Automated clinical analyzers are well known in the art and are generally used for the automated or semi-automated analysis of patient samples. Typically, prepared patient samples, such as blood, urine, spinal fluid, and the like are placed onto such an analyzer in sample containers such a test tubes. The analyzer pipettes a patient sample and one or more reagents to a reaction cell (e.g., a reaction vessel, cuvette or flow cell) where an analysis of the sample is conducted, usually for a particular analyte of interest, and results of the analysis are reported.
Automated pipettors are employed on such analyzers to transfer the patient samples and reagents as required for the specified analysis. Such pipettors can include a hollow probe having an open end or tip. The hollow probe is, for example, lowered into a sample container that holds a sample, a predetermined volume of the sample is withdrawn from the sample container, and the hollow probe is withdrawn from the sample container. The probe is moved, for example, to a position above a reaction cell, is again lowered, and the sample held in the hollow probe is expelled into the reaction cell. Similar actions may be used to pipette and deliver one or more reagents from reagent containers to the reaction cell, either with the same probe or with one or more reagent delivery probes.
Such hollow probes may be used to clean (i.e., rinse) the reaction cell at various stages of the analysis.
To prepare such a hollow probe for a subsequent delivery, the hollow probe may be washed to eliminate, as much as possible, any residue from the prior samples and/or reagents that were handled by the hollow probe. Probe washing may be accomplished by, for example, lowering the probe tip into a wash cell that contains a wash fluid such as water. The wash fluid washes an exterior of the probe tip, and an interior of the hollow probe may be cleaned by aspirating and discharging the wash fluid or, alternatively, discharging a wash fluid through the hollow probe into the wash cell.
A common problem with hollow probe washing, however, is carryover, that is, residual fluid or contaminates from a fluid that remain on or in or may be absorbed by the hollow probe despite washing. This residue mixes with subsequent sample or reagents drawn into the hollow probe and can interfere with subsequent analyses.
Another problem with hollow probe washing is the time needed to move the hollow probe to a wash station and accomplish the probe washing. Substantial time can be required to wash the hollow probe. For example, if the hollow probe has delivered a sample to a reaction cell, the hollow probe must be raised, moved to a position over a wash cell, and lowered into the cell for washing. Once washing is done, the hollow probe must again be raised and moved on to the next operation. Such cleaning of hollow probes may require that the hollow probe be moved away from stations involved in the substance evaluating processes. Having a remote wash station located outside and/or away from the fluidic evaluating stations may require that certain motions of the probe be decoupled from each other or have additional degrees-of-freedom.
Instruments known as UniCel® DxI 600 Access® Immunoassay System (i.e., DxI 600) and UniCel® DxI 800 Access® Immunoassay System (i.e., DxI 800), manufactured by Beckman Coulter, Inc. of Brea, Calif., USA, include a duck bill valve to accommodate washing various hollow probes without moving the hollow probes to a remote wash station. Instead, the duck bill valve allows the hollow probe to go through the wash station and thereby reach a container in which the fluidic substance is being evaluated. To wash the hollow probe, the hollow probe is positioned above the duck bill valve and vacuum is applied in an area above the duck bill valve while fluid is flushed through the hollow probe. However, the duck bill valve may leak (i.e., introduce contamination) and requires maintenance. It is recommended that the DxI 600 and DxI 800 users replace the duck bill valve every 5,000 tests as a preventative maintenance measure. Furthermore, as cleaning processes that use such a duck bill valve include applying vacuum above the duck bill valve, positive pressure above the duck bill valve is not possible, and the cleaning processes are therefore constrained from applying positive pressure above the duck bill valve.
Thus, there is a need for a probe washing arrangement and method of use of such an arrangement that overcomes these limitations of the prior art probe washing approaches. The needed improvements include, but are not limited to, reducing carryover, decreasing probe washing time, decreasing maintenance, and increasing available process parameters that may be employed in probe washing.
According to certain aspects of the present disclosure, a probe washing arrangement includes a hollow probe, a probe actuator, a probe washer, and a probe washer actuator. The hollow probe includes a tip. The probe actuator moves the hollow probe vertically along a probe path. The probe washer cleans the hollow probe, includes a cavity that is adapted to receive at least a portion of the hollow probe when the probe washer is positioned at a deployed position, intersects the probe path when the probe washer is positioned at the deployed position, and clears the probe path when the probe washer is positioned at a stowed position. The probe washer actuator moves the probe washer between the deployed position and the stowed position.
