Development of an Integrated Optofluidic Platform for Droplet and

Micro Particle Sensing

Microflow Analyzer for Interrogating Self Aligned Droplets and Droplet

Encapsulated Micro Objects

P. K. Shivhare

1,2

, A. Prabhakar

and A. K. Sen

Department of Electrical Engineering, Indian Institute of Technology Madras, Chennai, India

Department of Mechanical Engineering, Indian Institute of Technology Madras, Chennai, India

Keywords: Optofluidics, Microfluidics, Microflow Cytometry, Droplet Microfluidics, Microflow Analyser, Optical

Sensing, Single Cell Analysis, Emulsion, Scattered Signals, Fluorescence Detection, 3D Flow Focusing.

Abstract: Here we report the development of a micro flow analyser that integrates digital microfluidics technology with

optoelectronics for the detection of micron size droplets and particles. Digital microfluidics is employed for

the encapsulation of microparticles inside droplets that self-align at the centre of a microchannel thus

eliminates the need of complicated 3D focusing. Optoelectronics comprise a laser source and detectors for

the measurement of forward scatter (FSC), side scatter (SSC) and fluorescence (FL) signals from the

microparticles. The optoelectronics was first used with a simple 2D flow focusing channel to detect

microparticles which showed uncertainty in the data due to lack of 3D focusing. The integrated device with

digital microfluidics technology and optoelectronics was then used for the enumeration and detection of

Rhodamine droplets of different size. Rhodamine droplets of different size were characterized based on FSC,

SSC and FL. Finally, the device was used for the detection of fluorescent microbeads encapsulated inside

aqueous droplets.

1 INTRODUCTION

Integrated optical detection in a microfluidic platform

recently got an immense attention, and a new field of

study “Optofluidics” have emerged. On such

integrated platforms light and fluids are engineered

synergistically to implement a highly sensitive and

portable lab-on-chip bio-chemical sensors (Psaltis et

al. 2006; Testa et al. 2015). Innumerable integrated

optofluidic platforms were successfully demonstrated

in last few years for various applications for instance,

controlling liquid motion using light (Baigl 2012),

sunlight based fuel-production (Erickson et al. 2011),

microfabrication (Koh et al. 2015), and flow

cytometry (Godin et al. 2008). In particular

development of portable and economical microflow

cytometer is urgently required for addressing the

feeble diagnostic situations in rural areas of

developing countries. Various microflow analysers

were developed for different applications including

counting and studying biological cells (Zhang et al.),

bacteria (Verbarg et al. 2013), cellular DNA

(Ornatsky et al. 2008) droplets (Kunstmann-Olsen et

al. 2016).

Isolating and interrogating a micro-object from

bulk revealed that the differences in the micro objects

and biological cells exists due to the various natural

random processes (Xie et al. 2015). Traditional

methods, which involves measurement of the

probability distribution from a large population

ensemble of micro objects may prove to be

misleading (Carlo and Lee 2006; Huang et al. 2014)

since such study camouflages the unique behaviour

of the individual micro objects (Yang et al. 2016a).

The study and detection of this particularity may

prove to be helpful in early diagnosis of diseases like

cancer (Yang et al. 2016b), drug screening (Espulgar

et al. 2015), cellular drug metabolism (Chen et al.

2016), intracellular communication (Liu and Lin

2016), etc.

It is known from literature that Water in Oil

(W/O) or Oil in Water (O/W) droplets tends to move

toward the region with zero shear rate (Leal 1980),

this property can be exploited for eliminating the need

Shivhare P., Prabhakar A. and Sen A.

Development of an Integrated Optoﬂuidic Platform for Droplet and Micro Particle Sensing - Microﬂow Analyzer for Interrogating Self Aligned Droplets and Droplet Encapsulated Micro Objects.

DOI: 10.5220/0006174801710178

In Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2017), pages 171-178

ISBN: 978-989-758-216-5

171

of 3D flow focusing in microchannel for the

development of a microflow analyser. In addition,

ability of microfluidic platforms to manipulate small

volumes of fluids (~fL to ~nL) by efficiently

producing monodisperse droplets at very high speed

(kHz to MHz) makes it an ideal platform for single

particle analysis (Martino and Andrew 2016).

Miniaturization of traditional test tube into a

monodisperse droplet (Kintses et al. 2010) of few

micron size not only drastically decreases the volume

of sample required for analysis but also efficiently

compartmentalizes a particle for various single

particle analysis (Joensson and Andersson Svahn

2012). In addition recent developments in the field of

digital microfluidics (Jebrail and Wheeler 2010) have

equipped the researchers with a complete toolbox for

droplet manipulation which includes various

functional operations such as sorting, splitting,

mixing, incubation of droplets (Kintses et al. 2010).

