Scaffolds and other cell-growth structures using microfluidics to culture biological samples

Patent metadata

Field	Value
Publication number	US-9957481-B2
Application number	US-201313944776-A
Country	US
Kind code	B2
Filing date	Jul 17, 2013
Priority date	Oct 20, 2009
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

Methods and apparatuses for using microfluidics to generate bubbles and using the generated bubbles to construct scaffolds and cell-holding structures for culturing biological samples or analytes. In one implementation, a scaffold for growing cells is provided to include a matrix of interconnected cavities formed from mixing a gas and a liquid containing a cross linkable material to produce a matrix of gas bubbles of substantially the same size and cross linking the cross linkable material to form a structure in which cells are grown. In another implementation, a scaffold apparatus for growing cells includes a ball of a cross linked material forming an exterior shell that encloses to form a hollow interior inside the ball and biological samples embedded in the external shell.

First claim

What is claimed is:

1. An apparatus for producing gas bubbles, comprising:
an outer micropipette including an outer outlet having an outer outlet diameter, the outer micropipette configured to allow a liquid to flow through;
an inner micropipette located inside the outer micropipette to separate the interior within the outer micropipette into a gas flow region inside the inner micropipette and a liquid flow region between the inner micropipette and the outer micropipette, the inner micropipette including an inner outlet having an inner outlet diameter to allow a gas to flow through and to mix with the liquid before the liquid flows through the outer outlet to produce gas bubbles inside the liquid at the outer outlet, the outer micropipette and the inner micropipette being configured to make the gas bubbles as a single stream of gas bubbles uniform in size, one gas bubble at a time;
a first fluid inlet coupled to inner micropipette to receive the gas to pass through the inner micropipette;
a second fluid inlet coupled to the outer micropipette to receive the liquid to pass through the region inside the outer micropipette and between the outer micropipette and the inner micropipette,
wherein a surface of the inner outlet and a surface of the outer inlet are separated by a distance between and including 350 μm and 450 μm, the diameter of the inner outlet is between 25 μm and 35 μm, and the diameter of the outer outlet is between and including 60 μm and 75 μm; and
a formation device for collecting the produced gas bubbles to form a matrix structure, wherein the formation device includes
a reservoir that holds gas bubbles;
an input channel that is connected to the reservoir to direct the gas bubbles output by the outer micropipette into the reservoir;
an output channel that is connected to the reservoir to direct excessive gas bubbles out of the reservoir; and
a reservoir cover removably engaged to cover a top opening of the reservoir to form an enclosure for containing the gas bubbles in a shape defined by the reservoir and the reservoir cover to be crosslinked to form a matrix structure.

2. The apparatus of claim 1 , wherein the inner micropipette has a frusto-conical shape, and the outer micropipette has a frusto-conical shape.

3. The apparatus of claim 1 , wherein the inner outlet is parallel to the outer outlet, the inner outlet and the outer outlet forming a frusto-conical region between a plane on which the inner outlet lies and the outer outlet of the outer micropipette, the plane extending to intersect edges of the outer micropipette, wherein a diameter of a base of the frusto-conical region is between and includes 350 μm and 450 μm.

4. The apparatus of claim 1 , wherein the outer outlet has a square cross-section.

5. The apparatus of claim 1 , wherein the liquid is an aqueous solution including a salt and a surfactant.

6. The apparatus of claim 1 , wherein the inner outlet has a circular cross-section.

Assignees

• Academia Sinica

Inventors

• Lin Keng-Hui
• Mishra Narayan
• Liu Yen-Liang
• Wang Chen-Chie

Classifications

• C12N2533/74

  Alginate · CPC title

• C12N5/0655 Primary

  Chondrocytes; Cartilage · CPC title

• B29C44/00 Primary

  Shaping by internal pressure generated in the material, e.g. swelling or foaming {; Producing porous or cellular expanded plastics articles} · CPC title

• C12M25/14

  Scaffolds; Matrices (in general C12N5/0068) · CPC title

• C12N5/0068

  General culture methods using substrates (for specific animal cell type C12N5/06) · CPC title