International audienceIn this paper we demonstrate the capability to detect red blood cells mechanical disorders, in particular the sickle cell disease, using the electrical signature of the cell transit within a microfluidic restriction mimicking the blood capillaries

El Nemer, Wassim

Français, Olivier

Le Pioufle, Bruno

Lizarralde, Maria

Roman, Jean

Tieying, Xu

English

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Electrical Detection of the Mechanical Alteration of
Sickling Red Blood Cells within a Microfluidic Capillary
Network
Xu Tieying, Maria Lizarralde, Jean Roman, Wassim El Nemer, Bruno Le
Pioufle, Olivier Français
To cite this version:
Xu Tieying, Maria Lizarralde, Jean Roman, Wassim El Nemer, Bruno Le Pioufle, et al.. Electrical
Detection of the Mechanical Alteration of Sickling Red Blood Cells within a Microfluidic Capillary
Network. MicroTAS, Oct 2019, Basel, Switzerland. ￿hal-02387976￿
ELECTRICAL DETECTION OF THE MECHANICAL ALTERATION OF 
SICKLING RED BLOOD CELLS WITHIN A MICROFLUIDIC CAPILLARY 
NETWORK 
Xu Tieying1, Maria Lizarralde2, Jean Roman1, Wassim El Nemer2, Bruno Le Pioufle1, and  
Olivier Français1, 3, * 
1ENS Paris Saclay, CNRS,  SATIE, Institut d’Alembert, Cachan, France  
2BIGR, UMR_S 1134, INTS, Paris, France and 
3ESIEE-Paris, ESYCOM, UPE, Noisy-Le-Grand, France 
 
ABSTRACT 
In this paper we demonstrate the capability to detect red blood cells mechanical disorders, in particular the 
sickle cell disease, using the electrical signature of the cell transit within a microfluidic restriction mimicking the 
blood capillaries. 
 
KEYWORDS: Bioimpedance, Microfluidic Restriction, Red Blood Cell Deformability, Sickle Cell Disease 
 
INTRODUCTION 
Sickle cell disease (SCD) is a genetic disorder due to a single genetic mutation that induces alteration of the 
red blood cell (RBC) elasticity [1]. The change of cell deformability and cell shape, due to the polymerization of 
haemoglobin [2], leads to vasoocclusive crises that induces organ damages [3]. 
In this paper, the alteration in the RBC rigidity is detected through the electrical blockage induced by the cell 
flow within the microfluidic restriction. The microfluidic design is based on a progressive restriction channel 
which hydraulic diameter decreases from 30 µm down to 5 µm (Fig. 1B). When RBCs flow through one of those 
microchannels, their transit time though the restriction is highly dependent on their deformability. In such 
conditions the sickling state of cells can be detected [4]. 
 
THEORY 
To measure the transit time in the restriction, a pair of electrodes disposed at the fluidic inlet and outlet, 
detects the variation of the electric current (blockade amplitude) induced by the presence of the cell. A low cost 
dedicated device has been developed using an analog discovery card [5] associated to a homemade 
transimpedance amplifier on a dedicated printed circuit board. A lock-in amplifier treats the current signals that 
characterizes the blockade amplitude and duration. A statistical analysis on 250 successive measurements on cells 
is performed using Igor Software [6]. 
 
EXPERIMENTAL 
The microfluidic device is fabricated by the polydimethylsiloxane (PDMS) casting on a thick resist (SU8) 
mold (Fig. 1A) [7]. The electrodes are patterned after Cr/Au deposition using UV photolithography. In order to 
achieve a reversible packaging, the PDMS microfluidic part is assembled to the quartz substrate including the 
electrode network, using therefore depressurization to flow the sample. A coating of the device with parylen (t = 
3,5 µm) renders the PDMS non permeable and thus avoid bubbling.  
For measurement, an AC voltage of 2V and 10 kHz is applied to the pair of microelectrodes. The RBC 
passing through the restriction is recorded by a fast camera (sample rate: 1600 fps, period: 625 µs) under 
microscope (objective: 10X) (Fig. 1C). For statistical analysis, around 250 cells have been analyzed for each cell 
type (RBCs from healthy donors or SCD patients). 
 
RESULTS AND DISCUSSION 
The cell transit time for control and SCD RBCs is presented in Fig 2A. The transit time of control RBCs is 
very homogeneous (average transit time: 6.48 milliseconds, with a variance of 0.47 s2), while the transit time of 
SCD RBCs is more dispersed (average transit time: 9.00 milliseconds, with a variance of 0.93 s2). This statistical 
difference reflects differences in RBC elasticity between both cell types and indicates increased RBC rigidity in 
978-1-7334190-0-0/µTAS 2019/$20©19CBMS-0001 1264 23rd International Conference on Miniaturized
Systems for Chemistry and Life Sciences
27 - 31 October 2019, Basel, SWITZERLAND
the context of SCD. The impedance module was also analyzed and is presented as a blockade amplitude diagram 
(see Fig. 2B). 
 
Figure 1:  A. Process of microfluidic-electrical assemblage fabrication; B. Design of mimicking capillaries; C. RBC 
passing through the restriction by a fast camera under microscope. 
 
 
Figure 2:  A. The cell transit time for either RBC or sickle cells population; B. Their blockade amplitude. 
CONCLUSION 
Our method, based on the electrical detection of cell deformability variation, demonstrates to be promising to discriminate 
normal RBCs and sickled RBCs. 
ACKNOWLEDGEMENTS 
The authors acknowledge the Labex LaSIPS (ANR-10-LABX-0040-Lasips), the “Ecole Doctorale EOBE” of 
Université Paris-Saclay, the “Institut d’Alembert” and the “CNRS” for project fundings. 
 
REFERENCES 
[1] Barabino, G. A., Platt, M. O., & Kaul, D. K.. “Sickle Cell Biomechanics”. Annual Review of Biomedical 
Engineering, 12(1), 345–367, 2010. 
[2] Pauling, L., Itano, H. A., Singer, S. J., & Wells, I. C.. “Sickle Cell Anemia, a Molecular Disease”. Science, 
110(2865), 543–548, 1949. 
[3] Kaul, D. K., Fabry, M. E., & Nagel, R. L.. “Vaso-occlusion by sickle cells: evidence for selective trapping of 
dense red cells”. Blood, 68(5), 1162–1166, 1986. 
[4] Lizarralde Iragorri, M. A., El Hoss, S., Brousse, V., Lefevre, S. D., Dussiot, M., Xu, T., … El Nemer, W.. “A 
microfluidic approach to study the effect of mechanical stress on erythrocytes in sickle cell disease”. Lab on 
a Chip, 18(19), 2975–2984, 2018. 
[5] Digilentinc. Analog Discovery Technical Reference Manual. Revised March 18, 2015. 
[6] Français, O., & Le Pioufle, B.. “Single-Cell Electrical Characterization Techniques”. Springer International 
Publishing Switzerland Author, 293–326, 2016. 
[7] Fu, C., & Huang, H.. “Different methods for the fabrication of UV-LIGA molds using SU-8 with tapered de-
molding angles”. Microsystem Technologies, 13(3–4), 293–298, 2006. 
 
CONTACT 
* Olivier Français; phone: +33-145-926-694; olivier.francais@esiee.fr 
1265


Electrical Detection of the Mechanical Alteration of Sickling Red Blood Cells within a Microfluidic Capillary Network

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Electrical Detection of the Mechanical Alteration of Sickling Red Blood Cells within a Microfluidic Capillary Network

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