Nevertheless, challenges exists in realizing a

commercially viable products. The main hindrance in

the development of a microflow analyser are

complicated techniques required for 3D flow

focusing of sample and the control of interdistance

between the micro particles in order to avoid presence

of multiple objects in the optical window. (Shivhare

et al. 2016). Similarly, several challenges are present

for single particle analysis in terms of increasing

throughput, ultra-sensitive detection of extremely

small volume (Xie et al. 2015; Yang et al. 2016b), and

dynamic control of environment (Carlo and Lee

2006) for such measurement. Techniques such as

microdissection and micromanipulators are presently

employed for single particle analysis. However, these

methods require complex manipulations (Xie et al.

2015) and in addition costly equipments further limits

availability of these techniques. Further, the optical

detection of micro particle encapsulated inside

droplet was not paid any attention. Thus, techniques

for isolation and cost-effective detection of single

micro particle from bulk are urgently required.

In this work, we report the development of an

integrated optofluidic microflow analyser for non-

invasive optical detection of 2D-focused micro

particle. The inherent property of droplets to move

toward region with zero shear rate is employed for

generating self-aligned droplets thereby eliminating

the need of complicated 3D flow focusing

mechanisms. Forward scattered (FSC), side scattered

(SSC) and fluorescent (FL) signals are collected and

mapped in a scatter plot. Further, the platform is also

used for isolating and sensing of single micro objects

by trapping the object in the discrete droplet

surrounded by an immiscible phase.

2 EXPERIMENTS

2.1 Design and Microfabrication

Figure 1 shows image of the integrated optofluidic

device used for interrogating 2D flow focused

polystyrene beads, droplets, droplet generation rate,

and measurement of FSC, SSC, and FL from a droplet

encapsulated polystyrene fluorescent beads. The

device is incorporated with an on-chip droplet

generator to generate droplets and facilitate

compartmentalization of single micro particle for

optical interrogation. In all experiments the sample

(mostly aqueous phase) was infused using sample

inlet while continuous phase (mostly oil phase) was

infused through sheath inlet. As marked, the device is

equipped with four grooves for embedding an in-situ

optical detection zone by inserting optical fiber.

Groove 1 was used to illuminate the sample using a

lensed fiber to focus the laser beam to a spot of 10 µm

in the center of microchannel, whereas fibers in

Groove 2, Groove 3, and Groove 4 was placed at 5



anticlockwise, 45



clockwise, and 135



clockwise

with respect to incident beam and used to obtain FSC,

SSC, and FL signals respectively.

Figure 1: Image of the integrated optofluidics device

employed for the measurements.

The design of the device was made using CAD

software (Autodesk® AutoCAD 2015) and clear field

photomask was printed with the resolution of 40000

dpi. Finally, Polydimethylsiloxane (PDMS) based

microfluidic device was obtained employing standard

photolithography technique followed by soft

lithography process, a detailed description of the

process is provided in the literature (Sajeesh et al.

2014). In order to insert standard available multimode

62.5/125μm optical fiber, the depth of the device

was kept at130μm. The width of the main fluid

channel and throat of droplet generator junction were

100μm and 30μ respectively.

BIODEVICES 2017 - 10th International Conference on Biomedical Electronics and Devices

172

2.2 Materials and Methods

2.2.1 Aqueous and Oil Phases

Deionized (DI) water mixed with varying

concentrations of Rhodamine Dye (Sigma Aldrich,

Bangalore, India) was used as discrete phase while

olive oil (Sigma Aldrich, Bangalore, India) was used

as continuous phase in the experiments. First, a highly

concentrated 52.19mM Rhodamine solution was

prepared by adding 100mg of Rhodamine B (Sigma

Aldrich, Bangalore) dye in 4mL of aqueous glycerol

solution (22% wt/wt). Now this concentrated solution

was further diluted to get 130μM solution. Aqueous

Rhodamine solution and olive oil were filtered with

0.2 μm PTFE and nylon filters respectively (Axiva

Sichem Biotech, Chennai, India) to avoid clogging

due to unsolicited dust in the microfluidic channel. In

order to stabilize the droplets, 5% wt/wt of Tween 80

(Sigma Aldrich Bangalore, India) was added to the

Rhodamine solution as surfactant.

