WO2016142516A1 - Récipient pour le séchage et la préparation d'échantillons biologiques - Google Patents

Récipient pour le séchage et la préparation d'échantillons biologiques Download PDF

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Publication number
WO2016142516A1
WO2016142516A1 PCT/EP2016/055282 EP2016055282W WO2016142516A1 WO 2016142516 A1 WO2016142516 A1 WO 2016142516A1 EP 2016055282 W EP2016055282 W EP 2016055282W WO 2016142516 A1 WO2016142516 A1 WO 2016142516A1
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WO
WIPO (PCT)
Prior art keywords
container
region
biological sample
liquid
drying
Prior art date
Application number
PCT/EP2016/055282
Other languages
German (de)
English (en)
Inventor
Thomas Voit
Dirk Heckel
Thomas Doedt
Original Assignee
Qiagen Gmbh
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 Qiagen Gmbh filed Critical Qiagen Gmbh
Publication of WO2016142516A1 publication Critical patent/WO2016142516A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
    • B01D3/02—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping in boilers or stills
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4022—Concentrating samples by thermal techniques; Phase changes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0851—Bottom walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • B01L2300/1844—Means for temperature control using fluid heat transfer medium using fans
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4022—Concentrating samples by thermal techniques; Phase changes
    • G01N2001/4027—Concentrating samples by thermal techniques; Phase changes evaporation leaving a concentrated sample

Definitions

  • the invention relates to containers, devices, kits and methods for processing and storing biological samples.
  • Disposable plastic containers (“Eppendorf-Cups", Eppendorf, Hamburg) are often used for processing such biological samples, which are described, for example, in DE 10159804.
  • A1 Such containers have cylindrical outer walls and a conically downwardly sloping bottom In the central well, fluids can accumulate and be taken up with low fluid loss during pipetting Embodiment has the disadvantage that the surface of the liquid, especially for small amounts of liquid, is relatively small, which makes drying difficult and extends the drying time.
  • microtiter plates which are formed from a single plastic part are described for example in DE 10212761 A1.
  • Containers for processing biological samples on a micrometer scale may also have a flat bottom. With such containers just small samples in small amounts of liquid can be dried well, since the liquid is distributed on the floor and has a relatively large surface area.
  • the disadvantage is that the sample after resuming in a small amount of liquid can be removed only incompletely by pipetting soil, since the solution does not accumulate at one point of the soil, but distribute residues over the soil away. To completely remove the liquid, the vessel must be tilted. This is generally done manually and the yield is in need of improvement.
  • the invention has for its object to provide methods and apparatus which overcome the disadvantages of the prior art.
  • methods and devices are to be provided which allow biological samples to be dried in liquid in a simple manner, to be taken up again in liquid and further processed.
  • the methods are intended to make it easy to process a multitude of samples on a micrometer scale during routine procedures in biochemical or diagnostic laboratories.
  • the invention relates to a container for processing and storing biological samples, which has a bottom, a side wall and an opening, wherein the container has a capacity of 100 ⁇ to 5000 ⁇ ,
  • the container having an opening at the top
  • the bottom has a first region which substantially forms a plane and extends over the center of the bottom
  • the bottom has a second region laterally adjacent to the first region and having a depression (8).
  • biological sample refers to materials that are usually processed in biochemical, molecular biological or diagnostic laboratories.
  • the biological samples may be biological material or fractions or parts thereof, such as body fluids, tissues or tissues Cells.
  • the body fluids are preferably blood, saliva, urine, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) or sputum.
  • the biological materials may also be or contain biological molecules or mixtures thereof, such as nucleic acids, proteins, polysaccharides, fats or low molecular weight compounds.
  • the materials may be of natural origin or produced by biotechnological methods, such as recombinant nucleic acids or proteins.
  • the biological samples may also be of synthetic origin as far as they mimic biological materials or are derivatives or analogs thereof.
  • the biological sample is selected from body fluids, tissues, cells, biological molecules, such as nucleic acids, proteins, polysaccharides and lipids, as well as mixtures or fractions thereof, such as lysates.
  • body fluids are blood and urine.
  • the nucleic acids are preferably DNA or RNA.
  • process refers to processes in which the biological samples are chemically or physically altered in some way.
  • the biological samples are dried and / or resumed in liquid, that is dissolved or resuspended.
  • the biological sample has a liquid content before drying.
  • the biological sample which has liquid and is to be dried, is liquid. It can be present as a solution or suspension.
