Classifications

• • 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
• • G—PHYSICS
  • G02—OPTICS
  • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
  • G02B21/00—Microscopes
  • G02B21/32—Micromanipulators structurally combined with microscopes
• • 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
  • G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
  • G01N2001/2833—Collecting samples on a sticky, tacky, adhesive surface
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
  • Y10T436/2575—Volumetric liquid transfer

Definitions

• the invention relates to a device and a method for receiving, transporting and depositing - in summary the transfer - microscopic samples.
• biological and biomedical research but also in forensics, the smallest units of biological material have to be isolated at one sample location, transported from the sample location to a storage location, and then analyzed.
• the samples are taken from laboratory preparations such as tissue sections, which may be on microscope slides suitable for microscopy, for example.
• tissue sections which may be on microscope slides suitable for microscopy, for example.
• a sample must often be picked up from irregular or opaque surfaces, such as parts of a garment or cigarette butt. The samples must be recorded as accurately as possible, i. E. From a variety of spatially close to each other samples must be picked out and isolated.
• This sample must then be brought to a place of release without contamination, ideally also documented or at least controlled.
• the storage of the samples at a delivery location - for example, an Eppendorf vessel or a biochip - must be done as accurately as possible depending on the place of delivery or the vessel.
• a selectively activatable transfer surface is described in WO 97/13838 A1:
• the tissue section on a slide is covered with a transparent transfer film, which in turn is itself located on a support.
• the transfer film is polymeric and has thermoplastic properties, i. It melts during heat treatment.
• the film can then be adhered precisely to the parts of the tissue to be isolated, so that after the microdissection, when the film is lifted off the sample together with the carrier, only these tissue parts adhere to it.
• the cut-out sample parts can then be deposited in a reaction vessel with or without the transfer film.
• a multilayer transfer film which also has thermoplastic properties and contains at least one metal film and a support layer.
• This film is drawn onto a carrier, wherein the carrier is designed as a lid of an Eppendorf vessel.
• the lid with the film is brought into contact with the sample, by the laser treatment, the sample parts of interest remain adhered to the lid.
• the lid can be placed on the vessel, so that the Eppendorf vessel is closed and the sample can be brought directly into contact with a reaction solution.
• EP 1 250 583 Bl a method is described in which the sample is covered with a film.
• the pick-up tool an adhesively coated carrier, is placed on the foil. Subsequently, by means of laser microdissection, the parts of interest of the sample are isolated, whereby the laser cuts through the tissue and the foil.
• the carrier is preferably designed as a lid of an Eppendorf vessel, alternatively, an adhesive tape can be used.
• EP 0 879 408 B1 Another solution is described in EP 0 879 408 B1. Again, a microdissection is performed first. The microdissected material is then released from the slide by a laser pulse, catapulted upward and then hits the lid of an Eppendorf tube. Preferably, the lid is adhesively coated so that the material adheres to the lid. Alternatively, an adhä sives disk be used as a collecting surface, which is then stored in an Eppendorf vessel.
• the approaches described above have some disadvantages.
• the structure of the carrier layers for the adhesive material is complicated, the methods moreover require the use of a laser, either for microdissection with simultaneous activation of the adhesive properties of the carrier material or for subsequent catapulting of the dissected material from the slide onto a corresponding carrier ,
• Such methods are, for example, only conditionally usable in forensics, since a microdissection on the sample carriers occurring there is not readily possible.
• the catapulting of an object from the sample is a step with a degree of inaccuracy, but it must be ensured in forensics that the desired sample has actually been taken.
• inverse microscopes are used for the laser microdissection, overall the control and documentation capability is severely impaired.
• WO 97 / 13838A1 describes an adhesive tip with which tissue parts of microscope slides can be received.
• the tip is immersed in a mixture of a commercial polyterpene resin and xylene. This solution serves as an adhesive.
• the tip is then used to pick up the sample, which adheres to the mixture of resin and xylene.
• the recorded material is transferred to an analyzer.
