Shih-Kang Fan

Cross-scale electric manipulations of cells and droplets by frequency-modulated dielectrophoresis and electrowetting

Two important electric forces, dielectrophoresis (DEP) and electrowetting-on-dielectric (EWOD), are demonstrated by dielectric-coated electrodes on a single chip to manipulate objects on different scales, which results in a dielectrophoretic concentrator in an EWOD-actuated droplet. By applying appropriate electric signals with different frequencies on identical electrodes, EWOD and DEP can be selectively generated on the proposed chip. At low frequencies, the applied voltage is consumed mostly in the dielectric layer and causes EWOD to pump liquid droplets on the millimetre scale. However, high frequency signals establish electric fields in the liquid and generate DEP forces to actuate cells or particles on the micrometre scale inside the droplet. For better performance of EWOD and DEP, square and strip electrodes are designed, respectively. Mammalian cells (Neuro-2a) and polystyrene beads are successfully actuated by a 2 MHz signal in a droplet by positive DEP and negative DEP, respectively. Droplet splitting is achieved by EWOD with a 1 kHz signal after moving cells or beads to one side of the droplet. Cell concentration, measured by a cell count chamber before and after experiments, increases 1.6 times from 8.6 x 10(5) cells ml(-1) to 1.4 x 10(6) cells ml(-1) with a single cycle of positive DEP attraction. By comparing the cutoff frequency of the voltage drop in the dielectric layer and the cross-over frequency of Re(fCM) of the suspended particles, we can estimate the frequency-modulated behaviors between EWOD, positive DEP, and negative DEP. A proposed weighted Re(fCM) facilitates analysis of the DEP phenomenon on dielectric-coated electrodes.

Towards digital microfluidic circuits: creating, transporting, cutting and merging liquid droplets by electrowetting-based actuation

This paper reports a breakthrough in our quest for digital microfluidic circuits - full completion of all four fundamental microfluidic operations: (1) creating, (2) transporting, (3) cutting, and (4) merging of liquid droplets, based on electrowetting-on-dielectric (EWOD) actuation. All the operations were achieved with 25 V/sub DC/ lower than EWOD actuation voltages previously reported. We also report conditions to reduce the driving voltage even further and conditions to drive a droplet as fast as 250 mm/s.

Manipulation of multiple droplets on N/spl times/M grid by cross-reference EWOD driving scheme and pressure-contact packaging

This paper reports two recent breakthroughs in our development of EWOD-based (ElectroWetting On Dielectric) digital (droplet) microfluidic circuits: a driving scheme and a packaging scheme, both of which greatly simplify fabrication and make large-array chips a reality. This paper will explain (1) the concept of cross-reference driving, which allows single-layer electrode fabrication, including the techniques to allow simultaneous driving of multiple droplets and (2) pressure-contact connection, which greatly simplifies packaging and assembly for high-density EWOD devices. The efficacy of the driving concept is demonstrated by transporting four droplets simultaneously, each along its own path, on a 9/spl times/9 grid and performing essential fluidic functions such as creation, cutting, merging, and mixing of droplets.

General digital microfluidic platform manipulating dielectric and conductive droplets by dielectrophoresis and electrowetting

A general digital (droplet-based) microfluidic platform based on the study of dielectric droplet manipulation by dielectrophoresis (DEP) and the integration of DEP and electrowetting-on-dielectric (EWOD) is reported. Transporting, splitting, and merging dielectric droplets are achieved by DEP in a parallel-plate device, which expands the fluids of digital microfluidics from merely being conductive and aqueous to being non-conductive. In this work, decane, hexadecane, and silicone oil droplets were successfully transported in a 150 microm-high gap between two parallel plates by applying a DC voltage above threshold voltages. Non-volatile silicone oil droplets with viscosities of 20 and 50 cSt were studied in more detail in parallel-plate geometries with spacings of 75 microm, 150 microm, and 225 microm. The threshold voltages and the required driving voltages to achieve droplet velocities up to 4 mm/s in the different circumstances were measured. By adding a dielectric layer on the driving electrodes of the tested parallel-plate device, a general digital microfluidic platform capable of manipulating both dielectric and conductive droplets was demonstrated. DEP and EWOD, selectively generated by applying different signals on the same dielectric-covered electrodes, were used to drive silicone oil and water droplets, respectively. Concurrent transporting silicone oil and water droplets along an electrode loop, merging water and oil droplets, and transporting and separating the merged water-in-oil droplet were performed.