  • the content of solids in the liquid is preferably less than 20% by weight, less than 10% by weight or less than 5% by weight.
  • the biological sample can be present in the container in a solution, in particular in aqueous solution, or suspension, in particular aqueous suspension.
  • the biological sample is dried in the container.
  • container is used in the technical field to refer to conventional containers and containers for storage and processing of micron-scale liquids containing biological samples, the container having a bottom, a side wall and an opening.
  • the opening is formed by the upper ends of the sidewall, which means that the vessel does not have an upper side opposite to the floor
  • Such designs are common in processing biological specimens, such as Eppendorf tubes or microtiter plates.
  • the container has a side wall.
  • the term "sidewall” describes the entirety of the lateral walls adjacent to the floor.
  • the side wall may have any shape. In this case, side walls may be parallel to each other or taper towards the ground. Round or rounded side walls, in particular in the form of a cylinder or truncated cone tapering downwards, are preferred.
  • the side wall can also have a polygonal cross-section, preferably a quadrangular cross-section, wherein the corners can be rounded.
  • the cross section may be rectangular or square and thereby taper towards the ground.
  • the container has an opening at the top.
  • the liquid can not flow out of the container, the container has only one opening, preferably no top wall, and the opening closes directly to the upper ends of the side walls and is formed by these.
  • the container is waterproof except for the opening.
  • the container consists of the bottom and the side wall, wherein optionally still a lid or a seal with a film may be present.
  • the container has a capacity of 100 ⁇ to 5,000 ⁇ liquid in the interior, in particular between 500 ⁇ and 3000 ⁇ , or between 500 ⁇ and 1 .500 ⁇ . Such capacities are typical for such laboratory scale containers as Eppendorf cups, PCR cups or individual wells in microtiter plates.
  • the container has a bottom, which is significantly formed from the first and second region.
  • the first area essentially forms a plane that extends over the center of the floor.
  • the first area serves to dry biological samples on it.
  • the liquid evaporates and the biological sample remains on the first area.
  • Biological samples usually adhere to the soil after drying. Since a liquid spreads on the first area, the surface is increased during drying, thereby accelerating the drying process.
  • substantially is meant a first region that forms nearly one plane and still serves the purpose of allowing fluids to be dried on it.
  • a first region is included that is not completely flat, but is slightly curved, for example by an angle of less than 5 °, less than 2 ° or less than 1 °.
  • the curvature can run evenly over the plane or irregularly.
  • the curvature is concave, so that the plane has a depression.
  • a liquid sample can still be well dried in the first area, especially if only small amounts, for example in the form of a single drop, are dried up.
  • a slight concave curvature can assist in drying, as the liquid is prevented from flowing into the second area.
  • the floor has a second area that includes a recess.
  • the flat first area connects directly to the second area. Both areas are connected to one another laterally.
  • the second area is lower than the first area and the level when the vessel is in the normal position (upright).
  • the depression is therefore below the first area.
  • the second region is designed to assist in the downflow of liquid into the well and accumulation in the well.
  • the depression is preferably located centrally in the second region and preferably not at the edge of the second region.
  • the second region is preferably inclined or curved toward the depression.
  • Conceivable is a conical or inverted pyramidal shape, which may be symmetrical or irregular, or may have the grooves.
  • the second region is configured to receive a sufficient amount of liquid that flows down from the first region, for example, up to 50 ⁇ , up to 100 ⁇ , or up to 200 ⁇ .
  • the first area extends over the middle of the floor.
  • the "center of the soil” is the axial axis of the vessel called, which leads in (normal) normal position from above to the ground.
  • the radial axis thus points from the axial axis to the side wall.
  • the second area serves to collect a biological sample dried in the first area of the soil, which thus adheres to the first area, after being taken up in liquid. This is easily possible if the container is tilted in liquid during or after the resumption of the sample, to the second area. Then, the solution or suspension flows from the first to the second region and accumulates in particular in the depression. The liquid with the resuspended or redissolved biological sample can then be easily removed with a pipette.
  • the land should not be so high as to interfere with the transfer of the liquid from the first to the second area after resuming the sample in liquid after drying.
  • the first region may have a slight concave curvature. Such a slight curvature can prevent the liquid from entering the second area before drying.
  • the bottom consists of the first and second region.
  • the floor comprises that part of the outer wall of the container which defines it substantially downwards.
  • the side walls delimit the container mainly outward to the side.
  • the floor can connect directly to the side walls. It is preferred that the container in the interior and / or the bottom has no corners and edges. The interior and / or the floor preferably has only curves.
