Electroosmotic Flow Control in Microfluidic Chips Using a Self

Letter pubs.acs.org/Langmuir

Electroosmotic Flow Control in Microfluidic Chips Using a SelfAssembled Monolayer as the Insulator of a Flow Field-Effect Transistor Li-Chia Chen,† Ching-Chou Wu,*,∥ Ren-Guei Wu,⊥ and Hsien-Chang Chang*,†,‡,§ †

Department of Biomedical Engineering, ‡Center for Micro/Nano Science and Technology, and §Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan ∥ Department of Bio-industrial Mechatronics Engineering, National Chung Hsing University, Taichung, Taiwan ⊥ Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan ABSTRACT: A novel concept for electroosmotic flow (EOF) control in a microfluidic chip is presented by using a self-assembled monolayer as the insulator of a flow field-effect transistor. Bidirectional EOF control with mobility values of 3.4 × 10−4 and −3.1 × 10−4 cm2/V s can be attained, corresponding to the applied gate voltage at −0.8 and 0.8 V, respectively, without the addition of buffer additives. A relatively high control factor (approximately 400 × 10−6 cm2/V2 s) can be obtained. The method presented in this study offers a simple strategy to control the EOF.

was recently reported to modulate ζ dynamically by imposing a radial external electric field perpendicular to the microchannel.12−25 In this device, the external voltage of the fieldeffect flow is functionally equal to the gate voltage (Vg) of a field-effect transistor (FET) to manipulate the ζ beyond the channel wall, which is regarded as an insulator for FET. The ends of the channel are analogous to the source and drain contacts of an FET. The applied Vg can induce a change in ζ (Δζ) according to

1. INTRODUCTION In recent years, microfluidic technology has attracted widespread interest for applications related to sample transportation, solvent mixing, analyte separation, and bioanalysis because integrated microfluidic devices can be easily manufactured using microfabrication techniques. Nonmechanical electroosmotic pumps are most widely used to drive samples in microfluidic systems.1−5 Electroosmotic flow (EOF), which is the bulk motion of ionized liquid with respect to a stationary charged surface under the action of an electrokinetic body force, provides an efficient and simple method for fluid flow control without an extra pressure source or micropump. There are a number of effects on the separation efficiency, resolution, and reproducibility of capillary electrophoresis caused by changing the direction and velocity of EOF. The direction and velocity of EOF in a microchannel can be controlled by the externally applied electric field.6 However, this method has some drawbacks, such as significant hydrolysis, large Joule heating, and a slow switching rate of the power supply polarity, that limit practical applications. The alternative method is the adjustment of the zeta potential (ζ). Some examples are the addition of buffer additives or changes in buffer pH or ionic strength and capillary wall modification.7−11 Unfortunately, these methods cannot instantly alter the properties of the electric double layer in the buffer−microchannel wall interface during the measurement of capillary electrophoresis. Because the polarity and magnitude of ζ are greatly determined by the surface potential of the microchannel wall and charge density of counterions near the wall, a novel strategy © 2012 American Chemical Society

Δζ =

CwallVg Cd

where Cwall and Cd are the capacitances of the channel wall and the electrical diffusion double layer, respectively. The equation indicates that a thinner capillary wall is more efficient at inducing ζ. In previous reports, a semiconducting material was widely used to fabricate the channel wall for EOF control. On the basis of microelectromechanical systems, the thickness of the SiO2 film can be reduced from several micrometers to 100 nm, which greatly decreases the need for an applied Vg to induce the ζ of the channel wall surface. The SiO2 nanopore has also been used to modulate the ζ for further EOF control. Moreover, an electrically polarizable SiC, Al, or CNx interface was proposed to alter the ζ of the channel wall surface. However, these Received: May 29, 2012 Revised: July 9, 2012 Published: July 16, 2012 11281

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galvanometer (BAS 100W, Bioanalytical Systems, West Lafayette, IN) was connected in series with the high-voltage power supply and grounded with the drain to monitor the current change during the replacement of conductivity-varied buffers. Another 9 V dry battery connected with a variable resistor was used to adjust the power for the Vg, as shown in Figure 1. We found that if one of the terminals of the dry battery is connected to the ground of the high-voltage power supply, then the breakdown of the SAM occurs easily under the effect of high voltage. Therefore, in this study, the dry battery was connected to another electrode in reservoir 2 in order to isolate the effect of the high-voltage power supply. As for the leakage current measurement, the dry battery and resistances were replaced by a potentiostat. The potentiostat supply for the external Vg was connected to the gate electrode and the end of the channel to form a series connection. In this case, the reference and counter parts of the potentiostat were connected. The channel was filled with 10 mM MES. The Vg was set at 0.6 and 1.0 V to measure the leakage current passing through the gate electrode (thiol monolayer).

