[go: up one dir, main page]

WO2008003693A1 - Collecting device for biologically relevant samples - Google Patents

Collecting device for biologically relevant samples

Info

Publication number
WO2008003693A1
WO2008003693A1 PCT/EP2007/056668 EP2007056668W WO2008003693A1 WO 2008003693 A1 WO2008003693 A1 WO 2008003693A1 EP 2007056668 W EP2007056668 W EP 2007056668W WO 2008003693 A1 WO2008003693 A1 WO 2008003693A1
Authority
WO
WIPO (PCT)
Prior art keywords
collecting
punching
sample carrier
container
sample
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2007/056668
Other languages
French (fr)
Inventor
Beat Glauser
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tecan Trading AG
Original Assignee
Tecan Trading AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tecan Trading AG filed Critical Tecan Trading AG
Publication of WO2008003693A1 publication Critical patent/WO2008003693A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/02Devices for withdrawing samples
    • G01N1/04Devices for withdrawing samples in the solid state, e.g. by cutting
    • G01N1/08Devices for withdrawing samples in the solid state, e.g. by cutting involving an extracting tool, e.g. core bit
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5082Test tubes per se
    • B01L3/50825Closing or opening means, corks, bungs
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/021Identification, e.g. bar codes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/041Connecting closures to device or container
    • B01L2300/044Connecting closures to device or container pierceable, e.g. films, membranes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/046Function or devices integrated in the closure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/06Test-tube stands; Test-tube holders

