Fluorescently marked targets bind to a substrate 230 synthesized with polymer sequences at known locations. The targets are detected by exposing selected regions of the substrate 230 to light from a light source 100 and detecting the photons from the light fluoresced therefrom, and repeating the steps of exposure and detection until the substrate 230 is completely examined. The resulting data can be used to determine binding affinity of the targets to specific polymer sequences.

Method and apparatus for detection of fluorescently labeled materials

An automated immunostaining apparatus having a reagent application zone and a reagent supply zone. The apparatus has a carousel slide support supporting a plurality of slide supports thereon, and drive means engaging the carousel slide support for consecutively positioning each of a plurality of slide supports in the reagent application zone. The apparatus also has a carousel reagent support having a plurality of reagent container supports thereon, and drive means engaging the carousel for rotating the carousel and positioning a preselected reagent container support in the reagent supply zone. The apparatus also has a reagent delivery actuator means positioned for engaging a reagent container positioned on a container support in the reagent delivery zone and initiating reagent delivery from the reagent container to a slide supported on a slide support in the reagent receiving zone.

Automated biological reaction apparatus

The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Substrate preparation process

An automated microscope-slide-staining apparatus, having a supporting framework; an arm moveable in three dimensions attached to the framework; apparatus for moving the arm; a hollow tip head located on the arm; apparatus for alternatively supplying positive or negative gas pressure to the hollow tip head; a removable wash/blow tip having an exit slit, the wash/blow tip being adapted to be removably attached to the hollow tip head by a preselected movement of the arm; a wash/blow tip holder at a first fixed location on the framework; a reagent application tip holder at a second fixed location on the framework for holding a reagent application tip, the reagent application tip being adapted to be removably attached to the hollow tip head by a preselected movement of the arm; a reagent container holder at a third fixed location on the framework; a microscope slide holder at a fourth fixed location on the framework, the microscope slide holder being adapted to removably contain the microscope slide; and control apparatus for controlling movement of the arm between the locations, whereby the tip head picks up the wash/blow tip or the reagent application tip in response to movement of the arm under control of the control apparatus and moves to one or more of the locations to pick up a reagent in the reagent container or dispense the reagent on the slide or to dispense a gas through the wash/blow tip over the slide. Components of the apparatus and methods of staining are also part of the invention.

Automated staining apparatus

Apparatus and methods for automatically staining or treating multiple tissue samples mounted on microscope slides are provided. Individualized slide temperature control is accomplished by the heating system according to the present invention that has thermal platforms radially mounted to the carousel for heating the slides and sensing the temperature of each. The heating system also permits automated de-waxing if necessary.

Automated molecular pathology apparatus having independent slide heaters

An automated immunostaining apparatus having a reagent application zone and a reagent supply zone. The apparatus has a carousel slide support supporting a plurality of slide supports thereon, and drive device engaging the carousel slide support for consecutively positioning each of a plurality of slide supports in the reagent application zone. The apparatus also has a carousel reagent support having a plurality of reagent container supports thereon, and drive device engaging the carousel for rotating the carousel and positioning a preselected reagent container support in the reagent supply zone. The apparatus also has a reagent delivery actuator device positioned for engaging a reagent container positioned on a container support in the reagent delivery zone and initating reagent delivery from the reagent container to a slide supported on a slide support in the reagent receiving zone.

Automated slide processing apparatus with fluid injector

The present invention provides an improved method for staining slides using immunochemical reagents. The method comprises the following steps. The assay region of a slide (the region containing the tissue section)is washed with an improved rinsing solution comprising water and a detergent. An evaporation inhibitor liquid is applied to the slide to cover the assay region. For antigens requiring unmasking, the tissue section is combined with an improved, stabilized proteolytic enzyme solution. The slide is rinsed, and the evaporation inhibitor liquid is reapplied to the slide. A primary antibody in an improved diluent containing globulins from the same species as a second antibody is combined with the tissue section for a time sufficient for substantially complete antibody binding. The slide is rinsed, and the evaporation inhibitor liquid is reapplied. A labeled second antibody in the improved diluent is combined with the tissue section for a time sufficient for substantially complete antibody binding. The slide is rinsed, and the evaporation inhibitor liquid is reapplied to the slide. Color development reagents, including a stabilized peroxidase chromophore formulation, are combined with the tissue section for a time sufficient for color development. The stabilized peroxidase chromophore formulation consists essentially of a peroxidase chromophore, at a concentration in the working range of the enzyme, an acidic buffer, a reducing agent, and a glycol. Preferred chromophores include 3,3'-diaminobenzidine and tetrahydrochloride (DAB) and 3-amino-9-ethylcarbazole (AEC). After color development, the tissue section is washed and is then ready for analysis.

Immunohistochemical staining method and reagents therefor

The present invention provides an improved biotin-avidin formulation in which a biotinylated antibody conjugate or an avidin-enzyme conjugate is present in a suitable diluent for immunohistochemical staining. The diluent additionally comprises casein in an amount sufficient to prevent charge interactions of the conjugate with a tissue section and gamma globulin in an amount sufficient to prevent Fc receptor binding and any hydrophobic interaction of the conjugate with a tissue section. In a preferred embodiment, the immunoglobulin is from the same species as the biotinylated antibody conjugate. The formulation effectively reduces overall unwanted binding, irrespective of the source of the binding.

Biotin/avidin formulation

Embodiments of hapten conjugates including a hapten, an optional linker, and a peroxidase- activatable aryl moiety are disclosed. In some embodiments, the peroxidase- activatable aryl moiety is tyramine or a tyramine derivative. Embodiments of methods for making and using the hapten conjugates also are disclosed. In particular embodiments, the hapten conjugates are used in a signal amplification assay. In certain embodiments, the hapten is an oxazole, a pyrazole, a thiazole, a benzofurazan, a triterpene, a urea, a thiourea other than a rhodamine thiourea, a nitroaryl other than dinitrophenyl or trinitrophenyl, a rotenoid, a cyclolignan, a heterobiaryl, an azoaryl, a benzodiazepine, or 7-diethylamino-3- carboxycoumarin. The hapten is coupled to the peroxidase-activatable aryl moiety directly or indirectly via a linker. In certain embodiments, the hapten conjugates are used in multiplexed assays.

Phillip C. Miller

Papers

Automated biological reaction apparatus

Automated slide processing apparatus with fluid injector

Immunohistochemical staining method and reagents therefor

Biotin/avidin formulation

Hapten conjugates for target detection