Microfluidic chip

Inventors

Xia, ZhengZhou, YuLarsen, JohnSHAO, GuochengPeterson, ShaneFAUST, Marjorie

Assignees

ABS Global Inc

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Publication Number

US-11512691-B2

Patent

Publication Date

2022-11-29

Expiration Date


Abstract

A microfluidic chip orients and isolates components in a sample fluid mixture by two step focusing, where sheath fluids compress the sample fluid mixture in a sample input channel in one direction, such that the sample fluid mixture becomes a narrower stream bounded by the sheath fluids, and by having the sheath fluids compress the sample fluid mixture in a second direction further downstream, such that the components are compressed and oriented in a selected direction to pass through an interrogation chamber in single file formation for identification and separation by various methods. The isolation mechanism utilizes external, stacked piezoelectric actuator assemblies disposed on a microfluidic chip holder, or piezoelectric actuator assemblies on-chip, so that the actuator assemblies are triggered by an electronic signal to actuate jet chambers on either side of the sample input channel, to jet selected components in the sample input channel into one of the output channels.

Core Innovation

The invention describes a microfluidic chip system for sorting particles using a microfluidics-based flow cytometry apparatus. A fluid sample comprising a plurality of particles suspended in the fluid sample is flowed into a channel of a microfluidic chip while first sheath fluid flow and second sheath fluid flow are flowed into the microfluidic chip. The fluid sample is intersected with the first sheath fluid flow at a first intersection to focus the fluid sample while maintaining laminar fluid flow, and the fluid sample and the first sheath fluid flow are then intersected with the second sheath fluid flow at a second intersection to further focus the fluid sample while maintaining laminar fluid flow, causing the plurality of particles to flow in approximately single file formation.

At an interrogation location in the channel of the microfluidic chip, particles are interrogated individually by the emission of electromagnetic radiation. The particles are distinguished based on the interrogating, and the particles are sorted based on the distinguishing step. Sorting comprises diverting a subset of the plurality of particles from the focused flow into one of a plurality of output channels, and collecting the diverted subset from the output channel.

The invention further applies to sorting cells by obtaining a sample of live cells and staining the sample of live cells with a dye in a media to obtain a fluid sample comprising a plurality of cells. The live cells are focused into approximately single file formation by intersecting the fluid sample with first sheath fluid flow at a first intersection and intersecting the fluid sample and the first sheath fluid flow with the second sheath fluid flow at a second intersection, while maintaining laminar fluid flow. The cells are interrogated individually by emission of electromagnetic radiation, distinguished based on a physical characteristic identifiable by the interrogating, and sorted by diverting a subset of the plurality of cells into one of three output channels with maintained cross-section and length relationships that provide desired hydraulic resistance.

Claims Coverage

The partial content provides two independent claims. Each independent claim includes multi-intersection laminar focusing into approximately single file formation, individual interrogation by emitted electromagnetic radiation, distinguishing based on interrogation, and sorting by diverting a detected subset into output channels with maintained channel geometry for desired hydraulic resistance.

Two-step laminar focusing to approximately single file formation

Intersecting the fluid sample with the first sheath fluid flow at a first intersection to focus the fluid sample while maintaining laminar fluid flow, and intersecting the fluid sample and the first sheath fluid flow with the second sheath fluid flow at a second intersection to further focus the fluid sample into a focused fluid flow while maintaining the laminar fluid flow, causing the plurality of particles or cells to flow in approximately single file formation.

Individual interrogation by emission of electromagnetic radiation

Interrogating particles or cells individually at an interrogation location in the channel by the emission of electromagnetic radiation.

Distinguishing based on interrogation

Distinguishing the particles or cells based on the interrogating.

Sorting by diverting subset into output channels with hydraulic resistance

Sorting comprising diverting a subset of the plurality of particles or cells from the focused flow into one of a plurality of output channels, wherein a cross-section and length of each output channel is maintained to provide a desired hydraulic resistance, followed by collecting the diverted subset.

Live cell sample staining with dye

Obtaining a sample of live cells and staining the sample of live cells with a dye in a media to obtain a fluid sample comprising a plurality of cells suspended in the fluid sample.

Across the independent claims, the core claimed coverage is a microfluidics-based flow cytometry approach that uses first and second sheath-flow intersections to achieve approximately single file formation under laminar flow, interrogates particles or cells individually by emitted electromagnetic radiation, distinguishes them based on interrogation, and sorts them by diverting a detected subset into output channels sized to provide desired hydraulic resistance, followed by collecting the diverted subset.

Stated Advantages

Provides desired hydraulic resistance for diverting the subset by maintaining output channel cross-section and length relationships.

Documented Applications

Sorting particles using a microfluidics-based flow cytometry apparatus by focusing into approximately single file formation and collecting diverted subsets from output channels.

Sorting cells, including live cells, in a microfluidics-based flow cytometry apparatus by staining live cells with a dye, focusing into approximately single file formation, interrogating and distinguishing by physical characteristics, and collecting diverted subsets from output channels.

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