Harvard faculty David Mooney, Wendy Garrett, Dave Weitz, Charles Lieber, Adam Cohen, Amir Yacoby, David Clarke, John Collier, Xiaowei Zhuang, Matthew Shair, and George Whitesides are among the inventors issued U.S. patents during July 2017.

The innovations recognized are as follows:

Co-delivery of stimulatory and inhibitory factors to create temporally stable and spatially restricted zones
U.S. Patent 9,693,954 (July 4, 2017)

David J. Mooney, William W. Yuen, and Praveen Arany

Abstract: The invention provides methods and compositions for local manipulation of regenerative processes via exogenous factor delivery.

Method of increasing the quantity of colonic T regulatory cells via G-coupled protein receptor 43
U.S. Patent 9,693,977 (July 4, 2017)

Wendy S. Garrett and Patrick M. Smith

Abstract: Disclosed herein are compositions and methods that are useful for inducing the development of regulatory T cells (T_reg). Such compositions and methods are useful for treating inflammatory conditions and in particular inflammatory conditions affecting the gastrointestinal tract of a subject. In certain embodiments, the present inventions generally relate to short chain fatty acids and the discovery that such short chain fatty acids may be used to treat and/or prevent inflammatory conditions by enhancing the size and immune function of a subject's endogenous T_reg population.

Acoustic waves in microfluidics
U.S. Patent 9,695,390 (July 4, 2017)

David A. Weitz, Thomas Franke, Achim Wixforth, Lothar Schmid, Jeremy Agresti, and Adam R. Abate

Abstract: Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one set of embodiments, droplets may be sorted using surface acoustic waves. The droplets may contain cells or other species. In some cases, the surface acoustic waves may be created using a surface acoustic wave generator such as an interdigitated transducer, and/or a material such as a piezoelectric substrate. The piezoelectric substrate may be isolated from the microfluidic substrate except at or proximate the location where the droplets are sorted, e.g., into first or second microfluidic channels. At such locations, the microfluidic substrate may be coupled to the piezoelectric substrate (or other material) by one or more coupling regions. In some cases, relatively high sorting rates may be achieved, e.g., at rates of at least about 1,000 Hz, at least about 10,000 Hz, or at least about 100,000 Hz, and in some embodiments, with high cell viability after sorting.

VEGF-binding protein for blockade of angiogenesis
U.S. Patent 9,701,731 (July 11, 2017)

Bob Carter, Jeng-Shin Lee, Szofia S. Bullain, and Richard C. Mulligan

Abstract: Provided are chimeric VEGF-binding proteins and nucleic acids (e.g., a vector) encoding chimeric VEGF-binding proteins, methods and host cells for producing these proteins and nucleic acids, and pharmaceutical compositions containing these proteins and nucleic acids. Also provided are methods of treating an angiogenic disease or disorder that include administering at least one of the chimeric VEGF-binding proteins or at least one of the nucleic acids (e.g., a vector) encoding a chimeric VEGF-binding protein.

Nanopore sensing by local electrical potential measurement
U.S. Patent 9,702,849 (July 11, 2017)

Charles M. Lieber and Ping Xie

Abstract: There is provided a nanopore disposed in a support structure, with a fluidic connection between a first fluidic reservoir and an inlet to the nanopore and a second fluidic connection between a second fluidic reservoir and an outlet from the nanopore. A first ionic solution of a first buffer concentration is disposed in the first reservoir and a second ionic solution of a second buffer concentration, different than the first concentration, is disposed in the second reservoir, with the nanopore providing the sole path of fluidic communication between the first and second reservoirs. An electrical connection is disposed at a location in the nanopore sensor that develops an electrical signal indicative of electrical potential local to at least one site in the nanopore sensor as an object translocates through the nanopore between the two reservoirs.

Systems, methods, and workflows for optogenetics analysis
U.S. Patent 9,702,874 (July 11, 2017)

Adam E. Cohen, Joel Kralj, Adam D. Douglass, and Daniel Hochbaum

Abstract: The invention provides methods for characterizing cellular physiology by incorporating into an electrically excitable cell an optical reporter of, and an optical actuator of, electrical activity. A signal is obtained from the optical reporter in response to a stimulation of the cell. Either or both of the optical reporter and actuator may be based on genetically-encoded rhodopsins incorporated into the cell. The invention provides all optical methods that may be used instead of, or as a complement to, traditional patch clamp technologies and that can provide rapid, accurate, and flexible assays of cellular physiology.

Method and system for magnetic resonance imaging using nitrogen-vacancy centers
U.S. Patent 9,702,900 (July 11, 2017)

Amir Yacoby, Michael Grinolds, Marc Warner, Kristiaan De Greve, and Yuliya Dovzhenko

Abstract: A method for performing sub-nanometer three-dimensional magnetic resonance imaging of a sample under ambient conditions using a diamond having at least one shallowly planted nitrogen-vacancy (NV) center. A driving radio-frequency (RF) signal and a microwave signal are applied to provide independent control of the NV spin and the target dark spins. A magnetic-field gradient is applied to the sample with a scanning magnetic tip to provide a narrow spatial volume in which the target dark electronic spins are on resonance with the driving RF field. The sample is controllably scanned by moving the magnetic tip to systematically bring non-resonant target dark spins into resonance with RF signal. The dark spins are measured and mapped by detecting magnetic resonance of said nitrogen-vacancy center at each of said different magnetic tip positions. The dark-spin point-spread-function for imaging the dark spins is directly measured by the NV center.

