Massachusetts Institute of Technology

The General Hospital Corporation

Patrick Seamus Doyle

Daniel Colin Pregibon

Albert Joseph Swiston

Dhananjay Dendukuri

Jiseok Lee

Paul Bisso

Mehmet Toner

Trevor Alan Hatton

Ramin Haghgooie

Edwin Lorimer Thomas

Bernhardt Levy Trout

Allan Stuart Myerson

Rathi Lakshmi Srinivas

Matthew E Helgeson

Liang-Hsun Chen

Paul Douglas Godfrin

Stephen C Chapin

Greg Randall

Chaitanya K Ullal

Ji-Hyun Jang

Ying Diao

Ki Wan Bong

Compositions contain nanoparticles containing nanocrystals of hydrophobic therapeutic, diagnostic, prophylactic agents, or a combination thereof, encapsulated in thermogelling polymers, such as methyl cellulose. Because of the templating of the compositions on a thermogelling nanoemulsion system, the compositions can be formed with precise control of the sizes of the nanoparticles as well as the high loadings of these hydrophobic therapeutic, diagnostic, prophylactic agents, or a combination thereof. Also described are methods of making and using the compositions.

Thermogelling nanoemulsions for pharmaceutical manufacturing

Embodiments described herein relate to hydrogels, and in particular, hydrogels for crystal formation, and related compositions and methods.

Hydrogels and related compositions and methods

Polymer microparticles spatially and spectrally encoded using upconversion nanocrystals (UCN) are described for labeling of articles and tissues. UCN having spectrally distinguishable emission spectra are disposed in different portions of an encoding region of each microparticle.

Rare earth spatial/spectral microparticle barcodes for labeling of objects and tissues

Techniques for hydrogel microstructures with oil isolation for small reaction volumes include providing a hydrogel microstructure that has a plurality of pores and a hydrogel frame surrounding the pores. The microstructure has a volume in a range from about 1 picoliter to about 10,000 picoliters and is configured to repel an immiscible fluid. Each pore of the plurality of pores has a pore size configured to pass the target molecule in a first solution. The microstructure is contacted with the first solution, and with a second solution that includes a reactant molecule that reacts with the target molecule to produce an observable product molecule. The microstructure is encompassed with the immiscible fluid for an extended observation duration from about 1 to about 10,000 seconds, wherein the immiscible fluid does not pass into the pores but traps the product in the microstructure. The observable product molecule is measured at some time during the observation duration.

Hydrogel microstructures with immiscible fluid isolation for small reaction volumes

In a method for synthesizing polymeric microstructures, a monomer stream is flowed, at a selected flow rate, through a fluidic channel. At least one shaped pulse of illumination is projected to the monomer stream, defining in the monomer stream a shape of at least one microstructure corresponding to the illumination pulse shape while polymerizing that microstructure shape in the monomer stream by the illumination pulse. An article of manufacture includes a non-spheroidal polymeric microstructure that has a plurality of distinct material regions.

Microstructure synthesis by flow lithography and polymerization

Hydrogel microparticles spatially and spectrally encoded using upconverting phosphor nanoparticles are described for use in biochemical testing. In each microparticle, upconversion nanocrystals having spectrally distinguishable emission spectra are disposed in different pardons of an encoding region of the microparticle.

Rare earth spatial/spectral barcodes for multiplexed biochemical testing

Techniques are provided to independently control 3D shape and chemistry of rapidly produced colloids. A pre-polymer mixture including a monomer is made to flow into a channel with insular relief in a wall at a known location of the channel. A stimulus that polymerizes the pre-polymer mixture is directed onto the known location to form a structure locked in place at the known location by the insular relief. A pressure is applied to the channel that is sufficient to deflect the wall having the insular relief sufficiently to release a hydrogel particle comprising the structure.

Lock-release polymerization

Method for making multifunctional particles. The method includes flowing a first monomer stream loaded with a fluorescent entity along a microfluidic channel and flowing a second monomer stream loaded with a probe adjacent to the first monomer stream along the microfluidic channel. The monomer streams are polymerized to synthesize particles having a fluorescent, graphically encoded region and a probe-loaded region.

Multifunctional encoded particles for high-throughput analysis

The present invention generally relates to compositions, methods, and systems relating to controlled crystallization and/or nucleation of a molecular species. In some embodiments, the crystallization and/or nucleation of the molecular species may be controlled by tuning the surface chemistry and/or the morphology of a crystallization substrate. In some embodiments, the molecular species is a small organic molecule (e.g., pharmaceutically active agent).

Compositions, methods, and systems relating to controlled crystallization and/or nucleation of molecular species

Techniques are provided to produce and use non-spherical colloidal particles with independently tuned size, shape, flexibility, and chemical properties. A pre-polymer mixture for forming hydrogel particles includes a percentage of PEGDA selected to impart a target stiffness to the particles and includes, a percentage of acrylic acid selected to impart an independent target chemical function to the particles. The mixture also includes a percentage of photo-initiator to polymerize PEGDA upon exposure to a light source to impart an independently selected target size or shape or both to the particles.

Tunable hydrogel microparticles

Stop flow interference lithography system for high throughput synthesis of 3-dimensionally patterned polymer particles. The system includes a microfluidic channel containing a stationary oligomer film and a phase mask located adjacent to the microfluidic channel. A source of collimated light is provided for passing the collimated light through the phase mask and into the microfluidic channel for interaction with the oligomer. The passage of the collimated light through the phase mask generates a 3-dimensional distribution of light intensity to induce crosslinking of the oligomer in high intensity regions thereby forming 3-dimensional structures.

Stop flow interference lithography system

Apparatus and methods are described for achieving uniform stretching of polynucleotides in hybrid electrophoretic-gel, micro-constricting microfluidic channels. Polynucleotides in normally relaxed configurations are driven by an electric field along a microfluidic channel. The polynucleotides thread through a porous gel barrier formed in the channel and extend into a constriction where an electric field gradient exists. The combined action of the gel and field gradient acts to extend the polynucleotide configuration fully for direct linear analysis of the molecule.

System and methods for stretching polynucleotides

Techniques are provided for high precision scanning of hydrogel microparticles. The high precision is achieved by one or more modifications to the microparticle composition, or microfluidics apparatus that align the microparticles in a detection channel, or method of preparing a sample for introduction into the apparatus, or some combination. An apparatus comprises a body structure having formed therein a central channel and multiple focusing channels in fluid communication with the central channel through multiple junctions. A width of the central channel is smaller in a portion downstream of each junction. A particle comprises a hydrogel matrix and a probe molecule. The particle has an aspect ratio greater than about three. A method includes loading into a sample fluid inlet a mixture, wherein a number of particles lies within a range from about 15 to about 20 particles/&#x3bc;l.

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Boston, MA, United States of America

Patrick Seamus Doyle