Liquid sample dispensing methods for precisely delivering...

Fluent material handling – with receiver or receiver coacting mea – With conveying means to supply successive receivers – Sampler type

Reexamination Certificate

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Details

C422S091000, C422S105000, C436S043000, C436S180000, C356S246000

Reexamination Certificate

active

06463969

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to liquid sample dispensing in which a sampling pipette aspirates liquids from a sample or reagent container and dispenses the aspirated liquid into a reaction vessel. More particularly, the invention relates to a system for precisely delivering an amount of liquid from a sample or reagent container into a reaction tube and for reducing carry-over of liquid from one reaction tube to the next, thereby protecting the integrity of the solution within the reaction tube.
BACKGROUND OF THE INVENTION
Various types of tests related to patient diagnosis and therapy can be performed by analysis of a sample of a patient's infections, bodily fluids or abscesses. Such samples are typically placed in sample vials, extracted from the vials, combined with various reagents in special reaction vessels or tubes, incubated, and analyzed to aid in treatment of the patient. Automated clinical analyzers adapted to perform these operations typically handle liquids by aspiration and pressurized dispensing from the sample vials into a reaction vessel using a sampling probe or pipette. In general, a sampling pipette is immersed into a liquid held in a suitable container. A partial vacuum is produced in the pipette in an amount sufficient to draw the required amount of liquid up into the pipette through its nozzle, and the pipette is taken to a station holding a pre-treatment or reaction vessel. At that station, pressure is applied to the interior of the pipette in an amount sufficient to dispense the desired amount of liquid out of the nozzle. The clinical analyzer typically uses a portion or a liquot of the patient's sample that is aspirated from the vial by a sampling pipette. The entire aspirated aliquot or a portion thereof may then be dispensed from the sampling pipette into a reaction vessel or into a sample pre-treatment vessel from which treated sample is later aspirated. Automated clinical analyzers also typically include reagent pipettes adapted to aspirate reagent from reagent containers and to dispense the entire aspirated reagent or a portion thereof into the sample pre-treatment vessel or directly into the reaction vessel.
Conventional pipettes suffer the disadvantage that liquid tends to remain on the exterior surface of the pipette when the pipette is withdrawn after aspiration. In cases of small volumes of aspirated liquid, any excess liquid carried on the exterior of the pipette may be a significant volume with respect to or could even exceed the volume of the aspirated liquid. Pipettes are designed to accurately dispense a predicted volume of liquid; however, any liquid on the exterior surface of the nozzle at the orifice might also be dispensed. Alternatively, the presence of the liquid on the exterior surface might cause the dispensed quantity of liquid to perfuse up the exterior surface, rather than to move into a target vessel. In either case, the volume of liquid received by the vessel is altered in an unpredictable fashion.
Another disadvantage is that reusable probes used to deliver liquid aliquots from successive containers such as tubes or liquid reagent vessels are a source of intra-sample carryover or contamination. Regardless of application, the sampling pipette and reagent pipette must also be thoroughly cleaned and dried between aspirations of different liquids to avoid carryover contamination.
In the prior art are various solutions to the inter-related carryover and contamination problems. To prevent cross-contamination between samples, the pipette may be provided with a removable and disposable “pipette tip” which is the sole portion of the probe to contact the sample liquid. However, disposable pipettes are costly and over a long period of time, become an unexpectedly high item of unwanted expense. Some analyzers include a wiping operation between each aspiration. However, wiping is an extra potential source of contamination, and also introduces additional automated mechanisms that lower the throughput rate and increase the expense of an analyzer.
In order to minimize contamination and carry-over between samples, the probe may be flushed or washed with a diluent liquid such as water. It has also been proposed to utilize a separate probe wash sleeve through which a pressurized rinse liquid is flushed (U.S. Pat. No. 4,756,201). In general, a probe wash chamber is utilized including a wash fluid input into the pipette and a fluid output or exhaust for removing the fluid once the exterior of the pipette has been cleaned. Wash chambers can leak fluid and also can channel along only one side or a portion of the pipette which can leave residue on the pipette exterior. Additionally, if a last drop of wash diluent does not drop off the pipette and is carried back to an aspiration vessel, the droplets dilute the sample or reagent, introducing unwanted sources of error.
Another technique shown, for example in U.S. Pat. No. 3,266,322, aspirates air through the probe by means of a vacuum pump or the aspirating pump used to withdraw the sample liquid from the sample container. Such aspiration, however, introduces the possibility of drawing the unwanted carry-over contaminants deeper into the tubing and apparatus which comprises the sampling system.
U.S. Pat. No. 4,347,875 discloses a “self-cleaning” nozzle for causing liquid remaining behind on the exterior surface of the nozzle to automatically locate itself other than at the aspirating and dispensing orifice. The nozzle comprises a liquid-confining wall extending about a longitudinal axis and terminating in a liquid-dispensing orifice, and an exterior surface having a portion adjacent to the aperture that is adapted to be immersed into a source of the liquid during aspiration. The wall attracts liquid remaining on the adjacent exterior surface after aspiration to loci spaced from the orifice a distance effective to prevent liquid remaining on the exterior surface from interfering with the dispensing of the liquid.
U.S. Pat. No. 4,871,682 discloses an air knife positioned to direct a stream or blast of air across the tip of a sample probe as it is withdrawn from a vessel containing a reagent, diluent, and patient sample solution. After the probe is flushed with diluent, the air knife drives any droplets of diluent fluid off the probe tip into the vessel and thereby prevents contamination or dilution of the sample material in the sample containers.
U.S. Pat. No. 5,506,142 discloses a wash probe in which the simultaneous introduction of pressurized air and water creates a turbulent flow including the use of a pressurized gas stream of short duration to blow the residue of the previous sample out of the probe prior to washing with additional diluent liquid. Also, a waste receptacle is provided which uses a filtered air vent and a liquid saturated material around the probe receiving opening to prevent the escape of aerosols from the receptacle.
U.S. Pat. No. 5,506,142 provides for a probe wash in which the simultaneous introduction of pressurized air and water creates a turbulent flow including the use of a pressurized gas stream of short duration to blow the residue of the previous sample out of the probe prior to washing with additional diluent liquid. Also, a waste receptacle is provided which uses a filtered air vent and a liquid saturated material around the probe receiving opening to prevent the escape of aerosols from the receptacle.
U.S. Pat. No. 5,536,471 discloses a bubble flushing syringe for aspirating and dispensing fluids through an open-ended tip. The syringe comprises a piston within a bore formed by a cylindrical wall, wherein the piston forms an annulus with the wall and closed end of the bore, and is capable of reciprocating therein. The syringe further comprises an annular seal seated in the bore and circumventing the piston to retain fluid when the piston reciprocates therethrough. An inlet for directing fluid to the annulus through the wall of the bore and an outlet for directing fluid from the annulus through the wall of the bore to the open-ended t

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