Microfluidic Devices

Red blood cell (RBC) morphology device. A simple microfluidic device consisting of a high aspect ratio channel supported by pillars with gaps conforming to the field of view of a 64x magnification microscope. The device orients human RBCs into a single layer optimized for imaging. The pressure differential between inlet and outlet ports drives flow past the microscope camera which enables automated collection of images of large numbers of unique RBCs. An image analysis algorithm automatically measures features of individual RBCs and uses a decision tree to sort RBC images into morphology categories: discocyte (D), echinocyte 1 (E1), echinocyte 2 (E2), echinocyte 3 (E3), sphero-echinocyte (SE), stomatocyte 1 (ST1), stomatocyte 2 (ST2), and spherocyte (S). The device was used to analyze >1,000,000 individual stored human RBCs, the largest study of its kind at the time of publication.

Relevant Publications:

Piety NZ, Gifford SC, Yang X, Shevkoplyas SS (2015) “Quantifying morphological heterogeneity: a study of more than 1 000 000 individual stored red blood cells,” Vox Sanguinis, 109(3): 221 – 230 https://doi.org/10.1111/vox.12277
Routt AH, Yang N, Piety NZ, Lu M, Shevkoplyas SS (2023) “Deep ensemble learning enables highly accurate classification of stored red blood cell morphology,” Scientific Reports, 13(1): 3152 https://doi.org/10.1038/s41598-023-30214-w

Artificial microvascular network (AMVN) microfluidic device. The network consists of an interconnected network of 5um deep microchannels with a pattern inspired by the layout of mesenteric microvasculature (original pattern by Sergey Shevkoplyas, Ph.D.). Three side-by-side networks with separate inlets and a common outlet enable the simultaneous evaluation of up to 3 blood samples under nearly-physiological flow conditions. An automated image analysis algorithm measures the perfusion rate of RBCs through the larger "arteriole" channels and the smaller "capillary" channels. Perfusion rate measurements can be used to quantify the impact of various conditions/treatments on RBC rheological properties. The system was used to study the effects of anaerobic storage, RBC shape, osmolality, washing with albumin solution, RBC aggregation, hematocrit, perfusion pressure, washing with hypotonic saline, and hypothermic storage.

Relevant Publications:

Piety NZ, Reinhart WH, Pourreau PH, Abidi R, Shevkoplyas SS (2015) “Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network,” Transfusion, 56(4): 844 – 851 https://doi.org/10.1111/trf.13449
Piety NZ, Reinhart WH, Stutz J, Shevkoplyas SS (2017) “Optimal hematocrit in an artificial microvascular network,” Transfusion, 57(9): 2257 – 2266 https://doi.org/10.1111/trf.14213
Piety NZ, Stutz J, Yilmaz N, Xia H, Yoshida T, Shevkoplyas SS (2020) “Microfluidic capillary networks are more sensitive to storage-induced decline of red blood cell deformability than ektacytometry,” Scientific Reports, 11(1): 604 https://doi.org/10.1038/s41598-020-79710-3
Reinhart WH, Piety NZ, Shevkoplyas SS (2017) “Influence of feeding hematocrit and perfusion pressure on hematocrit reduction (Fåhræus effect) in an artificial microvascular network,” Microcirculation, 24(8): e12396 https://doi.org/10.1111/micc.12396
Reinhart WH, Piety NZ, Shevkoplyas SS (2016) “Influence of red blood cell aggregation on perfusion of an artificial microvascular network,” Microcirculation, 24(5): e12317 https://doi.org/10.1111/micc.12317
Reinhart WH, Piety NZ, Deuel JW, Makhro A, Schulzki T, Bogdanov N, Goede JS, Bogdanova A, Abidi R, Shevkoplyas SS (2015) “Washing stored red blood cells in an albumin solution improves their morphologic and hemorheologic properties,” Transfusion, 55(8): 1872 – 1881 (front cover) https://doi.org/10.1111/trf.13052
Reinhart WH, Piety NZ, Goede JS, Shevkoplyas SS (2015) “Effect of osmolality on erythrocyte rheology and perfusion of an artificial microvascular network,” Microvascular Research, 98: 102 – 107 https://doi.org/10.1016/j.mvr.2015.01.010
Vörös E, Piety NZ, Strachan BC, Lu M, Shevkoplyas SS (2018) “Centrifugation-free washing: A novel approach for removing immunoglobulin A from stored red blood cells,” American Journal of Hematology, 93(4): 518 – 526 https://doi.org/10.1002/ajh.25026
Xia H, Khanal G, Strachan BC, Vörös E, Piety NZ, Gifford SC, Shevkoplyas SS (2017) “Washing in hypotonic saline reduces the fraction of irreversibly-damaged cells in stored blood: a proof-of-concept study,” Blood Transfusion, 15(5): 463 https://doi.org/10.2450/2017.0013-17
Burns JM, Yoshida T, Dumont LJ, Yang X, Piety NZ, Shevkoplyas SS (2015) “Deterioration of red blood cell mechanical properties is reduced in anaerobic storage,” Blood Transfusion, 14(1): 80 – 88 (front cover) https://doi.org/10.2450/2015.0241-15

Multiplexed microcapillary network (MMCN) microfluidic device. The network consists of 32 parallel 5um deep microchannels which narrow from 5um to 3um (original pattern by Sergey Shevkoplyas, Ph.D.). Two side-by-side networks with separate inlets and a common outlet enable the simultaneous evaluation of up to 2 blood samples. An automated image analysis algorithm measures the net perfusion rate of RBCs through the network as well as the number/duration of plugging events (caused by poorly deformable RBCs) within individual microchannels. Perfusion rate and plugging measurements can be used to quantify the impact of various conditions/treatments on RBC rheological properties. The system was used to study the effect of both standard and hypoxic hypothermic storage (blood banking) on RBC mechanical properties.

Relevant Publications:

Piety NZ, Stutz J, Yilmaz N, Xia H, Yoshida T, Shevkoplyas SS (2020) “Microfluidic capillary networks are more sensitive to storage-induced decline of red blood cell deformability than ektacytometry,” Scientific Reports, 11(1): 604 https://doi.org/10.1038/s41598-020-79710-3
Burns JM, Yoshida T, Dumont LJ, Yang X, Piety NZ, Shevkoplyas SS (2015) “Deterioration of red blood cell mechanical properties is reduced in anaerobic storage,” Blood Transfusion, 14(1): 80 – 88 (front cover) https://doi.org/10.2450/2015.0241-15

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