Systems comprising a microfluidic device are provided for maintaining and analyzing tissue slices. Methods for maintaining tissue slices in a microfluidic device are further provided.

The disclosure generally relates to the preparation of representative samples from clinical samples, e.g., tumors (whole or in part), lymph nodes, metastases, cysts, polyps, or a combination or portion thereof, using mechanical and/or biochemical dissociation methods to homogenize intact samples or large portions thereof. The resulting homogenate provides the ability to obtain a correct representative sample despite spatial heterogeneity within the sample, increasing detection likelihood of low prevalence subclones, and is suitable for use in various diagnostic assays as well as the production of therapeutics, especially personalized anti-tumor vaccines or immune cell based therapies.

A molding apparatus for producing a biological tissue embedded in a block of an embedding material. The molding apparatus comprising a mold comprising a compartment configured for containing the embedding material. The compartment having a compartment floor and at least one wall extending upwards from said compartment floor. The compartment comprises at least one depression extending downwards from the compartment floor. The molding apparatus further comprising a sample sheet configured to attach to the biological tissue and hold the biological tissue thereon. The sample sheet being further dimensioned to be positioned in the compartment and to be constrained to the position thereof, at least along one direction, by the compartment. The depression is configured for accepting the biological tissue at least partially therein. Thereby the molding apparatus being configured for producing a block of an embedding material having at least one protrusion associated with the at least one depression wherein the biological tissue, attached to the sample sheet, is embedded at least partially in the protrusion.

A method of making a tissue reference control block is disclosed wherein cancer cells are selected with a known positivity or negativity for a specific marker and cancer cells are grown to a certain phase. The cancer cells are screened for an expression of the specific marker and the screened cancer cells are mixed with stromal cells and co-cultured in a bio-reactor bag. A spheroid grown from the co-cultured mixture of cells is harvested, fixed, and embedded in a core of a paraffin block.

A spheroid tissue microarray comprises an array of tissue spheroids embedded within a porous mold. The product may be impregnated with a wax or resin and sectioned, and contains spheroids which are precisely located in a regular geometric grid. A method of manufacturing a spheroid tissue microarray comprises the steps of: forming a mold of porous material from liquid mold material in a casting mold, and allowing the liquid mold material to set; removing the porous mold from the casting mold; topping up the porous mold with further liquid mold material, and allowing recesses to form in the surface of the mold by the drawing-in of liquid mold material through shrinkage as the liquid mold material sets; placing tissue spheroids into the recesses in the surface of the porous mold; and sealing the tissue spheroids within the mold by topping off with liquid mold material and allowing the liquid mold material to set. An alternative method comprises the steps of: forming a mold of porous material from liquid mold material in a casting mold; allowing the liquid mold material to set; removing the porous mold from the casting mold; placing spheroids in recesses at the bases of wells in the mold of porous material; and sealing the spheroids within the porous mold by adding further porous material on top of the spheroids; wherein the recesses at the bases of the wells in the porous material are formed by protrusions of the casting mold carrying further, nipple-shaped, protrusions.

The disclosure generally relates to the preparation of representative samples from clinical samples, e.g., tumors (whole or in part), lymph nodes, metastases, cysts, polyps, or a combination or portion thereof, using mechanical and/or biochemical dissociation methods to homogenize intact samples or large portions thereof. The resulting homogenate provides the ability to obtain a correct representative sample despite spatial heterogeneity within the sample, increasing detection likelihood of low prevalence subclones, and is suitable for use in various diagnostic assays as well as the production of therapeutics, especially personalized anti-tumor vaccines or immune cell based therapies.

A manufacturing method for mass production for a tissue or cell microarray, which is characterized in comprising: using a molding device to mold tissue particles, cultivated cells or collected exfoliated cells (such as exfoliated cells from pleural effusion and ascites), forming the tissue particles from blended fresh tissue, tissue fixed by formalin or another solvent (such as alcohol and so on) or a tissue block embedded in paraffin (blended by a tissue blender), implanting the molded tissue or cells cores in a receptor wax or adhering the molded tissue or cells cores onto a metal plate, and then slicing to obtain a tissue or cell microarray.

A method for making a microarray block with a recipient block formed from a material and having at least one bore therein. A cylindrical core of a biological sample and a carrier medium can be provided. At least a portion of the core can be disposed in the at least one bore of the recipient block. The core can be made compatible with the material of the recipient block before the disposing step. Related methods and assemblies are provided.

An in vitro experimental standard comprising sections cut from a homogenous cell block for use as a positive control for biomarkers in immunohistochemistry experiments. The homogenous cell block is produced using a three layered vertical apparatus to create an evenly distributed suspension of FFPE cells, wherein the cells are mixed with 3% agarose while still rotating within the apparatus's middle layer. The injection of the cell mixture into a mold creates a homogeneous cell block where each cell, or ratio of different types of cells, is evenly distributed. The cell mixture within the cell block may further comprise: a mixture of the same type of cell with different genetic modifications; a mixture of the same type of cell with different protein or nucleic acids expression; and a mixture of different types of cells with different genetic backgrounds, and/or different expression level of genes and/or proteins.

A tissue sample container including a base having a plurality of sample holding sections, which are configured to receive a plurality of tissue samples in a given orientation and are demarcated by section walls; and a lid configured to sealingly engage the base. The sample holding sections are sized and shaped to correspond to a specific tissue sample size and shape such that the base in cooperation with the section walls, maintain the given orientation and identity of the tissue samples within respective sample holding sections.