Volume 13 | N

umber 19 | 2013

Lab on a Chip

Pages 3767–3978 1473-0197(2013)13:19;1-Q

ISSN 1473-0197

Lab on a ChipMiniaturisation for chemistry, physics, biology, materials science and bioengineering

www.rsc.org/loc Volume 13 | Number 19 | 7 October 2013 | Pages 3767–3978

OFC COVER SCAN

TO FIT INTO THIS BOX

www.rsc.org/locRegistered Charity Number 207890

Featuring work from the laboratory of Dr. Carolyn Ren,

in the Department of Mechanical and Mechatronics

Engineering at the University of Waterloo.

Title: Microwave sensing and heating of individual droplets in

microf luidic devices

Our research primarily focuses on fundamental studies of microf luidic transport phenomena and Lab-on-a-Chip technology for a wide range of applications. Here we present a novel microwave system for simultaneous sensing and heating of individual nanoliter-sized droplets in microfl uidic devices.

PAPER David Sinton et al.Steam-on-a-chip for oil recovery: the role of alkaline additives in steam assisted gravity drainage

As featured in:

See Carolyn L. Ren Lab Chip, 2013, 13, 3840.

LC013019_cover_PRINT.indd 1LC013019_cover_PRINT.indd 1 8/26/2013 3:43:59 PM8/26/2013 3:43:59 PM

Cite this: Lab Chip, 2013, 13, 3840

Microwave sensing and heating of individual dropletsin microfluidic devices3

Received 4th April 2013,Accepted 25th June 2013

DOI: 10.1039/c3lc50418b

www.rsc.org/loc

Muhammed S. Boybay,a Austin Jiao,b Tomasz Glawdelc and Carolyn L. Ren*c

Droplet-based microfluidics is an emerging high-throughput screening technology finding applications in

a variety of areas such as life science research, drug discovery and material synthesis. In this paper we

present a cost-effective, scalable microwave system that can be integrated with microfluidic devices

enabling remote, simultaneous sensing and heating of individual nanoliter-sized droplets generated in

microchannels. The key component of this microwave system is an electrically small resonator that is able

to distinguish between materials with different electrical properties (i.e. permittivity, conductivity). The

change in these properties causes a shift in the operating frequency of the resonator, which can be used

for sensing purposes. Alternatively, if microwave power is delivered to the sensing region at the frequency

associated with a particular material (i.e. droplet), then only this material receives the power while passing

the resonator leaving the surrounding materials (i.e. carrier fluid and chip material) unaffected. Therefore

this method allows sensing and heating of individual droplets to be inherently synchronized, eliminating

the need for external triggers. We confirmed the performance of the sensor by applying it to differentiate

between various dairy fluids, identify salt solutions and detect water droplets with different glycerol

concentrations. We experimentally verified that this system can increase the droplet temperature from

room temperature by 42 uC within 5.62 ms with an input power of 27 dBm. Finally we employed this

system to thermally initiate the formation of hydrogel particles out of the droplets that are being heated

by this system.

Introduction

A critical need for enhancing the usability of droplet-basedmicrofluidic devices as an enabling high-throughput screeningtechnology is the development of new techniques for thedetection and manipulation of individual nanoliter-sizeddroplets at high frequencies (0.1–10 kHz). A key requirementfor these techniques is that they should be ‘remote’ (nophysical contact with the droplets) to eliminate any contam-ination. Although various optical methods are available forthis task1–3 a versatile non-optical technology that allows fordirect probing of droplets in real time is urgently needed asnon-optical methods in general are easier to scale up. Here, wedemonstrate the application of miniature microwave resona-tors to achieve simultaneous sensing and heating of individualdroplets generated in microchannels at high frequencies.

When operating as a sensor, the resonator is able to remotelydetect the content of each droplet based on its electricalproperties (permittivity, conductivity); and when operating as aheater, the resonator provides rapid, localized, selective, andself-triggered heating of individual droplets. The resultingresonator architecture should find uses as a sensor inmonitoring reaction output and as a thermal actuator invarious material synthesis strategies.

