A microfluidic chip having a micro channel for processing a sample is provided. The micro channel may focus the sample by using focusing fluid and a core stream forming geometry. The core stream forming geometry may include a lateral fluid focusing component and one or more vertical fluid focusing components. A microfluidic chip may include a plurality micro channels operating in parallel on a microfluidic chip.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
F16K 99/00 - Subject matter not provided for in other groups of this subclass
F17D 1/08 - Pipe-line systems for liquids or viscous products
F17D 5/00 - Protection or supervision of installations
G01N 15/1404 - Handling flow, e.g. hydrodynamic focusing
G01N 15/1409 - Handling samples, e.g. injecting samples
2.
METHOD AND APPARATUS FOR AN ANTI-SORTING FLOW CYTOMETER
A method, system and apparatus for anti-sorting particles is disclosed. In an example embodiment, particles move in a fluid along a microfluidic channel. A measurement device determines which particles are selected or desired particles by measuring a desired characteristic of the particles and outputting an associated signal. The energy source continuously imparts a force on unselected or undesired particles in a deflection region of the microfluidic channel to remove the unselected or undesired particles from the stream of particles. Based upon the signal outputted by the measurement device, the energy source is controlled to reduce or eliminate the force on selected particles such that the selected particles flow on a natural or expected flow path to a collection area such as an output channel. By avoiding application of force to desired particles, the anti-sorting systems and methods can improve viability and other characteristics of the desired particles.
A method, system and apparatus for selecting cells is disclosed. An example embodiment provides spatial information denoting the location, on a four part array of sensors, referred to as a quad array, of the center, of each particle that passes through the focused laser beam in a cell sorter. The center of a particle is commonly determined by the average fluorescence intensity within the field of view of a Side Fluorescence (SFL) collection lens. Fluorescence collected by an SFL lens from a particle having any orientation and any position in the core stream produces a spot large enough to illuminate all four segments of a quad array. By independently measuring the fluorescence intensity recorded by each of the four array segments for a particle, it is possible to calculate the x-y coordinate position across the quad array segments of the average total fluorescence emission collected from that particle.
A massively parallel microfluidic chip is provided having a plurality of sections that are stacked or layered along a stacking direction to form a plurality of microchannels at least partially oriented to flow along the stacking direction. The plurality of sections can include a transfer section for introduction of sample fluid including particles, a particle focusing section configured to focus the particles in the sample fluid, and an actuation section including a plurality of interrogation regions and a plurality of actuators. Each interrogation region and actuator is associated with at least one microchannel in the plurality of microchannels. The arrangement of the microfluidic channels along the stacking direction enables an extremely high packing density of channels and interrogation regions on a single chip to provide massively parallel processing of particles.
A method, system and apparatus for selecting cells is disclosed. An example embodiment provides spatial information denoting the location, on a four part array of sensors, referred to as a quad array, of the center, of each particle that passes through the focused laser beam in a cell sorter. The center of a particle is commonly determined by the average fluorescence intensity within the field of view of a Side Fluorescence (SFL) collection lens. Fluorescence collected by an SFL lens from a particle having any orientation and any position in the core stream produces a spot large enough to illuminate all four segments of a quad array. By independently measuring the fluorescence intensity recorded by each of the four array segments for a particle, it is possible to calculate the x-y coordinate position across the quad array segments of the average total fluorescence emission collected from that particle.
A massively parallel microfluidic chip is provided having a plurality of sections that are stacked or layered along a stacking direction to form a plurality of microchannels at least partially oriented to flow along the stacking direction. The plurality of sections can include a transfer section for introduction of sample fluid including particles, a particle focusing section configured to focus the particles in the sample fluid, and an actuation section including a plurality of interrogation regions and a plurality of actuators. Each interrogation region and actuator is associated with at least one microchannel in the plurality of microchannels. The arrangement of the microfluidic channels along the stacking direction enables an extremely high packing density of channels and interrogation regions on a single chip to provide massively parallel processing of particles.
Systems and methods for particle sorting are presented including a monitoring system downstream of a particle separator or sorter. The system can utilize the monitoring system to adjust or calibrate operational parameters of the system in real time. When a particle of interest is mis-sorted, the probability is high that the particle of interest has been sorted into a non-targeted sortable unit that was adjacent in sequence to the sortable unit that was expected to include the particle of interest. The monitoring system monitors non-targeted sortable units in the system that were adjacent in sequence to targeted sortable units that are predicted to contain particles of interest. Signals from the monitoring system enable automated adjustment or calibration of operational parameters of the system such as sort delay or purity mask parameters.
09 - Scientific and electric apparatus and instruments
Goods & Services
Fluidic-based instrumentation for cellular and molecular biology for scientific and laboratory use, namely, cell sorters, microscopic particle sorters; cytometers
09 - Scientific and electric apparatus and instruments
Goods & Services
Fluidic-based instrumentation for cellular and molecular biology for scientific and laboratory use, namely, cell sorters, microscopic particle sorters; cytometers
Systems and methods taught herein enable simultaneous forward and side detection of light originating within a microfluidic channel disposed in a substrate. At least a portion of the microfluidic channel is located in the substrate relative to a first side surface of the substrate to enable simultaneous detection paths with respect to extinction (i.e., 0°) and side detection (i.e., 90°). The location of the microfluidic channel as taught herein enables a maximal half-angle for a ray of light passing from a center of the portion of the microfluidic channel through the first side surface to be in a range from 25 to 90 degrees in some embodiments. By placing at least the portion of the microfluidic channel proximate to the side surface of the substrate, a significantly greater proportion of light emitted or scattered from a particle within the microfluidic channel can be collected and imaged on a detector as compared to conventional particle processing chips.
