DE102014110680A1 - Sample introduction system - Google Patents

Abstract

A sample introduction system for introducing a sample present on a sheet-shaped sample carrier into an empty or prepared sample container with means for cutting the sheet-shaped sample carrier is characterized by a nozzle; a high pressure fluid source connected to the nozzle; and means for controlling movement of the nozzle and / or the sample carrier such that selected portions of the sheet-shaped sample carrier are cut out.

Description

Technical area

The invention relates to a sample introduction system for introducing a sample present on a sheet-shaped sample carrier into an empty or prepared sample container with means for cutting the sheet-shaped sample holder.

Samples, such as organic samples such as blood, are tested in the laboratory for the presence of certain constituents or contaminants and their amount. One example is the screening of neonatal blood samples for hereditary disease screening. The Dried Blood Spots analysis (DBS) samples are applied as drops on cards made of filter paper. For this, the sample carrier is provided with a marking. The sample dries on the sample carrier.

State of the art

DE 20 2011 110 050 U1 discloses an arrangement for detecting dried samples on a support. The sample is extracted from the carrier and the extraction head used for this purpose is purified.

Under the product name "Panthera Puncher 9", the company PerkinElmer, Inc. distributes a sample punching system. For analysis, the marked area is punched out with the sample and transferred with the punched-out part of the sample carrier in a sample container. Accordingly, the sample carrier forms an undesirable sample matrix. A disadvantage of the known method is that the cutting means used for punching punched out successively different samples, which can lead to the contamination of samples with sample particles of the preceding samples. Therefore, a complex cleaning is required.

If a sample is not or not completely applied at the marked position on the sample carrier, a readjustment by hand is required or the sample is only partially punched out. Then there is less sample mass, which may worsen the detection limit.

Disclosure of the invention

It is an object of the invention to provide a device of the type mentioned, which simplifies the transfer of samples of sheet-shaped sample carriers in a sample container and avoids contamination.

• (a) eine Düse;
• (b) eine an die Düse angeschlossene Hochdruckfluidquelle; und
• (c) Mittel zum Steuern einer Bewegung der Düse und/oder des Probenträgers derart, dass ausgewählte Bereiche des blattförmigen Probenträgers ausgeschnitten werden.

According to the invention, the object is achieved in a sample introduction system for introducing a present on a sheet-shaped sample carrier sample into an empty or prepared sample container with means for cutting the sheet-shaped sample carrier of the type mentioned by

• (a) a nozzle;
• (b) a high pressure fluid source connected to the nozzle; and
• (C) means for controlling a movement of the nozzle and / or the sample carrier such that selected portions of the sheet-shaped sample carrier are cut out.

In this arrangement, the carrier is cut out by means of a high-pressure jet. So no cutting edge is required. Cross-over contamination from sample to sample at the cutting edge is avoided. The high pressure fluid may contain at least one fluid used in the sample preparation process. This has the advantage that no unnecessary fluids are used, which must be removed with difficulty in the later sample preparation process.

The location of the sample carrier with the sample can be completely cut out and transferred to the sample container. Alternatively, the location of the sample carrier may be partially cut out with the sample and means provided for folding the cut-out portion down into the region of the sample container and means for rinsing the sample from the sample carrier with the fluid from the high-pressure fluid source into the sample container. Then, a matrix generated by the sample carrier is avoided. In particular, the means for rinsing the sample may comprise a spray head with which the fluid from the high pressure fluid source is sprayed onto the sample. Then the pressure of the fluid need not be reduced.

In a particularly preferred embodiment of the invention, a scanner is provided with which the color, the degree of drying, the position of the sample, the extent of the sample and / or other optical detectable properties of the sample can be detected. The sample carrier and the nozzle with the high-pressure jet can be moved alone or both so that the sample is cut out exactly. The sample carrier can be moved under a fixed nozzle. For this purpose, the entire holder for sample carrier can be arranged on an xy table. The movement is controlled by the controller. Alternatively, the nozzle is moved. It is also possible to move both components. To record the type and degree of dryness of the sample, an image of the sample with different wavelengths of the spectrum can be taken. This prevents unwanted samples from entering the analysis system. The same camera can be used to collect identification data, such as a barcode.