  • the sidewalls are connected to the floor via a concave arched transition area.
  • the areal first area can be connected to the side walls via the arched transition area.
  • Such rounded transition areas have the advantage that there are no edges in which liquid can accumulate, making both drying and re-release difficult.
  • the area of the first area has a sufficient extent to dry it on a microliter scale.
  • the proportion of the first region at the bottom of the container, or at the sum of the first region and the second region is between 40% and 95%, more preferably between 50% to 90%, or between 60% to 80% %.
  • the first area is preferably larger than the second area, for example at least twice, three times or four times larger. there the proportions or ratios are preferably determined in the plan view of the container when the first region is horizontal.
  • the entire fluid is dried with the biological sample on the first area. This is possible, for example, if a drop is pipetted onto the first area, which remains at the position because of the adhesion forces.
  • the liquid is dried on the first and the second area. This is possible if a sufficiently large amount of liquid is used covering both the first and the second area. Regardless, if the second area is smaller than the first area, the overall drying process is accelerated.
  • the bottom consists of the first region and the adjoining second, lower region, as well as curved intermediate regions, which connect the first and second region with the side walls.
  • the first area may be flat or inclined. Overall, the first region may have an inclination angle of 0 to 45 °. Unless otherwise stated, the angle of inclination information in this application refers to the normal position when the vessel is standing or positioned on a horizontal surface.
  • the first region is inclined.
  • the angle of inclination between 10 ° and 45 °, more preferably between 15 ° and 40 °. With the inclination of the angle is called when the vessel is positioned in the normal position on a horizontal surface, in particular, is turned off.
  • the second region in this embodiment connects to the lowest edge of the first region.
  • the dried biological sample upon shutdown the container can be resumed particularly well, since the solution or resuspension flows down through the inclination of the first region and accumulates in the second region and in particular in the depression.
  • the biological sample is dried in the container when the container is positioned on an inclined ground whose inclination angle corresponds to the inclination angle of the first region, that is, the plane, so that the first region is oriented horizontally.
  • the biological sample is dried in this position. After drying, the container is removed from the inclined ground. It is available for later resumption of the sample in liquid and can be stored or transported in advance.
  • the first region is arranged horizontally in the container bottom. This means that the first area when placing the container on a horizontal surface is horizontal.
  • the drying of the biological sample takes place on a level surface, while the resumption of the biological sample takes place on a sloping ground.
  • the container may be made of materials common in the art.
  • the container is made of plastic.
  • Suitable plastics are in particular organic polymers.
  • Particularly suitable are thermoplastic elastomers, such as polyolefins, in particular polyethylene or polypropylene, or silicones.
  • the container is in one piece. It then preferably consists of a single plastic.
  • the container is made of conductive plastic. Thereby, the drying of the sample can be assisted by heating.
  • the container may have a lid or seal with a foil that can close the opening.
  • the lid can be fixed with the container be connected, and in particular locked by folding down.
  • the lid or seal is used to transport or store the samples.
  • the floor in particular the first area, is structured on the inside.
  • a structuring of the soil, and in particular of the first area, can contribute to the optimal distribution of the liquid and support the adhesion of the dried sample.
  • a suitable structuring can be produced by known measures, such as nanostructuring or irradiation of the plastic.
  • the good distribution of the liquid can also be improved by the choice of the plastic, in particular by using a hydrophilic polymer component.
  • the plastic is preferably selected so that it does not affect the dried sample even after prolonged storage, for example by migration of ingredients such as inhibitors.
  • the container additionally has at least one device for fixing and / or parking, which is arranged below the floor.
  • the container is accurately and detachably connectable to a microtiter plate, in particular via the device for fixing.
  • the fixing is preferably carried out positively, in particular by snapping.
  • the means for fixing obliquely downwards away from the ground. It may for example have the form of one or more, in particular four legs. These serve to allow the container to be turned off and / or fixed by snapping onto a suitable substrate, such as a microtiter plate. In this case, preferably a plurality of containers can be fixed on the substrate or the microtiter plate.
  • the invention also provides a device for biological samples comprising at least two containers according to at least one of preceding claims, wherein the containers are aligned and connected with each other.
  • “equi-aligned” means that the containers are combined with each other in the same spatial arrangement, so that all the openings and depressions point in the same direction.
  • the containers are connected together in rows and / or two-dimensional arrays.
  • the device preferably has 4 to 1536, in particular 4 to 384, particularly preferably 6, 12, 24, 48 or 96 containers. With such devices, a variety of biological samples can be routinely processed in a laboratory.
