Bruce K. Gale

Determining the optimal PDMS–PDMS bonding technique for microfluidic devices

A number of polydimethysiloxane (PDMS) bonding techniques have been reported in the literature over the last several years as the focus on multilayer PDMS microfluidic devices has increased. Oxygen plasma bonding, despite cost, additional fabrication time and inconsistent bonding results, has remained a widely used method for bonding PDMS layers. A comparative study of four rapid, inexpensive alternative PDMS?PDMS bonding approaches was undertaken to determine relative bond strength. These include corona discharge, partial curing, cross-linker variation and uncured PDMS adhesive. Partial curing and uncured PDMS adhesive demonstrated a considerable improvement in bond strength and consistency by retaining average bond strengths of over 600 kPa, which was more than double the average bond strength of oxygen plasma. A description of each technique and their performance relative to oxygen plasma bonding is included.

Microfluidic sample preparation: cell lysis and nucleic acid purification.

Due to the lack of development in the area of sample preparation, few complete lab-on-a-chip systems have appeared in recent years that can deal with raw samples. Cell lysis and nucleic acid extraction systems are sufficiently complex even before adding the complexity of an analysis system. In this review, a variety of microfluidic sample preparation methods are discussed and evaluated. Microsystems for cell lysis are discussed by grouping them into categories based on their lysis mechanisms: mechanical, chemical, thermal or electrical. We classify the nucleic acid purification techniques according to the mechanism that links nucleic acids to substrates: silica-based surface affinity, electrostatic interaction, nanoporous membrane filtration, and functionalized microparticles. The techniques for microfluidic cell lysis and nucleic acid purification are compared based on the ease of microfabrication and integration, and sample flexibility. These assessments can help us determine the appropriate sample preparation technique for generating a true lab-on-a-chip.

A monolithic PDMS waveguide system fabricated using soft-lithography techniques

A monolithic waveguide system using poly(dimethyl siloxane) (PDMS) was designed, fabricated, and characterized. The waveguide demonstrated good confinement of light and relatively low attenuation at 0.40 dB/cm. The robustness and handling properties of the completed waveguides were excellent, and the process yield exceeded 96%. The waveguide did exhibit moderate temperature and humidity sensitivity but no temporal variation, and insertion loss remained stable over extended periods of time. Applications of this waveguide system in microscale sensing are immense, judging by the frequency of use of PDMS as the substrate for microfluidic and biomedical systems. The monolithic nature of the waveguides also reduces their cost and allows integration of optical pathways into existing PDMS-based microsystems.

Spinning disk platform for microfluidic digital polymerase chain reaction.

An inexpensive plastic disk disposable was designed for digital polymerase chain reaction (PCR) applications with a microfluidic architecture that passively compartmentalizes a sample into 1000 nanoliter-sized wells by centrifugation. Well volumes of 33 nL were attained with a 16% volume coefficient of variation (CV). A rapid air thermocycler with aggregate real-time fluorescence detection was used, achieving PCR cycle times of 33 s and 94% PCR efficiency, with a melting curve to validate product specificity. A CCD camera acquired a fluorescent image of the disk following PCR, and the well intensity frequency distribution and Poisson distribution statistics were used to count the positive wells on the disk to determine the number of template molecules amplified. A 300 bp plasmid DNA product was amplified within the disk and analyzed in 50 min with 58-1000 wells containing plasmid template. Target concentrations measured by the spinning disk platform were 3 times less than that predicted by absorbance measurements. The spinning disk platform reduces disposable cost, instrument complexity, and thermocycling time compared to other current digital PCR platforms.

A PDMS-based gas permeation pump for on-chip fluid handling in microfluidic devices

We demonstrate a non-contact pumping mechanism for the manipulation of aqueous solutions within microfluidic devices. The method utilizes multi-layer soft lithography techniques to integrate a thin polydimethylsiloxane (PDMS) membrane that acts as a diffusion medium for regulated air pressure and a vacuum. Pressurized microchannels filter air through the PDMS membrane due to its high gas permeability causing a pressure difference in the liquid channel and generating flow. Likewise, a vacuum can be applied to pull air through the membrane allowing the filling of dead-end channels and the removal of bubbles. Flow rates vary according to applied pressure/vacuum, membrane thickness and diffusion area. A gas permeation pump is an inexpensive alternative to other micropumps. The pump is easily integrated with highly arrayed multi-channel/chamber applications for micro-total analysis systems, fluid metering and dispensing, and drug delivery. Flow rates of 200 nl min−1 have been achieved using this technique. Successful localized fluid turning at intersections, fluid metering and filling of dead-end chambers were also demonstrated.

