Automated systems and methods for preparing biological specimens for examination
The systems and methods disclosed herein permit automated preparation of biological specimens for examination. The disclosed systems and methods provide fast, efficient, and highly uniform specimen processing using minimal quantities of fluids. The methods include at least a fixing phase for fixing a biological specimen to a substrate such as a microscope slide, a staining phase for staining the specimen, and a rinsing phase for rinsing the specimen. One or more of the fixing, staining, and rinsing phases include one or more agitation cycles for distributing reagents evenly and uniformly across the specimen. The systems can be implemented as a standalone device or as a component in a larger system for preparing and examining biological specimens.
1. An apparatus for processing a specimen on a substrate, comprising:
a platform comprising a first surface;
first and second fluid ports positioned on or in proximity to the first surface;
a positioning mechanism configured to hold the substrate;
a fluid control system; and
a controller connected to the positioning mechanism and the fluid control system,
wherein the positioning mechanism is configured to position the substrate so that the specimen directly faces the platform;
wherein the controller is configured to activate the fluid control system to deliver a solution comprising a biological stain from the first fluid port to the second fluid port by flowing the solution across the first surface; and
wherein the solution contacts the specimen as it flows across the first surface.
2. The apparatus of claim 1 , wherein the apparatus comprises a third fluid port positioned on or in proximity to the first surface, and wherein the fluid control system delivers the solution from the first and third fluid ports to the second fluid port.
3. The apparatus of claim 2 , wherein the first and third fluid ports are spaced from one another in a direction approximately perpendicular to a direction of flow of the solution across the first surface.
4. The apparatus of claim 1 , further comprising at least one protrusion extending from the first surface so that the substrate contacts the at least one protrusion.
5. The apparatus of claim 4 , wherein the at least one protrusion comprises at least three protrusions.
6. The apparatus of claim 1 , wherein the positioning mechanism maintains a fixed spacing between the substrate and the first surface during the flow of the solution.
7. The apparatus of claim 6 , wherein the fixed spacing is at least about 50 microns.
8. The apparatus of claim 1 , wherein the first surface is positioned within a recess formed in the platform.
9. The apparatus of claim 1 , wherein the controller is configured to activate the fluid control system to deliver at least one additional solution from the first fluid port to the second fluid port, the at least one additional solution contacting the specimen as the at least one additional solution flows across the first surface, wherein the at least one additional solution comprises at least one member selected from the group consisting of: a rinse solution, a fixative solution, and a second stain solution.
10. The apparatus of claim 1 , wherein the positioning mechanism comprises an arm configured to rotate the substrate from a first position to a second position, and wherein in the second position, the specimen directly faces the platform.
11. The apparatus of claim 10 , wherein in the first position, the specimen faces a direction approximately away from the platform.
12. The apparatus of claim 1 , wherein the positioning mechanism comprises a substrate gripper that contacts the substrate, and wherein the substrate gripper comprises a suction port connected to a suction source to hold the substrate against the substrate gripper.
13. The apparatus of claim 1 , wherein the first and second fluid ports are positioned on or in proximity to opposite edges of the first surface.