A microfluidic chip having a micro channel for processing a sample is provided. The micro channel may focus the sample by using focusing fluid and a core stream forming geometry. The core stream forming geometry may include a lateral fluid focusing component and one or more vertical fluid focusing components. A microfluidic chip may include a plurality micro channels operating in parallel on a microfluidic chip.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
F16K 99/00 - Subject matter not provided for in other groups of this subclass
F17D 1/08 - Pipe-line systems for liquids or viscous products
F17D 5/00 - Protection or supervision of installations
G01N 15/1404 - Handling flow, e.g. hydrodynamic focusing
G01N 15/1409 - Handling samples, e.g. injecting samples
A fluid handling system for supplying a working fluid to a fluid flow instrument is disclosed. The system includes a controller configured to receive sensor signals indicative of a deformation of a flexible barrier located between a control fluid volume containing a control fluid and a working fluid volume containing the working fluid. Based on the sensor signals, the controller may send signals to control the operation of a working fluid flow generator in order to regulate or control the fluid characteristic of the working fluid being provided to the fluid flow instrument.
A method, system and apparatus for anti-sorting particles is disclosed. In an example embodiment, particles move in a fluid along a microfluidic channel. A measurement device determines which particles are selected or desired particles by measuring a desired characteristic of the particles and outputting an associated signal. The energy source continuously imparts a force on unselected or undesired particles in a deflection region of the microfluidic channel to remove the unselected or undesired particles from the stream of particles. Based upon the signal outputted by the measurement device, the energy source is controlled to reduce or eliminate the force on selected particles such that the selected particles flow on a natural or expected flow path to a collection area such as an output channel. By avoiding application of force to desired particles, the anti-sorting systems and methods can improve viability and other characteristics of the desired particles.
A fluid handling system for supplying a working fluid to a fluid flow instrument is disclosed. The system includes a controller configured to receive sensor signals indicative of a deformation of a flexible barrier located between a control fluid volume containing a control fluid and a working fluid volume containing the working fluid. Based on the sensor signals, the controller may send signals to control the operation of a working fluid flow generator in order to regulate or control the fluid characteristic of the working fluid being provided to the fluid flow instrument.
G01N 15/14 - Optical investigation techniques, e.g. flow cytometry
G05D 7/06 - Control of flow characterised by the use of electric means
G01F 1/38 - Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by using mechanical effects by measuring pressure or differential pressure the pressure or differential pressure being created by the use of flow constriction the pressure or differential pressure being measured by means of a movable element, e.g. diaphragm, piston, Bourdon tube or flexible capsule
G01F 1/661 - Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by measuring frequency, phase shift or propagation time of electromagnetic or other waves, e.g. using ultrasonic flowmeters using light
G01F 1/72 - Devices for measuring pulsing fluid flows
16.
Systems and methods for particle sorting with automated adjustment of operational parameters
Systems and methods for particle sorting are presented including a monitoring system downstream of a particle separator or sorter. The system can utilize the monitoring system to adjust or calibrate operational parameters of the system in real time. When a particle of interest is mis-sorted, the probability is high that the particle of interest has been sorted into a non-targeted sortable unit that was adjacent in sequence to the sortable unit that was expected to include the particle of interest. The monitoring system monitors non-targeted sortable units in the system that were adjacent in sequence to targeted sortable units that are predicted to contain particles of interest. Signals from the monitoring system enable automated adjustment or calibration of operational parameters of the system such as sort delay or purity mask parameters.
Systems and methods for particle sorting are presented including a monitoring system downstream of a particle separator or sorter. The system can utilize the monitoring system to adjust or calibrate operational parameters of the system in real time. When a particle of interest is mis-sorted, the probability is high that the particle of interest has been sorted into a non-targeted sortable unit that was adjacent in sequence to the sortable unit that was expected to include the particle of interest. The monitoring system monitors non-targeted sortable units in the system that were adjacent in sequence to targeted sortable units that are predicted to contain particles of interest. Signals from the monitoring system enable automated adjustment or calibration of operational parameters of the system such as sort delay or purity mask parameters.
An apparatus for processing or manipulating or sorting particles by acoustic wave is disclosed. The apparatus can include a plastic or glass microfluidic channel or chip coupled via an intermediate layer to a piezoelectric substrate. The intermediate layer is acoustically matched to an acoustic wave produced in the piezoelectric substrate for manipulating and/or sorting particles in the microfluidic channel or chip. In some embodiments, the microfluidic channel or chip is coupled to a sealing layer through the intermediate layer. This multiple-layer assembly has higher yield and lower failure rate than conventional instruments and improves acoustic-wave propagation into the polymer or glass microchannel for the purpose of processing or manipulating or sorting particles or any combination thereof.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B06B 1/06 - Processes or apparatus for generating mechanical vibrations of infrasonic, sonic or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction
G01N 15/14 - Optical investigation techniques, e.g. flow cytometry
19.