Temperature control is one of the key functions requiredfor many droplet-based microfluidic applications such aspolymerase chain reaction,4 thermally based protein analysis5

and thermally initiated material synthesis.6,7 Various externalheater designs (resistive, joule, Peltier modules)8–10 have beenincorporated into microfluidic devices; however, these meth-ods rely on thermal conduction to deliver energy and do notprovide sufficient localization to heat up a single droplet.Laser based techniques are able to achieve sufficient spatiallocalization but require complicated configurations to performsimultaneous heating and sensing (infrared laser, excitationlaser for fluorescence, etc.).11 Microwave heating, in contrast,can selectively deliver energy to or probe a single dropletwithout affecting its carrier fluid by taking advantage of thedisparity in dielectric properties between droplets. Microwavetechnology has been applied to material spectroscopy,12,13

sensing14 and dielectric heating, especially for drug discov-

aDepartment of Computer Engineering, Antalya International University, Universite

Caddesi No:2, 07190 Antalya, TurkeybNanotechnology Engineering, University of Waterloo, 200 University Avenue West,

Waterloo, Ontario, N2L 3G1, CanadacDepartment of Mechanical and Mechatronics Engineering, University of Waterloo,

200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada.

E-mail: c3ren@uwaterloo.ca; Fax: +1 519 885 5862; Tel: +1 519 888 4567 x 33030

3 Electronic supplementary information (ESI) available. See DOI: 10.1039/c3lc50418b

Lab on a Chip

PAPER

3840 | Lab Chip, 2013, 13, 3840–3846 This journal is � The Royal Society of Chemistry 2013

ery15 and polymerization.16,17 Microwave heating of droplets inmicrofluidic chips has also been demonstrated; however, thereported techniques cannot achieve selective heating ofindividual droplets due to their working mechanisms18,19 asexplained below.

The reported microwave techniques18,19 employ microwavecavities or transmission line resonators that are based on theconstructive interference of propagating waves to deliverenergy for heating purposes. In order to heat up individualnanoliter-sized droplets, such working mechanisms requireextremely high resonance frequencies which require theresonators to be fabricated to an extremely high accuracyadding prohibitive challenges to practical operations. This isbecause the size of such resonators is on the order of l/2,where l is the operating wavelength and normally ranges from1 mm to 1 m. Their corresponding operating frequenciesrange from 300 GHz to 0.3 GHz. The smaller the operatingwavelength, the higher the resonance frequency required. Ifthis type of resonator is chosen for heating up a singlenanoliter-sized droplet (i.e. a 100 mm sphere) with a highefficiency, its operating wavelength and corresponding reso-nance frequency would be on the order of 200 mm and 1500GHz, respectively. Such a high resonance frequency ispractically prohibitive because of the extremely high accuracyneeded in fabrication of electrodes. In addition, the electricfield distribution within the resonator is a sinusoidal functionwhich prevents localized heating with a high efficiency.Therefore, a different working mechanism is needed forselective heating of individual droplets, which prompts thisstudy.

Experimental

Device fabrication

The device consists of two parts, a base with the microwavecomponents and a polydimethylsiloxane (PDMS) mold withthe designed microchannels for making droplets, which arefabricated separately and then bonded together. The electricaltraces for the microwave components were fabricated using acombination of photolithography and electroplating (see Fig.S6 and S7, ESI3). Briefly, the positive photoresist, S1813 (Rohm-Haas), is spin coated at 1500 rpm for 60 s onto the 50 nm thickcopper film (EMF Corporation) that is pre-deposited on a glassslide and then baked at 120 uC for 75 s. The resonator design ispatterned into the photoresist via UV lithography andsubsequently developed with the developer, MF-319 (Rohm-Haas). The patterned slide is then immersed in an acidiccopper electroplating solution (0.2 M CuSO4, 0.1 M H3BO3, and0.1 M H2SO4) and electroplated at 2 mA and 4.3 V for 2 minand then 7 mA and 15 V for 24 min. After electroplating, thephotoresist is removed with acetone leaving an electroplatedcopper film approximately 5 mm thick. Next, the original baselayer of copper is removed by etching with dilute ferricchloride (MG Chemicals). A passivation layer of a PDMSvariant (EG-6301, Dow Corning) is then spin coated at 4000rpm onto the glass to protect the electrical traces. A

