High-throughput microcapillary pump with efficient integrated low aspect ratio micropillars

Prediction and reduction of pressure drop and resistance flow in micropillar arrays are important for the design of microfluidic circuits used in different lab-on-a-chip and biomedical applications. In this work, a diamond microchannel-integrated micropillar pump (dMIMP) with a resistance flow 35.5 % lower than a circular-based micropillar pump (cMIMP) has been developed via the optimization of the fluid dynamic behavior of different pillar shapes in a low aspect ratio (H/D ranged from 0.06 to 0.2) integrated pillar microchannel. The effect of different geometrical parameters (such as pillar shape and its distribution) has been considered to minimize the microchannel resistance flow. Six-micrometer-depth polidimetilsiloxane (PDMS) channels have been fabricated using a modified soft lithography process, which prevents the PDMS deformation under high-pressure operation. Flow through the fabricated samples has been numerically solved and experimentally measured, with an agreement higher than 90 %. The results have been used to validate the derived analytical formulation to determine the flow resistance in this type of channels, a fast approach to obtain the resistance flow in the design stage of microdevices. The analysis of the results indicates that, although porosity can be a determinant parameter to predict the resistance flow of MIMP, other geometrical parameters such as side distance between pillars and pillar shape play a major role in this scenario. Finally, a high-throughput optimized diamond MIMP pump has been designed, tested and validated as a capillary pump, showing that it can provide a flow rate 73 % higher than a circular MIMP pump.     

Optically induced electrohydrodynamic instability-based micro-patterning of fluidic thin films

Projected light patterns are used to induce electrohydrodynamic instabilities in a polymer thin film sandwiched between two electrodes. Using this optically induced electrohydrodynamic instability (OEHI) phenomenon, we have successfully demonstrated rapid, microscale patterning of polydimethylsiloxane (PDMS) pillar arrays on a thin-film hydrogenated amorphous silicon layer on top of an indium titanium oxide glass substrate. This glass substrate is the bottom electrode in a two-electrode, parallel-plate capacitor configuration with a micron-scale gap. Within this gap are a thin film of spin-coated PDMS and a thin layer of air. Primary pillar growth is first observed within 5–90 s in the dark regions of the projected patterns and pillar growth eventually spreads to the illuminated regions when the initial PDMS thickness is <2 μm. Experimental data characterizing the change in pillar diameters (between 15 and 30 μm in diameter) show that they can be decoupled from the inter-pillar spacing (maintaining a constant ~84 μm pitch between pillar centers) by controlling the applied DC voltage (between 110 and 210 V). Experimental results also show the importance of the optically induced lateral electric field on controlling pillar formation. This OEHI method of rapid pillar generation, with voltage control of the pillar diameter and control of pillar position via projected light patterns, presents new opportunities for low cost, efficient, and simple fabrication of micro, and perhaps nanoscale, polymer structures that could be used in many bioMEMS applications.     

Microfluidic system for electroelution of proteins from a clinical sampling strip

A clinical methylcellulose sampling strip is one of the popular means for collecting gingival crevicular fluid (GCF) from dental patients for dental disease diagnosis. In this research, a microfluidic device for protein elution from a sampling strip was fabricated with poly (dimethylsiloxane) (PDMS) polymer. Electoelution experiments were performed with fluorescein isothiocyanate (FITC) dye labeled bovine serum albumin (BSA) and ovalbumin (OVA). The total amount of eluted protein is measured by quantitative fluorescence imaging. About 50% of the initial concentration of BSA and OVA was eluted by the ~20 V/cm electric field. Electroelution is an appealing method for protein elution; however, the thickness of the wet strip (~400 μm) introduces interesting practical difficulties. During the electroelution process, unsteady electrokinetic phenomena by the pressure driven flow and the pH change of the reservoirs were observed. Several possible solutions to these problems are still under investigation including modifying reservoirs and thin polymer film coating of PDMS channel surfaces. This electroelution device would be a useful component of a fully integrated micro total analysis system for oral fluid samples.     

