A method includes flowing a first fluid through a first channel of a microfluidic apparatus and flowing a second fluid through a second channel of the microfluidic apparatus. The first fluid comprises biological material and a matrix material and is immiscible with the second fluid. The first and second fluids are combined at a junction to form droplets of the first fluid dispersed in the second fluid in a third channel. Multiple exposures of a droplet in the third channel are captured in a single image, comprising: illuminating a region of the third channel with multiple successive illumination pulses during a single frame of the imaging device; identifying the droplet and determining a velocity or a size of the droplet based on an analysis of the captured exposures; and controlling the flow of the first fluid or second fluid to obtain droplets of a target size or velocity.
A microfluidic apparatus includes a microfluidic chip for MicroOrganoSpheres (MOS) generation. A first channel is defined in a surface of the microfluidic chip and includes: a droplet generation portion including an inlet portion, a junction between the inlet portion and an emulsifying fluid channel, and a chamber downstream of the junction. A cross-sectional area of the chamber is larger than that of the inlet portion. The first channel includes a polymerization portion downstream of the droplet generation portion, the polymerization portion having a serpentine configuration. The apparatus includes a cartridge for MOS demulsification, including: a collection container; a substrate disposed on the collection container, and a membrane disposed between the collection container and the surface of the substrate. A second channel is defined in the surface of the substrate that faces the collection container and is fluidically connected to an output of the polymerization portion of the first channel.
A microfluidic apparatus includes a microfluidic chip for MicroOrganoSpheres (MOS) generation. A first channel is defined in a surface of the microfluidic chip and includes: a droplet generation portion including an inlet portion, a junction between the inlet portion and an emulsifying fluid channel, and a chamber downstream of the junction. A cross-sectional area of the chamber is larger than that of the inlet portion. The first channel includes a polymerization portion downstream of the droplet generation portion, the polymerization portion having a serpentine configuration. The apparatus includes a cartridge for MOS demulsification, including: a collection container; a substrate disposed on the collection container, and a membrane disposed between the collection container and the surface of the substrate. A second channel is defined in the surface of the substrate that faces the collection container and is fluidically connected to an output of the polymerization portion of the first channel.
A system includes a device configured to facilitate an interaction between a first fluid flow and a second fluid flow within a flow path of the device; an optical sensor configured to obtain one or more images representing the flow path; an image analysis module configured to: process the images to identify at least one droplet generated in a flow path of the device by the interaction between the first fluid flow and the second fluid flow, and estimate a size of the at least one droplet; and a control system configured to: determine that the size of the at least one droplet satisfies a threshold condition, and responsive to determining that the size of the at least one droplet satisfies the threshold condition, generate a signal that causes an adjustment to a flow rate of at least one of the first fluid flow or the second fluid flow.
The present disclosure relates to a method for testing immuno-oncology drugs and biologics using microorganospheres (MOSs). The method comprises forming a plurality of MOSs from cancerous tumor biopsy tissue with such forming comprising dissociating cells from the cancerous tumor biopsy tissue and combining the dissociated cells with a fluid matrix material. The dissociating itself comprises an enzyme digestion protocol, mincing the cancerous tumor biopsy tissue, and incubating the cancerous tumor biopsy tissue in a digestion solution with agitation. The method also comprises testing at least one immuno-oncology drug or biologic using the plurality of MOSs within 10 days after forming the plurality of MOSs.
A microfluidic apparatus includes a microfluidic chip for MicroOrganoSpheres (MOS) generation. A first channel is defined in a surface of the microfluidic chip and includes: a droplet generation portion including an inlet portion, a junction between the inlet portion and an emulsifying fluid channel, and a chamber downstream of the junction. A cross-sectional area of the chamber is larger than that of the inlet portion. The first channel includes a polymerization portion downstream of the droplet generation portion, the polymerization portion having a serpentine configuration. The apparatus includes a cartridge for MOS demulsification, including: a collection container; a substrate disposed on the collection container, and a membrane disposed between the collection container and the surface of the substrate. A second channel is defined in the surface of the substrate that faces the collection container and is fluidically connected to an output of the polymerization portion of the first channel.
Methods and materials for labeling and annotating live cells in MicroOrganoSpheres (MOS), and methods for assessing MOS containing labeled live cells, are provided herein. The methods being applied for use in detecting treatments for diseases, particularly cancer, in mammals.