Definitions

  • the present invention relates to a collecting device having a laminar sample carrier for collecting and providing biologically relevant samples
  • the nucleic acids are bound to the cellulose fibers and immobilized, while proteins are denatured and pathogens potentially hazardous to health are inactivated for safe handling of the user.
  • an FTA paper may be sent unrefrigerated in an envelope to a laboratory.
  • a punching is taken from the sample there, placed in a PCR reaction vessel, and washed with the cleaning reagent; the DNA remains immobilized on the matrix and may be stored for years at room temperature. Even RNA is stable on FTA paper at room temperature for several days.
  • the punchings are supplied to a polymerase chain reaction or "PCR" for amplification of the genetic material after the washing.
  • the collection of genetic samples in the meaning of a "genetic fingerprint" is becoming more and more important in two regards: firstly, the genetic code is to be acquired from criminals who have already been arrested and secondly the acquired data is to be compared to un- known traces found at a crime scene, for example. In the first case, fresh and clearly identified samples are used to build up a data bank, which may be accessed in the second case. However, the findable samples are often incomplete, contaminated, and damaged. Individual countries have changed over in the meantime to preventively acquiring the genetic code of all individuals entering the country or even all the inhabitants of the country.
  • Biologically relevant samples also comprise proteins (e.g., the prions causing Creutzfeld-Jacob syndrome, or bovine spongiform encephalopathy, or BSE respectively), viruses, bacteria, and other microorganisms, human or animal bodily fluids (such as blood, sputum, feces, sperm, and urine), and single cells (such as oral mucosa cells and hair follicles).
  • proteins e.g., the prions causing Creutzfeld-Jacob syndrome, or bovine spongiform encephalopathy, or BSE respectively
  • viruses e.g., the prions causing Creutzfeld-Jacob syndrome, or bovine spongiform encephalopathy, or BSE respectively
  • viruses e.g., the prions causing Creutzfeld-Jacob syndrome, or bovine spongiform encephalopathy, or BSE respectively
  • viruses e.g., the prions causing Creutzfeld-Jacob syndrome
  • Individual sample containers are identified on the basis of their identification, which is readable by a handling robot, and are removed from a storage apparatus using this robot.
  • the identification is additionally used for the purpose of correlating the sample with stored medical data of the corresponding patient.
  • the selected samples are delivered to a first preparation point, where they are transferred using an intake device and delivered to a second preparation point.
  • a portion is punched out of each sample there and laid by the punching head in a predetermined container (e.g., in the well of a microplate) for subsequent biological processing.
  • This processing has been known for some time in principle and comprises the washing of the sample and the performance of a PCR process. While the manual collection and archiving of the samples is relatively simple to execute, the access to the storage apparatus and the provision of the samples for the polymerase chain reaction is obviously very complex.
  • the object of the present invention is to suggest a device and a method, by which the collection and provision of biologically relevant samples, in particular for building up a data bank, is simplified.
  • This object is achieved according to a first aspect by a device having the features of independent Claim 1.
  • This collecting device comprises a laminar, i.e., flat sam- pie carrier for collecting and providing biologically relevant samples and is characterized in that it comprises a counterpart having a through hole.
  • This counterpart is implemented to support the laminar sample carrier upon punching using a punching tool and upon ejection of a sample carrier portion through the through hole into a container for sample processing.
  • the collecting device comprises a laminar sample carrier, from which a sample carrier portion may be ejected through the through hole in the counterpart directly into a container for sample processing.
  • the laminar sample carrier may be selected practically arbitrarily from flat materials, such as FTA paper, filter paper, or nitrocellulose.
  • the container for sample processing which, thanks to individual identification means, such as a 1-D or 2-D bar code, and/or an RFID tag, is clearly and correctly identifiable, is implemented as a PCR tube, the polymerase chain reaction may occur directly in the collecting unit.
  • a special punching tool may also be used for removing the collecting device from the PCR tube following the punching out of a sample carrier portion.
  • a collecting set having multiple collecting units preferably represents the basis for a redistribution of sample containers, which may be pushed roboti- cally downward out of the collecting set, for example, and placed from above into an archive rack or working rack positioned below the collecting set in the same work step.
  • Figure 1 shows a collecting device known from the prior art having multiple FTA papers and filter papers
  • Figure 2 shows a collecting unit according to the present invention having a collecting device and a container for sample processing implemented as a PCR tube, Figure 2A showing a first embodiment before the punching of a sample carrier portion, and Figure 2B showing a second embodiment after the punching of a sample carrier portion;
  • Figure 3 shows a horizontal section through a collecting rack having eight compartments, for example, every second one of which is occupied, Figure 3A showing a first embodiment without retention elements, and Figure 3B showing a second embodiment with retention elements;
  • Figure 4 shows vertical sections through the collecting rack of Figure 3;
  • Figure 4A showing a vertical longitudinal section through a collecting rack of the first embodiment
  • Figure 4A showing a vertical diagonal section along the dot-dash lines in Figure 3B through a collecting rack of the second embodiment
  • Figure 5 shows 3-D views of a collecting unit having a cover and twelve compartments, every second one of which is occupied, a first collecting device being provided for insertion into a working rack and the remaining five collecting devices being provided for insertion into an archive rack.
  • Figure 1 shows a collecting device known from the prior art having multiple FTA papers and filter papers.
  • This collecting device 1' according to the species comprises multiple laminar sample carriers 2' in the form of three FTA papers (upper half) and three filter papers (lower half) for collecting and providing biologically relevant samples.
  • this collecting device 1' known from the prior art comprises an area designed as identification means 14', in which handwritten notes about the subjects or patients from which the samples originate may be entered.
  • the shape of this collecting device 1' is well suitable for postal shipping, but it hardly supports robotic archiving and provision.
  • FIG. 2 shows a collecting unit according to the present invention having a col- lecting device and a container for sample processing implemented as a PCR tube.
  • This collecting device 1 comprises a laminar sample carrier 2 for collecting and providing biologically relevant samples.
  • This collecting device 1 comprises a counterpart 4 having a through hole 3.
  • This counterpart 4 is implemented to support the laminar sample carrier 2 upon punching using a punching tool 5 and upon ejection of a sample carrier portion 6 through the through hole 3 into a container 7 for sample processing.
  • This collecting device 1 according to the present invention preferably comprises retention means 8, using which the laminar sample carrier 2 is attached to the top side 9 of the counterpart 4.
  • the counterpart 4 preferably comprises insertion means 11 on its bottom side, using which the collecting device 1 is attachable to the intake opening 12 of a container 7.
  • the retention means 8 and/or the insertion means 11 may preferably be implemented as annular (cf. Figure 2) or finger- shaped (not shown).
  • a collecting device 1 in which the retention means 8 and the insertion means 11 are produced in one piece is especially preferred. This is advantageous in particular if the retention means 8 and the insertion means 11 are produced in one work step (e.g., using injection molding) and in one piece from an elastic plastic. In alternative collecting devices, only the retention means 8 or the insertion means 11 may be produced from an elastic plastic.
  • the insertion means 11 which is to be able to be plugged like a stopper into the intake opening 12 of the container 7, may be softer and more flexible than the retention means 8, which is to hold the laminar sample carrier 2 securely on the counterpart.
  • a harder material is advantageous in par- ticular if the uppermost part of the retention means, which overlaps the laminar sample carrier 2, is implemented as a finger.
  • the entire retention means 8 may be molded as multiple, for example, three or more fingers, on the insertion means 11.
  • the counterpart 4 is preferably also produced from a plastic, especially preferably a hard plastic. Notwithstanding the embodiments shown in Figure 2, the three parts of insertion means 11, retention means 8, and counterpart 4 may be injection molded in one piece, the insertion means preferably being implemented from a softer plastic.
  • the laminar sample carrier 2 is preferably selected from a group comprising FTA paper, filter paper, and nitrocellulose. However, other laminar sample carriers 2 may also be provided, if they are also suitable for punching.
  • Figure 2A shows a first embodiment of a collecting device 1 according to the present invention before the punching of a sample carrier portion.
  • the collecting device 1 comprises four parts, a hard counterpart 4, a softer insertion means 11, and an annular retention means 8, which is also softer and fixes the laminar sample carrier 2.
  • This retention means 8 made of a softer plastic allows, for example, the replacement of laminar sample carriers 2 and/or the insertion of such sample carriers as needed.
  • the insertion means 11 is preferably connected to the counterpart 4 by gluing, welding, or vulcanization here.
  • the laminar sample carrier 2 is fixed without the use of any adhesives on the counterpart 4.
  • a punching apparatus 22 having a punching tool 5 for punching out a sample carrier portion 6 from the laminar sample carrier 2 of the collecting device 1 is positioned over the sample carrier.
  • This punching tool 5 comprises a punching tube 23 having an annular punching blade 24 and an ejection tool 25, which is situ- ated in the punching tube 23 so it is movable.
  • the counterpart 4 of the collecting device 1 has a through hole 3, whose diameter is greater than the diameter of the punching tube 23. Therefore, the punching tool 5 may be used to punch a sample carrier portion 6 out of this laminar sample carrier 2 (arrow direction) and to convey the punching thus obtained through the through hole 3 into the con- tainer 7 and eject it there.
  • This ejection is preferably performed by the cylindrical ejection tool 25, which is displaceable downward.
  • the diameter of the punching blade 24 is preferably only slightly less than the diameter of the through hole 3, so that the laminar sample carrier 2 may not significantly deform during punching.
  • the fact that the laminar sample carrier 2 is clamped correctly by the reten- tion means 8 on the counterpart 4 also counteracts this deformation.
  • the punching tool 5 comprises barbs 26, which are folded in here and whose folded-out position is marked by dashed lines.
  • the collecting device 1, which is attached using insertion means 11 in the intake opening 12 of a container 7, is referred to as a collecting unit 13.
  • the container 7 of such a collecting unit 13 is used on one hand for holding the collecting device 1. On the other hand, this container may additionally be used for sample proc- essing or sample storage.
  • This container 7 preferably carries identification means 14 so that the sample may be identified correctly at any time on the laminar sample carrier 2 of the collecting device or in the container 7 of such a collecting unit 13.
  • These identification means preferably support the machine reading of the existing identification data and are therefore selected from a group which comprises a 1-D bar code, a 2-D barcode, an RFID transponder, and a RuBee transceiver.
  • the principle of 1-D and 2-D barcodes is known to those skilled in the art and is based on the optical scanning of a high-contrast identification marking.
  • the advantage of such identification means 14 is the relatively simple physical principle; however, there must be a visual contact between the scanning device and identification means 14.
  • the RFID transponders known per se which operate at high frequency (HF, such as 900 MHz) or ultra-high frequency (UHF), transmit and re- ceive radio signals, while the newer RuBee transceivers operate at wavelengths below 450 kHz and emit and receive signals which are primarily based on magnetism.
  • HF high frequency
  • UHF ultra-high frequency
  • the passive RFID transponders may receive approximately 100 (HF) or 150-200 (UHF) messages per second, in contrast, the active RuBee transceivers may only receive approximately 10 messages/second: visual contact is not needed in any case.
  • the type of identification means 14 used is thus a function, inter alia, of the density of the data transfer and the presence of a visual contact.
  • An RFID transponder or a RuBee transceiver is situated on the vertical wall of the container 7 here.
  • the container 7 is preferably implemented as a PCR tube, because of which the polymerase chain reaction for amplification of nucleic acids may be executed directly in the collecting container 7. Time-consuming transfers or even sample losses resulting due to incorrect manipulations may thus be avoided.