According to certain aspects of the present disclosure, a sample analysis system includes a probe washing arrangement including a probe and a probe washer for cleaning the probe. The probe is for aspirating and/or dispensing fluid from/into at least one receptacle. The probe is moveable along a probe path. The probe washer is moveable between at least a first position and a second position. When the probe washer is at the first position. The probe path clears the probe washer and thereby allows the probe to travel past the probe washer to the receptacle. When the probe washer is at the second position, the probe path intersects the probe washer and thereby allows the probe to travel into the probe washer.
According to certain aspects of the present disclosure, a sample analysis system includes at least two stations, a carrier, and a probe washing arrangement for cleaning the probe. The carrier is for transporting at least one sample vessel between the at least two stations. The probe washing arrangement includes a probe is for aspirating and/or dispensing fluid from/into the at least one sample vessel when the at least one sample vessel is at a probe receiving station of the at least two stations. The probe is moveable along a probe path. The probe washing arrangement includes a probe washer that is moveable between at least a first position and a second position. When the probe washer is at the first position. The probe path clears the probe washer and thereby allows the probe to travel past the probe washer to the sample vessel at the probe receiving station. When the probe washer is at the second position, the probe path intersects the probe washer and thereby allows the probe to travel into the probe washer.
According to certain other aspects of the present disclosure, the sample analysis system may further include a cleaning fluid supply for supplying cleaning fluid. The cleaning of the probe may include internal cleaning. The probe washing arrangement may include a drain and may be configured to facilitate the internal cleaning of the probe by draining the cleaning fluid via the drain after the cleaning fluid is passed from the cleaning fluid supply through the probe. The sample analysis system may further facilitate external cleaning of the probe, and the probe washing arrangement may further include an inlet. The inlet and the drain may be configured to facilitate the external cleaning of the probe by applying the cleaning fluid to at least an external portion of the probe and draining the cleaning fluid via the drain after the cleaning fluid is passed from the cleaning fluid supply through the inlet.
According to certain additional aspects of the present disclosure, the carrier of the sample analysis system may include a rotating ring and/or a rotating disk with a plurality of holders for individually transporting a plurality of the sample vessels. One or more of the probe receiving stations may be included in a wash unit. The at least one sample vessel may be a reaction vessel. The probe path may be a linear path. The probe path may be a vertical path. In certain embodiments, the probe may move only along the probe path when the sample analysis system is in normal analyzing operation. In certain embodiments, only one of the at least one sample vessel occupies any station of the at least two stations at a time. In certain embodiments, the probe washer includes a housing that includes the inlet and/or the drain, and the housing may further include a wall that blocks (i.e., intersects) the probe path when the probe washer is at the second position. In certain embodiments, the probe washer is rotationally movable between at least the first position and the second position about an axis. In certain embodiments, the axis is parallel to the probe path. In certain embodiments, the probe washer is movable between at least the first position and the second position with a single degree-of-freedom. In certain embodiments, the external portion of the probe includes a tip portion.
A variety of additional aspects will be set forth in the description that follows. These aspects can relate to individual features and to combinations of features. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the broad concepts upon which the embodiments disclosed herein are based.
Various embodiments will be described in detail with reference to the drawings, wherein like reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the claims attached hereto. Additionally, any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the appended claims.
According to the principles of the present disclosure, a probe washing arrangement may clean a probe P in a variety of sample analysis systems. As a variety of sample analysis systems with a variety of configurations are suitable for incorporating a probe washing arrangement for a probe P, the probe washer and/or the probe P may be configured in a variety of configurations suitable for a particular sample analysis system and/or sub-system. Several examples and characteristics of such sample analysis systems are mentioned and described herein. Other sample analysis systems may also be suitable for incorporating the various probe washers and/or probes P mentioned herein, as will be understood by one of ordinary skill in the art.
Instruments which may benefit from using a probe washing arrangement include but are not limited to diagnostic analyzers, such as immunoassay analyzers, clinical chemistry analyzers, hematology analyzers, nucleic acid analyzers, flow cytometry systems, and urinalysis analyzers. Instruments may also include liquid handling systems used for laboratory systems involving biological fluids, such as the Biomek i-Series Automated Workstations from Beckman Coulter, Inc., Brea, Calif., USA and similar laboratory automation platforms or multi-well plate handlers.
