MEASUREMENT OF HUMAN RED BLOOD CELL
DEFORMABILITY IN MICRO-CHANNELUSING ELECTRIC SENSORS
1Y. Katsumoto, K. Tatsumi, T. Doi and K. Nakabe
Department of Mechanical Engineering and Science, Kyoto University, JAPANABSTRACT
A sensor which can sequentially measure the deformability of a single red blood
cell (RBC) flowing in a micro-channel using membrane electrodes is proposed inthis study. The deformability of each cell is obtained by analysing the electric resistance profile which is correlated with the shape of the deformed RBC. Numericalsimulation on the electric field around the electrodes and RBC is carried out toevaluate the effects of the RBC positions, the electrode size, and the channel heighton the sensor sensitivity. The sensor feasibility is, then, evaluated experimently using the samples of normal human RBCs and rigidized ones.
KEYWORDS: Red Blood Cell, Deformability, Micro-sensor, Micro-flow
INTRODUCTION
Measurement of the deformability of a single red blood cell (RBC) is an important issue in terms of diagnosing initial symptoms of diseases in clinical investigation, for example, Plasmodium falciparum [1]. There are some methods in measuring the RBC deformability such as those using micro-channel and high resolution
camera [2], optical tweezer [3], and rheoscope [4]. These methods, however, haveproblems in the measuring resolution especially when the number density of infected
RBC is small, or the limitation of available sampling number of RBC. In this study,
an innovative micro-sensor, which can sequentially measure the deformability ofeach single RBC in high accuracy and sensitivity, is proposed and evaluated.
THEORY
Figures 1 and 2 illustrate the schematic of the measuring scheme and the microchannel applied in the present sensor, respectively. Membrane-type electrodes areattached to the bottom wall of the micro-channel, and the time-sequential signals of
the electric resistance are measured under 10kHz. RBCs supplied from the inlet are

Figure 1. Concept of the measuringmethod of RBC deformability.

Figure 2. Schematic of the sensor (electrodes and micro-channel).

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deformed when they pass between the electrodes owing to the high shear stress ofthe micro-channel flow. Since the conductivity of RBC cytomembrane is negligibly
small compared with the normal saline solution, the RBC interferes the current leading to significant increase in the resistance. The temporal distribution of the signal isaffected by the RBC shape, which is dependent on the cell deformability under uniform shear stress. The deformability of each RBC is, thus, electrically measured byanalyzing the resistance profile.
NUMERICAL
Numerical simulations solving the harmonic electric field around the electrodes
and RBC, which is modelled as an isotropic sphere or ellipsoid with an frequencydependant complex permittivity, are carried out to derive the resistance and capacitance between the electrodes. The effect of the sensor geometries are evaluated tooptimize the sensor sensitivity. Furthremore, the RBC shape effect on the temporal
disbtribtuion of the resistance is simulated to examine the feasibility of the sensor.
EXPERIMENTAL
The sensor size is designed on the basis of the numerical results. Namely, H2 =10μm, ws = 5.2μm, ls = 14.8μm (other parameters are shown in Fig. 1). Additionally,
several techniques are applied to the sensor as follows: The channel has three inlets
to control the spanwise positions of human RBCs with the sideflows. Backward- andforward-facing steps are placed upstream of the electrodes to control the RBCs
height positions. Guard electrodes are attached at both sides of the sensor electrodeto suppress the fringe effect of the current. Pt-nanoparticles are plated on the electrode surfaces to reduce the electric double layer effect. The sensor is tested by using
samples of normal human RBCs and glutaraldehyde-treated rigidized ones.
RESULTS AND DISCUSSIONFigure 3(a) shows one of the numerical results of current density isosurfaces
around the electrodes. The figure give us an insight where the RBC should flow to enhance the sensor sensitivity. Figures 3(b) ~ (e) show how the RBC position and thesensor geometries affect the resitance (ΔR0 = R – R∞ , R∞ = resitance of solution). Theeffect of applying the guard electrodes is also shown in Fig. 3(e). These figures show
ΔR0/R (%)

181(b)(d)0.1

0.10.01ls=15μm, ws=10μm, H2=50μm

1E-3
1100.01zRBC

ΔR0/R (%)

10ls=15μm, H2=15μm, zRBC=5μm
100 w (μm)

10(μm) 100s2.5(c)

ls=15μm, ws=10μm, zRBC=5μm

2.0(e)

w/o-guard electrodew-guard electrode

1.5

8 1

1.00.5

ws=10μm, H2=15μm, zRBC=5μm

0.00.110100

H2 (μm)050ls (μm)

100Figure 3. Numerical results: (a) Isosurfaces of current density. The effects of (b)height locations of the RBC center, (c) channel height, (d) gap width between theelectrodes, and (e) width of the sensor electrode, on the sensor sensitivity.
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Figure 5. Relation between the half bandFigure 4. Snapshots of a normal RBC width of resistance distribution, δ, and depassing between the electrodes.
formation index, DI.
that the decrease in RBC height, channel height, and distance between electrodes leads
to the increase of the sensor sensitivity. On the other hand, the width of the sensor electrode has an optimum value to achieve maximum sensitivity.
Figure 4 shows the snapshots of a normal RBC passing the electrodes, in which
the deformation of the RBC attributed to the high shear flow is observed. Figure 5
shows the relation between the deformation index DI and the halfwidth δ of the signal distributions converted from the time-sequentially obtained resistance signals. DIis DI = (a–b)/(a+b) where a and b are the major and minor axes of the RBC, respectively. A clear correlation between DI and δ is observed, which corresponds wellwith the numerical prediction (not shown in this article) and indicates the validity ofthe present sensor.
CONCLUSIONS
A micro-sensor which can electrically measure the deformability of single RBC
passing between the electrodes was fabricated, and its feasibility was examined using normal and rigidized RBCs. A good correlation was observed between the deformation index and the half bandwidth of the electric resistance signal distributions.
ACKNOWLEDGEMENTS
Parts of this study were financially supported by The Japanese Ministry of Education, Culture, Sports, and Science.
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Blood Cell Deformability in Severe Malaria, Parasitology Today, 16, pp. 228-232, (2000).
[2] N. Korin, A. Bransky, and U. Dinnar, Theoretical Model and Experimental Study of Red
Blood Cell Deformation in Microchannels, Journal of Biomechanics, 40, pp. 2088-2095,(2007).
[3] S. Hénon, G. Lenormand, A. Richert and F. Gallet, A New Determination of the Shear
Modulus of the Human Erythrocyte Membrane Using Optical Tweezers, Biophysical J.,
76, pp. 1145-1151, (1999).
[4] J. G. G. Dobbe, G. J. Streekstra, M. R. Hardeman, C. Ince and C. A. Grimbergen, Measurement of the Distribution of Red Blood Cell Deformability Using an Automated Rheoscope, Cytometry, 50, pp. 313-325, (2002).

Thirteenth International Conference on Miniaturized Systems for Chemistry and Life SciencesNovember 1 - 5, 2009, Jeju, Korea

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