  • the container 7 preferably has at least one flange 28, which, in especially preferred em- bodiment, projects beyond the outermost edge of the retention means 8 and thus protects the retention means from damage. Two flanges 28 situated parallel to one another and running around the container 7 allow the secure retention of the container 7 and collecting unit 13 in a collecting rack 16 (cf. also Figure 4B).
  • a first and second variant of the container 7 are illustrated in this Figure 2A.
  • the container 7 has two flanges 28, which run at the greatest possible distance to one another. The container 7 thus receives maximum guiding when it is inserted in a compartment 17.
  • the container 7 only has one flange 28, which is broader, however. The guiding of the container in a compartment 17 is thus re- Jerusalem somewhat, but the sliding friction or static friction of the flange surface in relation to the retention elements 27 is not less, however.
  • FIG 2B shows a second embodiment of a collecting device 1 according to the present invention after the punching of a sample carrier portion.
  • the collecting device 1 comprises three parts, a hard counterpart 4, a softer insertion means 11, and an annular retention means 8, which is also softer and fixes the laminar sample carrier 2.
  • the retention means 8 and the insertion means 11 are manufactured in one piece from a softer plastic and elastically grasp both the counterpart 4 and also the laminar sample carrier 2 positioned thereon, prefera- bly without any use of adhesives.
  • the punching tool 5 of a punching apparatus 22 having an annular punching blade 24 was thrust through the laminar sample carrier 2 and the through hole 3 of the counterpart 4.
  • the punching tool 5 comprises barbs 26, which are folded out here. If the punching tool 5 is moved upward (arrow direction) after the punching and ejection of the sample carrier portion 6, the extended barbs 26 impinge the bottom side 10 of the counterpart 4 in such a way that the collecting device 1 is lifted off of the container 7.
  • a third and fourth variant of the container 7 are shown in Figure 2B.
  • the container 7 has two flanges 28, which run at the greatest possible distance to one another, which is now reduced, however.
  • the tip of the container 7 may be implemented optimally here for the geometric re- quirements for the PCR method, which requires maximum heat transfer.
  • the container 7 only has one flange 28, which is broader, however.
  • the container 7 receives somewhat reduced guiding when it is inserted into a compartment 17 in both of these cases.
  • the sliding friction or the static friction of the flange surface in relation to the retention element 27 is not less than in the first two variants, however.
  • the container 7 is preferably implemented as a PCR tube, because of which the polymerase chain reaction for amplification of nucleic acids may be executed directly in the collecting container 7.
  • the container 7 has a slightly flattened floor here, which has identification means 14 in the form of a 1-D and 2-D bar code.
  • the punching tool 5 comprises barbs 26, which are pivotable into the counterpart 4 as it pushes through the through hole 3 in the counterpart 4 and are subsequently pivotable out.
  • This pivotability may be achieved according to a first variant in that the barbs 26 are situated on the punching tube 23 and are pivoted out by the advancement of the ejection tool 25.
  • this pivotability of the barbs 26 is achieved in that they are integrated in the punching tube 23, pivot inward during punching and elastically pivot outward after the punching.
  • FIGS 3A and 3B show a horizontal section through the collecting rack 16.
  • the eight compartments 17 illustrated here which are separated from one another by intermediate walls 29, are well recognizable here. Every second compartment 17 is equipped here with a collecting unit 13, so that a safety interval may be maintained between the individual collecting units.
  • the spacing of the collecting units 13 inserted into the compartments 17 makes handling easier, but is not required, so that a collecting rack 16 generally comprises compartments 17 for in- dividually receiving one collecting unit 13 each. Notwithstanding this illustration, such a collecting rack 16 may have a practically arbitrary number of compartments 17, although collecting racks 16 having four, eight, or twelve compartments 17 are especially preferred.
  • Figure 3A shows a first embodiment of a collecting rack 16 without retention elements.
  • the flanges 28 of a container 7 and/or their distance to the intermediate walls 29 of the collecting rack 16 are dimensioned in such a way that the diameter of the flanges 28 is slightly greater than the clearance of a compartment 17.
  • enough friction arises between the flanges 28 and the intermediate walls 29 upon insertion of a collecting unit 13 into the collecting rack so that the collecting unit 13 positioned in the collecting rack 16 is securely seated in its space.
  • FIG. 3B shows a second embodiment of a collecting rack 16 having retention elements.
  • the compartments 17 preferably comprise such retention elements 27, which hold an inserted collecting unit 13 friction locked.
  • These retention elements 27 are partially deformed upon insertion of the collecting unit 13 into a collecting rack 16 and enter into intensive contact (friction lock) with the flanges 28 of the collecting unit 13.
  • This friction lock may be varied by changing the thickness and/or the material of these retention elements 27.
  • the friction lock i.e., the force which must be applied to insert a collecting unit 13 into a collecting rack 16 or eject it therefrom, is optimally tailored to the remaining device components.
  • Such device components comprise a handling robot for inserting the collecting units 13 into a collecting rack 16, working rack 30, or archive rack 31. The same or another handling robot is used for ejecting the collecting unit 13 from a collecting rack 16, working rack 30, or archive rack 31.
  • FIGS 4A and 4B show vertical sections through a collecting rack 16 having eight compartments 17 separated from one another by intermediate walls 29.
  • a collecting unit 13 is inserted into every second of these compartments 17 in such a way that their laminar sample carriers 2 are located in the area of the upper edge 18 of the external wall 19 enclosing these compart- area of the upper edge 18 of the external wall 19 enclosing these compartments 17.
  • a collecting rack 16 having a number of collecting units 13 is identified as a collecting set 15.
  • FIG 4A shows a vertical longitudinal section through a collecting rack of the first embodiment, which has no retention elements 27 (cf. Figure 3A).
  • the compartments 17 illustrated here, which are separated from one another by intermediate walls 29, may be recognized well. Notwithstanding this illustration, such a collecting rack 16 may have a practically arbitrary number of compartments 17, although collecting racks 16 having four, eight, or twelve compartments 17 are especially preferred.
  • a collecting unit 13 having a container 7 according to the first embodiment (cf. Figure 2A, left) is inserted into the first compartment 17.
  • This container carries identification means 14, preferably an RFID transponder or a RuBee transceiver.
  • a collecting unit 13 having a container 7 according to a fifth embodiment is inserted in the third compartment 17.
  • the lower flange 28 of this container 7 has a peripheral edge, or at least a very narrow external surface (not shown), and is primarily used for correct orientation of the container 7 in its compartment 17.
  • the friction lock achievable using this cross-sectional shape of a flange 28 is rather small. Therefore, this container is primarily held in friction lock by the upper flange 28.
  • Figure 4B shows a vertical diagonal section along the dot-dash lines in Figure 3B through a collecting rack 16 of the second embodiment having retention elements 27.
  • These retention elements 27 may simply be implemented as linear (cf. fifth compartment), so that they hold an inserted collecting unit 13 in friction lock, as was already explained in connection with Figure 3B.
  • these retention elements 27 may additionally have a first protrusion 32 and/or a second protrusion 33 (cf. seventh compartment).
  • the lower flange 28 which has a peripheral edge according to the fifth embodiment of this container 7, may snap into the space between these protrusion 32,33 to engage.
  • the peripheral edge, or the at least one very narrow external surface is used for additionally retaining the container 7 in its compartment 17.
  • An upper insertion position, in which the collecting unit 13 projects above the upper edge 18 of the collecting rack 16, and a lower insertion position, in which the collecting unit 13 is inserted at a specific height in the collecting rack 16, may be defined by the two protrusions.
  • the collecting unit 13 is retained very securely in the collecting rack 16 by snapping the lower flange 28 implemented as a peripheral edge between the two protrusions 32,33 and may not fall out - even upon rough manipulations of the collecting device 1.
  • the external wall 19 of the collecting rack may define an essentially cuboid collecting rack 16, which stands on the lower edge 20 of the external wall 19 en- closing these compartments 17.
  • the collecting rack 16 may also have an outline which deviates from the rectangular shape shown.
  • the outline of a collecting rack 16 may thus also have a square or rounded shape.
  • the fact that the compartments 17 are open on the top and bottom is more essential than the external shape of the collecting rack 16, so that the collecting unit 13 may be inserted from top or bottom and ejected to the bottom or the top.
  • each collecting unit 13 may be inserted into a compartment 17 and ejected from this compartment 17 again in an arbitrary vertical direction.
  • a collecting set 15 according to the present invention preferably additionally comprises a cover 21 for the upper and/or lower terminus of the collecting rack 16 in addition to the collecting rack 16 and the collecting units 13.
  • the sample side of the collecting rack 16 may be protected from external influences or the entire collecting rack may be completely packaged by one or two such covers.
  • the present invention also comprises a method for collecting and providing bio- logically relevant samples using a collecting unit 13 according to Claim 9 or 10 and/or using a collecting set 15 according to one of Claims 11 through 15.
  • This method is characterized in that a biological sample is applied to the laminar sample carrier 2 of the collecting device 1 of a collecting unit 13, and a sample carrier portion 6 is punched out using a punching tool 5 and ejected through the through hole 3 in the counterpart 4 of the collecting device 1 into the container 7 for sample processing.
  • Figure 5 shows 3-D views of a collecting unit 13 having cover 21 and twelve compartments, every second one of which is occupied.
  • a first collecting device 13 is provided here for insertion into a working rack 30 and the remaining five collecting devices 13 are provided for insertion into an archive rack 31.
  • the working racks 30 and archive racks 31 put the collected samples in a standard raster, as is known from microplates. They therefore have an array of holes which are situated at a standard distance to one another (e.g., 9 mm axial distance in a 96- well microplate). The size and shape of the holes is preferably tailored to the collecting units 13 to be used.
  • the working racks 30 and archive racks 31 preferably also have the external dimensions of a microplate, so that they may be grasped and transported using a microplate robot.
  • a collecting unit 13 having a biologically relevant sample of a specific subject which is intended for immediate further processing, is ejected upward or downward against the friction resistance of the retention elements 27 in the compartments 17 of a collecting rack 16 before the punching and thus inserted into corresponding compartments 17 of a working rack 30.
  • This procedure is shown very schematically on the left side of Figure 5. This procedure allows the robotic and/or automated concentration of very many individual samples in a standardized working rack 30.
  • This working rack 30 preferably has the external dimensions of a standard microplate, so that it is transportable automatically using a microplate robot and positionable in processing stations constructed for microplates.
  • Further steps of the method according to the present invention relates to lifting the collecting device 1 off of the container 7 of a collecting unit 13 and extracting the biologically relevant sample from the sample carrier portion 6 in this collecting container 7.
  • the biologically relevant sample may be amplified and/or analyzed following the extraction from the sample carrier portion 6.
  • the biologically relevant sample may be selected from a group which comprises bodily fluids of humans and animals (such as blood, sputum, feces, sperm, urine), human and animal cells (such as oral mucosa cells, hair follicles), plant cells (such as seed cells, cambium cells), human, animal, and plant tissue parts, DNA, RNA, proteins (prions), microorganisms, and viruses.
  • bodily fluids of humans and animals such as blood, sputum, feces, sperm, urine
  • human and animal cells such as oral mucosa cells, hair follicles
  • plant cells such as seed cells, cambium cells
  • human, animal, and plant tissue parts DNA, RNA, proteins (prions), microorganisms, and viruses.
  • the collecting units 13, having biologically relevant samples of the same subject which are not intended for immediate further processing, are also ejected upward or downward against the frictional resistance of the retention elements 27 in the compartment 17 of the collecting rack 16 and thus inserted into compartments of an archive rack 31.
  • This procedure allows the robotic and/or automated placement of very many individual samples in a standardized archive rack 31.
  • This archive rack 31 preferably has the external dimensions of a standard microplate, so that it is automatically transportable using a microplate robot and storable in a microplate warehouse.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

