1. Field of the Invention
The present invention relates generally to immuno-histochemistry (IHC) staining of tissue samples and more specifically to a reagent bottle with dedicated pipette tip for use within an automated IHC system.
2. Discussion of Background Information
Immuno-histochemistry staining (IHC staining) requires several processing sequences such as, for example, (a) deparaffinization and tissue hydration; (b) target or antigen retrieval, (c) immuno-histochemical staining, (d) counter staining and (e) tissue dehydration. Several instruments have automated the process of IHC staining. In all cases, various instrument resources (e.g., reagents, heat, pipettes, physical locations for slides, wash buffers, etc.) are required for automation. The process of automation requires either (a) the sample (tissue on a slide) to be brought to those resources or (b) resources to be brought to the sample.
The IHC staining step involves using a pipette to transfer a series of reagents from reagent bottles to tissue samples undergoing processing. A single pipette requires washing between consecutive applications of various reagents. Each wash lengthens the duration of the overall process and, therefore, lessens system efficiency. Additionally, using a single pipette with various reagents presents the risk of crossing over reagents between distinct bottles if washing is insufficient.
A need therefore exists for a reagent bottle with dedicated pipette tip that eliminates a need for time consuming pipette washing and eliminates the risk of crossover while enabling efficient, accurate, on demand delivery of reagents within an IHC stainer.
One embodiment of the reagent bottle includes a reservoir adapted to contain a reagent, a pipette tip defining a fluid channel extending into the reservoir and a resilient seal fixedly disposed within the reservoir and surrounding the pipette tip, the seal functioning to reduce reagent loss when the pipette tip is withdrawn from the reagent bottle. The fluid channel is defined by the pipette tip being in direct fluid communication, or interrupted fluid communication, with the exterior of the reagent bottle, the pipette tip being directly or indirectly engageable through a fluid-tight fitting with a pipette.
In one embodiment, the reagent bottle includes a base member adapted for selective engagement with one or more rotation pins. In one embodiment, the reagent bottle includes a base member having an indexing feature for properly aligning the reagent bottle within an automated system. In one embodiment, the reagent bottle includes a base member adapted for selective engagement with one or more spring pins for raising and lowering the reagent bottle.
In one embodiment, the reagent bottle further includes a non-removable or tamper-evident fill port element. In one embodiment, the pipette tip is in interrupted fluid communication with the exterior of the reagent bottle, the fluid communication being interrupted by a valve. In one embodiment the valve is a poppet valve.
In one embodiment, the reagent bottle includes a fluid tight fitting between the pipette tip and the reservoir, and in one embodiment, the fluid-tight fitting is a threaded or non-threaded tapered fitting. In one embodiment, the threaded or non-threaded tapered fitting is a 6 degree tapered fitting, and the threaded or non-threaded tapered fitting further comprises a reversibly engageable Luer lock system. In one embodiment, the threaded or non-threaded tapered fitting further comprises a reversibly engageable press fit and trigger release system.
In one embodiment, the pipette tip has a double lugged Luer lock for reversibly engaging with the reservoir and the pipette. In one embodiment, the interior surface of the reservoir terminates in a conical well centered about the longitudinal axis of the fluid channel.
In one embodiment, the reservoir is manufactured from high density polyethylene and the resilient seal is manufactured from Saniprene®.
One will better understand these and other features, aspects, and advantages of the present invention following a review of the description, appended claims, and accompanying drawings in which:
The reagent bottle with dedicated pipette tip solves the problems left unaddressed by standard automated IHC stainers and eliminates time sinks and crossover contamination associated with washing and reusing a single pipette used across all reagents.
One embodiment of the reagent bottle 10 of the present invention is designed for use within an automated IHC staining system 1000 such as the embodiment shown in
The IHC staining system 1000 further includes an enclosure (not shown) that sections off the externally exposed slide input drawers 1005 and slide output drawers 1007 and encapsulates a pre-stainer slide handler 1010 (i.e. a robotic arm) that moves in an X-Y plane and operates a gripper 1015 thereon for transporting individual slides 1017 between treatment areas. The IHC staining system 1000 further includes within the enclosed area an oven 1020, a pre-processing carousel 1025, an antigen retrieval carousel 1030 and a post-processing carousel 1035. The gripper 1015 delivers slides 1017 to individual treatment pockets (not shown) positioned at one of two dedicated access ports 1022, 1027, 1032, 1037 within each carousel 1020, 1025, 1030, 1035 so that each slide 1017 receives individualized treatment reagents and/or sequences of processing steps within its dedicated slide pocket.
