Harvard faculty Bernardo Sabatini, John Assad, David Mooney, George Whitesides, David Liu, Michael Lawrence, Don Ingber, Steven Gygi, Federico Capasso, Xiaowei Zhuang, Joanna Aizenberg, and Robert Howe are among the inventors issued U.S. patents in September 2019.

The innovations recognized are as follows:

Optogenetic tool for multiple and independently addressing of patterned optical windows
U.S. Patent 10,398,293 (September 3, 2019)

Ferruccio Pisanello, Luigi Martiradonna, Leonardo Sileo, Ian Anton Oldenburg, Marco Pisanello, Bernardo Luis Sabatini, John Abraham Assad, and Massimo De Vittorio

Abstract: A multi-point light-delivering device, comprising a waveguide carrying light along a longitudinal axis and including multiple optical windows, through which the carried light is out-coupled from the waveguide. The waveguide comprises a tapered region along which the optical windows are distributed, wherein each optical window out-couples a specific subset of propagating modes of the carried light, to which the optical window is matched.

In situ antigen-generating cancer vaccine
U.S. Patent 10,406,216 (September 10, 2019)

Jaeyun Kim, David J. Mooney, Weiwei Aileen Li, Praveen Arany, and Or Gadish

Abstract: The invention provides compositions and methods for utilizing scaffolds in cancer vaccines.

Apparatus, systems, and methods for modular soft robots
U.S. Patent 10,406,698 (September 10, 2019)

Stephen A. Morin, Sen Wai Kwok, Robert F. Shepherd, and George M. Whitesides

Abstract: Apparatus, systems, and methods for providing modular soft robots are disclosed. In particular, the disclosed modular soft robot can include a flexible actuator having a plurality of molded flexible units. Each molded flexible unit can include a mechanical connector configured to provide a physical coupling to another molded flexible unit, and the plurality of molded flexible units are arranged to form an embedded fluidic channel. The modular soft robot can also include an inlet coupled to the embedded fluidic channel, where the inlet is configured to receive pressurized or depressurized fluid to inflate or deflate a portion of the flexible actuator, thereby causing an actuation of the flexible actuator.

Protein surface remodeling
U.S. Patent 10,407,474 (September 10, 2019)

David R. Liu, Kevin John Phillips, and Michael S. Lawrence

Abstract: Aggregation is a major cause of the misbehavior of proteins. A system for modifying a protein to create a more stable variant is provided. The method involves identifying non-conserved hydrophobic amino acid residues on the surface of a protein, suitable for mutating to more hydrophilic residues (e.g., charged amino acids). Any number of residues on the surface may be changed to create a variant that is more soluble, resistant to aggregation, has a greater ability to re-fold, and/or is more stable under a variety of conditions. The invention also provides GFP, streptavidin, and GST variants with an increased theoretical net charge created by the inventive technology. Kits are also provided for carrying out such modifications on any protein of interest.

Systems and methods for improved performance of fluidic and microfluidic systems
U.S. Patent 10,407,655 (September 10, 2019)

Christopher David Hinojosa, Josiah Sliz, Daniel Levner, Guy Thompson, Hubert Geisler, Jose Fernandez-Alcon, and Donald E. Ingber

Abstract: Systems and methods for improved flow properties in fluidic and microfluidic systems are disclosed. The system includes a microfluidic device having a first microchannel, a fluid reservoir having a working fluid and a pressurized gas, a pump in communication with the fluid reservoir to maintain a desired pressure of the pressurized gas, and a fluid-resistance element located within a fluid path between the fluid reservoir and the first microchannel. The fluid-resistance element includes a first fluidic resistance that is substantially larger than a second fluidic resistance associated with the first microchannel.

Methods, compositions and kits for high throughput kinase activity screening using mass spectrometry and stable isotopes
U.S. Patent 10,407,712 (September 10, 2019)

Steven P. Gygi, Kazuishi Kubota, Judit Villen, and Yonghao Yu

Abstract: A mass-spectrometry-based method and substrates are provided herein for large scale kinome activity profiling directly from crude lysates using 90 chemically synthesized peptide substrates with amino acid sequences derived from known phosphoproteins. Quantification of peptide phosphorylation rates was achieved via the use of stable isotope labeled synthetic peptides. A method and substrates for obtaining 90 simultaneous activity measurements in a single-reaction format were developed and validated. The kinome activity profiling strategy was successfully applied with lysates of: cells manipulated by combination of mitogen stimulation, pharmacological perturbation and siRNA-directed kinase knockdown; seven different breast cancer cell lines treated with gefitinib; and each of normal and cancerous tissue samples from renal cell carcinoma patients. This method concurrently measures multiple peptide phosphorylation rates to provide a diagnostic fingerprint pattern for activated kinases, protein phosphatases, modulators of these enzymes, and pathways (kinome) from as little starting material as a few cells.

