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

提案编号：1402242主要研究者：Richard M.骗子标题：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一组生殖激素的每周或每月变化。 该项目最初将检测促黄体生成素（LH），但预计在未来几年将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起来。 这种家庭监测概念的影响达到提供终身监测女性生殖健康的能力。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，通过廉价的传感设备实现这一转变，并（最终）与现有的电信融合。这一概念的更广泛影响还涉及为流行病学目的可能产生的医学和科学信息的价值。这些统计数据可用于国家政策和提高妇女病因学的科学认识？的生殖病理和疾病。流行病学统计数据也可用于提供原始数据的个人，其中与特定激素基线水平的理解相关的成功干预和治疗通过参与人口自己的智能手机反馈给他们。此外，基线激素水平的变化可以代表疾病状态的早期指标，对这个巨大数据库的适当挖掘可以导致早期干预，从而降低医疗成本。提出了一种纸基传感器制作的新方法。 它将在不牺牲简单性或可负担性的情况下增加功能。该提议的智力价值在于传感器设计的进步，该传感器设计不仅稳健，而且还利用了专门设计用于在廉价的纸基底上操作的定量电化学检测方案。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结合到检测电极处的磁珠的银纳米颗粒来实现。将优化电化学检测方案以在原始人尿液中操作。 进一步的知识价值来自于纸流体设备中微米和纳米尺度物体的使用和研究。迄今为止，该尺寸范围内的物体的非特异性吸附和尺寸排阻性质已经阻止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内物理移动。中空通道的拟议使用提供了一种绕过这些问题的方法，并将经过验证的真正的生物技术工具引入纸基传感领域（而不会增加复杂性），这可能为生物分析物检测提供了广泛的机会。通过将简单的滑动层集成到多层设计中，纸基传感技术的另一个主要障碍“即反应时间”也将被克服。这些进步将与强大，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，该设计由模板印刷的碳电极和蜡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.