Cell Biomechanics, Fatigue, and Mechanobiology of Circulating Cells
Red blood cells experience a tremendous amount of shearing, stretching and bending as they circulate through the body. Progressive damage occurs in the circulating cells before they are removed and replaced by the new ones. We integrate dielectrophresis, electrodeformation, and ASK techniques into microfluidic platform to characterize the fatigue behavior of cells. The results help us to better understand the mechanical origins of damage in circulating red blood cells as well as the mechanisms underlying the shortened lifespan of those abnormal, diseased ones. A recent example is to integrate on-chip oxygen control in the cell microenvironment, allowing us to quantify the effects of the repetitive hypoxia and oxidative damage on cellular mechanics.
Artificial oxygen carriers (AOCs) are developed as red blood cell substitutes for transfusion. They may be used to reduce the transfusion-associated harmful side effects, such as immunoreaction and inflammation from the donated blood, or to enable life-saving surgeries in patients when donated blood becomes a sparse source. However, development of safe and effective AOCs to replace physiological human RBCs is challenging. We intend to address several important questions regarding the post-transfusion behavior of AOCs and the potential impacts on the blood vessels, using a multi-scale experimental approach. This study will provide a fundamental understanding of the biomechanical mechanisms underlying the failure of AOCs, inflammatory response, and relevant therapeutic interventions.
Selected references:
Y Qiang, J Liu, M Dao, E Du, In Vitro Assay for Single-cell Characterization of Impaired Deformability in Red Blood Cells under Recurrent Episodes of Hypoxia, Lab on a Chip (2021) https://doi.org/10.1039/D1LC00598G (featured by NSF research news, Lab on a Chip inside cover art)
Y. Qiang, J. Liu, M. Dao, S. Suresh, E. Du, Mechanical fatigue of human red blood cells, Proceedings of the National Academy of Sciences 116(40) (2019) 19828-19834. (FAU News Report, Science Daily, NTUsg)
Y. Qiang, J. Liu, F. Yang, D. Dieujuste, E. Du, Modeling erythrocyte electrodeformation in response to amplitude modulated electric waveforms, Scientific Reports 8(1) (2018) 1-10.
Biosensors for Point-of-Care Disease Diagnostics and Monitoring
Sickle cell disease is caused by a single mutation in the β-globin gene, resulting in production of abnormal sickle hemoglobin (HbS). HbS polymerizes into rigid fibers under low oxygen tension, causing deformed, rigid red cells (known as cell sickling) and leading to abnormal blood rheology and vasooccclusive crisis, hemolytic anemia etc. Cell sickling can serve as a quantitative assessment of the efficacy of chemotherapy, gene editing and therapy that target HbS and its polymerization, directly and indirectly. Using microfluidic technologies, we are able to assess cell sickling and the associated characteristics (e.g. cell morphological change, deformability, and flow behavior) rapidly (~ few min) with small sample volume (~ few µL). We develop biosensors for quantitative analysis of sickle cells using imaging and electrical impedance techniques, at both single cell level (e.g. quantification of intracellular HbS, portable flow cytometry) and in suspension (e.g. vascular occlusion, cell sickling kinetics).
Selected references:
D Dieujuste, Y Qiang, E Du, A Portable Impedance Microflow Cytometer for Measuring Cellular Response to Hypoxia, Biotechnology and Bioengineering (2021) doi.org/10.1002/bit.27879
J. Liu, Y. Qiang, O. Alvarez, E. Du, Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease, ACS sensors 4(7) (2019) 1783-1790. (FAU News Report) (Journal Supplementary Cover Art)
J. Liu, Y. Qiang, O. Alvarez, E. Du, Electrical impedance microflow cytometry with oxygen control for detection of sickle cells, Sensors and Actuators B: Chemical 255 (2018) 2392-2398.
Microfluidics-based Organ-on-a-Chip Devices
We employ cell cultures in microfluidic environment to reconstitute the structure, biological function, mass transport, and dynamic flow environment of the organs and tissues that are difficult to study in human, e.g. nerve damage and regeneration (collaborating with Drs. Erik Engeberg, Jenny Wei, Emmanuelle Toglini, and Douglas Hutchinson) and placenta (collaborating with Dr. Andrew Oleinikov). Integration of biosensing into these microfluidic devices provides us a way to monitor and characterize in real time the mass transport, cell-cell interactions, and cellular response to physical and biochemical stimuli.
Selected references:
B. Mosavati, A.V. Oleinikov, E. Du, Development of an Organ-on-a-Chip-Device for Study of Placental Pathologies, International Journal of Molecular Sciences (2020) doi.org/10.3390/ijms21228755.
J. Liu, O. Chesnokova, I. Oleinikov, Y. Qiang, A.V. Oleinikov, E. Du, Optimization of in vitro trophoblast assay for real-time impedimetric sensing of trophoblast-erythrocyte interactions in Plasmodium falciparum malaria, Analytical and Bioanalytical Chemistry (2020) 1-9.