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采用数字微流控全血分离和预加载纸传感器测定血锂浓度。

Determination of blood lithium-ion concentration using digital microfluidic whole-blood separation and preloaded paper sensors.

机构信息

Graduate School of Chemical Sciences and Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, 060-8628, Japan.

Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita, Sapporo, 060-8628, Japan; Innovative Research Centre for Preventive Medical Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya, 464-8601, Japan; Institute of Nano-Life-Systems, Institute of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa, Nagoya, 464-8601, Japan.

出版信息

Biosens Bioelectron. 2022 Jan 1;195:113631. doi: 10.1016/j.bios.2021.113631. Epub 2021 Sep 13.

DOI:10.1016/j.bios.2021.113631
PMID:34571482
Abstract

Existing microfluidic technologies for blood tests have several limitations, including difficulties in integrating the sample preparation steps, such as blood dilution, and precise metering of tiny samples (microliter) for accurate downstream analyses on a chip. Digital microfluidics (DMF) is a liquid manipulation technique that can provide precise volume control of micro or nano-liter liquid droplets. Without using sensitive but complex detection methods for tiny droplets involving fluorescence, luminescence, and electrochemistry, this article presents a DMF device with embedded paper-based sensors to detect blood lithium-ion (Li) concentration by colorimetry. Dielectrophoresis on the DMF device between two parallel planar electrodes separates plasma droplets (from tens to hundreds of nanoliters in volume) from undiluted whole blood (a few microliters) within 4 min with an efficiency exceeding 90%. The embedded paper sensors contain a detection reagent to absorb the DMF-transported plasma droplets. These droplets change the color of the paper sensors in accordance with the Li concentration. Subsequently, colorimetry is used to reveal the Li concentration via image analysis. The proposed method meets the detection-sensitivity requirement for clinical diagnosis of bipolar disorder, making the DMF device a potential therapeutic tool for rapid whole-blood Li detection.

摘要

现有的用于血液检测的微流控技术存在一些局限性,包括难以整合样品制备步骤,如血液稀释,以及对芯片上的下游分析进行精确计量微小样本(微升)。数字微流控(DMF)是一种液体处理技术,可以实现微升或纳升液滴的精确体积控制。本文提出了一种 DMF 装置,该装置具有嵌入式纸质传感器,可通过比色法检测血液锂离子(Li)浓度,而无需使用涉及荧光、发光和电化学的微小液滴的敏感但复杂的检测方法。在 DMF 装置的两个平行平面电极之间进行电介质电泳,可以在 4 分钟内将血浆(体积从几十到几百纳升)与未经稀释的全血(几微升)分离,效率超过 90%。嵌入式纸质传感器包含一种检测试剂,用于吸收 DMF 输送的血浆液滴。这些液滴会根据 Li 浓度改变纸质传感器的颜色。随后,通过图像分析比色法来揭示 Li 浓度。该方法满足双相情感障碍临床诊断的检测灵敏度要求,使 DMF 装置成为快速全血 Li 检测的潜在治疗工具。

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