Achromatic metalens and metalens with reverse chromatic dispersion
U.S. Patent 10,408,416 (September 10, 2019)

Mohammadreza Khorasaninejad, Zhujun Shi, Alexander Y. Zhu, Wei Ting Chen, Vyshakh Sanjeev, and Federico Capasso

Abstract: An optical device includes a substrate, a reflective layer disposed over the substrate, and a metalens disposed over the reflective layer. The metalens includes a plurality of nanopillars, the plurality of nanopillars together specifying a phase profile such that the metalens has a focal length that is substantially constant over a wavelength range of an incident light of about 490 nm to about 550 nm.

Lighting device including a collimating metalens
U.S. Patent 10,408,419 (September 10, 2019)

Francesco Aieta and Federico Capasso

Abstract: Lighting devices including metalenses are disclosed. In some embodiments, the metalenses are in the form of a hybrid multi-region collimating metalens that includes a first region and a second region, wherein the hybrid multi-region collimating metalens is configured to collimate (e.g., visible) light incident thereon. In some instances the first region includes an array of first unit cells that contain sub-wavelength spaced nanostructures, such that the first region functions as a sub-wavelength high contrast grating (SWHCG), whereas the second region includes an array of second unit cell, wherein the array of second unit cells includes a near periodic annular arrangement of nanostructures such that the second region approximates the functionality of a locally periodic radial diffraction grating.

Sub-diffraction limit image resolution in three dimensions
U.S. Patent 10,412,366 (September 10, 2019)

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.

Embedding electronic structure in controllable quantum systems
U.S. Patent 10,417,574 (September 17, 2019)

Ryan Babbush, Peter Love, and Alan Aspuru-Guzik

Abstract: Generating a computing specification to be executed by a quantum processor includes: accepting a problem specification that corresponds to a second-quantized representation of a fermionic Hamiltonian, and transforming the fermionic Hamiltonian into a first qubit Hamiltonian including a first set of qubits that encode a fermionic state specified by occupancy of spin orbitals. An occupancy of any spin orbital is encoded in a number of qubits that is logarithmic in the number of spin orbitals, and a parity for a transition between any two spin orbitals is encoded in a number of qubits that is logarithmic in the number of spin orbitals. An eigenspectrum of a second qubit Hamiltonian, including the first set of qubits and a second set of qubit, includes a low-energy subspace and a high-energy subspace, and an eigenspectrum of the first qubit Hamiltonian is approximated by a set of low-energy eigenvalues of the low-energy subspace.

Stretchable conductive composites for use in soft devices
U.S. Patent 10,418,145 (September 17, 2019)

Joshua Aaron Lessing, Stephen A. Morin, and George M. Whitesides

Abstract: An elastically-deformable, conductive composite using elastomers and conductive fibers and simple fabrication procedures is provided. Conductive elastomeric composites offer low resistance to electrical current and are elastic over large (>25%) extensional strains. They can be easily interfaced/built into structures fabricated from elastomeric polymers.

Band-gap tunable elastic optical multilayer fibers
U.S. Patent 10,422,947 (September 24, 2019)

Joanna Aizenberg, Mathias Kolle, Peter Vukusic, and Robert D. Howe

Abstract: The rolled photonic fibers presents two codependent, technologically exploitable features for light and color manipulation: regularity on the nanoscale that is superposed with microscale cylindrical symmetry, resulting in wavelength selective scattering of light in a wide range of directions. The bio-inspired photonic fibers combine the spectral filtering capabilities and color brilliance of a planar Bragg stack compounded with a large angular scattering range introduced by the microscale curvature, which also decreases the strong directional chromaticity variation usually associated with flat multilayer reflectors. Transparent and elastic synthetic materials equip the multilayer interference fibers with high reflectance that is dynamically tuned by longitudinal mechanical strain. A two-fold elongation of the elastic fibers results in a shift of reflection peak center wavelength of over 200 nm.