Research

Even though increased vascularity has been commonly observed in bone marrows of patients with hematological malignancies (liquid tumors), the pathophysiology of leukemia induced angiogenesis in the bone marrow remains elusive. Herein, we demonstrated the usage of a microengineered 3D biomimetic model to study leukemic cell induced bone marrow angiogenesis. Rational design of the 3D angiogenesis chip provided an efficient biomimetic means to promote and visualize early angiogenic processes.

Related publication:

1. Y. Zheng, Y. Sun, X. Yu, Y. Shao, P. Zhang, G. Dai and J. Fu, "Angiogenesis in liquid tumors: An in-vitro assay for leukemic cell induced bone marrow angiogenesis," Advanced Healthcare Materials, Vol. 5, pp. 1014-1024, 2016

2. Y. Zheng, S. Wang*, W. Liao, A. Deng, X. Xue, A.P. Liu and J. Fu "Spatiotemporal investigation of Dll4-Notch signaling during angiogenesis using nanobiosensors in a 3D microenvironment," Lab on a Chip. 17: 1948-1959, 2016

1. High-throughput single-cell multiple biophysical property measurement

Electrical impedance measurement is made when single cells flow through a constriction channel that is marginally smaller than cells’ diameters. The multiple parameters quantified as mechanical and electrical signatures of each cell include transit time, impedance amplitude ratio, and impedance phase increase. This system is capable of testing 100-150 cells/second.

2. High-throughput single-cell electrical property characterization

This technique is for single-cell electrical property characterization at a speed of 5-10 cells per second (vs. minutes per cell using existing techniques). When a cell flows through a microfluidic constriction channel, electrical impedance at multiple frequencies is measured. Electrical and geometrical models are developed to determine the specific membrane capacitance and cytoplasm conductivity of individual cells.

Related publication:

1. J. Nguyen, Y. Wei, Y. Zheng, C. Wang, and Y. Sun, "On-chip sample preparation for complete blood count from raw blood," Lab on a Chip, Vol. 15, pp. 1533-44, 2015

2. Y. Zheng, J. Wen, J. Nguyen, M.A. Cachia, C. Wang, and Y. Sun, "Biophysical measurement of lymphocytes from chronic lymphocytic leukemia (CLL) patients," Scientific Reports, Vol. 5, article number: 7613, 2015

3. Y. Zheng, E. Shojaei-Baghini, C. Wang, and Y. Sun, "Microfluidic characterization of specific membrane capacitance and cytoplasm conductivity of single cells," Biosensors and Bioelectronics, Vol. 42, pp. 496-502, 2013

4. Y. Zheng, E. Shojaei-Baghini, A. Azad, C. Wang, and Y. Sun, "High-throughput biophysical measurement of human red blood cells," Lab on a Chip, Vol. 12, pp. 2560-2567, 2012

5. J. Chen*, Y. Zheng*, Q.Y. Tan, E. Shojaei-Baghini, et al., “Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells,” Lab on a Chip, Vol. 11, pp. 3174-3181, 2011 (*These authors contributed equally.)

6. J. Chen*, Y. Zheng*, Q.Y. Tan, Y.L. Zhang, et al., "A microfluidic device for simultaneous electrical and mechanical measurements," Biomicrofluidics, Vol. 5, pp. 014113, 2011 (*These authors contributed equally.)(top 20 most-cited articles in 2011)

1. Mechanical differences of sickle cell trait (SCT) and normal red blood cells

Sickle cell trait (SCT) is a condition in which an individual inherits one sickle hemoglobin gene (HbS) and one normal beta hemoglobin gene (HbA). Whether SCT should be treated as physiologically normal remains controversial. In this work, the mechanical properties of individual RBCs were quantified using a microsystem capable of precisely controlling the oxygen level of RBCs' microenvironment. The results demonstrate that RBCs from sickle cell trait individuals are inherently stiffer and more viscous than normal RBCs from healthy donors, but oxygen level variations do not alter their mechanical properties or morphology.

