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NASA Technical Reports Server (NTRS) 20130009000: Streamline-based microfluidic device PDF

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(12) United States Patent (lo) Patent No.: (cid:9) US 8,354,075 B1 Tai et al. (45) Date of Patent: (cid:9) Jan. 15, 2013 (54) STREAMLINE-BASED MICROFLUIDIC 2002/0041827 Al * (cid:9) 4/2002 Yager et al ...................... 422/57 DEVICE 2003/0159999 Al * (cid:9) 8/2003 Oakey et al . .................. 210/695 2004/0166025 Al * (cid:9) 8/2004 Chan et al ....................... 422/99 (75) Inventors: Yu-Chong Tai, Pasadena, CA (US); OTHER PUBLICATIONS Siyang Zheng, Pasadena, CA (US); Ayon, A.A. et al., "Characterization of a Time Multiplexed Induc- Harvey Kasdan, Sherman Oaks, CA tively Coupled Plasma Etcher," Journal of the Electrochemical Soci- (US) ety, 1999, vol. 146, No. 1, pp. 339-349. Huang, L.R. et al., "Continuous Particle Separation Through Deter- (73) Assignees: California Institute of Technology, ministic Lateral Displacement," Science, May 14, 2004, vol. 304, pp. Pasadena, CA (US); IRIS International, 987-990. Yamada, M. et al., "Pinched Flow Fractionation: Continuous Size Inc., Chatsworth, CA (US) Separation of Particles Utilizing a Laminar Flow Profile in a Pinched Microchannel,"Analytical Chemistry, Sep. 15, 2004, vol. 76, No. 18, (*) Notice: (cid:9) Subject to any disclaimer, the term of this pp. 5465-5471. patent is extended or adjusted under 35 Yamada, M. et al., "Hydrodynamic Filtration for On-Chip Particle U.S.C. 154(b) by 481 days. Concentration and Classification Utilizing Microfluidics," Lab on a Chip, 2005, vol. 5, pp. 1233-1239. Zheng, S. et al., "Deterministic Lateral Displacement MEMS Device (21) Appl. No.: 11/408,514 for Continuous Blood Cell Separation," Eighteenth IEEE Interna- tional Conference on Micro Electro Mechanical Systems (MEMS (22) Filed: (cid:9) Apr. 20, 2006 '05): Miami, USA, Jan. 30-Feb. 2, 2005, pp. 851-854. Related U.S. Application Data * cited by examiner (60) Provisional application No. 60/673,572, filed on Apr. Primary Examiner Dean Kwak 21, 2005. (74) Attorney, Agent, or Firm Kilpatrick Townsend & Stockton LLP. (51) Int. Cl. BOIL 3100 (cid:9) (2006.01) (57) (cid:9) ABSTRACT GOIN1/00 (cid:9) (2006.01) (52) U.S. Cl. ........ 422/503; 422/500; 422/501; 422/502; The present invention provides a streamline-based device and 422/504; 422/505; 436/180 a method for using the device for continuous separation of (58) Field of Classification Search ............ 422/99-104, particles including cells in biological fluids. The device 422/500-505; 436/180 includes a main microchannel and an array of side micro- See application file for complete search history. channels disposed on a substrate. The main microchannel has a plurality of stagnation points with a predetermined geomet- (56) (cid:9) References Cited ric design, for example, each of the stagnation points has a predetermined distance from the upstream edge of each of the U.S. PATENT DOCUMENTS side microchannels. The particles are separated and collected in the side microchannels. 5,091,328 A (cid:9) 2/1992 Miller 6,592,821 BI* (cid:9) 7/2003 Wada et al . .................. 422/68.1 6,632,619 BI* 10/2003 Harrison et al . ............... 435/7.2 12 Claims, 10 Drawing Sheets 600 610 630 625 U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 1 of 10 (cid:9) US 8,354,075 B1 100 /~ - 110 165 FIG. 1 U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 2 of 10 (cid:9) US 8,354,075 B1 E 3 t 2 O c ct ~ J C O n t~ CL 0 Cn 1 n ~ m E -6 (cid:9) -4 (cid:9) -2 (cid:9) 0 (cid:9) 2 (cid:9) 4 (cid:9) 6 (cid:9) 8 Side Channel Edge Distance AX (µm) FIG. 2 U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 3 of 10 (cid:9) US 8,354,075 B1 3.0 s 2.5 ca~ 2.0 J C O 1.5 m cn 1.0 m 0.5 500 (cid:9) 1000 (cid:9) 1500 2000 Side Channel Length (µm) FIG. 3 (cid:9) U.S. Patent (cid:9) Jan. 15, 2013 Sheet 4 of 10 (cid:9) US 8,354,075 B1 200 220 210 (cid:9) 230 (cid:9) 240 250 280 (cid:9) .~ 3u r 200 µm n n Flow ~ ' (cid:9) "e a ~`~ Inlet 1 0 Sgpgk I tibn (cid:9) 06,111 260 SY (cid:9) ;6 (cid:9) 4` ~ FIG. 4B , $ 265 270(cid:9) FIG. 4A FIG. 4 U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 5 of 10 (cid:9) US 8,354,075 B1 500 510 520 530 525 FIG. 5 U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 6 of 10 (cid:9) US 8,354,075 B1 600 f 610 630 620 625 FIG. 6 (cid:9) U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 7 of 10 (cid:9) US 8,354,075 B1 Sum 200 ®10um 25 c O U O N 150 20 .o v c ~ -m a 00~ 15 m 100 O CD w L. 100 E E Wi 50 5 (cid:9) 0 1 =® .=. i .-Alm. 1 (cid:9) 1 (cid:9) 1 (cid:9) 0 1 (cid:9) 2 (cid:9) 3 (cid:9) 4 (cid:9) 5 (cid:9) 6 (cid:9) 7 8 (cid:9) 9 10 FIG. 7 U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 8 of 10 (cid:9) US 8,354,075 B1 800 820 (cid:9) 810 840 830 FIG. 8 U.S. Patent (cid:9) Jan. 15, 2013 (cid:9) Sheet 9 of 10 (cid:9) US 8,354,075 B1 900 910 925 (cid:9) 920 930 940 FIG. 9

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