Collecting devices (1) according to the present invention having a laminar sample carrier (2) for collecting and providing biologically relevant samples are characterized in that they comprises a counterpart (4) comprising a through hole (3) which is implemented to support the laminar sample carrier (2) upon punching using a punching tool (5) and upon ejection of a sample carrier portion (6) through the through hole (3) into a container (7) for sample processing. The present invention additionally comprises a collecting set ( 15), which comprises a collecting rack (16) having a number of collecting units ( 13) inserted into compartments (17), a collecting unit (13) being formed by a collecting device (1) and a collecting container (7). The corresponding method for collecting and providing biologically relevant samples and a special punching apparatus (22) for use in this method are also disclosed.

Description

Collecting device for biologically relevant samples
The present invention relates to a collecting device having a laminar sample carrier for collecting and providing biologically relevant samples
The collection of samples containing nucleic acid to use the genetic code is cur- rently increasingly gaining in significance. In this context, animal and plant cultivation and monitoring in connection with health monitoring in animal husbandry are particularly cited. The firm Whatman developed a matrix, which is based on chemically treated cellulose cards and is used for simple collection, stabilization, and purification of nucleic acids. Blood and sputum samples may be applied di- rectly to this so-called "FTA paper" when placing the earmarks in cattle, for example. A leaf or plant fibers may also be simply pressed onto the matrix and/or a homogenate may be applied. The nucleic acids are bound to the cellulose fibers and immobilized, while proteins are denatured and pathogens potentially hazardous to health are inactivated for safe handling of the user. After the sample is dried at room temperature, such an FTA paper may be sent unrefrigerated in an envelope to a laboratory. A punching is taken from the sample there, placed in a PCR reaction vessel, and washed with the cleaning reagent; the DNA remains immobilized on the matrix and may be stored for years at room temperature. Even RNA is stable on FTA paper at room temperature for several days. The punchings are supplied to a polymerase chain reaction or "PCR" for amplification of the genetic material after the washing. In connection with combating crime, the collection of genetic samples in the meaning of a "genetic fingerprint" is becoming more and more important in two regards: firstly, the genetic code is to be acquired from criminals who have already been arrested and secondly the acquired data is to be compared to un- known traces found at a crime scene, for example. In the first case, fresh and clearly identified samples are used to build up a data bank, which may be accessed in the second case. However, the findable samples are often incomplete, contaminated, and damaged. Individual countries have changed over in the meantime to preventively acquiring the genetic code of all individuals entering the country or even all the inhabitants of the country.
Biologically relevant samples also comprise proteins (e.g., the prions causing Creutzfeld-Jacob syndrome, or bovine spongiform encephalopathy, or BSE respectively), viruses, bacteria, and other microorganisms, human or animal bodily fluids (such as blood, sputum, feces, sperm, and urine), and single cells (such as oral mucosa cells and hair follicles).
The manual collection of biologically relevant samples using FTA paper is known from the prior art (cf., for example, the article "Schnelle und effektive Methode zur Isolierung von Nukleinsauren in der Tier- und Pflanzenwelt [Rapid and Effective Methods for Isolating Nucleic Acids in the Animal and Plant World]" in BlOfo- rum 2/2006). The automatic removal of individual, biologically relevant samples immobilized on FTA paper from a storage apparatus and the individual preparation of the samples for their further processing or analysis is also known (cf., for example, US 2004/0014228 Al). Depending on the requirements, a group or population of samples stored in the storage apparatus is determined on the basis of a data bank. Individual sample containers are identified on the basis of their identification, which is readable by a handling robot, and are removed from a storage apparatus using this robot. The identification is additionally used for the purpose of correlating the sample with stored medical data of the corresponding patient. The selected samples are delivered to a first preparation point, where they are transferred using an intake device and delivered to a second preparation point. A portion is punched out of each sample there and laid by the punching head in a predetermined container (e.g., in the well of a microplate) for subsequent biological processing. This processing has been known for some time in principle and comprises the washing of the sample and the performance of a PCR process. While the manual collection and archiving of the samples is relatively simple to execute, the access to the storage apparatus and the provision of the samples for the polymerase chain reaction is obviously very complex.
The object of the present invention is to suggest a device and a method, by which the collection and provision of biologically relevant samples, in particular for building up a data bank, is simplified.
This object is achieved according to a first aspect by a device having the features of independent Claim 1. This collecting device comprises a laminar, i.e., flat sam- pie carrier for collecting and providing biologically relevant samples and is characterized in that it comprises a counterpart having a through hole. This counterpart is implemented to support the laminar sample carrier upon punching using a punching tool and upon ejection of a sample carrier portion through the through hole into a container for sample processing.
The collecting device according to the present invention comprises the following advantages in relation to the prior art:
• The collecting device comprises a laminar sample carrier, from which a sample carrier portion may be ejected through the through hole in the counterpart directly into a container for sample processing.
• The laminar sample carrier may be selected practically arbitrarily from flat materials, such as FTA paper, filter paper, or nitrocellulose.
• If the container for sample processing, which, thanks to individual identification means, such as a 1-D or 2-D bar code, and/or an RFID tag, is clearly and correctly identifiable, is implemented as a PCR tube, the polymerase chain reaction may occur directly in the collecting unit.
• A special punching tool may also be used for removing the collecting device from the PCR tube following the punching out of a sample carrier portion.
• A collecting set having multiple collecting units preferably represents the basis for a redistribution of sample containers, which may be pushed roboti- cally downward out of the collecting set, for example, and placed from above into an archive rack or working rack positioned below the collecting set in the same work step.
In the following, preferred and exemplary embodiments of the present invention are explained in greater detail on the basis of schematic drawings which do not restrict the scope of the present invention.
Figure 1 shows a collecting device known from the prior art having multiple FTA papers and filter papers;
Figure 2 shows a collecting unit according to the present invention having a collecting device and a container for sample processing implemented as a PCR tube, Figure 2A showing a first embodiment before the punching of a sample carrier portion, and Figure 2B showing a second embodiment after the punching of a sample carrier portion;
Figure 3 shows a horizontal section through a collecting rack having eight compartments, for example, every second one of which is occupied, Figure 3A showing a first embodiment without retention elements, and Figure 3B showing a second embodiment with retention elements; Figure 4 shows vertical sections through the collecting rack of Figure 3;
Figure 4A showing a vertical longitudinal section through a collecting rack of the first embodiment, and
Figure 4A showing a vertical diagonal section along the dot-dash lines in Figure 3B through a collecting rack of the second embodiment;
Figure 5 shows 3-D views of a collecting unit having a cover and twelve compartments, every second one of which is occupied, a first collecting device being provided for insertion into a working rack and the remaining five collecting devices being provided for insertion into an archive rack.
Figure 1 shows a collecting device known from the prior art having multiple FTA papers and filter papers. This collecting device 1' according to the species comprises multiple laminar sample carriers 2' in the form of three FTA papers (upper half) and three filter papers (lower half) for collecting and providing biologically relevant samples. In addition, this collecting device 1' known from the prior art comprises an area designed as identification means 14', in which handwritten notes about the subjects or patients from which the samples originate may be entered. The shape of this collecting device 1' is well suitable for postal shipping, but it hardly supports robotic archiving and provision.
Figure 2 shows a collecting unit according to the present invention having a col- lecting device and a container for sample processing implemented as a PCR tube. This collecting device 1 comprises a laminar sample carrier 2 for collecting and providing biologically relevant samples. This collecting device 1 comprises a counterpart 4 having a through hole 3. This counterpart 4 is implemented to support the laminar sample carrier 2 upon punching using a punching tool 5 and upon ejection of a sample carrier portion 6 through the through hole 3 into a container 7 for sample processing. This collecting device 1 according to the present invention preferably comprises retention means 8, using which the laminar sample carrier 2 is attached to the top side 9 of the counterpart 4. The counterpart 4 preferably comprises insertion means 11 on its bottom side, using which the collecting device 1 is attachable to the intake opening 12 of a container 7. The retention means 8 and/or the insertion means 11 may preferably be implemented as annular (cf. Figure 2) or finger- shaped (not shown). Such a collecting device 1 in which the retention means 8 and the insertion means 11 are produced in one piece is especially preferred. This is advantageous in particular if the retention means 8 and the insertion means 11 are produced in one work step (e.g., using injection molding) and in one piece from an elastic plastic. In alternative collecting devices, only the retention means 8 or the insertion means 11 may be produced from an elastic plastic.
