Harvard faculty Katia Bertoldi, David R. Liu, Jennifer Lewis, Robert Wood, Lene Hau, David Weitz, Yoshito Kishi, Andrew Myers, and Federico Capasso are among the inventors issued U.S. patents in April 2020.

The innovations recognized are as follows:

Negative poisson's ratio waffle structures
U.S. Patent 10,611,118 (April 7, 2020)

Katia Bertoldi, Matthew Christopher Innes, Farhad Javid, Minh Quan Pham, Megan Schaenzer, and Ali Shanian

Abstract: In at least some aspects, an auxetic structure includes a first sheet defining therein a plurality of a plurality of structural elements projecting from the first sheet, the plurality of structural elements being arranged to provide a negative Poisson's ratio, and a second sheet disposed adjacent the first sheet to define a first internal cavity between the first sheet and the second sheet. In yet other aspects, one or more additional sheets may be advantageously provided to provide a multi-layered structure having auxetic properties.

Evolution of TALENs
U.S. Patent 10,612,011 (April 7, 2020)

David R. Liu, Basil Hubbard, and Ahmed Hussein Badran

Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5' nucleotide of the target is specific for thymine (T). TALE domains with alternative 5' nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and/or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities. Some aspects of this disclosure provide engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with altered 5' nucleotide specificities of target sequences. Engineered TALEs that target ATM with greater specificity are also provided.

Printed stretchable strain sensor
U.S. Patent 10,612,986 (April 7, 2020)

Jennifer A. Lewis, Joseph T. Muth, Daniel M. Vogt, Ryan L. Truby, Yigit Menguc, David B. Kolesky, and Robert J. Wood

Abstract: A printed stretchable strain sensor comprises a seamless elastomeric body and a strain-sensitive conductive structure embedded in the seamless elastomeric body. The strain-sensitive conductive structure comprises one or more conductive filaments arranged in a continuous pattern. A method of printing a stretchable strain sensor comprises depositing one or more conductive filaments in a predetermined continuous pattern into or onto a support matrix. After the depositing, the support matrix is cured to embed a strain-sensitive conductive structure in a seamless elastomeric body.

Insole design and actuator placement for balance and gait
U.S. Patent 10,617,597 (April 14, 2020)

Arun Chawan, Hani Sallum, Robert Wood, James Niemi, and James J. Collins

Abstract: A wearable system is directed to neurological stimulation of a human foot, and includes a controller with at least one bias signal generator for outputting a driving signal. The system further includes a power source that provides electrical energy to the controller, including providing electrical energy to the bias signal generator. The system also includes a platform in the form of an insole insert of a shoe, the insole insert having a plurality of actuators positioned in a medial arch region of the foot. The plurality of actuators stimulate the medial arch region in response to receiving the driving signal from the controller. The stimulation of the plurality of actuators provides a subthreshold bias signal to target cells with a subthreshold bias signal magnitude that is below a threshold where the target cells are activated by a stimulus. The plurality of actuators is surrounded with a vibration dissipating material.

Photocatalytic systems comprising graphene and associated methods
U.S. Patent 10,625,250 (April 21, 2020)

Lene Vestergaard Hau

Abstract: The present invention generally relates to photocatalytic systems comprising graphene and associated methods. Some embodiments are directed to systems comprising one or more layers of graphene having a first surface and a second, opposed surface. A light-absorbing complex may be associated with the first surface of the one or more graphene layers, and an electron donor complex may be associated with the light-absorbing complex. A catalytic complex may be associated with the first surface or the second surface of the one or more graphene layers. For example, the catalytic complex may catalyze the formation of hydrogen gas, NADH, and/or NADPH.

