1887
banner image
No data available.
Please log in to see this content.
You have no subscription access to this content.
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
f
High-throughput size-based rare cell enrichment using microscale vortices
Rent:
Rent this article for
Access full text Article
/content/aip/journal/bmf/5/2/10.1063/1.3576780
1.
1.S. Harding, N. Ali, M. Brito-Martins, and J. Gorelik, Pharmacol. Ther. 113, 341 (2007).
http://dx.doi.org/10.1016/j.pharmthera.2006.08.008
2.
2.M. Laflamme, K. Chen, A. Naumova, V. Muskheli, J. Fugate, S. Dupras, H. Reinecke, C. Xu, M. Hassanipour, and S. Police, Nat. Biotechnol. 25, 1015 (2007).
http://dx.doi.org/10.1038/nbt1327
3.
3.D. Anderson, T. Self, I. Mellor, G. Goh, S. Hill, and C. Denning, Mol. Ther. 15, 2027 (2007).
http://dx.doi.org/10.1038/sj.mt.6300303
4.
4.D. Cha, K. Khosrotehrani, D. Bianchi, and K. Johnson, Prenat. Diagn. 25, 586 (2005).
http://dx.doi.org/10.1002/pd.1199
5.
5.M. Taylor, J. Rössler, B. Geoerger, A. Laplanche, O. Hartmann, G. Vassal, and F. Farace, Clin. Cancer Res. 15, 4561 (2009).
http://dx.doi.org/10.1158/1078-0432.CCR-08-2363
6.
6.M. Cristofanilli, G. Budd, M. Ellis, A. Stopeck, J. Matera, M. Miller, J. Reuben, G. Doyle, W. Allard, and L. Terstappen, N. Engl. J. Med. 351, 781 (2004).
http://dx.doi.org/10.1056/NEJMoa040766
7.
7.D. R. Gossett, W. M. Weaver, A. J. Mach, S. C. Hur, H. T. Tse, W. Lee, H. Amini, and D. Di Carlo, Anal. Bioanal. Chem. 397, 3249 (2010).
http://dx.doi.org/10.1007/s00216-010-3721-9
8.
8.S. Zheng, H. Lin, J. Liu, M. Balic, R. Datar, R. Cote, and Y. Tai, J. Chromatogr., A 1162, 154 (2007).
http://dx.doi.org/10.1016/j.chroma.2007.05.064
9.
9.M. Yamada, M. Nakashima, and M. Seki, Anal. Chem. 76, 5465 (2004).
http://dx.doi.org/10.1021/ac049863r
10.
10.J. Green, M. Radisic, and S. Murthy, Anal. Chem.81, 9178 (2009).
http://dx.doi.org/10.1021/ac9018395
11.
11.J. Davis, D. Inglis, K. Morton, D. Lawrence, L. Huang, S. Chou, J. Sturm, and R. Austin, Proc. Natl. Acad. Sci. U.S.A. 103, 14779 (2006).
http://dx.doi.org/10.1073/pnas.0605967103
12.
12.R. Huang, T. Barber, M. Schmidt, R. Tompkins, M. Toner, D. Bianchi, R. Kapur, and W. Flejter, Prenat. Diagn. 28, 892 (2008).
http://dx.doi.org/10.1002/pd.2079
13.
13.S. Choi, S. Song, C. Choi, and J. Park, Anal. Chem. 81, 1964 (2009).
http://dx.doi.org/10.1021/ac8024575
14.
14.D. Di Carlo, D. Irimia, R. G. Tompkins, and M. Toner, Proc. Natl. Acad. Sci. U.S.A. 104, 18892 (2007).
http://dx.doi.org/10.1073/pnas.0704958104
15.
15.D. Di Carlo, J. F. Edd, D. Irimia, R. G. Tompkins, and M. Toner, Anal. Chem. 80, 2204 (2008).
http://dx.doi.org/10.1021/ac702283m
16.
16.A. J. Mach and D. Di Carlo, Bioengineering and Biotechnology 107, 302 (2010).
http://dx.doi.org/10.1002/bit.22833
17.
17.H. Moffatt, J. Fluid Mech. 18, 1 (1964).
http://dx.doi.org/10.1017/S0022112064000015
18.
18.W. Cherdron, F. Durst, and J. Whitelaw, J. Fluid Mech. 84, 13 (1978).
http://dx.doi.org/10.1017/S0022112078000026
19.
19.T. Karino and H. Goldsmith, Microvasc. Res. 17, 217 (1979).
http://dx.doi.org/10.1016/S0026-2862(79)80001-1
20.
20.T. Karino and H. Goldsmith, Philos. Trans. R. Soc. London, Ser. B 279, 413 (1977).
