Integrated Lateral Flow Device for Flow Control with Blood Separation and Biosensing
Integrated Lateral Flow Device for Flow Control with Blood Separation and Biosensing
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DOI：
10.3390/mi8120367
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发表时间：
2017-12-01
期刊：
影响因子：
3.4
通讯作者：
Liu, Yuxin
中科院分区：
文献类型：
--
作者：
Betancur, Veronica;Sun, Jianbo;Liu, Yuxin
侧流装置是通用的并且用于各种各样的目的，包括医疗、农业、环境和军事应用。然而，这些设备用于诊断的最有前途的机会可能在于即时护理（POC）应用。一次性纸基横向流动条特别受关注，因为它们利用低成本材料并且不需要昂贵的制造仪器。然而，在论文中存在对调节流速和免疫测定功能化的限制，以及用于低丰度分子检测的传感器集成和浓缩单元的技术挑战。在目前的工作中，我们展示了一种集成的侧流装置，该装置将毛细管力与基于功能化聚合物的微流体作为实现便携式、简化和自供电的侧流装置（LFD）的策略。通过用不同浓度的Pluronic F127官能化，使聚二甲基硅氧烷（PDMS）表面亲水。受控流动是基于免疫测定的应用的关键变量，用于为蛋白质与抗体结合提供足够的时间。通过多种因素的组合来调节集成LFD的流速，包括Pluronic F127功能化的表面性质和微通道的表面处理、集成流阻器的阻力、毛细泵中微结构的尺寸和它们之间的间距、接触角和流体的粘度。在整个装置中调节并实现了各种血浆流速。LFD结合了通过使用高度不对称的血浆分离膜从人全血中分离高质量血浆的能力，并使用由界面张力产生的毛细管力产生受控和稳定的流体流动。用与LFD集成的石墨烯纳米电子传感器证明了来自血浆的生物标志物免疫球蛋白G（IgG）检测。所开发的LFD可用作灵活和通用的平台，并且具有检测来自全血的循环生物标志物的潜力。夹心免疫测定可以通过在所需基底上图案化分析物的受体而直接在LFD上进行，并且可以使用各种感测方法（包括纳米电子、比色或荧光传感器）进行检测。所描述的生物感测技术提供了使用人类全血的小样本进行POC测试的替代方案。它可以使医疗保健有限的地区受益，在这些地区，诊断延误可能导致生活质量迅速恶化，并增加发病率和死亡率。
Lateral flow devices are versatile and serve a wide variety of purposes, including medical, agricultural, environmental, and military applications. Yet, the most promising opportunities of these devices for diagnosis might reside in point-of-care (POC) applications. Disposable paper-based lateral flow strips have been of particular interest, because they utilize low-cost materials and do not require expensive fabrication instruments. However, there are constraints on tuning flow rates and immunoassays functionalization in papers, as well as technical challenges in sensors' integration and concentration units for low-abundant molecular detection. In the present work, we demonstrated an integrated lateral flow device that applied the capillary forces with functionalized polymer-based microfluidics as a strategy to realize a portable, simplified, and self-powered lateral flow device (LFD). The polydimethylsiloxane (PDMS) surface was rendered hydrophilic via functionalization with different concentrations of Pluronic F127. Controlled flow is a key variable for immunoassay-based applications for providing enough time for protein binding to antibodies. The flow rate of the integrated LFD was regulated by the combination of multiple factors, including Pluronic F127 functionalized surface properties and surface treatments of microchannels, resistance of the integrated flow resistor, the dimensions of the microstructures and the spacing between them in the capillary pump, the contact angles, and viscosity of the fluids. Various plasma flow rates were regulated and achieved in the whole device. The LFD combined the ability to separate high quality plasma from human whole blood by using a highly asymmetric plasma separation membrane, and created controlled and steady fluid flow using capillary forces produced by the interfacial tensions. Biomarker immunoglobulin G (IgG) detection from plasma was demonstrated with a graphene nanoelectronic sensor integrated with the LFD. The developed LFD can be used as a flexible and versatile platform, and has the potential for detecting circulating biomarkers from whole blood. Sandwich-immunoassays can be performed directly on the LFD by patterning receptors for analytes on a desired substrate, and detections can be performed using a variety of sensing methods including nanoelectronic, colorimetric, or fluorescence sensors. The described bio-sensing technology presents an alternative for POC testing using small samples of human whole blood. It could benefit regions with limited access to healthcare, where delays in diagnosis can lead to quick deterioration of the quality of life and increase the morbidity and mortality.