Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease

Liu, Jia; Qiang, Yuhao; Álvarez, Ofelia; Du, E.

doi:10.1021/acssensors.9b00263

Cited by 26 publications

(19 citation statements)

References 44 publications

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“…Additionally, existence of denatured hemoglobin and the increased HbS concentration [56], as a consequence of losses of potassium, chloride, and water from sRBC, probably decrease

σ_{i}

and

ε_{i}

, which could be further decreased by the polymerization of HbS under hypoxia. This observation is consistent with the results reported in our previous work [10]. Compared to normoxia, hypoxia induced a marked increase in

C_{m}

of SS2 and SS3.…”

Section: Resultssupporting

confidence: 94%

“…2C. The details of the fabrication process of the microfluidic chip was reported previously [10]. Attributed to the good gas permeability of the thin PDMS film, the concentration of the oxygen dissolved in the cell suspension in the bottom channel responds rapidly to the oxygen content (17.5/0% in O 2 ‐rich/‐poor gas) in the gas mixture supplied to the top channel.…”

Section: Methodsmentioning

confidence: 99%

“…Dielectric properties of biological cells have been widely used for differentiation [1–3] and separation [4,5] among different cell types, as well as for biomechanical characterization of cell membranes [6–9]. In our previous studies [10,11], we have demonstrated that deoxygenation changes the electrical impedance of sickle cells. The changes in the dielectric properties of the cell membrane and cytoplasm contribute to the overall impedance change.…”

Section: Introductionmentioning

confidence: 99%

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Dielectric spectroscopy of red blood cells in sickle cell disease

Liu

Qiang

2021

Electrophoresis

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Hypoxia‐induced polymerization of sickle hemoglobin and the related ion diffusion across cell membrane can lead to changes in cell dielectric properties, which can potentially serve as label‐free, diagnostic biomarkers for sickle cell disease. This article presents a microfluidic‐based approach with on‐chip gas control for the impedance spectroscopy of suspended cells within the frequency range of 40 Hz to 110 MHz. A comprehensive bioimpedance of sickle cells under both normoxia and hypoxia is achieved rapidly (within ∼7 min) and is appropriated by small sample volumes (∼2.5 μL). Analysis of the sensing modeling is performed to obtain optimum conditions for dielectric spectroscopy of sickle cell suspensions and for extraction of single cell properties from the measured impedance spectra. The results of sickle cells show that upon hypoxia treatment, cell interior permittivity and conductivity increase, while cell membrane capacitance decreases. Moreover, the relative changes in cell dielectric parameters are found to be dependent on the sickle and fetal hemoglobin levels. In contrast, the changes in normal red blood cells between the hypoxia and normoxia states are unnoticeable. The results of sickle cells may serve as a reference to design dielectrophoresis‐based cell sorting and electrodeformation testing devices that require cell dielectric characteristics as input parameters. The demonstrated method for dielectric characterization of single cells from the impedance spectroscopy of cell suspensions can be potentially applied to other cell types and under varied gas conditions.

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“…Additionally, existence of denatured hemoglobin and the increased HbS concentration [56], as a consequence of losses of potassium, chloride, and water from sRBC, probably decrease

σ_{i}

and

ε_{i}

C_{m}

of SS2 and SS3.…”

Section: Resultssupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dielectric spectroscopy of red blood cells in sickle cell disease

Liu

Qiang

2021

Electrophoresis

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“…To that end, we developed an in vitro vaso-occlusion assay with capillary-inspired structures allowing direct observations of biorheology and vascular obstruction of individual SS RBCs under microscope. 4 To overcome the limitation of the blood testing and the requirements of microscopic observations and video processing, we facilitate the vaso-occlusion assay by integration of an electrical impedance sensor 15,16 in the microfluidic channel. In this paper, we demonstrate the capability of this new assay for a real-time measurement of sickle cell traversing through microcapillaries including the progressive vaso-occlusion upon deoxygenation and resume of blood flow upon reoxygenation.…”

Section: Introductionmentioning

confidence: 99%

Electrical impedance detection of sickle cell vaso-occlusion in microfluidic capillary structures

Qiang¹,

Liu²,

Dieujuste³

et al. 2020

Preprint

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Sickle cell disease (SCD) is primarily associated with episodic vaso-occlusive events. Poorly deformable sickle cells may get stuck in small blood vessels, slow down or block blood flow, leading to local hypoxia that damages tissues and organs. In this paper, we present a novel electrical impedance sensing technique for detection of the progressive occlusion by sickle cells in microfluidic capillary structures. Changes in both resistance and reactance of the sickle blood flow were observed at multiple low frequencies (< 500 kHz), upon the deoxygenation and reoxygenation processes. In contrast, no obvious impedance changes were observed in the flow of normal blood cells and sickle blood cells treated with anti-sickling agent. Accuracy of the impedance-based detection of the vaso-occlusion process was verified by microscopic observation. The results show the distinct sensing performance of sickle cell vaso-occlusion by electrical impedance, which does not require sophisticated optical microscopy or video processing. The low frequency impedance sensing can be achieved by replacing the benchtop equipment with low-cost, high precision impedance converter system, allowing for detection of sickle cell vaso-occlusion in point-of-care settings.

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“…Electrical impedance-based flow cytometry of single cells has been demonstrated to be useful to discriminate red blood cell (RBC) that are affected by malaria [12,13] and sickle cell disease (SCD) [14]. In the study of cellular response to hypoxia, microfluidics technology can be used to precisely control the gaseous microenvironment and allow simultaneous microscopy and impedance sensing of cells in flow and in stationary conditions [15]. However, these electrical impedance analyses were performed using large benchtop equipment.…”

Section: Introductionmentioning

confidence: 99%

A Portable Impedance Microflow Cytometer for Measuring Cellular Response to Hypoxia

Dieujuste

Qiang

2020

Preprint

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This paper presents the development and testing of a low-cost, portable microflow cytometer based on electrical impedance sensing, for single cell analysis under controlled oxygen microenvironment. The cytometer system is based on an AD5933 impedance analyzer chip, a microfluidic chip, and an Arduino microcontroller operated by a custom Android application. A representative case study on human red blood cells (RBCs) affected by sickle cell disease is conducted to demonstrate the capability of the cytometry system. Equivalent circuit model of a suspending biological cell is used to interpret the electrical impedance of single flowing RBCs. In normal blood, cytoplasmic resistance and membrane capacitance do not change significantly with the change in oxygen tension. In contrast, RBCs affected by sickle cell disease show that upon hypoxia treatment, the cytoplasmic resistance decrease from 11.6 MΩ to 23.4 MΩ, and membrane capacitance decrease from 1.1 pF to 0.8 pF. Strong correlations are identified between the changes in these subcellular electrical components of single cells and the cell sickling process induced by hypoxia treatment. The representative results reported in this paper suggest that single cell electrical impedance can be used as a sensitive biophysical marker for quantifying cellular response to change in oxygen concentration. The developed flow cytometry system and the methodology can also be extended to analysis of cellular response to hypoxia in other cell types.

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Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease

Cited by 26 publications

References 44 publications

Dielectric spectroscopy of red blood cells in sickle cell disease

Dielectric spectroscopy of red blood cells in sickle cell disease

Electrical impedance detection of sickle cell vaso-occlusion in microfluidic capillary structures

A Portable Impedance Microflow Cytometer for Measuring Cellular Response to Hypoxia

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