Development of Active Centrifugal Pump for Microfluidic CD Platforms.

The continuous emerging of microfluidic compact disc (CD) platforms for various real-life applications motivates researchers to explore new innovative ideas towards more integrated active functions. However, microfluidic CDs have some drawbacks, including the unidirectional flow that limits the usable space for multi-stepped biological and chemical assays. In this work, a novel active and bidirectional centrifugal pump is developed and integrated on microfluidic CDs. The design of the developed pump partially replicates the designs of the conventional centrifugal pumps with a modification in the connecting channels' positions that allow the developed pump to be reversible. The main advantage of the proposed centrifugal pump is that the pumping speed can be accurately controlled during spinning or while the microfluidic CD is stationary. Performance tests show that the pumping speed can reach up to 164.93 mm3/s at a pump rotational speed (impellers speed) of 4288 rpm. At that speed, 1 mL of water could be pumped in 6.06 s. To present a few of the potential applications of the centrifugal pump, flow reciprocation, bidirectional pumping, and flow switching were performed and evaluated. Results show that the developed centrifugal pump can pump 1096 µL of liquid towards the CD center at 87% pumping efficiency while spinning the microfluidic CD at 250 rpm. This novel centrifugal pump can significantly widen the range of the applicability of microfluidic CDs in advanced chemical processes and biological assays.

Enhanced inertial focusing of microparticles and cells by integrating trapezoidal microchambers in spiral microfluidic channels.

In this work, manipulating width and equilibrium position of fluorescent microparticles in spiral microchannel fractionation devices by embedding microchambers along the last turn of a spiral is reported. Microchambers with different shapes and sizes were tested at Reynolds numbers between 15.7 and 156.6 (100-1000 µL min-1) to observe focusing of 2, 5 and 10 µm fluorescent microparticles. This paper also discusses the fabrication process of the microfluidic chips with femtosecond laser ablation on glass wafers, as well as a particle imaging velocimetry (µPIV) study of microparticle trajectories inside a microchamber. It could be demonstrated with an improved final design with inclined microchamber side walls, that the 2 µm particle equilibrium position is shifted towards the inner wall by ∼27 µm and the focusing line's width is reduced by ∼18 µm. Finally, Saccharomyces cerevisiae yeast cells were tested in the final chip and a cell focusing efficiency of 99.1% is achieved.

Spiral Microchannels with Trapezoidal Cross Section Fabricated by Femtosecond Laser Ablation in Glass for the Inertial Separation of Microparticles.

The fabrication and testing of spiral microchannels with a trapezoidal cross section for the passive separation of microparticles is reported in this article. In contrast to previously reported fabrication methods, the fabrication of trapezoidal spiral channels in glass substrates using a femtosecond laser is reported for the first time in this paper. Femtosecond laser ablation has been proposed as an accurate and fast prototyping method with the ability to create 3D features such as slanted-base channels. Moreover, the fabrication in borosilicate glass substrates can provide high optical transparency, thermal resistance, dimensional stability, and chemical inertness. Post-processing steps of the laser engraved glass substrate are also detailed in this paper including hydrogen fluoride (HF) dipping, chemical cleaning, surface activation, and thermal bonding. Optical 3D images of the fabricated chips confirmed a good fabrication accuracy and acceptable surface roughness. To evaluate the particle separation function of the microfluidic chip, 5 µm, 10 µm, and 15 µm particles were focused and recovered from the two outlets of the spiral channel. In conclusion, the new chemically inert separation chip can be utilized in biological or chemical processes where different sizes of cells or particles must be separated, i.e., red blood cells, circulating tumor cells, and technical particle suspensions.

New generation of spinning systems for robust active mixing on microfluidic CDs: oil/water emulsion as an evaluation test.