When taking samples and placing on the carrier, it is not always easy to hit the exact point that will be cut out. These placement tolerances can be taken into account when cutting with a controlled movement. The entire sample enters the sample container. It is understood that in such an arrangement also targeted only a portion of the sample can be cut out and rinsed if necessary, if a remainder should remain for other analyzes or as a reference.

Preferably, a housing tower is provided, in which the sample carriers can be stored stacked with spacers and means for moving a sample carrier from an opening in the housing tower into the region of the nozzle. In this case, the opening in the housing tower may be provided at the lower end and the housing tower have an upper opening for insertion of further sample carriers.

The arrangement works fully automatically and requires no personnel with special expertise. Only the samples need to be adequately provided. The individual steps are executed by the controller.

Embodiments of the invention are the subject of the dependent claims. Embodiments are explained below with reference to the accompanying drawings.

Brief description of the drawings

1 Figure 3 is a perspective view of a multiple station sample preparation assembly;

2 is a perspective view of the sample carousel and the centrifuge at rest, in an arrangement according to 1 be used.

3 shows the centrifuge from the arrangement 1 to 2 during the centrifuging process in detail.

4 shows a complete sample introduction system for dried samples on a sheet-shaped carrier.

5 shows the sample entry system 4 in detail.

6 shows three dosing systems from the arrangement 1 for dosing reagents for sample preparation from a reservoir.

7 shows an arrangement for expelling solvent in the assembly 1 at rest.

8th shows the arrangement 7 during the expulsion.

9 is a perspective view of a film dispenser from the arrangement 1 for closing a sample container in a carousel receptacle with a foil.

10 is a cross section through the film dispenser 9 ,

11 shows a heater in the arrangement 1 ,

12 shows the heater off 11 during heating.

13 shows a sampling device from the assembly 1 ,

14 is a cross section through a hollow needle for sampling with a filter.

15 shows a camera for determining the height of the liquid supernatant in the sample container in a first position.

16 shows the camera 15 in a second position.

17 shows the rotary valve of the sampling device for an arrangement 1 in a first position.

18 shows the rotary valve of the sampling device for an arrangement 1 in a second position.

19 shows the rotary valve of the sampling device for an arrangement 1 in a third position, the flushing position.

20 illustrates how the needle and sample container are discarded after sampling.

21 illustrates the disposal of the sample container after sampling in the bottom of the housing.

Description of the embodiment

1 shows a sample preparation arrangement, which generally with 10 is designated. The order 10 has a substantially circular housing 12 with a carousel 14 on. The carousel 14 consists of a ring with a variety of shots 16 for sample containers 18 , The sample containers 18 can in the radial direction in this provided openings of the recordings 16 be clipped. Alternatively, the sample containers 18 from above into the shots 16 be introduced. The carousel 14 can be about a center axis 20 be rotated. This is a drive and a controller 34 provided, which are not shown here for the sake of simplicity.

In the middle area of the carousel is a centrifuge 22 arranged. The centrifuge 22 also rotates about the center axis 20 , Outside on the housing 12 Several sample preparation stations are located, including sample entry and sampling. The stations include a sample entry system 24 for dried samples on a sheet-shaped carrier. Clockwise behind it are three dosing systems 26 arranged for dispensing reagents for sample preparation from a reservoir. The clockwise clockwise station 28 is a foil dispenser for closing one in a receptacle 16 in the carousel 14 located sample container 18 with a foil. Below the foil dispenser 28 is a vortex station 30 arranged. The vortex station 30 is in figures, 9 and 10 clearly visible.