A method includes flowing a first fluid through a first channel of a microfluidic apparatus and flowing a second fluid through a second channel of the microfluidic apparatus. The first fluid comprises biological material and a matrix material and is immiscible with the second fluid. The first and second fluids are combined at a junction to form droplets of the first fluid dispersed in the second fluid in a third channel. Multiple exposures of a droplet in the third channel are captured in a single image, comprising: illuminating a region of the third channel with multiple successive illumination pulses during a single frame of the imaging device; identifying the droplet and determining a velocity or a size of the droplet based on an analysis of the captured exposures; and controlling the flow of the first fluid or second fluid to obtain droplets of a target size or velocity.
Methods, systems, and apparatus for an imaging-based MicroOrganoSphere drug assay. In one aspect, a method includes obtaining image data of a well plate comprising a plurality of MicroOrganoSpheres; in response to applying a machine learning model configured to identify instances of at least some of the plurality of MicroOrganoSpheres in the image data, obtaining (i) indications indicative of each instance of the MicroOrganoSpheres and (ii) attributes of each instance of the MicroOrganoSpheres; and normalizing, based on the indications and the attributes, a well-to-well variation in the well plate.
A microfluidic apparatus includes a microfluidic chip for MicroOrganoSpheres (MOS) generation. A first channel is defined in a surface of the microfluidic chip and includes: a droplet generation portion including an inlet portion, a junction between the inlet portion and an emulsifying fluid channel, and a chamber downstream of the junction. A cross-sectional area of the chamber is larger than that of the inlet portion. The first channel includes a polymerization portion downstream of the droplet generation portion, the polymerization portion having a serpentine configuration. The apparatus includes a cartridge for MOS demulsification, including: a collection container; a substrate disposed on the collection container, and a membrane disposed between the collection container and the surface of the substrate. A second channel is defined in the surface of the substrate that faces the collection container and is fluidically connected to an output of the polymerization portion of the first channel.
A microfluidic apparatus includes a microfluidic chip for MicroOrganoSpheres (MOS) generation. A first channel is defined in a surface of the microfluidic chip and includes: a droplet generation portion including an inlet portion, a junction between the inlet portion and an emulsifying fluid channel, and a chamber downstream of the junction. A cross-sectional area of the chamber is larger than that of the inlet portion. The first channel includes a polymerization portion downstream of the droplet generation portion, the polymerization portion having a serpentine configuration. The apparatus includes a cartridge for MOS demulsification, including: a collection container; a substrate disposed on the collection container, and a membrane disposed between the collection container and the surface of the substrate. A second channel is defined in the surface of the substrate that faces the collection container and is fluidically connected to an output of the polymerization portion of the first channel.
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or propertiesManufacturing processes specially adapted therefor characterised by their properties
A method includes flowing a first fluid through a first channel of a microfluidic apparatus and flowing a second fluid through a second channel of the microfluidic apparatus. The first fluid comprises biological material and a matrix material and is immiscible with the second fluid. The first and second fluids are combined at a junction to form droplets of the first fluid dispersed in the second fluid in a third channel. Multiple exposures of a droplet in the third channel are captured in a single image, comprising: illuminating a region of the third channel with multiple successive illumination pulses during a single frame of the imaging device; identifying the droplet and determining a velocity or a size of the droplet based on an analysis of the captured exposures; and controlling the flow of the first fluid or second fluid to obtain droplets of a target size or velocity.
A system includes a device configured to facilitate an interaction between a first fluid flow and a second fluid flow within a flow path of the device; an optical sensor configured to obtain one or more images representing the flow path; an image analysis module configured to: process the images to identify at least one droplet generated in a flow path of the device by the interaction between the first fluid flow and the second fluid flow, and estimate a size of the at least one droplet; and a control system configured to: determine that the size of the at least one droplet satisfies a threshold condition, and responsive to determining that the size of the at least one droplet satisfies the threshold condition, generate a signal that causes an adjustment to a flow rate of at least one of the first fluid flow or the second fluid flow.
MicroOrganoSpheres (MOS) generated using cells from multiple myeloma bone marrow biopsies are provided herein, as are methods and materials for making and using such MOS.
Methods, systems, and apparatus for an imaging-based MicroOrganoSphere drug assay. In one aspect, a method includes obtaining image data of a well plate comprising a plurality of MicroOrganoSpheres; in response to applying a machine learning model configured to identify instances of at least some of the plurality of MicroOrganoSpheres in the image data, obtaining (i) indications indicative of each instance of the MicroOrganoSpheres and (ii) attributes of each instance of the MicroOrganoSpheres; and normalizing, based on the indications and the attributes, a well-to-well variation in the well plate.
Methods, systems, and apparatus for an imaging-based micro-organosphere drug assay. In one aspect, a method includes obtaining image data of a well plate comprising a plurality of micro-organospheres; in response to applying a machine learning model configured to identify instances of at least some of the plurality of micro-organospheres in the image data, obtaining (i) indications indicative of each instance of the micro-organospheres and (ii) attributes of each instance of the micro-organospheres; and normalizing, based on the indications and the attributes, a well-to-well variation in the well plate.
