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，用于持续监测前列腺癌患者的前列腺特异性抗原（PSA）。这种疾病的早期发现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纸条上的磁性报告纳米粒子（就像验孕棒一样），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在一起。这项工作的成功完成将产生一种即时PSA装置，它将允许医生在手术后的随访期间在他们的办公室对患者进行检测，或者允许患者在家中自我监测并将结果传递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种新的通用生物传感器平台，广泛应用于治疗监测、分子诊断、生物标志物检测和生物医学研究等其他领域，该平台将满足世界卫生组织制定的即时诊断标准（价格合理、敏感、特异、用户友好、快速和稳健、（几乎）不需要设备并可交付给最终用户）。与目前最先进的磁性生物传感器技术相比，所提出的生物传感器平台提供了许多技术进步。它具有超高灵敏度，完全电子读出，精度和高通量制造的成本优势，以及组装简单性。传感器嵌入到低成本的PCB（印刷电路板）组件中，中间夹有横向流动测定条。每个一次性传感器芯片都包含一条测试线和一条控制线，其读出电压与在各自的传感体积中捕获的磁报告粒子的数量成正比，并自动减去背景（由于非特异性结合）。电感传感设计的小型化使得更大的激发场和高频操作成为可能，从而使灵敏度显著提高到10皮emu，比传统的电感探测器提高了10万倍。传统的多线圈交流电纳计设计在低于1000 Hz的布朗松弛模式下工作时，灵敏度降低了100倍，但由于工作频率大幅提高（200 MHz）和显著更小、更高效的传感和激励元件，灵敏度提高了20万倍，从而抵消了灵敏度降低100倍的影响。特异性是通过横向流动夹心免疫分析法实现的。该系统的系统动态范围是电子可调的（激励频率和/或场），用于检测低浓度和高浓度的分析物。该系统有望对制造工艺变化具有特别的鲁棒性，并且不需要校准。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 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.