Micro-lens systems for particle processing systems
The present disclosure provides improved optical systems for particle processing (e.g., cytometry including microfluidic based sorters, drop sorters, and/or cell purification) systems and methods. More particularly, the present disclosure provides advantageous micro-lens array optical detection assemblies for particle (e.g., cells, microscopic particles, etc.) processing systems and methods (e.g., for analyzing, sorting, processing, purifying, measuring, isolating, detecting, monitoring and/or enriching particles).
A microfluidic chip assembly having a plurality of microfluidic flow channels is provided. Each channel has a switching region. The microfluidic chip may further include at least one bubble jet actuator configured to generate a pressure pulse in the switching regions of the channels to selectively deflect particles in the flow. The bubble jet actuator may be configured as a blind chamber, as an operative non-through flow chamber and/or as a self-replenishment chamber. The bubble jet actuator may include a trapped air bubble. The bubble jet actuator may include a plurality of heating elements individually controlled for pre-nucleation warmup and/or for triggering vapor bubble nucleation.
Systems and methods taught herein enable simultaneous forward and side detection of light originating within a microfluidic channel disposed in a substrate. At least a portion of the microfluidic channel is located in the substrate relative to a first side surface of the substrate to enable simultaneous detection paths with respect to extinction (i.e., 0°) and side detection (i.e., 90°). The location of the microfluidic channel as taught herein enables a maximal half-angle for a ray of light passing from a center of the portion of the microfluidic channel through the first side surface to be in a range from 25 to 90 degrees in some embodiments. By placing at least the portion of the microfluidic channel proximate to the side surface of the substrate, a significantly greater proportion of light emitted or scattered from a particle within the microfluidic channel can be collected and imaged on a detector as compared to conventional particle processing chips.
Systems and methods taught herein advantageously provide extended dynamic range capabilities to detect low intensity and high intensity emitted or scattered light from particles at high speeds with high sensitivity. Independently controlled first and second optical detector elements that handle light intensities in different dynamic ranges, large overall dynamic range is created. Signals from the detector elements can be combined to create a single combined signal that has excellent sensitivity over a large dynamic range. The detector systems and methods taught herein are particularly advantageous in particle processing where the population of particles can emit or scatter light over a large range of intensity values. Systems and methods taught herein enable a wide dynamic range, optical signals of related to particles of interest within a single detector's dynamic range can be acquired while other optical signals at light intensities outside the single detector's dynamic range can also be accurately captured.
A microfluidic chip having a micro channel for processing a sample is provided. The micro channel may focus the sample by using focusing fluid and a core stream forming geometry. The core stream forming geometry may include a lateral fluid focusing component and one or more vertical fluid focusing components. A microfluidic chip may include a plurality micro channels operating in parallel on a microfluidic chip.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
G01N 15/14 - Optical investigation techniques, e.g. flow cytometry
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
F17D 1/08 - Pipe-line systems for liquids or viscous products
F17D 5/00 - Protection or supervision of installations
F16K 99/00 - Subject matter not provided for in other groups of this subclass
A flow cell for particle processing such as particle sorting, may be operatively engaged to a particle processing apparatus. The fluid contact surfaces of the flow cell may be fully enclosed. Further, the flow cell may encapsulate all fluid contact surfaces in the particle processing apparatus. The enclosing or encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The flow cell may employ any suitable technique for processing particles. The flow cell may be disposable and suitable for use in droplet sorting. The flow cell may include an operatively sealed sort chamber having a particle stream focusing region, an orifice, an interrogation zone and a sorting region.
The present disclosure relates to optical crosstalk reduction in particle processing (e.g., cytometry including flow cytometry using microfluidic based sorters, drop formation based sorters, and/or cell purification) systems and methods in order to improve performance. More particularly, the present disclosure relates to assemblies, systems and methods for minimizing optical crosstalk during the analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting, monitoring and/or enriching) of particles (e.g., cells, microscopic particles, etc.). The exemplary systems and methods for crosstalk reduction in particle processing systems (e.g., cell purification systems) may be particularly useful in the area of cellular medicine or the like. The systems and methods may be modular and used singly or in combination to optimize cell purification based on the crosstalk environment and specific requirements of the operator and/or system.
A single disposable cartridge for performing a process on a particle, such as particle sorting, encapsulates all fluid contact surfaces in the cartridge for use with microfluidic particle processing technology. The cartridge interfaces with an operating system for effecting particle processing. The encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The cartridge may employ any suitable technique for processing particles.
The present disclosure provides improved optical systems for particle processing (e.g., cytometry including microfluidic based sorters, drop sorters, and/or cell purification) systems and methods. More particularly, the present disclosure provides advantageous micro-lens array optical detection assemblies for particle (e.g., cells, microscopic particles, etc.) processing systems and methods (e.g., for analyzing, sorting, processing, purifying, measuring, isolating, detecting, monitoring and/or enriching particles.