Zone electrophoresis of proteins in poly(dimethylsiloxane) (PDMS) microchip coated with physically adsorbed amphiphilic phospholipid polymer

The zone electrophoresis of protein in poly(dimethylsiloxane) (PDMS) microchip coated with the physically adsorbed amphiphilic phospholipid polymer (PMMSi) was investigated. PMMSi was composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and 3-(methacryloyloxy) propyltris (trimethylsiloxy) silane (MPTSSi) units in a random fashion. The membrane of PMMSi can be formed on the PDMS surface by a simple and quick dip-coating method. The membrane showed high hydrophilicity and good stability in water, as determined by contact angle measurement, fourier-transformed infrared absorption by attenuated total reflection (ATR-FTIR), and X-ray photoelectron spectroscopy (XPS) analysis. High suppression of protein adsorption to the PDMS surface and reduction in electroosmotic flow (EOF) were achieved by PMMSi coating due to an increase of hydrophilicity, and a decrease of the ζ-potential on the surface of PDMS. For zone electrophoresis, the PMMSi30 containing 30 % hydrophilic MPC was the most suitable molecular design in terms of the stability of the coated membrane on PDMS surface. The average value of EOF mobility of PDMS microchip coated with PMMSi30 was 1.4 × 10^?4 cm² V^?1 s^?1, and the RSD was 4.1 %. Zone electrophoresis of uranine was further demonstrated with high repeatability and reproducibility. Separation of two FITC-labeled proteins (BSA and insulin) was performed with high efficiency and resolution compared with non-treated PDMS microchip.     

Capacitive flexible pressure sensor: microfabrication process and experimental characterization

Kapton-based flexible pressure sensor arrays are fabricated using a new technology of film transfer. The sensors are dedicated to the non-invasive measurement of pressure/force in robotic, sport and medical applications. The sensors are of a capacitive type, and composed of two millimetric copper electrodes, separated by a polydimethylsiloxane (PDMS) deformable dielectric layer. On the flexible arrays, a very small curvature radius is possible without any damage to the sensors. The realized sensors are characterized in terms of fabrication quality. The inhomogeneity of the load free capacitances obtained in the same array is ±7 %. The fabrication process, which requires 14 fabrication steps, is accurate and reproducible: a 100 % transfer yield was obtained for the fabrication of 5 wafers gathering 4 sensor arrays each (215 elementary sensors). In the preliminary electro-mechanical characterization, a sensor (with a PDMS dielectric layer of 660 μm thickness and a free load capacitance of 480 fF) undergoes a capacitance change of 17 % under a 300 kPa normal stress.     

Microfluidic chips for cells capture using 3-D hydrodynamic structure array

Microfluidic chips were designed and fabricated to capture cells in a relative small volume to generate the desired concentration needed for analysis. The microfluidic chips comprise three-dimensional (3-D) cell capture structures array fabricated in PDMS. The capture structure includes two layers. The first layer consists of spacers to create small gap between the upper layer and glass. The second layer is a sharp corner U-shaped compartment with sharp corners at the fore-end. And another type capture structure with Y-shaped fluidic guide has been designed. It was demonstrated that the structures can capture cells in theory, using Darcy–Weisbach equation and COMSOL Multiphysics. Then yeast cell was chosen to test the performance of the chips. The chip without fluid guides captured ~1.44 × 10⁵ cells and the capture efficiency was up to 71 %. And the chip with fluid guides captured ~5.0 × 10⁴ cells and the capture efficiency was ~25 %. The chip without fluid guides can capture more cells because the yeast cells in the chip without fluid guides are subject to larger hydrodynamic drag force.     