strategies are usually time-consuming and need highly trained personnel. Moreover, because the signs of EOF and ζ are opposite to each other, a bidirectional EOF on one chip is still difficult to control. Therefore, a more convenient method for channel wall fabrication to modulate EOF widely is highly desired. In this study, the concept of the self-assembled monolayer (SAM) was proposed to construct an ultrathin channel wall. The ζ of the SAM surface can be modulated under a relatively low Vg to achieve bidirectional EOF control. No additional modifier was added to the buffer solution to improve the EOF characteristic.

2. EXPERIMENTAL SECTION The details of the poly(dimethylsiloxane) (PDMS) channel fabrication are the same as those in previously published procedures.5,7 The mixture of a PDMS monomer and curing agent was cast against the masters at 75 °C for 3 h and then stripped to yield an elastomeric replica. The PDMS replica containing the microchannel can be spontaneously sealed with the glass substrate. The dimensions of the PDMS channel were 1.2 cm in length, 13 μm in height, and 50 μm in width. The two ends of the channel were drilled to form 3-mmdiameter reservoirs for the inlet and outlet, as shown in Figure 1A.

3. RESULTS AND DISCUSSION Initially, the microchannel and the right-side reservoir were filled with 10 mM MES, and the left-side reservoir was filled with 50 mM MES. A high voltage, 80 V/cm, and the external Vg were applied simultaneously to drive the electrokinetic flow and induce ζ, respectively. Different Vg values were applied to modulate the electroosmotic flow mobility (μEOF). The μEOF can be calculated by the equation reported previously in the literature.5,6 The thicknesses of the ODT and MUDA monolayers measured by optical ellipsometry are approximately 2.9 and 2.0 nm, respectively.27 The performance of μEOF related to the applied Vg for the ODT-modified microchannel is almost the same at pH 3.0 and 6.0, as shown in Figure 2A. It is worth noting that bidirectional EOF control can be easily achieved by adjusting the applied Vg, which is much lower than the values reported previously.15−18 The values of μEOF are positive in the negative Vg range and decrease with increasing Vg from −0.8 to 0 V. The value of μEOF is equal to zero at Vg = 0 V. However, the values of μEOF reverse to negative ones and increase with increasing Vg in the positive range. It is generally known that the direction of EOF is highly dependent on the surface potential of the microchannel wall. This result indicates that the ζ of the ODT monolayer, which maintains electric neutrality in spite of the pH shift, can be easily induced by applying Vg. Because the value of μEOF changes significantly under the effect of Vg, we can conclude that the applied Vg is the main factor modulating the magnitude and direction of EOF in this study. As can be observed in Figure 2B, bidirectional EOF control also can be obtained in the MUDA-modified microchannel at pH 3.0, for which the end group of the MUDA surface is carboxylic acid (−COOH). Although MUDA has a shorter carbon chain than ODT does, the μEOF value of the MUDAmodified microchannel at pH 3.0 is slightly lower than that for the ODT-modified microchannel at the same Vg. This result suggests that the induced dipole of the alkylthiol greatly depends on the properties of its functional group, but not on the length of the carbon chain. However, it shows a different μEOF performance for the MUDA-modified microchannel at pH 6.0, at which the end group of the MUDA surface transfers to carboxylate (−COO−) with a negative charge. In the Vg range of −1.0 to 0 V, the μEOF value for the MUDA-modified microchannel at pH 6.0 decreases with the increasing potential but is obviously higher than that for the ODT-modified microchannel at the same Vg. It should be noted that without the effect of the induced ζ at Vg = 0 V the μEOF for the MUDA-

