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基于光流体技术的手机显微镜和流式细胞术用于血液分析。

Opto-fluidics based microscopy and flow cytometry on a cell phone for blood analysis.

作者信息

Zhu Hongying, Ozcan Aydogan

机构信息

Electrical Engineering Department, University of California, Los Angeles, CA, 90095, USA,

出版信息

Methods Mol Biol. 2015;1256:171-90. doi: 10.1007/978-1-4939-2172-0_12.

Abstract

Blood analysis is one of the most important clinical tests for medical diagnosis. Flow cytometry and optical microscopy are widely used techniques to perform blood analysis and therefore cost-effective translation of these technologies to resource limited settings is critical for various global health as well as telemedicine applications. In this chapter, we review our recent progress on the integration of imaging flow cytometry and fluorescent microscopy on a cell phone using compact, light-weight and cost-effective opto-fluidic attachments integrated onto the camera module of a smartphone. In our cell-phone based opto-fluidic imaging cytometry design, fluorescently labeled cells are delivered into the imaging area using a disposable micro-fluidic chip that is positioned above the existing camera unit of the cell phone. Battery powered light-emitting diodes (LEDs) are butt-coupled to the sides of this micro-fluidic chip without any lenses, which effectively acts as a multimode slab waveguide, where the excitation light is guided to excite the fluorescent targets within the micro-fluidic chip. Since the excitation light propagates perpendicular to the detection path, an inexpensive plastic absorption filter is able to reject most of the scattered light and create a decent dark-field background for fluorescent imaging. With this excitation geometry, the cell-phone camera can record fluorescent movies of the particles/cells as they are flowing through the microchannel. The digital frames of these fluorescent movies are then rapidly processed to quantify the count and the density of the labeled particles/cells within the solution under test. With a similar opto-fluidic design, we have recently demonstrated imaging and automated counting of stationary blood cells (e.g., labeled white blood cells or unlabeled red blood cells) loaded within a disposable cell counting chamber. We tested the performance of this cell-phone based imaging cytometry and blood analysis platform by measuring the density of red and white blood cells as well as hemoglobin concentration in human blood samples, which showed a good match to our measurement results obtained using a commercially available hematology analyzer. Such a cell-phone enabled opto-fluidics microscopy, flow cytometry, and blood analysis platform could be especially useful for various telemedicine applications in remote and resource-limited settings.

摘要

血液分析是医学诊断中最重要的临床检测之一。流式细胞术和光学显微镜是广泛用于血液分析的技术,因此将这些技术经济高效地应用于资源有限的环境对于各种全球健康以及远程医疗应用至关重要。在本章中,我们回顾了我们最近在将成像流式细胞术和荧光显微镜集成到手机上的进展,使用紧凑、轻便且经济高效的光流体附件集成到智能手机的相机模块上。在我们基于手机的光流体成像细胞术设计中,使用一次性微流体芯片将荧光标记的细胞输送到成像区域,该芯片位于手机现有相机单元上方。电池供电的发光二极管(LED)与该微流体芯片的侧面对接耦合,无需任何透镜,这有效地充当了多模平板波导,激发光在其中被引导以激发微流体芯片内的荧光靶标。由于激发光垂直于检测路径传播,一个廉价的塑料吸收滤光片能够阻挡大部分散射光,并为荧光成像创建一个良好的暗场背景。采用这种激发几何结构,手机相机可以记录颗粒/细胞在微通道中流动时的荧光视频。然后对这些荧光视频的数字帧进行快速处理,以量化被测溶液中标记颗粒/细胞的数量和密度。通过类似的光流体设计,我们最近展示了对一次性细胞计数室内加载的静态血细胞(例如标记的白细胞或未标记的红细胞)进行成像和自动计数。我们通过测量人类血液样本中的红细胞和白细胞密度以及血红蛋白浓度来测试这个基于手机的成像细胞术和血液分析平台的性能,结果显示与我们使用市售血液分析仪获得的测量结果非常匹配。这种基于手机的光流体显微镜、流式细胞术和血液分析平台对于远程和资源有限环境中的各种远程医疗应用可能特别有用。

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