http://dx.doi.org/10.1098/rstb.1977.0095
21.
21.E. O. Macagno and T. Hung, J. Fluid Mech. 28, 43 (1967).
http://dx.doi.org/10.1017/S0022112067001892
22.
22.F. Laine-Pearson and P. Hydon, Stud. Appl. Math. 122, 139 (2009).
http://dx.doi.org/10.1111/j.1467-9590.2008.00427.x
23.
23.D. Lim, J. Shelby, J. Kuo, and D. Chiu, Appl. Phys. Lett. 83, 1145 (2003).
http://dx.doi.org/10.1063/1.1600532
24.
24.Marcos and R. Stocker, Limnol. Oceanogr. Methods 4, 392 (2006).
25.
25.E. Sollier, M. Cubizolles, Y. Fouillet, and J. Achard, Biomed. Microdevices 12, 485 (2010).
http://dx.doi.org/10.1007/s10544-010-9405-6
26.
26.J. Park and H. Jung, Anal. Chem. 81, 8280 (2009).
http://dx.doi.org/10.1021/ac9005765
27.
27.D. Chiu, Anal. Bioanal. Chem. 387, 17 (2006).
http://dx.doi.org/10.1007/s00216-006-0611-2
28.
28.C. Lin, Y. Lai, H. Liu, C. Chen, and A. Wo, Anal. Chem. 80, 8937 (2008).
http://dx.doi.org/10.1021/ac800972t
29.
29.M. Khabiry, B. Chung, M. Hancock, H. Soundararajan, Y. Du, D. Cropek, W. Lee, and A. Khademhosseini, Small 5, 1186 (2009).
30.
30.J. Matas, J. Morris, and E. Guazzelli, J. Fluid Mech. 515, 171 (1999).
http://dx.doi.org/10.1017/S0022112004000254
31.
31.D. Di Carlo, J. Edd, K. Humphry, H. Stone, and M. Toner, Phys. Rev. Lett. 102, 094503 (2009).
http://dx.doi.org/10.1103/PhysRevLett.102.094503
32.
32.S. C. Hur, H. T. K. Tse, and D. Di Carlo, Lab Chip 10, 274 (2010).
http://dx.doi.org/10.1039/b919495a
33.
33.E. Asmolov, J. Fluid Mech. 381, 63 (1999).
http://dx.doi.org/10.1017/S0022112098003474
34.
34.D. Duffy, J. McDonald, O. Schueller, and G. Whitesides, Anal. Chem. 70, 4974 (1998).
http://dx.doi.org/10.1021/ac980656z
35.
35.S. Nagrath, L. Sequist, S. Maheswaran, D. Bell, D. Irimia, L. Ulkus, M. Smith, E. Kwak, S. Digumarthy, and A. Muzikansky, Nature (London) 450, 1235 (2007).
http://dx.doi.org/10.1038/nature06385
36.
36.R. Krivacic, A. Ladanyi, D. Curry, H. Hsieh, P. Kuhn, D. Bergsrud, J. Kepros, T. Barbera, M. Ho, and L. Chen, Proc. Natl. Acad. Sci. U.S.A. 101, 10501 (2004).
http://dx.doi.org/10.1073/pnas.0404036101
37.
37.B. Molnar, A. Ladanyi, L. Tanko, L. Sréter, and Z. Tulassay, Clin. Cancer Res. 7, 4080 (2001).
38.
38.C. K. W. Tam and W. Hyman, J. Fluid Mech. 59, 177 (1973).
http://dx.doi.org/10.1017/S0022112073001497
39.
39.S. C. Hur, N. K. Henderson-MacLennan, E. R. B. McCabe, and D. Di Carlo, Lab Chip11, 912 (2011).
http://dx.doi.org/10.1039/c0lc00595a
40.
40.See supplementary material at http://dx.doi.org/10.1063/1.3576780 for size distribution of HeLa cells captured using the device and viability of captured cells.[Supplementary Material]
41.
41.G. Gobert and H. Schatten, J. Electron Microsc. 49, 539 (2000).
42.
42.K. Rafferty, Virchows Arch. B Cell Pathol. 50, 167 (1986).
http://dx.doi.org/10.1007/BF02889899
43.
43.D. Marrinucci, K. Bethel, M. Luttgen, R. Bruce, J. Nieva, and P. Kuhn, Arch. Pathol. Lab. Med. 133, 1468 (2009).
44.
44.P. Fetsch, K. Cowan, D. Weng, A. Freifield, A. Filie, and A. Abati, Diagn. Cytopathol. 22, 323 (2000).
http://dx.doi.org/10.1002/(SICI)1097-0339(200005)22:5<323::AID-DC13>3.0.CO;2-L
http://aip.metastore.ingenta.com/content/aip/journal/bmf/5/2/10.1063/1.3576780
Loading

