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.

Introduction: This paper presents a new repeatable Open-Close switch valve (SV) for the CD microfluidic platforms. The SV is designed by using a combination of controlled phase change and capillary flow of Ferrowax. The phase change of the wax is controlled using a laser. When the wax is illuminated with a laser, the energy of the laser is absorbed by the Ferro particles embedded inside the wax, causing the wax to melt. The melted wax can spontaneously wick through capillary channels due to its low contact angle. The Open-Close nature of the valve is attained by rationally designing the capillary flow path of the wax. The capillary flow path design is such a way that the melted wax is directed to the open fluidic path (Normally open configuration) to block the channel (Close configuration). The reversal of the blocking is achieved by remelting the wax and driving it to the overflow chamber downstream. A unique wax flow path is also designed to enhance the capillary flow and the response time of the valve. Background: Centrifugal platform-based CD fluidics has created a new paradigm of inexpensive point-of-care diagnostics[1]. It is now widely used in applications like polymerase chain reaction assays, blood plasma separation, etc.[2,3] Since CD fluidics has presented an innovation in point-of-care diagnostics, it is essential to have a proper valving system for reliable opening/closing of the channels. Currently, there are two main types of valves in the CD platform: laser valves and z-axis wax valves. Both of these valves are good for one-time use only and have complex fabrication routes. Therefore, there is a need for simple, reusable SV in CD fluidic platforms. Theory: The capillary pressure drives the capillary flow in a channel. The capillary pressure difference between atmosphere and the liquid meniscus inside a rectangular microchannel (Pc) is given by Young-Laplace’s equation: -Pc = 2γ(cosθ)(1/w+1/h) (1) where γ is the surface tension, θ is the contact angle with the channel material, w is the width of the channel, and h is the height of the channel. In this design, the resistance offered by the trailing liquid is given by the equation: Rhyd = 12μL/(h3w*(1-0.63(h/w)) (2) For capillary flow, the flow rate (Q) can be obtained by Q = wh(dL/dt) = -Pc/Rhyd (3) For a shallow channel (h<<w), we can neglect the terms containing 1/w, giving the following simplified equation for the flow velocity dL/dt = γ(cosθ)h/(6μL) (4) Upon integration, the fluid length at an instant t is obtained L = √(γht(cosθ)/3μ) = W√t (5) where W is the Washburn’s constant. We use a new channel design and a flexible adhesive film, and the modified channel shows significant improvement in the capillary flow velocity. A modified empirical model capturing this effect is currently being developed. Materials and Method: The channels and the chambers are milled on an acrylic sheet of thickness 3 mm using Tormac PCNC CNC milling machine (Fig 1a). The Ferro-wax is prepared by mixing Sigma Aldrich Paraffin wax (MP 53 - 37oC) with Ferrofluid (Ferrotec EFHI 60 cc) at the ratio of 2:1 and stirring the mixture at 65oC for 12 hours. The mixture is brought down to room temperature and placed inside the designated chamber. Then, the CD is laminated using a single side pressure-sensitive adhesive (Fig 1a). To achieve Close configuration (Fig 1b), the wax inside the CD is heated up for 5 minutes at 65oC. The melted wax flows to the reagent flow path and solidifies to block the channel. Remelting the wax and directing the melted wax to the overflow chamber brings the valve back to the Open configuration (Fig 1b). The unique channel edges for enhanced capillary flow are fabricated by applying two layers of tape (Fig 1a). Experimental Results:- Experimental characterization of SV was performed by fabricating channels having cross-section areas ranging from 0.05 to 0.625 mm2. A 2.32 W laser placed at a distance of 3 mm from the top surface of the CD is used for heating the Ferrowax. The Normally Close configuration (Fig 1b) is achieved by heating the wax inlet chamber for 5 minutes at 65oC. The wax is driven to the reagent channel by moving along the edge gaps of the wax chamber. The solidified wax prevents the fluid from moving downstream. The sequential release of the reagent is achieved using SV as shown (Fig 1c, 5). A ‘teeth’ design is used at the bottom of the wax inlet to avoid bubble formation inside the chamber. This teeth design also ensures a large number of Open-Close operations for a given amount of wax. Finally, we demonstrate the fidelity of the SV closure (Close configuration) on the CD platform on upwards of 7000 RPM. A parametric study of the air gap is being carried out to determine an optimized design for a faster response. References [1] Gorkin, Robert, Jiwoon Park, Jonathan Siegrist, Mary Amasia, Beom Seok Lee, Jong-Myeon Park, Jintae Kim, Hanshin Kim, Marc Madou, and Yoon-Kyoung Cho. "Centrifugal microfluidics for biomedical applications." Lab on a Chip 10, no. 14 (2010): 1758-1773. doi:10.1039/B924109D [2] Amasia, Mary, and Marc Madou. "Large-volume centrifugal microfluidic device for blood plasma separation." Bioanalysis 2, no. 10 (2010): 1701-1710. doi:10.4155/bio.10.140 [3] Noroozi, Zahra, Horacio Kido, Régis Peytavi, Rie Nakajima-Sasaki, Algimantas Jasinskas, Miodrag Micic, Philip L. Felgner, and Marc J. Madou. "A multiplexed immunoassay system based upon reciprocating centrifugal microfluidics." Review of Scientific Instruments 82, no. 6 (2011): 064303. doi: 10.1063/1.3597578 Figure 1

Implementation of geometric nonlinearity in micro-electro-mechanical system (MEMS) resonators offers a flexible and efficient design to overcome the limitations of linear MEMS by utilizing beneficial nonlinear characteristics not attainable in a linear setting. Integration of nonlinear coupling elements into an otherwise purely linear microcantilever is one promising way to intentionally realize geometric nonlinearity. Here, we demonstrate that a nonlinear, heterogeneous micro-resonator system, consisting of a silicon micro-cantilever with a polymer attachment exhibits strong nonlinear hardening behavior not only in the first flexural mode but also in the higher modes (i.e., second and third flexural modes). In this design, we deliberately implement a drastic and reversed change in the axial vs. bending stiffness between the Si and polymer components by varying the geometric and material properties. By doing so, the resonant oscillations induce the large axial stretching within the polymer component, which effectively introduces the geometric stiffness and damping nonlinearity. The efficacy of the design and the mechanism of geometric nonlinearity are corroborated through a comprehensive experimental, analytical, and numerical (Finite Element) analysis on the nonlinear dynamics of the proposed system. 2

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.

In micro/nanometer scale mechanical resonators, constructive utilization of intentional nonlinearity has suggested ways to leverage beneficial nonlinear characteristics in their design for various applications. Previous studies have also shown that the geometric nonlinearity is effectively implemented and tailored through integration of nonlinear couplings to an otherwise linear microcantilever. Here, we demonstrate experimentally a nonlinear micromechanical resonator consisting of a silicon microcantilever axially constrained by a polymer attachment exhibiting a strong nonlinear hardening behavior not only in its first flexural mode but also in higher modes. A theoretical model representing the system with geometrically nonlinear stiffness and damping is analyzed by the method of multiple scales, which is favorably validated by good agreement with experimentally obtained nonlinear responses.

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.

No abstract