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January 04, 2021

Patents issued October-December 2020

The USPTO recognized Harvard innovations in soft robotics, antifungals, sub-diffraction-limit imaging, nanopore sensing, optogenetics, and much more

Many Harvard University faculty and researchers were among the inventors issued U.S. patents in the months of October, November, and December 2020.

The Harvard innovations recently recognized by the USPTO are as follows:

Flexible and stretchable electronic strain-limited layer for soft actuators
U.S. Patent 10,792,807 (October 6, 2020)

Joshua Aaron Lessing, Ramses V. Martinez, Alok Suryavamsee Tayi, Jason Ming Ting, and George M. Whitesides

Abstract: A soft robot having an integrated electrical component includes an expandable or collapsible body, the body comprising an inlet that is configured to communicate with a fluid source and a flexible strain limited layer secured to a portion of the expandable or collapsible body, wherein the strain limited layer includes at least one electrical component.

Antifungal compounds
U.S. Patent 10,793,590 (October 6, 2020)

Ethan Van Arnam, Clarissa Sit, Antonio Ruzzini, Jon Clardy, Cameron Currie, and Adrian Alberto Pinto-Tomas

Abstract: Compounds of formula (I) or formula (II), compositions and methods useful for treating and/or preventing a fungal infections are provided. wherein the substituents are as defined in the appended claims.

Sub-diffraction limit image resolution and other imaging techniques
U.S. Patent 10,794,828 (October 6, 2020)

Xiaowei Zhuang, Wilfred M. Bates, and Michael J. Rust

Abstract: The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques. 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 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 entities may be immobilized relative to each other and/or to a common entity. The emitted light may be used to determine the positions of the first and second entities, for example, using Gaussian fitting or other mathematical techniques, and in some cases, with sub-diffraction limit resolution. The methods may thus be used, for example, to determine the locations of two or more entities immobilized relative to a common entity, for example, a surface, or a biological entity such as DNA, a protein, a cell, a tissue, etc. The entities may also be determined with respect to time, for example, to determine a time-varying reaction. 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, methods for producing photoswitchable entities, and the like.

Nanopore sensor including fluidic passage
U.S. Patent 10,794,895 (October 6, 2020)

Ping Xie

Abstract: A nanopore sensor is provided, including a nanopore disposed in a support structure. A fluidic passage is disposed between a first fluidic reservoir and the nanopore to fluidically connect the first fluidic reservoir to the nanopore through the fluidic passage. The fluidic passage has a passage length that is greater than the passage width. A second fluidic reservoir is fluidically connected to the nanopore, with the nanopore providing fluidic communication between the fluidic passage the second reservoir. Electrodes are connected to impose an electrical potential difference across the nanopore. At least one electrical transduction element is disposed in the nanopore sensor with a connection to measure the electrical potential that is local to the fluidic passage.

Optogenetic probes for measuring membrane potential
U.S. Patent 10,800,829 (October 13, 2020)

Adam Ezra Cohen, Daniel Hochbaum, Peng Zou, Samouil Leon Farhi, Robert Earl Campbell, Yongxin Zhao, and Daniel Jed Harrison

Abstract: Provided herein are variants of an archaerhodopsin useful for application such as optical measurement of membrane potential. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, cells comprising the polynucleotides, and cells comprising the polypeptides; and methods of using the variants.

Nucleotide-specific recognition sequences for designer TAL effectors
U.S. Patent 10,801,017 (October 13, 2020)

Feng Zhang, Le Cong, and Sam Locascio

Abstract: The invention relates to methods of altering expression of a genomic locus of interest or specifically targeting a genomic locus of interest in an animal cell, which may involve contacting the genomic locus with a non-naturally occurring or engineered composition that includes a deoxyribonucleic acid (DNA) binding polypeptide having a N-terminal capping region, a DNA binding domain comprising at least five or more Transcription activator-like effector (TALE) monomers and at least one or more half-monomers specifically ordered to target the genomic locus of interest, and a C-terminal capping region, wherein the polypeptide includes at least one or more effector domains, and wherein the polypeptide is encoded by and translated from a codon optimized nucleic acid molecule so that the polypeptide preferentially binds to the DNA of the genomic locus.