On the sample entry system 24 opposite side is a sampling device 32 arranged. The removed, ready-prepared samples are then fed to an analyzer, which is formed in the present embodiment of an HPLC column with detector (not shown).

All stations and devices described above are connected to a common controller (not shown). The controller controls all required drives and receives and stores data and results. Settings can be made either directly at the station or via a user interface on the controller. There, also sample preparation methods with type and duration of the individual sample preparation steps can be entered and stored.

2 shows the case 12 again in detail. The housing 12 is closed with a transparent lid (not shown), so that a contamination of the samples is avoided. In addition, the ambient air is protected from evaporating solvents, etc.

The sample containers 18 be in the shots 16 held. Each sample container 18 has the shape of a test tube and is with a barcode 38 provided as a printed sticker on the sample container 18 is glued on. Outside on the housing 12 is a standard barcode scanner 36 arranged. The scanner 36 serves as a reader and reads in the data stored in the barcode. These data include an identification number in the present embodiment. The identification number is a sample type, e.g. As blood or urine and a sample preparation process assigned. The scanner 36 transmits the position, ie the angular position of the recording 16 in the carousel 14 and the identification number to the controller. Based on the identification number, the controller determines the required sample preparation steps and controls the individual stations accordingly.

The samples in the sample containers 18 The stations can start in the order of their positions. However, there are cases where individual stations need not be approached, a station is already occupied or a sample with higher priority is to be treated. For this purpose, the sample container with gripping arms 40 the centrifuge 22 into another recording 16 be offset. The gripping arms 40 are radially movable for this purpose. They come with the drive from a co-rotating holder 41 extended. They can be extended to the carousel. At the end of the gripper arms 40 sits a pincer claw 42 with which the sample containers 18 can be taken and held. For every gripper arm 40 and every claw 42 suitable drives are provided with sliding contacts for the power supply. By slow rotation of the centrifuge 22 can be a sample container 18 from one shot to another shot 16 to be moved.

In the present embodiment, two gripping arms 40 at the centrifuge 22 shown. But it is also conceivable, several pairs with opposite gripping arms 40 provided. In any case, the centrifuge has 22 a double function: on the one hand, as with conventional centrifuges, a sample can be centrifuged. This is in 3 shown. The other is the centrifuge 22 precisely controllable and used to transfer a sample container 18 from a recording 16 in another. For centrifuging, the centrifuge rotates very fast. This creates centrifugal forces and the solids in the sample are pressed outwards to the bottom of the sample container. The grippers 42 are to the gripping arms 40 hinged. In this way, the sample container 18 take an approximately horizontal position during centrifuging. This is in 3 shown.

4 and 5 show the sample entry system 24 , The sample entry system 24 Includes a removable and replaceable housing 46 , The housing 46 forms a tower in the sheet-shaped sample carrier 48 are stored stack-shaped. Spacers are provided between the sample carriers. On the sample carriers 48 are dried samples 50 , An example of such a dried sample is a dried drop of blood. The samples are located at defined locations, which are marked so that the sample can be applied directly to this site during sampling.

Every sample carrier 48 is with a barcode 54 Mistake. The barcode 54 comes with a standard barcode scanner 52 or a camera. The data is transferred to the tracking controller. For several samples, several barcodes may be provided. With the same scanner 52 Further, the exact position of the samples 50 on the sample carrier 56 determined. The scanner 52 works with different wavelengths of the spectrum and can thus also capture the type of sample. Samples of undesirable or unknown appearance may be excluded from the entry to avoid contamination of the assembly. It is also possible to detect the position with another scanner or to use a preset position.

The lowest sample carrier 56 gets into the area above a sample container 18 emotional. This is in the sample entry system 24 a suitable drive (not shown) is provided. The drive is designed as an xy drive, on which the holder for the sample carrier is attached. The drive thus not only allows a horizontal movement of the sample carrier 56 perpendicular to the housing 46 , but also laterally in a horizontal direction parallel to the front housing wall.

