Patent Application
20240102899
The present application claims priority to Luxembourg Patent Application No. LU 103022 filed on Sep. 27, 2022. The aforementioned application is hereby incorporated by reference in its entirety.
The invention relates to a device for the purification of samples.
Automated analyser systems for use in clinical diagnostics and life sciences are produced by a number of companies. For example, STRATEC® SE, Birkenfeld, Germany, produces a number of devices for specimen handling and detection for use in automated analyser systems and other laboratory instrumentation.
With respect to the analysis of specimen or samples, it may be necessary to purify specimen or samples. The purification may comprise dispensing and aspirating appropriate solutions. A container comprising a sample will be transferred to a section or device of an automated analyser system which is equipped for performing the respective washing steps.
Such a device for the purification of samples may comprise elements for moving racks comprising multiple containers. Alternatively, rotating carousels are known in the prior art providing positions for receiving container comprising a sample.
The processing of a sample comprises usually dispensing and aspirating fluids depending on the respective protocol of an assay that is to be performed with a sample. Numerous assays comprise washing steps where washing buffer is added to a sample and aspirated. Identical or different washing buffer may be used in a single or multiple washing steps to purify the sample which is to be analysed.
Published U.S. Pat. No. 7,427,376 B2 discloses a sample analyser which includes a liquid aspirator to be stuck into the closed container for aspirating a sample from a closed container; a preparing section for preparing an analysis sample using the aspirated sample; and an analysing section for analysing the prepared analysis sample; the liquid aspirator including an elongated pipe, the pipe having a liquid flow path extending therein and a plurality of communicating sections provided in an outer surface thereof, at least one of the communicating sections communicating between an inside and an outside of the container when the pipe is stuck into the container.
Published U.S. patent application US 2003/027206 A1 discloses an automated analyser for performing multiple diagnostic assays simultaneously includes multiple stations, or modules, in which discrete aspects of the assay are performed on fluid samples contained in reaction receptacles. The analyser includes stations for automatically preparing a specimen sample, incubating the sample at prescribed temperatures for prescribed periods, preforming an analyte isolation procedure, and ascertaining the presence of a target analyte. An automated receptacle transporting system moves the reaction receptacles from one station to the next. The analyser further includes devices for carrying a plurality of specimen tubes and disposable pipette tips in a machine-accessible manner, a device for agitating containers of target capture reagents comprising suspensions of solid support material and for presenting the containers for machine access thereto, and a device for holding containers of reagents in a temperature-controlled environment and presenting the containers for machine access thereto. A method for performing an automated diagnostic assay includes an automated process for isolating and amplifying a target analyte. The process is performed by automatically moving each of a plurality of reaction receptacles containing a solid support material and a fluid sample between stations for incubating the contents of the reaction receptacle and for separating the target analyte bound to the solid support from the fluid sample. An amplification reagent is added to the separated analyte after the analyte separation step and before a final incubation step.
Published U.S. Pat. No. 5,216,926 A discloses an automatic sampling apparatus to use bang-bang fluid driven actuators whose control system is modified to permit accurate positioning over its range of motion. The actuators are positioned to aspirate liquid contents held within stoppered sample containers and equilibrate pressure in the sample containers to atmospheric prior to aspiration.
Thus, there is a need for a device allowing the safe and independent handling of fluids required during the processing of a sample in a container.
The present invention provides a device for the purification of samples, comprising a circular carousel which is rotatable around a vertical central axis and provides a plurality with a plurality of container-receiving positions, and a fixed side wall attached to one side of the carousel, wherein the fixed side wall comprises a side wall PCB mounted to the fixed side wall, a toothed rack guiding for vertically moving an aspiration needle up and down, a motor for actuating the toothed rack, light barriers for determining the angle of rotation of the carousel, and bubble sensors for monitoring aspiration of fluids from the containers and for monitoring rinsing of the aspiration needle. The rotatable carousel comprises four vertically on top of each other arranged level, wherein a first level, which is the upper level, comprises injector assemblies which are arranged on a first level plate for dispensing fluids and an aspiration needle rinsing station for cleaning of the vertically crossing aspiration needle which is arranged onto said first level plate, a second level, below the upper level, comprises a plurality of container-receiving position, each for receiving a container, wherein each container-receiving position of the plurality of container-receiving position is arranged above a second level plate, a third level, below the second level, comprises stacked printed circuit boards, and a fourth level, below the third level, comprising a base plate comprising counter bearings for the centrally arranged rotor axis of a motor as a drive for rotating the carousel and a slide bearing between an upper end of the rotor axis and the first plate. One position of the plurality of container-receiving positions is configured for a loading and unloading of containers to the carousel, wherein one position of the plurality of container-receiving positions provides an injector assembly configured for aspirating fluids by a connected pump, and wherein the remaining positions of the plurality of container-receiving positions provide an injector assembly configured for dispensing a fluid by a connected pump.