  • the containers are firmly connected to each other.
  • the format of the device preferably corresponds to conventional laboratory formats, for example microtextile foams.
  • the device is then a microtiter plate with a special configuration of the containers (wells).
  • the formats of such devices are standardized according to the ANSI standard of the Society of Biomolecular Screening (SBS). The dimensions are usually 127.76 mm x 85.48 mm x 14.35 mm (length x width x height).
  • Common formats include 6, 12, 24, 48, 96, 384, or 1536 containers (wells).
  • a 96-format is preferred, in which 96 vessels are arranged in 8 parallel columns and 12 rows.
  • Corresponding formats are also described in DE 10212761 A1.
  • the containers are detachably connected to each other. With such formats, the device can be used particularly well in automated processes.
  • the device can be inserted into a microtiter plate and can be fixed in a soluble manner, so that each container is positioned on one or more wells of the microtiter plate
  • the invention also relates to a kit for drying and transporting biological samples, comprising at least the container according to the invention, wherein the first region is inclined, and / or the device and a heating block, the surface of which is inclined, the inclination angle corresponding to the inclination angle of the first area.
  • the invention also provides a method for drying a biological sample, comprising the steps:
  • the solution can be distributed on the horizontal, planar first region. This increases the surface area and facilitates drying.
  • a dried biological sample is obtained that is at least partially dried in the first area.
  • the biological sample can be completely obtained in the first region if it is deliberately added to the first region in step (c) without being able to run down during the process, especially if only a small amount of sample is pipetted.
  • the biological sample fluid may be a solution or a suspension.
  • the total volume of liquid used with the contained biological sample for example, between 1 ⁇ and 1 .000 ⁇ , in particular between 5 ⁇ and 800 ⁇ , preferably between 10 ⁇ and 500 ⁇ , more preferably between 10 ⁇ and 200 ⁇ are.
  • the liquid in step (c) is pipetted onto the first region after it has been aligned horizontally in step (b).
  • the liquid containing the biological sample according to step (c) is added to the container or device, and then only the first region in step (b) is aligned horizontally. This embodiment is possible if the volume of the liquid is so great that it would not remain on the first area anyway, but would spread evenly throughout the vessel.
  • the liquid is partially or completely removed from the biological sample.
  • the biological sample is largely dried so that a solid remains in the container.
  • the residual content of liquid after drying is less than 50%, 20%, 10% or 5%, based on the total weight of the dried residue.
  • Drying is preferably assisted by heating and / or low pressure. Heating takes place at temperatures suitable for such biological samples. Preferably, the drying is carried out between 30 ° C and 65 ° C.
  • the substrate supports the drying process.
  • the substrate is preferably a heating block.
  • the device or the container is adapted to the heating block so that they fit snugly and an optimal heat transfer is possible.
  • the heating block is releasably connectable to the container or the device.
  • a device for applying a vacuum or an exhaust device is preferably present.
  • the drying process can be particularly be accelerated.
  • the drying is carried out in a drying device having an airtight housing, such as a drying cabinet or an automated workstation. The drying process may be assisted by movement, such as slight rotation of the containers or device.
  • the invention also provides a method for processing a biological sample, comprising the steps:
  • step (g) dissolution or resuspension of the biological sample occurs.
  • any suitable liquid may be used, such as solvents or water, buffers or aqueous reaction mixtures.
  • step (h) the first area of the floor is inclined. Overall, the previously dried biological sample is resumed in a liquid, whereafter it flows from the inclined first region in the second region and accumulates in the depression. The liquid can be removed from the depression particularly easily by pipetting. Especially with small sample volumes, it is advantageous if they accumulate in a well to reduce fluid losses.
  • the method is carried out automatically. This means that at least partially Work steps, such as pipetting or heating, of machines and / or robots are performed. The process is preferably carried out completely automatically.
  • the containers or devices may be provided with markings to enable sample identification, such as bar codes.
  • the containers can then be integrated into a laboratory information management system.
  • the invention also relates to the use of a device according to the invention for drying, storing, resuspending and / or processing a biological sample.
  • the invention solves the underlying problem.
  • Methods and apparatus are provided which allow biological samples to be rapidly dried, effectively resuspend in liquid, and easily removed.
  • the methods and devices are easy to implement and can be integrated in routine procedures in biochemical and diagnostic laboratories. They can also be used in standard automated procedures.
  • Figure 1 shows schematically a container 1 according to the invention.
  • Figure 2 shows schematically and not to scale a container 1 according to the invention in the plan.
