Other

University of Toronto

Harvard College

Xerox Corporation

Kumacheva, Eugenia

Eugenia Kumacheva

Olga V Kalinina

George M Whitesides

Darren Roy Link

David A Weitz

Jaan Noolandi

Howard A Stone

Irina Gitlin

Willow Ruth Diluzio

Shelley L Anna

Nathalie Bontoux

Piotr Garstecki

Edward Hartley Sargent

James Harry Sharp

Hung H Pham

Bradley Siwick

Robert John Dwayne Miller

Elisabeth Prince

Mathieu Allard

Robert Kori Golding

Ilya Gourevich

Hong Zhang

Patrick Cameron Lewis

Min Seok Seo

Zhihong Nie

Shengqing Xu

Shelly L Anna

The present disclosure provides a method of producing uniformly sized organoids/multicellular spheroids using a microfluidic device having an array of microwells. The method involves several successive steps. First, a microfluidic device containing parallel rows of microwells that are connected with a supplying channel is filled with a wetting agent. The wetting agent is a liquid that is immiscible in water. For example, the wetting agent may be an organic liquid such as oil. In the next step, the agent in the supplying channel and the microwells is replaced with a suspension of cells in an aqueous solution that contains a precursor for a hydrogel. Next, the aqueous phase in the supplying channel is replaced with the agent, which leads to the formation of an array of droplets of cell suspension in the hydrogel precursor solution, which were compartmentalized in the wells. The droplets are then transformed into cell-laden hydrogels. Subsequently, the agent in the supplying channel is replaced with the cell culture medium continuously flowing through the microfluidic device and the cells within the hydrogels are transformed into multicellular spheroids.

Microfluidic platform for the rapid production of organoids/spheroids for compound screening

A microfluidic method and device for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid is provided. The device can be fabricated simply from readily-available, inexpensive material using simple techniques.

Method and apparatus for fluid dispersion

The present invention provides a method and apparatus for producing polymeric particles with pre-designed size, shape, morphology and composition, and more particularly the present invention uses a microfluidic polymerization reactor for producing same. The present invention disclosed herein provides a process for producing polymer particles with pre-selected shapes. The method includes injecting a first fluid comprising a polymerizable constituent with a controlled flow rate into a microfluidic channel and injecting a second fluid with a controlled flow rate into the microfluidic channel in which the second fluid mixes with the first fluid, the second fluid being immiscible with the first fluid so that the first fluid forms into droplets in the microfluidic channel. The microfluidic channel has pre-selected dimensions to give droplets of pre-selected size, morphology and shape. The microfluidic channel is sufficiently long so that the droplets have a sufficiently long residence time in the channel so that they polymerize or otherwise harden into droplets of pre-selected size and shape.

Method of producing polymeric particles with selected size, shape, morphology and composition

This present invention provides devices for the parallelization of the formation of droplets in a multiple droplet generator integrating two or more parallel flow-focusing devices (FFDs) with either identical, or different, geometries. In the parallel identical FFDs, emulsification generates droplets with a narrow (below 4%) polydispersity despite weak coupling between the identical flow-focusing devices. Formation of droplets in the integrated droplet generator comprising FFDs with different dimensions of the microchannels occurs with strong coupling between the FFDs and produces droplets with varying sizes and size distributions. For such devices the regime in which emulsification produces droplets with varying dimensions and a narrow size distribution have been identified. The results of this work can be used in scaling up the production of droplets and in the simultaneous production of droplets and particles with different dimensions.

Multiple continuous microfluidic reactors for the scaled up synthesis of gel or polymer particles

Hybrid composite materials with multiscale morphologies are formed by doping polymer submicrometer spheres with semiconductor or metal (e.g. CdS or Ag, respectively) nanoparticles and using these doped microspheres as functional building blocks in production of hybrid periodically structured materials. The preparation of hybrid polymer particles include the following stages: (i) synthesis of monodisperse polymer microspheres, (ii) in-situ synthesis of the inorganic nanoparticles either on the surface, or in the bulk with polymer beads, and (iii) encapsulation of hybrid microspheres with a hydrophobic shell.

