May 2015 patents: Microfluidics, genome engineering, graphene, and more
Professors David Liu, George Church, George Whitesides, David Weitz, Roy Gordon, Charles Lieber, and Robert Wood were among the faculty members issued U.S. patents this May. The patents include:
Continuous directed evolution of proteins and nucleic acids (U.S. Patent 9,023,594; May 5, 2015)
David R. Liu and Kevin M. Esvelt
The present invention discloses generalizable methods of evolving nucleic acids and proteins utilizing continuous directed evolution. The invention discloses methods of passing a nucleic acid from cell to cell in a desired function-dependent manner. The linkage of the desired function and passage of the nucleic acid from cell to cell allows for continuous selection and mutation of the nucleic acid.
RNA-guided human genome engineering (U.S. Patent 9,023,649; May 5, 2015)
Prashant G. Mali, George M. Church, and Luhan Yang
A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.
Fluorination of organic compounds (U.S. Patent 9,024,093; May 5, 2015)
Tobias Ritter, Takeru Furuya, and Pingping Tang
Methods for fluorinating organic compounds.
Self-regulating pressure source (U.S. Patent 9,027,336; May 12, 2015)
Cagdas Denizel Onal, Daniela Rus, Xin Chen, and George M. Whitesides
Self-regulating pressure source. The pressure source includes a chamber enclosing a chemical monopropellant. A moveable boss is attached to a deformable membrane sealing an air chamber, the moveable boss and air chamber being disposed within the chamber. A catalyst is disposed around the membrane so as to be covered by the boss in a retracted position so that the monopropellant is broken down by the catalyst to produce a gas. The gas pressure will increase within the chamber causing air in the air chamber to compress thereby to pull the boss into the retracted position to cover the catalyst thereby to regulate the pressure within the chamber. The self-regulating pressure source is particularly suited to power fluidic elastomeric actuators.
Copolymers for suppression of autoimmune diseases, and methods of use (U.S. Patent 9,028,835; May 12, 2015)
Jack L. Strominger and Masha Fridkis-Hareli
Random three- and four-amino acid copolymers having lengths of 14-, 35- and 50-amino acid residues are provided. The random copolymers have amino acids alanine, lysine and one or more of the hydrophobic amino acids valine, phenylalanine, tryptophan and tyrosine. Random three-amino acid copolymer FAK efficiently suppressed EAE induced in SJL/J (H-2S) mice with the encephalitogenic epitope PLP 139-151. Random four-amino acid copolymers VYAK and tryptophan-containing VWAK were efficacious in alleviating severity and duration of symptoms of EAE induced by MBP 85-99 (SEQ ID NO:2), in a humanized mouse model expressing genes for both an HLA-DR-2 linked to multiple sclerosis (MS) in humans and for a T cell receptor from an MS patient.
Vitro evolution in microfluidic systems (U.S. Patent 9,029,083; May 12, 2015)
Andrew David Griffiths, David Weitz, Darren Link, Keunho Ahn, and Jerome Bibette
The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; and (b) sorting the genetic elements which express the gene product having the desired activity; wherein at least one step is under microfluidic control. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.
Assays and other reactions involving droplets (U.S. Patent 9,029,085; May 12, 2015)
Jeremy Agresti, Liang-Yin Chu, David A. Weitz, Jin-Woong Kim, Amy Rowat, Morten Sommer, Gautam Dantas, and George Church
The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.
Microfluidic vortex-assisted electroporation system and method (U.S. Patent 9,029,109; May 12, 2015)
Soojung Claire Hur and Hoyoung Yun
A system and method include delivering cells of interest to multiple traps via a channel connecting the traps, maintaining a vortex flow in the traps to trap the cells of interest in the traps, providing first molecules of interest to the traps, and providing an electric field across the traps to perform electroporation of the first molecules of interest into the cells of interest in the traps.
Bicyclic guanidines, metal complexes thereof and their use in vapor deposition (U.S. Patent 9,029,189; May 12, 2015)
Roy Gerald Gordon and Leonard Neil Jacques Rodriguez
Bicyclic guanidine compounds are described. Metal bicyclic guanidinate and its use in vapor deposition processes to deposit a metal-containing thin film are also described. Methods of making alkaline earth metal N,N'dialkylacetamidinates or bicyclic guanidinates including dissolution of alkaline earth metal into liquid ammonia followed by addition of a solution of an amidine or guanidine ligand in the free base from are provided.