Compositions and methods for diagnosing, evaluating and treating cancer
U.S. Patent 10,801,070 (October 13, 2020)

Mark Kendell Clement, Gad Getz, Dan-Avi Landau, Alexander Meissner, and Catherine Ju-Ying Wu

Abstract: The present invention relates to methods of determining a cancer treatment prognosis for a subject in need thereof by evaluating epigenetic and genetic changes within a tumor sample from the subject. The present invention further provides methods of treating cancer in a subject by evaluating epigenetic and genetic changes within a tumor sample from the subject. In addition, the present invention provides methods of screening test agents to identify agents that decrease tumor cell plasticity.

Biomarkers for the early detection of breast cancer
U.S. Patent 10,802,026 (October 13, 2020)

Joshua Labaer, Karen Sue Anderson, Garrick Wallstrom, Sahar Sibani, Niroshan Ramachandran

Abstract: The present invention provides reagents and methods for breast cancer detection.

Pathogen vaccines and methods of producing and using the same
U.S. Patent 10,813,988 (October 27, 2020)

Michael Super, Edward J. Doherty), Mark Cartwright, Des White, Alexander G. Stafford, Omar Abdel-Rahman Ali, Amanda Graveline, Donald E. Ingber, David J. Mooney, and Benjamin Seiler

Abstract: The present invention provides vaccine compositions and methods of producing such compositions. Other embodiments of the invention include methods of treating a pathogen infection, methods of vaccinating a subject against a pathogen infection, and methods for treating an antibiotic-resistance bacterial infection in a subject in need thereof. In further embodiments, the invention includes methods of decreasing the level of a pathogen in a subject having a pathogen infection, methods of increasing the surviving rate of a subject having a pathogen infection, methods of reducing the level of pain associated with a pathogen infection, and methods of reducing the level of distress associated with a pathogen infection in a subject in need thereof. Novel scaffold compositions and opsonin-bound or lectin-bound pathogen compositions, and uses thereof, are also provided herein.

Microfluidic cartridge assembly
U.S. Patent 10,814,323 (October 27, 2020)

Donald E. Ingber, Daniel Levner, Guy Thompson, II, and Christopher David Hinojosa

Abstract: According to aspects of the present invention, a cartridge assembly for transporting fluid into or out of one or more fluidic devices includes a first layer and a second layer. The first layer includes a first surface. The first surface includes at least one partial channel disposed thereon. The second layer abuts the first surface, thereby forming a channel from the at least one partial channel. At least one of the first layer and the second layer is a resilient layer formed from a pliable material. At least one of the first layer and the second layer includes a via hole. The via hole is aligned with the channel to pass fluid thereto. The via hole is configured to pass fluid through the first layer or the second layer substantially perpendicularly to the channel. Embossments are also used to define aspects of a fluidic channel.

2,4,5-trisubstituted 1,2,4-triazolones useful as inhibitors of DHODH
U.S. Patent 10,815,215 (October 27, 2020)

Stefan Nikolaus Gradl, Duy Nguyen, Knut Eis, Judith Gunther, Timo Stellfeld, Andreas Janzer, Sven Christian, Thomas Muller, Sherif El Sheikh, Han Jie Zhou, Changjia Zhao, David B. Sykes, Steven James Ferrara, Kery Liu, Michael Krober, Claudia Merz, Michael Niehues, Martina Schafer, Katja Zimmermann, and Carl Friedrich Nising

Abstract: The present invention provides triazolone compounds of general formula (I): in which R1, R2, R3, R4 and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

Achromatic metasurface optical components by dispersive phase compensation
U.S. Patent 10,816,815 (October 27, 2020)

Francesco Aieta, Mikhail Kats, Patrice Genevet, Federico Capasso, and Mohammadreza Khorasaninejad

Abstract: Multi-wavelength light is directed to an optic including a substrate and achromatic metasurface optical components deposited on a surface of the substrate. The achromatic metasurface optical components comprise a pattern of dielectric resonators. The dielectric resonators have distances between adjacent dielectric resonators; and each dielectric resonator has a width, w, that is distinct from the width of other dielectric resonators. A plurality of wavelengths of interest selected from the wavelengths of the multi-wavelength light are deflected with the achromatic metasurface optical components at a shared angle or to or from a focal point at a shared focal length.

