Integrated multiplexed optical biosensors for rapid diagnostics

用于快速诊断的集成多重光学生物传感器

• 批准号: RGPIN-2020-05178
• 负责人: Kirk, Andrew
• 金额: $ 2.4万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717551
• 关键词: Integrated; multiplexed; optical; biosensors; rapid

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.

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应用于生物医学、环境和工业领域的许多不同应用，但该技术尚未充分发挥其潜力。光学微谐振器代表最灵敏的无标记光学传感器类别。光在谐振器内部传播多次，表面特性的任何变化都会影响可以测量的谐振频率。可以通过在表面涂上化学物质来制造生物传感器，这种化学物质可以与待检测的分子特异性结合。 当前微谐振器传感器的挑战是需要使用可调谐激光器来询问它们以测量谐振频率的变化。这增加了成本和复杂性，并成为集成的重大障碍。我们的目标是开发非常灵敏的集成多通道光学传感器，仅需要低成本、光源和光电探测器。 在过去的十年中，我们研究了时域技术，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。我们利用这样一个事实，即表面结合事件也会改变光子在腔中保留的时间长度，这可以通过检测注入正弦调制光时的信号相移来测量。这需要适度的 (RF) 调制速率和简单的光电探测器。在一系列实验中，我们证明了光学微腔中的 PS-CRDS 可用于测量生物分子的特定吸收和解吸，并且 PS-CRDS 可以使用具有跨越多个共振峰的带宽的源来实现，从而无需可调谐激光器。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重生物传感，从而能够检测到多种生物标记物。 我们必须克服器件设计、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领域的专家合作，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，并通过引入电信信号处理技术，我们将实现高度的复用。我们将与领域专家合作，通过实施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。这个跨学科项目将在 5 年内为 17 名研究生和本科生提供高质量的培训。