Apparatuses for contactless loading and imaging of microfluidic chips and related methods

Inventors

Johnson, Ross • Isom, Jonathan • Bussian, David • Arab, Nicolas

Assignees

Pattern Bioscience Inc

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Publication Number

US-10953404-B1

Patent

Publication Date

2021-03-23

Expiration Date


Abstract

An apparatus for loading and imaging a microfluidic chip can comprise a housing having walls that define a vacuum chamber and a first receptacle disposed within the vacuum chamber, the first receptacle defining a space for receiving one or more microfluidic chips. The apparatus can also include a negative pressure source, a light source, and an optical sensor coupled to the housing. The negative pressure source can be configured to reduce pressure within the vacuum chamber, the light source can be positioned to illuminate at least a portion of the space for receiving the chip(s), and the optical sensor can be positioned to capture an image of at least a portion of the space for receiving the chip(s).

Core Innovation

The invention relates to an apparatus and associated method for loading and imaging a microfluidic chip in a vacuum chamber defined by walls of a housing. One or more microfluidic chips are disposed within the vacuum chamber, and each chip includes one or more microfluidic networks having an inlet port containing liquid, a test volume containing gas, and a flow path extending between the inlet port and the test volume, including a droplet-generating region along which a minimum cross-sectional area increases along the flow path toward the test volume.

The method reduces pressure within the vacuum chamber so that, for each network of each chip, gas flows from the test volume and out of at least one port. After reducing pressure, the method increases pressure within the vacuum chamber such that, for each network, liquid flows from the inlet port, through the flow path, and into the test volume.

While the chip is disposed within the vacuum chamber, the method captures an image of liquid within the test volume for each network of each chip. The disclosure further includes vacuum loading and imaging arrangements that provide optical access through transparent wall portions and an optical sensor positioned outside the vacuum chamber, with optional movement of the optical sensor to image droplets in chip test volumes.

The disclosure characterizes droplet imaging in the test volume and includes optional enhancements such as integrating heating and using optical arrangements with excitation and fluorescence/spectral filters, including fluorescence compounds such as resazurin and spectrum-selective filtering for capturing images of fluorescence associated with droplets.

Claims Coverage

Independent claim 1 covers a method that combines staged vacuum evacuation and pressurization inside a housing-defined vacuum chamber with in-vacuum imaging of liquid in microfluidic test volumes. The primary inventive features are the pressure-driven gas evacuation, pressure-driven liquid loading through a droplet-generating region with increasing minimum cross-sectional area, and capturing an image while the chip remains disposed in the vacuum chamber. No additional independent claims are explicitly provided in the partial content.

Vacuum-chamber disposition of microfluidic chips with droplet-generating networks

Disposing one or more microfluidic chips within a vacuum chamber defined by walls of a housing, each chip having one or more microfluidic networks that include an inlet port containing liquid, a test volume containing gas, and a flow path between the inlet port and the test volume with a droplet-generating region along which a minimum cross-sectional area increases along the flow path toward the test volume.

Pressure reduction to evacuate gas from test volume through ports

Reducing pressure within the vacuum chamber such that, for each network of each chip, gas flows from the test volume and out of at least one of the port(s).

Pressure increase to drive liquid from inlet port through flow path into test volume

After reducing pressure within the vacuum chamber, increasing pressure within the vacuum chamber such that, for each network of each chip, liquid flows from the inlet port, through the flow path, and into the test volume.

In-vacuum imaging of liquid in the test volume while chip is disposed in vacuum chamber

For each network of each chip, capturing an image of liquid within the test volume while the chip is disposed within the vacuum chamber.

Based on the provided partial content, the claim coverage centers on staged vacuum evacuation and pressurization performed within a housing-defined vacuum chamber, where the microfluidic network structure includes an inlet port, a gas-filled test volume, and a flow path with a droplet-generating region having increasing minimum cross-sectional area, followed by capturing an image of liquid in the test volume while the chip remains in the vacuum chamber.

Stated Advantages

Maintaining the chip disposed within the vacuum chamber while capturing images of liquid within the test volume.

Maintaining droplet positioning without requiring chip sealing/transfer [as described in the provided partial summary].

Faster pressure equalization/imaging [as described in the provided partial summary].

Optional integration of heating and barcode scanning [as described in the provided partial summary].

Optical access through transparent wall portions and imaging via an optical sensor positioned outside the vacuum chamber [as described in the provided partial summary].

Documented Applications

Contactless vacuum loading and imaging of microfluidic chips that generate droplets [as described in the provided partial summary].

Imaging of droplets in chip test volumes in a vacuum chamber using fluorescence/spectral filters, including resazurin viability indicators [as described in the provided partial summary].

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