Figures

Image of FIG. 1.

Click to view

FIG. 1.

Device design and working principle. (a) The schematic describes that larger cells are trapped in the reservoir while smaller cells freely pass through the reservoir region due to difference in the lift forces that cells encounter. (b) The device consists of eight parallel high aspect ratio straight channels with ten cell trapping reservoirs in each channel. (c) Parallel trapping of fluorescent particles in microscale vortices. (d) A particle with diameter experiences wall effect lift and shear-gradient lift forces , in straight channels, resulting in a dynamic lateral equilibrium position and uniform particle velocities . Here, is defined as the distance between the center of particles/cells and the channel walls. At the reservoir, larger particles experiencing larger are pushed toward the vortex center and trapped, whereas smaller particles are flushed out of the region.

Image of FIG. 2.

Click to view

FIG. 2.

Two- and three-dimensional flow pattern visualization and critical diameter determination. (a) Fluorescent microscopic images using dilute fluorescent particles illustrate the evolution of the flow pattern within the reservoir as flow rate increases. Trapped particle size cutoff was determined using dilute fluorescent particles ( and ). While (b) particles freely pass through the reservoir, (c) particles are trapped and recirculated within the reservoir. (d) Confocal fluorescent microscopic images describing the vortex formation in the cell trapping reservoir in three-dimensional and (e) its cross-sectional view.

Image of FIG. 3.

Click to view

FIG. 3.

Rapid solution exchange, yielding off-chip target cell collection with high purity. (a) particles are trapped and recirculated within the reservoir when the sample solution is injected through the device at . (b) Untrapped particles in the straight regions were flushed with deionized water by a rapid solution exchange mechanism once the bright rings in the reservoirs were observed. (c) Comparison of the capturing efficiency of the device as a function of cell concentration. The number of cells indicates the number of HeLa cells processed through the device.

Image of FIG. 4.

Click to view

FIG. 4.

Massively parallel large cell enrichment from blood using microscale vortices. (a) Dilute whole blood samples spiked with HeLa cells were injected into the device at . (b) The device is flushed once the known volume of the cell solution has been flowed through the device. (c) The trapped HeLa cells were released from the reservoir by reducing the flow rate to achieve and collected off-chip for further analysis. (d) Capturing efficiency and (e) enrichment ratio of the system were found to be higher for MCF7 cells than HeLa cells .41,42

Image of FIG. 5.

Click to view

FIG. 5.

Still image from video showing massively parallel large cell enrichment using microscale laminar vortex. MCF7 cells (breast carcinoma cell line) spiked in dilute whole blood (1% hematocrit) were enriched using a simple one layer microfluidic system. The real-time movie shows all 80 reservoirs effectively capture and release the larger cancer cell from dilute blood solution with a high throughput of . The capturing and flushing steps in the movie were cropped in order to shorten overall play-time (enhanced online). [URL: http://dx.doi.org/10.1063/1.3576780.1]10.1063/1.3576780.1

video/mp4,video/x-flv,video/flv,audio.mp3,audio.mpeg

Multimedia

The following multimedia file is available:
Loading

Article metrics loading...

/content/aip/journal/bmf/5/2/10.1063/1.3576780
2011-06-29
2014-04-23

Abstract

Cell isolation in designated regions or from heterogeneous samples is often required for many microfluidic cell-based assays. However, current techniques have either limited throughput or are incapable of viable off-chip collection. We present an innovative approach, allowing high-throughput and label-free cell isolation and enrichment from heterogeneous solution using cell size as a biomarker. The approach utilizes the irreversible migration of particles into microscale vortices, developed in parallel expansion-contraction trapping reservoirs, as the cell isolation mechanism. We empirically determined the critical particle/cell diameter and the operational flow rate above which trapping of cells/particles in microvortices is initiated. Using this approach we successfully separated larger cancercells spiked in blood from the smaller blood cells with processing rates as high as . Viable long-term culture was established using cells collected off-chip, suggesting that the proposed technique would be useful for clinical and research applications in which in vitro culture is often desired. The presented technology improves on current technology by enriching cells based on size without clogging mechanical filters, employing only a simple single-layered microfluidic device and processing cell solutions at the ml/min scale.

Loading

Full text loading...

/deliver/fulltext/aip/journal/bmf/5/2/1.3576780.html;jsessionid=2367vpe106869.x-aip-live-01?itemId=/content/aip/journal/bmf/5/2/10.1063/1.3576780&mimeType=html&fmt=ahah&containerItemId=content/aip/journal/bmf
true
true
This is a required field
Please enter a valid email address
752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: High-throughput size-based rare cell enrichment using microscale vortices
http://aip.metastore.ingenta.com/content/aip/journal/bmf/5/2/10.1063/1.3576780
10.1063/1.3576780
SEARCH_EXPAND_ITEM