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

利用便携式装置对痕量化学和生物分子的检测、区分和量化在诸如能源、环境、执法和健康的许多应用中具有极大的兴趣。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、检测范围广、功耗低等优点。然而，使用化学选择性界面（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是困难的。一直是个挑战尽管它们有许多优点，但依赖于化学选择性界面的MEMS/NEMS装置不具有足够的化学选择性。基于弱分子相互作用的化学选择性是部分特异性的，即使使用像电子鼻这样的阵列格式。另一方面，基于受体如适体、抗体和肽的生物传感被认为是非常有选择性的，但是遭受非靶背景分子的非特异性吸附、有限的保质期以及缺乏稳健和可再现的受体固定方法。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、区分和定量仍然是一个关键的挑战。目前可用的技术，如离子迁移光谱法，气相色谱-质谱法，和标记的荧光光谱法通常是庞大的，耗时的，昂贵的。因此，开发不依赖于化学选择性界面，而是具有选择性和定量性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相结合，可以在不牺牲微型传感器件灵敏度的前提下提供化学选择性。例如，光热悬臂梁偏转光谱，它结合了高的热灵敏度的一个微悬臂梁与中红外（IR）光谱的高选择性，是能够获得极少量的吸附分子（几十皮克级）的分子签名。传统的红外光谱法依赖于比尔-朗伯定律，是基于使用低温冷却的红外检测器检测通过样品的透射光的小强度变化。增加入射IR功率会增加固有背景信号，而不会提高信噪比（SNR）。相比之下，在具有MEMS/NEMS的光热/光声IR光谱中，IR吸收引起样品温度的变化，并且这些微小的温度变化被MEMS/NEMS转换，这导致随着入射IR功率的增加而增强的SNR。通过采用宽可调谐的高功率量子级联激光器，申请人已经进行并报道了概念验证实验，这里提出了通过将光机械光谱部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态传感器件。这些新的微型传感器将作为一个高灵敏度的谐振器以及温度计，可以提供至少两个正交的信号，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、区分和定量所需的极高灵敏度和选择性。这些多模式传感设备将立即应用于能源，环境，执法和健康，为所有加拿大人的福利。

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.