2.2.2 Microbeads

Fluorescent polystyrene beads (Sigma Aldrich

Bangalore, India) of diameter 10μm and 15μm was

mixed in aqueous glycerol solution (22% wt/wt) in

order to avoid sedimentation of beads. 0.5% wt/wt of

surfactant Tween 80 (Sigma Aldrich Bangalore,

India) was added to the solution to prevent the

aggregation of the beads present in the solution. The

original bead solution was diluted with the aqueous

solution.

2.3 Optical Sensing Setup

A block diagram of optical detection system

incorporated for measurements is shown in Fig. 2.

Graded index multimode (62.5/125μm) fiber

coupled20mW, 532nm turnkey laser system

(VTEC Lasers and Sensors, The Netherlands) was

employed for illuminating the sample (Using Groove

1). The FSC data was collected using Si PIN

photodiode (DET02AFC/M, Thorlabs Inc., USA),

whereas for collecting feeble SSC and FL signal

highly sensitive Si semiconductor based avalanche

photodiode (C10508-01, Hamamatsu Photonics,

Japan) and single photon counting module

(SPCM50A/M, Thorlabs Inc., USA) are used

respectively, as compared to traditional slower and

bulky photomultiplier tubes (PMT). The use of

smaller semiconductor detectors increases portability

of the system. All these detectors were connected to

the microfluidic chip using multimode fibers (62.5/

125μm) inserted in the fiber grooves as explained in

Section 2.1 of the manuscript. An optical band pass

filter at 575/50 nm (ET575/50m, Chroma Technology

Corp., USA) was attached to single photon counting

module (SPCM) to filter out the illuminating

wavelength of 532 nm and measure fluorescence

signal.

The FSC and SSC signals were sampled at 10kHz

while FL signal was sampled at 5kHz. The data was

collected using data acquisition system (NI-USB-

6251, National Instruments, India) and in-house

software written in LabVIEW®. Data was analysed

on a computer using an in-house built Python

software to obtain width, amplitude, and area for each

pulse (each particle/droplet crossing the detection

region).

2.4 Experimental Setup

Pressure based pumping system (MFCS-EZ, Fluigent

SA, France) were used to infuse the fluids into the

microchannels. Inverted microscope (Axiovert A1,

Carl Ziess GmbH, Gemany) attached with high speed

camera (SA3, Phtoron, USA) was used to capture the

videos at 1000 frames. ImageJ (Rasband, W. S.,

ImageJ, USA) was used to analyse the videos to

obtain the droplet generation rate (



), and droplet

diameter (



Figure 2: Block diagram of the optical detection system.

Lasersource PINPhotodiode APD SPCM

NI‐DAQ

ToGroove1FromGroove2FromGroove3FromGroove4

ToComputer

Development of an Integrated Optoﬂuidic Platform for Droplet and Micro Particle Sensing - Microﬂow Analyzer for Interrogating Self

Aligned Droplets and Droplet Encapsulated Micro Objects

173

3 RESULTS AND DISCUSSION

3.1 2-D focused Micro Particles

Microbeads solution and DI water were infused in the

microchannel from sample and sheath inlet

respectively. The focused streams of microbeads

were passed through detection region and FSC of

each event was obtained. Fig. 3(a) shows the scatter

plot of scattered signal 



vs. residence time 

(pulse-width) for large number of beads passing

through detection region. Fig. 3(b) represents the

normalized distribution of the scattered signal 



for micro particles of 10μm and 15μm, data was fit

to normal distribution with 



value of 0.87 and 0.79

respectively. It can be clearly observed that micro

particles of different sizes form different colonies in

the scatter plot marked with ellipses in Fig. 3(a).

Remark that residence time of beads of different

sizes are comparable, this is attributed to the fact that

the beads are focused only in horizontal plane and are

free to move in any vertical plane. Since, mobility

(Sajeesh et al. 2014) profile is parabolic along the

vertical plane (Shivhare et al. 2016), particle along

center line requires less time to traverse detection

region, as compared to the particle travelling near the

wall. The scattered signal 



is proportional to size

of micro particle crossing the detection region (Cho

et al. 2010), and thus the amplitude of scattered signal

in case of bigger beads is higher than smaller beads

as can be observed from Fig. 3(a). This can also be

observed from Fig. 3(b), where mean value of signal

for normal distribution corresponding to 15μm is

higher than 10μm. However, we can clearly notice the

presence of 10μm particles in the colony of 15μm

and vice versa. This is due to the fact that since the

particles are focused in only horizontal plane multiple

beads can pass the detection region at the same instant

which introduces the error in the measurement

(Shivhare et al. 2016). Thus 2D focused micro

particles of varying sizes can be segregated with FSC

signal, however, varying mobility in the vertical plane

and presence of multiple particles in the detection

region introduce error in the measurement. This error

introduced due to the variation of mobility can be

eliminated by focusing the particle from all direction.