Integration of microfluidic sample delivery system on silicon nanowire-based biosensor

Silicon nanowire-based (SiNW) biosensors have gained a lot of attention during recent years. However, studies often totally neglect, or only briefly describe, the incorporation of microfluidic channel into the sensor architecture, although it is a crucial step towards a real lab-on-chip device. This paper proposes a process that can be applied to integration of microfluidic sample delivery system onto different SiNW biosensors. The sample delivery system includes a hydrophilic channel that enables the use of capillary action in delivering sample directly onto the sensor array, which leads to reduced sample loss, faster detection process, and frees from the use of external pumps. In addition, the microfluidic channel system protects the fragile SiNWs from mechanical shocks, chemical spatters, and dust. The sample delivery system was fabricated of surface treated polydimethylsiloxane (PDMS), using a four-step approach, as follows: (1) master molds for soft lithography were etched onto Si. (2) PDMS replicas of the molds were fabricated and (3) bonded onto example sensor chips using oxygen plasma. (4) Oxygen plasma treatment also enabled the attachment of polyvinylpyrrolidone (PVP) to the sample channel surfaces to synthesize hydrophilic polymer coating. A contact angle for the PVP treated PDMS was 21 after 17 days, indicating the formation of a long-term hydrophilic PDMS surface. Finally, the example SiNW sensor is modified to allow direct real-time detection of thyroid-stimulating hormone (TSH). The sensor was able to detect as low TSH concentration values as 0.5 mIU/l, which indicates a successfully integrated sample delivery system.     

Design and fabrication of microlens arrays as beam relay for free-space optical interconnection

In this paper we report the design and fabrication of a beam relay for free space optical interconnection using microlens arrays. Multiple microlens arrays with same focal lengths were designed and fabricated in an out-of-plane layout. This design can be easily integrated with silicon-based optical interconnection devices. The beam relay was fabricated using direct lithography of SU-8 photoresist, and then replicated using UV curable polymer molded with a PDMS intermediate mold. The optical performance was tested and the experimental results show that the optical performances are mainly limited by the aberration of microlenses. Further study needs to be conducted to improve the surface quality of the lenses to reduce the aberrations.     

Micro-optofluidic switch realized by 3D printing technology

This paper presents a PDMS micro-optofluidic chip that allows a laser beam to be driven directly toward a two-phase flow stream in a micro-channel while at the same time automatically, detecting the slug’s passage and stirring the laser light, without the use of any external optical devices. When the laser beam interacts with the microfluidic flow, depending on the fluid in the channel and the laser angle of incidence, a different signal level is detected. So a continuous air–water segmented flow will generate a signal that switches between two values. The device consists of a T-junction, which generates the two-phase flow, and three optical fiber insertions, which drive the input laser beam toward a selected area of the micro-channel and detects the flow stream. Three micro-channel sections of different widths were considered: 130, 250, 420 μm and the performance of the models was obtained by comparing ray-tracing simulations. The master of the device has been realized by 3D printing technology and a protocol which realizes the PDMS chip is presented. The static and dynamic characterizations, considering both single flows and two-phase flows, were carried out, and in spite of the device’s design simplicity, the sensitivity of the system to capture changes in the segmented flows and to stir the laser light in different directions was fully confirmed. The experimental tests show the possibility of obtaining satisfactory results with channel diameters in the order of 200 μm.     

Inhibition of on-chip PCR using PDMS–glass hybrid microfluidic chips

In the course of developing a microfluidic analytical platform incorporating the polymerase chain reaction (PCR) and subsequent capillary electrophoresis (CE) analysis for a variety of bio-assays, we examined PCR inhibition through surface interactions with the chip materials. Our devices perform PCR in a three-layer chip, a glass–poly(dimethylsiloxane)–glass sandwich in which the poly(dimethylsiloxane) (PDMS, a silicone rubber) layer is used for pneumatic membrane pumping and valving of the PCR reagents. Initial on-chip PCR–CE tests of BK virus replicated in multiple uncoated chips showed variable results, usually yielding no detectable product at the target sample concentrations used. Subsequent “chip-flush” experiments, where water or reagents were flushed through a chip and subsequently incorporated in off-chip PCR, highlighted bovine serum albumin (BSA) amongst other pre-treatments, chip materials and PCR recipes as being effective in mitigating inhibition. When the BSA channel pre-coating was applied to on-chip PCR–CE experiments, a substantial improvement (10× to 40×) in signal-to-noise (S/N) of the CE product peak was conferred, and was shown with high confidence despite high S/N variability. This is the first study to quantitatively examine BSA’s ability to reduce inhibition of PCR performed on PDMS chips, and one of very few microfluidic PCR inhibition studies of any kind to use a large number of microfluidic chips (~400). The simplicity and effectiveness of our BSA coating suggest that passivating materials applied to microfluidic device channel networks may provide a viable pathway for development of bio-compatible devices with reduced complexity and cost.     

