Local streamline generation by mechanical oscillation in a microfluidic chip
for noncontact cell manipulations
Masaya Hagiwara, Tomohiro Kawahara, and Fumihito Arai
Citation: Appl. Phys. Lett. 101, 074102 (2012); doi: 10.1063/1.4746247
View online: http://dx.doi.org/10.1063/1.4746247
View Table of Contents: http://apl.aip.org/resource/1/APPLAB/v101/i7
Published by the American Institute of Physics.
Related Articles
Wireless power transfer to a cardiac implant
Appl. Phys. Lett. 101, 073701 (2012)
Microfluidic impedance spectroscopy as a tool for quantitative biology and biotechnology
Biomicrofluidics 6, 034103 (2012)
Treatment of enterococcus faecalis bacteria by a helium atmospheric cold plasma brush with oxygen addition
J. Appl. Phys. 112, 013304 (2012)
Biosensors for immune cell analysis—A perspective
Biomicrofluidics 6, 021301 (2012)
The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal
women
AIP Advances 2, 011206 (2012)
Additional information on Appl. Phys. Lett.
Journal Homepage: http://apl.aip.org/
Journal Information: http://apl.aip.org/about/about_the_journal
Top downloads: http://apl.aip.org/features/most_downloaded
Information for Authors: http://apl.aip.org/authors
APPLIED PHYSICS LETTERS 101, 074102 (2012)
Local streamline generation by mechanical oscillation in a microfluidic chip
for noncontact cell manipulations
Masaya Hagiwara,1,a) Tomohiro Kawahara,2,3 and Fumihito Arai4
1
Aerospace and Mechanical Engineering Department, University of California, Los Angeles, Los Angeles,
California 90095, USA
2
Kyushu Institute of Technology, Kitakyushu 808-0196, Japan
3
Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
4
Department of Micro-Nano Systems Engineering, Nagoya University, Nagoya 464-8603, Japan
(Received 26 June 2012; accepted 25 July 2012; published online 14 August 2012)
This paper presents a method to manipulate cells in a microfluidic chip without contact. A local
streamline is generated when high-frequency oscillation of the microtool is induced in a
microfluidic chip. The streamline can be controlled by tuning the oscillation parameters of the tool,
such as the amplitude and phase of the oscillation. Cells then flow in the microchannel in
accordance with the streamline, and their position, posture, and trajectories are controlled.
Bovine oocyte manipulations, which were attraction, repulsion, and rotation, were
conducted to demonstrate the capability of the proposed method without any contact by the
C 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4746247]
oscillation tool. V
The importance of cell or microorganism manipulation
has grown rapidly in recent years for various fields, such as
drug discovery, regenerative medicine, and the investigation
of new energy sources. There are two types of methods for
cell manipulation: contact and noncontact manipulation. One
of the most reliable tools for contact cell manipulations is a
mechanical micromanipulator. It is widely used for medical
and life science applications because of the high accuracy,
high power output, and flexibility of its manipulation.1–3
Microrobots are other representative contact manipulation
tools and many different actuation methods have been investigated; these methods involve magnetic fields,4–6 optics,7–9
and bio-actuation.10,11 These microrobots can be actuated in
a microfluidic chip, which gives many advantages such as
low contamination and continuous process in microchannels.
The main advantage of contact manipulation is that it allows
for a precise physical approach such as cutting, injecting,
and stimulating a single cell. On the other hand, noncontact
cell manipulation methods that use field forces such as surface acoustic waves,12–14 dielectrophoresis,15–17 and fluid inertial forces18,19 have also been investigated because of their
capability of manipulation in a broad range and controlling a
number of cells simultaneously. They can separate or gather
cells with high throughput; however, they cannot conduct
single cell manipulation and physical operation tasks. Fluid
streams are also used to manipulate particles by oscillating
bubbles20–22; however, the pattern of the streamline is fixed,
and thus the application is limited.
Achieving the advantages of both contact and noncontact manipulations would produce a very strong tool for cell
manipulation. In this paper, we propose a method for noncontact cell manipulation by oscillating a microtool at high
frequency in a microfluidic chip. A local streamline can be
generated when the tool is oscillated at a high frequency, and
the fluid stream manipulates cells without contact with the
tool. Figure 1 shows the concept of noncontact manipulation
by using the generated streamline. The form of the streamline varies depending on the tool oscillation form; thus, it
can be controlled by changing several parameters such as the
oscillation amplitude, phase, and relative position between
the tool and microchannel wall. The cells flow into or away
from the tool or are trapped at the vortex and rotated in two
dimensions. By tuning the oscillation parameters of the tool,
the dynamics of the viscous fluid change accordingly, and
cells can be manipulated away from the tool without contact.