An improved actuator for use in a microfluidic particle sorting system utilizes a staggered packing scheme for a plurality of actuators used to selectively deflect a particle in an associated sorting channel from a stream of channels. An actuator block may be provided for housing a two-dimensional array of actuators, each configured to align with an actuation port in an associated sorting chip containing a plurality of sorting channels. The actuator block may include a built-in stressing means to pre-stress each actuator housed by the block. An actuator comprising a piezo-electric stack may employ contact-based electrical connection rather than soldered wires to improve packing density. The actuator may be an external actuator. That is, the external actuator is external to the substrate in which the sorting channels are formed.
The present disclosure provides improved particle processing (e.g., cytometry and/or cell purification) systems and methods that can operate in an autonomous fashion. More particularly, the present disclosure provides for assemblies, systems and methods for analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting and/or enriching) particles (e.g., cells, microscopic particles, etc.) where human intervention is not required and/or is minimized. The systems, assemblies and methods of the present disclosure advantageously improve run performance of particle processing systems (e.g., cell purification systems, cytometers) by significantly reducing and/or substantially eliminating the burden of operation for human intervention by automating numerous functions, features and/or steps of the disclosed systems and methods.
A microfluidic chip assembly having a plurality of microfluidic flow channels is provided. Each channel has a switching region. The microfluidic chip may further include at least one surface acoustic wave generator configured to generate a pressure pulse in the switching regions of the channels to selectively deflect particles in the flow. Attenuation elements and/or channel configurations may be used to prevent acoustic signals from interfering with neighboring switching regions. Alternatively, a microfluidic particle processing system may include a microfluidic chip assembly, a particle processing instrument, and a coupling element. The surface acoustic wave generator may be provided on the particle processing instrument. The microfluidic chip assembly may be configured for operative engagement, via the coupling element, with the particle processing instrument. The coupling element may transmit acoustic energy from the surface acoustic wave generator to the switching regions and/or to focusing regions of the flow channels.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
G01N 1/00 - SamplingPreparing specimens for investigation
G01N 1/10 - Devices for withdrawing samples in the liquid or fluent state
G01N 15/14 - Optical investigation techniques, e.g. flow cytometry
G01N 29/22 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic wavesVisualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object Details
A single disposable cartridge for performing a process on a particle, such as particle sorting, encapsulates all fluid contact surfaces in the cartridge for use with microfluidic particle processing technology. The cartridge interfaces with an operating system for effecting particle processing. The encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The cartridge may employ any suitable technique for processing particles.
A microfluidic multiple channel particle analysis system which allows particles from a plurality of particle sources to be independently simultaneously entrained in a corresponding plurality of fluid streams for analysis and sorting into particle subpopulations based upon one or more particle characteristics.
A microfluidic chip assembly having a plurality of microfluidic flow channels is provided. Each channel has a switching region. The microfluidic chip may further include at least one surface acoustic wave generator configured to generate a pressure pulse in the switching regions of the channels to selectively deflect particles in the flow. Attenuation elements and/or channel configurations may be used to prevent acoustic signals from interfering with neighboring switching regions. Alternatively, a microfluidic particle processing system may include a microfluidic chip assembly, a particle processing instrument, and a coupling element. The surface acoustic wave generator may be provided on the particle processing instrument. The microfluidic chip assembly may be configured for operative engagement, via the coupling element, with the particle processing instrument. The coupling element may transmit acoustic energy from the surface acoustic wave generator to the switching regions and/or to focusing regions of the flow channels.
G01N 29/22 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic wavesVisualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object Details
G01N 1/10 - Devices for withdrawing samples in the liquid or fluent state
The present disclosure relates to optical crosstalk reduction in particle processing (e.g., cytometry including flow cytometry using microfluidic based sorters, drop formation based sorters, and/or cell purification) systems and methods in order to improve performance. More particularly, the present disclosure relates to assemblies, systems and methods for minimizing optical crosstalk during the analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting, monitoring and/or enriching) of particles (e.g., cells, microscopic particles, etc.). The exemplary systems and methods for crosstalk reduction in particle processing systems (e.g., cell purification systems) may be particularly useful in the area of cellular medicine or the like. The systems and methods may be modular and used singly or in combination to optimize cell purification based on the crosstalk environment and specific requirements of the operator and/or system.
An improved actuator for use in a microfluidic particle sorting system utilizes a staggered packing scheme for a plurality of actuators used to selectively deflect a particle in an associated sorting channel from a stream of channels. An actuator block may be provided for housing a two-dimensional array of actuators, each configured to align with an actuation port in an associated sorting chip containing a plurality of sorting channels. The actuator block may include a built-in stressing means to pre-stress each actuator housed by the block. An actuator comprising a piezo-electric stack may employ contact-based electrical connection rather than soldered wires to improve packing density. The actuator may be an external actuator. That is, the external actuator is external to the substrate in which the sorting channels are formed.
B07C 5/00 - Sorting according to a characteristic or feature of the articles or material being sorted, e.g. by control effected by devices which detect or measure such characteristic or featureSorting by manually actuated devices, e.g. switches
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
B07C 5/34 - Sorting according to other particular properties
38.