• In this vessel there is a reaction solution, which eliminates the adhesive effect of the tip or the mixture of resin and xylene.
• the absorbed material thus separates from the tip and remains in the solution.
• the tip is again immersed in the adhesive solution. Since it continues to work with the same stick tip, a freedom from contamination is not guaranteed.
• EP 0 539 888 B1 describes a cell cluster selecting device and cells enclosed in gel granules.
• the device includes i.a. a capillary for receiving the objects.
• This capillary is dipped in a starch-like adhesive which imparts adhesion of the cell to the tip of the capillary.
• the capillary is guided with the cell adhering to it via a collecting vessel with liquid.
• compressed air which is blown through capillary, adhesive and cell dissolve from the top and fall into the liquid.
• the process of delivery can not be reproduced - is therefore difficult to document - and also allows no precise positioning of the cell cluster.
• adhesive is also blown off, which can cover the cell and thus make the analysis more difficult or even impossible.
• a needle serves as a transfer tool.
• the uptake and release is assisted by suction or pressure, electrostatic or magnetic interactions.
• a needle is described, adhering to the biological material due to electrostatic interaction.
• a major disadvantage of using a needle as a transfer tool is that when the cell is detached from the needle, the cell can not be accurately positioned. This is particularly disadvantageous in the use of Eppendorf vessels, in which it depends on the precise positioning in the area with the reaction liquid from the amount of a drop.
• WO 2005/033668 A1 describes another microdissection method in which the excised tissue is electrostatically fixed to the slide.
• the cut-out tissue can then either be absorbed or sucked in electrostatically via an electrode or via a relatively wide contact surface provided with air channels with a diameter of approximately 500 ⁇ m.
• the air channels themselves have only a diameter of 8 microns.
• a deposit of the tissue section is again on an adhesive pad.
• the contact surface is used, then due to the high diameter, this surface can not be realized with pinpoint accuracy. Due to the expansion of the contact surface is also a risk of contamination.
• WO 2004/046734 A1 describes a device for harvesting cells and cell colonies from liquid cultures and semisolid media.
• a cell is sucked through a glass capillary, a robotic arm then moves the glass capillary to a suitable analysis medium, such as a microtiter plate, and there they are.
• a suitable analysis medium such as a microtiter plate
• the method described in WO 2004/046734 A1 is designed for high throughputs and is thus only poorly suited for the investigation of individual samples.
• a liquid is forcibly required as a receiving and discharging medium.
• the object of the invention is therefore to develop a device and a method can be taken with the samples of the size of a cell from a variety of substrates and can then be stored as accurately as possible at a designated location.
• the transport should take place without contamination.
• the recording, transport and storage of the sample can be documented.
• a device for receiving, transporting and depositing microscopic specimens comprising at least one interchangeable adhesive body and a gripping tool for receiving, transporting and depositing the adhesive body comprises, wherein the adhesive body has at least one outwardly curved surface which is configured at least partially adhesive with respect to the sample. Gripping tool and adhesive body are thus two different components, the gripping tool takes on the adhesive body.
• the curved surface of the adhesive body can be arbitrarily shaped. By means of the outwardly curved surface of the adhesive body, it is possible to record targeted smallest amounts of biological material the size of a cell.
• the curved surface is at least partially adhesive with respect to the sample.
• the type of adhesion can be varied from sample to sample, for example, different coated adhesive body can be provided, one of which is selected depending on the sample by the gripping tool or an operator who leads the gripping tool.
• the adhesive configuration of the surface can be limited to a very small area. In this way, the assurance that only the desired sample is taken can be increased.
• the adhesive body or its curved surface can also be designed to be adhesive over the entire surface.
• the adhesive surface of the adhesive body is ideally designed so that although a single cell adheres to it, but not a larger cell composite, and a correspondingly easy detachment from the surface is possible.
