RESONANT FLUIDIC CIRCUITS FOR SOUND-CONTROLLED POINT-OFCARE DIAGNOSTICS

Reid Phillips, Rachana Shah, Yoni Browning, Paul Yager, Barry Lutz*
Department of Bioengineering, University of Washington, Seattle, WA, USA ABSTRACT Microfluidic systems can be represented by an analogy to electrical circuits. Nearly all microfluidic devices are based on steady (DC) flow through simple channels (resistors). Here, we describe microfluidic networks driven by oscillating (AC) flow that are designed to operate as resonant RLC circuits. Resonant circuits are used to create frequency-selectable pumps that can be controlled by audio tones, as well as audio-based detectors. Together, these provide two core functions--fluidic control and detection--that could allow point-of-care diagnostics to be controlled by cell phone audio signals. KEYWORDS: point-of-care diagnostics, global health, cell phones, microfluidic networks INTRODUCTION One of the primary remaining challenges in creating useful point-of-care diagnostics is reducing the expense and physical burden of the instrumentation [1]. Nearly every person on the planet has access to a sophisticated portable instrument, i.e., a cell phone, that has many key features needed for portable diagnostics--they are inexpensive, battery-powered, and easy to operate--and they are capable of generating and detecting information-rich audio signals. Smart phones have been used as instruments to support diagnostics using imaging or electrical sensing. We aim to use the audio capability found on all phones to control devices and detect assay results. The field of microfluidics was preceded by the Cold-War-era fluidics movement, which developed flow-based analogues of electrical circuits to create radiation-resistant control systems. In this analogy, current corresponds to flowrate; voltage corresponds pressure; and resistors (R), inductors (L), capacitors (C), and diodes can be related to device geometry and fluid properties. However, in the transition to microfluidic scales, much of this functionality was lost. Today, nearly all microfluidic devices are resistors driven by DC flow. In electrical circuits, sophisticated functions can be created using simple combinations of resistors, inductors, capacitors, and diodes. For example, classic radio tuners are simply band-pass filters based on resonant RLC circuits, where the station is tuned by changing the capacitance or other component using a dial. By using AC (oscillating) flow in microfluidic devices, the rich behavior of RLC circuits can be resurrected. The Landers group recently exploited this analogy to create a 2-channel frequency-tunable RC pump [2-3]. Here, as suggested by that group, we introduce inductive elements (L) to create complete RLC fluidic circuits with the high selectivity needed to turn pumps on and off. We also show that RLC fluidic circuits can create an audio-based detector that measures changes in circuit elements via the shift in peak circuit resonance. Thus, simple plastic cards connected to a cell phone could be used to carry out multi-step assays and detect the assay results via audio signals (Fig. 1, left). Unlike emerging smartphone-based diagnostics, this approach exploits the inherent audio capabilities found on every cell phone. THEORY Fluid channels acts as resistors and inductors, flexible elements (e.g., diaphragm, bubble) act as capacitors, and a piezodriven diaphragm acts as a voltage source driven through a capacitor (Fig. 1, right). Equivalent electrical circuits can be constructed by treating capacitors as parallel elements and connecting all other circuit elements in series as would be expected. Component values can be estimated based on fluid and material properties [2-3]. In our work, R and L values were calculated using more complete expressions that correctly account for frequency dependence and channel aspect ratio [4]. It is important to note that the physics includes no acoustic effects, rather the piezo drives back-and-forth oscillation of fluid in the channels (direct analogy to AC current); resonance is created based on the interaction of components in the circuit.

Figure 1. Vision concept for using cell phone audio to control point-of-care diagnostics. (Left) The audio output (speaker) controls a multi-step assay sequence, and the audio input (microphone) detects the assay result. (Right) Channels and flexible elements (diaphragm, bubble) create fluidic analogies to electrical components (resistors, inductors, capacitors).
978-0-9798064-4-5/TAS 2011/$2011CBMS-0001 1203
15th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 2-6, 2011, Seattle, Washington, USA

EXPERIMENTAL Devices were fabricated from laser-cut adhesive laminates, but the single-layer devices are compatible with highthroughput manufacturing methods (e.g., injection molding). Oscillating flows were generated by a single piezo disk attached to a diaphragm and driven at audible frequencies (400-2000 Hz) by a sine wave generator or cell phone. The AC flowrate was calculated from measurement of the oscillating streak length of 5 micron fluorescent beads in solution. Diaphragm capacitors were made with 10 mil Mylar film, and bubble capacitors were created by laser cutting dead end cavities in the channels. Diaphragm capacitance values were measured directly via RLC resonance in separate experiments. RESULTS AND DISCUSSION By choosing resistive (R), inductive (L), and capacitive (C) contributions that are approximately balanced in the range of audible frequency, we have created microfluidic networks with sharp resonant peaks (high Q-factor). The resonant frequency of each channel was set during fabrication by using a different fluidic capacitor (a diaphragm of different size) in otherwise identical fluidic circuits (Fig. 2, left), and the entire system was driven by a single piezo disk oscillator attached to a diaphragm. The AC flowrate magnitude was measured in each of the three channels across a range of audible driving frequencies (measured at the location of colored R and L components). Figure 2 (right) shows that each channel resonates at a distinct frequency, and the model accurately predicts the resonant behavior (no adjustable parameters were used in the model). A small amount of cross-talk between channels can be seen in the data and model prediction (discussed below).