Fluid handling system for a particle processing apparatus
A fluid handling system for a particle processing instrument includes a pump, a pulse attenuator, a pressure transducer, and a pump controller. The pump may be configured to supply a pulsed flow of fluid having a first pulse characteristic to the pulse attenuator. The pulse attenuator may have a single, undivided, volume, fluid inlets, fluid outlets, and a pressure sensor port. The pulse attenuator may supply an outlet flow of fluid having a second pulse characteristic different from the first pulse characteristic. The pressure transducer may be in fluid communication with the pressure sensor port and in control communication with the pump controller. The pump controller may be in control communication with the pump to maintain a substantially constant nominal pressure within the pulse attenuator by controlling the pump motor.
A microfluidic chip assembly having a plurality of microfluidic flow channels is provided. Each channel has a switching region. The microfluidic chip may further include at least one bubble jet actuator configured to generate a pressure pulse in the switching regions of the channels to selectively deflect particles in the flow. The bubble jet actuator may be configured as a blind chamber, as an operative non-through flow chamber and/or as a self-replenishment chamber. The bubble jet actuator may include a trapped air bubble. The bubble jet actuator may include a plurality of heating elements individually controlled for pre-nucleation warmup and/or for triggering vapor bubble nucleation.
A fluid handling system for supplying a working fluid to a fluid flow instrument is disclosed. The system includes a controller configured to receive sensor signals indicative of a deformation of a flexible barrier located between a control fluid volume containing a control fluid and a working fluid volume containing the working fluid. Based on the sensor signals, the controller may send signals to control the operation of a working fluid flow generator in order to regulate or control the fluid characteristic of the working fluid being provided to the fluid flow instrument.
A microfluidic multiple channel particle analysis system which allows particles from a plurality of particle sources to be independently simultaneously entrained in a corresponding plurality of fluid streams for analysis and sorting into particle subpopulations based upon one or more particle characteristics.
An improved actuator for use in a microfluidic particle sorting system utilizes a staggered packing scheme for a plurality of actuators used to selectively deflect a particle in an associated sorting channel from a stream of channels. An actuator block may be provided for housing a two-dimensional array of actuators, each configured to align with an actuation port in an associated sorting chip containing a plurality of sorting channels. The actuator block may include a built-in stressing means to pre-stress each actuator housed by the block. An actuator comprising a piezo-electric stack may employ contact-based electrical connection rather than soldered wires to improve packing density. The actuator may be an external actuator. That is, the external actuator is external to the substrate in which the sorting channels are formed.
B07C 5/00 - Sorting according to a characteristic or feature of the articles or material being sorted, e.g. by control effected by devices which detect or measure such characteristic or featureSorting by manually actuated devices, e.g. switches
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B07C 5/34 - Sorting according to other particular properties
43.
Microfluidic flow-through elements and methods of manufacture of same
Microfluidic flow-through elements and methods for forming and using the same, particularly, low cost, easily sterilized, disposable microfluidic flow-through elements may include an orifice region suitable, for example, for fluid jet formation (such as in a droplet sorter or flow cell) or sample injection or hydrodynamic focusing (such as in a non-droplet flow cytometer). Laser drilling, for example laser ablation, may be used to form an orifice region extending through an orifice wall section of a base substrate. The base substrate may be unitarily-formed by injection molding a polymeric material. The orifice region may be advantageously configured to form a predetermined geometry by controlling the characteristics of the ablating beam.
B23K 26/38 - Removing material by boring or cutting
B23K 26/388 - Trepanning, i.e. boring by moving the beam spot about an axis
B05B 1/02 - Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops
B23K 26/382 - Removing material by boring or cutting by boring
44.
Assemblies and methods for reducing optical crosstalk in particle processing systems
The present disclosure relates to optical crosstalk reduction in particle processing (e.g., cytometry including flow cytometry using microfluidic based sorters, drop formation based sorters, and/or cell purification) systems and methods in order to improve performance. More particularly, the present disclosure relates to assemblies, systems and methods for minimizing optical crosstalk during the analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting, monitoring and/or enriching) of particles (e.g., cells, microscopic particles, etc.). The exemplary systems and methods for crosstalk reduction in particle processing systems (e.g., cell purification systems) may be particularly useful in the area of cellular medicine or the like. The systems and methods may be modular and used singly or in combination to optimize cell purification based on the crosstalk environment and specific requirements of the operator and/or system.
Systems, methods and non-transitory storage medium are disclosed herein for adjusting an output of a particle inspection system representative of a particle characteristic for a particle flowing in a flow-path of a particle processing system. More particularly, the output may be processed and a calibrated output of the particle characteristic generated. In other embodiments, one or more calibration particles are used. Thus, an output of a particle inspection system representative of a particle characteristic for one or more calibration particles flowing in a flow-path of a particle processing system may be compared relative to a standard and an action may be taken based on a result of the comparing the output to the standard.
The present disclosure provides improved optical systems for particle processing (e.g., cytometry including microfluidic based sorters, drop sorters, and/or cell purification) systems and methods. More particularly, the present disclosure provides advantageous micro-lens array optical detection assemblies for particle (e.g., cells, microscopic particles, etc.) processing systems and methods (e.g., for analyzing, sorting, processing, purifying, measuring, isolating, detecting, monitoring and/or enriching particles.
A microfluidic chip having a micro channel for processing a sample is provided. The micro channel may focus the sample by using focusing fluid and a core stream forming geometry. The core stream forming geometry may include a lateral fluid focusing component and one or more vertical fluid focusing components. A microfluidic chip may include a plurality micro channels operating in parallel on a microfluidic chip.