According to the principles of the present disclosure, various probes P may be used to handle various fluids within a sample analysis system (e.g., a biological testing instrument). The various fluids or components thereof may tend to adhere to the probes P and may be hydrophobic, colloidal, sticky, tacky, viscous, etc. Fluids handled include samples, specimens, reagents, chemicals, agents, rinses, particles, substrates, enzymes, unreacted substances, whole blood, serum, plasma, other blood components or fractions, immune complexes, urine, saliva, cerebral spinal fluid, amniotic fluid, feces, mucus, cell or tissue extracts, nucleic acid extracts, biological fluids, etc. Often fluids handled are biological fluids, assay reagents, or mixtures thereof. Biological fluids, may also be called samples or specimens, and may include blood or blood components or fractions (such as whole blood, serum, plasma, red blood cells, white blood cells, platelets), urine, saliva, cerebral spinal fluid, amniotic fluid, feces, mucus, cell or tissue extracts, nucleic acid extracts. Assay reagents may include: wash buffers, rinses, sample pretreatments, diluents, stains, dyes, substrates, antibody conjugates, enzymes or enzyme conjugates, nucleic acid conjugates, cell lysis reagents, and the like, in reacted or unreacted states. Components of assay reagents typically include: water, buffers, chemicals, particles, substrates, enzymes, fixatives, preservatives, nucleic acids, antibodies, acids, bases, and mixtures thereof, in reacted or unreacted states. Mixtures of Biological Fluids and Assay reagents, may be in reacted or unreacted states, resulting in new combinations such as immune complexes, nucleic acid complexes, enzyme-substrate complexes and the like. Biological fluids, assay reagents, or mixtures thereof as well as sub-sets of components thereof, reacted or unreacted, may be aspirated, delivered, retained or removed via methods utilizing the probe washing arrangement consistent with the present application.
Such repeated pipetting of the various fluids with the probes P may result in a portion of an early sample adhering to the probe P and then being introduced to a subsequent sample by the probe P and thereby result in the contamination of the subsequent sample. Similar carryover is possible with assay reagents. Probe washing assemblies may be used to clean the probes P of sample analysis systems for various reasons, including avoiding such contamination, cross-contamination, carryover, etc. In certain embodiments, the probe washing arrangement may be arranged and/or implemented to minimize or eliminate time lost to cleaning the probe P. In certain embodiments, the probe washing arrangement may be arranged to minimize space lost to the probe washer.
The probe washing arrangement by cleaning the probes P with the probe washer, sample to sample carryover can be reduced to an acceptable level or eliminated, and the biological testing instrument may thereby meet various carryover protocols. Under certain conditions, not cleaning the probes P leads to sample to sample carryover and thereby leads to analytical laboratory error.
The probes P may aspirate and/or dispense the various fluids from and/or to various probe receiving stations PS within and/or adjacent to the sample analysis system. The probe receiving stations PS may be fixed or may be moveable.
One or more receptacles (e.g., vessels) may be positioned at some or all of the probe receiving stations PS. The probes P may dispense and/or aspirate various fluids into and/or from the one or more receptacles. The one or more receptacles may include tubes, sample tubes, wells, capped tubes, uncapped tubes, microtainers, cuvettes, Microtiter™ wells, flow cells, inlets fluidically connected to flowcells, etc. Each of the one or more receptacles may be positioned at a single probe receiving station PS or may be moveable between probe receiving stations PS and/or other positions that are not probe receiving.
Certain probes P may be specialized in dispensing fluids and may therefore only dispense fluids and not aspirate fluids. Likewise, certain probes P may be specialized in aspirating fluids and may therefore only aspirate fluids and not dispense fluids. Still other probes P may both aspirate and dispense fluids, as desired. To include probes P that may dispense only, aspirate only, and both dispense and aspirate, the conjunction “and/or” is used herein. Thus, mentioning a probe P for aspirating and/or dispensing fluid includes dispense only probes P, aspirate only probes P, and dispense and aspirate probes P.
Probes P may be actuated in a variety of ways suited to their particular functions in a particular sample analysis system. Certain probes P may be actuated along a single degree-of-freedom. The single degree-of-freedom may be a linear degree-of-freedom parallel to an axis of the probe P. Other probes P may be actuated along multiple degrees-of-freedom. Certain probes P may service a single location, while other probes P may service multiple locations. Certain probes P may receive fluid from a source (e.g., from a tank via a tube) and deliver (i.e., dispense) the fluid to one or more locations, while other probes P may remove (i.e., aspirate) the fluid from one or more locations and deliver fluid to a sink (e.g., to a tank via a tube). Still other probes P may aspirate one or more fluids from one or more locations and dispense one or more fluids to one or more locations and may thereby transfer one or more fluids between several locations. Various pumps, plumbing, valves, and conduits may be used to connect the probes P.
