Harvard faculty Jennifer Lewis, Xiaowei Zhuang, David Liu, Adam Cohen, David Mooney, Don Ingber, Greg Verdine, and George Whitesides are among the inventors issued U.S. patents in September 2018.

The innovations recognized are as follows:

Molecular sleds and uses thereof
U.S. Patent 10,065,989 (September 4, 2018)

Walter F. Mangel, Paul Blainey, Vito Graziano, Andreas Herrmann, William J. McGrath, Antonius Martinus Van Oijen, and Xiaoliang Sunney Xie

Abstract: The present invention relates to compositions which may comprise a molecular sled linked to cargo and uses thereof. In particular, the present invention relates to a non-naturally occurring or engineered composition which may comprise a molecular sled, linkers and a molecular cargo connected to the sled via the linkers. Methods involving the use of molecular sleds and their cargoes and pharmaceutical compositions, methods for treating cancer, a degenerative disease, a genetic disease or an infectious disease as well as diagnostic methods are also contemplated by the present invention.

Microfluidic active mixing nozzle for three-dimensional printing of viscoelastic inks
U.S. Patent 10,071,350 (September 11, 2018)

Jennifer A. Lewis and Thomas J. Ober

Abstract: The present disclosure relates to a device for three-dimensional ink deposition from an impeller-driven active mixing microfluidic printing nozzle. The device is configured to receive a material property associated with the plurality of fluids and receive a structure property of the printing nozzle. The device then determines a threshold relation between a rotating speed ω of an impeller in the nozzle and a volumetric flow rate Q of fluids that flow through the nozzle based on the material property of the plurality of fluids, the structure property of the printing nozzle. Based on the threshold relation, the device then determines an actual volumetric flow rate of the fluids and actual rotation speed of the impeller.

Sub-diffraction limit image resolution and other imaging techniques
U.S. Patent 10,073,035 (September 11, 2018)

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.

Systems and methods for Bayesian optimization using non-linear mapping of input
U.S. Patent 10,074,054 (September 11, 2018)

Ryan P. Adams, Roland Jasper Snoek, Kevin Swersky, and Richard Zemel

Abstract: Techniques for use in connection with performing optimization using an objective function that maps elements in a first domain to values in a range. The techniques include using at least one computer hardware processor to perform: identifying a first point at which to evaluate the objective function at least in part by using an acquisition utility function and a probabilistic model of the objective function, wherein the probabilistic model depends on a non-linear one-to-one mapping of elements in the first domain to elements in a second domain; evaluating the objective function at the identified first point to obtain a corresponding first value of the objective function; and updating the probabilistic model of the objective function using the first value to obtain an updated probabilistic model of the objective function.

Cas9 proteins including ligand-dependent inteins
U.S. Patent 10,077,453 (September 18, 2018)

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.

Optical selection of cells
U.S. Patent 10,077,463 (September 18, 2018)

Adam E. Cohen and Miao-Ping Chien

Abstract: Provided herein are photochemical crosslinkers and photocleavable crosslinkers and their uses in methods for cell selection from cell cultures. The photochemical crosslinkers comprise a fluorescent dye and a radical generator. The photocleavable crosslinkers comprise a photocleavable linker linking two electrophilic groups to each other. Also provided are systems for imaging cells comprising a plurality of cells crosslinked to extracellular matrix proteins using a crosslinker as described, an imaging apparatus, an illuminating apparatus, and software for image processing.

Programming of cells for tolerogenic therapies
U.S. Patent 10,080,789 (September 25, 2018)

Roger Warren Sands, Eduardo Alexandre Barros E. Silva, Toshihisa Kawai, and David J. Mooney

Abstract: Biomaterial systems, e.g., gel scaffolds, are used in vivo to recruit immune cells and promote their activation towards a non-inflammatory phenotype, thereby leading suppression of inflammation. The compositions and methods are useful to reduce the severity of autoimmunity, chronic inflammation, allergy, and periodontal disease.

Systems and methods for monitoring, managing, and treating asthma and anaphylaxis
U.S. Patent 10,080,841 (September 25, 2018)

Andy H. Levine, Christoph Matthias Kanzler, Daniel Leo Miranda, Joseph Mooney, Huy Lam, John Osborne, Mustafa Karabas, Alan Dunne, James Niemi, Benjamin Matthews, Donald E. Ingber, Olivier Henry, and Premananda Pai Indic

Abstract: A physiologic sensor module includes at least one wearable sensor that is configured for wearing on a human body part and for measuring at least one biological signal. The module further includes at least one controller communicatively coupled to the wearable sensor and configured to receive the biological signal from the wearable sensor. The controller is further configured to process the biological signal in real-time, extract one or more clinical features from the biological signal, and based on the clinical features, determine detection of anaphylaxis.

Stapled and stitched polypeptides and uses thereof
U.S. Patent 10,081,654 (September 25, 2018)

Gregory L. Verdine and Gerard Hilinski

Abstract: [See patent 10,081,654 for original formatting.]

Assay device and method
U.S. Patent 10,082,507 (September 25, 2018)

Samuel K. Sia, Vincent Linder, Babak Parviz, Adam Siegel, and George M. Whitesides

Abstract: An assay method is described, which comprises the steps of immobilizing a binding partner (e.g., an antigen or antibody) for an analyte to be detected (e.g., an antibody or antigen) on a portion of a surface of a microfluidic chamber; passing a fluid sample over the surface and allowing the analyte to bind to the binding partner; allowing a metal colloid, e.g., a gold-conjugated antibody, to associate with the bound analyte; flowing a metal solution, e.g., a silver solution, over the surface such as to form an opaque metallic layer; and detecting the presence of said metallic layer, e.g., by visual inspection or by measuring light transmission through the layer, conductivity or resistance of the layer, or metal concentration in the metal solution after flowing the metal solution over the surface.