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

【摘要】该项目的长期目标是开发一种低成本的传感器系统，妇女可以在家中定期使用该系统来自我监测尿液中生殖激素的每周或每月变化。该项目最初将针对黄体生成素（LH）的检测，但未来几年将设想多种激素的多路监测。传感概念最终将与先进的电信技术联系起来。这种家庭监测概念的影响是能够提供对女性生殖健康的终身监测。更广泛的影响将诊断的概念从事件的检测转移到生物系统的监测，使其能够通过廉价的传感设备过渡到（最终）与现有电信的融合。这一概念的更广泛影响还涉及可能为流行病学目的产生的医学和科学信息的价值。这些统计数据可用于制定国家政策和提高对妇女病因的科学认识。S生殖病理和疾病。流行病学统计数据也可以用于提供原始数据的个人，其中成功的干预和治疗与了解特定激素的基线水平有关，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以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以导致早期干预，从而降低医疗保健成本。提出了一种基于纸张的传感器制造新方法。它将在不牺牲简单性或可负担性的情况下增加功能。该提案的智力价值在于传感器设计的进步，不仅坚固耐用，而且还利用了定量电化学检测方案，该方案专门设计用于在廉价的纸基材上操作。此外，该平台将实现高信号放大因子，而不需要脆弱，缓慢和介质敏感的酶。最大可能的信号放大将通过使用磁场来定位与检测电极上的磁珠结合的银纳米颗粒来实现。电化学检测方案将被优化，以在未经处理的人类尿液中运行。进一步的智力价值来自于在纸流体装置中使用和研究微米和纳米尺度的物体。迄今为止，该尺寸范围内物体的非特异性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，因为它们无法在纤维素基质中物理移动。中空通道的建议使用提供了一种绕过这些问题的方法，并将经过验证的真正的生物技术工具引入基于纸张的传感世界（而不会增加复杂性），潜在地为生物分析物检测开辟了广泛的机会。通过将简单的滑动层整合到多层设计中，纸张传感技术的另一个主要障碍“即反应的时间”也将被克服。这些进步将与一个强大、灵敏的信号检测和放大平台以及一个高度可制造的生产设计相结合，该设计由模板印刷的碳电极和蜡印刷的纸折叠成最终的设备配置。

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.