Microfluidic devices and methods for cell processing

Inventors

Collins, John

Assignees

Biopico Systems Inc

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Publication Number

US-10232371-B2

Patent

Publication Date

2019-03-19

Expiration Date


Abstract

Microfluidic devices and methods that use cells such as cancer cells, stem cells, blood cells for preprocessing, sorting for various biodiagnostics or therapeutical applications are described. Microfluidics electrical sensing such as measurement of field potential or current and phenomena such as immiscible fluidics, inertial fluidics are used as the basis for cell and molecular processing (e.g., characterizing, sorting, isolation, processing, amplification.) of different particles, chemical compositions or biospecies (e.g., different cells, cells containing different substances, different particles, different biochemical compositions, proteins, enzymes etc.). Specifically, the present invention discloses a number of sorting schemes for stem cells, whole blood and circulating tumor cells, and extracting serum from whole blood.

Core Innovation

A spiral microfluidic channel system is provided for processing a plurality of cells. An inlet flows the plurality of cells into a primary spiral microfluidic channel comprising a plurality of pinching regions, and a plurality of secondary spiral microfluidic channels are coupled to separate the plurality of cells.

At least one of the plurality of secondary spiral microfluidic channels has progressively varying widths. The system further includes substantially concentric primary and secondary spiral microfluidic channels, and expansion structures whose widths increase from an inlet to an outlet along the spiral channels.

The spiral microfluidic channel system is configured to separate circulating tumor cells (CTCs) using the primary spiral microfluidic channel and to separate red blood cells (RBCs) using at least one secondary spiral microfluidic channel. The disclosure is also described as inertial microfluidic CTC separation from whole blood using spiral “yoked” channels with width gradients and periodic pinching regions for fractionation of RBCs, leukocytes, and CTCs.

Claims Coverage

The independent claim defines a spiral microfluidic channel system with an inlet, a primary spiral channel with pinching regions, and secondary spiral channels for separating cells, with the key inventive feature being progressively varying widths in at least one secondary spiral microfluidic channel. Dependent claims further specify concentric channel architecture, interconnect coupling and size-based trapping, expansion structures, and separation of CTCs and RBCs.

Spiral microfluidic channel system for separating a plurality of cells

A spiral microfluidic channel system comprising an inlet for flowing a plurality of cells, a primary spiral microfluidic channel coupled to the inlet and comprising a plurality of pinching regions, and a plurality of secondary spiral microfluidic channels for separating the plurality of cells.

Progressively varying widths in secondary spiral channels

At least one of the plurality of secondary spiral microfluidic channels has progressively varying widths.

Substantially concentric primary and secondary spiral channels

The primary spiral microfluidic channel and the plurality of secondary spiral microfluidic channels are substantially concentric.

Secondary-channel coupling via interconnect channels and size-based trapping

One secondary spiral microfluidic channel is coupled to another via a second plurality of interconnect channels smaller than the first, trapping larger cells in the primary channel and passing smaller cells to the secondary channels.

Increasing widths from inlet to outlet via expansion structures

The spiral microfluidic channel system includes expansion structures whose widths increase from the inlet to the outlet along the spiral channels.

Separating circulating tumor cells using the primary spiral channel

The spiral microfluidic channel system is configured to separate circulating tumor cells (CTCs) from said plurality of cells using the primary spiral microfluidic channel.

Separating red blood cells using at least one secondary spiral channel

The spiral microfluidic channel system includes at least one secondary spiral microfluidic channel configured to separate red blood cells (RBCs) from a plurality of cells.

Claim coverage centers on a spiral microfluidic channel system that separates a plurality of cells using a primary spiral channel with pinching regions and multiple secondary spiral channels, with progressively varying widths in at least one secondary spiral channel providing the core separation geometry. Dependent claims further specify concentric layouts, interconnect coupling with larger/smaller cell behavior, increasing width expansion structures, and separation of CTCs and RBCs.

Stated Advantages

Enables separation of a plurality of cells using a spiral microfluidic channel system with pinching regions and secondary spiral channels.

Provides separation of circulating tumor cells (CTCs) using the primary spiral microfluidic channel.

Provides separation of red blood cells (RBCs) using at least one secondary spiral microfluidic channel.

Documented Applications

Inertial microfluidic CTC separation from whole blood with fractionation of RBCs, leukocytes, and CTCs.

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