A further aspect relates to the toothed rack guiding which may comprise a bore and guiding with at least one slide bearing which is crossed vertically by the toothed rack.
In another embodiment, the needle holder may be arranged at the upper end of the toothed rack, and wherein the aspiration needle is fixed to the needle holder.
It is further intended that the aspiration needle can be mounted horizontally movable in x- and y-direction to the needle holder.
The invention relates further to a device, wherein the gear wheel connected to the motor for actuating the toothed rack engages into the gearing of the toothed rack.
In another embodiment, a single injector unit may comprise an injector manifold which is fixed on top of the first level plate, and which carries two valves.
The invention relates also to a device, wherein each injector unit comprises two fluid supply connectors for connecting a hose coming from a fluid supply and a single waste connector for connecting a hose to a waste.
It is also envisaged that the aspiration needle rinsing station comprises an outer part and an inner part, wherein a rinsing channel runs through both parts.
Another aspect of the invention relates to an embodiment, wherein the inner part of the aspiration needle rinsing station is sealed against the outer part of the aspiration needle rinsing station and the rinsing channel surrounds in the inner part the bore and guiding for the vertically crossing aspiration needle.
The outer part of the aspiration needle rinsing station may comprise a first and a second hose connector, wherein the first hose connector connects a hose coming from a rinsing buffer supply and the second hose connector connects a hose leading to a first bubble sensor on the fixed circuit board.
In a further embodiment have each container-receiving position of the plurality of container-receiving positions a cylindrical shape and a recess one side at its bottom end.
It is further intended that each container-receiving position of the plurality of container-receiving positions is connected eccentrically through a motor shaft to the motor.
The motor for actuating the container-receiving positions can be an EC motor comprising a plurality of Hall sensors.
An optical sensor can be arranged on the fixed circuit board at the level of the recesses of the container-receiving position for reflective distance measuring.
The PCBs of the third level may comprise plugs for the connection of the stacked printed circuit boards to each other and plugs for the connection of the stacked printed circuit boards to an external controller and the motors as drives for each container-receiving position.
It is further intended that the fixed circuit board is arranged vertically on one side of the rotatable carousel, wherein the fixed circuit board is a control unit comprising a data storage.
Another object of the present invention relates to a system comprising a device as described above and a housing, wherein the rotatable carousel is arranged in the housing in a manner allowing the loading and unloading of containers only at one position during rotation of the carousel.
Still other aspects, features, and advantages of the present invention are readily apparent from the following detailed description, simply by illustrating preferable embodiments and implementations. The present invention is also capable of other and different embodiments and its several details can be modified in various obvious respects, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and descriptions are to be regarded as illustrative in nature, and not as restrictive. Additional objects and advantages of the invention will be set forth in part in the description which follows and in part will be obvious from the description or may be learned by practice of the invention.
The invention will be described based on figures. It will be understood that the embodiments and aspects of the invention described in the figures are only examples and do not limit the protective scope of the claims in any way. The invention is defined by the claims and their equivalents. It will be understood that features of one aspect or embodiment of the invention can be combined with a feature of a different aspect or aspects of other embodiments of the invention, in which:
The technical problem is solved by the independent claims. The dependent claims cover further specific embodiments of the invention.
The term container relates to a consumable which relates within the present disclosure to a device which provides cavities, receptacles, or recesses for receiving a fluid which can be a liquid like a patient sample for instance. A container can be a tube.
The term fluid refers to a liquid or gas which both may comprise solids. The term patient sample relates to any body liquid like whole blood, urine, lymph or saliva. A sample may already have undergone prior treatments like centrifugation so that the sample is provided in a specific state.
The present invention relates to an assembly or system comprising a wash carousel. A wash carousel within the meaning of the present disclosure relates to a circular carousel which is rotatable around a vertical central axis and provides a plurality of container-receiving positions The system comprises electronics (printed circuit boards) which can be identical, but which are stacked in three different sub-level for addressing different tasks. The PCBs in each level are protected from overflowing liquids.
The system comprises an aspiration needle which is used for aspirating fluids from a container. The aspiration needle is movable in x- and y-direction for tolerance compensation in these planes. The aspiration needle can be made of metal. Rinsing of the aspiration needle is possible in an aspiration needle rinsing station which is an integral part of the system so that contaminations which may adhere to the outer surface of the needle can be removed prior to using a tip or needle, in particular in a different fluid.