Thus 3D flow focusing is required for sensitive

cytometric application.

3.2 Rhodamine Droplets

Continuous stream of Rhodamine water droplets were

generated with olive oil as continuous phase and

rhodamine dye solution as discrete phase. The size of

the droplets was varied by varying the pressure of

continuous and discrete phases. FSC, SSC, and FL

were measured for these droplets. Figure 4 shows the

signal collected from a train of droplets crossing the

microchannel. It can be observed from the data that

as the droplet passes the detection zone it hinders the

path of continuous beam of laser light and scatters the

light in various direction which results in pulse in

scattered signals. Note that when droplet passes the

detection zone FSC encounters a negative pulse due

to the obstruction of continuous beam of light. This

light gets scattered in different direction due to

interface between droplet and continuous phase

which results in positive pulse in SSC. Also since

droplet is devised using fluorescent dye, a pulse in FL

signal is captured by SPCM as droplet crosses the

detection zone.

Figure 3: (a) Scatter plot of Scattered Signal (



) vs. Residence Time () (b) Normalized distribution of scattered signal





for 2D focused micro particles of sizes 10μm and 15μm.

(a)

(b)

0.000 0.003 0.006 0.009

0.4

0.6

0.8

1.0

Scattered Signal (V)

Residence Time

(

)

10 um

15 um

0.4 0.6 0.8

0.0

0.1

0.2

0.3

0.4

Normalized Count

Scattered Signal (V)

10 um

15 um

BIODEVICES 2017 - 10th International Conference on Biomedical Electronics and Devices

174

Figure 4: FSC, SSC, and FL data from a stream of

continuous Rhodamine droplet.

Figure 5(a) illustrates the images of the

Rhodamine droplets generated in the microchannel,

whereas Figure 5(b) represents the 3D scatter plot of

FSC-SSC-FL signal of each droplet passing the

detection zone from droplet of varying sizes. The size

(in μm) of the corresponding droplets is mentioned as

legend in the figure and scale on all images in Figure

5(a) represents 100μm. It can be observed from the

Figure 5(b) that droplets of different sizes form the

different colony in the scatter plot.

Droplets in microfluidic channel tends to move

towards the region with zero shear rate due to the

deformability induced lift forces (Leal 1980). In the

present design, due to symmetric flow conditions the

region with zero shear rate tends to be the centreline

of the microchannel which results in self 3D flow

focusing of the interrogated objects. Thus this self-

alignment of droplets eliminated the need of complex

3D flow focusing setup (Shivhare et al. 2016) and

hence need of extra bulky pumping system required.

This improves the portability of the system and also

makes it relatively less complex.

The impact of this 3D flow focusing is clearly

visible in the scattered plot (Figure 5(b)) where the

various colonies are well separated as compared to

the 2D focused micro particles as shown in Figure 3

(b). This distinction in the colonies is critical for

measurement of properties like size, type, velocity of

the object. Thus the use of droplets as the

miniaturized test tube in the cytometric applications

reduces the error due to mobility variation of micro

particles.

The other important concern in the cytometric

measurement is the control of minimum interdistance

between the particles in order to avoid the multiple

objects in the optical window (Shivhare et al. 2016).

This issue can also be addressed using droplet

microfluidics since the droplet generation rate can be

controlled using flow rate of discrete and continuous

phase (Nguyen et al. 2006).

3.3 Particle Encapsulation

The polystyrene beads were compartmentalized in the

water in oil (W/O) droplets with Olive oil as

continuous phase and microbeads solution described

in the Section 2.2.2 as discrete phase. As droplets are

generated a bead present in the solution gets trapped

inside the droplet, and thus gets completely isolated

from the rest of beads (bulk). Now using the already

reported tools for droplet manipulation (Jebrail and

Wheeler 2010) various single particle experiments

can be performed on the isolated micro particle. The

number of positive droplets (droplets containing a

micro particle) can be increased by increasing the

concentration of the micro particle. The relation

between the numbers of micro-particles in the droplet

is given by Poisson’s distribution 









exp











/!, where  represents the

probability of presence of  beads in a droplet with 

representing mean number of beads in the volume of

each droplet (Mazutis et al. 2013). Thus, as the

concentration of bead in the solution increses,

droplets containing multiple particle, also increases.