However, it is also possible to process plastics using a multicomponent injection method in such a way that the retention means 8 and the insertion means 11 are produced in one piece. The insertion means 11, which is to be able to be plugged like a stopper into the intake opening 12 of the container 7, may be softer and more flexible than the retention means 8, which is to hold the laminar sample carrier 2 securely on the counterpart. A harder material is advantageous in par- ticular if the uppermost part of the retention means, which overlaps the laminar sample carrier 2, is implemented as a finger. In addition, the entire retention means 8 may be molded as multiple, for example, three or more fingers, on the insertion means 11.
The counterpart 4 is preferably also produced from a plastic, especially preferably a hard plastic. Notwithstanding the embodiments shown in Figure 2, the three parts of insertion means 11, retention means 8, and counterpart 4 may be injection molded in one piece, the insertion means preferably being implemented from a softer plastic. The laminar sample carrier 2 is preferably selected from a group comprising FTA paper, filter paper, and nitrocellulose. However, other laminar sample carriers 2 may also be provided, if they are also suitable for punching. Figure 2A shows a first embodiment of a collecting device 1 according to the present invention before the punching of a sample carrier portion. In this case, the collecting device 1 comprises four parts, a hard counterpart 4, a softer insertion means 11, and an annular retention means 8, which is also softer and fixes the laminar sample carrier 2. This retention means 8 made of a softer plastic allows, for example, the replacement of laminar sample carriers 2 and/or the insertion of such sample carriers as needed. The insertion means 11 is preferably connected to the counterpart 4 by gluing, welding, or vulcanization here. The laminar sample carrier 2 is fixed without the use of any adhesives on the counterpart 4.
A punching apparatus 22 having a punching tool 5 for punching out a sample carrier portion 6 from the laminar sample carrier 2 of the collecting device 1 is positioned over the sample carrier. This punching tool 5 comprises a punching tube 23 having an annular punching blade 24 and an ejection tool 25, which is situ- ated in the punching tube 23 so it is movable. The counterpart 4 of the collecting device 1 has a through hole 3, whose diameter is greater than the diameter of the punching tube 23. Therefore, the punching tool 5 may be used to punch a sample carrier portion 6 out of this laminar sample carrier 2 (arrow direction) and to convey the punching thus obtained through the through hole 3 into the con- tainer 7 and eject it there. This ejection is preferably performed by the cylindrical ejection tool 25, which is displaceable downward. The diameter of the punching blade 24 is preferably only slightly less than the diameter of the through hole 3, so that the laminar sample carrier 2 may not significantly deform during punching. The fact that the laminar sample carrier 2 is clamped correctly by the reten- tion means 8 on the counterpart 4 also counteracts this deformation. The punching tool 5 comprises barbs 26, which are folded in here and whose folded-out position is marked by dashed lines.
The collecting device 1, which is attached using insertion means 11 in the intake opening 12 of a container 7, is referred to as a collecting unit 13. The container 7 of such a collecting unit 13 is used on one hand for holding the collecting device 1. On the other hand, this container may additionally be used for sample proc- essing or sample storage. This container 7 preferably carries identification means 14 so that the sample may be identified correctly at any time on the laminar sample carrier 2 of the collecting device or in the container 7 of such a collecting unit 13. These identification means preferably support the machine reading of the existing identification data and are therefore selected from a group which comprises a 1-D bar code, a 2-D barcode, an RFID transponder, and a RuBee transceiver.
The principle of 1-D and 2-D barcodes is known to those skilled in the art and is based on the optical scanning of a high-contrast identification marking. The advantage of such identification means 14 is the relatively simple physical principle; however, there must be a visual contact between the scanning device and identification means 14. The RFID transponders known per se, which operate at high frequency (HF, such as 900 MHz) or ultra-high frequency (UHF), transmit and re- ceive radio signals, while the newer RuBee transceivers operate at wavelengths below 450 kHz and emit and receive signals which are primarily based on magnetism. The passive RFID transponders may receive approximately 100 (HF) or 150-200 (UHF) messages per second, in contrast, the active RuBee transceivers may only receive approximately 10 messages/second: visual contact is not needed in any case. The type of identification means 14 used is thus a function, inter alia, of the density of the data transfer and the presence of a visual contact. An RFID transponder or a RuBee transceiver is situated on the vertical wall of the container 7 here.
The container 7 is preferably implemented as a PCR tube, because of which the polymerase chain reaction for amplification of nucleic acids may be executed directly in the collecting container 7. Time-consuming transfers or even sample losses resulting due to incorrect manipulations may thus be avoided. The container 7 preferably has at least one flange 28, which, in especially preferred em- bodiment, projects beyond the outermost edge of the retention means 8 and thus protects the retention means from damage. Two flanges 28 situated parallel to one another and running around the container 7 allow the secure retention of the container 7 and collecting unit 13 in a collecting rack 16 (cf. also Figure 4B).
A first and second variant of the container 7 are illustrated in this Figure 2A. In the first variant (shown on the left), the container 7 has two flanges 28, which run at the greatest possible distance to one another. The container 7 thus receives maximum guiding when it is inserted in a compartment 17. In the second variant (shown on the right), the container 7 only has one flange 28, which is broader, however. The guiding of the container in a compartment 17 is thus re- duced somewhat, but the sliding friction or static friction of the flange surface in relation to the retention elements 27 is not less, however.
Figure 2B shows a second embodiment of a collecting device 1 according to the present invention after the punching of a sample carrier portion. In this case, the collecting device 1 comprises three parts, a hard counterpart 4, a softer insertion means 11, and an annular retention means 8, which is also softer and fixes the laminar sample carrier 2. The retention means 8 and the insertion means 11 are manufactured in one piece from a softer plastic and elastically grasp both the counterpart 4 and also the laminar sample carrier 2 positioned thereon, prefera- bly without any use of adhesives.
The punching tool 5 of a punching apparatus 22 having an annular punching blade 24 was thrust through the laminar sample carrier 2 and the through hole 3 of the counterpart 4. The cylindrical ejection tool 25, situated in the punching tube 23 so it is movable, was then moved downward and the punched-out sample carrier portion 6 was ejected into the container 7. The punching tool 5 comprises barbs 26, which are folded out here. If the punching tool 5 is moved upward (arrow direction) after the punching and ejection of the sample carrier portion 6, the extended barbs 26 impinge the bottom side 10 of the counterpart 4 in such a way that the collecting device 1 is lifted off of the container 7. A third and fourth variant of the container 7 are shown in Figure 2B. In the third variant (shown on the left), the container 7 has two flanges 28, which run at the greatest possible distance to one another, which is now reduced, however. The tip of the container 7 may be implemented optimally here for the geometric re- quirements for the PCR method, which requires maximum heat transfer. In the fourth variant (shown on the right) the container 7 only has one flange 28, which is broader, however. The container 7 receives somewhat reduced guiding when it is inserted into a compartment 17 in both of these cases. The sliding friction or the static friction of the flange surface in relation to the retention element 27 is not less than in the first two variants, however.
The container 7 is preferably implemented as a PCR tube, because of which the polymerase chain reaction for amplification of nucleic acids may be executed directly in the collecting container 7. The container 7 has a slightly flattened floor here, which has identification means 14 in the form of a 1-D and 2-D bar code.
As shown in Figures 2A and 2B, the punching tool 5 comprises barbs 26, which are pivotable into the counterpart 4 as it pushes through the through hole 3 in the counterpart 4 and are subsequently pivotable out. This pivotability may be achieved according to a first variant in that the barbs 26 are situated on the punching tube 23 and are pivoted out by the advancement of the ejection tool 25. According to a second variant, this pivotability of the barbs 26 is achieved in that they are integrated in the punching tube 23, pivot inward during punching and elastically pivot outward after the punching.
Figures 3A and 3B show a horizontal section through the collecting rack 16. The eight compartments 17 illustrated here, which are separated from one another by intermediate walls 29, are well recognizable here. Every second compartment 17 is equipped here with a collecting unit 13, so that a safety interval may be maintained between the individual collecting units. The spacing of the collecting units 13 inserted into the compartments 17 makes handling easier, but is not required, so that a collecting rack 16 generally comprises compartments 17 for in- dividually receiving one collecting unit 13 each. Notwithstanding this illustration, such a collecting rack 16 may have a practically arbitrary number of compartments 17, although collecting racks 16 having four, eight, or twelve compartments 17 are especially preferred.
Figure 3A shows a first embodiment of a collecting rack 16 without retention elements. In this case, the flanges 28 of a container 7 and/or their distance to the intermediate walls 29 of the collecting rack 16 are dimensioned in such a way that the diameter of the flanges 28 is slightly greater than the clearance of a compartment 17. Thus, enough friction arises between the flanges 28 and the intermediate walls 29 upon insertion of a collecting unit 13 into the collecting rack so that the collecting unit 13 positioned in the collecting rack 16 is securely seated in its space.
