Automated on-chip droplet dispensing with volume control by electro-wetting actuation and capacitance metering

https://doi.org/10.1016/j.snb.2003.09.030Get rights and content

Abstract

In this work, a method is presented for controlling on-chip droplet dispensing by electro-wetting actuation in conjunction with capacitance feedback. The method exploits the built-in capacitance of an electro-wetting device to meter the droplet volume and control the dispensing process. A self-contained system is built to provide continuous-flow loading, capacitance measurement, and electro-wetting chip control. Automated droplet generation at rates up to 120 droplets/min is demonstrated for droplets of 0.1 M KCl aqueous solution dispensed onto 1 mm pitch buried electrodes and a 500 μm channel gap. The reproducibility of the droplet volumes is tested against dispensing parameters including production rate, fluid viscosity, channel aspect ratio, dispensing needle position and dispensing volume. The overall reproducibility is ±5% for production rates varying from 8 to 45 droplets/min and ±6% for fluidic viscosity ranging from 1 to 58 Cst, which implies the application of the method to wide ranges of solutions and pressures. Feedback metering compares well with droplet dispensing without capacitance feedback, which gives a reproducibility of ±13% for on-chip dispensing from a reservoir and ±12% for constant pressure-assisted dispensing.

Introduction

In micro total analysis systems (μTAS), liquid handling with high precision is of paramount importance, since the accuracy of assays is largely determined by the fluid volume control of the reagent dosing. Precision, often referred to as reproducibility, is measured by the standard deviation of a set of volumes divided by the mean. In drug discovery applications, this figure of merit must be below ±10% and preferably ±5% for some applications [1]. Microdialysis applications, which monitor human glucose, lactate, and glutamate/pyruvate require that the precision in dosing of preset liquid volumes be controlled within ±2%.

In continuous-flow systems, volume control is achieved by incorporating feedback in liquid handling either though a flow sensor [2], [3], [4] or using Chronoflow [5] such that flow rates can be regulated against varying pressure differences. Another option is by direct liquid metering based on an electrochemical principle [6], [7]. For microfluidic systems, where liquids are manipulated as droplets, Handique et al. [8] described an approach to droplet metering by introducing a hydrophobic patch in a microcapillary channel. By stopping the wetting of the solution at the boundary of a hydrophobic patch, the precise position of the air/liquid interface was achieved. Then by pneumatic actuation with an external or on-chip pressure chamber, individual droplets were split off and propelled to the next section of the device. An alternative method was proposed by Nisisako [9] by which pico/nanoliter-sized droplets were generated through permeating a dispersed phase (sample) into a continuous flow (oil) at a T-junction of a microchannel.

The drawbacks of current droplet dispensing techniques include the difficulty in fabrication and integration with existing droplet manipulation methods, such as pneumatic handling [10], dielectrophoresis [11], thermocapillary [12], electrostatic [13], electrochemical [7] and electro-wetting [14], and the precision as well as flexibility in liquid volume control.

Droplet creation by electro-wetting actuation was demonstrated by Fair and co-workers [15], [16] and Cho et al. [17]. It was shown that droplets could be created from on-chip reservoirs by forming a liquid protrusion from the liquid in the reservoir followed by subsequent droplet pinch off with proper control of an electrode actuation sequence. Another option was to use an off-chip pressure source through which liquid could protrude and retract along a series of electrodes. A droplet could then be formed on a selected electrode that remained activated while the liquid was retracted [15], [18].

A few issues arise when droplets are formed with simple electro-wetting actuation without pressure assistance. One is that a high actuation electric field is required to conform the liquid front to the electrode dimensions when the liquid protrusion is formed. In addition, the dependence of the electrode control sequence on liquid properties and surface conditions makes it a difficult task to automate the dispensing process. Furthermore, on-chip reservoir dimensions set the upper limit on the total number of droplets that can be produced. Finally, it is impossible to generate droplets at high production rates due to the physical limitation of the dispensing process. The same controllability issues arise when droplets are dispensed with pressure assistance. Variations in liquid properties and system dimensions make it difficult to determine the magnitude of the required pressure to adjust the corresponding flow rate of liquid feeding. Most essentially, both methods suffer from degeneration of channel surfaces and insulating layers at high electrode voltages, which largely determine the reproducibility of droplet volumes, especially when large numbers of droplets are desired.

Static capacitance was used by Verheijena and Prins [19] in measuring the contact angle and wetting velocity in an electro-wetting configuration. For a droplet sandwiched in the channel of the electro-wetting chip in [14], the droplet volume can be approximated by the contact area multiplied by the gap between two parallel plates used to confine the droplet. With the contact area measured by static capacitance, droplets of high precision in volume can be dispensed with feedback control in an electro-wetting chip. In this work, a device that uses capacitance feedback to meter droplet volume for dispensing has been developed [20]. High reproducibility, controllability as well as reasonable droplet production rates have been achieved for dispensing droplets of aqueous solutions of different viscosities in the microliter/nanoliter scale. The system can be used for sample loading and reagent dosing as well as real-time control of droplet volumes during on-chip liquid handling. The overall schematic of the system is discussed in Section 3. The principle of droplet volume control with capacitance metering is described and analyzed in the section on design and analysis. The droplet dispensing process is demonstrated and discussed in the section on results and discussion. In the same section, the issues of on-chip droplet volume calibration are taken into account.