The present disclosure provides improved particle processing (e.g., cytometry and/or cell purification) systems and methods that can operate in an autonomous fashion. More particularly, the present disclosure provides for assemblies, systems and methods for analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting and/or enriching) particles (e.g., cells, microscopic particles, etc.) where human intervention is not required and/or is minimized. The systems, assemblies and methods of the present disclosure advantageously improve run performance of particle processing systems (e.g., cell purification systems, cytometers) by significantly reducing and/or substantially eliminating the burden of operation for human intervention by automating numerous functions, features and/or steps of the disclosed systems and methods.
The present disclosure provides improved particle processing (e.g., cytometry and/or cell purification) systems and methods that can operate in an autonomous fashion. More particularly, the present disclosure provides for assemblies, systems and methods for analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting and/or enriching) particles (e.g., cells, microscopic particles, etc.) where human intervention is not required and/or is minimized. The systems, assemblies and methods of the present disclosure advantageously improve run performance of particle processing systems (e.g., cell purification systems, cytometers) by significantly reducing and/or substantially eliminating the burden of operation for human intervention by automating numerous functions, features and/or steps of the disclosed systems and methods.
The present disclosure provides improved particle processing (e.g., cytometry and/or cell purification) systems and methods that can operate in an autonomous fashion. More particularly, the present disclosure provides for assemblies, systems and methods for analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting and/or enriching) particles (e.g., cells, microscopic particles, etc.) where human intervention is not required and/or is minimized. The systems, assemblies and methods of the present disclosure advantageously improve run performance of particle processing systems (e.g., cell purification systems, cytometers) by significantly reducing and/or substantially eliminating the burden of operation for human intervention by automating numerous functions, features and/or steps of the disclosed systems and methods.
51.
ASSEMBLIES AND METHODS FOR REDUCING OPTICAL CROSSTALK IN PARTICLE PROCESSING SYSTEMS
The present disclosure relates to optical crosstalk reduction in particle processing (e.g., cytometry including flow cytometry using microfluidic based sorters, drop formation based sorters, and/or cell purification) systems and methods in order to improve performance. More particularly, the present disclosure relates to assemblies, systems and methods for minimizing optical crosstalk during the analyzing, sorting, and/or processing (e.g., purifying, measuring, isolating, detecting, monitoring and/or enriching) of particles (e.g., cells, microscopic particles, etc.). The exemplary systems and methods for crosstalk reduction in particle processing systems (e.g., cell purification systems) may be particularly useful in the area of cellular medicine or the like. The systems and methods may be modular and used singly or in combination to optimize cell purification based on the crosstalk environment and specific requirements of the operator and/or system.
A microfluidic chip having a micro channel for processing a sample is provided. The micro channel may focus the sample by using focusing fluid and a core stream forming geometry. The core stream forming geometry may include a lateral fluid focusing component and one or more vertical fluid focusing components. A microfluidic chip may include a plurality micro channels operating in parallel on a microfluidic chip.
A fluid stream imaging apparatus having either optics for manipulating the aspect ratio or sensing elements configured for manipulating the aspect ratio of an image of the fluid stream. This application may also relate to a system for acquiring images of a portion of a fluid stream at high speeds for image processing to measure and predict droplet delays for individual forming particles.
A flow cell for particle processing such as particle sorting, may be operatively engaged to a particle processing apparatus. The fluid contact surfaces of the flow cell may be fully enclosed. Further, the flow cell may encapsulate all fluid contact surfaces in the particle processing apparatus. The enclosing or encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The flow cell may employ any suitable technique for processing particles. The flow cell may be disposable and suitable for use in droplet sorting. The flow cell may include an operatively sealed sort chamber having a particle stream focusing region, an orifice, an interrogation zone and a sorting region.
A single disposable cartridge for performing a process on a particle, such as particle sorting, encapsulates all fluid contact surfaces in the cartridge for use with microfluidic particle processing technology. The cartridge interfaces with an operating system for effecting particle processing. The encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The cartridge may employ any suitable technique for processing particles.
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Fluidic-based instrumentation for cellular and molecular biology for scientific and laboratory use, namely, cell sorters, microscopic particle sorters; cytometers Research and development of fluidic-based instrumentation for cellular and molecular biology
09 - Scientific and electric apparatus and instruments
Goods & Services
Fluidic-based instrumentation for cellular and molecular biology for scientific and laboratory use, namely, cell sorters, microscopic particle sorters; cytometers
A flow cell for particle processing such as particle sorting, may be operatively engaged to a particle processing apparatus. The fluid contact surfaces of the flow cell may be fully enclosed. Further, the flow cell may encapsulate all fluid contact surfaces in the particle processing apparatus. The enclosing or encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The flow cell may employ any suitable technique for processing particles. The flow cell may be disposable and suitable for use in droplet sorting. The flow cell may include an operatively sealed sort chamber having a particle stream focusing region, an orifice, an interrogation zone and a sorting region.
