Integrated Lateral Flow Device for Flow Control with Blood Separation and Biosensing

摘要

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.