The IHC staining system 1000 further includes an IHC stainer 1100 into which slides 1017 are fed by an IHC gripper 1105 for treatment with one or more reagents and hema-blue. The IHC gripper 1105 is mated to short support arm (not shown) that pivots on a single axis. The short support arm includes a series of mechanisms that move the IHC gripper 1105 vertically in the Z-axis as well as rotate a slide 1017 from a vertical to a horizontal (X-Y plane) orientation for delivery into one of the ICH processing bays 1110. In the embodiment of
The automated staining system 1000 with moveable pipette 1125 is designed for interactive use with a specially-designed reagent bottle 10. As depicted in
In one embodiment, the reagent bottle 10 includes a base member 105 adapted for selective engagement with one or more rotation pins (not shown). The pins extend into a plurality of bores 110 formed through the base member 105. In one embodiment, the base member 105 is adhered to the reservoir 100. In another embodiment, the base member 105 is integrally formed with the reservoir 100 through a process such as, but not limited to, injection molding. In one embodiment, the base member 105 has an indexing feature 115, such as but not limited to a notch, for properly aligning and orienting the reagent bottle 10 within an automated transport mechanism of the reagent compartment 1115 and within the presentation areas 1120. In one embodiment, the base member 105 provides a groove 120 into which one or more spring pins (not shown) securely snap such that the spring pins may raise and lower the reagent bottle 10 into and out of the reagent compartment 1115 and into and out of the presentation areas 1120.
Turning to the enlarged sectional view of
In one embodiment, the reagent bottle 10 includes a fluid tight fitting 135 between the pipette tip 200 and the reservoir 100, and in one embodiment, the fluid-tight fitting 135 is a threaded or non-threaded tapered fitting. In one embodiment, the threaded or non-threaded tapered fitting 135 is a tapered fitting having a taper angle a of six (6) degrees as measured from the longitudinal axis 215 of the pipette tip 200. In one embodiment, the tapered fitting 135 further comprises a reversibly engageable Luer lock system comprised of an angled groove 137 designed to receive a first pipette tip post 225 through rotational engagement. In another embodiment, a non-threaded tapered fitting 135 is designed for use in a reversibly engageable press fit and trigger release system.
In use, the reagent bottle 10 is housed within the refrigerated reagent compartment 1115 (shown in
The pipette tip 200 remains in interrupted fluid communication with the exterior of the reagent bottle 10 until the pipette 1125 engages with the pipette tip 200 via a pipette arm interface head 300, as shown in the embodiment of
The rotational movement requires knowing the orientation of the second pipette tip post 230 relative to the angled groove 320 on the tapered protrusion 310. As indicated in the embodiment of
Although the embodiment described here with regard to
Returning now to the system overview of
The IHC stainer 1100 is the rate limiting step in the IHC staining system 1000. An IHC staining process comprises the steps of, for example, delivering reagent onto tissue on a slide 1017, incubating reagent on the tissue, and washing reagent from the tissue (e.g. with an air knife). These steps occur with, on average, 7 or 8 different reagents for each tissue sample in the IHC stainer 1100. In the embodiment of
In addition to the features of embodiments of the reagent bottle 10 described herein, additional optional features enable agitation of reagent prior to aspiration by the pipette 1125. For example, in one embodiment, the reagent bottle 10 may include fins (not shown) integrally formed with the interior walls of the reservoir 100. The fins, like washing machine fins, cause turbulent vortices in the reagent when the refrigerated reagent compartment 1115 lifts and spins the reagent bottle 10. In one such embodiment, the IHC staining system 1000 may run a protocol specifically for agitating contents the reagent bottle 10 by rotating the reagent bottle 10 back and forth. In another embodiment, the reservoir 100 of the reagent bottle 10 may further include therein mixing marbles (not shown) like those of a spray paint can that agitate the reagent upon movement of the reagent bottle 10 by the refrigerated reagent compartment 1115. In another embodiment, the reservoir 100 of the reagent bottle 10 may further include magnets (not shown) that spin in the presence of magnetic flux such that the reagent is agitated by the rotating magnets. In another embodiment, the IHC staining system 1000 may run a protocol specifically for aspirating contents the reagent bottle 10 into the pipette tip 200 and dispensing the reagent back into the reservoir 100, thereby agitating the reagent within the reservoir.
It is noted that the foregoing examples have been provided merely for the purpose of explanation and are in no way to be construed as limiting of the present invention. While the present invention has been described with reference to an exemplary embodiment, it is understood that the words, which have been used herein, are words of description and illustration, rather than words of limitation. Changes may be made, within the purview of the appended claims, as presently stated and as amended, without departing from the scope and spirit of the present invention in its aspects. Although the present invention has been described herein with reference to particular means, materials and embodiments, the present invention is not intended to be limited to the particulars disclosed herein; rather, the present invention extends to all functionally equivalent structures, methods and uses, such as are within the scope of the appended claims.
Number | Date | Country | |
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61592864 | Jan 2012 | US |