US 20150285765A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0285765 A1 Chung et al. (43) Pub. Date: Oct. 8, 2015 (54) ACTIVE TRANSPORT OF CHARGED (52) U.S. Cl. MOLECULES INTO, WITHIN, AND/OR FROM CPC. G0IN 27/44756 (2013.01); G0IN 27/44704 CHARGED MATRICES (2013.01); G0IN 27/44708 (2013.01) (71) Applicant: Massachusetts Institute of Technology, Cambridge, MA (US) (57) ABSTRACT (72) Inventors: Kwanghun Chung, Cambridge, MA (US); Sung-Yon Kim, Cambridge, MA Articles and methods for the active transport of molecules (US); Kimberly Ohn, Boston, MA (US); into, within, and/or from a matrix are generally described. In Evan Murray, Cambridge, MA (US); some embodiments, an electric field may be used to alter the Jae Hun Cho, Cambridge, MA (US) position of the molecule with respect to the matrix. The elec tric field may be used to move the molecule to a new location (73) Assignee: Massachusetts Institute of Technology, within the matrix, remove the molecule from the matrix, or Cambridge, MA (US) infuse the molecule into the matrix. For instance, the electric field may be used to move a molecule having a binding (21) Appl. No.: 14/678,660 partner within the matrix into or away from the vicinity of the binding partner. In some embodiments, the position of the (22) Filed: Apr. 3, 2015 molecule may be altered by exposing the molecule to an electrodynamic field. In some Such embodiments, the mol Related U.S. Application Data ecule exposed to the dynamic electric field may have (60) Provisional application No. 61/975,575, filed on Apr. enhanced mobility and minimal adverse matrix interactions 4, 2014. relative to conventional molecular transport methods, and in Some cases, a molecule exposed to an electrostatic field. The Publication Classification active transport methods and articles, described herein, may be particularly well-suited for a variety of applications (51) Int. C. including histological, biological, and pharmaceutical appli GOIN 27/2447 (2006.01) cations. 20 40 40 135 50 AO 1 130 35 Patent Application Publication Oct. 8, 2015 Sheet 1 of 11 US 2015/0285765 A1 s xxxx: F.G. 2A 40A 40A AB 1. 4:08 FG, 3A : :k:texxxxtetic sexios w8k. Patent Application Publication Oct. 8, 2015 Sheet 2 of 11 US 2015/0285765 A1 F.G. 5B F.G. 5C Patent Application Publication Oct. 8, 2015 Sheet 3 of 11 US 2015/0285765 A1 A a a. A a. a F.G. 6A 4a 1 105-A a 63 a? 305-B 3. 4a 3. 110 5 0 A. (3 a. 3. ame) A. a A & 3. £) A. 63 305-A 105-8 110 (Ham F.G. 6B Patent Application Publication Oct. 8, 2015 Sheet 4 of 11 US 2015/0285765 A1 120 140 140 150 140 30 3S 25 FG, 7 Patent Application Publication Oct. 8, 2015 Sheet 5 of 11 US 2015/0285765 A1 & ... ... - - - - ; : &xxx8: is rexicxxxii. 8xxxxx 8xis: 88. 3k: 88.3: 33 & wigs: 3: six888 &xxxxx xxxxx FIG. 3D FIG. 8E FIG. 8F Patent Application Publication Oct. 8, 2015 Sheet 6 of 11 US 2015/0285765 A1 88x33xxx: stic:38 as 88.88 W. 88:38-38s 8:8: cxxxis electricf: re 88: FIG. 9A FIG. 9B FIG. 9C Patent Application Publication Oct. 8, 2015 Sheet 7 of 11 US 2015/0285765 A1 3888-833X: 88:::::::::::::: 8:38:88::::::::. tax:388xxii. 8883: 8. y::::::: : Patent Application Publication Oct. 8, 2015 Sheet 8 of 11 US 2015/0285765 A1 83-833 iss inxia 8. ... i. kotics: 8xiii. 8883 Anole FG. 1OB FIG. 1OC F.G. 10A Passig sixtskaiting 32cs: Psy& ice his fasciutor FIG 10D FIG 10E hig3 &sitions feasietieg 883-88: s: atar:-8:3:38 :::::::::::::::::::::: 8 FIG 1 OF FIG 10G Patent Application Publication Oct. 8, 2015 Sheet 9 of 11 US 2015/0285765 A1 88:XX8: :::::::::::: F.G. 1B F.G. 11A && FG 11C Patent Application Publication Oct. 8, 2015 Sheet 10 of 11 US 2015/0285765 A1 & www. FG, 12A F.G. 12B Patent Application Publication Oct. 8, 2015 Sheet 11 of 11 US 2015/0285765 A1 *8ty 388xxy $3:8: $8xxx:y 388xxy $888 8:8; 3:S 8 ::s 23:8 38s FG. 3A F.G. 13B US 2015/0285765 A1 Oct. 8, 2015 ACTIVE TRANSPORT OF CHARGED field, wherein the variation in concentration of the molecules MOLECULES INTO, WITHIN, AND/OR FROM throughout the matrix is less than 25%. CHARGED MATRICES 0010. In one embodiment, a method comprises distribut ing molecules throughout a matrix comprising binding part RELATED APPLICATIONS ners for the molecules under a condition that inhibits binding 0001. This application claims the benefit of U.S. Provi between at least a portion of the molecules and the binding sional Patent Application Ser. No. 61/975,575, filed Apr. 4, partners. 