At the front housing wall of the housing 46 is a high pressure nozzle 58 held. This is in 5 shown. The high pressure nozzle 58 is via a high pressure line 60 connected to a solvent reservoir. With a pump (not shown), a high-pressure jet can be generated. The high pressure jet passes over the high pressure nozzle 58 in the direction of the sample carrier 56 out. The high pressure jet is sized so that the sample carrier 56 thereby being cut. By suitable movement of the sample carrier 56 will be under the high pressure nozzle 58 Part located cut out. The movement is controlled by the common control unit. In the present embodiment, the sample 56 only partially cut out. Subsequently, the sample 50 with the solvent from the sample carrier 56 in the sample container 18 rinsed. For rinsing a spray head is provided, which is also acted upon by high-pressure fluid. Alternatively, the entire area of the slide becomes 56 cut out and the sample 50 falls with the part of the sample carrier underneath 56 in the sample container 18 ,

The solvent is a solvent that is used anyway in the further process for sample preparation. It therefore does not need to be laboriously removed from the sample container.

Depending on the application and the type of sample carrier, several samples can be cut out at the same time. In the present embodiment, in each case two adjacent samples 50 cut out with two high-pressure jets arranged side by side. For this purpose are two high-pressure nozzles 58 on the housing 46 intended.

In an alternative, not shown embodiment is not the sample carrier 56 but the high-pressure nozzle moves. However, the same result is always achieved.

6 shows three dosing systems 26 for dosing reagents for sample preparation from a reservoir 62 , An example of a reagent is a precipitant to precipitate interfering parts of the sample matrix. However, it is also possible to add solvents or diluents if this makes sense for the analysis. The reagent is in a reservoir 62 , Each of the three reservoirs 62 is via a hose connection 64 connected to a metering pump. The metering pump is controlled by the control unit. The reagent from the reservoir 62 with the selected volume via a dosing output 66 in the sample container underneath 18 dosed. The three metering outputs 66 are in 6 to recognize.

In the present embodiment, three metering systems 26 provided that can work simultaneously. In this way, the same reagent can be dosed simultaneously into three sample containers. This achieves a high throughput. However, depending on the application, it is also possible to use different reagents for different applications or sample preparations.

7 and 8th show how unwanted solvent is expelled from the sample. A neutral gas, in this case pressurized nitrogen gas, is supplied by means of a needle 67 introduced into the sample. Solvent present in the sample is thereby released and released to the outside. The needle 67 is from a resting position in 7 is shown, movable in an operating position. The operating position is in 8th shown. The direction of movement is by an arrow 71 represents. In the associated bracket 69 a suitable drive is arranged. In the present embodiment, two needles 67 provided for expelling solvent. A nitrogen supply line is driven from the outer edge of the carousel through the foil. A second needle is used to dispose of exhaust gases. Gas is supplied and forms a cyclone in the sample container. The solvent evaporates and exits through the second needle.

9 and 10 show two foil dispensers 28 for closing a sample container in a carousel receptacle with a foil 68 , 10 is a cross section through the film dispenser 28 , The foil 68 is from a roll of film 70 above the sample container 18 unrolled. The film roll 70 is attached to a holder 72 held. The holder 72 has a radially projecting arm 74 on. The foil 68 is over the arm 74 and a pulley 76 led down. This is the film 68 in the horizontal direction between a stamp 78 and the top edge 80 of the sample container 18 curious; excited. The Stamp 78 has essentially the dimensions of the upper edge 80 of the sample container 18 , The upper edge 80 of the sample container 18 is rounded so that the film does not travel. Inside the stamp 78 a heater (not shown) is arranged whose temperature is adjusted by the controller. The heater is formed by a filament arranged in a cartridge.