The locations serviced by the probes P may also vary according to their particular functions in a particular sample analysis system. For example, a probe P may aspirate and/or dispense fluid from and/or to various vessels, drains, supply reservoirs, waste collection reservoirs, tubes, sample tubes, wells, capped tubes, uncapped tubes, microtainers, cuvettes, Microtiter™ wells, etc. In certain embodiments, a probe P may receive and/or deliver fluids to a component that processes the fluid, such as a flow cell. The flow cell may include an aperture and various instrumentation to measure various aspects of the fluid. The term “receptacle”, as used herein, refers to various interfacing features serviced (dispensed to and/or aspirated from) by the probe P, including receptacles included with the examples herein.
Various configurations of probe washing arrangements may be suited for various configurations of probes P, including the examples herein, and various applications in which the probes P and the probe washers are employed. In certain embodiments, both the probe P and the probe washer move relative to the sample analysis system (e.g., a frame of the sample analysis system). In certain embodiments, the receptacle does not move relative to the sample analysis system, at least when the receptacle is being aspirated from and/or dispensed into or when the sample analysis system is in operation. In other embodiments, the receptacle moves or is moved to align with the probe in preparation for aspiration and/or dispensing and may further move to align with another probe for further aspiration and/or dispensing.
In example embodiments where the probes P move to multiple positions (e.g., probe receiving stations) about the sample analysis systems, the probe washer may travel with the probe P. In particular, an actuator, gantry, robot, or other mechanism that moves the probe P to the various positions may also move the probe washer. This combined movement allows the probe P to be washed by the probe washer while the probe P is moving or being moved. This combined movement may save cycle time as the probe moving operation and the probe washing operation may be performed simultaneously.
In certain embodiments of probe washing arrangements, probe P and the probe washer may be co-located (e.g., positioned adjacent to each other). Co-locating the probe P and the probe washer may accommodate their combined movement. Co-locating the probe P and the probe washer may save space on the sample analysis system. The combination of the probe P and the probe washer may form a self-washing probe arrangement. In certain embodiments, the probe washer may be arranged to minimize space lost to the probe washer. In certain embodiments, analyzer/assay performance time lost to cleaning the probe P is minimized or eliminated.
In certain embodiments, the probe washer is actuated by the probe washer actuator about a single degree-of-freedom (e.g., parallel to a linear displacement or a rotational displacement) and thereby moves the probe washer relative to the probe path about the single degree-of-freedom. In certain embodiments, the probe washer may be actuated from a stowed position to a washing position by an actuator. In certain embodiments, the actuation includes only a single degree-of-freedom. In certain embodiments, the probe washer may be actuated relative to the sample analysis system (e.g., a frame of the sample analysis system). In other embodiments, the probe washer may be actuated relative to a carrier (e.g., an actuator, a gantry, a robot, etc.) that moves the probe P and the probe washer. In still other embodiments, the probe washer may be actuated relative to another moveable component of the sample analysis system (e.g., a probe platform of the sample analysis system).
Turning now to
In certain embodiments, the probe actuator 20 is adapted to move the hollow probe P between a stowed probe position ap1, AP1 and a probe washing position ap2, AP2 similar to or the same as that shown at
In certain embodiments, the probe washing arrangement 10 may include a cleaning fluid supply 304, 404 for supplying cleaning fluid 302, 402 similar to or the same as that shown at
In certain embodiments, the probe washer 30 includes a housing similar to or the same as the housing 530 shown at
In certain embodiments, the probe washer 30 is actuated by the probe washer actuator 20 about a single degree-of-freedom (e.g., parallel to a linear displacement d, illustrated at
In certain embodiments, the hollow probe P only moves vertically along the probe path 300 (e.g., see
Turning now to
In the embodiment illustrated at
In the embodiment illustrated at
A first actuator 114 may be mounted to the first frame 112. As depicted, the first actuator 114 is a linear actuator. In other embodiments, the first actuator 114 may be non-linear (e.g., rotary). As depicted, the first actuator 114 provides a single degree-of-freedom. The first actuator 114 may be powered by a variety of means (e.g., rotary motor, linear motor, stepper motor, pneumatic cylinder, etc.). As depicted, the first actuator 114 provides movement along displacement d1. A sign convention has been defined with respect to the displacement d1. In particular, a first direction d1+ and an opposite second direction d1− have been defined for displacement d1.
In the embodiment illustrated at
A second actuator 118 may be mounted to the second frame 116. As depicted, the second actuator 118 is a linear actuator. In other embodiments, the second actuator 118 may be non-linear (e.g., rotary). As depicted, the second actuator 118 provides a single degree-of-freedom. The second actuator 118 may be powered by a variety of means, as mentioned above in regard to the first actuator 114. As depicted, the second actuator 118 provides movement along displacement d2. A sign convention has been defined with respect to the displacement d2. In particular, a first direction d2+ and an opposite second direction d2− have been defined for displacement d2. As depicted, the displacements d1 and d2 are perpendicular. In other embodiments, the displacements d1 and d2 may be non-perpendicular (e.g., skew, parallel, etc.).
