Harvard faculty Hongkun Park, Ulrich von Andrian, Shigemi Nagai, Mikhail Lukin, Sandeep Robert Datta, Amin I. Kassis, Matthew Shair, David Liu, and George Whitesides are among the inventors issued U.S. patents during April 2016.

The innovations recognized are as follows:

Methods, apparatus and systems for production, collection, handling, and imaging of tissue sections
U.S. Patent 9,304,067 (April 5, 2016)

Kenneth Jeffrey Hayworth and Amy Au Hayworth

Abstract: Methods, apparatus and systems for collecting thin tissue samples for imaging. Thin tissue sections may be cut from tissue samples using a microtome-quality knife. In one example, tissue samples are mounted to a substrate that is rotated such that thin tissue sections are acquired via lathing. Collection of thin tissue sections may be facilitated by a conveyor belt. Thin tissue sections may be mounted to a thin substrate (e.g., by adhering thin tissue sections to a thin substrate via a roller mechanism) that may be imaged, for example, by an electron beam (e.g., in an electron microscope). Thin tissue sections may be strengthened before cutting via a blockface thinfilm deposition technique and/or a blockface taping technique. An automated reel-to-reel imaging technique may be employed for collected/mounted tissue sections to facilitate random-access imaging of tissue sections and maintaining a comprehensive library including a large volume of samples.

Molecular delivery with nanowires
U.S. Patent 9,304,132 (April 5, 2016)

Hongkun Park, EunGyeong Yang, Alexander K. Shalek, JinSeok Lee, Jacob Robinson, Amy Sutton, Myung-Han Yoon, and Marsela Jorgolli

Abstract: A molecular delivery system including a plurality of nanowires (e.g., Si NWs), each of the nanowires having a surface layer formed of a silicon-containing material and a covalently bound linker (e.g., silane linker) attached to the surface layer, and optionally including a substrate to which the nanowires are adhered or a molecule to be delivered attached to the linker. Also disclosed is a method of delivering into a cell an exogenous molecule.

Targeting of antigen presenting cells with immunonanotherapeutics
U.S. Patent 9,308,280 (April 12, 2016)

Jinjun Shi, Frank Alexis, Matteo Iannacone, Elliott Ashley Moseman, Pamela Basto, Robert S. Langer, Omid C. Farokhzad, Ulrich H. von Andrian, and Elena Tonti

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface. The nanocarriers are capable of targeting antigen presenting cells when administered to a subject. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Methodology of dental caries detection
U.S. Patent 9,310,355 (April 12, 2016)

Shigemi Nagai and Masazumi Nagai

Abstract: Disclosed are methods for detecting demineralization of a surface of a tooth, comprising a) contacting the tooth of a subject with an orally acceptable, binding composition comprising a binding agent that binds to a demineralized surface of the tooth; b) removing unbound binding compound; c) contacting the tooth with an orally acceptable, detector composition comprising a probe compound that reacts with the binding agent to form a visually detectable reaction product; and d) detecting formation of the reaction product as an indication of the presence or extent of surface demineralization of the tooth. Systems, kits, and compositions for practicing the methods are also provided.

Scalable room temperature quantum information processor
U.S. Patent 9,317,473 (April 19, 2016)

Norman Y. Yao, Liang Jiang, Alexey V. Gorshkov, Peter C. Maurer, Geza Giedke, Juan Ignacio Cirac, and Mikhail D. Lukin

Abstract: A quantum information processor (QIP) may include a plurality of quantum registers, each quantum register containing at least one nuclear spin and at least one localized electronic spin. At least some of the quantum registers may be coherently coupled to each other by a dark spin chain that includes a series of optically unaddressable spins. Each quantum register may be optically addressable, so that quantum information can be initialized and read out optically from each register, and moved from one register to another through the dark spin chain, though an adiabatic sequential swap or through free-fermion state transfer. A scalable architecture for the QIP may include an array of super-plaquettes, each super-plaquette including a lattice of individually optically addressable plaquettes coupled to each other through dark spin chains, and separately controllable by confined microwave fields so as to permit parallel operations.