Focal plane shift elements and optical systems with focal plane shifting features for illuminating flow-paths in a fluidic processing system are disclosed. An optical system may include a light source providing an incident first light beam. The optical system may include at least one optical element configured to collect and focus the incident first light beam to produce a second light beam having different portions simultaneously focused at two or more different locations along an optical path, with each location corresponding to a different flow-path of the fluidic processing system. The focal plane shift elements and optical systems with focal plane shifting features may be particularly useful in a microfluidic system.
Large area, low f-number optical systems, and microfluidic systems incorporating such optical systems, are disclosed. Large area, low f-number optical systems may be used to collect light from plurality of micro channels associated with a plurality of flow cytometers. The optical systems may be configured to collect light from a source area having an object lateral length or width within a range of 25 mm and 75 mm, configured to have an f-number within a range of 0.9 to 1.2, and configured to have a working distance within a range of 10 mm to 30 mm.
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Fluidic-based instrumentation for cellular and molecular biology for scientific and laboratory use, namely, cell sorters; cytometers Research and development of fluidic-based instrumentation for cellular and molecular biology
A microfluidic multiple channel particle analysis system (1) which allows particles (2) from a plurality of particle sources (3) to be independently simultaneously entrained in a corresponding plurality of fluid streams (4) for analysis and sorting into particle subpopulations (5) based upon one or more particle characteristics (6).
Particle processing systems and methods utilize a sort monitoring system to monitor an operational characteristic for a particle sorting system. The operational characteristic may be related to the performance and operation of a sorter or a group of sorters in the particle sorting system. The operational characteristic may be monitored based on monitoring particles for an output of a sorter or of a group of sorters. Operational characteristics which may be monitored include sort error, sort fraction, yield, purity and recovery percentage. The sort monitoring system may evaluate the monitored operational characteristic, for example, as related to sort performance, and take an action, for example, a corrective action or a notifying action, based on the evaluation of the operational characteristic.
A particle analyzing and/or sorting apparatus and the associated methods. One aspect of the described embodiments relates to an analyzer, or a sorter, having acquisition and sort electronics in the form of a field programmable gate array for processing detected signals. Another aspect relates to a droplet based approach of analyzing and sorting particles and may further include a dynamic element, such a dynamic drop delay. In still another broad aspect, an apparatus and method for dynamically varying other sorting parameters.
A particle analyzing and/or sorting apparatus and the associated methods. One aspect of the described embodiments relates to an analyzer, or a sorter, having acquisition and sort electronics in the form of a field programmable gate array for processing detected signals. Another aspect relates to a droplet based approach of analyzing and sorting particles and may further include a dynamic element, such a dynamic drop delay. In still another broad aspect, an apparatus and method for dynamically varying other sorting parameters.
A particle analyzing and/or sorting apparatus and the associated methods. One aspect of the described embodiments relates to an analyzer, or a sorter, having acquisition and sort electronics in the form of a field programmable gate array for processing detected signals. Another aspect relates to a droplet based approach of analyzing and sorting particles and may further include a dynamic element, such a dynamic drop delay. In still another broad aspect, an apparatus and method for dynamically varying other sorting parameters.
A fluid stream imaging apparatus having either optics for manipulating the aspect ratio or sensing elements configured for manipulating the aspect ratio of an image of the fluid stream. This application may also relate to a system for acquiring images of a portion of a fluid stream at high speeds for image processing to measure and predict droplet delays for individual forming particles.
A fluid stream imaging apparatus having either optics for manipulating the aspect ratio or sensing elements configured for manipulating the aspect ratio of an image of the fluid stream. This application may also relate to a system for acquiring images of a portion of a fluid stream at high speeds for image processing to measure and predict droplet delays for individual forming particles.
Particle processing systems and methods utilize a sort monitoring system to monitor an operational characteristic for a particle sorting system. The operational characteristic may be related to the performance and operation of a sorter or a group of sorters in the particle sorting system. The operational characteristic may be monitored based on monitoring particles for an output of a sorter or of a group of sorters. Operational characteristics which may be monitored include sort error, sort fraction, yield, purity and recovery percentage. The sort monitoring system may evaluate the monitored operational characteristic, for example, as related to sort performance, and take an action, for example, a corrective action or a notifying action, based on the evaluation of the operational characteristic.
An improved actuator for use in a microfluidic particle sorting system utilizes a staggered packing scheme for a plurality of actuators used to selectively deflect a particle in an associated sorting channel from a stream of channels. An actuator block may be provided for housing a two-dimensional array of actuators, each configured to align with an actuation port in an associated sorting chip containing a plurality of sorting channels. The actuator block may include a built-in stressing means to pre-stress each actuator housed by the block. An actuator comprising a piezo-electric stack may employ contact-based electrical connection rather than soldered wires to improve packing density. The actuator may be an external actuator. That is, the external actuator is external to the substrate in which the sorting channels are formed.
B07C 5/00 - Sorting according to a characteristic or feature of the articles or material being sorted, e.g. by control effected by devices which detect or measure such characteristic or featureSorting by manually actuated devices, e.g. switches
B07C 5/34 - Sorting according to other particular properties
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
A single disposable cartridge for performing a process on a particle, such as particle sorting, encapsulates all fluid contact surfaces in the cartridge for use with microfluidic particle processing technology. The cartridge interfaces with an operating system for effecting particle processing. The encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The cartridge may employ any suitable technique for processing particles.