Figure 3B shows a second embodiment of a collecting rack 16 having retention elements. The compartments 17 preferably comprise such retention elements 27, which hold an inserted collecting unit 13 friction locked. These retention elements 27 are partially deformed upon insertion of the collecting unit 13 into a collecting rack 16 and enter into intensive contact (friction lock) with the flanges 28 of the collecting unit 13. This friction lock may be varied by changing the thickness and/or the material of these retention elements 27. The friction lock, i.e., the force which must be applied to insert a collecting unit 13 into a collecting rack 16 or eject it therefrom, is optimally tailored to the remaining device components. Such device components comprise a handling robot for inserting the collecting units 13 into a collecting rack 16, working rack 30, or archive rack 31. The same or another handling robot is used for ejecting the collecting unit 13 from a collecting rack 16, working rack 30, or archive rack 31.
Figures 4A and 4B show vertical sections through a collecting rack 16 having eight compartments 17 separated from one another by intermediate walls 29. In this example, a collecting unit 13 is inserted into every second of these compartments 17 in such a way that their laminar sample carriers 2 are located in the area of the upper edge 18 of the external wall 19 enclosing these compart- area of the upper edge 18 of the external wall 19 enclosing these compartments 17. A collecting rack 16 having a number of collecting units 13 is identified as a collecting set 15.
Figure 4A shows a vertical longitudinal section through a collecting rack of the first embodiment, which has no retention elements 27 (cf. Figure 3A). The compartments 17 illustrated here, which are separated from one another by intermediate walls 29, may be recognized well. Notwithstanding this illustration, such a collecting rack 16 may have a practically arbitrary number of compartments 17, although collecting racks 16 having four, eight, or twelve compartments 17 are especially preferred. A collecting unit 13 having a container 7 according to the first embodiment (cf. Figure 2A, left) is inserted into the first compartment 17. This container carries identification means 14, preferably an RFID transponder or a RuBee transceiver. A collecting unit 13 having a container 7 according to a fifth embodiment is inserted in the third compartment 17. The lower flange 28 of this container 7 has a peripheral edge, or at least a very narrow external surface (not shown), and is primarily used for correct orientation of the container 7 in its compartment 17. The friction lock achievable using this cross-sectional shape of a flange 28 is rather small. Therefore, this container is primarily held in friction lock by the upper flange 28.
Figure 4B shows a vertical diagonal section along the dot-dash lines in Figure 3B through a collecting rack 16 of the second embodiment having retention elements 27. These retention elements 27 may simply be implemented as linear (cf. fifth compartment), so that they hold an inserted collecting unit 13 in friction lock, as was already explained in connection with Figure 3B. As an alternative to this, these retention elements 27 may additionally have a first protrusion 32 and/or a second protrusion 33 (cf. seventh compartment). The lower flange 28, which has a peripheral edge according to the fifth embodiment of this container 7, may snap into the space between these protrusion 32,33 to engage. In this case, the peripheral edge, or the at least one very narrow external surface (not shown) is used for additionally retaining the container 7 in its compartment 17. An upper insertion position, in which the collecting unit 13 projects above the upper edge 18 of the collecting rack 16, and a lower insertion position, in which the collecting unit 13 is inserted at a specific height in the collecting rack 16, may be defined by the two protrusions. The collecting unit 13 is retained very securely in the collecting rack 16 by snapping the lower flange 28 implemented as a peripheral edge between the two protrusions 32,33 and may not fall out - even upon rough manipulations of the collecting device 1.
Upon observation of Figures 3 and 4 it is clear that providing two annular flanges 28 per container 7 is preferable, because these flanges 28 enter into a friction lock with the vertical retention elements 27, so that the inserted collecting unit 13 is retained securely in its assigned compartment 17. If necessary, these retention elements 27 implemented as vertical webs may have a setback (not shown) at the height of the lower edge of the upper flange 28 and/or at the height of the upper edge of the lower flange 28, which further improves the retention of a collecting unit 13 in its assigned compartment 17.
The external wall 19 of the collecting rack may define an essentially cuboid collecting rack 16, which stands on the lower edge 20 of the external wall 19 en- closing these compartments 17. Notwithstanding the illustration in Figures 3 through 5, the collecting rack 16 may also have an outline which deviates from the rectangular shape shown. The outline of a collecting rack 16 may thus also have a square or rounded shape. The fact that the compartments 17 are open on the top and bottom is more essential than the external shape of the collecting rack 16, so that the collecting unit 13 may be inserted from top or bottom and ejected to the bottom or the top. Thus, each collecting unit 13 may be inserted into a compartment 17 and ejected from this compartment 17 again in an arbitrary vertical direction.
A collecting set 15 according to the present invention preferably additionally comprises a cover 21 for the upper and/or lower terminus of the collecting rack 16 in addition to the collecting rack 16 and the collecting units 13. The sample side of the collecting rack 16 may be protected from external influences or the entire collecting rack may be completely packaged by one or two such covers.
The present invention also comprises a method for collecting and providing bio- logically relevant samples using a collecting unit 13 according to Claim 9 or 10 and/or using a collecting set 15 according to one of Claims 11 through 15. This method is characterized in that a biological sample is applied to the laminar sample carrier 2 of the collecting device 1 of a collecting unit 13, and a sample carrier portion 6 is punched out using a punching tool 5 and ejected through the through hole 3 in the counterpart 4 of the collecting device 1 into the container 7 for sample processing.
Figure 5 shows 3-D views of a collecting unit 13 having cover 21 and twelve compartments, every second one of which is occupied. A first collecting device 13 is provided here for insertion into a working rack 30 and the remaining five collecting devices 13 are provided for insertion into an archive rack 31. The working racks 30 and archive racks 31 put the collected samples in a standard raster, as is known from microplates. They therefore have an array of holes which are situated at a standard distance to one another (e.g., 9 mm axial distance in a 96- well microplate). The size and shape of the holes is preferably tailored to the collecting units 13 to be used. The working racks 30 and archive racks 31 preferably also have the external dimensions of a microplate, so that they may be grasped and transported using a microplate robot.
According to the method according to the present invention, a collecting unit 13, having a biologically relevant sample of a specific subject which is intended for immediate further processing, is ejected upward or downward against the friction resistance of the retention elements 27 in the compartments 17 of a collecting rack 16 before the punching and thus inserted into corresponding compartments 17 of a working rack 30. This procedure is shown very schematically on the left side of Figure 5. This procedure allows the robotic and/or automated concentration of very many individual samples in a standardized working rack 30. This working rack 30 preferably has the external dimensions of a standard microplate, so that it is transportable automatically using a microplate robot and positionable in processing stations constructed for microplates.
Further steps of the method according to the present invention relates to lifting the collecting device 1 off of the container 7 of a collecting unit 13 and extracting the biologically relevant sample from the sample carrier portion 6 in this collecting container 7. The biologically relevant sample may be amplified and/or analyzed following the extraction from the sample carrier portion 6.
When the method according to the present invention is performed, the biologically relevant sample may be selected from a group which comprises bodily fluids of humans and animals (such as blood, sputum, feces, sperm, urine), human and animal cells (such as oral mucosa cells, hair follicles), plant cells (such as seed cells, cambium cells), human, animal, and plant tissue parts, DNA, RNA, proteins (prions), microorganisms, and viruses.
The collecting units 13, having biologically relevant samples of the same subject which are not intended for immediate further processing, are also ejected upward or downward against the frictional resistance of the retention elements 27 in the compartment 17 of the collecting rack 16 and thus inserted into compartments of an archive rack 31. This procedure allows the robotic and/or automated placement of very many individual samples in a standardized archive rack 31. This archive rack 31 preferably has the external dimensions of a standard microplate, so that it is automatically transportable using a microplate robot and storable in a microplate warehouse.
Identical and/or corresponding parts are marked by the same reference numerals, even if not all of these reference numerals used in the figures are expressly noted in the description. Reference numerals:
1 collecting device 19 external wall 2 laminar sample carrier 20 lower edge of the external 3 through hole 25 wall 4 counterpart 21 cover 5 punching tool 22 punching apparatus 6 sample carrier portion 23 punching tube 7 container for sample processing 24 punching blade 8 retention means 30 25 ejection tool 9 top side of the counterpart 26 barb 10 bottom side of the counterpart 27 retention element 11 insertion means 28 flange 12 intake opening of a container 29 intermediate walls 13 collecting unit 35 30 working rack 14 identification means 31 archive rack 15 collecting set 32 first protrusion 16 collecting rack 33 second protrusion 17 compartment 18 upper edge of the external waflO