System and method for automatically discovering, characterizing, classifying and semi-automatically labeling animal behavior and quantitative phenotyping of behaviors in animals
U.S. Patent 9,317,743 (April 19, 2016)

Sandeep Robert Datta and Alexander B. Wiltschko

Abstract: A method for studying the behavior of an animal in an experimental area including stimulating the animal using a stimulus device; collecting data from the animal using a data collection device; analyzing the collected data; and developing a quantitative behavioral primitive from the analyzed data. A system for studying the behavior of an animal in an experimental area including a stimulus device for stimulating the animal; a data collection device for collecting data from the animal; a device for analyzing the collected data; and a device for developing a quantitative behavioral primitive from the analyzed data. A computer implemented method, a computer system and a nontransitory computer readable storage medium related to the same. Also, a method and apparatus for automatically discovering, characterizing and classifying the behavior of an animal in an experimental area. Further, use of a depth camera and/or a touch sensitive device related to the same.

Compounds and methods for enzyme-mediated tumor imaging and therapy
U.S. Patent 9,320,815 (April 26, 2016)

Amin I. Kassis

Abstract: The invention provides methods and compositions, e.g., for tumor imaging and therapy.

Hyperforin analogs, methods of synthesis, and uses thereof
U.S. Patent 9,321,713 (April 26, 2016)

Matthew D. Shair, Brian A. Sparling, and David Moebius

Abstract: The present invention provides a novel 11-step enantioselective approach to the natural product hyperforin, which enables access to a wide variety of hyperforin analogs. The present invention also provides pharmaceutical compositions comprising inventive hyperforin analogs. Hyperforin analogs synthesized using the present synthetic method are envisioned useful in the treatment of various conditions, including, but not limited to, depression and conditions characterized by depression, inflammatory skin conditions, diabetes, asthma, chronic obstructive pulmonary disease (COPD), kidney disorders, and ischemic brain damage.

Evaluation and improvement of nuclease cleavage specificity
U.S. Patent 9,322,006 (April 26, 2016)

David R. Liu, John Paul Guilinger, and Vikram Pattanayak

Abstract: Engineered nucleases are promising tools for genome manipulation and determining off-target cleavage sites of these enzymes is of great interest. We developed an in vitro selection method that interrogates 10¹¹ DNA sequences for their ability to be cleaved by nucleases. The method revealed hundreds of thousands of DNA sequences that can be cleaved in vitro by two ZFNs, CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGF-A genes, respectively. Analysis of the identified sites in cultured human cells revealed CCR5-224-induced mutagenesis at nine off-target loci. Similarly, we observed 31 off-target sites cleaved by VF2468 in cultured human cells. Our findings establish an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage and suggest strategies for the improvement of future nuclease design. It was also observed that TALENs can achieve cleavage specificity similar to or higher than that observed in ZFNs.

Cas9-FokI fusion proteins and uses thereof
U.S. Patent 9,322,037 (April 26, 2016)

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). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Quality control of diamagnetic materials using magnetic levitation
U.S. Patent 9,322,804 (April 26, 2016)

George M. Whitesides, Audrey Ellerbee, and Simon Tricard

Abstract: The ability to levitate and detect height and orientation of diamagnetic objects suspended in paramagnetic solutions using an inhomogeneous magnetic field is described. By comparing the measured height and orientation of a sample material with the measured height and orientation of a reference material, quality control of objects can be carried out. The major advantages of this quality control technique are: i) it is a simple apparatus that does not require electric power (a set of permanent magnets and gravity are sufficient for the diamagnetic separation and collection system to work); ii) it is compatible with simple optical detection; iii) it is a cost-effective and simple method that can carry out quality control between sample and reference materials rapidly.