Systems and methods consistent with the present disclosure relate to MicroOrganoSpheres (MOSs). More particularly, methods relate to delivering components into a MOS. The methods also relate to delivering components into a MOS for screening drugs and biologics.
Disclosed herein are systems, apparatuses, and methods for forming micro-organospheres. In some variations, a system may comprise a micro-organosphere generator configured to form a set of micro-organospheres from a mixture of a biological sample and a fluid. A controller may be coupled to an imaging device. The controller may be configured to receive the imaging data corresponding to one or more of the mixture or the set of micro-organospheres, and estimate one or more characteristics of the set of micro-organospheres based at least on the imaging data.
Methods and materials for generating and using patient-derived MicroOrganoSpheres (e.g., MicroOrganoSpheres derived from tumor tissue) are provided herein.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
25.
METHODS AND APPARATUSES FOR TESTING HEPATOCYTE TOXICITY USING MICROORGANOSPHERES
Systems and methods consistent with the present invention generally relate to microorganospheres (MOSs), and methods and apparatuses for forming and using MOSs. More particularly, in some embodiments, systems and methods consistent with the invention relate to the methods and apparatuses for forming and using MOSs generated from hepatocytes. MOSs that are generated from hepatocytes are suitable for testing liver toxicity and drug induced liver injury effects of various agents.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
The present disclosure describes, in part, a Micro-organosphere immune-oncology assay and methods of making and using same. The assay quickly measures the potency of effector immune cells, such as tumor infiltrating lymphocytes, at killing a patient's tumor cells. Understanding the potency of effector immune cells is critical for adoptive T cell therapy.
The present disclosure relates to a method for testing immuno-oncology drugs and biologics using microorganospheres (MOSs). The method comprises forming a plurality of MOSs from cancerous tumor biopsy tissue with such forming comprising dissociating cells from the cancerous tumor biopsy tissue and combining the dissociated cells with a fluid matrix material. The dissociating itself comprises an enzyme digestion protocol, mincing the cancerous tumor biopsy tissue, and incubating the cancerous tumor biopsy tissue in a digestion solution with agitation. The method also comprises testing at least one immuno-oncology drug or biologic using the plurality of MOSs within 10 days after forming the plurality of MOSs.
Micro-Organosphers, including Patient-Derived Micro-Organospheres (PMOSs), apparatuses and methods of making them, and apparatuses and methods of using them. Also described herein are methods and systems for screening a patient using these Patient-Derived Micro-Organospheres, including personalized therapies.
Micro-Organospheres, including Patient-Derived Micro-Organospheres (PMOSs), apparatuses and methods of making them, and apparatuses and methods of using them. Also described herein are methods and systems for screening a patient using these Patient-Derived Micro-Organospheres, including personalized therapies.
Precision drug screening methods and apparatuses for personalized cancer therapies include the formation of a library of mature Micro-Organospheres, including Patient-Derived Micro-Organospheres (PMOSs), from a single patient tissue sample, such as from a tumor sample, are described. Also described herein are methods and systems for screening a patient using these Patient-Derived Micro-Organospheres, including personalized therapies.
Disclosed herein are systems, apparatuses, and methods for forming micro-organospheres. In some variations, a system may comprise a micro-organosphere generator configured to form a set of micro-organospheres from a mixture of a biological sample and a fluid. A controller may be coupled to an imaging device. The controller may be configured to receive the imaging data corresponding to one or more of the mixture or the set of micro-organospheres, and estimate one or more characteristics of the set of micro-organospheres based at least on the imaging data.
The present disclosure describes, in part, a Micro-organosphere immune-oncology assay and methods of making and using same. The assay quickly measures the potency of effector immune cells, such as tumor infiltrating lymphocytes, at killing a patient's tumor cells. Understanding the potency of effector immune cells is critical for adoptive T cell therapy.
Disclosed herein are systems, apparatuses, and methods for forming micro-organospheres. In some variations, a system may comprise a micro-organosphere generator configured to form a set of micro-organospheres from a mixture of a biological sample and a fluid. A controller may be coupled to an imaging device. The controller may be configured to receive the imaging data corresponding to one or more of the mixture or the set of micro-organospheres, and estimate one or more characteristics of the set of micro-organospheres based at least on the imaging data.
The present disclosure describes, in part, a Micro-organosphere immune-oncology assay and methods of making and using same. The assay quickly measures the potency of effector immune cells, such as tumor infiltrating lymphocytes, at killing a patient's tumor cells. Understanding the potency of effector immune cells is critical for adoptive T cell therapy.
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