Claims

Patent Claims
1. A collecting device (1) having a laminar sample carrier (2) for collecting and providing biologically relevant samples, characterized in that it comprises a counterpart (4) comprising a through hole (3), which is implemented to support the laminar sample carrier (2) upon punching using a punching tool (5) and upon ejection of the sample carrier portion (6) through the through hole (3) into a container (7) for sample processing.
2. The collecting device (1) according to Claim 1, characterized in that it comprises retention means (8), using which the laminar sample carrier (2) is attached to the top side (9) of the counterpart (4).
3. The collecting device (1) according to Claim 1 or 2, characterized in that the counterpart (4) comprises insertion means (11) on its bottom side (10), using which the collecting device (1) is attachable to the intake opening (12) of a container (7).
4. The collecting device (1) according to Claim 2 or 3, characterized in that the retention means (8) and/or the insertion means ( 11) are implemented as annular or finger-shaped.
5. The collecting device (1) according to one of Claims 2 through 4, characterized in that the retention means (8) and the insertion means (11) are produced in one piece.
6. The collecting device (1) according to one of Claims 2 through 5, characterized in that the retention means (8) and/or the insertion means (11) are produced from an elastic plastic.
7. The collecting device (1) according to one of the preceding claims, characterized in that the counterpart (4) is produced from a hard plastic.
8. The collecting device (1) according to one of the preceding claims, characterized in that the laminar sample carrier (2) is selected from a group which comprises FTA paper, filter paper, and nitrocellulose.
9. A collecting unit (13) having a collecting device (1) according to one of the preceding claims, characterized in that it comprises a container (7) for sample processing or sample storage.
10. The collecting unit (13) according to Claim 9, characterized in that each container (7) carries identification means (14), which are selected from a group comprising a 1-D bar code, a 2-D bar code, an RFID transponder, and a RuBee transceiver.
11. The collecting unit (13) according to Claim 9 or 10, characterized in that the container (7) is implemented as a PCR tube.
12. A collecting set (15) having a number of collecting units (13) according to one of Claims 9 to 11, characterized in that it comprises a collecting rack (16) having compartments (17) for individually receiving one collecting unit (13) each.
13. The collecting set ( 15) according to Claim 12, characterized in that a collecting unit (13) is inserted into one of these compartments (17) in such a way that its laminar sample carrier (2) is located in the area of the upper edge (18) of the external wall (19) enclosing these compartments (17).
14. The collecting set (15) according to Claim 13, characterized in that this external wall ( 19) defines an essentially cuboid collecting rack (16), which stands on the bottom edge (20) of the external wall (19) enclosing these compartments (17).
15. The collecting set (15) according to one of Claims 12 through 14, characterized in that the compartments (17) are open on the top and bottom, so that the collecting units (13) may be inserted from top or bottom and may be ejected to the bottom or top.
16. The collecting set (15) according to one of Claims 12 through 15, characterized in that the compartments (17) comprise retention elements (27), which retain an inserted collecting unit (13).
17. The collecting set (15) according to one of Claims 12 through 16, characterized in that it comprises at least one cover (21) for the upper and/or lower terminus of the collecting rack (16).
18. A punching apparatus (22) having a punching tool (5) for punching out a sample carrier portion (6) from the laminar sample carrier (2) of a collecting device (1) according to one of Claims 1 through 8, characterized in that the punching tool (5) comprises a punching tube (23) having an annular punching blade (24) and an ejection tool (25), which is situated in the punching tube (23) so it is movable.
19. The punching apparatus (22) according to Claim 18, characterized in that the punching tool (5) comprises barbs (26), which are pivotable into the counterpart (4) as they push through the through hole (3) and are subsequently pivotable out.
20. The punching apparatus (22) according to Claim 19, characterized in that the barbs (26) are situated on the punching tube (23), and are pivoted out by the advancement of the ejection tool (25).
21. The punching apparatus (22) according to Claim 19, characterized in that the barbs (26) are integrated in the punching tube (23), pivot in during punching, and pivot out elastically after the punching.
22. A method for collecting and providing biologically relevant samples using a collecting unit (13) according to one of Claims 9 through 11 and/or using a collecting set (15) according to one of Claims 12 through 17, characterized in that a biological sample is applied to the laminar sample carrier (2) of a collecting unit ( 13), and a sample carrier portion (6) is punched out using a punching tool (5) and ejected through the through hole (3) into the container (7) for sample processing.
23. The method according to Claim 22, characterized in that a collecting unit (13) having a biologically relevant sample of a specific subject intended for immediate further processing is ejected upward or downward before the punching against the frictional resistance of the retention elements (27) in the compartments (17) of a collecting rack (16) and thus inserted into corresponding compartments (17) of a working rack (30).
24. The method according to Claim 20 or 21, characterized in that a punching apparatus according to one of Claims 18 through 21 is used
25. The method according to Claim 24, characterized in that the pivoted-out barbs (26) push against the bottom side (10) of the counterpart (4) upon retraction of the punching tool (5) after the punching and ejection of the sample carrier portion (6) in such a way that a collecting device (1) according to one of Claims 1 through 8 is lifted off of the container (7).
26. The method according to Claim 25, characterized in that the biologically relevant sample from the sample carrier portion (6) is processed further after the collecting device ( 1) is lifted off.
27. The method according to Claim 26, characterized in that the biologically relevant sample from the sample carrier portion (6) is amplified and/or analyzed.
28. The method according to Claim 23, characterized in that collecting units (13) having biologically relevant samples of the same subject in the compartments (17) of the collecting rack (16) which are not intended for immediate further processing are ejected upward or downward and thus inserted into compartments of an archive rack (31).
29. The method according to one of Claims 20 through 26, characterized in that the biologically relevant sample is selected from a group which comprises bodily fluids of humans and animals, human and animal cells, plant cells, human, animal, and plant tissue parts, DNA, RNA, protein, microorganisms, and viruses.
PCT/EP2007/056668 2006-07-04 2007-07-03 Collecting device for biologically relevant samples Ceased WO2008003693A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH1074/06 2006-07-04
CH10742006 2006-07-04
US80655406P 2006-07-05 2006-07-05
US60/806,554 2006-07-05

Publications (1)

Publication Number Publication Date
WO2008003693A1 true WO2008003693A1 (en) 2008-01-10

Family

ID=38474216

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/056668 Ceased WO2008003693A1 (en) 2006-07-04 2007-07-03 Collecting device for biologically relevant samples

Country Status (1)

Country Link
WO (1) WO2008003693A1 (en)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009105818A1 (en) * 2008-02-26 2009-09-03 Allan David Morrison Cassette and method for plant sampling
FR2939281A1 (en) * 2008-12-10 2010-06-11 Affflex Europ DEVICE FOR SAMPLING AN ANIMAL TISSUE SAMPLE
WO2011154510A1 (en) * 2010-06-09 2011-12-15 Allflex Europe Tool for collecting a sample of animal tissue
EP2492015A1 (en) * 2011-02-28 2012-08-29 Deutsches Institut für Lebensmitteltechnik e.V. Sample container, system and analysis method
DE102011075039A1 (en) * 2011-04-29 2012-10-31 Hamilton Bonaduz Ag Punching device with illuminated mounting plate
DE102011075035A1 (en) * 2011-04-29 2012-10-31 Hamilton Bonaduz Ag Punching device with modular punching means
CN103105323A (en) * 2013-01-22 2013-05-15 江苏省血吸虫病防治研究所 Filter paper blood sample cutting box
FR2998369A1 (en) * 2012-11-20 2014-05-23 Centre Nat Rech Scient Method for manufacturing e.g. painting, fixed on flat surface of solid support for determining product, involves using punch including jaw and matrix, and arranging flat solid support disk for carrying analyte on one of its faces
CN103815935A (en) * 2014-03-03 2014-05-28 吴建华 Collecting cup of sputum culturing sample
US9301497B2 (en) 2008-12-19 2016-04-05 Allflex Europe Device for sampling tissue from an animal and corresponding storage means
US10039263B2 (en) 2010-07-30 2018-08-07 Allflex Europe Unit for marking and/or sampling animal tissue and corresponding marking and/or sampling tool
EP3514550A4 (en) * 2016-09-13 2019-09-11 FUJIFILM Corporation PCR TUBE, RFID SAMPLE MANAGEMENT SYSTEM, AND RFID SAMPLE MANAGEMENT METHOD
CN112924364A (en) * 2021-01-22 2021-06-08 贝克曼库尔特生物科技(苏州)有限公司 Nozzle, carrier, nozzle assembly and sample treatment instrument
US20230408377A1 (en) * 2022-06-17 2023-12-21 Curated Leaf Services LLC dba PhenoXpress Systems and Methods for Plant Sample Collection and Extraction