Controlled synthesis of monolithically integrated graphene structure (U.S. Patent 9,029,836; May 12, 2015)
Jung-Ung Park, SungWoo Nam, and Charles M. Lieber
In a method for fabricating a graphene structure, there is formed on a fabrication substrate a pattern of a plurality of distinct graphene catalyst materials. In one graphene synthesis step, different numbers of graphene layers are formed on the catalyst materials in the formed pattern. In a method for fabricating a graphene transistor, on a fabrication substrate at least one graphene catalyst material is provided at a substrate region specified for synthesizing a graphene transistor channel and at least one graphene catalyst material is provided at a substrate region specified for synthesizing a graphene transistor source, and at a substrate region specified for synthesizing a graphene transistor drain. Then in one graphene synthesis step, at least one layer of graphene is formed at the substrate region for the graphene transistor channel, and at the regions for the transistor source and drain there are formed a plurality of layers of graphene.
Systems and methods for medium access control (U.S. Patent 9,032,075; May 12, 2015)
Hsiang-Tsung Kung and Tsung-Han Lin
Techniques for medium access control. Some techniques include receiving, at a first computing device, a solicitation for at least a first medium access request that specifies at least one time period for transmitting the first medium access request to the second computing device; encoding the first medium access request at least in part by using a compressive sensing encoding technique to obtain a first encoded medium access request; and transmitting the first encoded medium access request to the second computing device during the at least one time period specified in the received solicitation.
Formation and control of fluidic species (U.S. Patent 9,038,919; May 26, 2015)
Darren Roy Link, David A. Weitz, Manuel Marquez-Sanchez, and Zhengdong Cheng
This invention generally relates to systems and methods for the formation and/or control of fluidic species, and articles produced by such systems and methods. In some cases, the invention involves unique fluid channels, systems, controls, and/or restrictions, and combinations thereof. In certain embodiments, the invention allows fluidic streams (which can be continuous or discontinuous, i.e., droplets) to be formed and/or combined, at a variety of scales, including microfluidic scales. In one set of embodiments, a fluidic stream may be produced from a channel, where a cross-sectional dimension of the fluidic stream is smaller than that of the channel, for example, through the use of structural elements, other fluids, and/or applied external fields, etc. In some cases, a Taylor cone may be produced. In another set of embodiments, a fluidic stream may be manipulated in some fashion, for example, to create tubes (which may be hollow or solid), droplets, nested tubes or droplets, arrays of tubes or droplets, meshes of tubes, etc. In some cases, droplets produced using certain embodiments of the invention may be charged or substantially charged, which may allow their further manipulation, for instance, using applied external fields. Non-limiting examples of such manipulations include producing charged droplets, coalescing droplets (especially at the microscale), synchronizing droplet formation, aligning molecules within the droplet, etc. In some cases, the droplets and/or the fluidic streams may include colloids, cells, therapeutic agents, and the like.
Passive torque balancing in a high-frequency oscillating system (U.S. Patent 9,038,942; May 26, 2015)
Pratheev Sabaratnam Sreetharan and Robert J. Wood
A passively torque-balanced device includes (a) a frame; (b) a drivetrain including a drive actuator mounted to the frame and configured for reciprocating displacement, an input platform configured for displacement by the drive actuator, a plurality of rigid links, including a proximate link and remote links, wherein the rigid links are collectively mounted to the frame, and a plurality of joints joining the rigid links and providing a plurality of non-fully actuated degrees of freedom for displacement of the rigid links, the plurality of joints including a fulcrum joint that is joined both to the input platform and to the proximate rigid link; and (c) at least two end effectors respectively coupled with the remote links and configured for displacement without full actuation.
Method and apparatus for forming multiple emulsions (U.S. Patent 9,039,273; May 26, 2015)
David A. Weitz, Darren Roy Link, and Andrew S. Utada
The present invention generally relates to multiple emulsions, and to methods and apparatuses for making multiple emulsions. A multiple emulsion generally describes larger droplets that contain one or more smaller droplets therein. The larger droplets may be suspended in a third fluid in some cases. These can be useful for encapsulating species such as pharmaceutical agents, cells, chemicals, or the like. In some cases, one or more of the droplets can change form, for instance, to become solidified to form a microcapsule, a liposome, a polymerosome, or a colloidosome. Multiple emulsions can be formed in one step in certain embodiments, with generally precise repeatability, and can be tailored to include one, two, three, or more inner droplets within a single outer droplet (which droplets may all be nested in some cases).