Figure 1. Microfluidic chip composed of a PDMS slab (A) and an electrode-containing glass substrate (B). Rs and Rv stand for the resistance and variable resistance, respectively. The dry battery and resistances were replaced by a potentiostat for leakage current measurements. Reservoirs 1 and 2 are connected via microchannel C. The SAM insulator provides only 40% of the channel surface coverage for field-effect flow control. Thin films consisting of 30 nm of Ti and 100 nm of Au were sputterdeposited and patterned on a clean glass substrate. The 1.2-cm-long, 100-μm-wide gate electrode was aligned with the microchannel. The drain and source electrodes were externally placed in the two reservoirs, as shown in Figure 1B. The running buffers were 10 and 50 mM 2-(N-morpholino)ethanesulfonic acid (MES, Sigma), which had the pH adjusted to 3.0 and 6.0 by H2SO4 and NaOH, respectively. Before SAM modification, the Au electrode surface is cleaned with piranha solution (H2SO4/ H2O2 = 1: 3 (v/v)) for 2 min and then electrochemically in MES (pH 6) by cycling the potential between 0 and −1.5 V (vs Ag/AgCl) in order to remove the surface oxide layer. Finally, a 2 mM 1octadecanethiol (ODT) or 11-mercaptoundecanoic acid (MUDA) ethanolic solution was placed on the gate electrode overnight (more than 12 h) at 4 °C to form the SAM, respectively. The framework of the EOF measurement based on the current-monitoring method is shown in Figure 1.26 A high-voltage power supply (series 225, Bertan High-Voltage Corp., Plainview, NY) connecting to the source and drain was used to supply the EOF driving force only. The 11282

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Figure 3. Leakage currents of ODT () and MUDA (···) insulators as a function of repeatable frequencies at gate potentials of 0.6 (○, ●) and 1.0 V (△,▲), respectively. Solid shapes, positive gate potential; hollow shapes, negative gate potential.

BR =

I nFA

where I represents the current passing through the SAM, and n, F, and A are the electron-transfer number for Au−S bond break (n = 1), Faradaic constant (96 487 C/mol), and the geometric area of the SAM (50 μm × 1.2 cm), respectively. In this study, 10 pA was used for the I in the above equation because the alkylthiol monolayer is defined as the dielectric breakdown when the leakage current is greater than 10 pA, which is close to the current change when replacing the buffer by the currentmonitoring method in this study (data not shown).26 Therefore, the BR in this study can be calculated to be 1.73 × 10−14 mol/cm2 s. The breakdown of SAM for each EOF driving in 100 s is about 1.73 × 10−12 mol/cm2. However, the maximum coverage of the alkylthiol monolayer (C > C11) is general about 7.5 × 10−10 mol/cm2 according to the literature.30 The breakdown ratio is about 0.23% for each EOF driving in 100 s. This result suggests that the effect of the voltage drop across the SAM significantly depends on the time of voltage application. Although the high-voltage drop possibly causes the SAM breakdown, the breakdown ratio of ODT- and MUDA-SAM can be negligible before the EOF driving for 9 and 15 times, respectively (Figure 3). Accordingly, the SAM fabricated by ODT or MUDA can be regarded as an insulator of a flow field-effect transistor for the preliminary EOF measurement in this study. Under this condition, the concept of our device can be analogous to the metal oxide semiconductor field-effect transistor. The SAM insulator can be polarized by applying Vg to control its surface potential. When negative or positive Vg is applied, the end of the SAM insulator facing the electrolyte exhibits a negative or positive surface potential, respectively. Correspondingly, net hydrated cations or anions are attracted to the SAM/electrolyte interface to form the electric double layer in order to neutralize the negative or positive surface potential of the SAM insulator. When a voltage is applied across the fluid at the two ends of the channel, the hydrated cations or anions in the double layer will move under the influence of the longitudinal electric field and drag the fluid with them through viscous coupling to produce the EOF. The signs of μEOF and ζ

Figure 2. Relationship between the electroosmotic mobility and applied gate voltage on the ODT (A) and MUDA (B) insulators in MES buffers of pH 3.0 (red) and 6.0 (black). Error bars stand for the standard deviation calculated from three sets of measurements.