Microfluidic CDs (or Lab-on-Disc) continue to emerge in various applications of real life sciences, including biomedical and pharmaceutical fields. However, microfluidic CDs with advanced and efficient unit operation tools, such as pumping, valving, and mixing, need to be implemented to achieve the required applications in these fields. In this work, a novel generation of a spinning system to perform robust active mixing is developed for microfluidic CDs. The developed system is equipped with a dual-motor and dual-CD configuration to perform magnetically driven active mixing. The results show that the developed spinning system can provide a wide range of mixing frequencies independent of the spinning speed of the microfluidic CD. To evaluate the performance of this system under extreme conditions, an emulsion process of oil and water was conducted. Although the oil produced high drag force on the mixing magnet, the emulsion process successfully reached a steady state of mixing within a few seconds (approximately 3.5 s), and the mixture became homogeneous at 75 seconds. To demonstrate one of the potential applications of the proposed developed spinning setup, microparticles were successfully extracted from water to oil using water/oil emulsion on the microfluidic CD. In conclusion, mixing can be performed without influencing the integrated microfluidic components such as valves or pumps. This improvement can widen the range of applicability of microfluidic CDs in multi-step and complex processes where mixing is essential.

Low Cost Lab on Chip for the Colorimetric Detection of Nitrate in Mineral Water Products.

The diagnostics of health status and the quality of drinking water are among the most important United Nations sustainable development goals. However, in certain areas, wars and instability have left millions of people setting in refugee camps and dangerous regions where infrastructures are lacking and rapid diagnostics of water quality and medical status are critical. In this work, microfluidic testing chips and photometric setups are developed in cheap and portable way to detect nitrate concentrations in water. The performed test is designed to work according to the Griess procedure. Moreover, to make it simple and usable in areas of low resource settings, commercially available Arduino mega and liquid crystal display (LCD) shield are utilized to process and display results, respectively. For evaluation purposes, different local products of tap water, bottled drinking water, and home-filter treated water samples were tested using the developed setup. A calibration curve with coefficient of determination (R²) of 0.98 was obtained when absorbance of the prepared standard solutions was measured as a function of the concentrations. In conclusion, this is the first step towards a compact, portable, and reliable system for nitrate detection in water for point-of-care applications.

Design and Development of Micro-Power Generating Device for Biomedical Applications of Lab-on-a-Disc.

The development of micro-power generators for centrifugal microfluidic discs enhances the platform as a green point-of-care diagnostic system and eliminates the need for attaching external peripherals to the disc. In this work, we present micro-power generators that harvest energy from the disc's rotational movement to power biomedical applications on the disc. To implement these ideas, we developed two types of micro-power generators using piezoelectric films and an electromagnetic induction system. The piezoelectric-based generator takes advantage of the film's vibration during the disc's rotational motion, whereas the electromagnetic induction-based generator operates on the principle of current generation in stacks of coil exposed to varying magnetic flux. We have successfully demonstrated that at the spinning speed of 800 revolutions per minute (RPM) the piezoelectric film-based generator is able to produce up to 24 microwatts using 6 sets of films and the magnetic induction-based generator is capable of producing up to 125 milliwatts using 6 stacks of coil. As a proof of concept, a custom made localized heating system was constructed to test the capability of the magnetic induction-based generator. The heating system was able to achieve a temperature of 58.62 °C at 2200 RPM. This development of lab-on-a-disc micro power generators preserves the portability standards and enhances the future biomedical applications of centrifugal microfluidic platforms.

Sequential push-pull pumping mechanism for washing and evacuation of an immunoassay reaction chamber on a microfluidic CD platform.