Method of producing hybrid polymer-inorganic materials

The present invention describes a new approach to producing hybrid composite materials with multiscale morphologies. We doped polymer submicrometer spheres with semiconductor or metal (e.g. CdS or Ag, respectively) nanoparticles and used these doped microspheres as the functional building blocks in production of hybrid periodically structured materials. The preparation of hybrid polymer particles included the following stages: (i) synthesis of monodisperse polymer microspheres, (ii) in-situ synthesis of the inorganic nanoparticles either on the surface, or in the bulk of the polymer beads, and (iii) encapsulation of hybrid microspheres with a hydrophobic shell. We demonstrated that by changing the composition of the polymer beads good control could be achieved over the size of the nanoparticles.

Polymeric-based nanocomposites with different structures using core-shell particles. The present invention provides a method for producing polymer-based core-shell nanocomposite structures. The nanocomposite materials may be produced with voids in them which may be partially or completely filled with other materials. The core and shell materials may be formed from multicomponent materials, in the case of the cores these may be for example multiple oxides, semiconductors and in the case of the polymer shell material multiple polymers in blends or copolymers.

Polymer-based nanocomposite materials and methods of production thereof

An optical data storage device comprised of periodic nanostructured polymer-based material produced from core-shell particles containing one dye in the core and a second dye in the shell. The combinations of dyes can be UV-Vis-dyes or Vis-NIR or UV-NIR. It is shown that selective single-photon photobleaching of the two dyes leads to increase in density of data storage and allows one to employ single-photon photobleaching to achieve the same storage density as in two-photon-writing.

Multicolored polymer nanocomposites for optical memory storage and security data encryption

Method of synthesis of confined colloidal crystals using electrodeposition. The present invention provides a method of growing confined colloidal crystal structures using electrodeposition of monodispersed charged colloid spheres onto a substrate patterned with an array of electroconductive surface relief features on a surface of a substrate. In this approach, control over large-scale ordering is achieved via a planar pattern whose scale is on the order of tens of microns, a regime readily accessed through coarse lithography, laser micromachining, and holography.

Method of colloid crystal growth on patterned surfaces

A nanocomposite material having a plurality of core particles formed of a core material. The core material has a first glass transition temperature. A shell encapsulates each core particle. The shell is formed of a shell material that has a second glass transition temperature less than the first glass transition temperature. When subjected to a temperature greater than the second glass transition temperature and less than the first glass transition temperature, the shells form a continuous matrix surrounding the core particles. The shell material includes a functional component that can be activated in response to an external excitation. This functional component can include either photosensitive, semiconductor, magnetic, piezoelectric or electro-active components just to mention a few. The different components may be chemically or physically bound to the shell or cores. These nanocomposite materials are used as storage media.

Polymeric nanocomposite materials with a functional matrix and method of reading and writing thereto

A method for providing three dimensional optical memory storage for computers. The method comprises subjecting a nanocomposite to irradiation. The nanocomposite comprises a matrix of particles of a liquid core resin within an inner shell resin and an outer shell resin. The inner shell resin retains the liquid core resin while the outer shell resin forms a continuous phase of the matrix. The particles of core resin contain at least one photosensitive compound and are in an array in the matrix. The continuous phase is substantially free of photosensitive compound. The irradiation may be a single beam of irradiation selectively focused on individual particles in the array to effect photobleaching of individual particles or a two-photon irradiation of a wavelength to effect photobleaching.

Three dimensional optical memory storage

A method of producing three dimensional ordered arrays of particles. The method may be used for the preparation of nanocomposite materials with highly periodic structures. More particularly the invention provides a method of producing three dimensional arrays based on applying a controlled oscillatory motion to settling dispersions of colloid particles. The controlled oscillatory motion is characterized by G&equals;A&ohgr;,/g, wherein g is the gravitational constant, A is the displacement and &ohgr; is angular frequency. G is maintained in the desired range by varying values of A within an effective range of displacements and &ugr; within an effective range of frequencies.

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Toronto, Canada

Eugenia Kumacheva