Tzer Hwai Gilbert Thio

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.

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.

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.

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.

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.

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.

The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.

Hybrid Capillary-Flap Valve for Vapor Control in Point-of-Care Microfluidic CD

Microfluidics allows for the miniaturization of laboratory processes onto a compact disc (CD). A microfluidic CD provides a cost-effective, portable and automated diagnostic platform without the use of bulky equipment and complex machinery. This reduction in the cost, footprint, and user input allows for the development of tools suitable for point-of-care applications. One of the criteria for point-of-care applications is the ability to have long storage life. During storage, the reagents/chemicals in typical microfluidic CDs might evaporate and mix together before actual usage, compromising on the integrity of the result. To complement the use of capillary valves, this paper presents various available valves for vapor control, and introduces a hybrid capillary-flap valve for use in microfluidic CDs for point-of-care applications.

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.

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.