A centrifugal compact disc (CD) microfluidic platform with reservoirs, micro-channels, and valves can be employed for implementing a complete immunoassay. Detection or biosensor chambers are either coated for immuno-interaction or a biosensor chip is inserted in them. On microfluidic CDs featuring such multi-step chemical/biological processes, the biosensor chamber must be repeatedly filled with fluids such as enzymes solutions, buffers, and washing solutions. After each filling step, the biosensor chamber needs to be evacuated by a passive siphoning process to prepare it for the next step in the assay. However, rotational speed dependency and limited space on a CD are two big obstacles to performing such repetitive filling and siphoning steps. In this work, a unique thermo-pneumatic (TP) Push-Pull pumping method is employed to provide a superior alternative biosensor chamber filling and evacuation technique. The proposed technique is demonstrated on two CD designs. The first design features a simple two-step microfluidic process to demonstrate the evacuation technique, while the second design shows the filling and evacuation technique with an example sequence for an actual immunoassay. In addition, the performance of the filling and evacuation technique as a washing step is also evaluated quantitatively and compared to the conventional manual bench top washing method. The two designs and the performance evaluation demonstrate that the technique is simple to implement, reliable, easy to control, and allows for repeated push-pulls and thus filling and emptying of the biosensor chamber. Furthermore, by addressing the issue of rotational speed dependency and limited space concerns in implementing repetitive filling and evacuation steps, this newly introduced technique increases the flexibility of the microfluidic CD platform to perform multi-step biological and chemical processes.

Development of a passive liquid valve (PLV) utilizing a pressure equilibrium phenomenon on the centrifugal microfluidic platform.

In this paper, we propose an easy-to-implement passive liquid valve (PLV) for the microfluidic compact-disc (CD). This valve can be implemented by introducing venting chambers to control the air flow of the source and destination chambers. The PLV mechanism is based on equalizing the main forces acting on the microfluidic CD (i.e., the centrifugal and capillary forces) to control the burst frequency of the source chamber liquid. For a better understanding of the physics behind the proposed PLV, an analytical model is described. Moreover, three parameters that control the effectiveness of the proposed valve, i.e., the liquid height, liquid density, and venting chamber position with respect to the CD center, are tested experimentally. To demonstrate the ability of the proposed PLV valve, microfluidic liquid switching and liquid metering are performed. In addition, a Bradford assay is performed to measure the protein concentration and evaluated in comparison to the benchtop procedure. The result shows that the proposed valve can be implemented in any microfluidic process that requires simplicity and accuracy. Moreover, the developed valve increases the flexibility of the centrifugal CD platform for passive control of the liquid flow without the need for an external force or trigger.

Liquid density effect on burst frequency in centrifugal microfluidic platforms.

Centrifugal microfluidic platforms are widely used in various advanced processes such as biomedical diagnostics, chemical analysis and drug screening. This paper investigates the effect of liquid density on the burst frequency of the centrifugal microfluidic platform. This effect is experimentally investigated and compared to theoretical values. It is found that increasing the liquid density results in lower burst frequency and it is in agreement with theoretical calculations. Moreover, in this study we proposed the use of the microfluidic CD platform as an inexpensive and simple sensor for liquid density measurements. The proposed liquid sensor requires much less liquid volume (in the range of microliters) compared to conventional density meters. This study presents fundamental work which allows for future advance studies with the aim of designing and fabricating centrifugal microfluidic platforms for more complex tasks such as blood analysis.

Latex micro-balloon pumping in centrifugal microfluidic platforms.

Centrifugal microfluidic platforms have emerged as point-of-care diagnostic tools. However, the unidirectional nature of the centrifugal force limits the available space for multi-step processes on a single microfluidic disc. To overcome this limitation, a passive pneumatic pumping method actuated at high rotational speeds has been previously proposed to pump liquid against the centrifugal force. In this paper, a novel micro-balloon pumping method that relies on elastic energy stored in a latex membrane is introduced. It operates at low rotational speeds and pumps a larger volume of liquid towards the centre of the disc. Two different micro-balloon pumping mechanisms have been designed to study the pump performance at a range of rotational frequencies from 0 to 1500 rpm. The behaviour of the micro-balloon pump on the centrifugal microfluidic platforms has been theoretically analysed and compared with the experimental data. The experimental data show that the developed pumping method dramatically decreases the required rotational speed to pump liquid compared to the previously developed pneumatic pumping methods. It also shows that within a range of rotational speed, a desirable volume of liquid can be stored and pumped by adjusting the size of the micro-balloon.

Novel liquid equilibrium valving on centrifugal microfluidic CD platform.