2014, entitled 'Active Transport of Charged Molecules, into, 0011. In another embodiment, a method comprises driv Within, and/or from Charged Matrices, which is incorpo ing a molecule through a charged matrix using an electric rated herein by reference in its entirety. field having a magnitude greater than or equal to 10 V/m. 0012. Other advantages and novel features of the present TECHNICAL FIELD invention will become apparent from the following detailed description of various non-limiting embodiments of the 0002 Articles and methods for the active transport of mol invention when considered in conjunction with the accompa ecules into, within, and/or from matrices, including biologi nying figures. In cases where the present specification and a cal matrices, are provided. document incorporated by reference include conflicting and/ or inconsistent disclosure, the present specification shall con BACKGROUND trol. 0003. The transport of molecules is fundamental to life as well as many engineered systems. Transport processes may BRIEF DESCRIPTION OF THE DRAWINGS be passive or active. One example of passive transport is 0013 Non-limiting embodiments of the present invention diffusion. Diffusion is the process by which molecules move will be described by way of example with reference to the from regions of high concentration to regions of low concen accompanying figures, which are schematic and are not tration. In diffusion, the molecules move via Brownian intended to be drawn to Scale. In the figures, each identical or motion and undergo a random walk that results in a net nearly identical component illustrated is typically repre displacement of the molecules in the direction of lower con sented by a single numeral. For purposes of clarity, not every centration. Active transport processes utilize energy to move component is labeled in every figure, nor is every component molecules. In some active transport processes, a force is of eachembodiment of the invention shown where illustration applied to the system comprising the molecules, such that the is not necessary to allow those of ordinary skill in the art to molecules move in the direction of the force. Though mol understand the invention. In the figures: ecules may be transported via passive or active means, the 0014 FIG. 1A illustrates Brownian motion of molecules active transport of molecules is advantageous for many appli in the presence of a matrix, according to certain embodi cations. Accordingly, improved articles and methods for the ments; active transport of molecules are needed. 0015 FIG. 1B illustrates passive transport of molecules into a matrix via diffusion, according to certain embodiments; SUMMARY 0016 FIG. 2A illustrates active transport in the presence 0004 Articles and methods for the active transport of mol of a matrix using an electric field, according to one set of ecules into, within, and/or from matrices are provided. The embodiments; Subject matter of the present invention involves, in some 0017 FIG.2B illustrates active transport of molecules into cases, interrelated products, alternative solutions to a particu a matrix via electrophoretic linear motion, according to one lar problem, and/or a plurality of different uses of one or more set of embodiments; systems and/or articles. 0018 FIG. 3A illustrates active transport in the presence 0005. In one set of embodiments, articles are provided. In of a matrix using an electric field, according to certain one embodiment, an article comprises an electric field gen embodiments; erator, a chamber capable of being positioned in a field pro 0019 FIG.3B illustrates active transport of molecules into vided by the generator, wherein at least a portion of the a matrix via electrophoretic linear motion, according to cer chamber is defined by a semipermeable material, and a tain embodiments; sample positioner in the chamber. 0020 FIG. 4A illustrates active transport in the presence 0006. In another set of embodiments, methods are pro of a matrix using an electric field, according to one set of vided. In one embodiment, a method comprises driving a embodiments; molecule through at least a portion of a matrix using an 0021 FIG. 4B illustrates active transport of molecules into electrodynamic field. a matrix via electrophoretic random walk, according to one 0007. In another embodiment, a method comprises driv set of embodiments; ing molecules through at least a portion of a charged matrix, 0022 FIG. 5A illustrates the infusion of molecules into a using an electric field, thereby changing the concentration of matrix, according to certain embodiments; the molecules in at least about 10% of the matrix, while 0023 FIG. 5B illustrates removal of molecules from a deforming the matrix in an amount less than 10%. matrix, according to certain embodiments; 0008. In one embodiment, a method comprises exposing a 0024 FIG.5C illustrates distribution of molecules within molecule to an electric field in the presence of a matrix and a matrix using an electric field, according to certain embodi associating the molecule with a binding partner within the ments; matrix.