subminiature version A (SMA) connector (Tab Contact,Johnson Components) is then soldered to the electrodes ofthe microwave components to provide an external connectionto the microwave function generator (HMC-T2100, Hittite) forheating or to the vector network analyzer (VNA) (MS2028C,Anritsu) for characterizing the microwave sensor (Fig. S4,ESI3). Microchannels are fabricated from PDMS using stan-dard soft-lithography techniques. The PDMS is mixed in a10 : 1 ratio of base to curing agent and moulded against SU-8/silicon masters and then cured at 90 uC for 2 h. The mouldsare then cut out from the masters and fluidic access holes aremade using a 500 mm biopsy punch. Both the finishedmicrowave parts and the PDMS chip are then treated withoxygen plasma at 29.7 W, 500 mTorr for 45 s. The plasmatreatment process renders the PDMS hydrophilic; however, forwater in oil droplets, the PDMS channels should be hydro-phobic to form the oil phase. To do so, the chip is heated at200 uC for 24 h.

Materials

All aqueous NaCl and glycerol solutions were prepared withdouble-distilled water. Similarly, 2 mM aqueous fluorescein(Invitrogen) solutions were buffered at 7.1 pH with Tris-HCland at 9.0 pH with sodium bicarbonate, for heating andmixing experiments, respectively. For droplets we usedFluorinert FC-40 with 2% perfluoro-1-octanol surfactant(Sigma-Aldrich) as the continuous phase.

Microwave characterization and control

Resonance of the microwave device was characterized bymeasuring the reflection coefficient (dB) for a range offrequencies using the VNA. For heating, the resonator wasconnected to the high power microwave signal generator. Eachchip was mounted onto an inverted epifluorescence micro-scope system (Eclipse Ti, Nikon) with a high speed CMOScamera (Phantom v210, Vision Research) and a low speed,high sensitivity CCD Camera (Retiga 2000R, QImaging). Fluidswere connected to the device by ETFE (ethyltrifluoroethylene)tubing (Tefzel, Upchurch Scientific) and driven by a highprecision microfluidic pressure system (MFSC-8C, Fluigent) ora dual syringe pump (Pump33, Harvard Apparatus).

Temperature measurements

The temperatures of single-phase fluids and droplets in thechannels were experimentally measured using a microscopyfluorescence thermometry technique.20 Fluorescein dye wasdissolved in 10 mM Tris-HCl buffered at pH 7.1. Althoughfluorescein is normally a poor candidate for thermometrymeasurements because its quantum efficiency shows weaktemperature dependence, it does possess strong pH depen-dence in the pH range of 6–7. Concurrently, Tris-HCl has astrong pH–temperature dependence, which allows the pH–fluorescence behaviour of fluorescein to be converted into atemperature dependent fluorescence response. A calibrationcurve was obtained using the methods outlined previously.20

Images of the microchannel with the microwave heater on arenormalized against images with the heater off to removeartifacts associated with variation in geometry, illuminationand detector sensitivity. For droplet experiments, long

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Lab on a Chip Paper

exposure times (4 s) and frame averaging (160 frames) wereemployed to obtain steady profiles due to the periodic natureof the flow.

Results and discussion

Sensor and heater design

To meet the urgent need for a new working mechanism thatenables heating of individual nanoliter-sized droplets, wepropose the use of electrically small microwave resonatorsbecause they allow the maximized power to be transferred to asmall volume.21 Electrically small resonator structures arebased on metamaterial unit cell designs,22,23 which wereoriginally developed to engineer artificial materials withspecific electromagnetic responses and to control plasmonicbehaviours at frequencies lower than the optical spectrum.24,25

Resonator structures have been previously used for sensingpurposes,26 although we use such a structure for both heatingand sensing of droplets.