• the adhesive body is replaceable, i. for the removal of the next sample, the used adhesive body is exchanged for an unused, so that the sampling can always be carried out without contamination. Since the area in which the curved surface comes into contact with the sample at a sample location is very small, in addition to a pinpoint recording even a pinpoint storage is made possible when the curvature of the surface is correspondingly strong. It is also possible to use non-curved, but even surfaces, but this does not allow for a precisely placed receiving / dispensing if the surface is too large.
• the flat surface is small enough, it can be used equivalently, but with curved surfaces the corresponding adhesive bodies are easier to manufacture and use because they can be made larger. Finally, inwardly curved surfaces are usable. With slight curvature, the effect is similar to that of a flat surface, with larger curvatures, the contact - inverse to the outwardly curved surface - preferably take place at the edge, if the surface corresponds for example to an inwardly inverted membrane.
• the gripping tool is designed as tweezers.
• These tweezers can also be designed as inverse tweezers, in the ground state, the legs are closed.
• the tweezers can be made of a single workpiece, in which case a solid-body joint ensures mobility of the legs.
• the gripping tool is made interchangeable, in this way it is possible to use, for example, different types of tweezers, which are adapted to the sizes of different adhesive body. Also, so tweezers made of different materials can be used.
• the gripping tool expediently has a gripping mechanism which can be driven piezoelectrically, electromechanically, magnetically or pneumatically, for example. Other drive types are conceivable, if they can reach the necessary smallest travel paths with them.
• the gripping tool is preferably at least partially provided with a fluorescent material layer. This also makes it possible, for example, to remove a fluorescent or fluorescence-labeled sample without the influence of interfering ambient light. Depending on the sample, various gripping tools may be provided, which are provided with layers fluorescent at different frequencies and can be replaced if necessary.
• the adhesive body is designed as a ball, wherein the ball preferably has a diameter between lO ⁇ m and 500 ⁇ m.
• the surface can then be made completely adhesive.
• the advantage of balls lies in their shape, which allows the smallest contact surfaces. Moreover, they are easy to manufacture and easy to store. If the ball is completely executed with an adhesive surface, so it does not matter how the ball is picked up by the gripping tool, so handling is simplified.
• a variety of other shapes are also suitable as adhesive bodies, for example lenses, ellipsoids, cylindrical bodies with rounded head and / or foot surfaces.
• the adhesive body may consist of fluorescent material or at least be provided with a fluorescent material layer, so that the recording of material, which is selected based on its fluorescence, is possible.
• the adhesive bodies are at least partially made of plastic, preferably of polystyrene. Alternatively, they may also be made of cellulose or a cellulose derivative. The production of such balls is particularly inexpensive, moreover the materials are inactive with respect to reactions with the commonly included biological materials.
• the adhesive bodies may also consist at least partially of a magnetic or at least magnetizable material. This can be advantageous, for example, if the ball is deposited on a magnetised surface. This can be on the one hand a storage location where the sample is prepared for further analysis, or after dropping the sample a container in which used adhesive bodies are collected and then cleaned. It does not have the entire adhesive body made of magnetic material, it is sufficient if it has a core of magnetic or magnetizable material.
• the at least one curved surface of the adhesive body is at least partially provided with an adhesive layer of a polypeptide or a polymer.
• a polypeptide or a polymer for example, biosynthetic polypeptides of non-animal origin, or cellulose derivatives may be used.
• Such a coating has the great advantage that the layer with respect to conventional surfaces such as metal, glass, etc., ie such surfaces, as they are found in a slide or gripping tool, no adhesive effect, the adhesive effect is thus selective. It is limited to biological samples, especially cells. This considerably facilitates the handling of the combination of gripping tool and adhesive body. All other coatings that exhibit this selective adhesion are also suitable and considered equivalent.
• the adhesive body may also have the properties of hydrogels and advantageously at least locally liquefied by heat and / or force, which in turn may facilitate the uptake of cells.
• the device therefore expediently has a reservoir with a plurality of adhesive bodies. Then, a new adhesive body can be removed with the gripping tool from the reservoir.
• the reservoir is a shell.
