Bills Matthew V, Nguyen Brandon T, Yoon Jeong-Yeol
Department of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721, USA.
IEEE Sens J. 2019;19(18):7822-7828. doi: 10.1109/jsen.2019.2920235. Epub 2019 Sep 15.
Sorting and measuring blood by cell type is extremely valuable clinically and provides physicians with key information for diagnosing many different disease states including: leukemia, autoimmune disorders, bacterial infections, etc. Despite the value, the present methods are unnecessarily costly and inhibitive particularly in resource poor settings, as they require multiple steps of reagent and/or dye additions and subsequent rinsing followed by manual counting using a hemocytometer, or they require a bulky, expensive equipment such as a flow cytometer. While direct on-paper imaging has been considered challenging, paper substrate offers a strong potential to simplify such reagent/dye addition and rinsing. In this work, three-layer paper-based device is developed to automate such reagent/dye addition and rinsing via capillary action, as well as separating white blood cells (WBCs) from whole blood samples. Direct onpaper imaging is demonstrated using a commercial microscope attachment to a smartphone coupled with a blue LED and 500 nm long pass optical filter. Image analysis is accomplished using an original MATLAB code, to evaluate the total WBC count, as well as differential WBC count, i.e., granulocytes (primarily neutrophils) vs. agranulocytes (primarily lymphocytes). Only a finger-prick of whole blood is required for this assay. The total assay time from finger-prick to data collection is under five minutes. Comparison with a hemocytometry-based manual counting corroborates the accuracy and effectiveness of the proposed method. This approach could be potentially used to help make blood cell counting technologies more readily available, especially in resource poor, point-of-care settings.
按细胞类型对血液进行分类和计数在临床上具有极高的价值,能为医生提供诊断多种不同疾病状态的关键信息,这些疾病包括:白血病、自身免疫性疾病、细菌感染等。尽管有价值,但目前的方法成本过高且具有局限性,特别是在资源匮乏的环境中,因为它们需要多个添加试剂和/或染料以及后续冲洗的步骤,然后使用血细胞计数器进行手动计数,或者需要诸如流式细胞仪等体积庞大、价格昂贵的设备。虽然直接在纸上成像一直被认为具有挑战性,但纸质基底具有简化此类试剂/染料添加和冲洗的巨大潜力。在这项工作中,开发了一种三层纸质设备,通过毛细作用实现试剂/染料添加和冲洗的自动化,以及从全血样本中分离白细胞(WBC)。使用连接到智能手机的商用显微镜附件以及蓝色发光二极管和500纳米长波通光学滤光片进行直接在纸上成像。使用原始的MATLAB代码完成图像分析,以评估白细胞总数以及白细胞分类计数,即粒细胞(主要是中性粒细胞)与无粒细胞(主要是淋巴细胞)。该检测仅需一滴全血。从采血到数据收集的总检测时间不到五分钟。与基于血细胞计数法的手动计数进行比较,证实了所提出方法的准确性和有效性。这种方法有可能用于使血细胞计数技术更容易获得,特别是在资源匮乏的即时医疗环境中。