Harvard faculty Jennifer Lewis, John Collier, Isaac Chiu, Piotr Sliz, David R. Liu, George Whitesides, Jeff Lichtman, David Weitz, Mikhail Lukin, George Church, Don Ingber, Gu-Yeon Wei, Kit Parker, and Marko Loncar are among the inventors issued U.S. patents in July 2020.

The innovations recognized are as follows:

Tubular tissue construct and a method of printing
U.S. Patent 10,702,630 (July 7, 2020)

Jennifer A. Lewis, Kimberly A. Homan, David B. Kolesky, Ryan L. Truby, and Mark A. Skylar-Scott

Abstract: A 3D printed tubular construct, such as a nephron, with or without embedded vasculature as well as methods of printing tubular tissue constructs are described.

Compositions and methods for treatment of pain
U.S. Patent 10,704,035 (July 7, 2020)

R. John Collier, Isaac Chiu, and Bradley L. Pentelute

Abstract: Embodied herein are engineered fusion proteins that bind and target nociceptor neurons, compositions comprising these engineered fusion proteins, and methods for treatment of pain using these engineered fusion proteins or compositions containing the engineered fusion proteins. The engineered fusion proteins contain domains derived from protein toxins such as the anthrax toxin, clostridial botulinum family of toxins, disulphide-containing toxins, and AB component type toxins.

Lin28/let-7 crystal structures, purification protocols, and molecular probes suitable for screening assays and therapeutics
U.S. Patent 10,704,049 (July 7, 2020)

Piotr Sliz and Yunsun Nam

Abstract: The invention provides compositions and methods for regulating microRNA (miRNA) biogenesis. The invention also relates to compositions and methods for treating or preventing cancer in a subject in need thereof.

CAS9 proteins including ligand-dependent inteins
U.S. Patent 10,704,062 (July 7, 2020)

David R. Liu and Kevin Davis

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

High throughput fabrication of soft machines
U.S. Patent 10,704,537 (July 7, 2020)

Jason Ming Ting, Alok Suryavamsee Tayi, Bobak Mosadegh, and George M. Whitesides

Abstract: A soft robot device includes at least a first thermoplastic layer and a second thermoplastic layer, wherein at least one layer is comprised of an extensible thermoplastic material; at least one layer is an inextensible layer; and at least one layer comprises a pneumatic network, wherein the pneumatic network is configured to be in fluidic contact with a pressurizing source, wherein the first and second thermoplastic layers are thermally bonded to each other.

Methods, apparatuses and systems for collection of tissue sections
U.S. Patent 10,704,992 (July 7, 2020)

Kenneth Jeffrey Hayworth, Richard Schalek, Juan Carlos Tapia, Narayanan Kasthuri, and Jeff W. Lichtman

Abstract: Methods, apparatuses and systems for facilitating automated or semi-automated collection of tissue samples cut by a microtome. In one example, a collection apparatus may be moved back and forth between respective positions at which the collection apparatus is operatively coupled to a microtome so as to collect cut tissue samples, or routine access to the microtome is provided. Relatively easy movement and positioning of the collection apparatus is facilitated, while at the same time ensuring structural stability and appropriate alignment and/or isolation between the collection apparatus and the microtome. A fluid reservoir receives samples cut by the microtome, and the collection apparatus may collect samples via a conveyor-like substrate disposed near/in the reservoir. A linear movement of the substrate may be controlled based on a cutting rate of the microtome, and the fluid level in the reservoir may be automatically maintained to facilitate effective sample collection.

Compartmentalised screening by microfluidic control
U.S. Patent 10,705,078 (July 7, 2020)

Andrew David Griffiths, David A. Weitz, Darren Roy Link, Keunho Ahn, Jerome Bibette

Abstract: The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalising the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

System and method for biomimetic fluid processing
U.S. Patent 10,710,073 (July 14, 2020)

Joseph Italiano, Linas Mazutis, Jonathan N. Thon, and David A. Weitz

Abstract: A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.

Optimized CRISPR-Cas double nickase systems, methods and compositions for sequence manipulation
U.S. Patent 10,711,285 (July 14, 2020)

Feng Zhang, Patrick Hsu, Chie-yu Lin, and Fei Ran

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.