Because it is a noncontact operation, there are no concerns
regarding cell adhesion to the tool, whereas there are occasional issues when the manipulator handles adherent cells. In
addition, the tool can also manipulate cells with contact as
well because it has enough physical strength to handle cells.
Thus, it can conduct both contact and noncontact
manipulation.
A steady stream is generated when an object is oscillated in viscous fluid, and the steady stream is a function of
lateral and normal oscillations.23–25 However, the Reynolds
number is generally small at a microscale, and a high frequency is required to generate the streamline. Assuming that
the steady stream occurs two-dimensionally when a plate
oscillates in a microfluidic chip, the local fluid velocity (Ux,
Uy) can be calculated by Wang et al.’s model using the
modified Reynolds number R ¼ xa2 =t, where x is the
a)
FIG. 1. Concept of noncontact cell manipulation by high-frequency oscillation in a microfluidic chip.
Author to whom correspondence should be addressed. Electronic mail:
hagiwara@ucla.edu.
0003-6951/2012/101(7)/074102/4/$30.00
101, 074102-1
C 2012 American Institute of Physics
V
074102-2
Hagiwara, Kawahara, and Arai
Appl. Phys. Lett. 101, 074102 (2012)
frequency of the plate oscillation, a is the gap between the
oscillating plate and channel wall, and is the kinematic viscosity.26 Then,
Ux ¼ xAx d
iBx eib
jðy; kÞ;
f ðy; kÞ þ
2 sinh k
dt
Uy ¼ xAx f ðy; kÞ;
pffiffiffiffiffiffiffiffi
k ¼ ð1 þ iÞ R=2;
(1)
(2)
(3)
where f(y, k) and j(y, k) are functions that consider the
effects of normal and lateral oscillations, respectively, A and
B are amplitudes of the normal and lateral oscillations,
respectively, and b is the phase lag of the lateral oscillation.
Figures 2(a) and 2(b) show the simulation results when
an infinite plate was oscillated with 60.25 mm amplitude in
the normal direction only, and the distance to the channel
wall was 2 mm. When the oscillating frequency was 1 Hz,
the streamline barely appeared. Under this condition, it was
impossible to conduct noncontact cell manipulation. On the
other hand, when the frequency was 25 Hz, a streamline of
the order of tens of millimeters per second was generated,
and the flow came to the plate from several millimeters away
in an arc. In addition, when the oscillation configurations
were changed, the streamline changed as well. Figure 2(c)
shows the case when the plate was oscillated in the normal
and lateral directions with a circular trajectory. The flow
came from the left to right along the oscillation plate. This
result implies that a plate with high-frequency oscillation in
a microfluidic chip can pull cells from far away without contact and that the streamline can be controlled by configuring
the oscillation.
Using the above calculation results, the drag force from
the generated streamline acting on a single cell can be estimated by
1
FD ¼ qCd SðU vÞ2 ;
2
where q is the fluid density, Cd is the drag coefficient, S is
the cross-sectional area, U is the streamline velocity, and v is
the cell velocity. The drag coefficient can be approximated
as follows27 when the Reynolds number is up to 2 105.
(4)
Cd 24
6
pffiffiffiffiffiffi þ 0:4:
þ
Re 1 þ Re
(5)
Figure 3 shows the calculated drag force results on /
30 lm and / 150 lm single cells at various distances from
the oscillating plate (0.2 mm, 0.8 mm, 1.6 mm) when the
plate began to oscillate (initial condition: v ¼ 0 mm/s) in the
normal direction at a 60.25 mm amplitude. In all cases, the
drag force on the single cell reached more than the nanoNewton order when the plate frequency was more than
40 Hz. This drag force caused the cells to move and flow
along with the steady stream.
Experiments were conducted to observe the actual
streamline when the plate was oscillated in a microfluidic
channel. Fluorescent beads that were 2 lm in diameter were
used to visualize the generated streamline. It was not possible to use electrically induced oscillation devices, such as
piezoelectric ceramics, as an oscillation tool in a closed liquid environment. Thus, a magnetically driven microtool28
(MMT) was used for the oscillating plate because of its highspeed actuation29 (up to 90 Hz) and precise positioning accuracy30 (micrometer order) in the x–y plane. Four of the permanent magnets were set on an x–y linear stage beneath the
microfluidic chip to actuate an MMT made of silicon and
nickel. The tool width was 100 lm, and its height was
200 lm; the channel height was 300 lm. The size of the
microchamber was 16 mm2.
