1. Technical Field
This invention generally relates to a plate washing system with ultrasonic cleaning of pipes and a control method thereof. The ultrasonic cleaning system can provide cleaning of the plate washing system's dispense and aspirate pipes, and monitor the performance in terms of volumetric accuracy and precision.
2. Discussion of Related Art
Certain laboratory operations, such as immuno assays, require the testing of small samples which are carried out in an arrangement of microwells having volumes of, for example 50-300 microliters or less formed in microtiter plates, hereinafter referred to generically as well plates. An example of this type of laboratory operation is an Enzyme Linked ImmunoSorbent Assay (“ELISA”) reaction which is performed for measuring the presence or absence of an antigen/antibody complex formed within the wells of the well plate.
Reactions of this type involve the addition and removal of liquid reagents within each well. Intentionally, some of the components in the reagent chemically bond to the well. Therefore, at several stages of the reactions, the unbound liquid and components remaining in the wells must be removed and the insides of the wells must be washed by dispensing a wash solution such as water, a buffer solution, or other fluid in the wells using and gravity feed or a pump, and then evacuating the liquid under a vacuum.
The wells can be arranged in a strip or in-line format, or can be arranged in a matrix format. Until recently, commonly used matrices were configured to have 8×12 wells spaced at 9 mm apart between centers, hereinafter referred to as a 96-well plate. However, with the advent of High Throughput Screening (“HTS”), two more matrixes were introduced which increased the total number of wells while keeping the overall size of the well plate the same: 1) the 384-well plate, as shown in FIG. 1, configured to 16×24 wells spaced at 4.5 mm apart between centers, and 2) the 1536-well plate configured to have 32×48 wells spaced at 2.25 mm apart between centers (not shown). Since the overall foot print of the these new well plates are the same as the 96-well plate, the size of the wells in the new micro titer well plates is necessarily smaller than those in the 96-well plates while the depth of the wells remains generally the same. However, this is not always the case.
A conventional washer used for removing the unbound contents in wells of a well plate includes dispense pipes for dispensing the wash solution into the wells of the plate (e.g., by a pump or gravity feed), and aspirate pipes for evacuation the solution from the wells of the well plate (e.g., by a vacuum or a suction device). In order to quickly wash the well plates, the washing process is performed simultaneously on as many wells of the well plate as possible. A commercial example of such a microplate washer is the Texan PW384.
As discussed in U.S. Pat. No. 5,951,783 issued to Kontorovich et al., which is herein incorporated by reference, the dispense and aspirate pipes can be provided on a single manifold assembly or separate dispense and aspirate manifolds.
In order to accommodate the well plates having smaller wells, the dispense and aspirate pipes must have small diameters. However, as a result of evaporation, the dispensed materials leave solid materials (such as salts from the assay reagents) within the pipes. The solid material residue can impact the performance of the pipes or even render the pipes inoperable. Impact on performance issues is currently not detectable within the microplate washing system and requires external instrumentation to detect volumetric dispense and aspiration errors.
Ultrasonic cleaning techniques have been used to remove the residual material from the aspirate and dispense pipes and return the pipes to an operative condition. These ultrasonic cleaning techniques use a commercially available ultrasonic tank of suitable size to allow immersion of the impaired pipe assemblies.
Although the use of ultrasonic cleaning is effective, ultrasonic cleaning using a commercially available tank is a complex process. It requires the addition of cleaning liquid in order to fill the tank, removal of the pipe assemblies from the microtiter plate washing system before the pipe assembly is inserted into the tank, removal of the waste material from the tank once the cleaning process has been completed, installation of the pipe assemblies on the plate washing system, and purging cleaning fluid from the pipe assemblies by dispensing.