Click-crosslinked hydrogels and methods of use
U.S. Patent 10,821,208 (November 3, 2020)

Rajiv Desai, Neel Satish Joshi, David J. Mooney, Sandeep T. Koshy, and Alexander G. Stafford

Abstract: The present disclosure provides click-crosslinked hydrogels and methods of use.

T cell balance gene expression, compositions of matters and methods of use thereof
U.S. Patent 10,822,587 (November 3, 2020)

Aviv Regev, Vijay Kuchroo, Hongkun Park, Nir Yosef, Alexander K. Shalek, Jellert Gaublomme, Nicole C. Joller, Chuan Wu, and Ana Carrizosa Anderson

Abstract: This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences T cell balance, for example, Th17 cell differentiation, maintenance and/or function, as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences T cell balance in a variety of therapeutic and/or diagnostic indications. This invention also relates generally to identifying and exploiting target genes and/or target gene products that modulate, control or otherwise influence T cell balance in a variety of therapeutic and/or diagnostic indications.

Void structures with repeating elongated-aperture pattern
U.S. Patent 10,823,409 (November 3, 2020)

Katia Bertoldi, Michael Taylor, Ali Shanian, Miklos Gerendas, and Carl Carson

Abstract: Void structures, systems and devices with void structures, and methods of fabricating void structures are disclosed. A void structure is disclosed with a repeating elongated-aperture pattern designed to provide negative Poisson's Ratio behavior under macroscopic stress and strain loading. The pattern can include horizontal and vertical elliptically shaped apertures that are arranged on horizontal and vertical lines in a way that the lines are equally spaced in both dimensions. The centers of each aperture is on a crossing point of two of the lines. The vertical and horizontal elliptically shaped apertures alternate on the vertical and horizontal lines such that any vertical aperture is surrounded by horizontal apertures along the lines (and vice versa), and the next vertical apertures are found on both diagonals. The voids can also act as cooling and/or damping holes and, due to their arrangement, also as stress reduction features.

Microfluidic device for storage and well-defined arrangement of droplets
U.S. Patent 10,828,641 (November 10, 2020)

Christian Boehm, Amy Rowat, Sarah Koester, Jeremy Agresti, and David A. Weitz

Abstract: The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time-resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.

Distributed pressurization and exhaust systems for soft robots
U.S. Patent 10,828,788 (November 10, 2020)

Joshua Aaron Lessing and George M. Whitesides

Abstract: A soft robot is described, including: a flexible and/or stretchable body; a common fluid pressurization unit; and a plurality of fluid chambers each embedded in the flexible and/or stretchable body and capable of fluidic connection with the common fluid pressurization unit through a pressurizing valve; wherein the pressurizing valve is capable of being activated to allow the pressurized fluid to flow from the common fluid pressurization unit into the fluid chamber to result in actuation. Methods of using the soft robot are also described.

Cellular poration using laser radiation
U.S. Patent 10,829,729 (November 10, 2020)

Eric Mazur, Nabiha Saklayen, Marinna Madrid, Marinus Huber, and Valeria Nuzzo

Abstract: In one aspect, a method of cell processing is disclosed, which includes disposing a plurality of cells on a substrate across which a plurality of projections are distributed and an electrically conductive layer at least partially coating said projections, exposing the cells to a cargo to be internalized by the cells, irradiating the substrate surface (and in particular the projections) with continuous wave or pulsed laser radiation. For example, one or more laser pulses having a pulse width in a range of about 1 ns to about 1000 ns can be applied so as to facilitate uptake of the cargo by at least a portion of the cells (e.g., the cells positioned in the vicinity of the projections (e.g., within hundreds of nanometer (such as less than 100 nm) of the projections)). In some embodiments, the laser pulses have a pulse width in a range of about 10 ns to about 500 ns, e.g., in a range of about 5 ns to about 50 ns.

Quantitative pathology analysis and diagnosis using neural networks
U.S. Patent 10,832,406 (November 10, 2020)

Kun-Hsing Yu

Abstract: Histological images are preprocessed and classified among pathology states using a neural network. In preprocessing, the digital image is electronically partitioned into a grid of identically sized, overlapping subimages, and images are selected for analysis based on a parameter such as density.

