Jr-Lung Lin

Integrated microfluidic systems for cell lysis, mixing/pumping and DNA amplification

The present paper reports a fully automated microfluidic system for the DNA amplification process by integrating an electroosmotic pump, an active micromixer and an on-chip temperature control system. In this DNA amplification process, the cell lysis is initially performed in a micro cell lysis reactor. Extracted DNA samples, primers and reagents are then driven electroosmotically into a mixing region where they are mixed by the active micromixer. The homogeneous mixture is then thermally cycled in a micro-PCR (polymerase chain reaction) chamber to perform DNA amplification. Experimental results show that the proposed device can successfully automate the sample pretreatment operation for DNA amplification, thereby delivering significant time and effort savings. The new microfluidic system, which facilitates cell lysis, sample driving/mixing and DNA amplification, could provide a significant contribution to ongoing efforts to miniaturize bio-analysis systems by utilizing a simple fabrication process and cheap materials.

Active micro-mixers using surface acoustic waves on Y-cut 128° LiNbO3

This study presents an active method for micro-mixers using surface acoustic waves (SAW) to rapidly mix co-fluent fluids. Mixing is challenging work in microfluidic systems due to their low-Reynolds-number flow conditions. SAW devices were fabricated on 128? Y-cut lithium niobate (LiNbO3). The micro-mixers are these piezoelectric actuators integrated with polydimethylsiloxane microchannels. The effects of the applied voltages on interdigitated transducers (IDTs) and two layouts, parallel- and transversal-type, of micro-mixers on the mixing performance were experimentally explored. The experimental results revealed that the parallel-type mixer achieved a higher mixing effect. Meanwhile, a higher applied voltage on the IDTs led to a significant improvement in the mixing performance of the active micro-mixer. Typical temperature effects associated with the applied voltages on the IDTs were also investigated. Finally, a digestion reaction between a protein (hemoglobin) and an enzyme (trypsin) was performed to verify the capability of the micro-mixers. The protein?enzyme mixture was qualitatively analyzed using mass spectrometry. Using these SAW-based mixers, the amount of digested peptides increased. Additionally, the protein?enzyme mixture was also quantitatively analyzed using high-performance liquid chromatography. Experimental data showed that the amount of digested peptides increased 21.1% using the active mixer. Therefore, the developed micro-mixers can be applied in microfluidic systems for improving mixing efficiency and thus enhancing the bio-reaction.

A vortex-type micromixer utilizing pneumatically driven membranes

Micromixers are commonly employed for chemical or biological analysis in micro-total-analysis-system applications. Mixing performance is important since it allows for rapid and efficient chemical or biological reactions. This study, therefore, reports a new vortex-type micromixer which utilizes pneumatically driven membranes to generate a swirling flow in a mixing chamber. The micromixer chip is fabricated by using micro-electro-mechanical-systems technology as well as a computer-numerically controlled machine for rapid prototyping. Two different membrane layouts and driving frequencies are evaluated to determine if there is a significant improvement in the mixing performance. Experimental results indicate that the mixing efficiency increases with increasing driving frequencies and the mixing time is reduced by approximately tenfold as the driving frequency increases from 1 to 6 Hz. A mixing efficiency as high as 95% can be achieved, in time periods as short as 0.6 and 0.7 s for the two- and four-membrane layouts, respectively. Furthermore, numerical simulations are also employed to characterize the swirling flow field, the concentration distribution and the mixing mechanism as well. Combined experimental data and numerical results illustrate the fluid dynamic phenomena that allow for rapid mixing in this vortex-type micromixer.

Numerical simulation of electrokinetic focusing in microfluidic chips

In this paper, we adopt the Nernst–Planck equation and the full Navier–Stokes equation in the modeling of electro-osmotic flow in microfluidic chips. A voltage control model is proposed, which achieves electrokinetic focusing in a pre-focused cross injection system and which allows the volume of the sample to be controlled. In addition to the traditional cross system, we also present a design for a novel pre-focused 1 × 3 (i.e. one sample inlet port and three outlet ports) injection system, which is capable of continuous sample switching and injection for bio-analytical applications. Using the proposed injection system, the sample may be electrokinetically pre-focused and then guided into the required outlet port by suitable manipulations of the applied voltage. The unique microfluidic chip presented within this paper has an exciting potential for use in high-throughput chemical analysis, fast sample mixing and many other applications in the field of micro-total-analysis systems.