A device according to the present invention relates to a rotatable carousel which may comprise in an embodiment five independent positions for the processing of a sample in a container. Injectors are used in certain positions for dispensing up to six different fluids like buffer or reagents.
The loading and unloading of a container will always be done at the same position of the wash carousel. Besides the position for loading or unloading there are five further positions present. The containers are placed into container-receiving position which are mounted on a rotatable plate. Each container-receiving position itself is mounted above a motor as a drive for mixing of the respective contents in a container by eccentric rotation resulting in an orbital movement. Each container-receiving position comprises an integrated unbalance correction. The transfer container-receiving position for loading or unloading is accessible by a user or a device for the loading or unloading. It is the only position of the carousel which is accessible from the outside. The transfer position can be arranged behind a flap or a movable part of a housing for making the position accessible.
Aspiration and rinsing of a pipette tip or needle are monitored by optical air bubble sensors. An optical sensor is further used for the initialization of the container-receiving position drives by a combination of absolute encoder and detection of the container-receiving position by said optical sensor.
The four level of the rotatable wash carousel can be characterised in an embodiment referring to
The following sequence of steps is exemplary for a system according to the present invention. It is obvious for a person having ordinary skill in the art that the kind of steps or their sequence may vary. Turning is usually performed clockwise and counterclockwise during operation of the carousel, depending on the required movement of the rotatable carousel.
There may also be processes in which at least one fluid is only dispensed via the injectors and no aspiration takes place. The following steps are exemplary for an embodiment of a method that is performed using an embodiment of a device according to the present invention:
The aspiration needle 3 is driven in the vertical z-direction by a motor (shown in
Rinsing channel 404 extends from a first hose connector 405 which connects rinsing channel 404 to a first hose (not shown) for the supply of rinsing buffer. A second hose connector 406 is used for a connection to a drain (shown in
Due to the integrated rinsing channel 404 the needle 3 is guided vertically through the needle rinsing station 4 and can thus be rinsed on its outer surface along its entire length—if necessary—during a vertical movement by flushing rinsing buffer through rinsing channel 404. Only the lower part of the needle 3 may get in contact with the liquid, so that only that part of the needle is rinsed which has been in contact with a fluid in a container.
In an embodiment of a method in an automated analyser system, it may be intended that the tip of aspiration needle 3 is rinsed with every upwards movement. For that, the z-drive first moves quickly upwards, and the rinsing pump is not yet active until the area of the needle tip is reached which is to be cleaned. Then, the z-drive slows down movement of the needle and the rinsing pump are activated so that the rinsing process commences.
Three injector units 12 which can be connected to a maximum of six different fluids allow the use of six different fluids to be dispensed via the injector units. The valves may be solenoid valves. Two different pumps may be used for providing the fluids, one for larger volumes and one for small volumes, with a higher precision regarding the dispensed volume. In an embodiment of the wash carousel, three injector units 12 may be present for a single wash carousel.
Valves 12b, c are connected through electrical connectors 121b, c to a controller which is located on the side wall PCB 7.
Each of the five container-receiving position 21 are identically formed. Between the fluid protective element 23 and the lower end of each container-receiving position 23 are sealing elements 24 arranged for sealing of the transition area, respectively the motor shaft (not visible) between container-receiving position 21 and fluid protective element 23 or between second and third level which is spanned motor shaft 33. Said sealing elements 24 can be disc-shaped silicone plates for instance, as can be taken from
The aspiration of unneeded fluid by the aspirating needle 3 must take place centrally in the container 5, as the desired components of the sample may have settled at the edge due to a centrifugation step prior to loading of the container into the container-receiving position. The aspiration needle 3 will only hit the centre of the container 5 at a certain angle of rotation of the carousel comprising the container-receiving position 21 when the container is in a centralised position below an opening 13.
The EC motor of holder drive 32 comprises Hall sensors (not shown) for motor commutation. The signals from these Hall sensors are also used to determine the position of the container. Since the position of the container is not unambiguously determined by the integrated Hall sensors, because a Hall sensor signal repeats after a half revolution, another sensor is necessary for determining in which half of the revolution the container-receiving position 21 is currently located. An optical sensor 27 for an optical reflection measurement by a time-of-light method is mounted on the fixed circuit board 7 and can thus distinguish between the two possible positions of the container-receiving position by measuring the light reflection which differs between a reflection from the recess 25 providing a straight surface towards the sensor or the round bottom end of the container-receiving position 21 providing a curved surface. The two possible revolutions determined by the Hall sensor can thus be distinguished with the additional optical sensor so that a centralised position of container-receiving position 21 below an opening 13 can be ensured.
