices which can be fabricated using micro/nanofabrication techniques is proposed. These new miniature sensors will work as a highly sensitive resonator as well as a thermometer which can provide at least two orthogonal signals such as mass and spectral information of adsorbed molecules. The combination of information from these devices will provide the extremely high sensitivity and selectivity needed for chemical and biological agent detection, differentiation, and quantification. These multimodal sensing devices will find immediate applications in energy, environment, law-enforcement, and health for the welfare of all Canadians.