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基于实验设计优化的用于基于磁性颗粒免疫分析的自动化数字微流控平台。

Automated digital microfluidic platform for magnetic-particle-based immunoassays with optimization by design of experiments.

作者信息

Choi Kihwan, Ng Alphonsus H C, Fobel Ryan, Chang-Yen David A, Yarnell Lyle E, Pearson Elroy L, Oleksak Carl M, Fischer Andrew T, Luoma Robert P, Robinson John M, Audet Julie, Wheeler Aaron R

机构信息

Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.

出版信息

Anal Chem. 2013 Oct 15;85(20):9638-46. doi: 10.1021/ac401847x. Epub 2013 Aug 26.

DOI:10.1021/ac401847x
PMID:23978190
Abstract

We introduce an automated digital microfluidic (DMF) platform capable of performing immunoassays from sample to analysis with minimal manual intervention. This platform features (a) a 90 Pogo pin interface for digital microfluidic control, (b) an integrated (and motorized) photomultiplier tube for chemiluminescent detection, and (c) a magnetic lens assembly which focuses magnetic fields into a narrow region on the surface of the DMF device, facilitating up to eight simultaneous digital microfluidic magnetic separations. The new platform was used to implement a three-level full factorial design of experiments (DOE) optimization for thyroid-stimulating hormone immunoassays, varying (1) the analyte concentration, (2) the sample incubation time, and (3) the sample volume, resulting in an optimized protocol that reduced the detection limit and sample incubation time by up to 5-fold and 2-fold, respectively, relative to those from previous work. To our knowledge, this is the first report of a DOE optimization for immunoassays in a microfluidic system of any format. We propose that this new platform paves the way for a benchtop tool that is useful for implementing immunoassays in near-patient settings, including community hospitals, physicians' offices, and small clinical laboratories.

摘要

我们推出了一种自动化数字微流控(DMF)平台,该平台能够以最少的人工干预从样品到分析进行免疫测定。该平台具有以下特点:(a)用于数字微流控控制的90针弹簧针接口;(b)用于化学发光检测的集成(且电动)光电倍增管;(c)一种磁透镜组件,可将磁场聚焦到DMF设备表面的狭窄区域,便于同时进行多达八次数字微流控磁分离。新平台用于对促甲状腺激素免疫测定进行三级全因子实验设计(DOE)优化,改变(1)分析物浓度、(2)样品孵育时间和(3)样品体积,从而得到一种优化方案,相对于之前的工作,该方案将检测限和样品孵育时间分别降低了多达5倍和2倍。据我们所知,这是关于任何形式的微流控系统中免疫测定的DOE优化的首次报告。我们认为,这个新平台为一种台式工具铺平了道路,该工具可用于在包括社区医院、医生办公室和小型临床实验室在内的近患者环境中进行免疫测定。

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