Patents by Inventor David A. Weitz
David A. Weitz has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20210178395Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.Type: ApplicationFiled: February 24, 2021Publication date: June 17, 2021Inventors: Seth Fraden, Hakim Boukellal, Yanwei Jia, Seila Selimovic, Amy Rowat, Jeremy Agresti, David A. Weitz
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Publication number: 20210164971Abstract: The invention provides high-sensitivity methods for detection and quantification of target analytes in liquid samples (e.g., biological or environmental samples). The methods can be multiplexed to allow simultaneous detection and quantification of multiple target analytes that are contained in the same sample. The invention also provides related compositions and kits.Type: ApplicationFiled: August 15, 2019Publication date: June 3, 2021Inventors: David R. Walt, Limor Cohen, David A. Weitz, Nai Wen Cui, Yamei Cai
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Patent number: 11000849Abstract: The present invention is generally related to systems and methods for producing droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, at least one droplet is used to create a plurality of droplets, using techniques such as flow-focusing techniques. In one set of embodiments, a plurality of droplets, containing varying species, can be divided to form a collection of droplets containing the various species therein. A collection of droplets, according to certain embodiments, may contain various subpopulations of droplets that all contain the same species therein. Such a collection of droplets may be used as a library in some cases, or may be used for other purposes.Type: GrantFiled: October 23, 2017Date of Patent: May 11, 2021Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Adam R. Abate
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Patent number: 11001883Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: GrantFiled: September 5, 2014Date of Patent: May 11, 2021Assignees: The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Assaf Rotem, Oren Ram, Bradley E. Bernstein, David A. Weitz
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Patent number: 10960397Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.Type: GrantFiled: June 30, 2020Date of Patent: March 30, 2021Assignees: President and Fellows of Harvard College, Brandeis UniversityInventors: Seth Fraden, Hakim Boukellal, Yanwei Jia, Seila Selimovic, Amy Rowat, Jeremy Agresti, David A. Weitz
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Publication number: 20210086183Abstract: The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time-resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.Type: ApplicationFiled: October 1, 2020Publication date: March 25, 2021Applicant: President and Fellows of Harvard CollegeInventors: David A. Weitz, Christian Boehm, Amy Rowat, Sarah Koester, Jeremy Agresti
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Patent number: 10941430Abstract: The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer.Type: GrantFiled: January 31, 2020Date of Patent: March 9, 2021Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Jeremy Agresti, Liang-Yin Chu, Jin-Woong Kim, Amy Rowat, Morten Sommer, Gautam Dantas, George M. Church
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Patent number: 10919008Abstract: The present invention generally relates to systems and methods for the control of fluids and, in some cases, to systems and methods for flowing a fluid into and/or out of other fluids. As examples, fluid may be injected into a droplet contained within a fluidic channel, or a fluid may be injected into a fluidic channel to create a droplet. In some embodiments, electrodes may be used to apply an electric field to one or more fluidic channels, e.g., proximate an intersection of at least two fluidic channels. For instance, a first fluid may be urged into and/or out of a second fluid, facilitated by the electric field. The electric field, in some cases, may disrupt an interface between a first fluid and at least one other fluid. Properties such as the volume, flow rate, etc.Type: GrantFiled: July 25, 2017Date of Patent: February 16, 2021Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Adam R. Abate, Tony Hung, Pascaline Mary
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Patent number: 10876156Abstract: The present invention generally relates to microfluidics and, in particular, to systems and methods for determining cells using amplification. In one set of embodiments, cells are encapsulated within droplets and nucleic acids from the cells amplified within the droplets. The droplets may then be pooled together and the amplified nucleic acids can be determined using PCR or other suitable techniques. In some embodiments, techniques such as these can be used to detect relatively rare cells that may be present, e.g., if the droplets are amplified using conditions able to selectively amplify nucleic acids arising from the relatively rare cells.Type: GrantFiled: March 11, 2016Date of Patent: December 29, 2020Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Huidan Zhang