Microfluidic device having offset, high-shear seeding channels
U.S. Patent 10,836,987 (November 17, 2020)

Karel Domansky, Christopher David Hinojosa, Donald E. Ingber, Daniel Levner, and Guy Thompson II

Abstract: A microfluidic device for determining a response of cells comprises a microchannel and a seeding channel. The microchannel is at least partially defined by a porous membrane having cells adhered thereto. The microchannel has a first cross-sectional area. The seeding channel delivers a working fluid to the cells within the microchannel. The seeding channel has a second cross-sectional area that is less than the first cross-sectional area such that a flow of the working fluid produces a substantially higher shear force within the seeding channel to inhibit the attachment of cells within the seeding channel. And when multiple seeding channels are used to deliver fluids to multiple microchannels that define an active cellular layer across the membrane, the seeding channels are spatially offset from each other such that fluid communication between the fluids occurs only at the active region via the membrane, not at the seeding channels.

Flow battery with electrolyte rebalancing system
U.S. Patent 10,840,532 (November 17, 2020)

Qing Chen, Roy G. Gordon, and Michael J. Aziz

Abstract: The present invention relates to flow battery systems including a flow battery and an electrolyte rebalancing system. In accordance with certain embodiments, the electrolytes used in the systems of the present invention are aqueous, and in one embodiment, bromine species are used as redox-active species.

Magnetic assembly of soft robots with hard components
U.S. Patent 10,843,336 (November 24, 2020)

Sen Wai Kwok, Stephen A. Morin, Bobak Mosadegh, Ju-Hee So, Robert F. Shepherd, and George M. Whitesides

Abstract: Reconfigurable soft robotic actuators with hard components are described. Magnetic attraction is used to couple flexible molded bodies capable of actuation upon pressurization with other flexible molded bodies and/or with hard components (e.g., frames and connectors) to form a seal for fluidic communication and cooperative actuation. Pneumatic de-coupling chambers built into the hard components to de-couple the hard components from the magnetically-coupled soft molded bodies are described. The use of magnetic self-alignment coupling and pneumatic de-coupling allows for the remote assembly and disassembly of complex structures involving hard and soft components. The magnetic coupling allows for rapid, reversible reconfiguration of hybrid soft-hard robots for repair, testing new designs, and carrying out new tasks.

Zero-porosity NPR structure and tuning of NPR structure for particular localities
U.S. Patent 10,843,505 (November 24, 2020)

Katia Bertoldi, Fabian Enrique Sanchez Guerrero, Matthew Christopher Innes, Farhad Javid, Minh Quan Pham, Megan Schaenzer, Sr., Ali Shanian, and Evelyne Smith-Roberge

Abstract: The present concepts include a zero-porosity structure having a plurality of structural elements arranged to provide a negative Poisson's ratio and, further, a new mechanism to generate negative Poisson's ratio is single material, zero-porosity structure.

Palladium-mediated ketolization
U.S. Patent 10,844,073 (November 24, 2020)

Jung Hwa Lee, Yoshito Kishi, Ayumi Osawa, and Zhanjie Li

Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).

Engineered botulinum neurotoxin
U.S. Patent 10,844,362 (November 24, 2020)

Min Dong, Lisheng Peng, Pal Erik Gustav Stenmark, and Ronnie Per Arne Berntsson

Abstract: Disclosed herein are botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial botulinum serotype B (B-H.sub.c), comprising one or more substitution mutations corresponding to substitution mutations in serotype B, strain 1, V1118M; Y1183M; E1191M; E1191I; E1191Q; E1191T; S1199Y; S1199F; S1199L; S1201V; or combinations thereof. Specific combination mutations include E1191M and S1199L, E1191M and S1199Y, E1191M and S1199F, E1191Q and S1199L, E1191Q and S1199Y, or E1191Q and S1199F. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.

Neuronal axon mimetics for in vitro analysis of neurological diseases, myelination, and drug screening
U.S. Patent 10,845,360 (November 24, 2020)

Krystyn J. Van Vliet, Anna Jagielska, Kimberly Homan, Jennifer A. Lewis, and Travis Alexander Busbee

Abstract: Aspects of the present invention provide improved methods and apparatus for use in in vitro modeling of the interaction of cells with cellular constructs/parts/axons, including axon mimetics and use of three-dimensional fibers.