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0171072A2 (en) * 1984-08-06 1986-02-12 Akademie der Wissenschaften der DDR Method and device for the solid-phase sequencing of nucleic-acid fragments
WO1999015875A1 (en) * 1997-09-25 1999-04-01 Macquarie Research Ltd. Apparatus for removing a sample from an array of samples and a cutting tool for use with that apparatus
US6659338B1 (en) * 1997-09-11 2003-12-09 Biopsytec Gmbh Method and device for withdrawing biological samples
US20040014228A1 (en) * 1999-10-26 2004-01-22 Genometrix Genomics Inc. Method and apparatus for selectively retrieving biological samples for processing
DE10313340B3 (en) * 2003-03-25 2004-08-26 GSF - Forschungszentrum für Umwelt und Gesundheit GmbH Animal tissue punch, to determine the genotype of genetically modified animals for medical research, has a container filled with reaction fluid and a punch opening in the closure for the sample to pass through
WO2006056658A1 (en) * 2004-11-24 2006-06-01 Wallac Oy A punching tool for taking biological samples

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0171072A2 (en) * 1984-08-06 1986-02-12 Akademie der Wissenschaften der DDR Method and device for the solid-phase sequencing of nucleic-acid fragments
US6659338B1 (en) * 1997-09-11 2003-12-09 Biopsytec Gmbh Method and device for withdrawing biological samples
WO1999015875A1 (en) * 1997-09-25 1999-04-01 Macquarie Research Ltd. Apparatus for removing a sample from an array of samples and a cutting tool for use with that apparatus
US20040014228A1 (en) * 1999-10-26 2004-01-22 Genometrix Genomics Inc. Method and apparatus for selectively retrieving biological samples for processing
DE10313340B3 (en) * 2003-03-25 2004-08-26 GSF - Forschungszentrum für Umwelt und Gesundheit GmbH Animal tissue punch, to determine the genotype of genetically modified animals for medical research, has a container filled with reaction fluid and a punch opening in the closure for the sample to pass through
WO2006056658A1 (en) * 2004-11-24 2006-06-01 Wallac Oy A punching tool for taking biological samples

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009105818A1 (en) * 2008-02-26 2009-09-03 Allan David Morrison Cassette and method for plant sampling
US8668655B2 (en) 2008-12-10 2014-03-11 Allflex Europe Device for collecting a tissue sample from an animal
FR2939281A1 (en) * 2008-12-10 2010-06-11 Affflex Europ DEVICE FOR SAMPLING AN ANIMAL TISSUE SAMPLE
WO2010066475A1 (en) * 2008-12-10 2010-06-17 Allflex Europe Device for collecting a tissue sample from an animal
CN102245013B (en) * 2008-12-10 2014-07-30 奥福来克斯欧洲联合股份有限公司 Device for collecting a tissue sample from an animal
US9301497B2 (en) 2008-12-19 2016-04-05 Allflex Europe Device for sampling tissue from an animal and corresponding storage means
WO2011154510A1 (en) * 2010-06-09 2011-12-15 Allflex Europe Tool for collecting a sample of animal tissue
FR2961087A1 (en) * 2010-06-09 2011-12-16 Allflex Europ TOOL FOR SAMPLING AN ANIMAL TISSUE SAMPLE.
US9955954B2 (en) 2010-06-09 2018-05-01 Allflex Europe Tool for collecting a sample of animal tissue
US10039263B2 (en) 2010-07-30 2018-08-07 Allflex Europe Unit for marking and/or sampling animal tissue and corresponding marking and/or sampling tool
EP2492015A1 (en) * 2011-02-28 2012-08-29 Deutsches Institut für Lebensmitteltechnik e.V. Sample container, system and analysis method
DE102011075039A1 (en) * 2011-04-29 2012-10-31 Hamilton Bonaduz Ag Punching device with illuminated mounting plate
DE102011075039A9 (en) * 2011-04-29 2013-01-03 Hamilton Bonaduz Ag Punching device with illuminated mounting plate
US10478990B2 (en) 2011-04-29 2019-11-19 Hamilton Bonaduz Ag Punching device with illuminated receiving plate
CN103492854A (en) * 2011-04-29 2014-01-01 哈美顿博纳图斯股份公司 Stamping equipment with illuminated receiver plate
CN103492854B (en) * 2011-04-29 2016-01-27 哈美顿博纳图斯股份公司 Stamping equipment with illuminated receiver plate
US9289913B2 (en) 2011-04-29 2016-03-22 Hamilton Bonaduz Ag Punching device with modular punching means
DE102011075035A1 (en) * 2011-04-29 2012-10-31 Hamilton Bonaduz Ag Punching device with modular punching means
FR2998369A1 (en) * 2012-11-20 2014-05-23 Centre Nat Rech Scient Method for manufacturing e.g. painting, fixed on flat surface of solid support for determining product, involves using punch including jaw and matrix, and arranging flat solid support disk for carrying analyte on one of its faces
CN103105323A (en) * 2013-01-22 2013-05-15 江苏省血吸虫病防治研究所 Filter paper blood sample cutting box
CN103815935A (en) * 2014-03-03 2014-05-28 吴建华 Collecting cup of sputum culturing sample
EP3514550A4 (en) * 2016-09-13 2019-09-11 FUJIFILM Corporation PCR TUBE, RFID SAMPLE MANAGEMENT SYSTEM, AND RFID SAMPLE MANAGEMENT METHOD
US11307211B2 (en) 2016-09-13 2022-04-19 Fujifilm Corporation PCR tube, RFID sample management system, and RFID sample management method
CN112924364A (en) * 2021-01-22 2021-06-08 贝克曼库尔特生物科技(苏州)有限公司 Nozzle, carrier, nozzle assembly and sample treatment instrument
US20230408377A1 (en) * 2022-06-17 2023-12-21 Curated Leaf Services LLC dba PhenoXpress Systems and Methods for Plant Sample Collection and Extraction

Similar Documents

Publication Publication Date Title
WO2008003693A1 (en) Collecting device for biologically relevant samples
JP6387387B2 (en) Process tube and transfer tray
AU2023263460B2 (en) Systems and methods for reading machine-readable marks on racks and receptacles
US9297728B2 (en) Storage unit and transfer system for biological samples
US9108193B2 (en) Collection/extraction container for biological material in forensic samples
US11268885B2 (en) Sample collection device
US20040101966A1 (en) Sealed sample storage element system and method
US20070116613A1 (en) Sample tube and system for storing and providing nucleic acid samples
EP3259071A1 (en) Sample vessel rack, method for locking sample vessels in a sample vessel rack and sample vessel rack system
US8241593B2 (en) Specimen tray
EP2186878A1 (en) Coding for a sample carrier
WO2012116932A2 (en) Biological sample holder and method of assembling same
US20230085565A1 (en) Process tube and carrier tray
US10486157B2 (en) Device for sample collection, transportation, and processing
JP6902509B2 (en) Process tube and transport tray
US20140298926A1 (en) Biological sample storage apparatus and method
EP2186566A2 (en) Container seal with integrated safety arrangement for a sample carrier
JP7810685B2 (en) System and method for reading machine-readable marks on racks and receptacles
CN202351101U (en) Card holder for treating biological sample and stacking of at least two card holders
EP3834938A1 (en) Insert for an array of wells , application method and use
WO2012098083A2 (en) Biological sample holder and method of assembling a storage device

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07765772

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2009517250

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU

NENP Non-entry into the national phase

Ref country code: JP

122 Ep: pct application non-entry in european phase

Ref document number: 07765772

Country of ref document: EP

Kind code of ref document: A1