Three-dimensional microfluidic metastasis array

A method comprising:

• three-dimensionally (3D) printing a device comprising:
• a body extending away from a substrate, wherein a first end of the body comprises an open-facing port configured to allow introduction of a tissue sample chosen from multicellular tumor spheroids derived from established cell lines, engineered animal models, patient-derived xenografts, or primary tumor biopsies, wherein the tissue sample has a diameter of greater than about 500 microns, wherein a second end of the body opposite the first end forms an open outlet proximal the major surface of the substrate, and wherein at least a portion of the body comprises therein a primary tissue chamber;
• at least one microfluidic channel on the major surface of the substrate, wherein the microfluidic channel is fluidly connected to the tissue chamber, and wherein the microfluidic channel comprises an inlet upstream of the tissue chamber and an outlet downstream of the tissue chamber;
• and
• a separation element between the primary tissue chamber and the at least one microfluidic channel;
• and wherein the tissue chamber, the separation element and the microfluidic channel occupy a single layer on the substrate.

An in vitro assay system comprising:

• a substrate;
• a body extending away from a major surface of the substrate, wherein the body comprises an open first end sized to allow introduction of a tissue sample chosen from multicellular tumor spheroids derived from established cell lines, engineered animal models, patient-derived xenografts, or primary tumor biopsies, wherein the tissue sample has a diameter of greater than about 500 microns and an open second end opposite the first end, wherein the body comprises therein a tissue chamber, an extracellular matrix material in at least a portion of the tissue chamber;
• at least one microfluidic channel on the major surface of the substrate, wherein the at least one microfluidic channel comprises a media inlet upstream of the tissue chamber and a media outlet downstream of the tissue chamber;
• a separation element between the tissue chamber and the microfluidic channel, wherein the separation element is configured to retain the extracellular matrix material in the tissue chamber, and wherein the separation element comprises at least one passage containing the extracellular matrix material;
• and
• an interface region downstream of the at least one passage in the separation element, wherein the interface region provides fluid communication between the extracellular matrix material and a media composition in the at least one microfluidic channel.