Portable digital microfluidics platform with active but disposable Lab-On-Chip

This paper reports successful development of a stand-alone microfluidics platform based on our electrowetting-on-dielectric (EWOD) droplet technologies. Four new major developments that empowered us to achieve the portable digital microfluidic system are presented: (1) time-multiplexed driving scheme that enables simultaneous driving of a large number of droplets; (2) electric sensing mechanism of droplet positions, opening the door for feedback control and Lab-On-Chip (LOG) performance monitoring; (3) fabrication of disposable and sealed LOC capable of full droplet manipulation; and (4) completion of stand-alone portable electronics board. Leaving the issue of biofluids manipulation to other reports, this paper will focus on the technology developments.

Micromachining of mesoporous oxide films for microelectromechanical system structures

The high porosity and uniform pore size of mesoporous oxide films offer unique opportunities for microelectromechanical system (MEMS) devices that require low density and low thermal conductivity. This paper provides the first report in which mesoporous films were adapted for MEMS applications. Mesoporous SiO 2 and Al 2 O 3 films were prepared by spin coating using block copolymers as the structure-directing agents. The resulting films were over 50% porous with uniform pores of 8-nm average diameter and an extremely smooth surface. The photopatterning and etching characteristics of the mesoporous films were investigated and processing protocols were established which enabled the films to serve as the sacrificial layer or the structure layer in MEMS devices. The unique mesoporous morphology leads to novel behavior including extremely high etching rates and the ability to etch underlying layers. Surface micromachining methods were used to fabricate three basic MEMS structures, microbridges, cantilevers, and membranes, from the mesoporous oxides.

Encapsulated droplets with metered and removable oil shells by electrowetting and dielectrophoresis

A water-core and oil-shell encapsulated droplet exhibits several advantages including enhanced fluidic manipulation, reduced biofouling, decreased evaporation, and simplified device packaging. However, obtaining the encapsulated droplet with an adjustable water-to-oil volume ratio and a further removable oil shell is not possible by reported techniques using manual pipetting or droplet splitting. We report a parallel-plate device capable of generation, encapsulation, rinsing, and emersion of water and/or oil droplets to achieve three major aims. The first aim of our experiments was to form encapsulated droplets by merging electrowetting-driven water droplets and dielectrophoresis-actuated oil droplets whose volumes were precisely controlled. 25 nL water droplets and 2.5 nL non-volatile silicone oil droplets with various viscosities (10, 100, and 1000 cSt) were individually created from their reservoirs to form encapsulated droplets holding different water-to-oil volume ratios of 10:1 and 2:1. Secondly, the driving voltages, evaporation rates, and biofouling of the precise encapsulated droplets were measured. Compared with the bare and immersed droplets, we found the encapsulated droplets (oil shells with lower viscosities and larger volumes) were driven at a smaller voltage or for a wider velocity range. In the dynamic evaporation tests, at a temperature of 20 ± 1 °C and relative humidity of 45 ± 3%, 10 cSt 10:1 and 2:1 encapsulated droplets were moved at the velocity of 0.25 mm s(-1) for 22 and 35 min until losing 16.6 and 17.5% water, respectively, while bare droplets followed the driving signal for only 6 min when 11.4% water was lost. Evaporation was further diminished at the rate of 0.04% min(-1) for a carefully positioned stationary encapsulated droplet. Biofouling of 5 μg ml(-1) FITC-BSA solution was found to be eliminated by the encapsulated droplet from the fluorescent images. The third aim of our research was to remove the oil shell by dissolving it in an on-chip rinsing reservoir containing hexane. After emersion from the rinsing reservoir, the bare droplet was restored as hexane rapidly evaporated. Removal of the oil shell would not only increase the evaporation of the core droplet when necessary, but also enhance the signal-to-noise ratio in the following detection steps.