Adaptive optic and acoustic devices
U.S. Patent 9,703,019 (July 11, 2017)

Samuel Shian, Roger Diebold, and David Clarke

Abstract: According to some aspects, an adaptive lens is provided. One such adaptive lens comprises at least one fluid-filled chamber located within an optical and/or acoustic path of the lens, and at least one elastomeric and substantially optically and/or acoustically transparent membrane, located within an optical and/or acoustic path of the lens and at least partially bounding one or more of the at least one fluid-filled chambers, wherein one or more of the at least one membranes is configured such that a shape of the membrane is altered upon receipt of an electric field. Some aspects provide a method of producing a lens comprising providing at least one chamber bounded at least in part by first and second membranes, and providing a fluid into the at least one chamber such that the fluid is located within an optical and/or acoustic path of the lens.

Modified microbial toxin receptor for delivering agents into cells
U.S. Patent 9,708,374 (July 18, 2017)

Adva Mechaly, Andrew J. McCluskey, and John R. Collier

Abstract: We described a novel system of targeted cell therapy with a protein toxin, such as anthrax toxin, that has been modified to re-direct it to a desired cell target instead of its natural cell target. The system can be used for, e.g., targeted killing of undesired cells in a population of cells, such as cancer or overly active immune system cells.

Porous electrolytic polymer cryogels for enhanced electrical collapsibility
U.S. Patent 9,708,455 (July 18, 2017)

Stephen Michael Kennedy, Sidi Ahmed Bencherif, and David J. Mooney

Abstract: The invention provides cryogels whose porosity, pore size, pore connectivity, swelling agent concentration, and/or specific volume undergoes a change from a first value to a second value in response to an electrical stimulus. The cryogels have interconnected macropores which greatly enhance their ability to rapidly undergo volumetric collapse when subjected to moderate electric fields. The cryogels of the invention can be easily integrated into arrays capable of rapid configurational and chromatic optical modulations, and when loaded with drugs, are able to coordinate the delivery profile of multiple drugs. The cryogel can be prepared by polymerizing an aqueous solution of charged monomers and cross-linker monomers at a temperature below the freezing temperature of the solvent.

HiC: method of identifying interactions between genomic loci
U.S. Patent 9,708,648 (July 18, 2017)

Job Dekker, Erez Lieberman Aiden, Nynke Van Berkum, Andreas Gnirke, Eric Lander, Chad Nusbaum, Louise Williams, Alexandre Melnikov, and Georgia Giannoukos

Abstract: The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.

Sub-diffraction limit image resolution in three dimensions
U.S. Patent 9,712,805 (July 18, 2017)

Xiaowei Zhuang, Bo Huang, Wilfred M. Bates, and Wenqin Wang

Abstract: The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques, including imaging in three dimensions. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. For example, the entities may be separated by a distance of less than about 1000 nm, or less than about 300 nm for visible light. In some cases, the position of the entities can be determined in all three spatial dimensions (i.e., in the x, y, and z directions), and in certain cases, the positions in all three dimensions can be determined to an accuracy of less than about 1000 nm. In one set of embodiments, the entities may be selectively activatable, i.e., one entity can be activated to produce light, without activating other entities. A first entity may be activated and determined (e.g., by determining light emitted by the entity), then a second entity may be activated and determined. The emitted light may be used to determine the x and y positions of the first and second entities, for example, by determining the positions of the images of these entities, and in some cases, with sub-diffraction limit resolution. In some cases, the z positions may be determined using one of a variety of techniques that uses intensity information or focal information (e.g., a lack of focus) to determine the z position. Non-limiting examples of such techniques include astigmatism imaging, off-focus imaging, or multi-focal-plane imaging. Other aspects of the invention relate to systems for sub-diffraction limit image resolution, computer programs and techniques for sub-diffraction limit image resolution, methods for promoting sub-diffraction limit image resolution, and the like.

Cortistatin analogues and syntheses thereof
U.S. Patent 9,714,255 (July 25, 2017)

Alec Nathanson Flyer, Hong Myung Lee, Andrew G. Myers, Cristina Montserrat Nieto-Oberhuber, Matthew D. Shair, and Chong Si

Abstract: The present invention relates to analogs of cortistatin A, J, K, and L, having the general formula:

and salts thereof, wherein R₁, R₂, R₃, R₄, n, and m are as defined herein; processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; methods for treating a proliferative disease; methods for treating a disease associated with aberrant angiogenesis; methods for inhibiting angiogenesis; and processes for preparing cortistatin A, J, K, and L, and analogs thereof.

Monolayer stress microscopy
U.S. Patent 9,714,932 (July 25, 2017)

Dhananjay T. Tambe, Jeffrey J. Fredberg, James Butler, and Xavier Trepat

Abstract: Disclosed are systems, apparatus, devices and methods, including a method that includes determining traction forces exerted by a cellular monolayer on a substrate on which the monolayer is placed, and determining internal forces within and between cells of the monolayer based on the determined traction forces. In some embodiments, determining the internal forces of the cellular monolayer may include determining internal stresses within the cellular monolayer that act to balance the determined traction forces over at least part of the cellular monolayer. In some embodiments, determining of the internal stresses may also include setting boundary conditions at a boundary determined based on an optical field of view of an observed section of the monolayer.

Multiphase systems and uses thereof
U.S. Patent 9,714,934 (July 25, 2017)

Charles R. Mace, Ozge Akbulut Halatci, Ashok A. Kumar, Nathan D. Shapiro, and George M. Whitesides

Abstract: A multi-phase system includes a phase-separated solution comprising at least two phases, each phase having a phase component selected from the group consisting of a polymer, a surfactant and combinations thereof, wherein at least one phase comprises a polymer, wherein the phases, taken together, represent a density gradient. Novel two-phase, three-phase, four-phase, five-phase, or six-phase systems are disclosed. Using the disclosed multi-phase polymer systems, particles, or other analyte of interest can be separated based on their different densities or affinities.