Figures 4(a) and 4(b) show stationary pictures when an
MMT was oscillated in the normal direction at 1 and 25 Hz,
respectively (multimedia file is available online). The fluorescent beads barely moved at 1 Hz, which was the same as
the simulation result. On the other hand, the fluorescent
beads were attracted to the MMT area at 25 Hz from all over
FIG. 2. Simulation results of streamline in a microfluidic chip (arrow represents the velocity vector, and the contour is the magnitude).
074102-3
Hagiwara, Kawahara, and Arai
FIG. 3. Applied drag force on two types of cell (diameters of 30 and
150 lm) at three different positions in a chip.
the chamber. Figure 4(c) shows the measured velocity vectors of the fluorescent beads when MMT was oscillated in
the normal direction with an amplitude of 60.25 mm and frequency of 25 Hz. The streamline was slightly different from
that shown in Figure 2(b) because of the end effect of MMT.
The beads attracted to the MMT from the upper or lower
sides flew to the left side, and a vortex was generated around
the edge of the MMT, as shown in Figure 4(c). This vortex
can be used to keep a cell at the edge of the MMT and rotate
it two-dimensionally. In addition, the streamline changed
with the oscillation configuration, as mentioned previously.
Figure 4(d) shows the measured velocity vectors of fluores-
FIG. 4. Experimental result using fluorescent beads (/ 2 lm): (a) stationary
picture at 1 Hz, (b) 25 Hz, (c) and (d) measured velocity vectors (enhanced
online) [URL: http://dx.doi.org/10.1063/1.4746247.1] [URL: http://
dx.doi.org/10.1063/1.4746247.2].
Appl. Phys. Lett. 101, 074102 (2012)
cent beads when the MMT was oscillated in the normal and
lateral directions at 25 Hz in a circular trajectory. The fluorescent beads flew in a concentric fashion and in the same
direction as the MMT oscillation. These are just some of the
examples to show that the high-frequency oscillating plate
can generate various streamlines; however, numerous
streamline patterns can be generated by changing the modified Reynolds number (R), amplitude (A, B), and phase (b) of
the oscillation in the normal and lateral directions.
To demonstrate one of the examples of cell manipulation using generated streamline without contact, single bovine oocyte manipulation was conducted using the MMT.
The experimental configuration was the same as that using
the fluorescent beads, but the size of the oocyte was about
150 lm in diameter. The MMT was oscillated in the normal
direction at 25 Hz. The relative positions of the MMT and
the oocyte could be adjusted either by dragging the oocyte
through direct contact with the MMT or by moving
the MMT itself to the desired position. Figure 5(a) shows the
case when the oocyte was far below the MMT. First, the
oocyte was attracted to the MMT area; it then flew to the left
direction without being stuck in the vortex flow around the
MMT edge. On the other hand, when the oocyte was set
around the MMT edge before oscillation (Figure 5(b)), the
oocyte was trapped in the vortex, and it was rotated in two
dimensions. The MMT could also rotate the oocyte physically, but there were occasional instances where the oocyte
adhered to the MMT. There was no need to worry about cell
adhesion during noncontact manipulation. After certain preoperations, the MMT can also conduct physical operations
such as cutting and injection after a certain rotation if necessary, as presented in our previous works.28–30
In summary, high-frequency oscillation of a solid tool in
a microfluidic chip can generate a streamline, which can be
controlled by tuning the oscillation parameters. Cells are
then manipulated in many different ways, such as attraction,
repulsion, and rotation, by the generated streamline without
contact with the oscillation tool. The advantage of the noncontact manipulation is that it broadens the manipulation
FIG. 5. Bovine oocyte manipulation using the streamline: (a) attraction and
repulsion, (b) rotation (enhanced online) [URL: http://dx.doi.org/10.1063/
1.4746247.3] [URL: http://dx.doi.org/10.1063/1.4746247.4].
074102-4
Hagiwara, Kawahara, and Arai
area and cells can be controlled away from the tool. In addition, there is no need to worry about adhesion to the tool,
which is a possible problem for contact manipulation.
Because the oscillation tool has enough physical strength, it
can also conduct physical manipulations on the cell.28–30
In this paper, we only demonstrated the single cell
manipulation but it can be also applied to a number of cells
simultaneously. It is assumed that floating cells such as red
blood cells will flow just like the fluorescent beads did in the
experiment and the flow pattern can be controlled by the tool
oscillation configurations. It is our future work to apply this
method for high through cell manipulations such as sorting
and separations, in a microfluidic chip.
