IDBR: A label-free biomolecular sensing instrument based on monolithic optical resonators and an optoelectronic swept-frequency semiconductor laser

项目摘要本项目提出了一种基于集成电控线性扫频半导体激光器、具有共价表面功能化的高质量因数(Q)光学谐振器和用于输送分析物的微流控池的无标签传感仪器的开发和演示。它将解决目前阻碍这项技术成为可获得、负担得起和有用的工具的一些关键问题。这些努力将把光学腔传感平台发展到一个坚固和可重复的点，并提供至少比任何可用的替代生物分子分析仪器高一个数量级的灵敏度和成本效益。建议的系统将结合光学和激光物理领域最近两个主要发展的结果：高Q光学谐振器和锁相电子控制扫频半导体激光器。高Q光学谐振器是集成光波导单片单元的一部分，使用基于标准半导体光刻的方法制造。光电扫频激光器将在与水气传感相关的波长上开发，并将取代昂贵而脆弱的机械调谐激光光源，后者的扫频速度、精度和可靠性有限。谐振器将使用提供适应性和选择性表面化学的已知技术来功能化。该传感器将包括一个集成的微流控流动池，用于将分析物精确和低容量地输送到共振器表面。该仪器代表了一个适应性和成本效益高的平台，能够进行与生物物理、生物分子相互作用、细胞信号和广泛的其他生命科学领域相关的各种敏感的、无标记的测量。它将能够约束分析、热力学和动力学测量，并有可能通过整合到现有仪器中来取代不那么灵敏的分析方法，从而产生额外的影响。该传感器在医疗诊断方面也有潜在的应用，它可以早期检测相关的抗原。该项目本质上是多学科的，将发展半导体激光、光学纳米制造、高速电子、控制系统、光纤、微流体、生物分子结合分析、传质和集成仪器设计等不同领域之间的相互作用的专业知识和更好的理解。它为两名研究生和一名本科生提供了在私人投资者关系密切指导下参与合作研究的机会，教育学生科学发现的文化，以及工程和应用方面的考虑。在项目过程中获得的成果将在主要的科学期刊和会议上发表。

Project AbstractThis project proposes the development and demonstration of a label-free sensing instrument based on the integration of an electronically controlled linear swept-frequency semiconductor laser, a high quality factor (Q) optical resonator with covalent surface functionalization, and a microfluidic cell for analyte delivery. It will address a number of key issues that currently prevent this technology from becoming an accessible, affordable, and useful tool. These efforts will develop the optical cavity sensing platform to a point where it is robust and repeatable, and provides sensitivity and cost-effectiveness that are at least an order of magnitude better than any available alternative biomolecular assay instrument.The proposed system will combine the results of two major recent developments in the field of optical and laser physics: the high-Q optical resonator and the phase-locked electronically controlled swept-frequency semiconductor laser. The high-Q optical resonator is part of a monolithic unit with an integrated optical waveguide, and is fabricated using standard semiconductor lithography-based methods. Optoelectronic swept frequency lasers will be developed at wavelengths relevant for aqueous sensing, and will replace expensive and fragile mechanically-tuned laser sources whose frequency sweeps have limited speed, accuracy and reliability. The resonator will be functionalized using known techniques providing an adaptable and selective surface chemistry. The sensor will include an integrated microfluidic flow cell for precise and low volume delivery of analytes to the resonator surface.The proposed instrument represents an adaptable and cost-effective platform capable of various sensitive, label-free measurements relevant to the study of biophysics, biomolecular interactions, cell signaling, and a wide range of other life science fields. It will be capable of binding assays, thermodynamic and kinetics measurements, and has the potential for additional impact through integration into existing instruments to replace less sensitive analytical methods. The sensor also has potential applications in point-of-care medical diagnostics, where it can enable early detection of relevant antigens.The project is inherently multidisciplinary and will develop expertise in and better understanding of the interplay between such diverse fields as semiconductor lasers, optical nanofabrication, high speed electronics, control systems, fiber-optics, microfluidics, biomolecular binding assays, mass transfer, and integrated instrument design. It affords the opportunity for two graduate students and an undergraduate student to take part in a collaborative research effort under the close guidance of the PIs, educating the students in the culture of scientific discovery, alongside engineering and application considerations. The results obtained during the course of the project will be published in leading scientific journals and conferences.