USOO8721936 B2 (12) United States Patent (10) Patent No.: US 8,721,936 B2 Mao et al. (45) Date of Patent: May 13, 2014 (54) DEVICES AND METHODS FOR FORMING 7,709,544 B2 5/2010 Doyle et al. NON-SPHERICAL PARTICLES 8,114,319 B2 * 2/2012 Davis et al. ..................... 264/11 8, 183,540 B2 5, 2012 Ward et al. (75) Inventors: Leidong Mao, Athens, GA (US); Jason 20060105012 AI 52006 Chinn et al. J. Locklin, Bogart, GA (US); Taotao 2006, O135639 A1 6, 2006 Singh s s s 2006, O147413 A1 7/2006 Alferiev et al. Zhu, Athens, GA (US); Gareth 2006/0148982 A1 7/2006 Uchegbu et al. Sheppard, Athens, GA (US) 2007/0054119 A1 3/2007 Garstecki et al. 2007/0231291 A1 10/2007 Huang et al. (73) Assignee: University of Georgia Research 2008.OO25503 A1 1/2008 Choi et al. Foundation, Inc., Athens, GA (US) 2009/O162767 A1 6, 2009 Wu 2009,0196826 A1 8, 2009 Gao et al. (*) Notice: Subject to any disclaimer, the term of this 2011/0081643 A1* 4/2011 Fournier-BidoZ. et al. ........ 435/5 patent is extended or adjusted under 35 2013/0183246 A1* 7/2013 Wang et al. .................... 4249.3 U.S.C. 154(b)(b) bybV 137 days.days FOREIGN PATENT DOCUMENTS (21) Appl. No.: 13/450,650 WO 2010.096444 A2 8, 2010 (22) Filed: Apr. 19, 2012 OTHER PUBLICATIONS (65) Prior Publication Data Goyal; Nanoscale Approaches for Biomolecule Separtion and Detec US 2012/O26781.0 A1 Oct. 25, 2012 tion. Master in Science in Biomedical Engineering Requirement— O O Graduate School of The University of Texas at Arlington. Dec. 2009. Related U.S. Application Data Dendukuri, et al.; The Synthesis and Assembly of Polymeric (60) Provisional application No. 61/477,766, filed on Apr. Microparticles Using Microfluidics. Advanced Review, vol. 21. 21, 2011. 2009. 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim pp. s 4071-4086. (51) Int. Cl. Yuan, et al.; Large scale manufacture of magnetic polymer particles B29B 9/00 (2006.01) using membranes and microfluidic devices. China Particuology. Vol. BOI. I./00 (2006.01) 5, 2007. pp. 26-42. (52) U.S. Cl. (Continued) CPC ...... B01J 19/0093 (2013.01); B01J 2219/0852 (2013.01) USPC .......................... 264/11; 264/5; 425/3; 425/6 Primary Examiner — Mary F Theisen (58) Field of Classification Search (74) Attorney, Agent, or Firm — Thomas Horstemeyer, LLP O See application file for complete search history. (57) ABSTRACT (56) References Cited Embodiments of the present disclosure provide for devices, U.S. PATENT DOCUMENTS methods for forming non-spherical particles, and the like. 3,697.402 A 10, 1972 Clifton et al. 5,510,468 A 4, 1996 Lamm et al. 5,714,360 A 2f1998 Swan et al. 21 Claims, 4 Drawing Sheets sts 38 xxx x: s: US 8,721.936 B2 Page 2 (56) References Cited Wang, et al.; Fabrication of Monodisperse Toroidal Particles by Poly mer Solidification in Microfluidics. ChemPhysChem. vol. 10, 2009. OTHER PUBLICATIONS 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp. 641 645. Chen, et al., Microfluidic Assembly of Magnetic Hydrogel Particles Office Action in related Chinese Application No. 201080008259.0 with Uniformly Anistrophic Structure. Advanced Review, vol. 21. dated Jun. 18, 2013. 2009. 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim pp. Extended European Search Report dated Oct. 18, 2013. 32O1-3204. International Search Report and Written Opinion dated Sep. 16. Hwang, et al., Microfluidic-based synthesis of non-spherical mag 2010. PCIUS2010/024422. netic hydrogel microparticles. Lab on a Chip. vol. 8, 2008. The Royal Examination Reporton related New Zealand Application No. 602911 Society of Chemistry 2008 pp. 1640-1647. dated Jun. 18, 2013. Shum, et al.; Droplet Microfluidics for Fabrication of Non-Spherical International Search Report and Written Opinion dated Jan. 19, 2012. Particles. Macromolecular Rapid Communications. vol. 32, 2010. PCT/US 2011/034268. 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp. 108 118. * cited by examiner U.S. Patent May 13, 2014 Sheet 1 of 4 US 8,721,936 B2 U.S. Patent May 13, 2014 Sheet 2 of 4 US 8,721,936 B2 U.S. Patent May 13, 2014 Sheet 3 of 4 US 8,721,936 B2 U.S. Patent May 13, 2014 Sheet 4 of 4 US 8,721,936 B2 US 8,721,936 B2 1. 