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A microfluidic system can measure the deformability and adhesion of red blood cells (RBCs) in samples from patients with sickle cell disease (SCD), according to research published in Technology.
The researchers noted that RBC deformability has been associated with vaso-occlusion in SCD, but we have limited knowledge on deformation characteristics of RBCs adhered to endothelium-associated proteins in microphysiological fluid flow conditions.
In the past, various approaches have been used to measure RBC deformability, including optical tweezers, micropipette aspiration, and atomic force microscopy. These methods have enabled sensitive and controlled measurement of RBC mechanical properties, but they are typically performed in open environments without fluid flow.
“Microfluidic techniques allow incorporation of physiological flow conditions, as well as biologically relevant adhesion surfaces in a closed setting, which better mimic the natural physiological environment of the RBCs in blood flow,” said study author Umut Gurkan, PhD, of the Case Western Reserve University in Cleveland, Ohio.
For their system, Dr Gurkan and his colleagues integrated a microfluidic approach with a cell-dimensioning algorithm.
They introduced a new parameter to assess the deformability of RBCs. It is known as the dynamic deformability index (DDI), which they defined as the time-dependent change of the cell’s aspect ratio in response to fluid flow shear stress.
The researchers assessed the deformability and adhesion of RBCs containing healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS). And they found the DDI of HbS-containing RBCs was significantly lower than the DDI of HbA-containing RBCs.
The team also found they could divide HbS-containing RBCs into 2 groups—deformable and non-deformable RBCs.
“We report, for the first time, on the subpopulations of RBCs in terms of dynamic deformation characteristics in SCD: deformable and non-deformable RBCs,” said Yunus Alapan, a PhD candidate at Case Western Reserve University.
“Furthermore, we analyzed adhesion of non-deformable RBCs, in comparison to deformable RBCs, quantitatively at physiological and above physiological flow shear stresses in blood samples obtained from SCD patients.”
“We observed significantly greater numbers of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.”
Now, the researchers are working to further characterize deformability and adhesion of RBCs in a greater number of SCD patients to analyze their associations with clinical phenotypes and complications.
The team said their system may provide important biophysical insights into disease pathophysiology when widely applied in SCD.
They also believe the microfluidic platform has the potential to be used as an in vitro assay for monitoring disease activity at baseline, during clinical flux after treatment, during painful episodes, and in association with long-term complications. 
and a normal one
Image by Betty Pace
A microfluidic system can measure the deformability and adhesion of red blood cells (RBCs) in samples from patients with sickle cell disease (SCD), according to research published in Technology.
The researchers noted that RBC deformability has been associated with vaso-occlusion in SCD, but we have limited knowledge on deformation characteristics of RBCs adhered to endothelium-associated proteins in microphysiological fluid flow conditions.
In the past, various approaches have been used to measure RBC deformability, including optical tweezers, micropipette aspiration, and atomic force microscopy. These methods have enabled sensitive and controlled measurement of RBC mechanical properties, but they are typically performed in open environments without fluid flow.
“Microfluidic techniques allow incorporation of physiological flow conditions, as well as biologically relevant adhesion surfaces in a closed setting, which better mimic the natural physiological environment of the RBCs in blood flow,” said study author Umut Gurkan, PhD, of the Case Western Reserve University in Cleveland, Ohio.
For their system, Dr Gurkan and his colleagues integrated a microfluidic approach with a cell-dimensioning algorithm.
They introduced a new parameter to assess the deformability of RBCs. It is known as the dynamic deformability index (DDI), which they defined as the time-dependent change of the cell’s aspect ratio in response to fluid flow shear stress.
The researchers assessed the deformability and adhesion of RBCs containing healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS). And they found the DDI of HbS-containing RBCs was significantly lower than the DDI of HbA-containing RBCs.
The team also found they could divide HbS-containing RBCs into 2 groups—deformable and non-deformable RBCs.
“We report, for the first time, on the subpopulations of RBCs in terms of dynamic deformation characteristics in SCD: deformable and non-deformable RBCs,” said Yunus Alapan, a PhD candidate at Case Western Reserve University.
“Furthermore, we analyzed adhesion of non-deformable RBCs, in comparison to deformable RBCs, quantitatively at physiological and above physiological flow shear stresses in blood samples obtained from SCD patients.”
“We observed significantly greater numbers of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.”
Now, the researchers are working to further characterize deformability and adhesion of RBCs in a greater number of SCD patients to analyze their associations with clinical phenotypes and complications.
The team said their system may provide important biophysical insights into disease pathophysiology when widely applied in SCD.
They also believe the microfluidic platform has the potential to be used as an in vitro assay for monitoring disease activity at baseline, during clinical flux after treatment, during painful episodes, and in association with long-term complications.
and a normal one
Image by Betty Pace
A microfluidic system can measure the deformability and adhesion of red blood cells (RBCs) in samples from patients with sickle cell disease (SCD), according to research published in Technology.
The researchers noted that RBC deformability has been associated with vaso-occlusion in SCD, but we have limited knowledge on deformation characteristics of RBCs adhered to endothelium-associated proteins in microphysiological fluid flow conditions.
In the past, various approaches have been used to measure RBC deformability, including optical tweezers, micropipette aspiration, and atomic force microscopy. These methods have enabled sensitive and controlled measurement of RBC mechanical properties, but they are typically performed in open environments without fluid flow.
“Microfluidic techniques allow incorporation of physiological flow conditions, as well as biologically relevant adhesion surfaces in a closed setting, which better mimic the natural physiological environment of the RBCs in blood flow,” said study author Umut Gurkan, PhD, of the Case Western Reserve University in Cleveland, Ohio.
For their system, Dr Gurkan and his colleagues integrated a microfluidic approach with a cell-dimensioning algorithm.
They introduced a new parameter to assess the deformability of RBCs. It is known as the dynamic deformability index (DDI), which they defined as the time-dependent change of the cell’s aspect ratio in response to fluid flow shear stress.
The researchers assessed the deformability and adhesion of RBCs containing healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS). And they found the DDI of HbS-containing RBCs was significantly lower than the DDI of HbA-containing RBCs.
The team also found they could divide HbS-containing RBCs into 2 groups—deformable and non-deformable RBCs.
“We report, for the first time, on the subpopulations of RBCs in terms of dynamic deformation characteristics in SCD: deformable and non-deformable RBCs,” said Yunus Alapan, a PhD candidate at Case Western Reserve University.
“Furthermore, we analyzed adhesion of non-deformable RBCs, in comparison to deformable RBCs, quantitatively at physiological and above physiological flow shear stresses in blood samples obtained from SCD patients.”
“We observed significantly greater numbers of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.”
Now, the researchers are working to further characterize deformability and adhesion of RBCs in a greater number of SCD patients to analyze their associations with clinical phenotypes and complications.
The team said their system may provide important biophysical insights into disease pathophysiology when widely applied in SCD.
They also believe the microfluidic platform has the potential to be used as an in vitro assay for monitoring disease activity at baseline, during clinical flux after treatment, during painful episodes, and in association with long-term complications.