Quinone and hydroquinone based flow battery
U.S. Patent 10,847,829 (November 24, 2020)

Brian Huskinson, Michael Marshak, Michael J. Aziz, Roy G. Gordon, Alan Aspuru-Guzik, Suleyman Er, Changwon Suh, Liuchuan Tong, and Kaixiang Lin

Abstract: The invention provides an electrochemical cell based on a new chemistry for a flow battery for large scale, e.g., gridscale, electrical energy storage. Electrical energy is stored chemically in quinone molecules having multiple oxidation states, e.g., three or more. During charging of the battery, the quinone molecules at one electrode are oxidized by emitting electrons and protons, and the quinone molecules at the other electrode are reduced by accepting electrons and protons. These reactions are reversed to deliver electrical energy. The invention also provides additional high and low potential quinones that are useful in rechargeable batteries.

Compositions and methods for treating multiple myeloma
U.S. Patent 10,851,051 (December 1, 2020)

Shrikanta Chattopadhyay, Stuart L. Schreiber, and Zarko Boskovic

Abstract: In one aspect, the present invention provides a method of inhibiting proliferation of a multiple myeloma cell, the method comprising contacting the cell with BRD9647, thereby inhibiting proliferation of the cell. In another aspect, the present invention provides a method of treating multiple myeloma in a pre-selected subject, the method comprising administering an effective amount of BRD9647 to the subject, wherein the subject is pre-selected by detecting a mutation in an AZIN1 polynucleotide or polypeptide relative to a reference in a biological sample obtained from the subject. In another aspect, the present invention provides a method of modulating benzoylation of an agent in a cell, the method comprising contacting the cell with BRD9647, thereby modulating benzoylation of an agent in the cell.

Antibody molecules to PD-L1 and methods of treating cancer
U.S. Patent 10,851,165 (December 1, 2020)

Gordon James Freeman, Arlene Helen Sharpe, Gerhard Johann Frey, Hwai Wen Chang, Jennifer Marie Mataraza, and Glenn Dranoff

Abstract: Antibody molecules that specifically bind to PD-L1 are disclosed. Combination therapies comprising the anti-PD-L1 antibody molecules are also disclosed. The anti-PD-L1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.

Block copolymer ink formulation for 3D printing and method of making a 3D printed radiofrequency (RF) device
U.S. Patent 10,851,251 (December 1, 2020)

Theodore H. Fedynyshyn, Michael T. Lis, and Jennifer Ann Lewis

Abstract: An ink formulation for 3D printing comprises a triblock copolymer in a solvent, where the triblock copolymer includes end blocks comprising an aromatic or acrylate polymer and a midblock between the end blocks comprising an aliphatic polymer. The ink formulation exhibits a shear thinning threshold of about 0.02 rad/sec or less. A method of making a 3D printed radiofrequency (RF) device comprises extruding an ink formulation from a deposition nozzle moving relative to a substrate, where the ink formulation comprises a triblock copolymer in a solvent and the triblock copolymer includes end blocks comprising an aromatic or acrylate polymer and a midblock between the end blocks comprising an aliphatic polymer. One or more continuous filaments comprising the ink formulation are deposited in a predetermined pattern on the substrate, and the ink formulation is treated to remove or cure the solvent, thereby forming a printed RF device.

Frequency-based modulation of diverse species in a nucleic acid library
U.S. Patent 10,851,369 (December 1, 2020)

Reza Kalhor, Javier Fernandez Juarez, Henry Hung-yi Lee, and George M. Church

Abstract: A method of processing a collection of nucleic acid sequences is provided including connecting an adaptor to one or more or each nucleic acid sequence in the collection to create a processed nucleic acid template library, wherein the adaptor includes a first DNA sequence encoding a PAM sequence and at least a tracr mate.

Lipidated PSA compositions and methods
U.S. Patent 10,857,177 (December 8, 2020)

Sungwhan Oh, Deniz Erturk-Hasdemir, and Dennis L. Kasper

Abstract: The invention provides various isolated and synthetic forms of lipidated PSA as well as isolated or synthetic forms of the glycolipid component of lipidated PSA, and compositions thereof, methods of making including methods of isolating such forms, and methods of use thereof.