2. Characterization of Red Blood Cell Deformability Change during Blood Storage

Stored red blood cells (RBCs) show progressive deformability changes during blood banking/storage. Their deformability changes over an 8 weeks’ storage period were measured using a microfluidic device and high-speed imaging. Compared to previous studies on stored RBC deformability, our results include a significantly higher number of cells (>1,000 cells/sample vs. a few to tens of cells/sample) and, for the first time, reveal deformation changes of stored RBCs when traveling through human-capillary-like microchannels.

3. Electrical Measurement of Red Blood Cell Deformability

The device consists of two stages of microchannels as two measurement units for measuring cell size/volume and cell deformability. A low frequency voltage signal is established across the microfluidic channel, and electrical current signal is sampled continuously when RBCs pass through the measurement areas. Mechanical opacity is defined to mitigate the coupled effect of cell size/volume and deformability. The results proved the capability of the system for distinguishing different RBC populations based on their deformability with a throughput of ~10 cells/sec.

Related publication:

1. Y. Zheng, M.A. Cachia, J. Ge, Z.S. Xu, C. Wang, and Y. Sun, "Mechanical differences of sickle cell trait (SCT) and normal red blood cells," Lab on a Chip, Vol. 15, pp. 3138 - 3146, 2015 (highlighted as the back cover)

2. Y. Zheng, J. Chen, T. Cui, N. Shehata, C. Wang, and Y. Sun, "Characterization of Red Blood Cell Deformability Change during Blood Storage," Lab on a Chip, Vol. 14, pp. 577-583, 2014

3. Y. Zheng, J. Nguyen, C. Wang, and Y. Sun, "Electrical measurement of red blood cell deformability on a microfluidic device," Lab on a Chip, Vol. 13, pp. 3275-3283, 2013

4. Y. Zheng, J. Nguyen, Y. Wei, and Y. Sun, "Recent advances in microfluidic techniques for single-cell biophysical characterization," Lab on a Chip, Vol. 13, pp. 2464-2483, 2013

This study investigates whether mechanical differences exist between benign and malignant urothelial cells in voided urine. The Young’s modulus of individual cells was measured using the micropipette aspiration technique. Malignant urothelial cells showed significantly lower Young’s modulus values compared to benign urothelial cells. The results indicate that Young’s modulus as a biomechanical marker could possibly provide additional information to conventional urinary cytology.

Related publication:

1. E. Shojaei-Baghini*, Y. Zheng*, W. Geddie, M. Jewett, and Y. Sun, "Mechanical characterization of benign and malignant urothelial cells from voided urine," Applied Physics Letters, Vol. 102, pp. 123704, 2013 (*These authors contributed equally.)

2. E. Shojaei-Baghini, Y. Zheng, and Y. Sun, "Automated micropipette aspiration of single cells," Annals of Biomedical Engineering, Vol. 41, pp. 1208-1216, 2013

A fabrication method based on the restricting effect of laminar flow is developed. Experimental results revealed that the topography of micro structures patterned with the proposed method is mainly determined by the flow patterns of separator and etchant. The computational model on the interface between multiple streams was established for analyzing the causes of various micro topographies. The investigation depicted here provides sufficient references for the understanding on the microscale mass transport at the liquid-liquid surface and can be used to pattern complex micro structures with high aspect ratios.

Related publication:

1. H. Xie, Y. Zheng, Y. Fan, X. Fu and H.Yang, "Flow-restricted etching method on isotropic substrates and its mechanism," Chin. J. Mech. Eng-EN. 23: 560-567, 2010

2. H. Xie, Y. Zheng, Y. Fan, X. Fu and H. Yang, "A novel restricted-flow etching method for glass," J. Zhejiang Univ. Sci. A, Vol. 10, No.11, pp. 1601-1608, 2009

3. Y. Zheng, H. Xie, X. Fu and H. Yang, "Interface position and diffusion of two-phase laminar flow in Y-sensor," J. Zhejiang Univ. Eng., Vol. 43, No.10, pp. 1757-1761, 2009