A high-shear, low Reynolds number microfluidic rheometer

We present a microfluidic rheometer that uses in situ pressure sensors to measure the viscosity of liquids at low Reynolds number. Viscosity is measured in a long, straight channel using a PDMS-based microfluidic device that consists of a channel layer and a sensing membrane integrated with an array of piezoresistive pressure sensors via plasma surface treatment. The micro-pressure sensor is fabricated using conductive particles/PDMS composites. The sensing membrane maps pressure differences at various locations within the channel in order to measure the fluid shear stress in situ at a prescribed shear rate to estimate the fluid viscosity. We find that the device is capable to measure the viscosity of both Newtonian and non-Newtonian fluids for shear rates up to 10⁴ s^?1 while keeping the Reynolds number well below 1.     

Design and fabrication of microfluidic devices integrated with an open‐ended MEMS probe for single‐cell impedance measurement

When an electrical current with a low frequency is applied to a cell, the current passes through the outside of the cell. Thus, impedance measurements at low frequencies cannot be used to determine the pathological change of the cellular organelle taking place inside the cell. However, increasing the frequency of the electrical current makes the capacitive impedance of the cell decrease, allowing the electrical current to flow through the cell. This study presents the design and fabrication of a microfluidic device integrated with a coplanar waveguide open-ended micro-electro-mechanical-systems (MEMS) probe for the impedance measurement of the single HeLa cell in frequencies between 1 MHz and 1 GHz. The device includes a poly-dimethlysiloxane (PDMS) cover with a microchannel and microstructures to capture the single HeLa cell and a conductor-backed CPW fabricated using a silicon chip and two printed circuit boards (PCB). The effects of the substrate on the characteristic impedance of the conductor-backed coplanar waveguide (CBCPW) structure were investigated under three conditions by utilizing a time-domain reflectometer (TDR). Finally, impedance measurements using the proposed device and a vector network analyzer (VNA) are demonstrated for de-ionized (DI) water, alcohol, PBS, and a single HeLa cell.     

Integration of optical waveguide on pneumatic balloon actuator for flexible scanner in endoscopic imaging diagnosis applications

This paper reports a flexible scanner consisting of a scanning actuator and optical waveguides for medical imaging applications such as endoscopic fluorescence imaging diagnosis. The 0.3-mm-thick and 5-mm-wide functional scanner was designed to be smaller enough than the 10 mm-diameter of channel of endoscope. The proposed device can be used to introduce an excitation light into the abdominal cavity or digestive tract. A pneumatic balloon actuator (PBA) consisting of polydimethylsiloxane (PDMS) is used as the scanning actuator for the scanner in consideration of its small, soft, and safe features. The SU-8 optical waveguides with high refractive index (n_SU-8 = 1.575) are integrated onto the PBA structure made of PDMS with a lower refractive index (n_PDMS = 1.405). Excitation light at a wavelength of 405 nm is transmitted through an optical fiber to the SU-8 waveguides. The outgoing light from the waveguide can be scanned by the bending motion of the PBA. The waveguide functions as a detector as well. Our developed device has successfully scanned, excited, and detected light from fluorescence beads at a wavelength of 540 nm distributed in a pseudo-tissue.     