modified microchannel at pH 6.0 is 1.54 × 10−4 cm2/V s, whereas it is close to zero for that with a neutral surface. Only the EOF with a positive value can be obtained when a positive Vg is applied to the MUDA-SAM with a negative charge. We can also observe that the value of μEOF induced by positive Vg is smaller than that induced by negative Vg in Figure 2B. It strongly suggests that the positive surface potential induced by the positive Vg cannot overcome the natively negative surface potential caused by the carboxylate groups of MUDA with the negative charge in the MES solution of pH 6. Although the performance of EOF can be easily controlled through the regulation of the applied Vg in the range of ±0.8 V, only the SAM surface with electric neutrality can be induced to exhibit the arbitrary ζ for bidirectional EOF control. In this device, the conductive current mainly passes through the microchannel via the electrolytic conductance owing to the high resistance of the alkylthiol monolayer. In this study, the SAM suffers a large voltage drop from the difference potential between the EOF driving power and Vg. Most voltage drops across the SAM are larger than the breakdown voltage of the alkylthiol monolayer.28,29 The SAM endurance has been described by the relationship between the leakage current passing through the alkylthiol monolayer and the repeatable frequencies of EOF driving, as shown in Figure 3. The breakdown rate (BR, mol/cm2 s) of the SAM can be calculated on the basis of the experimental parameters and results. If the leakage current (I) completely results from the oxidative or reductive breakage reaction of Au−S bonds, then the BR of the SAM can be calculated from the equation 11283

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are opposite to each other. Under a constant high voltage for EOF driving, the absolute value of the μEOF is positively proportional to that of ζ, which can be modulated by the applied Vg in this study. A comparison of the induced EOF control in this study with those reported in the literature is given in Table 1. The

ref

pH

12 12 14 17 17 † †

3.6 4.5 3.0 3.0 5.0 3.0 6.0

390 390 50000 2000 2000 2.9 2.9

Vg (V)

μEOF ( × 10−4 cm2/V s)

control factor (ΔμEOF /ΔVg) ( × 10−6 cm2/V2 s)

25 to −37 50 to −50 172 to 52 460 to −300 460 to −300 0.8 to −0.8 0.8 to −0.8

−2.0 to 1.5 4.3 to 6.0 −1.1 to −1.9 −0.9 to 2.9 1.2 to 3.4 −3.1 to 3.3 −3.1 to 3.4

5.6 1.7 4.0 0.5 0.3 400.0 406.3

AUTHOR INFORMATION

Corresponding Author

*(C.-C.W.) E-mail: [email protected]. Tel: +886-4228-51268. Fax: +886-4-228-79351. (H.-C.C.) E-mail: [email protected]. Tel: +886-6-275-7575 ext 63426. Fax: +886-6-234-3270. Notes

Table 1. Comparison of the Efficiency for the Induced EOF of the ODT-Modified Monolayer (†) in This Study with Those Reported in the Literaturea thickness of insulator (nm)

Letter

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Multidisciplinary Center of Excellence for Clinical Trial and Research (DOH100-TD-B111-002) and the NSC under grant no. NSC 99-2628-B-006001-MY3. We also thank the National Nano Device Laboratory (NDL99-C06S-058) and the Southern Taiwan Nanotechnology Research Center for supplying the equipment for microfabrication.

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REFERENCES

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a

Data from the literature was calculated from experimental details or figures.

reported values of applied Vg are usually 10 to several hundred volts, the control factors are relatively low, and it is also very difficult to obtain bidirectional EOF control. In our device, we can easily achieve bidirectional EOF control in the range from 3.3 × 10−4 to −3.1 × 10−4 cm2/V s by using an alkylthiol monolayer as an insulator of the field-effect transistor. The linear velocity would be in the range from 2.72 × 10−2 to −2.48 × 10−2 cm/s. Furthermore, because a significantly low Vg is required for the ζ induction of the SAM, a relatively high control factor (approximately 400 × 10−6 cm2/V2 s) can be obtained. It strongly suggests that this novel method can control the EOF more effectively than those approaches reported in the literature. EOF is the important factor in the applicability of capillary electrophoresis to a large range of analytes. Extending the range of EOF control by an FET analogous device can improve the resolution and efficiency of these analytical systems. Because an easy method for a wide range of EOF control is achieved, this FET analogous device can be used for highly sensitive biomolecular detection, such as clinical diagnostics and environmental monitoring.

4. CONCLUSIONS In this study, we succeeded in fabricating an alkylthiol monolayer on a microfluidic chip as the insulator of a fieldeffect transistor to modulate the direction and magnitude of EOF. This novel method offers a number of important advantages over other existing flow-control transistors. The ultrathin thickness of the alkylthiol monolayer reduces the demand of the applied Vg. The performance of EOF is highly dependent on the electric charge of the SAM surface. Bidirectional EOF control can be obtained in the monolayer surface with electric neutrality. Although it is essential to increase the duration of the alkylthiol monolayer under high voltage to drive the EOF, this device will improve the dynamic control of the EOF for microfluidic chip applications. 11284

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