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

使用便携式设备对微量化学和生物分子进行检测、区分和定量，在能源、环境、执法和健康等许多应用中具有重要意义。基于微/纳米机电系统（MEMS/NEMS）的化学和生物传感器具有灵敏度高、尺寸小、多次检测和低功耗等优点。然而，利用化学选择性界面（例如，自组装单层，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的挑战。尽管MEMS/NEMS器件具有许多优点，但依赖于化学选择性接口的MEMS/NEMS器件没有足够的化学选择性。基于弱分子相互作用的化学选择性即使在使用电子鼻等阵列格式时也是部分特定的。另一方面，基于适配体、抗体和肽等受体的生物传感被认为是非常有选择性的，但存在非目标背景分子的非特异性吸附、有限的保质期以及缺乏可靠和可重复的受体固定方法的问题。因此，使用实时、微型传感器平台进行高灵敏度和选择性的化学和生物分子检测、分化和定量仍然是一个关键的挑战。目前可用的技术，如离子迁移率光谱法、气相色谱-质谱法和标记荧光光谱法通常体积大、耗时且昂贵。因此，开发不依赖化学选择性界面而具有选择性和定量的新型微型多模态传感平台是非常有吸引力的。**将光热/光声光谱技术与MEMS/NEMS结合，可以在不牺牲小型化传感器件灵敏度的情况下提供化学选择性。例如光热悬臂偏转光谱，它结合了双金属微悬臂的高热灵敏度和中红外光谱的高选择性，能够获得极少量（几十皮图级）吸附分子的分子特征。传统的红外光谱学依赖于比尔-朗伯定律，它是基于使用低温冷却的红外探测器检测透射光通过样品时的微小强度变化。增加入射红外功率会增加固有背景信号，但不会提高信噪比。相比之下，在MEMS/NEMS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转导，导致信噪比随着入射红外功率的增加而提高。通过采用宽可调谐的高功率量子级联激光器，已经进行了概念验证实验并由申请人报告。**本文提出了将光-机械光谱元件集成到微/纳米器件中的新型多模态传感器件的开发，这些器件可以使用微/纳米加工技术制造。这些新的微型传感器将作为一个高灵敏度的谐振器和温度计，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组合将为化学和生物制剂的检测、分化和定量提供极高的灵敏度和选择性。这些多模态传感装置将立即应用于能源、环境、执法和健康领域，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.