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: 1509799
• 负责人: Seunghyun Kim
• 金额: $ 22.09万
• 依托单位: LeTourneau University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1509799&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：用于多重免标记分子诊断的独立微流控光学腔生物传感平台2-项目目标简介：我们的目标是展示一种独立的微流控光学腔传感器，它能够实现简单、经济、无标记和高灵敏度的生物标记物筛选。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重大慢性病。为了提高患者的存活率，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。诊断这些疾病最常见的方法是使用生化测试，通过使用抗体来测量溶液中大分子的存在或浓度。目前检测这些生物标志物的金标准生化试验称为酶联免疫吸附试验(ELISA)。这类检测在所需样本量、总检测时间、昂贵的荧光检测以及无法同时检测多个生物标志物方面有很大限制。仍然需要一种更简单和更具成本效益的方法来实现更高效的生化测试平台。在这个研究项目中，我们将展示一种新型的光学腔式生物传感器，这种传感器具有简单的两个部分反射镜结构，与简单的微流控器件集成在一起，可以检测生物标志物的浓度。这一集成设备实现了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、简单且具有成本效益的无标签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，将采用一种新的生物样本处理技术，使整个测试程序变得简单。这项计划的教育和推广活动与研究方法和结果保持一致。通过暑期研究经验、新课程和研讨会培养本科生和研究生，我们将能够提供与微/纳米技术相关的最新技术。更具体地说，通过将微流控系统和光学传感器的使用应用到新课程中，我们将加强对微制造和半导体/微流控工艺的实践学习。对于K-12的学生，我们将使用这种先进的生物传感工具进行STEM教育。将通过开展和分发有关光学物理和微流现象的教育活动来扩大这项工作的真正示范。3B.技术：标准的ELISA法包括费时费力的样品制备和标记过程，涉及复杂的多步骤化学反应、昂贵的荧光和激光设备来检测标记的分子。仍然需要一种更简单、更具成本效益的方法来实现更高效的免疫分析平台。通过发展光学腔式生物传感器阵列，我们将实现生物传感器的最终目标，即无标记、低成本、高灵敏度和高选择性的组合。此外，采用多二极管系统的差示检测方法，实现了多路免疫分析，提高了传感器的灵敏度，并增加了线性动态范围。通过将光学腔传感器与自容式微流控平台相结合，我们将设计SMDx(自容式多路可复用无标签诊断)，以实现无标签、多路可复用微流控分子诊断系统。在这个平台上，可以使用无泵技术来实现各种生物检测协议。此外，SMDx平台可以很容易地扩展到便携式系统，通过整合一个模块化的生物传感系统来实现可靠的医疗诊断。这个项目有多个目标：(1)开发一种负担得起的医疗点生物传感器，使用光学腔结构，实现高灵敏度的多路生物检测。(2)通过差示检测方法提高传感器的响应度，了解灵敏度的增强。(3)展示了一种具有通道表面特性和芯吸力的包含被动流动控制的无缝微流控装置。(4)实现了一个独立的用于心脏面板筛查的多路无标签诊断(SMDx)平台。