To close the sample container 18 a piece of unused film is deducted. This is at the bottom of the film a role 82 provided with a (not shown) drive. The unused foil is located between the stamp 78 and edge 80 , Subsequently, the holder 72 with the arm 74 and the attached, heated stamp 78 moved down. For this purpose, a drive (not shown) is provided. The drive is controlled by the controller. Due to the resulting pressure and the elevated temperature, the film is melted onto the edge. In the process, the film in the area of the sample container is released from the remainder of the film 68 from. The sample container 18 is tightly sealed. The melting takes place in a way that prevents the penetration of vapors into the sample container.

Depending on the application, the sample container 18 continue to be pressed down. Below the sample container 18 and the stamp 78 is the vortex station 30 arranged. When pressure is applied to the sample container 18 a vortex movement is performed. The sample in the sample container 18 is mixed.

Depending on the desired sample throughput, multiple foil dispensers 28 be arranged side by side. Then you can have several sample containers 18 be closed at the same time. Alternatively, only a plurality of punches are used, the multiple sample container 18 simultaneously with a wider slide 68 close. In the present embodiment, two film dispensers 28 used with two foils (s. 1 and 9 ).

Next to the vortex station 30 is a heater 73 arranged. This is in 11 shown. The heating system 73 has a housing with two shots 75 on. The heating system 73 is arranged movable in the vertical direction. For this purpose, a controlled by the controller drive (not shown) is provided. The housing of the heater 73 is driven up. The shots enclose 75 the lower part of the sample container arranged above it 18 and can heat them. This situation is in 12 shown.

To separate solids, two of the sample containers 18 with opposite gripping arms 40 the centrifuge 22 gripped and rotated.

To remove the sample and transfer to the analyzer is the sampling device 32 intended. This is in 13 shown. The sampling device 32 includes a hollow needle 84 on a movable, conical head 86 , The head 86 is attached to a pole and there up and down movable. For this purpose, a suitable drive (not shown) is provided, which is controlled by the controller. To remove the sample, the sample container 18 under the area of the hollow needle 84 emotional. Subsequently, the hollow needle 84 moved down until it dips into the sample. The immersion depth is controlled by a vertically moving video camera 53 controlled with image processing, so that the immersion depth is always on the half of the liquid regardless of the amount of solids. 15 shows the video camera 53 in a lower position. 16 shows the video camera 53 in an upper position.

In the hollow needle 84 is filter material 88 , This is in 14 to recognize. If now some sample liquid in the hollow needle 84 is sucked in, remain solid particles and suspended particles in the filter material 88 hang. For this purpose, a piston pump 114 intended. The sample prepared in this way can be introduced directly into an HPLC column or another analyzer.

For each sample, a fresh needle with unconsumed filter material is used. These are in a depot 90 with an ejector. So before another sample is taken can, the used needle is loosened and a fresh needle attached to the head.

With the sampling device 32 the sample is taken from the sample container 18 transferred to the analyzer. In the present embodiment, a chromatography column (not shown) is used for analysis. This is a rotary valve 94 with 6 connections 96 . 98 . 100 . 102 . 104 and 106 intended. The rotary valve is connected to a measuring device, a pump and the filter needle. This is in 17 to 19 shown.

At the connection 98 is supplied to eluent from a solvent source. This is by an arrow 108 represents. connection 100 leads to a chromatography column. In the present embodiment, an HPLC column, not shown, is used. This is by an arrow 110 represents. connection 102 is over a line 116 with a connection 112 a piston system 114 connected. The piston system 114 comes with a stepper motor 118 operated. This is by an arrow 120 represents. connection 96 is over a line 122 with a second connection 124 of the piston system 114 connected.

17 shows the valve position at which the needle 84 in the sample container 18 immersed sample liquid is immersed. In this position, eluent is pumped into the HPLC column. The piston 126 of the piston system 114 is with the stepper motor 118 in the direction of the arrow 120 emotional. This is a well-defined volume of sample liquid 128 through the needle 84 to the connection 104 and over the connection 102 into the loop formed as a loop 116 reared. The dead volume of the needle and the valve are taken into account.