CAS9 variants and uses thereof
U.S. Patent 10,858,639 (December 8, 2020)

David R. Liu, John Paul Guilinger, and David B. Thompson

Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Barcoded protein array for multiplex single-molecule interaction profiling
U.S. Patent 10,858,698 (December 8, 2020)

George M. Church and Liangcai Gu

Abstract: Methods for attaching barcodes to polypeptides are provided. Methods for detecting molecular interactions at the single molecule level are provided. Embodiments of the invention are directed to a ONA barcoded protein array technology for parallel protein interaction profiling on a single molecule basis. DNA barcodes are attached to proteins collectively via ribosome display or individually via enzymatic conjugation. Novel methods are described herein that measure protein interactions based on the statistical analysis of co-localized polonies arising from barcoding DNAs of interacting proteins.

Orthopedic device including protruding members
U.S. Patent 10,864,100 (December 15, 2020)

Conor James Walsh, Alan T. Asbeck, Matthew W. Yarri, Jillian Christine Cochran, and Stefano Marco Maria De Rossi

Abstract: Orthopedic devices may include rigid members for coupling to portions of a limb that includes a joint, and a cable that couples to the rigid members and extends up to a powered element. The orthopedic devices are configured to produce beneficial forces using the rigid member and the cable, which beneficial forces are translated to the wearer. The orthopedic devices include control systems that generate control signals for controlling the powered element.

Engineered microbe-targeting molecules and uses thereof
U.S. Patent 10,865,235 (December 15, 2020)

Donald E. Ingber, Michael Super, Jeffrey Charles Way, Mark J. Cartwright, Julia B. Berthet, Dinah R. Super, Martin Rottman, and Alexander L. Watters

Abstract: Described herein are engineered microbe-targeting or microbe-binding molecules, kits comprising the same and uses thereof. Some particular embodiments of the microbe-targeting or microbe-binding molecules comprise a carbohydrate recognition domain of mannose-binding lectin, or a fragment thereof, linked to a portion of a Fc region. In some embodiments, the microbe-targeting molecules or microbe-binding molecules can be conjugated to a substrate, e.g., a magnetic microbead, forming a microbe-targeting substrate (e.g., a microbe-targeting magnetic microbead). Such microbe-targeting molecules and/or substrates and the kits comprising the same can bind and/or capture of a microbe and/or microbial matter thereof, and can thus be used in various applications, e.g., diagnosis and/or treatment of an infection caused by microbes such as sepsis in a subject or any environmental surface. Microbe-targeting molecules and/or substrates can be regenerated after use by washing with a low pH buffer or buffer in which calcium is insoluble.

Broadband multifunctional efficient meta-gratings based on dielectric waveguide phase shifters
U.S. Patent 10,866,360 (December 15, 2020)

Mohammadreza Khorasaninejad and Federico Capasso

Abstract: A phase shift element includes a substrate and a dielectric ridge waveguide (DRW) disposed on the substrate. The DRW includes a dielectric material, and a width of the DRW is less than 500 nanometers (nm). A meta-grating includes a substrate and multiple dielectric ridge wave-guides (DRWs) disposed on the substrate.

Enzymatic nucleic acid synthesis
U.S. Patent 10,870,872 (December 22, 2020)

Henry Hung-yi Lee, George M. Church, and Reza Kalhor

Abstract: The disclosure provides methods for making a polynucleotide wherein the addition of nucleotides can be physically, chemically and/or enzymatically controlled. The methods include combining a selected nucleotide, cations, an error prone or template independent DNA polymerase at a reaction site including an initiator sequence attached thereto and having a 3' terminal nucleotide, wherein the reaction reagents can be modulated and under conditions that allow covalent addition of one or more of a selected nucleotide to the 3' terminal nucleotide such that the selected nucleotide becomes a 3' terminal nucleotide, and repeating the addition step until the polynucleotide is formed.

