Microfluidic electrical impedance assessment of red blood cell-mediated microvascular occlusion.
Microfluidic electrical impedance assessment of red blood cell-mediated microvascular occlusion.
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DOI：
10.1039/d0lc01133a
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发表时间：
2021-03-21
期刊：
影响因子：
6.1
通讯作者：
Gurkan UA
中科院分区：
文献类型：
--
作者：
Man Y;Maji D;An R;Ahuja SP;Little JA;Suster MA;Mohseni P;Gurkan UA
红细胞（RBC）变形能力的改变，发生在溶血性血液疾病，如镰状细胞病（SCD），有助于血管闭塞和疾病的病理生理学。有几个功能性的体外测定RBC介导的微血管闭塞的标准化评估。在这里，我们提出了微流控阻抗红细胞检测（MIRCA）的设计，制造和临床测试与嵌入式毛细管网络为基础的微柱阵列和集成电阻抗测量电极，以满足这一需求。微柱阵列由12 μm至3 μm的微毛细管组成，每个阵列与两个溅射金电极配对，以测量样品通过微流控装置灌注前后阵列的阻抗变化。我们定义了红细胞阻塞指数（ROI）和红细胞电阻抗指数（REI），分别代表累积阻塞百分比和累积阻抗变化百分比。我们证明了MIRCA在两种常见的红细胞疾病，SCD和遗传性球形红细胞增多症的承诺。我们表明，电阻抗测量反映了微血管闭塞，其中REI显着相关的ROI，通过高分辨率显微镜成像的微毛细管阵列。此外，我们表明，RBC介导的微血管闭塞，代表ROI和REI，与临床治疗结果，并与体内溶血生物标志物，乳酸脱氢酶（LDH）水平和绝对网织红细胞计数（ARC）在SCD。阻抗测量消除了对高分辨率成像的需求，使该技术能够在未来广泛应用于便携式和即时护理。我们的研究结果表明，提出的微流体设计和集成电阻抗测量提供了一个可重复的功能测试RBC介导的微血管闭塞的标准化评估。MIRCA和新定义的REI可作为评估新兴RBC修饰靶向治疗和治愈性治疗的临床结局的体外疗效基准。
Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contribute to vaso-occlusion and disease pathophysiology. There are few functional in vitro assays for standardized assessment of RBC-mediated microvascular occlusion. Here, we present the design, fabrication, and clinical testing of the Microfluidic Impedance Red Cell Assay (MIRCA) with embedded capillary network-based micropillar arrays and integrated electrical impedance measurement electrodes to address this need. The micropillar arrays consist of microcapillaries ranging from 12 μm to 3 μm, with each array paired with two sputtered gold electrodes to measure the impedance change of the array before and after sample perfusion through the microfluidic device. We define RBC Occlusion Index (ROI) and RBC Electrical Impedance Index (REI), which represent the cumulative percentage occlusion and cumulative percentage impedance change, respectively. We demonstrate the promise of MIRCA in two common red cell disorders, SCD and hereditary spherocytosis. We show that the electrical impedance measurement reflects the microvascular occlusion, where REI significantly correlates with ROI that is obtained via high resolution microscopy imaging of the microcapillary arrays. Further, we show that RBC-mediated microvascular occlusion, represented by ROI and REI, associates with clinical treatment outcomes and correlates with in vivo hemolytic biomarkers, lactate dehydrogenase (LDH) level and absolute reticulocyte count (ARC) in SCD. Impedance measurement obviates the need for high-resolution imaging enabling future translation of this technology for widespread access, portable and point-of-care use. Our findings suggest that the presented microfluidic design and the integrated electrical impedance measurement provide a reproducible functional test for standardized assessment of RBC-mediated microvascular occlusion. MIRCA and the newly defined REI may serve as an in vitro therapeutic efficacy benchmark for assessing clinical outcome of emerging RBC modifying targeted and curative therapies.
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影响因子：
12.6
作者：
Dou, Wenkun;Zhao, Qili;Sun, Yu
通讯作者：
Sun, Yu
DOI：
10.1016/j.trsl.2016.03.008
发表时间：
2016-07
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Alapan Y;Kim C;Adhikari A;Gray KE;Gurkan-Cavusoglu E;Little JA;Gurkan UA
通讯作者：
Gurkan UA
影响因子：
4.9
作者：
Duez, Julien;Holleran, John P.;Buffet, Pierre A.
通讯作者：
Buffet, Pierre A.
影响因子：
5
作者：
Diez-Silva M;Dao M;Han J;Lim CT;Suresh S
通讯作者：
Suresh S
影响因子：
20.3
作者：
Carden, Marcus A.;Fay, Meredith E.;Lam, Wilbur A.
通讯作者：
Lam, Wilbur A.