Cytonome/st, LLC

Inguran, LLC

Union Biometrica, Inc.

Donald Francis Perrault, Jr

Johnathan Charles Sharpe

Blair D Morad

Nemanya Sedoglavich

Emanuel Tito Mendes Machado

Erin Koksal

Rudolf Hulspas

Vladimir Shapiro

Stuart R Ehrlich

Peter Kiesel

W Peter Hansen

Kris S Buchanan

Russell J Gershman

Anthony A Ferrante

Petra B Krauledat

This disclosure relates to methods for sorting sperm cells in a microfluidic chip. In particular, various steps are incorporated to align and orienting sperm in flow channels, as well as, to determining sperm orientation and measure relative DNA content for analysis and/or sorting.

Systems for high throughput sperm sorting

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.

Edge chip

Methods for high throughput sperm sorting

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.

Systems and methods for extended dynamic range detection of light

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.

Thermal activated microfluidic switching

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).

Micro-lens systems for particle processing systems

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&#xb0;) and side detection (i.e., 90&#xb0;). 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.

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.

Assemblies and methods for reducing optical crosstalk in 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.

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.

Operatorless particle processing systems and methods

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.

Growing community of inventors

Brighton, MA, United States of America

Donald Francis Perrault, Jr