Figure 2. RLC fluidic circuits driven by audio tones. Three input legs with different diaphragms (capacitance) create RLC circuits that are selectively excited at different frequencies by a piezo oscillator. An equivalent circuit model accurately predicts measured circuit resonances. When diodes are added (Fig. 3) each leg becomes a frequency-selectable pump. Classic diffuser valves [5] were added to the circuit in Figure 2 at the location of the colored R and L components. The channel dimensions were changed slightly to maintain the same overall R and L values in each channel (the diode has little effect). Resonance within a given leg produces large oscillating flow across the diffuser valve, and partial rectification of the oscillating flow produces a net flow (a pump). Figure 3 shows a 3-step fluid delivery using audio tones; each fluid (blue, red, colorless) was driven in sequence by selecting the corresponding audio tone for resonance in each channel. The on-off behavior is excellent. Figure 2 showed some cross-talk between channels, but this did not result in observable cross-talk in

Figure 3. Frequency-selectable pumps based on RLC resonant circuits driven by audio tones. Diffuser valves were added to each leg of the device from Figure 2 to act as flow rectifiers (leaky diodes), and oscillation (AC flow) within a leg creates a frequency-selectable pump (DC flow). A series of audio tones turns pumps on and off in a timed sequence blue (1800 Hz), red (800 Hz), and colorless (1300 Hz). This ability to deliver multiple fluids in a timed sequence is the basis of most laboratory assays. Assay chemistries (e.g., immobilized antibodies) would be placed in the rightmost channel.
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the pumping behavior. This is expected since the efficiency of the diffuser valves is a non-linear function of the AC flowrate, such that small oscillations may not be sufficient to drive net flow. The high selectivity in this RLC design allowed each fluid to be turned on and off by simply changing the driving frequency. These pumps can be driven from the audio jack of a phone without amplification, although the magnitude of flow is significantly smaller. The same RLC resonant behavior can be used to create audio-based detectors when one component of the circuit changes. As shown in Figure 4, a bubble (capacitor, Cb=Vb/Patm) in an otherwise uninteresting channel creates an RLC circuit with resonant frequency determined by the size of the bubble. The model is derived directly from the equivalent electrical circuit, and the model result is fullypredictive using parameters from measured device Figure 4. Audio detection using RLC resonant circuits. A dimensions (no adjustable parameters). Thus, a simple variable circuit component (bubble capacitor) was added to RLC circuit produces a resonance that detects the size of create an RLC circuit with resonance determined by the the bubble. The sensitivity is greatest for small bubble bubble size (red 310 nL, green 160 nL, blue 60 nL). The ratio sizes. It is important to note that the classic volumetric of downstream/upstream fluid displacement magnitude resonance for a bubble in free solution occurs at much (current) was measured optically from bead displacement higher frequency; the resonance observed here arises from images. The model predictions use no adjustable parameters. the interaction of all circuit components, and the bubble Unknown bubble sizes can be detected by varying the simply acts as a capacitor (just like the diaphragms above). capacitance in the fitted model. Changes in viscosity (resistance) or density (inductance) can provide similar detectable changes. If one of the circuit elements can be made to respond to the presence of analyte, a resonant RLC circuit can be used as an audio-based detector. We are currently working to develop chemistries to provide signal transduction for audio-based detection. CONCLUSIONS Many groups have demonstrated the potential for smart phones to support point-of-care diagnostics, most commonly through imaging or electrochemical measurements. Here, we exploited the audio capability found on all phones to control fluids in simple microfluidic cards and to detect a property of the fluid in a channel. By using RLC circuits, we created sharp resonant peaks that could be easily resolved within the audio frequency range. Equivalent electrical circuits provided excellent prediction of the behavior, and thus can serve as useful design tools for designing circuits. ACKNOWLEDGEMENTS R.P. was funded by scholarships from the Washington Research Foundation, UW Mary Gates Scholar Program, UW NASA Space Grant Consortium, and the UW Department of Bioengineering (Senior Capstone Scholarship). R.S. was funded as an NSF Graduate Research Fellow. We thank Paul Yager for his role in the conception of the idea and for financial support, and we thank Peter Kauffman, James Wong, and Stephen Marshall for technical contributions. REFERENCES [1] Yager, P., Edwards, T., Fu, E., Helton, K., Tam, M. R., and Weigl, B. H. Microfluidic diagnostic technologies for global public health. Nature 442, 412-418 (2006). [2] Begley, M.R., Utz, M., Leslie, D.C., Haj-Hariri, H., Landers, J.P. Periodic response of fluidic networks with passive deformable features. Applied Physics Letters, 95(20), 203501/1-3 (2009). [3] Leslie, C. D., Easley, C. J., Seker, E., Karlinsey, J. M., Utz, M., Begley, M. R., and Landers, J. P. Frequency specific flow control in microfluidic circuits with passive elastomeric features. Nature Physics, 5, 231-235 (2009). [4] Morris, C. J. and Forster, F. K. The correct treatment of harmonic pressure-flow behavior in microchannels. MicroElectro-Mechanical Systems (MEMS), 2, 473-479 (2000). [5] Olsson, A., Stemme, G., and Stemme, E. Diffuser-element design investigation for valve-less pumps. Sensors and Actuators A, 57, 137-143 (1996).
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CONTACT Barry Lutz, blutz@uw.edu.

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