  • Figure 3 shows a device of four containers 1 in a row.
  • Figure 4 shows a device 9 of 24 containers 1, which are arranged in a two-dimensional array, and a container 1 in the plan view and a container 1, is pipetted into the liquid.
  • FIG. 5b shows a device 9 of four containers 1 according to the invention in series with an inclined first area on an inclined heating block 11.
  • Figure 5a shows schematically the addition of liquid with a pipette.
  • Figure 5c shows schematically the removal of liquid with a pipette.
  • Figure 6 shows a device for drying devices 9 on microtiter arrays with a tilted heating block 1 1 and means 14, 15 for drying.
  • Figure 7 graphically shows results of the embodiments. Plotted for each of the 12 examples, the specific amount of DNA in g, wherein the respective first bar (A, dashes) corresponds to the drying with heating block, the second bar (B, white) corresponds to the drying with hot plate and the respective third bar ( C, black) corresponds to drying in the sterile bench with draft.
  • a container 1 according to the invention with a bottom 2, a side wall 3 and an opening 4 is shown schematically.
  • the container has a device 10 for fixing and parking in the form of four legs.
  • the container is shown in the normal position in an upright position, in which it is parked (or fixed) on a level surface.
  • the floor 2 has a first area 5 which is inclined.
  • a deeper second region 6 is present, which has a recess 8.
  • the recess is arranged laterally and is not in the middle of the floor.
  • the first region 5 of the floor is designed flat.
  • the first area is connected to the side wall 3 via a curved transition area.
  • the connection of the second region 6 with the side wall is also partially curved.
  • Figure 2 shows a container 1 as shown in Figure 1 in the plan view.
  • the illustration is not to scale and the dimensions are not exactly as shown in Figure 1.
  • the first area is smaller than in Figure 2.
  • the side wall 3 of the container is vertical.
  • the floor is subdivided into the first region 5, which essentially forms a plane, and the second region 6, which has a depression 8.
  • the first region extends over the center of the bottom 7, while the second region laterally adjoins the first region.
  • Figure 3 shows a device 9 of four containers 1, which are arranged in a row and are aligned in the same way.
  • the containers can be releasably or firmly connected to each other.
  • Figure 4 shows a device 9 in which 24 containers 1 are connected in a two-dimensional array.
  • the containers are preferably firmly connected to each other.
  • the containers 1 are aligned in the same way, so that liquids react in the same way to changes in the device 9 in the containers. Since the device 9 consists of 24 containers 1, each with four evenly distributed legs, the device can be inserted into a 96-well microtiter plate, with each of the 96 legs engaging in or resting on an opening in the microtiter plate.
  • a single container 1 is schematically enlarged and schematically shown in plan view with side walls 3, which are inclined in this case, and a recess 8 in the second area. To the right of the array, a single container 1 is shown schematically and enlarged in which liquid is removed from the depression 8 with a pipette 12.
  • FIG. 5b shows a device 9 of four containers 1 in series, which have a first portion inclined in the normal position.
  • the device is placed on an inclined heating block 1 1. This results in the first area lying horizontally, since the inclination angles of the areal first area and the heating block balance each other out.
  • the liquid 13 thus spreads evenly on the flat first area and can be dried effectively.
  • FIG. 5a schematically shows a single container of the device 9 into which liquid 13 is pipetted with a pipette 12.
  • FIG. 5c schematically shows a single container 1 of the device 9 in the normal position, ie on a level surface. The liquid 13 is accumulated in the well and is removed from the well with a pipette 12.
  • FIG. 6 shows a drying device 16 with a housing 17.
  • the drying device has an inclined heating block 1 1. This contains bulges for fixing devices 9.
  • a device 9 can be releasably engaged.
  • a device 9 of four containers is shown in series, which is inserted into the device 10 for fixing.
  • the containers have inclined first areas that are horizontally aligned by the balancing inclination of the heating block.
  • the drying device 16 enables efficient drying of the biological samples. Drying is assisted by a low pressure device 15, which may be a vacuum pump, and by a ventilator 14, which may be a fan or a fan.
  • Examples 1-4 blood was added in the indicated amounts to the containers of standard 24-well flat bottom culture plates. In Examples 5-8, blood was added to common containers of 48 flat bottom culture plates. In Examples 9-12, blood was placed in standard containers of 96-well EMT plates (Elution Microtubes CL, trademark of Qiagen, NL) which taper conically toward the bottom. The shape resembles "Eppendorf tubes.” In each example, three samples each were prepared, which were dried with different drying devices, namely on a tilted heating block, which was heated to 45 ° C, on a hot plate and in a sterile bench with exhaust device at approx 20 ° C.
