Microfluidic capsule

Inventors

Thorslund, SaraKreuger, JohanNguyen, Hugo

Assignees

Gradientech AB

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Publication Number

US-8828332-B2

Patent

Publication Date

2014-09-09

Expiration Date


Abstract

A microfluidic capsule (1) comprises a top lid (100), a middle piece (200) and a bottom piece (300) to be assembled to enclose a microfluidic substrate (400) for analysis of cells and biochemical reactions. The middle piece (200) comprises support structures in the form of support pillars (250) and walls (240) around a central light window (220) to provide mechanical support and prevent tension-induced structural deformations. When fully assembled, light windows (120, 220, 230) in the top lid (100), middle piece (200) and bottom piece (300) allows inspection of biological and/or biochemical samples positioned in the enclosed microfluidic substrate (400).

Core Innovation

The invention relates to a microfluidic capsule having a top lid, a middle piece, and a bottom piece assembled to provide aligned light windows for microscopy and visual inspection. The top lid includes a lid sheet comprising a light window, and the bottom piece includes a bottom sheet with a light window that aligns with the light windows of the top lid and the middle piece when assembled, so that observation through the capsule is supported while the microfluidic components are enclosed.

The middle piece includes a middle sheet with a perimeter and at least one fluid inlet and at least one fluid outlet provided as through holes in the middle sheet, together with a light window positioned to align with the light window of the top lid. A circumferential or circumferentially distributed wall surrounds the perimeter, and multiple circumferential raised walls are distributed around the perimeter with raised connection structures between them, the raised connection structures having a height lower than the multiple raised walls. At least one support pillar is attached to the middle sheet between the perimeter of the middle sheet and the perimeter of the light window.

The capsule further includes inlet connectors in the form of tubes with a first end connected to the fluid inlets and a second end protruding through an opening of a wall of the multiple raised walls, and a bottom piece that locks to the middle piece via multiple circumferential snap-fit structures aligned with raised connection structures. The microfluidic substrate is enclosed between the bottom piece and the middle piece so that an open culture chamber aligned with the light windows becomes closed by a transparent cover sheet, while at least one fluid channel of the microfluidic substrate becomes connected to the fluid inlet and fluid outlet.

Claims Coverage

Independent claim clm-00001 defines a layered microfluidic capsule structure with aligned light windows, fluid inlet/outlet through holes and tube inlet connectors, mechanically reinforced middle-sheet wall geometry with support pillars, snap-fit locking, and a transparent cover that closes an aligned open culture chamber while connecting microfluidic fluid channels to the inlet and outlet. Overall, it specifies seven inventive features spanning optical alignment, fluid coupling, mechanical reinforcement, and enclosure of the microfluidic substrate.

Layered microfluidic capsule with aligned light windows

A microfluidic capsule comprising a top lid in the form of a lid sheet comprising a light window; a bottom piece comprising a bottom sheet having a light window allowing visual inspection through the light window of the top lid and the light window of the middle piece when the bottom piece is attached to the middle piece and the top lid.

Middle sheet with through-hole fluid inlet/outlet and aligned light window

A middle piece comprising a middle sheet having a perimeter and comprising at least one fluid inlet and at least one fluid outlet in the form of through holes in said middle sheet and a light window positioned to be aligned with said light window of said top lid when said top lid is attached to said middle piece.

Circumferential wall and raised wall reinforcement with raised connection structures

A circumferential or circumferentially distributed wall around its perimeter; multiple raised walls circumferentially distributed around said perimeter separated by raised connection structures having a height relative said middle sheet that is lower than a height of said multiple raised walls relative said middle sheet.

Support pillar positioned between middle-sheet perimeter and light window perimeter

At least one support pillar attached to said middle sheet at a position between said perimeter of said middle sheet and said perimeter of said light window, wherein the ends of said multiple raised walls, said circumferential or circumferentially distributed wall and said at least one support pillar facing opposite to said middle sheet are arranged to be attached to said top lid.

Tube inlet connectors protruding through openings of multiple raised walls

At least one inlet connector in the form of a tube having a first end connected to said at least one fluid inlet and having a second, opposite end protruding out through an opening of a wall of said multiple raised walls.

Bottom piece snap-fit locking structures aligned with raised connection structures

Multiple snap-fit structures circumferentially distributed around said perimeter of said bottom sheet and extending from said bottom sheet and positioned to be aligned with said raised connection structures to lock said bottom piece to said middle piece.

Transparent cover sheet closing an aligned open culture chamber while connecting fluid channels

A transparent cover sheet, wherein said microfluidic capsule is designed to enclose a microfluidic substrate between said bottom piece and said middle piece so that an open culture chamber of said microfluidic substrate aligned with said light windows of said top lid, said middle piece and said bottom piece becomes closed by said transparent cover sheet and at least one fluid channel of said microfluidic substrate becomes connected to said at least one fluid inlet and said at least one fluid outlet.

The claim coverage centers on a microfluidic capsule architecture that aligns light windows across a top lid, middle piece, and bottom piece, while reinforcing the middle sheet using circumferential and raised wall structures separated by lower-height raised connection structures and supported by support pillars. It also includes tube-based inlet connectors through openings in the raised walls, bottom-piece snap-fit locking aligned with the raised connection structures, and a transparent cover sheet that encloses and closes an open culture chamber while connecting the microfluidic substrate’s fluid channels to the capsule’s inlet and outlet.

Stated Advantages

Reduces bending deformation of the middle sheet, supported by FEM modeling results.

Prevents tension-induced deformation by mechanically reinforcing the middle sheet using circumferential wall, raised walls, raised connection structures, and support pillars.

Maintains functionality and viability in an assembled capsule, as described in a proof-of-concept cell culture and FITC-dextran concentration gradient formation.

Documented Applications

Microscopy and visual inspection through aligned light windows of the assembled microfluidic capsule.

Enclosed open culture chamber operation for cell culture within the microfluidic substrate, as demonstrated with human endothelial cells and maintained viability.

Formation of an FITC-dextran concentration gradient within the microfluidic substrate in the assembled capsule, with maintained functionality.

Waste collection by using a waste absorber to absorb fluid entering from at least one fluid outlet.

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