Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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 selected direction. A sheath flow system may comprise a plurality of sheath flow structures operating in parallel on a microfluidic chip.

Abstract: 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.

Abstract: 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).

Abstract: 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 selected direction. A sheath flow system may comprise a plurality of sheath flow structures operating in parallel on a microfluidic chip.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A microfluidic device includes a microchannel having an interior bounded by a side wall, an inlet, a switching region, and a plurality of outlet channels downstream of the switching region. The microchannel is formed in a microfluidic chip substrate and configured to accommodate a flow of liquid through the microchannel. The microfluidic device includes a valve operatively coupled to the switching region comprising a sealed reservoir. A side passage extends between the reservoir and the interior of the microchannel via an aperture in the side wall and is configured to accommodate a volume of liquid between the interior of the microchannel and the reservoir. The microfluidic device includes an actuator integrated into the microfluidic chip and configured to increase an internal pressure of the reservoir and move at least a portion of the volume of the liquid from the side passage into the microchannel to deflect a portion of the liquid flowing through the microchannel.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A method and apparatus for sorting particles moving through a closed channel system of capillary size comprises actuators and chambers for selectively generating a pressure pulse to separate a particle having a predetermined characteristic from a stream of particles. The particle sorting system may further include a buffer for absorbing the pressure pulse. The particle sorting system may include a plurality of closely coupled sorting modules which are combined to further increase the sorting rate. The particle sorting system may comprise a multi-stage sorting device for serially sorting streams of particles, in order to decrease the error rate.