As depicted, a probe P, including a probe tip PT, is mounted to the second actuator 118. In the depicted embodiment, a single probe P is mounted to the second actuator 118. In other embodiments, multiple probes P may be mounted to the second actuator 118. By actuating the first and second actuators 114 and 118, the probe P and the probe tip PT can be moved to a plurality of locations within a two-dimensional space including the probe receiving stations PS1 and PS2. In other embodiments, an additional frame and/or an additional actuator may be provided (e.g., between the first frame 112 and the frame 108 of the instrument 100) thereby allowing the probe P and the probe tip PT to be moved to a plurality of locations within a three-dimensional space.
The probe P may define an axis A. The probe receiving station PS may define an axis A0. The probe P may be aligned with the corresponding probe receiving station PS when the axes A and A0 are aligned within an acceptable tolerance.
In typical use, the first actuator 114 axially aligns the probe P with the desired probe receiving station PS, PS1 and thereby aligns the axes A and A0. As illustrated at
As the probe P may become contaminated with the various fluids that it aspirates and/or dispenses, the probe washer 130 is provided to clean the probe P. The probe washer 130 may include various features of a probe washer 500, described and illustrated herein. The probe washer 130 may further interact with various elements that the probe washer 500 interacts with, including the probe P itself, as described and illustrated herein. The probe washer 130 is actuated by the third actuator 120, described in detail below.
In the depicted embodiment illustrated at
As mentioned above, the probe washer 130 may clean the probe P similar to or the same as the probe washer 500 cleans the probe P, as described and illustrated herein. As depicted at
The cleaning cavity 132 of the probe washer 130 may include a revolved boundary that is axisymmetric about a cavity axis. The probe P is typically aligned with the cleaning cavity 132 when the axis A and the cavity axis are aligned within an acceptable tolerance. As shown at
Upon the axis A and the cavity axis being aligned, the second actuator 118 may advance the probe P from the actuated position ap1 to the actuated position ap2 (e.g., a washing position) and thereby position at least a portion of the probe P within the cleaning cavity 132 of the probe washer 130. Upon the probe P or a portion thereof entering the cleaning cavity, the probe P may be internally and/or externally cleaned. Additional details of probe cleaning are given below with the description of the probe washer 500.
Upon the probe P being cleaned, the second actuator 118 may retract the probe P from the actuated position ap2 to the actuated position ap1 (e.g., a stowed position) and thereby remove the probe P or portion thereof from the cleaning cavity 132 of the probe washer 130.
As illustrate at
As illustrated at
An example method for immunological analysis using the example probe P and probe washer 30, 130, 500 will now be described in detail. A vessel 220 (e.g., a reaction vessel, a container, etc.) may be transported to a predetermined position S (e.g., a station), and a first reagent including magnetic particles is dispensed into the vessel 220 by a probe P. The probe P may be washed with the probe washer 30, 130, 500 before and/or after the dispensing. In certain embodiments, the vessel 220 is a reaction vessel. For purposes of this disclosure, the term “fluid” includes fluids with particles (e.g., suspended particles) such as the first reagent with magnetic particles.
A sample or specimen (e.g., a fluid, a sample or specimen suspended or mixed in a fluid, etc.) is dispensed into the vessel 220 by a probe P. The probe P may be washed with the probe washer 30, 130, 500 before and/or after the dispensing. In certain embodiments, the sample pipetting device, aspirates, with a probe P, the sample from a sample vessel that has been transported to a predetermined position S. The probe P may be washed with the probe washer 30,130, 500 before and/or after the aspirating. Once the sample is dispensed into the vessel 220, the vessel 220 may be subjected to mixing and/or incubating, if required, so as to produce magnetic particle carriers each formed of the antigen and the magnetic particle in the sample bonded together.
The vessel 220 may be subjected to a first cleaning process in which the magnetic particle carriers are magnetically collected by a magnetic collecting unit. A bound-free separation is carried out by a bound-free cleaning dispense nozzle (i.e., a probe P) dispensing a rinsing fluid and by a bound-free cleaning aspiration nozzle (i.e., a probe P) aspirating the uncollected fluid. The probes P may be washed with one or more of the probe washers 30, 130, 500 before and/or after the dispensing and/or aspirating. The bound-free separation may include a series of dispensing the rinsing fluid and aspirating uncollected fluid, with either being first and/or last. As a result, an unreacted substance or substances (e.g., unbound reactants, particles, and/or fluid, etc.) in the vessel 220 is removed (e.g., rinsed away) by the bound-free cleaning aspiration nozzle.