Digital microfluidic operations on micro-electrode dot array architecture

As digital microfluidics-based biochips find more applications, their complexity is expected to increase significantly due to the trend of multiple and concurrent assays on the chip. There is a pressing need to deliver a top-down design methodology that the biochip designer can leverage the same level of computer aided design support as the semiconductor industry now does. Moreover, as microelectronics fabrication technology scaling and integrated device performance improving, it is expected that these microfluidic biochips will be integrated with microelectronic components in next-generation system-on-chip designs. This paper presents a novel electrowetting-on-dielectric (EWOD) based “micro-electrode array architecture” that fosters a development path for hierarchical top-down design approach for digital microfluidics, and also allows easy integration of microfluidics and microelectronics on a single chip. In addition, this novel architecture provides a number of advantages and flexibilities over the conventional digital microfluidics such as dynamic activations of variable-sized electrodes and dynamic manipulations of multiple droplets.

Reconfigurable liquid pumping in electric-field-defined virtual microchannels by dielectrophoresis

Dielectrophoresis (DEP), widely used to generate body forces on suspended particles, is investigated to provide surface forces at the liquid-medium interfaces and pump a high-permittivity liquid in a low-permittivity medium along a virtual microchannel defined by an electric field between parallel plates. Because the pumping pressure is proportional to the square of the intensity of the electric field and independent of the channel width, DEP pumping is advantageous as the dimension of the microchannel shrinks down. The absence of the channel walls simplifies the fabrication processes and further increases its feasibility in nanofluidic applications. We demonstrate water pumping in an immiscible silicone oil medium at adjustable velocities by applying voltages above the threshold value whose square is linearly proportional to the cross-sectional aspect ratio (AR), i.e., the height to width ratio, of the microchannel. With a properly designed AR, liquid valve is achieved by appropriate voltage applications. Without the barriers of channel walls, merging multiple streams and capillary filling of the spacing between electric-field-defined virtual microchannels are observed and studied. Moreover, in situ reconfigurable liquid pumping is demonstrated by a four way switching valve on a programmable crossing electrode set.

Electrorheological operation of low-/high-permittivity core/shell SiO2/Au nanoparticle microspheres for display media.

In this study, we synthesized core/shell structures comprising monodisperse 3-μm SiO(2) microspheres and gold nanoparticles (AuNPs, ca. 6.7 nm) as the core and shell components, respectively. Using a layer-by-layer cross-linking process with a dithiol cross-linking agent, we prepared low-permittivity AuNP-encapsulated high-permittivity SiO(2) core/shell microspheres with variable AuNP shell thicknesses. The dispersivity of the microspheres in solution was enhanced after grafting poly(ethylene glycol) monomethyl ether thiol (PEG-SH) onto the AuNP layer on the SiO(2) microspheres. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images revealed sesame ball-like structures for these SiO(2)@AuNP@PEG microspheres. We encapsulated aqueous dispersions of these SiO(2)@AuNP microspheres into sandwich structured displays (SSDs) to investigate their electrorheological properties, observing reversibly electroresponsive transmittance that is ideally suited for display applications. Increasing the thickness of the AuNP layer dramatically enhanced the stringing behavior of the SiO(2) microspheres, resulting in increased transmittance of the SSD. The response time of the electroresponsive electrorheological fluids also decreased significantly after modifying the SiO(2) with the AuNP layers. The effective permittivities of these composites could be predicted from the real (έ) and imaginary (έ́) parts of the Clausius-Mossotti formalism.