Dendritic cell response gene expression, compositions of matters and methods of use thereof
U.S. Patent 10,870,885 (December 22, 2020)

Aviv Regev, Alexander K. Shalek, Rahul Satija, and Hongkun Park

Abstract: This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences dendritic cell (DC) response(s), for example, dendritic cell maturation, dendritic cell antiviral response(s) and/or dendritic cell inflammatory response(s), as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences dendritic cell response(s) in a variety of therapeutic and/or diagnostic indications.

Multiple emulsions created using jetting and other techniques
U.S. Patent 10,874,997 (December 29, 2020)

David A. Weitz, Julian W. P. Thiele, and Adam R. Abate

Abstract: The present invention generally relates to emulsions, and more particularly, to multiple emulsions. In one aspect, multiple emulsions are formed by urging a fluid into a channel, e.g., by causing the fluid to enter the channel as a "jet." Multiple fluids may flow through a channel collinearly before multiple emulsion droplets are formed. The fluidic channels may also, in certain embodiments, include varying degrees of hydrophilicity or hydrophobicity. In some cases, the average cross-sectional dimension may change, e.g., at an intersection. Unexpectedly, systems such as those described herein may be used to encapsulate fluids in single or multiple emulsions that are difficult or impossible to encapsulate using other techniques, such as fluids with low surface tension, viscous fluids, or viscoelastic fluids. Other aspects of the invention are generally directed to methods of making and using such systems, kits involving such systems, emulsions created using such systems, or the like.

Determination of cells using amplification
U.S. Patent 10,876,156 (December 29, 2020)

David A. Weitz and Huidan Zhang

Abstract: The present invention generally relates to microfluidics and, in particular, to systems and methods for determining cells using amplification. In one set of embodiments, cells are encapsulated within droplets and nucleic acids from the cells amplified within the droplets. The droplets may then be pooled together and the amplified nucleic acids can be determined using PCR or other suitable techniques. In some embodiments, techniques such as these can be used to detect relatively rare cells that may be present, e.g., if the droplets are amplified using conditions able to selectively amplify nucleic acids arising from the relatively rare cells.

Compositions and methods relating to nucleic acid-protein complexes
U.S. Patent 10,876,177 (December 29, 2020)

Mounir Ahmad Koussa and Wesley Philip Wong

Abstract: Provided are methods and compositions relating to conjugation of nucleic acids and proteins of interest under conditions that maintain protein activity. The nucleic acid-protein conjugates may be used in nucleic acid nanostructures such as those generated using DNA origami methods.

Rapid production of droplets
U.S. Patent 10,876,688 (December 29, 2020)

David A. Weitz and Esther Amstad

Abstract: The present invention generally relates to the production of fluidic droplets. Certain aspects of the invention are generally directed to systems and methods for creating droplets by flowing a fluid from a first channel to a second channel through a plurality of side channels. The fluid exiting the side channels into the second channel may form a plurality of droplets, and in some embodiments, at very high droplet production rates. In addition, in some aspects, double or higher-order multiple emulsions may also be formed. In some embodiments, this may be achieved by forming multiple emulsions through a direct, synchronized production method and/or through the formation of a single emulsion that is collected and re-injected into a second microfluidic device to form double emulsions.

Nucleic acid nanostructure barcode probes
U.S. Patent 10,876,971 (December 29, 2020)

Chenxiang Lin, Chao Li, William M. Shih, Peng Yin, and Ralf Jungmann

Abstract: Provided herein are, inter alia, barcode probes comprised of transiently or stably fluorescently labeled nucleic acid nanostructures that are fully addressable and able to be read using standard fluorescent microscope and methods of use thereof including methods of use as detectable labels for probes.

Predictive control model for the artificial pancreas using past predictions
U.S. Patent 10,878,964 (December 29, 2020)

Eyal Dassau, Alejandro J. Laguna Sanz, and Francis J. Doyle III

Abstract: Presented herein are methods, and devices of adaptively tuning a zone based Model Predictive Control (MPC) controller, using at least one processor, which include determining, residuals based on prediction models storing, in a memory, the determined residuals, calculating a trust index by quantifying uncertainty of the prediction models using the stored residuals and tuning the MPC controller, in real time based on the calculated value of the trust index.

Press Contact

Caroline Perry, (617) 495-4157

Press Contact

Caroline Perry
(617) 495-4157