Size and density measurements of single sickle red blood cells using microfluidic magnetic levitation

Goreke, Utku; Bode, Allison; Yaman, Sena; Gürkan, Umut A.; Durmus, Naside Gözde

doi:10.1039/d1lc00686j

Cited by 20 publications

(11 citation statements)

References 50 publications

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“…Compared to the murine hybrid cell line, mPBMCs had a lower levitation height at all the paramagnetic conditions tested ( Figure 3a-c ). mPBMC levitation heights also correlated with changes in the paramagnetic medium concentration, consistent with previous experiments and literature 21–25 . For instance, the average levitation height of mPBMCs cells was 226 ± 58 μm at 30 mM paramagnetic media ( Figure 3a ), and their heights increased to 295 ± 75 μm ( Figure 3b ) and 400 ± 84 μm ( Figure 3c ), at 50 mM and 80 mM paramagnetic media, respectively.…”

Section: Resultssupporting

confidence: 91%

Magnetic Levitation and Sorting of Neoplastic Circulating Cell Hybrids

Liang

Yaman

Patel

et al. 2022

Preprint

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Circulating hybrid cells (CHCs) are a novel, rare cell population that harbor tumor and immune cell phenotypes and genotypes and are detectible in peripheral blood. Several recent reports implicated CHCs in the metastatic cascade and found their enumeration to provide better prognostic value than conventionally-defined circulating tumor cells (CTCs). However, methods for isolation and enrichment of CHCs are not well-studied or established. Here, we developed an ultrasensitive, antigen-independent platform leveraging the principles of magnetic levitation for the detection and isolation of disseminated neoplastic CHCs. For the first time, we demonstrate that CHCs can be magnetically focused to different levitation heights, under various paramagnetic conditions using a static levitation system, and we quantified the biophysical properties of CHCs (i.e., levitation heights). In addition, we investigated whether magnetic levitation approach can be combined with the affinity-based strategies to enrich CHCs under the magnetic field. Using clinical samples from breast and colorectal cancer patients, we demonstrated that neoplastic cells can be sorted with a magnetic levitation-based sorting device, without relying on any surface markers. Overall, we demonstrated the feasibility of the magnetic levitation method for unbiased enrichment of rare neoplastic-immune hybrid cells from peripheral blood specimens from cancer patients. This approach can be expanded to more clinical samples and cancer types to unprecedentedly explore the biology of rare neoplastic cells and develop metastasis-tailored therapies broadly impacting personalized and precision clinical treatments.

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Section: Resultssupporting

confidence: 91%

Magnetic Levitation and Sorting of Neoplastic Circulating Cell Hybrids

Liang

Yaman

Patel

et al. 2022

Preprint

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“…The technique is based on the detection of a magnetically labeled biomolecule interacting with a biofunctionalized magnetic-field sensor in the external strong magnetic field provided by two magnets. Another work by Gokere et al [ 42 ] made an extra step forward and developed a label-free magnetic levitation-based assay that detects density differences of individual red blood cells down to 0.0001 g/mL resolution. The main advantages of the assay is that it does not require magnetic particles and corresponding biofunctionalization.…”

Section: Biosensor Technologymentioning

confidence: 99%

Device Processing Challenges for Miniaturized Sensing Systems Targeting Biological Fluids

Stoukatch

Dupont

Redouté

2022

Biomedical Materials & Devices

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This article presents a review of device processing technologies used in the fabrication of biomedical systems, and highlights the requirements of advanced manufacturing technology. We focus on biomedical systems that perform diagnostics of fluidic specimens, with analytes that are in the liquid phase. In the introduction, we define biomedical systems as well as their versatile applications and the essential current trends. The paper gives an overview of the most important biomolecules that typically must be detected or analyzed in several applications. The paper is structured as follows. First, the conventional architecture and construction of a biosensing system is introduced. We provide an overview of the most common biosensing methods that are currently used for the detection of biomolecules and its analysis. We present an overview of reported biochips, and explain the technology of biofunctionalization and detection principles, including their corresponding advantages and disadvantages. Next, we introduce microfluidics as a method for delivery of the specimen to the biochip sensing area. A special focus lies on material requirements and on manufacturing technology for fabricating microfluidic systems, both for niche and mass-scale production segments. We formulate requirements and constraints for integrating the biochips and microfluidic systems. The possible impacts of the conventional microassembly techniques and processing methods on the entire biomedical system and its specific parts are also described. On that basis, we explain the need for alternative microassembly technologies to enable the integration of biochips and microfluidic systems into fully functional systems.

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“…5 HbS-containing erythrocytes undergo deleterious membrane changes and become abnormally adhesive, dense, and less deformable. [5][6][7][8][9] HbS polymerization affects both reticulocytes (nucleic acid-bearing immature red blood cells) and mature erythrocytes. Most well studied sickle red blood cell adhesion mechanisms involve adhesion through proteins including integrins and BCAM/LU, [10][11][12][13][14] which are more relevant to reticulocyte phenotype rather than mature erythrocyte phenotype.…”

Section: Introductionmentioning

confidence: 99%

Membrane bending and sphingomyelinase-associated, sulfatide-dependent hypoxic adhesion of sickle mature erythrocytes

et al. 2023

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Abnormal erythrocyte adhesion due to polymerization of sickle hemoglobin is central to the pathophysiology of sickle cell disease (SCD). Mature erythrocytes constitute >80% of all erythrocytes in SCD, and the relative contributions made by erythrocytes to acute and chronic vasculopathy in SCD are not well understood. Here, we show that the bending stress exerted on the erythrocyte plasma membrane by the sickle hemoglobin polymerization under hypoxia enhances sulfatide-mediated abnormal mature erythrocyte adhesion. We hypothesized that sphingomyelinase activity that is upregulated by accumulated bending energy leads to elevated membrane sulfatide availability and thus hypoxic mature erythrocyte adhesion. We found that mature erythrocyte adhesion to laminin in controlled microfluidic experiments is significantly greater under hypoxia than under normoxia (1856±481 vs. 78±23, mean±SEM), while sickle reticulocyte (early erythrocyte) adhesion, high to begin with, does not change (1281 ±299 vs. 1258±328, mean±SEM). We show that greater mean accumulated bending energy of adhered mature erythrocytes is associated with higher acid SMase activity and increased mature erythrocyte adhesion (p=0.022, for the acid SMase activity and p=0.002 for the increase in mature erythrocyte adhesion with hypoxia, N=5). In addition, hypoxia results in sulfatide exposure on the erythrocyte membrane, and sphingomyelinase increases while anti-sulfatide inhibits the enhanced adhesion of erythrocytes. These results suggest that lipid components of the plasma membrane contribute to the complications in SCD. Therefore, sulfatide and the components of its upregulation pathway, particularly sphingomyelinase should be further explored as potential therapeutic targets to inhibit sickle erythrocyte adhesion.

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Size and density measurements of single sickle red blood cells using microfluidic magnetic levitation

Abstract: Single cells have unique biophysical signatures that can rapidly change during various disease states.

Cited by 20 publications

References 50 publications

Magnetic Levitation and Sorting of Neoplastic Circulating Cell Hybrids

Magnetic Levitation and Sorting of Neoplastic Circulating Cell Hybrids

Device Processing Challenges for Miniaturized Sensing Systems Targeting Biological Fluids

Membrane bending and sphingomyelinase-associated, sulfatide-dependent hypoxic adhesion of sickle mature erythrocytes

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