Diffusion-free valve for preprogrammed immunoassay with capillary microfluidics

Abstract

By manipulating the geometry and surface chemistry of microfluidic channels, capillary-driven microfluidics can move and stop fluids spontaneously without external instrumentation. Furthermore, complex microfluidic circuits can be preprogrammed by synchronizing the capillary pressures and encoding the surface tensions of microfluidic chips. A key component of these systems is the capillary valve. However, the main concern for these valves is the presence of unwanted diffusion during the valve loading and activation steps that can cause cross-contamination. In this study, we design and validate a novel diffusion-free capillary valve: the π-valve. This valve consists of a 3D structure and a void area. The void acts as a spacer between two fluids to avoid direct contact. When the valve is triggered, the air trapped within the void is displaced by pneumatic suction induced from the capillary flow downstream without introducing a gas bubble into the circuit. The proposed design eliminates diffusive mixing before valve activation. Numerical simulation is used to study the function and optimize the dimensions of the π-valve, and 3D printing is used to fabricate either the mould or the microfluidic chip. A comparison with a conventional valve (based on a constriction-expansion valve) demonstrates that the π-valve eliminates possible backflow into the valve and reduces the mixing and diffusion during the loading and trigger steps. As a proof-of-concept, this valve is successfully implemented in a capillary-driven circuit for the determination of benzodiazepine, achieving the successive release of 3 solutions in a 3D-printed microfluidic chip without external instrumentation. The results show a 40% increase in the fluorescence intensity using the π-valve relative to the conventional value. Overall, the π-valve prevents cross-contamination, minimizes sample use, and facilitates a sophisticated preprogrammed release of fluids, offering a promising tool for conducting automated immunoassays applicable at point-of-care testing.

Coupling Capillary-Driven Microfluidics with Lateral Flow Immunoassay for Signal Enhancement

“…A mediator gap filled by air can isolate the liquids to avoid these issues [ 4 ]. However, utilizing an air gap can later result in bubbles entering the circuit and microfluidic malfunction [ 8 ]. Therefore, a deliberate valve configuration is required to displace the air and avoid introducing bubbles ( Figure 1 ); this workflow is discussed in the next section and illustrated in Figure 3 a–e.…”

“…Therefore, the reservoir venting opens the triggering liquid is emptied from the main microchannel, securing a successiv lease. At a trigger junction, after breaking the liquid-air meniscus until compelling upstream retention and release, diffusive mixing of fluids' molecules can lead to sam dilution, washing buffer contamination, and experiencing non-lateral flow patterns do stream [8]. A mediator gap filled by air can isolate the liquids to avoid these issues However, utilizing an air gap can later result in bubbles entering the circuit and micr idic malfunction [8].…”

“…At a trigger junction, after breaking the liquid-air meniscus until compelling upstream retention and release, diffusive mixing of fluids' molecules can lead to sam dilution, washing buffer contamination, and experiencing non-lateral flow patterns do stream [8]. A mediator gap filled by air can isolate the liquids to avoid these issues However, utilizing an air gap can later result in bubbles entering the circuit and micr idic malfunction [8]. Therefore, a deliberate valve configuration is required to displac air and avoid introducing bubbles (Figure 1); this workflow is discussed in the next sec and illustrated in Figure 3a-e.…”

“…On the other hand, lateral flow diagnostic tests rely on paper-based microfluidics, a broadly used inexpensive diagnostic substrate utilizing capillary wicking, and pre-dried reagents, which mostly provide qualitative yes/no signals for a wide range of analytes [ 5 , 6 ]. Recently, the combination of reagent manipulation by capillary-driven microfluidics (channel-based) and the lateral flow immunoassays presented the enzymatic amplificated quantitative POC detections [ 7 , 8 , 9 ]. For example, a quantitative measurement for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies [ 7 ], and benzodiazepine drug abuse detection using quantum-dot-labeled antibodies [ 8 ] were reported.…”

“…Recently, the combination of reagent manipulation by capillary-driven microfluidics (channel-based) and the lateral flow immunoassays presented the enzymatic amplificated quantitative POC detections [ 7 , 8 , 9 ]. For example, a quantitative measurement for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies [ 7 ], and benzodiazepine drug abuse detection using quantum-dot-labeled antibodies [ 8 ] were reported. These new studies prospect that appending lateral flow into the preprogrammed capillary-driven chips has great potential for future POC devices.…”