Point-of-Care Detection of Luteinizing Hormone: A Step Toward Lifetime Reproductive Healthcare Monitoring for Women

项目编号：1402242主要调查者：理查德·M·克鲁克斯标题：黄体生成素的护理点检测：迈向女性终身生殖健康监测的一步外行人员摘要该项目的长期目标是开发一种低成本的传感器系统，女性可以在家中定期使用，每周或每月自我监测尿液中生殖荷尔蒙的变化。该项目最初的目标是黄体生成素(LH)的检测，但未来几年将设想对多种激素进行多重监测。传感概念最终将与先进的电信技术联系在一起。这一家庭监测概念的影响达到了对女性生殖健康提供终身监测的能力。更广泛的影响将诊断的概念从检测事件转移到监测生物系统，通过廉价的传感设备实现这一过渡，并(最终)与现有电信融合。这一概念的更广泛影响还涉及可用于流行病学目的的医疗和科学信息的价值。这些统计数据可用于国家政策，提高对妇女S生殖病理和疾病病因的科学认识。流行病学统计数据也可能对提供基本数据的个人有用，成功的干预和治疗与了解特定激素的基线水平有关，并通过他们自己的智能手机反馈给参与人群。此外，基线激素水平的变化可能代表疾病状态的早期指标，对这个庞大数据库的适当挖掘可能会导致早期干预，从而降低医疗成本。技术摘要提出了一种新的纸基传感器制造方法。它将在不牺牲简单性或可负担性的情况下增加功能。这一建议的智能优点在于传感器设计的进步，这种设计不仅坚固耐用，而且利用了专门设计用于在廉价纸张衬底上运行的定量电化学检测方案。此外，该平台将实现高信号放大系数，而不需要脆弱、缓慢和介质敏感的酶。通过使用磁场来定位结合在检测电极上的磁珠上的银纳米颗粒，将实现最大可能的信号放大。电化学检测方案将进行优化，以在未经处理的人类尿液中运行。在纸上的流体装置中使用和研究微米和纳米尺度的物体将带来更多的智力优势。到目前为止，这种尺寸范围内的物体的非特定吸附和尺寸排除特性阻碍了它们在这种情况下的广泛使用，因为它们不能在纤维素基质中物理移动。中空通道的拟议使用提供了一种绕过这些问题的方法，并将久经考验的真实生物技术工具引入纸基传感世界(而不增加复杂性)，潜在地为生物分析物检测打开了广泛的机会。通过将简单的滑动层集成到多层设计中，还将克服纸基传感技术中的另一个主要障碍，即反应时间。这些进步将与坚固、灵敏的信号检测和放大平台以及高度可制造的生产设计相结合，该设计由模版印刷碳电极和折叠到最终设备配置中的蜡印纸组成。

Proposal Number: 1402242Principal Investigator: Richard M. CrooksTitle: Point-of-Care Detection of Luteinizing Hormone: A Step Toward Lifetime Reproductive Healthcare Monitoring for WomenLayperson AbstractThe long-term goal of this project is development of a low-cost sensor system that women can use at home on a regular basis to self-monitor weekly or monthly variations of a panel of reproductive hormones in urine. This project will initially target detection of luteinizing hormone (LH), but multiplexed monitoring of multiple hormones is envisioned in future years. The sensing concept will eventually linked to advanced telecommunications technology. The impact of this home-monitoring concept reaches toward the ability to provide life-long monitoring of female reproductive health. The broader impacts move the concept of diagnostics from the detection of an event to the monitoring of biological systems, enabling that transition through inexpensive sensing devices and (ultimately) convergence with existing telecommunications. The broader impacts of this concept also address the value of the medical and scientific information that could be generated for epidemiological purposes. These statistics could be used for national policy and for improving the scientific understanding of the etiology of women?s reproductive pathologies and maladies. The epidemiological statistics could also be of use to the individuals providing the primary data, where successful interventions and therapies tied to an understanding of baseline levels of particular hormones are fed back to the participating population via their own smart phones. Additionally, changes in baseline hormone levels could represent early indicators of disease states, and appropriate mining of this enormous database could result in early intervention, thus reducing healthcare costs. Technical AbstractA new approach to paper-based sensor fabrication is proposed. It will lead to increased functionality without sacrificing simplicity or affordability. The intellectual merit of this proposal lies in the advancement of a sensor design that is not only robust, but also utilizes a quantitative electrochemical detection scheme that is specifically designed to operate on inexpensive paper substrates. Moreover, this platform will achieve a high signal amplification factor without the need for fragile, slow, and media-sensitive enzymes. Maximum possible signal amplification will be achieved by the use of a magnetic field to localize silver nanoparticles bound to magnetic beads at the detection electrode. The electrochemical detection scheme will be optimized to operate in raw human urine. Further intellectual merit derives from the use and study of micron- and nanometer-scale objects in paper fluidic devices. To date, the non-specific adsorption and size exclusion properties of objects in this size range have prevented their widespread use in this context, as they are unable to physically move within a cellulose matrix. The proposed use of hollow channels provides a means to bypass these issues and introduce tried and true biotechnology tools to the world of paper-based sensing (without increasing complexity), potentially opening up a broad range of opportunities in biological analyte detection. By integrating simple slip layers into a multi-level design, another major roadblock in paper-based sensing technology " namely, timing of reactions " will also be overcome. These advances will be combined with a robust, sensitive signal detection and amplification platform and a highly manufacturable production design that consists of stencil-printed carbon electrodes and wax-printed paper folded into the final device configuration.