The proposed microwave resonator consists of two electricaltraces as shown in Fig. 1: (i) the resonator, a circular inner loopwith a small gap through which the microchannel is to bealigned; (ii) a concentric excitation loop that supplies micro-wave power to the resonator. The resonator was designed tooperate below 3 GHz as microwave components in thisfrequency range are inexpensive and widely available.Microwave energy is inductively coupled to the resonator bythe excitation loop and there is no physical contact betweenthe two loops. Here we fabricate the excitation and resonatorloops in a coplanar arrangement for easy alignment; however,the excitation loop can be made independent and the

resonator can be activated off-chip allowing for remotecontrol.

In such a microwave structure, the electric field energy isstored within the capacitor of the resonator (the gap region)and the magnetic field energy is stored in the inductor of theresonator. If a microfluidic channel is aligned with thecapacitive gap, the passing fluid interacts with the electricfield generated by the capacitor causing a frequency shift asillustrated in Fig. 2. When there is a perturbation in thepermittivity of the medium, the resonance frequency shiftsby27

Df

f~

{Ð

V0DeE|E�0dv

ÐV0

eE|E�0zmH|H�0� �

dv(1)

where E0 and E are the electric fields before and after theperturbation, H0 and H are the magnetic fields before andafter the perturbation, f is the resonance frequency before theperturbation, e is the permittivity of the medium and m is thepermeability of the medium. This shift can be used to sensethe presence of a single droplet and its content. In addition, ifpower is sent at the shifted frequency, only the droplet isinternally heated without affecting its surrounding medium(such as oil) or the chip material. A powerful feature of such adesign is that power transfer can be set to a specific frequencyrelated to the content so that the appearance of a droplet ofthe right type triggers the heater.

Sensing performance

As shown in eqn (1), the frequency shift, which also indicatesthe sensitivity of the sensor, is a function of the permittivitycontrast between the droplet and its surrounding medium and

Fig. 1 (a) The electrically small resonator is designed to operate below 3 GHz since the microwave components at this frequency are widely available and cheap. A Tshaped capacitive region is used as the sensing and heating region. The resonator is excited by a loop and the microwave energy is transmitted to the loop by acoplanar transmission line. The excitation structure was optimized to provide highest energy coupling to the resonator by using Ansoft HFSS, a commercial finiteelement method based full wave simulator. For this particular design all the microwave components are in the same plane for fabrication simplicity. (b) An illustrationof the alignment of the microchannel with the resonator. When the droplets pass above the capacitive region, the capacitance changes, which shifts the resonancefrequency. The shifted resonance frequency is unique to the size, but most importantly, the composition of the droplet. In order to use the structure as a heater, thisresonance frequency is measured and the resonator is excited at this frequency. Resonance and absorption of incoming power only occurs for the specific fluid thathas this resonance frequency. (c) Microscope image of the fabricated chip.

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the volume of the droplet. It can be seen that the sensitivityincreases with the permittivity contrast. The effect of thedroplet size on the sensitivity depends on the relative size ofthe droplet and the sensor. As a result of the confinement ofthe electric field in the sensing region, when the size of thedroplet is larger than the sensing region, droplet size does notaffect the resonance frequency and thus the detectionsensitivity. The focus of this work is to demonstrate thefeasibility and potential of the microwave technique forsimultaneous sensing and heating of individual droplets, sothe droplet size is chosen to be larger than the sensing region.

To determine the resonator’s sensing capability, we mea-sured the reflection coefficient of the resonator for variousfluids in microchannels as a function of frequency assummarised in Fig. 2. It can be seen that the sensor is ableto differentiate between fluids of different permittivity (Fig. 2a)

and conductivity (Fig. 2b). The resonance frequency shift withrespect to air was found to be 18.5 MHz for silicon oil, 12.5MHz for FC-40, 174.5 MHz for water and 161 MHz and 149MHz for the 25% and 50% glycerol–water mixtures (wt.%),respectively.

