A palm-size μNMR relaxometer using a digital microfluidic device and a semiconductor transceiver for chemical/biological diagnosis

被引:29
作者
Lei, Ka-Meng [1 ,2 ]
Mak, Pui-In [1 ,2 ]
Law, Man-Kay [1 ]
Martins, Rui P. [1 ,2 ]
机构
[1] Univ Macau, State Key Lab Analog & Mixed Signal VLSI, Macau, Peoples R China
[2] Univ Macau, Dept ECE, Fac Sci & Technol, Macau, Peoples R China
关键词
POLYMERASE-CHAIN-REACTION; BIOSENSOR; POINT; CHIP; PLATFORM; PROTEIN; SYSTEM; SENSOR; TOOL;
D O I
10.1039/c5an00500k
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Herein, we describe a micro-nuclear magnetic resonance (mu NMR) relaxometer miniaturized to palm-size and electronically automated for multi-step and multi-sample chemical/biological diagnosis. The co-integration of microfluidic and microelectronic technologies enables an association between the droplet managements and mu NMR assays inside a portable sub-Tesla magnet (1.2 kg, 0.46 Tesla). Targets in unprocessed biological samples, captured by specific probe-decorated magnetic nanoparticles (NPs), can be sequentially quantified by their spin-spin relaxation time (T-2) via multiplexed mu NMR screening. Distinct droplet samples are operated by a digital microfluidic device that electronically manages the electrowetting-on-dielectric effects over an electrode array. Each electrode (3.5 x 3.5 mm(2)) is scanned with capacitive sensing to locate the distinct droplet samples in real time. A cross-domain-optimized butterfly-coil-input semiconductor transceiver transduces between magnetic and electrical signals to/from a sub-10 mu L droplet sample for high-sensitivity mu NMR screening. A temperature logger senses the ambient temperature (0 to 40 degrees C) and a backend processor calibrates the working frequency for the transmitter to precisely excite the protons. In our experiments, the mu NMR relaxometer quantifies avidin using biotinylated Iron NPs (Phi: 30 nm, [Fe]: 0.5 mM) with a sensitivity of 0.2 mu M. Auto-handling and identification of two targets (avidin and water) are demonstrated and completed within 2.2 min. This mu NMR relaxometer holds promise for combinatorial chemical/biological diagnostic protocols using closed-loop electronic automation.
引用
收藏
页码:5129 / 5137
页数:9
相关论文
共 39 条
[1]  
[Anonymous], 2001, ANGEW CHEM-GER EDIT
[2]   Digital microfluidics for cell-based assays [J].
Barbulovic-Nad, Irena ;
Yang, Hao ;
Park, Philip S. ;
Wheeler, Aaron R. .
LAB ON A CHIP, 2008, 8 (04) :519-526
[3]   A microfluidic platform for complete mammalian cell culture [J].
Barbulovic-Nad, Irena ;
Au, Sam H. ;
Wheeler, Aaron R. .
LAB ON A CHIP, 2010, 10 (12) :1536-1542
[4]   Integrated polymerase chain reaction chips utilizing digital microfluidics [J].
Chang, Yi-Hsien ;
Lee, Gwo-Bin ;
Huang, Fu-Chun ;
Chen, Yi-Yu ;
Lin, Jr-Lung .
BIOMEDICAL MICRODEVICES, 2006, 8 (03) :215-225
[5]   Lab-on-a-chip devices for global health: Past studies and future opportunities [J].
Chin, Curtis D. ;
Linder, Vincent ;
Sia, Samuel K. .
LAB ON A CHIP, 2007, 7 (01) :41-57
[6]   On the droplet velocity and electrode lifetime of digital microfluidics: voltage actuation techniques and comparison [J].
Dong, Cheng ;
Chen, Tianlan ;
Gao, Jie ;
Jia, Yanwei ;
Mak, Pui-In ;
Vai, Mang-I ;
Martins, Rui P. .
MICROFLUIDICS AND NANOFLUIDICS, 2015, 18 (04) :673-683
[7]   A protein-based electrochemical biosensor for detection of tau protein, a neurodegenerative disease biomarker [J].
Esteves-Villanueva, Jose O. ;
Trzeciakiewicz, Hanna ;
Martic, Sanela .
ANALYST, 2014, 139 (11) :2823-2831
[8]   An intelligent digital microfluidic system with fuzzy-enhanced feedback for multi-droplet manipulation [J].
Gao, Jie ;
Liu, Xianming ;
Chen, Tianlan ;
Mak, Pui-In ;
Du, Yuguang ;
Vai, Mang-I ;
Lin, Bingcheng ;
Martins, Rui P. .
LAB ON A CHIP, 2013, 13 (03) :443-451
[9]   Drivers of biodiagnostic development [J].
Giljohann, David A. ;
Mirkin, Chad A. .
NATURE, 2009, 462 (7272) :461-464
[10]   Scalable NMR spectroscopy with semiconductor chips [J].
Ha, Dongwan ;
Paulsen, Jeffrey ;
Sun, Nan ;
Song, Yi-Qiao ;
Ham, Donhee .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (33) :11955-11960