Vacuum-loaded, droplet-generating microfluidic chips and related methods

Inventors

Arab, NicolasJohnson, RossBussian, DavidIsom, Jon

Assignees

Pattern Bioscience Inc

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Publication Number

US-11344890-B2

Patent

Publication Date

2022-05-31

Expiration Date


Abstract

A microfluidic chip that can have a body defining a microfluidic network including a test volume, one or more ports, and one or more channels in fluid communication between the port(s) and the test volume. Gas can be removed from the test volume before a sample liquid is introduced therein by reducing pressure at a first one of the port(s), optionally while the liquid is disposed in the port. Liquid in the first port can be introduced into the test volume by increasing pressure at the first port. The microfluidic network can define one or more droplet-generating regions in which at least one of the channel(s) defines a constriction and/or two or more of the channels connect at a junction. Liquid flowing from the first port can pass through at least one of the droplet-generating region(s) and to the test volume.

Core Innovation

The disclosed invention relates to a microfluidic chip having a body that defines one or more microfluidic networks including one or more ports, a test volume in fluid communication with each port, and one or more channels each in fluid communication between at least one port and the test volume. The network also includes one or more droplet-generating regions each in fluid communication between at least one port and the test volume and configured to produce droplets. The network is configured such that, for each port, fluid is permitted to flow from the port to each other port without flowing through the test volume.

The droplet-generating region includes an expansion region, and the expansion region can include a constant-height portion allowing liquid to transition into an expanding portion. The expansion region minimum height is defined relative to a network portion leading into the expansion region, and these geometric constraints are intended to support manufacturing precision and reduce droplet-size variability. The droplet-generating region can also be implemented using multi-channel junction droplet generation and shear at a T-junction.

The invention also discloses loading of the microfluidic chip by a pressure-based two-step process. Liquid is disposed within a first port, and at least a portion of the liquid is introduced into the test volume by reducing pressure at the first port such that gas flows from the test volume through a channel and out of the first port, followed by increasing pressure at the first port such that the portion of the liquid flows from the first port through a droplet-generating region and into the test volume.

Claims Coverage

The independent claims define two inventive features: a microfluidic chip architecture with constrained port-to-port routing relative to a test volume and droplet-generating regions, and a loading method using a two-step pressure sequence at a first port to drive gas flow and then liquid flow into the test volume.

Microfluidic chip with port-to-port flow without test-volume traversal

A microfluidic chip comprising a body and one or more microfluidic networks defined by the body, each network including one or more ports, a test volume in fluid communication with each port, one or more channels in fluid communication between at least one port and the test volume, and one or more droplet-generating regions in fluid communication between at least one port and the test volume and configured to produce droplets; wherein the network is configured such that, for each port, fluid is permitted to flow from the port to each other port without flowing through the test volume.

Two-step pressure loading of droplets into a test volume

A method of loading a microfluidic chip comprising disposing a liquid within a first one of one or more ports of a microfluidic network of a microfluidic chip, and introducing at least a portion of the liquid into the test volume by reducing pressure at the first port such that gas flows from the test volume through at least one channel and out of the first port, and then increasing pressure at the first port such that the portion of the liquid flows from the first port through at least one droplet-generating region and into the test volume.

Across the independent claims, the inventive scope centers on a microfluidic chip network that supports droplet generation while constraining how fluid routes between ports relative to a test volume, and a loading method that introduces liquid into the test volume using a reduced-pressure gas-flow step followed by an increased-pressure liquid-flow step through the droplet-generating regions.

Stated Advantages

Reinforces seals during loading.

Avoids positive-pressure leak/seal issues.

Obviates extra oil and downstream pressure-equalization mechanisms.

Supports manufacturing precision and reduces droplet-size variability.

Documented Applications

Vacuum-loaded droplet microfluidic chip loading, including single-port loading and multi-port loading, using a microfluidic network that includes droplet-generating regions.

Loading systems and example structures for microfluidic chips with one or more microfluidic networks.

Droplet generation within constriction-to-expansion regions and multi-channel junction droplet generation, including shear at a T-junction, as part of vacuum-loaded droplet microfluidic chips.

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