Low-cost polymer microfluidic device for on-chip extraction of bacterial DNA

A polymer microfluidic device for on-chip extraction of bacterial DNA has been developed for molecular diagnostics. In order to manufacture a low-cost, disposable microchip, micropillar arrays of high surface-to-volume ratio (0.152 μm⁻¹) were constructed on polymethyl methacrylate (PMMA) by hot embossing with an electroformed Ni mold, and their surface was modified with SiO₂ and an organosilane compound in subsequent steps. To seal open microchannels, the organosilane layer on top plane of the micropillars was selectively removed through photocatalytic oxidation via TiO₂/UV treatment at room temperature. As a result, the underlying SiO₂ surface was exposed without deteriorating the organosilane layer coated on lateral surface of the micropillars that could serve as bacterial cell adhesion moiety. Afterwards, a plasma-treated PDMS substrate was bonded to the exposed SiO₂ surface, completing the device fabrication. To optimize manufacturing throughput and process integration, the whole fabrication process was performed at 6 inch wafer-level including polymer imprinting, organosilane coating, and bonding. Preparation of bacterial DNA was carried out with the fabricated PDMS/PMMA chip according to the following procedure: bacterial cell capture, washing, in situ lysis, and DNA elution. The polymer-based microchip presented here demonstrated similar performance to Glass/Si chip in terms of bacterial cell capture efficiency and polymerase chain reaction (PCR) compatibility.     

Dielectrophoresis measurement of bovine endothelial cells adhesion on different materials

In this study, the design, fabrication, and characterization of dielectrophoresis based devices for the measurement of bovine endothelial cell adhesion on different biomaterials are conducted. During the design stage, the finite element analysis software COMSOL is used to determine a better design for the dielectrophoretic electrode. Accordingly, a dielectrophoretic device that contains several micro electrodes for producing unbalanced electrical fields is fabricated using the microelectromechanical fabrication technique. The proposed device is then used for the detection of cell adhesion on polydimethylsiloxane (PDMS) and poly lactide (PLA) substrates. The hydrophilicity measurement results reveal that PLA is more hydrophilic than PDMS. It is inferred that bovine endothelial cell (BEC) should have better adhesion on PLA than on PDMA. However, the cell detachment results do not fully agree with this inference. It is further suggested that other features of the substrate are more crucial for the adhesion of BEC than the hydrophilicity. Cell detachment experiments demonstrate that the applied electrophoresis cannot detach the adhered BECs from a PDMS substrate when the seeding time is longer than 4 h. However, the dielectrophoretic force caused by a 6 V applied potential is enough to lift those cells cultured on the PLA for 4 and 6 h respectively. When the culture time is increased to 8 h, the cells apparently stretch out and a higher voltage is required to lift and move them. The results of the cell detachment experiments may suggest that the adherence of BEC to PLA is more stable after 8 h of seeding.     

Drop-on-demand printed microfluidics device with sensing electrodes using silver and PDMS reactive inks

For this work, a cure-in-place polydimethylsiloxane (PDMS) reactive ink was developed and its utility demonstrated by printing a complete microfluidic mixer with integrated electrodes to measure fluid conductivity, concentration, and mixing completeness. First, a parameter-space investigation was conducted to generate a set of PDMS inks and printing parameters compatible with drop-on-demand (DOD) printing constraints. Next, a microfluidic mixer was fabricated using DOD-printed silver reactive inks, PDMS reactive inks, and a low-temperature polyethylene glycol fugitive ink. Lastly, the device was calibrated and tested using NaCl solutions with concentrations ranging from 0.01 to 1.0 M to show that electrolyte concentration and mixing completeness can be accurately measured. Overall, this work demonstrates a set of reactive inks and processes to fabricate sophisticated microfluidic devices using low-cost inks and DOD printing techniques.     

A micro PDMS flow sensor based on time-of-flight measurement for conductive liquid

Transdermal extraction of interstitial fluid (ISF) offers an attractive method for non-invasive blood glucose monitoring. In order to calculate blood glucose concentration accurately, precise volume measurement of transdermally extracted ISF is required due to human skin’s varying permeability. In this paper, we presented a novel flow sensor fabricated from polydimethylsiloxane (PDMS), designed to measure the volume of conductive liquid. The flow sensor consists of two pairs of metal electrodes, which are fabricated in the PDMS channel. The volume of liquid is measured utilizing the time-of-flight of the two electrode pairs’ resistance while the liquid is flowing through the flow sensor. 1–14 μL normal saline solution was measured, the flow sensor measured volumes correlate very well (R ² = 0.9996 and R ² = 0.9975 for vacuum pump and syringe pump situations respectively) with the actual volumes. And the coefficient of variation for 10 times 10 μL normal saline solution measurement is 0.0077 (vacuum pump) and 0.0381 (syringe pump), respectively. The demonstrated flow sensor provides excellent functionality for conductive liquid.     

