Self-Digitization of Sample Volumes

被引:101
作者
Cohen, Dawn E. [1 ]
Schneider, Thomas [1 ]
Wang, Michelle [1 ]
Chiu, Daniel T. [1 ]
机构
[1] Univ Washington, Dept Chem, Seattle, WA 98195 USA
基金
美国国家科学基金会;
关键词
DROPLETS; CRYSTALLIZATION; MICROFLUIDICS; POLYMORPHISM; SIZE;
D O I
10.1021/ac100713u
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
This paper describes a very simple and robust microfluidic device for digitizing samples into an array of discrete volumes. The device is based on an inherent fluidic phenomenon, where an incoming aqueous sample divides itself into an array of chambers that have been primed with an immiscible phase. Self-digitization of sample volumes results from the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the digitized samples in the chambers. Here, we describe experiments and simulations that were used to characterize these parameters and the conditions under which the self-digitization process occurred. Unlike existing methods used to partition samples into an array, our method is able to digitize 100% of a sample into a localized array without any loss of sample volume. The final volume of the discretized sample at each location is defined by the geometry and size of each chamber. Thus, we can form an array of samples with varying but predefined volumes. We exploited this feature to separate the crystal growth of otherwise concomitant polymorphs from a single solution. Additionally, we demonstrated the removal of the digitized samples from the chambers for downstream analysis, as well as the addition of reagents to the digitized samples. We believe this simple method will be useful in a broad range of applications where a large array of discretized samples is required, including digital PCR, single-cell analysis, and cell-based drug screening.
引用
收藏
页码:5707 / 5717
页数:11
相关论文
共 42 条
[1]  
Bernstein J, 1999, ANGEW CHEM INT EDIT, V38, P3440, DOI 10.1002/(SICI)1521-3773(19991203)38:23<3440::AID-ANIE3440>3.0.CO
[2]  
2-#
[3]  
Bernstein J., 2020, Polymorphism in molecular crystals 2e, Vvol. 30
[4]   Self-propelling slugs [J].
Bico, J ;
Quéré, D .
JOURNAL OF FLUID MECHANICS, 2002, 467 :101-127
[5]   SELF-ORGANIZATION OF ORGANIC LIQUIDS ON PATTERNED SELF-ASSEMBLED MONOLAYERS OF ALKANETHIOLATES ON GOLD [J].
BIEBUYCK, HA ;
WHITESIDES, GM .
LANGMUIR, 1994, 10 (08) :2790-2793
[6]   Simple, robust storage of drops and fluids in a microfluidic device [J].
Boukellal, Hakim ;
Selimovic, Seila ;
Jia, Yanwei ;
Cristobal, Galder ;
Fraden, Seth .
LAB ON A CHIP, 2009, 9 (02) :331-338
[7]   Microfluidic methods for generating continuous droplet streams [J].
Christopher, G. F. ;
Anna, S. L. .
JOURNAL OF PHYSICS D-APPLIED PHYSICS, 2007, 40 (19) :R319-R336
[8]   Experimental observations of the squeezing-to-dripping transition in T-shaped microfluidic junctions [J].
Christopher, Gordon F. ;
Noharuddin, N. Nadia ;
Taylor, Joshua A. ;
Anna, Shelley L. .
PHYSICAL REVIEW E, 2008, 78 (03)
[9]   Electrochemical analysis in picoliter microvials [J].
Clark, RA ;
Hietpas, PB ;
Ewing, AG .
ANALYTICAL CHEMISTRY, 1997, 69 (02) :259-263
[10]   Dyeing polymorphs: The MALDI host 2,5-dihydroxybenzoic acid [J].
Cohen, Dawn E. ;
Benedict, Jason B. ;
Morlan, Brian ;
Chiu, Daniel T. ;
Kahr, Bart .
CRYSTAL GROWTH & DESIGN, 2007, 7 (03) :492-495