Detecting gases and respiration by the conductivity of water within a porous substrate sensor
U.S. Patent 10,712,337 (July 14, 2020)

Firat Guder, Bobak Mosadegh, Alar Ainla, and George M. Whitesides

Abstract: A method of and system for detecting a gas or vapor includes providing a sensor comprising an electrode pair in electrical contact with a layer of porous material, the porous material layer having water adsorbed on its surface; contacting the sensor with a gas or vapor sample to be analysed; applying a voltage across the electrode pair of the sensor; and measuring a response, the response correlating to the presence of a target gas or vapor.

Quantum metrology based on strongly correlated matter
U.S. Patent 10,712,406 (July 14, 2020)

Mikhail D. Lukin, Soonwon Choi, and Norman Yao

Abstract: A method for quantum metrology using stable non-equilibrium states of quantum matter, such as many-body quantum spin systems, is disclosed. The approach can utilize quantum correlations in such many-body quantum spin systems stabilized by strong interactions and periodic driving for reduction of noise. As an example, an exemplary protocol to perform Floquet enhanced measurements of an oscillating magnetic field in Ising-interacting spin systems is provided. These approaches allow for circumvention of the interaction-induced decoherence associated with high density spin ensembles and is robust to the presence of noise and imperfections. The protocol is applicable to nanoscale magnetic sensing and other precision measurements.

RNA-guided human genome engineering
U.S. Patent 10,717,990 (July 21, 2020)

Prashant G. Mali, George M. Church, and Luhan Yang

Abstract: 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.

Manufacturing soft devices out of sheet materials
U.S. Patent 10,718,358 (July 21, 2020)

Kevin C. Galloway

Abstract: A soft composite actuator is described, including a first elastomeric layer; a strain limiting layer; and a first radially constraining layer, wherein the first elastomeric layer is disposed between the first radially constraining layer and the strain limiting layer; and the elastomeric layer, the strain limiting layer, and the radially constraining layer are bonded together to form at least one bladder for holding pressurized fluid. Methods of using and making of the soft composite actuator are described.

Assays for antimicrobial activity and applications thereof
U.S. Patent 10,718,766 (July 21, 2020)

Mark J. Cartwright, Nazita Gamini, Donald E. Ingber, Martin Rottman, Michael Super, Julie A. Tomolonis, Karen A. Sinclair

Abstract: The disclosure provides methods, compositions, and kits for enhanced detection of microbes in samples and monitoring of antimicrobial activity in a subject.

Area efficient single-ended analog-to-digital converter
U.S. Patent 10,720,841 (July 21, 2020)

Simon Chaput and Gu-Yeon Wei

Abstract: A single ended n-bit hybrid digital-to-analog converter is configured to receive as an input an analog signal and produce an n-bit digital output. The converter includes a split main sub-digital-to-analog converter capacitor array, a most significant bit capacitor array, and a main capacitor array. A coupling capacitor couples the main array to the split main sub-digital-to-analog convert.

Alpha/beta-polypeptide analogs of glucagon-like peptide 1
U.S. Patent 10,723,779 (July 28, 2020)

Samuel H. Gellman, Lisa M. Johnson, Alan Attie, Mark P. Keller, and Alan Saghatelian

Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one .alpha.-amino acid found in the native GLP-1 is replaced with a .beta.-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Muscle chips and methods of use thereof
U.S. Patent 10,725,021 (July 28, 2020)

Kevin Kit Parker, Josue A. Goss, Anna Grosberg, Patrick W. Alford, Adam W. Feinberg, Ashutosh Agarwal, Megan Laura McCain, and Johan Ulrik Lind

Abstract: The present invention provides high throughput assays for identifying compounds that modulate a contractile function, as well as devices suitable for use in these assays.

System and method for wafer-scale fabrication of free standing mechanical and photonic structures by ion beam etching
U.S. Patent 10,727,072 (July 28, 2020)

Haig Avedis Atikian and Marko Loncar

Abstract: A method for fabrication of free standing mechanical and photonic structures is presented. A resist mask is applied to a bulk substrate. The bulk substrate is attached to a movable platform. The bulk substrate is exposed to an ion stream produced by a reactive ion beam etching source. The platform is moved relative to the ion stream to facilitate undercutting a portion of the bulk substrate otherwise shielded by the mask.