A second reagent, such as a labeling reagent including a labeled antibody and/or a fluid, may be dispensed into the vessel 220 by a probe P. The probe P may be washed with the probe washer 30, 130, 500 before and/or after the dispensing. As a result, immune complexes, each formed of the magnetic particle carrier and the labeled antibody bonded together, are produced.
A second bound-free cleaning process is performed to magnetically collect the magnetic particle carriers by a magnetic collecting structure. Further, a bound-free separation, similar to or the same as that mentioned above, is performed by a bound-free cleaning dispense nozzle (i.e., a probe P) dispensing a rinsing fluid and by a bound-free cleaning aspiration nozzle (i.e., a probe P) aspirating the uncollected fluid. The probes P may be washed with one or more of the probe washers 30, 130, 500 before and/or after the dispensing and/or aspirating. As a result, the labeled antibody that is not bonded with the carrier of the magnetic particles is removed from the vessel 220 by the bound-free cleaning aspiration nozzle 248.
A substrate including an enzyme and/or a fluid is dispensed into the vessel 220 by a substrate nozzle (i.e., a probe P), for example at station S26 of wash unit 176, describe in detail herein. The probe P may be washed with the probe washer 30, 130, 500 before and/or after the dispensing. The contents of the vessel 220 are then mixed. After a certain reaction time necessary for the enzyme reaction passes (e.g., in an incubator), the vessel 220 is transported to a photometric system, such as to a station of a light measurement device.
The enzyme and the immune complex are bonded together through the substrate reactions with the enzyme on the labeled antibody, and light is emitted from the immune complex and measured by a photometric system, such as the light measurement device. The light measurement device operates to calculate an amount of antigen, which is included in the specimen, according to the quantity of light measured.
As the above method uses probes P to aspirate and/or dispense the various fluids from and/or to the various stations S at which the vessel 220 is located, the above method may further incorporate the probe washing arrangement, according to the principles of the present disclosure.
Turning now to
The wash unit 176 includes a carrier arrangement 260, further illustrated at
As depicted, the first probe arrangement 280 and the second probe arrangement 290 together form another example pipetting system, according to the principles of the present disclosure. The pipetting system of probe arrangements 280 and 290 are tailored to the configuration of the wash unit 176 and interface with the carrier arrangement 260 of the wash unit 176.
Turning again to
In the example depicted, the wash unit 176 defines 27 stations S about which the carrier 270 moves the holders 272 between. In particular, the carrier 272 rotates about an axis A1 and thereby moves the holders 272 from station S to station S about a rotational displacement R1. In the example embodiment, the carrier 270 is indexed 13⅓ degrees per cycle and thereby advances each of the 27 holders 272 one station forward per cycle. In the depicted embodiment, the carrier 270 is rotary. In other embodiments, other carriers may be non-rotary. In the example embodiment, the carrier 270 includes a single holder 272 at each station at one time. In other embodiments, other carriers may include multiple holders per station at the same time.
At
A description of the various stations S will now be given. Station S0 is a no-function station, but may transfer the vessel 320 between neighboring stations S. Station S1 is an entrance/exit station. The vessel 320 is introduced to one of the holders 272 of the carrier 270 at station S1. From station S1, the vessel 320 is indexed around to the other stations S and eventually returns to the station S1 where it is removed from the holder 272 of the carrier 270.
As illustrated at
At station S2, the vessel 320, if present, receives fluid from a probe P of a probe assembly 288A (see
Station S10 receives a probe P of a probe assembly 288B which dispenses fluid into the vessel 320. The station S10 further includes a spin-mixer 278 (see
Station S18 receives a probe P of a probe assembly 288C which dispenses fluid into the vessel 320. Like the station S10, the station S18 includes a spin-mixer 278 and thereby spin-mixes the contents of the vessel 320. Stations S19-S24 are magnetic stations, like magnetic stations S3-S9 and S11-S17. Station S25 receives a probe P of a probe assembly 298C and thereby aspirates fluid from the vessel 320. Station S25 is also a magnetic station, like magnetic stations S3-S9, S11-S17, and S19-S24.
Station S26 receives a probe P of a probe assembly 288D which dispenses a substrate into the vessel 320. Like the stations S10 and S18, the station S26 includes a spin-mixer 278 and thereby spin-mixes the contents of the vessel 320. From the station S26, the carrier 270 advances the vessel 320 to the station S0. As mentioned above, no function occurs at station S0, other than the transport of the vessel 320.