Electronic control of fluidic species
U.S. Patent 10,625,256 (April 21, 2020)

David A. Weitz, Darren Roy Link, Galder Cristobal-Azkarate, Zhengdong Cheng, and Keunho Ahn

Abstract: Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In some cases, the droplets may each have a substantially uniform number of entities therein. For example, 95% or more of the droplets may each contain the same number of entities of a particular species. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets according to another aspect of the invention, for example, through charge and/or dipole interactions. In some cases, the fusion of the droplets may initiate or determine a reaction. In a related aspect of the invention, systems and methods for allowing fluid mixing within droplets to occur are also provided. In still another aspect, the invention relates to systems and methods for sorting droplets, e.g., by causing droplets to move to certain regions within a fluidic system. Examples include using electrical interactions (e.g., charges, dipoles, etc.) or mechanical systems (e.g., fluid displacement) to sort the droplets. In some cases, the fluidic droplets can be sorted at relatively high rates, e.g., at about 10 droplets per second or more. Another aspect of the invention provides the ability to determine droplets, or a component thereof, for example, using fluorescence and/or other optical techniques (e.g., microscopy), or electric sensing techniques such as dielectric sensing.

Early developmental genomic assay for characterizing pluripotent stem cell utility and safety
U.S. Patent 10,626,445 (April 21, 2020)

Alexander Meissner, Alexander Tsankov, and Veronika Akopian

Abstract: The present invention generally relates to a set of early developmental reference data or "lineage scorecard" for stem cells, and methods, systems and kits to generate a lineage scorecard for predicting the functionality and suitability of stem cell lines. In some aspects, methods for generating a scorecard comprises measuring the gene expression of a plurality of early developmental genes, such as pluripotent, early ectoderm, early mesoderm and early endoderm genes to predict the pluripotency and differentiation potential of the stem cell line and its functionality and/or suitability for a desired use. In some embodiments, a reference scorecard can be compared with the test stem cell line scorecard to accurately predict the utility and/or identify specific characteristics of the stem cell line, e.g., to determine its suitability for downstream applications, e.g., therapeutic use, drug screening, toxicity assays, differentiation into a desired cell lineage, etc.

Chromium-mediated coupling and application to the synthesis of halichondrins
U.S. Patent 10,633,392 (April 28, 2020)

Yoshito Kishi, Wuming Yan, Jingwei Li, Zhanjie Li, and Kenzo Yahata

Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

14-membered ketolides and methods of their preparation and use
U.S. Patent 10,633,407 (April 28, 2020)

Andrew G. Myers, Ian Bass Seiple, and Ziyang Zhang

Abstract: Provided herein are methods of preparing new 14-membered ketolides via coupling of an eastern and western half moiety, followed by macro-cyclization, and optional functionalization. Intermediates in the synthesis of these ketolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using these ketolides are also provided.

Systems and methods for nucleic acid sequencing
U.S. Patent 10,633,701 (April 28, 2020)

David A. Weitz, Jeremy Agresti, Michael P. Weiner, Adam R. Abate, and Tony Hung

Abstract: The present invention relates to systems and methods for sequencing nucleic acids, including sequencing nucleic acids in fluidic droplets. In one set of embodiments, the method employs sequencing by hybridization using droplets such as microfluidic droplets. In some embodiments, droplets are formed which include a target nucleic acid, a nucleic acid probe, and at least one identification element, such as a fluorescent particle. The nucleic acid probes that hybridize to the target nucleic acid are determined, in some instances, by determining the at least one identification element. The nucleic acid probes that hybridize to the target nucleic acid may be used to determine the sequence of the target nucleic acid. In certain instances, the microfluidic droplets are provided with reagents that modify the nucleic acid probe. In some cases, a droplet, such as those described above, is deformed such that the components of the droplets individually pass a target area.

Super-dispersive off-axis meta-lenses for high resolution compact spectroscopy
U.S. Patent 10,634,557 (April 28, 2020)

Mohammadreza Khorasaninejad, Federico Capasso, Wei Ting Chen, and Jaewon Oh

Abstract: A meta-lens having a phase profile includes a substrate and a plurality of nanostructures disposed on the substrate. The nanostructures together define the phase profile of the meta-lens. The phase profile achieves an off-axis focus. Each nanostructure is designed according to at least one design parameter of the nanostructure that imparts a phase shift of light passing through the nanostructure.