Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability

Red blood cell (RBC) deformability plays an important role in the pathology of various diseases, including malaria, hemoglobinopathies, and micronutrient deficiencies. Specifically, in malaria, the analysis of RBC deformability presents new approaches for detecting infections and for rapidly evaluat...

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Main Author: Myrand-Lapierre, Marie-Eve
Language:English
Published: University of British Columbia 2014
Online Access:http://hdl.handle.net/2429/46615
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spelling ndltd-UBC-oai-circle.library.ubc.ca-2429-466152018-01-05T17:27:22Z Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability Myrand-Lapierre, Marie-Eve Red blood cell (RBC) deformability plays an important role in the pathology of various diseases, including malaria, hemoglobinopathies, and micronutrient deficiencies. Specifically, in malaria, the analysis of RBC deformability presents new approaches for detecting infections and for rapidly evaluating the response to drugs by patients. A key challenge, however, is that the infected RBCs represent only a small subpopulation of clinical blood specimens. Therefore effective detection of infection and analysis require methods that can measure a large number of individual RBCs. Traditional technologies for measuring RBC deformability either cannot evaluate single cells to identify diseased subpopulations or do not have sufficient measurement throughput to detect rare subpopulations. In additions, they require delicate experiments, expensive equipment, and skilled technicians. To address these issues, we developed a new microfluidic mechanism, known as the Multiplexed Fluidic Plunger (MFP), to measure RBC deformability using many microscale-tapered constrictions in parallel. The deformability of each RBC is determined by the threshold pressure required to squeeze the cell through a constriction. Our mechanism overcomes a key challenge where the pressure applied to each cell is dependent on the presence or absence of other cells and thereby produces in an inconsistent measurement result. We devised a mechanism to avoid this error and showed that a consistent measurement is obtained independent of constrictions occupancy. Furthermore, the sensitivity of the MFP device is comparable or superior to existing techniques since it can distinguish control and 0.0005% glutaraldehyde-treated RBCs (p<0.005). The high sensitivity of this mechanism, potential low production cost, and simplified experimental procedures facilitates its application in a clinical context such as in areas where malaria is endemic. Therefore, we further determined the deformability profiles of RBCs parasitized by P. falciparum (concentrations ranging from 1-16%). The MFP device was able to detect the deformability of RBCs with a parasitemia as low as 1.8% and can therefore potentially be used to evaluate the parasitemia of infected samples. Applied Science, Faculty of Graduate 2014-04-29T21:39:43Z 2015-04-30T00:00:00Z 2014 2014-09 Text Thesis/Dissertation http://hdl.handle.net/2429/46615 eng Attribution-NonCommercial-NoDerivs 2.5 Canada http://creativecommons.org/licenses/by-nc-nd/2.5/ca/ University of British Columbia
collection NDLTD
language English
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description Red blood cell (RBC) deformability plays an important role in the pathology of various diseases, including malaria, hemoglobinopathies, and micronutrient deficiencies. Specifically, in malaria, the analysis of RBC deformability presents new approaches for detecting infections and for rapidly evaluating the response to drugs by patients. A key challenge, however, is that the infected RBCs represent only a small subpopulation of clinical blood specimens. Therefore effective detection of infection and analysis require methods that can measure a large number of individual RBCs. Traditional technologies for measuring RBC deformability either cannot evaluate single cells to identify diseased subpopulations or do not have sufficient measurement throughput to detect rare subpopulations. In additions, they require delicate experiments, expensive equipment, and skilled technicians. To address these issues, we developed a new microfluidic mechanism, known as the Multiplexed Fluidic Plunger (MFP), to measure RBC deformability using many microscale-tapered constrictions in parallel. The deformability of each RBC is determined by the threshold pressure required to squeeze the cell through a constriction. Our mechanism overcomes a key challenge where the pressure applied to each cell is dependent on the presence or absence of other cells and thereby produces in an inconsistent measurement result. We devised a mechanism to avoid this error and showed that a consistent measurement is obtained independent of constrictions occupancy. Furthermore, the sensitivity of the MFP device is comparable or superior to existing techniques since it can distinguish control and 0.0005% glutaraldehyde-treated RBCs (p<0.005). The high sensitivity of this mechanism, potential low production cost, and simplified experimental procedures facilitates its application in a clinical context such as in areas where malaria is endemic. Therefore, we further determined the deformability profiles of RBCs parasitized by P. falciparum (concentrations ranging from 1-16%). The MFP device was able to detect the deformability of RBCs with a parasitemia as low as 1.8% and can therefore potentially be used to evaluate the parasitemia of infected samples. === Applied Science, Faculty of === Graduate
author Myrand-Lapierre, Marie-Eve
spellingShingle Myrand-Lapierre, Marie-Eve
Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
author_facet Myrand-Lapierre, Marie-Eve
author_sort Myrand-Lapierre, Marie-Eve
title Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
title_short Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
title_full Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
title_fullStr Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
title_full_unstemmed Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
title_sort multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
publisher University of British Columbia
publishDate 2014
url http://hdl.handle.net/2429/46615
work_keys_str_mv AT myrandlapierremarieeve multiplexedfluidicplungermechanismforthemeasurementofredbloodcelldeformability
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