As mentioned above, upon the carrier 270 indexing the vessel 320 from the station S0 to the station S1, the vessel 320 is ready to be removed from the carrier 270. In particular, the reaction vessel transfer unit 174 may retrieve the vessel 320 from the station S1 of the carrier arrangement 260 of the wash unit 176 and bring the vessel 320 to a station S of the incubator.
Turning now to
Turning now to
As mentioned above, the example vessel 320 is substantially axisymmetric. The first exterior portion 328, the second exterior portion 332, and the interior 338, excluding the bottom portion 340, are substantially cylindrical, but may include draft for molding purposes and/or other purposes. When inserting the example vessel 320 into the holder 272, the rounded third exterior portion 334 may assist in guiding the vessel 320 into the holder 272. Upon further insertion of the example vessel 320 into the holder 272, the flange portion 330 of the vessel 320 abuts a bottom of the counter bore 276 of the holder 272 and thereby seats the vessel 320 in the holder 272. A small radial clearance is present between the second exterior portion 332 and the through hole 274 and thereby allows the vessel 320 to spin within the holder 272 when spin-mixing occurs.
Turning again to
Turning now to
The first probe arrangement 280 is actuated by a first actuator 282. Similarly the second probe arrangement 290 is actuated by a second actuator 292. The first actuator 282 includes a pulley 282P and a belt 282B. Likewise, the second actuator 292 includes a pulley 292P and a belt 292B. The first actuator 282 actuates a first probe platform 286 (e.g., a frame, a moveable frame, a mounting platform, etc.), and the second actuator 292 actuates a second probe platform 296 (e.g., a frame, a moveable frame, a mounting platform, etc.). In particular, the first probe platform 286 includes a platform attachment 286B that attaches to the belt 282B, and the second probe platform 296 includes a platform attachment 296B that attaches to the belt 292B. As illustrated at
The first probe arrangement 280 may thereby be actuated to various positions along displacement D1. In particular,
The second probe arrangement 290 may also be actuated to a plurality of positions. In particular, the second probe arrangement 290 may be actuated along displacement D2 to a first actuated position or range of positions AP1, a second actuated position (e.g., a washing position) or range of positions AP2, a third actuated position or range of positions AP3, and a fourth actuated position (e.g., an operating position) or range of positions AP4. As illustrated at
As mentioned above, in certain embodiments, the actuated positions AP1, AP2, AP3, AP4, DP1, DP2, and DP3 may vary within a range of position. For example, when aspirating, a probe tip PT may follow a fluid level within the vessel 320 down as fluid is removed from the vessel 320. Thus, the aspirating position AP4 moves in the direction D2− as aspirating progresses.
As mentioned above, the first probe arrangement 280 includes probe assemblies 288A, 288B, 288C, and 288D. In the discussion below, probe assemblies 288A, 288B, 288C, and 288D may be generically referred to as probe assembly 288. Likewise, the second probe arrangement 290 includes probe assemblies 298A, 298B, and 298C. Probe assemblies 298A, 298B, and 298C may be generically referred to as probe assembly 298.
In describing the details of the wash station arrangement 400, the probe assembly 298 is described and illustrated. The wash station arrangement 400 may be adapted to the various other probes P, described and/or mentioned herein.
The probe assembly 298 is attached to the probe platform 296 of the probe arrangement 290 at a platform attachment 296P. In the depicted embodiment, the platform attachment 296P is spring-loaded and thereby provides protection to the probe assembly 298 during a collision. Such collisions are typically inadvertent. In other embodiments, the platform attachment 296P may fixedly attached the probe assembly 298 to the probe platform 296. As the probe assembly 298 is attached to the probe platform 296, the probe assembly 298 follows the probe platform 296 when the probe arrangement 290 is actuated. In the example embodiment, the probe platform 296 is guided along linear displacement D2. Thus, the probe assembly 298 also moves along displacements D2.
As illustrated at
Turning now to
Turning now to
As illustrated at
Turning now to
The depicted probe washer 500 further includes a housing 530. As illustrated at
Turning now to
The actuator 420 may be sensed and/or controlled by the computer 194. The wiring harness 196 may connect the computer 194 to the actuator 420. The actuator 420 may further be connected to a power supply by the wiring harness 196. The wash station arrangement 400 may further include a washer position sensor 450. As depicted, the washer position sensor 450 includes a mount 452 and is thereby attached to the mount 422 of the actuator 420. The washer position sensor 450 further includes a slot 454. The sensor flag 440 of the probe washer mount 430 is positioned within the slot 454 and the washer position sensor 450 can thereby determine the position of the probe washer 500 including the positions PW1 and PW2. The washer position sensor 450 may communicate the position of the probe washer 500 to the computer 194 via the wiring harness 196.