Since the position of the motor shaft belonging to the assembly of holder drive 32 and container-receiving position 21 (not shown) in relation to the position of the container-receiving position 21 is undetermined at the time of assembly, the position must be taught to the system or a controller of the system once after its assembly.
Each motor must still be uniquely controlled, so that each PCB 31 and thus the respective motor must be uniquely addressed. Each PCB may comprise one switch for addressing the respective PCB 31. However, since manual intervention is always a possible source of error, the motor drivers in this invention are addressed automatically by plugging them together through plug connectors 603.
For this purpose, it may be intended that four address lines (ID1 . . . ID4) are passed from PCB to PCB, but offset by one connector pin, thus creating the unique address for each PCB. With these four address lines, a maximum of five stacked PCBs can be uniquely addressed.
The position of the wash carousel is controlled and monitored by an EC motor and encoder. The EC motor may optionally comprise or is connected to a gearbox. Since this motor, like the motors for actuating the container-receiving positions 21, cannot measure unique wash carousel positions, it must be initialised once or after each switch-on.
The vertical position of the aspiration needle 3 is initialised each time the unit is switched on by using a light barrier 306 for the toothed rack 302 which is also mounted on the fixed circuit board 7. The toothed rack 302 comprises a flag 307 that interrupts the light barrier so that the position of the toothed rack 302 can be determined.
The fluid in a container is in an embodiment of the present invention aspirated with a peristaltic pump, which is connected to the aspiration needle via a hose. Aspiration will continue until no further fluid is aspirated, because a peristaltic pump is not suitable for a precise control of the flow rate. The volume is determined by precisely adjusting the vertical position of the aspiration needle.
In order to be able to aspirate volumes precisely, or to leave a certain volume in the container, the vertical position of the aspiration needle must therefore be very well adapted to the vertical position of the respective container.
For each of the five container-receiving positions of the wash carousel comprising an injector assembly, the ratio between the position of the aspiration needle and the position of the container must therefore be taught once during initialisation of the system. The aspiration needle moves down as far as possible, even to the bottom of the container, in each container position for storing this position in a controller in relation to the initialisation position determined with the light barrier for each container-receiving position. The determined and stored data can then be used during operation of the wash carousel.
In addition, the vertical position of the aspiration needle in relation to the aspiration needle rinsing station must be very precisely determined in order to be able to rinse the needle tip in a defined manner. For this reason, this position is also taught during initialisation. As with the other teaching methods, a defined distance between the needle holder in the Z-axis and the aspiration needle rinsing station is set using the teach tool.
The rinsing channel extends on the opposite side of the inner part 401 of the rinsing station 4 in the outer part of the rinsing station 402 and it ends at a second hose connector 406 for connecting a hose leading to a drain or waste for the rinsing buffer (not shown).
The contents of the aspiration and rinsing hoses are each monitored by an optical bubble sensor system by air/water detection. The bubble sensors 408 can be mounted on the fixed circuit board 7 and each comprises in an embodiment a light barrier 409 in a housing 410. The housing 410 can be opened, the hose is inserted and is then located between the two light barrier arms. The hose is fixed by closing cover 411 of housing 410.
The light barrier of bubble sensors 408 allows to distinguish whether air or liquid is present in the hose. For controlling and monitoring the aspiration it follows from the detection of air in the hose that the fluid level in the container has dropped to a level where the pump can be stopped because the tip of the aspiration needle is no longer dipped in the respective fluid to be aspirated.
The bubble sensor which is connected to the rinsing channel 404 of the aspiration needle rinsing station is used for monitoring whether flushing is taking place. For this purpose, is mounted between the second hose connector 406 of the aspiration needle rinsing station 4 and a liquid-waste (not shown). There is no complete sealing between aspiration needle 3 and the inner part of the rinsing station 401 for allowing the vertical movement of the aspiration needle 3 in the inner part of the rinsing station 401. Thus, an air-water mixture will always be sucked during rinsing of the aspiration needle 3 when rinsing buffer flushes around the part present in the rinsing channel 404 and thus in the hose leading to a waste or drain. The air-water mixture can be detected by the respective bubble sensor 408 as a kind of “noise”. Continuous air or liquid in the hose would mean that there is a failure regarding the rinsing process.
The advantages of a device according to the present disclosure can be summarised as follows:
The foregoing description of the preferred embodiment of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. The embodiment was chosen and described in order to explain the principles of the invention and its practical application to enable one skilled in the art to utilize the invention in various embodiments as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto, and their equivalents. The entirety of each of the aforementioned documents is incorporated by reference herein.
| Number | Date | Country | Kind |
|---|---|---|---|
| 103022 | Sep 2022 | LU | national |
