CAREER: Multiplexed Paper-Based Biosensor Enabled by Interfacial Interactions

在资源有限的环境中，使用现代仪器进行生化分析是不切实际的，在这些环境中，电力和训练有素的操作人员可能无法获得，并且分析解决方案必须低成本，便携式和操作简单。从根本上说，需要专门为解决资源有限环境的挑战而设计的新方法。利用纸作为衬底来开发生物传感器是有吸引力的，因为生产它们所需的资源很少，材料无处不在且价格低廉。这个项目将创造新的设备设计，使基于纸张的生物传感成为可能。亲水（可湿性）通道将使用疏水（不可湿性）屏障在纸上绘制图案，以便通过吸湿来控制样品流体的运输。除了为有限资源环境下的生物分析设计新策略外，该研究项目的更广泛影响还包括为中学生（动手研讨会）、高中生（设备设计挑战和暑期实习）和科学教师（课堂工具包开发）创造教育机会。由于其低成本和易于使用，基于纸张的微流体装置作为开发使用点生物测定的平台受到了关注。独立于分析发展的进步，基于纸张的设备本身，尽管它们具有促进生物分析的巨大潜力，却很少受到关注。该项目旨在建立一个综合研究和教育计划，以开发新型纸基微流体装置为中心，该装置可以促进基于化学和生物化学反应的生物传感，这些反应发生在会聚液体前缘之间形成的界面上。利用这种方法的设备将促进使用传统上被认为与基于流动的设备（例如，化学反应）不兼容的分析格式的多路生物传感。本研究的中心假设是，纸张的材料特性（如孔隙度）和反应产物的传输（如扩散）将最终控制这些基于纸张的生物传感器的分析性能。通过系统地研究这些变量，将开发出低成本、基于纸张的生物传感新策略。在流体界面上的分析将导致可见颜色的形成，这将允许用户通过视觉阈值（定性），视觉比较读取指南的强度（半定量）或图像分析（定量）轻松解释分析结果。这项研究意义重大，因为从该项目中衍生的设备在生物分析中具有广泛的应用范围，并将作为各种形式的分析化学的通用工具。潜在的应用包括：(i)重金属的环境监测，（ii）粮食安全和营养密度，（iii）核酸和蛋白质的检测，以及（iv）开发专门为在资源有限的环境中使用而设计的诊断分析。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The use of modern instrumentation for biochemical analysis is impractical in limited-resource settings where electrical power and trained operators may not be available and where analytical solutions must be low-cost, portable, and operationally simple. Fundamentally new approaches that are designed specifically to address the challenges of limited-resource settings are needed. Utilizing paper as a substrate to develop biosensors is attractive because the resources required to produce them are minimal and the materials are ubiquitous and inexpensive. This project will create new device designs that can enable paper-based biosensing. Hydrophilic (wettable) channels will be patterned in paper using hydrophobic (non-wettable) barriers in order to control the transport of sample fluids by wicking. In addition to devising a new strategy for bioanalysis in limited-resource settings, the broader impacts of this research program include the creation of educational opportunities for middle school students (hands-on workshops), high school students (device design challenges and summer internships), and science teachers (classroom kit development).Due to their low cost and ease of use, paper-based microfluidic devices have gained attention as a platform to develop point-of-use bioassays. Independent of the advances in assay development, the paper-based devices themselves, in spite of their vast potential to facilitate bioanalysis, have received surprisingly little attention. This project aims to build an integrated research and education program centered on developing novel paper-based microfluidic devices that can facilitate biosensing based on chemical and biochemical reactions that occur at the interfaces formed between converging liquid fronts. Devices exploiting this approach will facilitate multiplexed biosensing using assay formats that are traditionally considered to be incompatible with flow-based devices (e.g., chemical reactions). The central hypothesis of this research is that the material properties of the paper (e.g., porosity) and the transport of reaction products (e.g., by diffusion) will ultimately control the analytical performance of these paper-based biosensors. By studying these variables systematically, new strategies for low-cost, paper-based biosensing will be developed. Assays at fluidic interfaces will result in the formation of visible colors that will allow users to easily interpret the results of an assay via visual threshold (qualitative), visual comparisons of intensities to read guides (semi-quantitative), or with image analysis (quantitative). This research is significant because the devices derived from this program span a broad range of applications in bioanalysis and will serve as versatile tools for all forms of analytical chemistry. Potential applications include: (i) environmental monitoring of heavy metals, (ii) food security and nutrient density, (iii) detection of nucleic acids and proteins, and (iv) the development of diagnostic assays that are designed specifically for use in limited-resource settings.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.