As depicted, the mount 422 of the actuator 420 is further attached to the probe platform 286 and thereby moves with the probe platform 286 (e.g., when actuated by the actuator 282). As the actuator 420 provides a single degree-of-freedom between the probe washer 500 and the mount 422 of the actuator 420, a single degree-of-freedom exists between the probe washer 500 and the probe platform 286. As depicted, the actuator 282 provides a single degree-of-freedom between the probe platform 286 and the frame 108 of the instrument 100. Therefore, the actuator 282 and the actuator 420 together provide two degrees-of-freedom between the probe washer 500 and the frame 108 of the instrument 100. In the depicted embodiment, these two degrees-of-freedom are parallel with each other. In other embodiments, they may be perpendicular or non-parallel with each other. In other embodiments, the probe platform 286 may not necessarily serve as a probe platform, but still serve as a frame for the purpose of carrying the wash station arrangement 400.
In other embodiments, the mount 422 of the actuator 420 may be directly or indirectly attached to the frame 108 of the instrument 100. The actuator 420 may thereby be fixedly mounted to the frame 108 of the instrument 100. In such embodiments, the actuator 420 provides a single degree-of-freedom between the probe washer 500 and the mount 422 of the actuator 420 and thereby provides a single degree-of-freedom between the probe washer 500 and the frame 108 of the instrument 100.
As depicted at
Turning now to
A back-flow cleaning function may be provided for cleaning the internal portion 366 of the probe body 360. The back-flow cleaning function employs a cleaning fluid flow direction that is generally opposite the fluid flow direction of the primary function of the probe P. As the probe 298 is an aspirating probe, the fluid flow direction of the primary function of the probe 298 is upward when aspirating fluid from the vessel 320. To provide the back-flow cleaning function for the internal portion 366 of the probe body 360 of the aspirating probe 298, a cleaning fluid supply 304 and a pump 306 may be provided. A valve 308 or a plurality of valves may be provided to separate the back-flow cleaning function from the aspirating function.
As illustrated at
A forward-flow cleaning function may be provided for cleaning the internal portion 366 of the probe body 360. The forward-flow cleaning function employs a cleaning fluid flow direction that is generally the same as the fluid flow direction of the primary function of the probe P. If the probe P, illustrated at
As illustrated at
To provide the forward-flow cleaning function for the internal portion 366 of the probe body 360, a cleaning fluid supply 404 and a pump 406 may be provided (see
A back-flow cleaning function may be similarly provided for cleaning the internal portion 366 of the probe body 360. The back-flow cleaning function employs a cleaning fluid flow direction that is generally opposite the fluid flow direction of the primary function of the probe P. If the probe P, illustrated at
The forward-flow cleaning functions, described above, may reduce carryover. In particular, in forward-flow cleaning the aspirating probe 298 is also aspirating during the washing cycle, which allows for cleaning of the internal portion 366 of the probe body 360 without pushing contaminants in the probe 298 down into the cleaning cavity 544 or closer to the probe tip PT. Similarly, a forward-flow cleaning function does not send contamination upstream in a dispense probe.
The wash station arrangement 400 may further provide external cleaning of the probe body 360. In particular, the wash station arrangement 400 may provide external cleaning to an external portion 368 of the probe body 360. The external portion 368 may be adjacent to the distal end 364 of the probe body 360. Turning now to
The external and the back-flow internal cleaning of the probe body 360, described above, may be done simultaneously. In particular, the drain 510 may carry the waste fluid 412 and the waste fluid 312. In the illustrated embodiment, a single drain 510 is illustrated. In other embodiments, multiple drains may be employed.
The external and the forward-flow internal cleaning of the probe body 360, described above, may be done simultaneously. In particular, the probe P, for example via the opening 370 (see
The various features of the various embodiments may be combined in various combinations with each other and thereby yield further embodiments according to the principles of the present disclosure.
Various modifications and alterations of this disclosure will become apparent to those skilled in the art without departing from the scope and spirit of this disclosure, and it should be understood that the scope of this disclosure is not to be unduly limited to the illustrative embodiments set forth herein.
This application is being filed on Dec. 28, 2018, as a PCT International Patent application and claims the benefit of priority to U.S. Provisional patent application Ser. No. 62/612,054, filed Dec. 29, 2017, the entire disclosure of which is incorporated by reference in its entirety.
Filing Document | Filing Date | Country | Kind |
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PCT/US2018/067948 | 12/28/2018 | WO | 00 |
Number | Date | Country | |
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62612054 | Dec 2017 | US |