Section snippets

The capacitance of a droplet

A cross-section of an electro-wetting actuator is shown in Fig. 1. When a discrete droplet aligns with the bottom electrode, a capacitor is formed between the bottom surface of the droplet and the buried control electrode [15]. Contact to the capacitor is made through the liquid droplet and the top ground electrode. The equivalent capacitance between the control electrode and the droplet is a function of the droplet volume, which only depends upon the area that the droplet covers. This area is

Continuous-flow loading and coupling

Fig. 3 is a schematic of the overall system for droplet dispensing. An electric motor driven pump provided the pressure source for loading liquid samples. A pressure regulator from Cole-Parmer was employed to adjust the pressure range from 0 to 60 psig. A solenoid three-way valve controlled by a computer was used to provide continuous-flow cut-off. The valve was shown in the experiment to be removable at flow rates smaller than 5 μl/min. The continuous liquid feeding channel was coupled to the

Results and discussion

Initially, regular unit size electrodes were used for droplet metering. Droplet dispensing is demonstrated in Fig. 6, which shows time-lapse pictures of a droplet being formed from a source of 0.1 M KCl solution. The process is automated by simply setting the value of cut-off capacitance.

The dynamic capacitance measurement associated with droplet generation is shown in Fig. 7. Frequency is the direct readout of the oscillation circuit and is used to represent the capacitance measurement. The

Conclusions

A capacitance feedback method has been demonstrated for controlled volume generation of droplets with electro-wetting actuation. In this method, the droplet volume is metered by measuring the intrinsic capacitance value between electrolyte droplet and a buried control electrode. By regulating the pressure differences caused by fluidic properties, channel geometry, and external pressure values, the dispensing mechanism allows good control of droplet volume and fast, automated droplet creation.

Acknowledgements

The authors wish to thank Vijay Srinivasan for his assistant in the experimental work and Junhua Wu for his previous work in droplet dispensing.

Hong Ren received her M.S. degree in electrical engineering from Duke University in 2000, and currently she is working toward the PhD degree at Duke University. Her research interests include microfluidics, lab-on-chip design, microsystem design, modeling and simulation, and analog interface circuit design.

References (21)

  • V. Gass et al.

    Integrated flow-regulated silicon micropump

    Sens. Actuators A

    (1994)
  • N.T. Nguyen et al.

    Hybrid-assembled micro dosing system using silicon-based micropump/valve and mass flow sensor

    Sens. Actuators A

    (1998)
  • D. Rose, Microdispensing technologies in drug discovery, Drug Discov. Technol. 4 (September (9)) (1999)...
  • M. Elwenspoek et al.

    Towards integrated microliquid handling systems

    J. Micromech. Microeng.

    (1994)
  • ...
  • S. Böhm et al.

    An integrated micromachined electrochemical pump and dosing system

    J. Biomed. Microdev.

    (1999)
  • S. Böhm et al.

    A closed-loop controlled electrochemically actuated micro-dosing system

    J. Micromech. Microeng.

    (2000)
  • K. Handique, D.T. Burke, C.H. Mastrangelo, M.A. Burns, Nanoliter-volume discrete drop injection and pumping in...
  • T. Nisisako et al.

    Droplet formation in a microchannel network

    Lab Chip

    (2002)
  • K. Hosokawa, T. Fujii, I. Endo, Hydrophobic microcapillary vent for pneumatic manipulation of liquid in μTAS, in:...
There are more references available in the full text version of this article.

Cited by (173)

  • Fully automatic integrated continuous-flow digital PCR device for absolute DNA quantification

    2020, Analytica Chimica Acta
    Citation Excerpt :

    The microwell digital PCR system requires a professional chip loader to load and seal the chips. The Droplet Digital PCR System not only relies on expensive droplet generation chips and oils but also requires a bulky pneumatic pump and interfaces that connect the specific hip to a pressure source, which provides power for droplet generation [28,29] and generates water-in-oil droplets through the droplet generation chip. Droplet reaction is realized by a temperature cycler with the disadvantages of large volume, high energy consumption, and high cost.

  • Introduction to microfluidics

    2020, Drug Delivery Devices and Therapeutic Systems
View all citing articles on Scopus

Hong Ren received her M.S. degree in electrical engineering from Duke University in 2000, and currently she is working toward the PhD degree at Duke University. Her research interests include microfluidics, lab-on-chip design, microsystem design, modeling and simulation, and analog interface circuit design.

Richard B. Fair is professor of electrical and computer engineering at Duke. He received the PhD from Duke University in 1969. He then spent 12 years at Bell Labs working on semiconductor devices and integrated circuit technology. He returned to North Carolina in 1981 and spent 13 years as an officer of MCNC, having responsibilities in chip design, computer-aided design, packaging, process technology, and MEMS. His current research interests include bio-MEMS and bio chips. He has published over 120 papers in refereed journals and conference proceedings, written 10 book chapters, edited eight books or conference proceedings, and given over 100 invited talks, mostly in the area of semiconductor devices or the fabrication thereof. Dr. Fair is also a fellow of the Institute of Electrical and Electronic Engineers (IEEE), and fellow of the Electrochemical Society, past editor-in-chief of the Proceedings of the IEEE, and he has served as associate editor of the IEEE Transactions on Electron Devices. He is a recipient of the IEEE Third Millennium Medal and the 2003 Solid State Science and Technology Award from the Electrochemical Society.

Michael Pollack received the PhD degree in electrical and computer engineering from Duke University in 2001. Currently, he is a post-doctoral research fellow at Duke. His research interests include microfluidics, lab on the chip technology, and applications of digital microfluidics.

View full text