Automated Digital Microfluidic Platform for Magnetic-Particle-Based Immunoassays with Optimization by Design of Experiments

被引：122

作者：

Choi, Kihwan ^{[1
,3
]}

Ng, Alphonsus H. C. ^{[2
,3
]}

Fobel, Ryan ^{[2
,3
]}

Chang-Yen, David A. ^{[4
]}

Yarnell, Lyle E. ^{[5
]}

Pearson, Elroy L. ^{[4
]}

Oleksak, Carl M. ^{[5
]}

Fischer, Andrew T. ^{[5
]}

Luoma, Robert P. ^{[5
]}

Robinson, John M. ^{[6
]}

Audet, Julie ^{[2
,3
]}

Wheeler, Aaron R. ^{[1
,2
,3
]}

机构：

[1] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada

[2] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada

[3] Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada

[4] AbbVie, Abbott Pk, IL 60064 USA

[5] Abbott Diagnost, Irving, TX 75038 USA

[6] Abbott Diagnost, Abbott Pk, IL 60064 USA

来源：

ANALYTICAL CHEMISTRY | 2013年 / 85卷 / 20期

基金：

加拿大自然科学与工程研究理事会;

关键词：

POINT;

D O I：

10.1021/ac401847x

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

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.

引用

页码：9638 / 9646

页数：9

共 35 条

[1] Assay optimization: A statistical design of experiments approach [J].

Altekar, Maneesha ;

Homon, Carol A. ;

Kashem, Mohammed A. ;

Mason, Steven W. ;

Nelson, Richard M. ;

Patnaude, Lori A. ;

Yingling, Jeffrey ;

Taylor, Paul B. .

CLINICS IN LABORATORY MEDICINE, 2007, 27 (01) :139-+

[2] Adventures in Time and Space: Non linearity and Complexity of Cytokine Effects on Stem Cell Fate Decisions [J].

Audet, Julie .

BIOTECHNOLOGY AND BIOENGINEERING, 2010, 106 (02) :173-182

[3] The clinical significance of subclinical thyroid dysfunction [J].

Biondi, Bernadette ;

Cooper, David S. .

ENDOCRINE REVIEWS, 2008, 29 (01) :76-131

[4] Commercialization of microfluidic point-of-care diagnostic devices [J].

Chin, Curtis D. ;

Linder, Vincent ;

Sia, Samuel K. .

LAB ON A CHIP, 2012, 12 (12) :2118-2134

[5] Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits [J].

Cho, SK ;

Moon, HJ ;

Kim, CJ .

JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, 2003, 12 (01) :70-80

[6] Digital Microfluidics [J].

Choi, Kihwan ;

Ng, Alphonsus H. C. ;

Fobel, Ryan ;

Wheeler, Aaron R. .

ANNUAL REVIEW OF ANALYTICAL CHEMISTRY, VOL 5, 2012, 5 :413-440

[7] Novel microfluidic platform for automated lab-on-chip testing of hypercoagulability panel [J].

Emani, Sirisha ;

Sista, Ramakrishna ;

Loyola, Hugo ;

Trenor, Cameron C., III ;

Pamula, Vamsee K. ;

Emani, Sitaram M. .

BLOOD COAGULATION & FIBRINOLYSIS, 2012, 23 (08) :760-768

[8] DropBot: An open-source digital microfluidic control system with precise control of electrostatic driving force and instantaneous drop velocity measurement [J].

Fobel, Ryan ;

Fobel, Christian ;

Wheeler, Aaron R. .

APPLIED PHYSICS LETTERS, 2013, 102 (19)

[9] Magnetic forces produced by rectangular permanent magnets in static microsystems [J].

Gassner, Anne-Laure ;

Abonnenc, Melanie ;

Chen, Hong-Xu ;

Morandini, Jacques ;

Josserand, Jacques ;

Rossier, Joel S. ;

Busnel, Jean-Marc ;

Girault, Hubert H. .

LAB ON A CHIP, 2009, 9 (16) :2356-2363

[10] Drivers of biodiagnostic development [J].

Giljohann, David A. ;

Mirkin, Chad A. .

NATURE, 2009, 462 (7272) :461-464

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