High-throughput tissue microarray technology and applications

An apparatus for constructing tissue arrays from a plurality of donor tissue specimens, comprising:

• a donor source containing a plurality of identifiable donor tissue specimens;
• a retriever that retrieves the donor tissue specimens from the donor source;
• a tissue array constructor receiving donor tissue specimens retrieved by the retriever, the tissue array constructor obtaining tissue samples from different tissue specimens retrieved by the retriever and inserting the tissue samples into recipient blocks, thereby constructing a tissue array;
• and
• a controller operating the retriever and array constructor, the controller further identifying tissue samples within the array.

An apparatus for assembling tissue arrays, comprising:

• a donor specimen station which includes compartments for assigned tissue specimens;
• a computer readable identifier which identifies the tissue specimens in the donor specimen station;
• a donor block scanner for determining a location of the tissue specimens in the carrier;
• a tissue array fabricator for obtaining a plurality of elongated tissue samples from a plurality of tissue specimens, and placing the plurality of elongated tissue samples in a recipient block;
• a sectioner that sections the recipient block sufficiently transverse to the elongated tissue samples to form a series of block sections which retain a relationship of the elongated tissue samples in the recipient block;
• a processing station that exposes different sections to different biological markers that associate with biological substrates of interest in the sections, if the biological substrates are present;
• and
• a scanner that scans the different sections to detect the presence of the biomarkers in the different sections.

A device for performing molecular analysis of biological specimens, comprising:

• storage means for storing a plurality of biological specimens embedded in embedding medium;
• automated array forming means for obtaining multiple tissue samples from a biological specimen, inserting the tissue samples in corresponding positions in different recipient substrates to make multiple arrays of similar biological specimens, and sectioning the recipient substrates to make multiple corresponding sections of each recipient substrate;
• automated reaction means for reacting the multiple corresponding sections of the different recipient substrates with biological reagents that react with biological substrates of interest in the sections;
• automated detection means for detecting a presence, or a quantity, or both a presence and a quantity, of the biological reagent in the sections;
• and
• computer means for recording information about subjects from whom the biological specimens were obtained, and correlating that information with the presence, quantity, or presence and quantity of the biological reagent in the sections.

A method for performing molecular analysis of biological specimens, comprising:

• providing multiple sections each comprising multiple biological samples;
• exposing different sections to different biological reagents that react with biological markers in the biological samples
• obtaining images of the different sections after exposing the sections to the different biological reagents;
• and
• analyzing the images to determine whether a reaction with a biological marker has occurred in the different specimens.

A method for constructing tissue microarrays from a plurality of donor specimens, comprising:

• providing a donor array of tissue donor blocks, each block including a tissue specimen embedded in embedding medium and being identifiable in a donor block array;
• retrieving identified tissue donor blocks from the donor block array;
• obtaining tissue samples from retrieved tissue donor blocks and inserting tissue samples from the tissue specimen into different recipient blocks;
• and
• sectioning the blocks.

A computer implemented system for rapid construction and analysis of tissue microarray sections, comprising:

• a recipient block retriever obtaining recipient blocks from a recipient block array, and transferring recipient blocks to a sectioner;
• the sectioner cutting sections from recipient blocks, and mounting the sections on a solid support;
• a conveyor transferring the mounted sections to a processor;
• the processor processing the mounted samples for biological analysis;
• an image analyzer, imaging tissue microarray sections and analyzing them for presence of biological markers;
• a database, storing information identifying tissue samples analyzed, and information obtained from analysis of tissue microarray sections for presence of biological markers.

A method of examining a biological sample, comprising:

• providing a plurality of biological samples at identifiable positions in an array;
• subjecting the biological samples in the array to a biological analysis;
• examining the array to detect a biological marker;
• wherein the biological analyses are performed or analyzed at multiple different locations.

A method of examining biological samples, comprising:

• placing a plurality of elongated biological samples at identifiable positions in a substrate that is capable of being sectioned;
• sectioning the substrate to provide a plurality of substantial copies of an array of the biological samples, with the samples at the identifiable positions;
• identifying one or more reference copies;
• disseminating one or more dissemination copies to others;
• and
• comparing a biological interpretation of one or more dissemination copies to a biological interpretation of one or more reference copies.

A method for reviewing biological specimens, comprising:

• providing multiple sections each comprising multiple biological samples;
• obtaining images of the different sections after exposing the sections to the different biological reagents;
• and
• disseminating the images to different recipients.

A method for standardizing pathological evaluations, comprising:

• visualizing a cellular specimen at a specific location in a cross-section of an microarray of a plurality of cellular specimens, wherein the array comprises a plurality of cellular specimens in a matrix, with the cellular specimens positioned at predetermined known positions in the matrix, such than when multiple sections of the matrix are provided, a two dimensional microarray of specimens is obtained, with each specimen at a predetermined position in the microarray;
• analyzing the cellular specimen at the specific location to produce an evaluation of a particular biological characteristic;
• and
• comparing the evaluation to a standard.

A method for parallel evaluation of a cross-section of a cellular specimen, comprising:

• (a) visualizing a first cross-section of the cellular specimen in a microarray of a plurality of cellular specimens of interest at a work-site, wherein the microarray comprises a plurality of cellular specimens in a matrix, with the cellular specimens positioned at predetermined known positions in the matrix, such than when multiple sections of the matrix are provided, a two dimensional microarray of specimens is provided, with each specimen at a predetermined position in the microarray, and wherein an immunological analysis, a histological stain, or a nucleic acid hybridization has been performed on each cellular specimen;
• (b) analyzing a cross-section of the cellular specimen by examining the results of the immunological analysis, the histological stain, or the nucleic acid hybridization in the array to produce an evaluation of the cellular specimen for a clinical parameter;
• and
• (c) comparing the evaluation of the cellular specimen to a standard evaluation in a data set comprising an evaluation of each of the cellular specimens of interest positioned at the predetermined known position in the microarray, wherein the data in the data set is accessible by position, and the data set is stored at the work-site or at a remote location.

A method for parallel evaluation of a cross-section of a cellular specimen, comprising:

• (a) visualizing a first cross-section of the cellular specimen in a microarray of a plurality of cellular specimens of interest, wherein the microarray comprises a plurality of cellular specimens in a matrix, with the cellular specimens positioned at predetermined known positions in the matrix, such than when multiple sections of the matrix are provided, a two dimensional microarray of specimens is provided, with each specimen at a predetermined position in the microarray, and wherein an biological analysis comprising an immunological analysis, a histological stain, or a nucleic acid hybridization has been performed on each cellular specimen, wherein the cellular specimens has been produced in a first location;
• (b) analyzing the first cross-section of the cellular specimen by examining the results of the immunological analysis, the histological stain, or the nucleic acid hybridization in the first cellular specimen to produce a first evaluation of the first cellular specimen for a clinical parameter;
• (c) visualizing a second cross-section of a second cellular specimen in the microarray of a plurality of cellular specimens of interest, wherein the second cellular specimen has been produced in a second location distinct from the first location;
• (d) analyzing the second cross-section of the cellular specimen by examining the results of the immunological analysis, the histological stain, or the nucleic acid hybridization in the second cellular specimen to produce a second evaluation of the cellular specimen for a clinical parameter;
• (e) comparing the first evaluation of the first cellular specimen with the second evaluation of the second specimen, in order to compare the biological analysis performed on the first cellular specimen with the biological analysis performed on the second cellular specimen.