Dataset Information

An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation.

ABSTRACT: An on-chip deformability checker is proposed to improve the velocity?deformation correlation for red blood cell (RBC) evaluation. RBC deformability has been found related to human diseases, and can be evaluated based on RBC velocity through a microfluidic constriction as in conventional approaches. The correlation between transit velocity and amount of deformation provides statistical information of RBC deformability. However, such correlations are usually only moderate, or even weak, in practical evaluations due to limited range of RBC deformation. To solve this issue, we implemented three constrictions of different width in the proposed checker, so that three different deformation regions can be applied to RBCs. By considering cell responses from the three regions as a whole, we practically extend the range of cell deformation in the evaluation, and could resolve the issue about the limited range of RBC deformation. RBCs from five volunteer subjects were tested using the proposed checker. The results show that the correlation between cell deformation and transit velocity is significantly improved by the proposed deformability checker. The absolute values of the correlation coefficients are increased from an average of 0.54 to 0.92. The effects of cell size, shape and orientation to the evaluation are discussed according to the experimental results. The proposed checker is expected to be useful for RBC evaluation in medical practices.

SUBMITTER: Tsai CD

PROVIDER: S-EPMC6190329 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation.

Tsai Chia-Hung Dylan CD Tanaka Junichi J Kaneko Makoto M Horade Mitsuhiro M Ito Hiroaki H Taniguchi Tatsunori T Ohtani Tomohito T Sakata Yasushi Y

Micromachines 20161001 10

An on-chip deformability checker is proposed to improve the velocity⁻deformation correlation for red blood cell (RBC) evaluation. RBC deformability has been found related to human diseases, and can be evaluated based on RBC velocity through a microfluidic constriction as in conventional approaches. The correlation between transit velocity and amount of deformation provides statistical information of RBC deformability. However, such correlations are usually only moderate, or even weak, in practic ...[more]

PMID: 30404351

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Project description:The malignancy potential is correlated with mechanical deformability of the cancer cells. Therefore, mechanical properties of individual patient cells can contribute essential knowledge in cancer diagnostics and in precision therapies. However, clinical applications are limited by lack of current knowledge and of reliable and robust cell mechanical tests. In a comprehensive study, we found a Triangular Correlation (TrC) between cell deformability, phagocytic like capacity, and cancer aggressiveness. A significant application of the TrC is that phagocytic measurements can be a surrogate marker for detecting malignancy of cancer cells based on mechanical properties. We found that the uptake of inert sub-micron and micro-beads was massively higher in cancer cells compared with non-cancerous cells. Moreover, cells with a higher malignancy potential had greater uptake capacity. Importantly, in a reciprocal approach, we sorted either human bladder cancer cells or melanoma cells into subpopulations, solely based on their phagocytic capacity. The more phagocytic subpopulations showed elevated phenotypes of cancer aggressiveness ex vivo and in vivo. The uptake potential was found to be an imprinted feature preserved genetically and enriched over the sorting cycles. A gene expression profile revealed differences in gene sets associated with regulation of cell-cell and extracellular matrix adhesions and epithelial-to-mesenchymal transition. Chromatin immunoprecipitation sequencing showed that differences in gene expression were reflected also at the chromatin level. Importantly, in all cases studied here, enhanced phagocytic ability and elevated aggressiveness phenotypes were correlated with greater cell deformability, providing the mechanical link of the TrC. A computational model supported the notion that the uptake capacity can be a marker for malignancy mediated by cell mechanics. Our multidisciplinary approach, which involved complementary directions of study in several types of cancer cells, provides the proof of concept that phagocytic measurements can be applied for cancer diagnostics and precision medicine.

Project description:OBJECTIVES:Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values. DESIGN:Prospective study measuring cerebral blood flow and oxygen extraction fraction using O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5?mL/100?g/min. SETTING:PET facility located within the Neurology/Neurosurgery ICU. PATIENTS:Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7-13?g/dL. INTERVENTIONS:Transfusion of one unit of RBCs over 1 hour. MEASUREMENTS AND MAIN RESULTS:Baseline hemoglobin was 9.7?g/dL (range, 6.9-12.9), and cerebral blood flow was 43?±?11?mL/100?g/min. After transfusion, hemoglobin rose from 9.6?±?1.4 to 10.8?±?1.4?g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4-6.6) to 5.5?mL/100?g/min (interquartile range, 4.8-7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions). CONCLUSIONS:This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that restrictive transfusion practices may not be appropriate in this population. Large prospective trials are necessary to determine if these physiologic benefits translate into clinical improvement and outweigh the risk of transfusion.

Dataset Information

An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation.

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An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation.

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