Point-of-care ultrahigh sensitivity magnetic lateral flow assay

床旁超高灵敏度磁性侧流检测

• 批准号: 1928334
• 负责人: Dmitri Litvinov
• 金额: $ 40万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1928334&HistoricalAwards=false
• 关键词: Point; care; ultrahigh; sensitivity; magnetic

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.

这项拟议的研究旨在证明一种用于前列腺癌患者持续前列腺特异性抗原(PSA)监测的超灵敏护理点生物传感器。及早发现这种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在纸条上检测磁性报告纳米颗粒(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在一起。成功完成这项工作将产生一种医疗点PSA设备，它将允许医生在手术后的后续访问期间在他们的办公室对患者进行测试，或者允许患者在家里自我监测并将结果传输给护理人员，以便进行后续和咨询。这项研究还将帮助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、生物标记物检测和生物医学研究的其他领域，它将满足世界卫生组织为医疗点诊断建立的保证标准(负担得起、敏感、特异、用户友好、快速和强大，(几乎)无需设备，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，拟议的生物传感器平台提供了许多技术进步。它实现了超高灵敏度、全电子读数、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印刷电路板(印刷电路板)组件中，中间夹着一条横向流动分析试纸。每个一次性传感器芯片包括测试线和控制线，其中读出电压与在各个感测体积中捕获的磁性报告颗粒的数量成比例，并且具有自动减去(由于非特定结合)的背景。感应式传感设计的小型化使其能够产生更大的激励场和高频工作，从而使灵敏度显著提高，达到10皮EMU，比传统感应式探测器提高了100,000倍。在低于1000赫兹布朗松弛模式下工作的传统多线圈交流磁感计设计中，信号灵敏度降低了100倍，但由于极高的工作频率(200 MHz)和显著更小、更高效的传感和激励元件，灵敏度提高了200,000倍，抵消了这一影响。特异性是通过横向流动夹心免疫分析实现的。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工艺变化非常稳健，不需要校准。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Smartphone-read phage lateral flow assay for point-of-care detection of infection

• DOI: 10.1039/d2an01499h
• 发表时间: 2023-01-05
• 期刊: ANALYST
• 影响因子: 4.2
• 作者: Chabi，Maede;Vu，Binh;Kourentzi，Katerina
• 通讯作者: Kourentzi，Katerina

PCB-Based Magnetometer as a Platform for Quantification of Lateral-Flow Assays

• DOI: 10.3390/s19245433
• 发表时间: 2019-12-02
• 期刊: SENSORS
• 影响因子: 3.9
• 作者: Khodadadi, Mohammad;Chang, Long;Litvinov, Dmitri
• 通讯作者: Litvinov, Dmitri

Carbon combustion synthesis of Janus-like particles of magnetoelectric cobalt ferrite and barium titanate

• DOI: 10.1016/j.ceramint.2020.10.123
• 发表时间: 2020-10
• 期刊: Ceramics International
• 影响因子: 5.2
• 作者: C. D. Leo;G. C. Dannangoda-;M. Hobosyan;Jacob T. Held;F. S. Samghabadi;M. Khodadadi;D. Litvinov;K. Mkhoyan;K. Martirosyan

Recombinant expression, characterization, and quantification in human cancer cell lines of the Anaplastic Large-Cell Lymphoma-characteristic NPM-ALK fusion protein

间变性大细胞淋巴瘤特征性 NPM-ALK 融合蛋白在人类癌细胞系中的重组表达、表征和定量

• DOI: 10.1038/s41598-020-61936-w
• 发表时间: 2020
• 期刊: Scientific Reports
• 影响因子: 4.6
• 作者: Kourentzi, Katerina;Crum, Mary;Patil, Ujwal;Prebisch, Ana;Chavan, Dimple;Vu, Binh;Zeng, Zihua;Litvinov, Dmitri;Zu, Youli;Willson, Richard C.
• 通讯作者: Willson, Richard C.

Scalable, cost-efficient synthesis and properties optimization of magnetoelectric cobalt ferrite/barium titanate composites

• DOI: 10.1063/5.0036518
• 发表时间: 2021-02
• 期刊: APL Materials
• 影响因子: 6.1
• 作者: Farnaz Safi Samghabadi;Long Chang;M. Khodadadi;K. Martirosyan;D. Litvinov