This work was supported in part by the Research Fellowship for Young Scientists, Japan Society for the Promotion of Science, and JST-SENTAN.
1
Y. Murayama, C. E. Constantinou, and S. Omata, J. Biomech. 37, 67–72
(2004).
2
T. Wakayama, A. C. F. Perry, M. Zuccotti, K. R. Johnson, and R. Yanagimachi, Nature 394, 369–374 (1998).
3
X. Liu, R. Fernandes, A. Jurisicova, R. F. Casper, and Y. Sun, Lab Chip
10, 2154–2161 (2010).
4
M. S. Sakar, E. B. Steager, D. H. Kim, M. J. Kim, G. J. Pappas, and V.
Kumar, Appl. Phys. Lett. 96, 043705 (2010).
5
E. Diller, S. Floyd, C. Pawashe, and M. Sitti, IEEE Trans. Rob. 28(1),
172–182 (2012).
6
S. Tottori, L. Zhang, F. Qiu, K. K. Krawczyk, A. F. Obregon, and B. J.
Nelson, Adv. Mater. 24, 811–816 (2012).
7
W. Hu, K. S. Ishii, and A. T. Ohta, Appl. Phys. Lett. 99, 094103 (2011).
Appl. Phys. Lett. 101, 074102 (2012)
8
Y. Sun, J. S. Evans, T. Lee, B. Senyuk, P. Keller, S. He, and I. I. Smalyukh, Appl. Phys. Lett. 100, 241901 (2012).
K. Onda and F. Arai, Opt. Express 20(9), 3633–3641 (2012).
10
D. H. Kim, U. Kei Cheang, L. Kohidai, D. Byun, and M. J. Kim, Appl.
Phys. Lett. 97, 173702 (2010).
11
Y. Akiyama, K. Iwabuchi, Y. Furukawa, and K. Morishima, Lab Chip
9(1), 140–144 (2009).
12
L. Y. Yeo and J. R. Friend, Biomicrofluidics 3, 012002 (2009).
13
L. Meng, F. Cai, J. Chen, L. Niu, Y. Li, J. Wu, and H. Zheng, Appl. Phys.
Lett. 100, 173701 (2012).
14
J. Shi, D. Ahmed, X. Mao, S.-C. S. Lin, A. Lawit, and T. J. Huang, Lab
Chip 9, 2890–2895 (2009).
15
S. Grilli and P. Ferraro, Appl. Phys. Lett. 92, 232902 (2008).
16
S. K. Srivastava, A. Gencoglu, and A. R. Minerick, Anal. Bioanal. Chem.
399, 301–321 (2010).
17
W. A. Braff, A. Pignier, and C. R. Buie, Lab Chip 12, 1327–1331 (2012).
18
A. A. S. Bhagat, H. W. Hou, L. D. Li, C. T. Lim, and J. Han, Lab Chip 11,
1870–1878 (2011).
19
H. A. Nieuwstadt, R. Seda, D. S. Li, J. B. Fowlkes, and J. L. Bull, Biomed.
Microdevices 13, 97–105 (2011).
20
R. S. Taylor and C. Hnatovsky, Opt. Express 12(5), 916–928 (2004).
21
S. K. Chung and S. K. Cho, J. Micromech. Microeng. 18, 125024 (2008).
22
S. K. Chung and S. K. Cho, Microfluid. Nanofluid. 6, 261–265 (2009).
23
C.Y. Wang, J. Fluid Mech. 32, 55–68 (1968).
24
T. Sarpkaya, J. Fluid Mech. 165, 61–71 (1986).
25
M. Tatsuno and P. W. Bearman, J. Fluid Mech. 211, 157–182 (1990).
26
C. Y. Wang and B. Drachman, Appl. Sci. Res. 39, 55–68 (1982).
27
J. P. Owen and W. S. Ryu, Eur. J. Phys. 26, 1085–1091 (2005).
28
M. Hagiwara, T. Kawahara, Y. Yamanishi, and F. Arai, Appl. Phys. Lett.
97, 013701 (2010).
29
M. Hagiwara, T. Kawahara, Y. Yamanishi, T. Masuda, L. Feng, and F.
Arai, Lab Chip 11, 2049–2054 (2011).
30
M. Hagiwara, T. Kawahara, T. Iijima, Y. Yamanishi, and F. Arai, in Proceedings of IEEE International Conference on Robotics and Automation
(ICRA), St. Paul Minnesota, USA, 2012, pp. 2517–2522.
9