Integrated multiplexed optical biosensors for rapid diagnostics

光作为其环境的非接触式探针的能力为光学传感器提供了许多有吸引力的功能。虽然各种光学传感技术已经广泛用于生物医学、环境和工业部门的许多不同应用，但这项技术尚未充分发挥其潜力。光学微谐振器是最灵敏的一类无标签光学传感器。光在谐振器内部传播多次，任何表面特性的变化都会影响谐振频率，这是可以测量的。生物传感器可以通过在表面涂上一层化学物质来制造，这种化学物质可以与要检测的分子特异性结合。当前微谐振器传感器面临的挑战是，它们需要使用可调谐激光来测量谐振频率的变化。这增加了成本和复杂性，并对集成构成了重大障碍。我们的目标是开发非常敏感和集成的多通道光学传感器，只需要低成本的光源和光电探测器。在过去的十年里，我们研究了一种时域技术，即相移腔衰荡光谱（PS-CRDS）在光学微谐振器生物检测中的应用。我们利用了这样一个事实，即表面结合事件也会改变光子在腔内停留的时间长度，这可以通过检测正弦调制光注入时的信号相移来测量。这需要适度的（RF）调制速率和一个简单的光电探测器。在一系列的实验中，我们已经证明了PS-CRDS在光学微腔中可以用于测量生物分子的特定吸收和解吸，并且PS-CRDS可以通过具有跨越多个共振峰带宽的源来实现，从而消除了对可调谐激光器的需求。然而，下一个挑战，也是本研究计划的主题，是在微环谐振器的集成阵列中实现多路生物传感，允许检测多种生物标志物。我们必须克服在器件设计、建模、制造、信号处理和封装方面的重大挑战。我们将设计用于氮化硅和二氧化硅制造的传感器，并将与微流体和表面功能化方面的专家合作，开发合适的样品输送和捕获技术。我们将开发一个散射模型来了解表面吸收如何影响信号，并通过引入来自电信的信号处理技术，我们将实现高度的多路复用。与领域专家合作，我们将通过实现用于检测肝癌和前列腺癌、水传播病原体和创伤性脑损伤的传感器阵列来验证我们的传感器。该跨学科项目将在5年内为17名研究生和本科生提供高质量的培训。

The ability of light to act as a non-contact probe of its environment provides optical sensors with many attractive capabilities. Whilst various optical sensing technologies are already widely used for many different applications in the biomedical, environmental and industrial sector, this technology has not yet achieved its full potential. Optical micro-resonators represent the most sensitive class of label-free optical sensors. Light propagates multiple times around the inside of the resonator and any change to the surface properties will influence the resonant frequency, which can be measured. A biosensor can be made by coating the surface with a chemistry that will bind specifically to the molecules to be detected. The challenge of current micro-resonator sensors is that they need to be interrogated by using tunable lasers to measure the change of resonant frequency. This adds to cost and complexity and represent a significant barrier to integration. Our objective is to develop very sensitive and integrated multi-channel optical sensors that require only low cost and light sources and photodetectors. Over the past ten years we have investigated the application of a time-domain technique, namely phase shift cavity ring down spectroscopy (PS-CRDS) to bio-detection in optical micro-resonators. We make use of the fact that a surface binding event will also change the length of time that a photon remains in the cavity, which can be measured by detecting the signal phase shift when sinusoidally modulated light is injected. This requires modest (RF) modulation rates and a simple photodetector. In a series of experiments we have demonstrated that PS-CRDS in optical microcavities can be used to measure specific absorption and desorption of biomolecules, and that PS-CRDS can be implemented with a source that has a bandwidth spanning multiple resonance peaks, removing the need for a tunable laser. However, the next challenge, and the subject of this research program, is to implement multiplexed biosensing in an integrated array of micro-ring resonators, allowing multiple biomarkers to be detected. We must overcome significant challenges in terms of device design, modeling, fabrication, signal processing and packaging. We will design sensors for fabrication in silicon nitride and silica and will collaborate with experts in microfluidics and surface functionalization to develop suitable sample delivery and capture techniques. We will develop a scattering model to understand how surface absorption influences the signal, and by introducing signal processing techniques from telecommunications we will be implement a high degree of multiplexing. Working with domain experts we will validate our sensors by implementing a sensor array for the detection of liver and prostate cancers, water-borne pathogens and traumatic brain injury. This interdisciplinary program will provide high quality training to 17 graduate and undergraduate students over 5 years.