Collaborative Research: A self-contained microfluidic optical cavity biosensing platform for multiplex label-free molecular diagnostics

合作研究：用于多重无标记分子诊断的独立微流控光学腔生物传感平台

• 批准号: 1707049
• 负责人: Seunghyun Kim
• 金额: $ 13.24万
• 依托单位: Baylor University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-10-24 至 2020-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1707049&HistoricalAwards=false
• 关键词: Collaborative; Research; self; contained; microfluidic

1- Proposal Title: Proposal #1509746Collaborative Research: A self-contained microfluidic optical cavity biosensing platform for multiplex label-free molecular diagnostics 2- Brief description of project Goals: We aim to demonstrate a self-contained microfluidic optical cavity sensor which enables simple, cost-effective, label-free and highly sensitive biomarker screenings.3- Abstract:3a. Nontechnical:Millions of people suffer from major chronic diseases such as cancers, diabetes, cardiovascular and pulmonary disease, and infectious disease. To improve survival rates of patients and give the right treatment at the right time, early diagnosis of these diseases is required. The most common way to diagnose these diseases is to use a biochemical test that measures the presence or concentration of a macromolecule in a solution through the use of an antibody. The current gold standard biochemical test for detecting these biomarkers is called an enzyme linked immunosorbent assay (ELISA). Such tests have significant limitations with respect to the required sample volume, total testing time, expensive fluorescence detection and an inability to test for many biomarkers simultaneously. A simpler and more cost effective approach is still needed to achieve a more efficient biochemical testing platform. In this research project, we will demonstrate a novel optical cavity biosensor, a sensor that detects the concentration of biomarkers with simple two partially reflecting mirror structure, integrated with a simple microfluidic device. This integrated device enables automated, low-cost, and highly sensitive sensing which is required for various molecular diagnostic fields. Such rapid, simple and cost effective label-free biosensors have the potential to transform the field of early disease screening and to make significant impact on various clinical and healthcare applications. In addition, a new bio-sample handling technique will be implemented to make overall testing procedures simple.The education and outreach activity of this project is well-aligned with the research approach and outcomes. By educating undergraduate and graduate students through summer research experiences, new courses, and seminars, we will be able to deliver the state-of-art techniques related with micro/nanotechnologies. More specifically, by adapting the use of microfluidic system and optic sensors into new courses, we will enhance hands-on learning of microfabrication and semiconductor/microfluidic processes. For K-12 students, we will use this advanced biosensing tool for STEM education. Real demonstration of this work will be broadened through the development and distribution of educational activities on the optical physics and micro-flow phenomena. 3b. Technical:A standard ELISA process includes a laborious and time-consuming sample preparation and labeling processes that involve complicated multi-step chemical reactions, expensive fluorescence and laser equipment to detect a labeled molecule. A simpler and cost effective approach is still needed to achieve a more efficient immunoassay platform. By developing optical cavity biosensor arrays, we will achieve the ultimate goal in biosensors which is a combination of label-free, low cost, high sensitivity, and high selectivity. In addition, adapting a differential detection method with multiple diode systems enables a multiplexing immunoassay, enhances the sensor`s sensitivity and increases the linear dynamic range. By integrating the optical cavity sensor with the self-contained microfluidic platform, we will design SMDx (self-contained multiplexable label-free diagnostics) to achieve a label-free, multiplexable microfluidic molecular diagnostic system. In this platform, various bioassay protocols can be implemented using pumpless technology. Furthermore, the SMDx platform can be readily extended to a portable system by incorporating a modular biosensing system for reliable medical diagnostics.This project has multiple aims: (1) Develop an affordable point-of-care biosensor using optical cavity structure enabling multiplexing bioassay with high sensitivity.(2) Understand sensitivity enhancement by increasing the responsivity of the transducer through the differential detection method. (3) Demonstrate a seamless microfluidic device containing passive flow control with channel surface properties and wicking force.(4) Implement a self-contained multiplex label-free diagnostics (SMDx) platform for cardiac panel screenings.

1-提案标题：提案#1509746合作研究：一个独立的微流体光学腔生物传感平台，用于多重无标记分子诊断2-项目目标的简要描述：我们的目标是展示一个独立的微流体光学腔传感器，它可以实现简单，成本效益高，无标记和高度灵敏的生物标志物筛选。3-摘要：3a.非技术性：数百万人患有癌症、糖尿病、心血管和肺部疾病以及传染病等主要慢性疾病。为了提高患者的生存率并在正确的时间给予正确的治疗，需要对这些疾病进行早期诊断。诊断这些疾病的最常见方法是使用生化测试，通过使用抗体测量溶液中大分子的存在或浓度。目前用于检测这些生物标志物的金标准生化试验被称为酶联免疫吸附试验（ELISA）。这样的测试在所需的样品体积、总测试时间、昂贵的荧光检测和不能同时测试许多生物标志物方面具有显著的限制。仍然需要一种更简单和更成本有效的方法来实现更有效的生化测试平台。在这个研究项目中，我们将展示一种新型的光腔生物传感器，一种用简单的两个部分反射镜结构检测生物标志物浓度的传感器，与一个简单的微流体装置集成。这种集成器件能够实现各种分子诊断领域所需的自动化、低成本和高灵敏度的传感。这种快速、简单和具有成本效益的无标记生物传感器有可能改变早期疾病筛查领域，并对各种临床和医疗保健应用产生重大影响。此外，我们亦会采用新的生物样本处理技术，简化整体测试程序。这个项目的教育和外展活动与研究方法和成果配合得很好。通过暑期研究经验，新课程和研讨会教育本科生和研究生，我们将能够提供与微/纳米技术相关的最先进的技术。更具体地说，通过调整微流体系统和光学传感器的使用到新的课程，我们将加强微制造和半导体/微流体工艺的实践学习。对于K-12学生，我们将使用这种先进的生物传感工具进行STEM教育。通过开展和分发关于光学物理和微流现象的教育活动，将扩大这项工作的真实的示范。3b.技术：标准ELISA过程包括费力耗时的样品制备和标记过程，涉及复杂的多步化学反应，昂贵的荧光和激光设备来检测标记的分子。仍然需要更简单且成本有效的方法来实现更有效的免疫测定平台。通过研制光腔生物传感器阵列，可以实现无标记、低成本、高灵敏度、高选择性的生物传感器的最终目标。此外，采用多个二极管系统的差分检测方法可以实现多重免疫测定，增强传感器的灵敏度并增加线性动态范围。通过将光腔传感器与自容式微流控平台相结合，我们将设计SMDx（self-contained multiplexable label-free diagnostics），以实现无标记、可复用的微流控分子诊断系统。在该平台中，可以使用无泵技术实施各种生物测定方案。此外，SMDx平台还可以通过集成模块化生物传感系统扩展为便携式系统，从而实现可靠的医疗诊断。本项目有多个目标：（1）开发一种经济实惠的床旁生物传感器，使用光学腔结构实现高灵敏度的多路生物测定。(2)了解通过差分检测方法提高传感器的响应度来提高灵敏度。(3)展示一个无缝的微流体装置，它包含具有通道表面特性和芯吸力的被动流量控制。(4)实施一个独立的多重无标记诊断（SMDx）平台，用于心脏面板筛查。