Arrays of high aspect ratio magnetic microstructures for large trapping throughput in lab-on-chip systems

Here we report a novel technology to obtain arrays of highly efficient magnetic micro-traps that relies on simple fabrication process. Developed micro-traps consist in chains of iron particles diluted in polydimethylsiloxane (PDMS). We analyzed the microstructure of the composite membrane by X-ray tomography. It revealed the predominance of aligned chain-like agglomerates. Largest traps, with diameter ranging from 4 to 11 µm, are found to be the most efficient. The trap arrays were characterized by a density of 1300 magnetic micro-traps/mm², an average nearest neighbor distance of 21 µm. Implemented in a microfluidic channel operating at a relatively high flow rate of 0.97 µL/s—a flow velocity of 8.3 mm/s—we measured a trapping efficiency of more than 99.7%, with a throughput of up to 7100 trapped beads/min. These performances are competitive with other approaches like hydrodynamic trapping. The strengths of this technology are its simple fabrication and easy handling.     

Low-cost credit card-based microfluidic devices for magnetic bead immobilisation

We report a simple low-cost magnetic microfluidic device for magnetic bead separation and immobilisation. One dimensional arrays of localised high magnetic field gradients are constructed at the interfaces between regions magnetised with opposing polarities on the magnetic Fe₂O₃ composite stripes of credit cards. The localised high magnetic field gradients are employed to trap magnetic beads on the surface of the magnetic stripe, without the need for external magnetic components. A magnetic card writer was used to deterministically pattern the magnetic stripes of credit cards to define arrays of magnetic reversals. The fabrication of the device is based on PDMS to credit card bonding of simple flow channels. Experimental results demonstrate that magnetic beads can be captured with efficiencies of 85, 67 and 27 % at flow rates of 25, 50 and 100 μL min^?1, respectively. The results show that the credit card-based magnetic separator might offer an efficient, simple, low-cost alternative to traditional microfluidic magnetic separators for applications such as immunomagnetic cell separation.     

Design and fabrication of 3-dimensional helical structures in polydimethylsiloxane for flow control applications

Soft lithography in 2-dimensional (2-D) was developed for polymer MEMS applications about two decades back. The technique was highly useful for replication of microstructure molds using a soft polymeric material called PDMS (polydimethylsiloxane). From its inception the process has been widely applied to microfluidics, biochips, hybrid biomedical microdevices etc. However, it was limited to only surface microstructures and 3-Dimensional (3-D) soft lithography although performed by some research groups involved some very precise and expensive techniques like stereolithography etc. The exploration of soft lithography in three dimensions by using a replication technique with copper wires with micron size diameters was performed by our group relatively recently (Singh et al. in International conference on MEMS, IIT Madras, Chennai, 2009). In this work we have used the 3-D replication and molding technique to develop concentric solenoid patterns around micro-channels in the bulk of PDMS. The solenoidal paths of various pitches ranging from 0.4 to 1.2 mm have been replicated in PDMS using an innovatively designed fixture. The solenoids have been structurally characterized using an inverted fluorescence microscope (Nikon 80i) for dimensional parameters like pitch, length etc. Further, the solenoidal path designs have been simulated, optimized and fabricated around a central channel of 80 μ diameter and we have observed the repeatability of this fabrication process multiple times. The purpose of this architecture is to initiate valving action wherein fluid movement in the central channel can be restricted by filling the surrounding solenoidal track with compressed air at high pressure so that it can squeeze the centrally located micro-channel carrying the liquid. This valving structure may find a lot of applications in lab on chip devices, PCR biochips, biomedical micro-devices etc.