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Patent number: 10876688Abstract: The present invention generally relates to the production of fluidic droplets. Certain aspects of the invention are generally directed to systems and methods for creating droplets by flowing a fluid from a first channel to a second channel through a plurality of side channels. The fluid exiting the side channels into the second channel may form a plurality of droplets, and in some embodiments, at very high droplet production rates. In addition, in some aspects, double or higher-order multiple emulsions may also be formed. In some embodiments, this may be achieved by forming multiple emulsions through a direct, synchronized production method and/or through the formation of a single emulsion that is collected and re-injected into a second microfluidic device to form double emulsions.Type: GrantFiled: October 30, 2018Date of Patent: December 29, 2020Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Esther Amstad
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Patent number: 10874997Abstract: The present invention generally relates to emulsions, and more particularly, to multiple emulsions. In one aspect, multiple emulsions are formed by urging a fluid into a channel, e.g., by causing the fluid to enter the channel as a “jet.” Multiple fluids may flow through a channel collinearly before multiple emulsion droplets are formed. The fluidic channels may also, in certain embodiments, include varying degrees of hydrophilicity or hydrophobicity. In some cases, the average cross-sectional dimension may change, e.g., at an intersection. Unexpectedly, systems such as those described herein may be used to encapsulate fluids in single or multiple emulsions that are difficult or impossible to encapsulate using other techniques, such as fluids with low surface tension, viscous fluids, or viscoelastic fluids. Other aspects of the invention are generally directed to methods of making and using such systems, kits involving such systems, emulsions created using such systems, or the like.Type: GrantFiled: July 21, 2017Date of Patent: December 29, 2020Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Julian W. P. Thiele, Adam R. Abate
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Patent number: 10828641Abstract: The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time-resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.Type: GrantFiled: April 25, 2017Date of Patent: November 10, 2020Assignee: President and Fellows of Harvard CollegeInventors: Christian Boehm, Amy Rowat, Sarah Koester, Jeremy Agresti, David A. Weitz
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Publication number: 20200330993Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.Type: ApplicationFiled: June 30, 2020Publication date: October 22, 2020Inventors: Seth Fraden, Hakim Boukellal, Yanwei Jia, Seila Selimovic, Amy Rowat, Jeremy Agresti, David A. Weitz
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Publication number: 20200333334Abstract: 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.Type: ApplicationFiled: July 6, 2020Publication date: October 22, 2020Inventors: Andrew David Griffiths, David A. Weitz, Darren Roy Link, Keunho Ahn, Jerome Bibette
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Publication number: 20200316597Abstract: 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.Type: ApplicationFiled: June 17, 2020Publication date: October 8, 2020Inventors: Joseph Italiano, Linas Mazutis, Jonathan Thon, David A. Weitz
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Publication number: 20200306706Abstract: Parallel uses of microfluidic methods and devices for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid are described. In some aspects, the present invention relates generally to flow-focusing-type technology, and also to microfluidics, and more particularly parallel use of microfluidic systems arranged to control a dispersed phase within a dispersant, and the size, and size distribution, of a dispersed phase in a multi-phase fluid system, and systems for delivery of fluid components to multiple such devices.Type: ApplicationFiled: October 29, 2019Publication date: October 1, 2020Inventors: David A. Weitz, Mark Romanowsky, Adam R. Abate
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Publication number: 20200276578Abstract: 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.Type: ApplicationFiled: March 9, 2020Publication date: September 3, 2020Applicant: President and Fellows of Harvard CollegeInventors: David A. Weitz, Darren Roy Link, Galder Cristobal-Azkarate, Zhengdong Cheng, Keunho Ahn
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Publication number: 20200254400Abstract: The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; and (b) sorting the genetic elements which express the gene product having the desired activity; wherein at least one step is under microfluidic control. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.Type: ApplicationFiled: May 1, 2020Publication date: August 13, 2020Inventors: Andrew David Griffiths, David A. Weitz, Darren Roy Link, Keunho Ahn, Jerome Bibette
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Publication number: 20200255781Abstract: Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. 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, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.Type: ApplicationFiled: February 17, 2020Publication date: August 13, 2020Inventors: Jonathan N. Thon, Joseph E. Italiano, Linas Mazutis, David A. Weitz
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Patent number: 10738337Abstract: The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer.Type: GrantFiled: June 4, 2019Date of Patent: August 11, 2020Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Jeremy Agresti, Liang-Yin Chu, Jin-Woong Kim, Amy Rowat, Morten Sommer, Gautam Dantas, George M. Church