(Chabert and Viovy 2008).

Figure 6(a) and Figure 6(b) represents the image

of a negative (droplet without micro particle) and

positive droplets (droplet with micro particle)

respectively. It can be clearly perceived from the

image that Figure 6(b) contains a micro particle.

Figure 6 (c), (d), and (e) shows the FSC, SSC, and FL

data captured from the stream of mixture of positive

and negative droplet crossing the detection zone. The

0.0 0.2 0.4 0.6 0.8 1.0

FSC (V)

Time (s)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.5

1.0

1.5

2.0

SSC (V)

Time (s)

0.0 0.2 0.4 0.6 0.8 1.0

100

200

300

400

500

FL (Count)

Time

(

)

Development of an Integrated Optoﬂuidic Platform for Droplet and Micro Particle Sensing - Microﬂow Analyzer for Interrogating Self

Aligned Droplets and Droplet Encapsulated Micro Objects

175

Figure 5: (a) Images of droplets of varying sizes flowing inside the microchannel (b) 3D scatter plot of FSC-SSC-FL signal

from Rhodamine droplets of varying sizes.

dashed rectangle (8

and 9

pulse) in the graph are

the positive droplets, while other pulses are from

negative droplets. It can be observed from the Figure

6(c) that the FSC of positive (8

and 9

pulse) and

negative droplets (except 8

and 9

pulse) are almost

similar, this is attributed to the fact that the FSC signal

is proportional to the size of droplets which remains

unaltered for positive and negative droplets.

However, SSC is proportional to the internal

granularity of the object which is being interrogated.

Since, the positive droplet contains the micro particle

the internal structure of these droplets differ from

negative ones, this change in the granularity can

clearly be observed in the SSC signal shown in Figure

6(d). Note that positive droplets (8

and 9

pulse)

possess two peaks as compared to the single peak in

negative droplets. This is further confirmed by the FL

signal shown in Figure 6(e) where peaks are present

only for the droplets containing fluorescent beads.

The developed integrated platform

simultaneously exploits the advancements in the field

of digital microfluidics and optofluidics for isolating

a particle from bulk and real time non-invasive

optical interrogation. Further, sorting mechanism can

be employed to separate and collect the positive

droplets for further analysis. This device provides a

low cost alternative to the presently employed

complex techniques for single particle analysis.

4 CONCLUSIONS

In this work, we reported the development of an

integrated optofluidic microflow analyser which

consists of a microfluidic channel and a set of optical

fiber grooves for simultaneous measurement of

various scattered signal viz. FSC, SSC, and FL signal.

An optical illumination and detection system

comprising of green laser source, Si PIN photodiode,

Si avalanche photodiode, and Single Counting

Photon Module was designed. Polystyrene beads of

10μm and 15μm were focused in horizontal plane

(two dimensional focusing) and scattered signals

were collected. The obtained scatter plot shows that

error in the measurement is introduced due to the

variation in mobility of particles and presence of

multiple objects in the optical detection window since

particles were not focused in vertical plane. Both of

these error, which are measure concern for the

development of microflow analyser, were eliminated

with the formulation of self-focused droplet inside the

microchannel. The collected scattered signals formed

the distinct colonies for droplet of varying sizes on

the scatter plot, which is critical for various

BIODEVICES 2017 - 10th International Conference on Biomedical Electronics and Devices

176

Figure 6: (a) Image of droplet without micro particle (b) Image of droplet with micro particle (c) FSC (d) SSC (e) FL signal

from a stream of mixture of positive and negative droplets in the microchannel.

cytometric measurements. Finally the proof of

concept was demonstrated for single particle analysis

by encapsulating and optically interrogating 10μm

fluorescent polystyrene beads inside the droplet.

Also, the use of droplets to compartmentalize the

micro particles drastically reduced the volume of

sample required. Thus the developed platform

incorporating droplets encapsulation of micro particle

and optical interrogation can prove to be low cost,

portable, non-invasive alternative for single particle

analysis.

ACKNOWLEDGEMENTS

The authors would like to thank SERB, DST (Project

No. MEE/15-16/340/DSTXASHS) and IIT Madras

for providing financial support for the project. We

acknowledge support of Centre of NEMS and

Nanophotonics (CNNP), IIT Madras with the

photolithography work. Also, we thank the

Interdisciplinary Research Program, IIT Madras,

which enabled this work.

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