Integrating Bio-Sensing Array with Blood Plasma Separation on a Centrifugal Platform.

Numerous immunoassays have been successfully integrated on disc-based centrifugal platforms (CDs) over the last 20 years. These CD devices can be used as portable point-of-care (POC) platforms with sample-to-answer capabilities where bodily fluids such as whole blood can be used as samples directly without pre-processing. In order to use whole blood as a sample on CDs, centrifugation is used to separate red blood cells from plasma on CDs. There are several techniques for using specific fluidic patterns in the centrifugal fluidic network, such as reciprocation, that enhances the sensitivity of the immunoassays, including those using microarray antigen membranes. Present work demonstrates, for the first time, simultaneous integration of blood plasma separation (BPS) and reciprocation on the CD platform. The integrated design allows plasma that is separated from the red blood cells in a sedimentation chamber to flow into the reciprocation chamber via a narrow connecting channel of 0.5 mm × 0.5 mm cross-section. Due to the small cross-section of the connecting channel, there is no inflow of the red blood cell into the reciprocation chamber during subsequent fluidic operations of the CD. While no inflow of the red blood cells into the reciprocation chamber was observed, the conditions of 20 g jerk acceleration were also simulated in ANSYS finite element analysis software, and it was found that the CD design that was used is capable of retaining red blood cells in the sedimentation chamber. Experimentally, the isolation of red blood cells in the sedimentation chamber was confirmed using the ImageJ image processor to detect the visible color-based separation of the plasma from the blood. A fluorescent analyte testing on the bio-sensing array of the presented novel integrated design and on the standard reciprocation design CD was conducted for 7 min of reciprocation in each case. The test analyte was Europium Streptavidin Polystyrene analyte (10-3 mg/mL) and the microarray consisted of Biotin bovine serum albumin (BSA) dots. The fluorescent signals for the standard and integrated designs were nearly identical (within the margin of error) for the first several minutes of reciprocation, but the fluorescent signal for the integrated design was significantly higher when the reciprocation time was increased to 7 min.

Microvalves for Applications in Centrifugal Microfluidics.

Centrifugal microfluidic platforms (CDs) have opened new possibilities for inexpensive point-of-care (POC) diagnostics. They are now widely used in applications requiring polymerase chain reaction steps, blood plasma separation, serial dilutions, and many other diagnostic processes. CD microfluidic devices allow a variety of complex processes to transfer onto the small disc platform that previously were carried out by individual expensive laboratory equipment requiring trained personnel. The portability, ease of operation, integration, and robustness of the CD fluidic platforms requires simple, reliable, and scalable designs to control the flow of fluids. Valves play a vital role in opening/closing of microfluidic channels to enable a precise control of the flow of fluids on a centrifugal platform. Valving systems are also critical in isolating chambers from the rest of a fluidic network at required times, in effectively directing the reagents to the target location, in serial dilutions, and in integration of multiple other processes on a single CD. In this paper, we review the various available fluidic valving systems, discuss their working principles, and evaluate their compatibility with CD fluidic platforms. We categorize the presented valving systems into either "active", "passive", or "hybrid"-based on their actuation mechanism that can be mechanical, thermal, hydrophobic/hydrophilic, solubility-based, phase-change, and others. Important topics such as their actuation mechanism, governing physics, variability of performance, necessary disc spin rate for valve actuation, valve response time, and other parameters are discussed. The applicability of some types of valves for specialized functions such as reagent storage, flow control, and other applications is summarized.

Capillary Flow-Driven and Magnetically Actuated Multi-Use Wax Valves for Controlled Sealing and Releasing of Fluids on Centrifugal Microfluidic Platforms.

Compact disc (CD)-based centrifugal microfluidics is an increasingly popular choice for academic and commercial applications as it enables a portable platform for biological and chemical assays. By rationally designing microfluidic conduits and programming the disc's rotational speeds and accelerations, one can reliably control propulsion, metering, and valving operations. Valves that either stop fluid flow or allow it to proceed are critical components of a CD platform. Among the valves on a CD, wax valves that liquify at elevated temperatures to open channels and that solidify at room temperature to close them have been previously implemented on CD platforms. However, typical wax valves on the CD fluidic platforms can be actuated only once (to open or to close) and require complex fabrication steps. Here, we present two new multiple-use wax valve designs, driven by capillary or magnetic forces. One wax valve design utilizes a combination of capillary-driven flow of molten wax and centrifugal force to toggle between open and closed configurations. The phase change of the wax is enabled by heat application (e.g., a 500-mW laser). The second wax valve design employs a magnet to move a molten ferroparticle-laden wax in and out of a channel to enable reversible operation. A multi-phase numerical simulation study of the capillary-driven wax valve was carried out and compared with experimental results. The capillary wax valve parameters including response time, angle made by the sidewall of the wax reservoir with the direction of a valve channel, wax solidification time, minimum spin rate of the CD for opening a valve, and the time for melting a wax plug are measured and analyzed theoretically. Additionally, the motion of the molten wax in a valve channel is compared to its theoretical capillary advance with respect to time and are found to be within 18.75% of the error margin.