  • the solid residue was then taken up in 200 ⁇ of water each time
  • the DNA was isolated with a kit (QIAamp Sample Prep; Brand of Qiagen, NL) and the amount of DNA analyzed spectroscopically and by gel electrophoresis. The results are shown in Figure 7.
  • the amount of isolated DNA in micrograms is shown in the form of bars for Embodiments 1 to 12. Each embodiment has three samples associated with it, the first one (A, dashes) of drying with heating block, the second bar (B, white) drying with hot plate and the third bar (C, black) corresponding to dehydration in the dumbbell ,
  • Embodiments 1 and 2 With the 24-well flat-bottom culture plate, good recovery was observed with Embodiments 1 and 2 with water (30 minutes, 56 ° C). In Embodiments 3 and 4, the residue was partially dissolved and partly remained as a solid film on the bottom, especially the samples which were dried with hot plate. Even with lysis with AL (56 ° C, 30 minutes), the residue for Examples 3 and 4 could not be completely redissolved. In Examples 5-8 with 48-well culture plate, good redissolution in water (30 minutes, 56 ° C) was observed for Examples 5 and 6, but only partial resolution in Examples 7 and 8. After lysis with AL (56 ° C, 30 minutes), the residue could be redissolved in all samples, leaving a small, insoluble residue at the edges in Example 8.

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  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Biochemistry (AREA)
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Abstract

Récipient pour traiter et conserver des échantillons biologiques, lequel présente un fond, une paroi latérale et une ouverture, ce récipient ayant une contenance comprise entre 100 μΙ et 5000 μΙ, l'ouverture étant agencée sur le dessus, le fond présentant une première zone qui forme sensiblement un plan qui s'étend sur le centre du fond, et le fond présentant une deuxième zone qui est adjacente latéralement à la première et qui présente une cavité (8). L'invention concerne également des dispositifs, des kits et des procédés pour traiter et conserver des échantillons biologiques.
PCT/EP2016/055282 2015-03-12 2016-03-11 Récipient pour le séchage et la préparation d'échantillons biologiques WO2016142516A1 (fr)

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DE102015103634.7A DE102015103634A1 (de) 2015-03-12 2015-03-12 Behälter zum Trocknen und Aufbereiten biologischer Proben
DE102015103634.7 2015-03-12

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3902477A (en) * 1973-09-26 1975-09-02 Becton Dickinson Co Blood specimen container
DE4419971A1 (de) * 1994-06-08 1995-12-14 Eppendorf Geraetebau Netheler Gefäß zum Temperieren kleiner Flüssigkeitsmengen in einem Thermostaten
WO2000045956A1 (fr) * 1999-02-03 2000-08-10 Büchi Labortechnik AG Ensemble evaporateur dote d'un dispositif de retenue de recipient pour echantillon et procede d'evaporation d'un echantillon
DE10159804A1 (de) 2001-12-05 2003-06-26 Eppendorf Ag Deckelgefäß
DE10212761A1 (de) 2002-03-22 2003-10-16 Eppendorf Ag Mikrotiterplatte
US20040115099A1 (en) * 2001-07-09 2004-06-17 Smith James C. Reagent vial for automated processing apparatus
US20130037059A1 (en) * 2009-07-31 2013-02-14 Simon Stafford Means for improved liquid handling in a microplate

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3902477A (en) * 1973-09-26 1975-09-02 Becton Dickinson Co Blood specimen container
DE4419971A1 (de) * 1994-06-08 1995-12-14 Eppendorf Geraetebau Netheler Gefäß zum Temperieren kleiner Flüssigkeitsmengen in einem Thermostaten
WO2000045956A1 (fr) * 1999-02-03 2000-08-10 Büchi Labortechnik AG Ensemble evaporateur dote d'un dispositif de retenue de recipient pour echantillon et procede d'evaporation d'un echantillon
US20040115099A1 (en) * 2001-07-09 2004-06-17 Smith James C. Reagent vial for automated processing apparatus
DE10159804A1 (de) 2001-12-05 2003-06-26 Eppendorf Ag Deckelgefäß
DE10212761A1 (de) 2002-03-22 2003-10-16 Eppendorf Ag Mikrotiterplatte
US20130037059A1 (en) * 2009-07-31 2013-02-14 Simon Stafford Means for improved liquid handling in a microplate

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