2 DEVICES AND METHODS FOR FORMING FIG. 1(A) illustrates a schematic representation of the fer NON-SPHERICAL PARTICLES rofluid-based droplet microfluidic device. Arrows in magnets indicate the directions of magnetizations. Magnetic flux den CROSS-REFERENCE TO RELATED sity in the channel is estimated to be ~500 mT. FIG. 1(B) APPLICATION illustrates a prototype device, scale bar is 10 mm. Generation (FIG. 1(C): flow-focusing area, and FIG. (D): chamber area) This application claims priority to U.S. provisional appli and polymerization (FIG. (E) left: with ferrofluids, and cation entitled “MAGNETIC FIELD-ASSISTED FABRI FIG. (E)—right: without ferrofluids) of droplets within the CATION AND MANIPULATION OF NON-SPHERICAL device. Scale bars in FIGS. 1(C), (D), and (E) are 400 nm. POLYMER PARTICLES IN FERROFLUID-BASED 10 FIG. 2(A) illustrates a spherical polymer droplet genera DROPLET MICROFLUIDICS. having Ser. No. 61/477, tion with no magnetic field. Sizes of the droplets can be 766, filed on Apr. 21, 2011, which is entirely incorporated controlled by adjusting flow rates ratio between polymer herein by reference. phase and continuous ferrofluid phase. FIG. 2(B) illustrates a non-spherical polymer droplet generation with magnetic BACKGROUND 15 fields. Shaping of droplets can be controlled via magnetic fields and flow rates ratio. Scale bars in are 400 nm. Functional polymer particles with uniform sizes and FIGS. 3(A) to 3(D) illustrates chain formation of polymer shapes have been proven useful in a wide variety of applica droplets under magnetic fields. In particular, FIG.3(A) illus tions including cosmetics, biotechnology, and pharmaceuti trates the length of chain: 2: FIG.3(B) illustrates the length of cals. Traditionally, the dominant shape of polymer particles chain: 5; FIG.3(C) illustrates the length of chains: 8; and FIG. has been spherical because of the manufacturing technique, 3(D) illustrates the long chains forming at higher polymer which typically involves emulsion and Suspension polymer phase flow rate. Scale bars are 400 nm. ization. Non-spherical particles, on the other hand, are highly FIG. 4 illustrates the photopolymerization of droplets beneficial to many applications including drug delivery, bio chains under magnetic fields. FIGS. 4(A) and 4(B) are micro imaging, and biomimetics due to the large Surface area and 25 scopic images of solidified droplets after UV exposure. FIG. anisotropic responses to external hydrodynamic, electrical, 4(C) illustrates an SEM image of solidified droplets chain. and magnetic stimulations. However, it remains difficult to Scale bars are 400 nm. fabricate large quantities of monodispersed particles with tunable shapes and sizes. DETAILED DESCRIPTION 30 SUMMARY Before the present disclosure is described in greater detail, it is to be understood that this disclosure is not limited to Embodiments of the present disclosure provide for particular embodiments described, as such may, of course, devices, methods for forming non-spherical particles, and the vary. It is also to be understood that the terminology used like. 35 herein is for the purpose of describing particular embodi An embodiment of the present disclosure includes a ments only, and is not intended to be limiting, since the scope device, among others, that includes a first fluid inlet for flow of the present disclosure will be limited only by the appended ing a first liquid; a second fluid inlet for flowing a second claims. liquid, wherein the first fluid inlet and the second fluid inlet Where a range of values is provided, it is understood that are configured to flow the first fluid and the second fluid, 40 each intervening value, to the tenth of the unit of the lower respectively, into a flow chamber, a magnetic device config limit (unless the context clearly dictates otherwise), between ured to direct a magnetic force onto a first portion of the flow the upper and lower limit of that range, and any other stated or chamber; and a light source device configured to direct a light intervening value in that stated range, is encompassed within energy at a second portion of the flow chamber. In an embodi the disclosure. The upper and lower limits of these smaller ment the first fluid is a polymer Such as a photopolymer or 45 ranges may independently be included in the Smaller ranges thermal-curable polymer. In an embodiment, the second fluid and are also encompassed within the disclosure, Subject to is a ferrofluid. any specifically excluded limit in the stated range. Where the An embodiment of the present disclosure includes a stated range includes one or both of the limits, ranges exclud method for forming non-spherical polymer particles, among ing either or both of those included limits are also included in others, that includes: disposing a first fluid in a second fluid; 50 the disclosure. causing the first fluid to form a non-spherical shape within the Unless defined otherwise, all technical and scientific terms second fluid using a magnetic energy; and exposing the first used herein have the same meaning as commonly understood fluid having a non-spherical shape to a light energy to form a by one of ordinary skill in the art to which this disclosure non-spherical polymer particle. In an embodiment, the non belongs. Although any methods and materials similar or spherical polymer particles are monodispersed.