To demonstrate the sensor’s effectiveness in handling non-ideal solutions, we tested the sensor against various dairyfluids (Fig. 2c). Each fluid shows distinct profiles that may beused to identify fat and dissolved salt content, both of whichare important parameters in dairy herd health.28,29 Inaddition, the microwave resonator was also applied to detectthe presence of water droplets (Fig. 2d), suggesting that itcould potentially be used as a coulter counter in manyapplications.

Fig. 2 (a) The reflection coefficient of the resonator was monitored to detect the changes in the channel. The commonly used fluids for the continuous and dispersedphases were tested including silicon oil (typical e = 2.2–2.7), FC-40 (e = 1.9), and a series of water (e = 78)–glycerol (e = 42) mixtures (0%, 25% and 50% glycerol, wt.%).(b) Saline water was used to study the response of the sensor to changes in the conductivity of the fluid flowing through the channel. The conductivity of the fluidaffects the quality factor of the resonator and was sensed by monitoring the reflection magnitude at the resonance frequency. Salinity levels of 0%, 0.5%, 1%, 2%,3%, 5%, and 10% correspond to ionic conductivity values of 0 S m21, 0.79 S m21, 1.53 S m21, 2.90 S m21, 4.17 S m21, 6.59 S m21 and 10.67 S m21, respectively at 20uC.31 (c) The response of the sensor against dairy fluids, 2% milk and 35% cream diluted with different ratios, were compared. (d) Droplets were sensed as they werepassing through the capacitive region by tracking the resonance frequency. Water droplets in FC-40 with 2% perfluoro-1-octanol surfactant were generated at afrequency of 1.25 Hz. The resonance frequency dropped to 2621.25 MHz when the droplets were detected. Our experiments were limited by the response time of theVNA. The detection speed can be increased by developing a customized microwave circuitry for this application. Fundamentally, since the operating frequency of thesensor is in the GHz regime, the operating speed of the sensor is not a limiting factor.

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Heating performance

The resonator dissipates energy by three mechanisms. Thefirst is by radiation, which is negligible for a small resonatordue to its low radiation resistance. The second mechanism isthe conductive loss in the resonator, which is spread throughthe loop, therefore heating due to the conductive loss is notlocalized. The third mechanism is the dielectric loss within thecapacitive gap region. According to our numerical analysis ofthe microwave resonator structure, 45% of the energy isdissipated within a 2 nL volume in the capacitive gap region(see Fig. S1, ESI3 for the details on the design andcharacterization of the resonator), which shows that theelectrically small resonator can deposit the microwave energywith a high efficiency.

To quantitatively evaluate the resonator’s heating perfor-mance, several single phase fluids and then water-in-oildroplets were heated using the resonator. Pumping only purewater through the microchannel, the temperature at the exit ofthe resonator was measured for a range of the applied powersand frequencies as shown in Fig. 3a. The resonance frequencyis associated with the highest heating efficiency and thus themaximum temperature achieved for an applied power. Wenote that there is a shift in the resonance frequency at higherpowers which is caused by the temperature based permittivitychange of water (y0.3%/uC).30,31 In fact, this property can alsobe used to extract the temperature of the fluid if the resonatoris operated as a sensor. Subsequently, the resonator was usedto heat individual water droplets in oil streams and the

Fig. 3 (a) The heater is tested on single phase water. The water temperature depends on the excitation frequency and input power. The optimum operatingfrequency (the black curve) for achieving the maximum temperature depends on the permittivity of the water. Since the permittivity of the water reduces as thetemperature increases, the optimum frequency shifts to higher frequencies. (b) The droplet temperature is a function of the input power. The excitation frequencywas 2.69 GHz. The blue points present the measured data and the black line is the average of four different measurements. (c) The temperature distribution over thechannel where the droplets are being heated at different frequencies shows that the temperature reduces by 20 uC with a shift of 60 MHz in the operating frequency.(d) The temperature distribution along the channel at 2.69 GHz is plotted for 27 dBm and 25 dBm input powers. The temperature increases with the operatingfrequency within the heating zone. In this experiment, the droplets are 367 mm long generated based on flow rates of 11.63 mL min21 and 7.71 mL min21 for thecontinuous and dispersed phases, respectively, in a 200 mm wide, 50 mm high channel.