Active micro-mixers utilizing a gradient zeta potential induced by inclined buried shielding electrodes

This study presents a new active micro-mixer which enhances the mixing efficiency by means of a gradient distribution of the surface zeta potential generated by applying a control voltage to an arrangement of inclined buried shielding electrodes. A theoretical model is developed to predict the distribution of the zeta potential and the thickness of the transition layer. The validity of this model is confirmed experimentally. Numerical simulations are performed to characterize the fluid flow patterns and to optimize the design of the micro-mixer. It is shown that optimizing the arrangement of the inclined shielding electrodes leads to a significant enhancement in the mixing performance of the active micro-mixer. The numerical results indicate that a localized flow circulation is generated when the control voltage is applied to the inclined shielding electrodes. The shape of this circulation is dependent on the distribution of the gradient zeta potential, which is determined in turn by the arrangement of the electrodes. The effect of the number of electrode pairs and the layout of the shielding electrodes on the mixing performance of the micro-mixer is explored both numerically and experimentally. It is revealed that the inclined electrode layouts with five electrode pairs provide the highest mixing efficiency of almost 93%. The active micro-mixer developed in this study represents a crucial advancement in microfluidic systems.

Active micro-mixers utilizing moving wall structures activated pneumatically by buried side chambers

In this study, a new active micro-mixer utilizing moving wall structures has been demonstrated. Rapid and reliable fabrication techniques involving standard SU-8 lithography and a polydimethylsiloxane (PDMS) replication process were employed for the formation of this micro chip device. The moving wall structures are activated pneumatically by buried side chambers which deform the channel walls and generate a rapid mixing of the confluent sample streams. The deformation of the moving wall structure can be controlled by the applied air pressure. A maximum deformation of 96.5 µm (about 96.5% of the channel width) can be achieved at an applied pressure of 50 psi for a wall structure with a width of 50 µm and a thickness of 100 µm. In this study, two pairs of moving wall structures were used for active mixing of the samples. Two dynamic operation modes, namely symmetric and asymmetric wall activation, are employed to alternately perturb the flow field and to generate a significant mixing effect. Mixing efficiency as high as 93.6% and 96.4%, respectively, can be achieved for these two modes. The effect of the operation frequency was also investigated. Experimental results indicate that the mixing efficiency increases with increasing operation frequency. However, once the operation frequency is higher than the frequency response of the device, the mixing efficiency drops sharply since the moving wall cannot be completely deflected within one actuation cycle. A numerical simulation was employed to investigate the mixing mechanism and to identify how the moving wall affected the sample flow field. Numerical data are in reasonable agreement with the experimental data with a variation less than 5%. Experimental results and numerical data indicate that the developed chip device can mix two confluent samples successfully. The development of active micro-mixers is a crucial component in many microfluidic applications.

Integrated Microfluidic Systems for DNA Analysis

This study reports the integration of an electrokinetically-driven micro-mixer with a on-chip temperature control system, and applies the integrated microfluidic chip to the DNA amplification process. Using the integrated chip, the cultured cells are initially broken down in a microanalysis reactor. Extracted DNA, primers and reagents are then driven electroosmotically into a mixing region where they are mixed by an electrokinetically-driven micro-mixer. The mixture is then cycled in a micro-PCR (polymerase chain reaction) chamber to perform DNA amplification. Experimental results show that the proposed device can automate the sample pretreatment operation for DNA amplification, thereby achieving significant time and effort savings. This novel integrated microfluidic device, which facilitates cell analysis, sample driving/mixing, and DNA amplification, could make a promising contribution to the continuing efforts aimed at miniaturizing bio-analysis systems