Point-of-care ultrahigh sensitivity magnetic lateral flow assay

该研究旨在展示一种超灵敏的护理点生物传感器，用于前列腺癌患者的持续前列腺特异性抗原（PSA）监测。早期发现疾病将有助于及时确定适当的治疗方案，并改善患者的长期预后。拟议中的生物传感器是基于检测试纸上的磁性报告纳米颗粒（如怀孕测试），并将与成本低于300美元的读出电子设备和成本低于3美元的一次性测试芯片集成。这项工作的成功完成将产生一个即时PSA设备，允许医生在手术后的随访期间在办公室对患者进行测试，或者允许患者在家中自我监测并将结果传输给护理提供者进行随访和咨询。这项研究还将有助于建立一个新的通用生物传感器平台，广泛用于治疗监测，分子诊断，生物标志物检测和生物医学研究的其他领域，这将满足世界卫生组织为护理点诊断建立的ASSURED（负担得起，灵敏，特异性，用户友好，快速和强大，（几乎）无设备和可交付给最终用户）标准。 所提出的生物传感器平台提供了许多技术进步，超过目前最先进的磁生物传感器技术。它实现了高灵敏度、完全电子读出、高精度和高通量制造的成本优势以及组装的简单性。传感器被嵌入到低成本的PCB（印刷电路板）组件中，在它们之间夹着侧向流测定条。每个一次性传感器芯片包含测试线和对照线，其中读出电压与在相应的感测体积中捕获的磁性报告物颗粒的数量成比例，并且自动减去背景（由于非特异性结合）。感应传感设计的小型化使更大的激励场和高频操作成为可能，从而使灵敏度显著提高到10 pico-emu，比传统感应探测器提高了100，000倍。当远离在低于1000 Hz布朗弛豫模式下操作的常规多线圈AC磁力计设计时，灵敏度的100倍信号降低被由于根本上更高的操作频率（200 MHz）和显著更小、更有效的感测和激励元件而导致的200，000倍灵敏度增加所抵消。通过侧流夹心免疫测定实现专属性。该系统的系统动态范围是电子可调的（激发频率和/或场），用于检测低浓度和高浓度的分析物。该系统预计将对制造过程的变化异常强大，将不需要校准。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The proposed research aims to demonstrate an ultrasensitive point of care biosensor for ongoing prostate-specific antigen (PSA) monitoring in prostate cancer patients. Early detection of the disease will help timely identification of the appropriate treatment options and improve the long-term patient outcomes. The proposed biosensor is based on detection of magnetic reporter nanoparticles on a paper strip (like a pregnancy test) and will be integrated with the readout electronics costing under $300 and disposable test chips costing under $3. Successful completion of this work would yield a point-of-care PSA device that will allow physicians to test patients in their offices during follow-up visits after surgery, or allow patients to self-monitor themselves at home and transmit results to care providers for follow-up and consultation. This research will also help establish a new general biosensor platform broadly useful in other areas of therapy monitoring, molecular diagnostics, biomarker detection, and biomedical research, which will satisfy the ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, (almost) equipment-free and deliverable to end users) criteria established by the World Health Organization for point-of-care diagnostics. The proposed biosensor platform offers a number of technological advancements over the current state-of-the-art magnetic biosensor technologies. It enables ultrahigh sensitivity, completely electronic readout, precision and the cost advantages of high-throughput manufacturing, and simplicity of assembly. The sensors are embedded into low-cost PCB (printed circuit board) components sandwiching an lateral flow assay strip in between. Each disposable sensor chip incorporates a test line and a control line with the readout voltages proportional to the number of magnetic reporter particles captured in the respective sensing volumes and with the background (due to non-specific binding) automatically subtracted. The miniaturization of the inductive sensing design enables larger excitation fields and high-frequency operation resulting in a significantly higher sensitivity of 10 pico-emu, a 100,000 fold improvement over conventional inductive detectors. The 100-fold signal reduction in sensitivity as one moves away from conventional multi-coil AC susceptometer design operating in the sub-1000 Hz Brownian relaxation mode is offset by the 200,000-fold sensitivity increase due to radically higher operation frequency (200 MHz) and significantly smaller, more efficient sensing and excitation elements. Specificity is achieved by a lateral flow sandwich immunoassay. The system dynamic range of the system is electronically adjustable (excitation frequency and/or field) for detection of both low and high concentrations of the analyte. The system is expected to be exceptionally robust against fabrication process variations and will not require calibration.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.