Subsequently, the valve in the in 18 shown position. The in the loop 116 The sample is now over the connection 102 with the connection 100 and thus connected to the exit to the HPLC column. When moving the piston 126 to the left in the illustration, the sample is pumped to the HPLC column. At the same time, eluent flows through the connection 98 to the connection 96 and through the line 122 to the piston system 114 ,

For rinsing, the valve is set back, as in 19 is shown. The piston will 126 in the direction of the arrow 130 emotional. It is in the system running solvent on the line 116 through the connections 102 and 104 to the needle 84 directed. Sample remains are taken and into the sample container 18 rinsed. The eluent flows through the interconnected in this position connections 98 and 100 in the HPLC column and rinsed this as well.

After taking the sample and rinsing the valve becomes the needle 84 dissolved over the sample container and the sample container 18 with a gripper arm 40 the centrifuge 22 grabbed and in an opening 92 in the bottom of the case 12 conveyed by the gripper 42 above the opening 92 to open. This is in 21 shown. Below the opening 92 There is a waste container containing the spent sample containers 18 absorbs with the rinsing liquid. At the same time a new needle is put on.

With movement of the piston to the right in the illustration, the next sample can be sucked up and the cycle repeated.

The controller sits together with the power supply and the required electronic components in a ventilated and shielded against chemicals and vapors housing, for example, next to or below the housing 12 , With the controller, higher priority samples can be passed through the sample preparation faster, even if the system is already occupied by other samples. A sensor can identify empty positions in the carousel, count and report to the controller. During placement, the user can enter the number of required positions with the associated priority. These are then taken into account accordingly by the controller. Samples whose contents can not be analyzed by the system in the current configuration, for example a column configuration, are returned untreated. In this way, excessive contamination is avoided.

With the controller, the temperatures in the punch and in the heater are adjusted rotational speed and angle of rotation on the centrifuge, dosing volume and type and sequence of the sample preparation steps. The controller evaluates the signals from the sensors, cameras and scanners.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• DE 202011110050 U1 [0003]

Claims (9)

Sample introduction system for introducing a present on a sheet-shaped sample carrier sample into an empty or prepared sample container with means for cutting the sheet-shaped sample carrier, characterized by (a) a nozzle; (b) a high pressure fluid source connected to the nozzle; and (C) means for controlling a movement of the nozzle and / or the sample carrier such that selected portions of the sheet-shaped sample carrier are cut out. Sample introduction system according to claim 1, characterized in that the high-pressure fluid contains at least one fluid which is used in a subsequent sample preparation and / or measurement method. Sample introduction system according to claim 1 or 2, characterized in that the location of the sample carrier is completely cut out with the sample and transferred to the sample container. Sample introduction system according to claim 1 or 2, characterized in that the position of the sample carrier with the sample is partially cut out and means are provided with which the cut-out part is folded down into the region of the sample container, and means for rinsing the sample from the sample carrier with the fluid from the high pressure fluid source into the sample container. Sample introduction system according to claim 4, characterized in that the means for rinsing the sample comprise a spray head, with which the fluid from the high-pressure fluid source is sprayed onto the sample. Sample introduction system according to one of the preceding claims, characterized in that a scanner is provided with which the color, the degree of drying, the position of the sample, the extent of the sample and / or other optical detectable properties of the sample can be detected. Sample entry system according to one of the preceding claims, characterized by a reading device for reading out identification data and / or data for the sample preparation to be carried out from a barcode, RFID memory or another data memory provided on the sample or the sample container. Probeneintragssystem according to any one of the preceding claims, characterized in that is provided in the housing tower, in which the sample carrier with spacers are stored in stacked and means for moving a sample carrier from an opening in the housing tower in the region of the nozzle. Sample introduction system according to claim 8, characterized in that the opening in the housing tower is provided at the lower end and the housing tower has an upper opening for insertion of further sample carriers.

Images