Systems, methods and non-transitory storage medium are disclosed herein for adjusting an output of a particle inspection system representative of a particle characteristic for a particle flowing in a flow-path of a particle processing system. More particularly, the output may be processed and a calibrated output of the particle characteristic generated. In other embodiments, one or more calibration particles are used. Thus, an output of a particle inspection system representative of a particle characteristic for one or more calibration particles flowing in a flow-path of a particle processing system may be compared relative to a standard and an action may be taken based on a result of the comparing the output to the standard.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
A microfluidic multiple channel particle analysis system (1) which allows particles (2) from a plurality of particle sources (3) to be independently simultaneously entrained in a corresponding plurality of fluid streams (4) for analysis and sorting into particle subpopulations (5) based upon one or more particle characteristics (6).
C12Q 1/04 - Determining presence or kind of microorganismUse of selective media for testing antibiotics or bacteriocidesCompositions containing a chemical indicator therefor
Systems, methods and non-transitory storage medium are disclosed herein for adjusting an output of a particle inspection system representative of a particle characteristic for a particle flowing in a flow-path of a particle processing system. More particularly, the output may be processed and a calibrated output of the particle characteristic generated. In other embodiments, one or more calibration particles are used. Thus, an output of a particle inspection system representative of a particle characteristic for one or more calibration particles flowing in a flow-path of a particle processing system may be compared relative to a standard and an action may be taken based on a result of the comparing the output to the standard.
An improved actuator for use in a microfluidic particle sorting system utilizes a staggered packing scheme for a plurality of actuators used to selectively deflect a particle in an associated sorting channel from a stream of channels. An actuator block may be provided for housing a two-dimensional array of actuators, each configured to align with an actuation port in an associated sorting chip containing a plurality of sorting channels. The actuator block may include a built-in stressing means to pre-stress each actuator housed by the block. An actuator comprising a piezo-electric stack may employ contact-based electrical connection rather than soldered wires to improve packing density. The actuator may be an external actuator. That is, the external actuator is external to the substrate in which the sorting channels are formed.
B07C 5/00 - Sorting according to a characteristic or feature of the articles or material being sorted, e.g. by control effected by devices which detect or measure such characteristic or featureSorting by manually actuated devices, e.g. switches
An improved actuator for use in a microfluidic particle sorting system utilizes a staggered packing scheme for a plurality of actuators (158) used to selectively deflect a particle in an associated sorting channel from a stream of channels. An actuator block may be provided for housing a two-dimensional array of actuators, each configured to align with an actuation port in an associated sorting chip containing a plurality of sorting channels (152). The actuator block (400) may include a built-in stressing means to pre-stress each actuator housed by the block. An actuator comprising a piezo-electric stack (1581) may employ contact-based electrical connection rather than soldered wires to improve packing density. The actuator may be an external actuator. That is, the external actuator is external to the substrate in which the sorting channels are formed.
A single disposable cartridge for performing a process on a particle, such as particle sorting, encapsulates all fluid contact surfaces in the cartridge for use with microfluidic particle processing technology. The cartridge interfaces with an operating system for effecting particle processing. The encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The cartridge may employ any suitable technique for processing particles.
A single disposable cartridge for performing a process on a particle, such as particle sorting, encapsulates all fluid contact surfaces in the cartridge for use with microfluidic particle processing technology. The cartridge interfaces with an operating system for effecting particle processing. The encapsulation of the fluid contact surfaces insures, improves or promotes operator isolation and/or product isolation. The cartridge may employ any suitable technique for processing particles.
A microfabricated sheath flow structure for producing a sheath flow includes a primary sheath flow channel for conveying a sheath fluid, a sample inlet for injecting a sample into the sheath fluid in the primary sheath flow channel, a primary focusing region for focusing the sample within the sheath fluid and a secondary focusing region for providing additional focusing of the sample within the sheath fluid. The secondary focusing region may be formed by a flow channel intersecting the primary sheath flow channel to inject additional sheath fluid into the primary sheath flow channel from a to selected direction. A sheath flow system may comprise a plurality of sheath flow structures operating in parallel on a microfluidic chip.
B65G 51/00 - Conveying articles through pipes or tubes by fluid flow or pressureConveying articles over a flat surface, e.g. the base of a trough, by jets located in the surface
An optical system for acquiring fast spectra from spatially channel arrays includes a light source for producing a light beam that passes through the microfluidic chip or the channel to be monitored, one or more lenses or optical fibers for capturing the light from the light source after interaction with the particles or chemicals in the microfluidic channels, and one or more detectors. The detectors, which may include light amplifying elements, detect each light signal and transducer the light signal into an electronic signal. The electronic signals, each representing the intensity of an optical signal, pass from each detector to an electronic data acquisition system for analysis. The light amplifying element or elements may comprise an array of phototubes, a multianode phototube, or a multichannel plate based image intensifier coupled to an array of photodiode detectors.
B81B 1/00 - Devices without movable or flexible elements, e.g. microcapillary devices
B81B 7/02 - Microstructural systems containing distinct electrical or optical devices of particular relevance for their function, e.g. microelectro-mechanical systems [MEMS]
G01N 21/00 - Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
G01N 21/27 - ColourSpectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
G02B 26/08 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