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temperature rise as a function of the applied power (at theresonance frequency) was recorded as shown in Fig. 3b.Micrographs of the fluid temperature distribution near theresonator for two input powers are presented in Fig. 3c. Theimages show that droplets are being heated slightly before theheater due to the fringing fields generated by the capacitor andheat conduction through the surrounding chip material.Nevertheless, as droplets pass through the capacitance regionthey are heated very rapidly. In this example, the droplets (367mm long) have a residence time of 5.62 ms in the heatingregion and their temperature increases by 42 uC with an inputpower of 27 dBm. The average energy in each droplet isestimated to be 0.647 mJ by assuming the specific heat ofwater is 4.186 kJ kg21 K21 and the water droplets arerectangular cuboids of 367 mm 6 200 mm 6 50 mm. Bychanging the residence time (through decreasing the speed) orthe applied power, the temperature of the droplets can befinely tuned (Fig. 3b).

A sudden and well controlled heating pulse has the potentialto initiate thermal based polymerization within droplets. Thedeveloped microwave heater has the capability to providecontrolled heating pulses. To demonstrate this, we applied themicrowave heater to polymerize poly(N-isopropylacrylamide)(PNIPAM) hydrogel particles within microdroplets. Precursorchemicals, 0.5 g mL21 N-isopropylacrylamide monomer, 0.02 gmL21 N,N9-methylenebisacrylamide as a cross-linking agent,and 4,4-azobis (4-cyanovaleric acid) for the thermal initiator,were combined in water and used as the dispersed phase.Hexadecane was used as the continuous phase. By targetingthe resonance frequency of water, the initiator woulddisassociate into radicals and the hydrogel is generated byfree radical polymerization. The results can be seen in Fig. 4,where a precursor droplet approaches the microwave gen-erator. Subsequently, a separate, round hydrogel particle isformed behind the droplet. The hydrogel, due to being heated,exhibits temperature dependent hydrophobicity and repelsitself out of the aqueous droplet. Moreover, the cohesion of thehydrogel, in addition to it repelling both water and thesurrounding hexadecane oil, causes it to self-assemble into acircular shape at the back end of the droplet.

Another interesting application of confined heating is themanipulation of droplets using Marangoni stresses created by

temperature gradients. Previously, laser based localized heat-ing has been applied to stop, direct, merge and mix droplets inmicrochannels using this technique.11 It was hypothesizedthat the same manipulations could be achieved with themicrowave resonator structure. However, we found that thetemperature gradients were insufficient to provoke suchmanipulations (see ESI S33).

Conclusions

The microwave structure presented here can be used effec-tively as a sensor and heater and should find broadapplicability in various microfluidic devices. For example, itcould be used to detect the outcome in various conductivitybased bioassays in microdroplets where conventional contactelectrodes would lead to cross-contamination.32 It can also beapplied to detect conductive metal particles or traces in oilstreams as a feedback control tool for engine systems to avoidunnecessary oil replacements and testing.

Acknowledgements

Authors acknowledge the financial support from NaturalScience and Engineering Research Council of Canada andCanada Foundation for Innovation through grants to DrCarolyn L. Ren and scholarships to Dr Tomasz Glawdel. Wealso acknowledge the postdoctoral fellowship provided to DrMuhammed S. Boybay by Mitacs.

Authors fully acknowledge Zeyad Almutairi’s support inprocessing the high speed video files associated with thefigures and conducting calculations based on the video files.

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