Characterization of interconnects used in PDMS microfluidic systems

This paper reports the characterization of a microfluidic packaging technique involving the use of press-fit interconnects to microfluidic channels molded in PDMS. This packaging technique is implemented by, first, coring a small hole in the PDMS to access molded or buried microchannels using a modified 20 gauge needle; and second, inserting an unmodified needle into the hole to create a direct connection to the microchannel that requires no bonding or molding. The needles can then easily be removed and reinserted multiple times since the seal is created purely by the compression of the PDMS around the needle. The luer fitting on the needles can easily be connected to standard fluid fittings. The quality of the interconnects is correlated with observations of the PDMS after coring. Methods of coring examined include pushing straight through and twisting the coring tool by hand or by machine. These comparisons demonstrated that all methods can produce viable interconnects; however, machine coring was the most consistent. The interconnects were characterized mechanically primarily by measuring their leak resistance under pressure. Leak tests were performed on interconnects (1) fabricated using different methods, (2) experiencing rotation or bending and (3) fabricated at various linear densities. Static pressure testing revealed that interconnect pressure limits varied from 100 kPa to over 700 kPa depending on the fabrication method. Suggestions are presented on how the technique could be modified to reach much higher pressures. Interconnect flexibility testing demonstrated a minimum of 30° of bending and a maximum of 60° before failure depending on the direction rotated. Density testing showed that PDMS was strong enough to allow at least six interconnects on a 1 cm linear channel.

Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery

Solid silicon microneedle arrays with different needle lengths (ranging from 100 to 1100 microm) and needle densities (ranging from 400 to 11,900 needles/cm(2)) were used to penetrate epidermal membrane of human cadaver skin. After this pretreatment, the electrical resistance of the skin and the flux of acyclovir across the skin were monitored. A linear correlation between the acyclovir flux and the inverse of the skin electric resistance was observed. Microneedle arrays with longer needles (>600 microm) were more effective in creating pathways across skin and enhancing drug flux, and microneedle arrays with lower needle densities (<2000 needles/cm(2)) were more effective in enhancing drug flux if the microneedles with long enough needle length (>600 microm). In addition, the microneedle arrays were used to penetrate hairless rat skin in vivo, and the trans-epidermal water loss (TEWL) of the rat skin was measured before and after the pretreatment. Treating rat skin with microneedle arrays of lower needle density and longer needle length was more effective in increasing TEWL. Integrity of the stratum corneum barrier of the penetrated rat skin as measured by TEWL recovered back to its base line level within 24h after the microneedle pretreatment.

Rapid prototyping of microfluidic systems using a PDMS/polymer tape composite

Rapid prototyping of microfluidic systems using a combination of double-sided tape and PDMS (polydimethylsiloxane) is introduced. PDMS is typically difficult to bond using adhesive tapes due to its hydrophobic nature and low surface energy. For this reason, PDMS is not compatible with the xurography method, which uses a knife plotter and various adhesive coated polymer tapes. To solve these problems, a PDMS/tape composite was developed and demonstrated in microfluidic applications. The PDMS/tape composite was created by spinning it to make a thin layer of PDMS over double-sided tape. Then the PDMS/tape composite was patterned to create channels using xurography, and bonded to a PDMS slab. After removing the backing paper from the tape, a complete microfluidic system could be created by placing the construct onto nearly any substrate; including glass, plastic or metal-coated glass/silicon substrates. The bond strength was shown to be sufficient for the pressures that occur in typical microfluidic channels used for chemical or biological analysis. This method was demonstrated in three applications: standard microfluidic channels and reactors, a microfluidic system with an integrated membrane, and an electrochemical biosensor. The PDMS/tape composite rapid prototyping technique provides a fast and cost effective fabrication method and can provide easy integration of microfluidic channels with sensors and other components without the need for a cleanroom facility.

Effects of rectangular microchannel aspect ratio on laminar friction constant

In this paper, the effects of rectangular microchannel aspect ratio on laminar friction constant are described. The behavior of fluids was studied using surface micromachined rectangular metallic pipette arrays. Each array consisted of 5 or 7 pipettes with widths varying from 150 micrometers to 600 micrometers and heights ranging from 22.71 micrometers to 26.35 micrometers . A downstream port for static pressure measurement was used to eliminate entrance effects. A controllable syringe pump was used to provide flow while a differential pressure transducer was used to record the pressure drop. The experimental data obtained for water for flows at Reynolds numbers below 10 showed an approximate 20% increase in the friction constant for a specified driving potential when compared to macroscale predictions from the classical Navier-Stokes theory. When the experimental data are studied as a function of aspect ratio, a 20% increase in the friction constant is evident at low aspect ratios. A similar increase is shown by the currently available experimental data for low Reynolds number (< 100) flows of water.

A micromachined electrical field-flow fractionation (/spl mu/-EFFF) system

Micromachining technologies are employed to develop a miniaturized electrical field-flow fractionation (EFFF) separation system. EFFF systems are used to separate colloidal particles such as cells, liposomes, proteins, or other particulates, and to characterize emulsions and other mixtures according to particle charge density. Macromachining techniques have been used to develop existing EFFF technologies. At the present time, the limiting factor in the development of higher precision EFFF separation systems has been the manufacturing approach. In this paper, the theory behind the operation and resolution of a micron-sized EFFF (/spl mu/-EFFF) system is described and the advantages to be gained from application of micromachining technologies are given, thus motivating the need for further miniaturization. A completely fabricated /spl mu/-EFFF system is developed, separations are performed, and the /spl mu/-EFFF system is compared to the theoretically predicted results as well as the results from current macro EFFF systems.