One of the main challenges faced by researchers in the field of microfluidic compact disc (CD) platforms is the control of liquid movement and sequencing during spinning. This paper presents a novel microfluidic valve based on the principle of liquid equilibrium on a rotating CD. The proposed liquid equilibrium valve operates by balancing the pressure produced by the liquids in a source and a venting chamber during spinning. The valve does not require external forces or triggers, and is able to regulate burst frequencies with high accuracy. In this work, we demonstrate that the burst frequency can be significantly raised by making just a small adjustment of the liquid height in the vent chamber. Finally, the proposed valve ng method can be used separately or combined with other valving methods in advance microfluidic processes.

Multi-level 3D implementation of thermo-pneumatic pumping on centrifugal microfluidic CD platforms.

Thermo-pneumatic (TP) pumping is a method employing the principle of expanding heated air to transfer fluids back towards the CD center on the centrifugal microfluidic CD platform. While the TP features are easy to fabricate as no moving parts are involved, it consumes extra real estate on the CD, and because heating is involved, it introduces unnecessary heating to the fluids on the CD. To overcome these limitations, we introduce a multi-level 3D approach and implement forced convection heating. In a multi-level 3D CD, the TP features are relocated to a separate top level, while the microfluidic process remains on a lower bottom level. This allows for heat shielding of the fluids in the microfluidic process level, and also improve usage of space on the CD. To aid in future implementations of TP pumping on a multi-level 3D CD, studies on the effect of heat source setting, and the effect of positioning the TP feature (it distance from the CD center) on CD surface heating are also presented. In this work, we successfully demonstrate a multi-level 3D approach to implement TP pumping on the microfluidic CD platform.

Push pull microfluidics on a multi-level 3D CD.

A technique known as thermo-pneumatic (TP) pumping is used to pump fluids on a microfluidic compact disc (CD) back towards the CD center against the centrifugal force that pushes liquids from the center to the perimeter of the disc. Trapped air expands in a TP air chamber during heating, and this creates positive pressure on liquids located in chambers connected to that chamber. While the TP air chamber and connecting channels are easy to fabricate in a one-level CD manufacturing technique, this approach provides only one way pumping between two chambers, is real-estate hungry and leads to unnecessary heating of liquids in close proximity to the TP chamber. In this paper, we present a novel TP push and pull pumping method which allows for pumping of liquid in any direction between two connected liquid chambers. To ensure that implementation of TP push and pull pumping also addresses the issue of space and heating challenges, a multi-level 3D CD design is developed, and localized forced convection heating, rather than infra-red (IR) is applied. On a multi-level 3D CD, the TP features are placed on a top level separate from the rest of the microfluidic processes that are implemented on a lower separate level. This approach allows for heat shielding of the microfluidic process level, and efficient usage of space on the CD for centrifugal handling of liquids. The use of localized forced convection heating, rather than infra-red (IR) or laser heating in earlier implementations allows not only for TP pumping of liquids while the CD is spinning but also makes heat insulation for TP pumping and other fluidic functions easier. To aid in future implementations of TP push and pull pumping on a multi-level 3D CD, study on CD surface heating is also presented. In this contribution, we also demonstrate an advanced application of pull pumping through the implementation of valve-less switch pumping.

Vacuum/compression valving (VCV) using parrafin-wax on a centrifugal microfluidic CD platform.

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control.

Theoretical development and critical analysis of burst frequency equations for passive valves on centrifugal microfluidic platforms.

This paper presents a theoretical development and critical analysis of the burst frequency equations for capillary valves on a microfluidic compact disc (CD) platform. This analysis includes background on passive capillary valves and the governing models/equations that have been developed to date. The implicit assumptions and limitations of these models are discussed. The fluid meniscus dynamics before bursting is broken up into a multi-stage model and a more accurate version of the burst frequency equation for the capillary valves is proposed. The modified equations are used to evaluate the effects of various CD design parameters such as the hydraulic diameter, the height to width aspect ratio, and the opening wedge angle of the channel on the burst pressure.