• the reservoir is preferably provided with a metering device for metering in each case one adhesive body. provided. In this way, the removal of the adhesive body can also be automated if the Creiftechnikmaschine is guided by a corresponding control device, since the location for a detention body in this case is always the same place.
• the device advantageously has a microscope, preferably a stereomicroscope. This allows the constant control of the process.
• a micromanipulator is provided in the device, with which the gripping tool is guided.
• a micromanipulator has a holder in which the Creiftechnikmaschine is attached and connected to the micromanipulator.
• a micromanipulator is movable in all three spatial directions, so that the gripping tool can be guided in any desired manner in a limited spatial area. If the device also has a microscope, then it makes sense to provide the micromanipulator in the immediate vicinity, so that the gripping tool can be guided with the adhesive body into the field of view of the microscope.
• the micromanipulator is preferably connected to a control device, so that manual control is possible, for example via a joystick, in order to guide the gripping tool with the adhesive body over the sample, to pick up the sample and to transport it to the storage location.
• This process can also be partially automated if the spatial position of the adhesive body with respect to the storage location is known. The position can be determined, for example, with a position measuring device, as described in DE 10 2005 053 669.7. After the sample has been taken, the transport to the storage location, for example a biochip, which is arranged at a designated place and whose coordinates are known, can take place automatically. If the sample is released without adhesive body, the storage of the used adhesive body and the inclusion of a new adhesive body can also be done automatically.
• means for generating a microvibration are provided in the gripping tool. If the gripping tool is held, for example, by a micromanipulator, the microvibration can be generated in the manipulator. This can be offset, for example piezoelectrically or by means of other suitable drives in vibrations with amplitudes of a few micrometers. This device can also be provided in the manipulator itself, so that only the gripping tool is set in vibration. Finally, the gripping tool itself can be designed so that it has a corresponding piezoelectric, electromotive or other vibration generating mechanism has. For example, in the case of tweezers as a gripping tool, the mechanism may be disposed between the two legs and cause them to oscillate in parallel so that the ends of the tweezers are deflected in parallel from their rest positions.
• a micro-vibration is generated in the gripping tool, then in some cases this facilitates the pick-up of the sample: If the adhesive body comes into contact with the sample, it remains adherent to it. In general, however, the sample also adheres to the surface from which it is to be removed, so that it may u.U. is difficult to solve or even destroyed when the gripping tool with the adhesive body and the sample adhering to it is removed, since in particular in the case of a single cell too large tensile forces can occur, so that the cell tears. However, if additionally an activatable microvibration is switched on in the gripping tool, this helps to reduce the adhesion on the surface from which the sample is to be removed.
• a surge amplitude in the gripping tool in the device is particularly helpful in depositing, in order to facilitate the deposition of the adhesive body - with or without a sample - at a location provided for this purpose, since the adhesive body may be broken down. the tendency is to stick to the gripping tool.
• This surge amplitude can be generated, for example, with a small hammer on a piezoelectric base. The hammer may for example be integrated in the micro manipulator or in the gripping tool itself.
• means are provided for at least partially controlling the recording of the transport and / or the storage of the sample.
• the transfer can also be observed through the microscope.
• An observer such as a certified assessor, can then confirm that a sample has actually been taken and deposited at the appropriate location.
• the means for control suitably include a camera. With such a camera can then continuously or at intervals the whole process of the transfer, ie documented from the sample recording to filing and controlled.
• the camera can be connected, for example, to its own outlet on the tube, this is particularly advantageous if the recording of the sample is to be monitored.
• the camera can also be arranged externally.
• the micromanipulator has the possibility to open and close the gripping tool, ie to apply the gripping function.
• the control of the micromanipulator is designed so that - with automatic guidance or manual guidance, for example via a joystick - the speed of the manipulator with which he moves through the image field, which is to be viewed in the microscope or in the camera moves , depends on the magnification chosen on the microscope.
• the drive of the micromanipulator is thus controlled as a function of the selected magnification.
• the dependence is selected so that at low magnification, the manipulator is moved at a greater speed, at a large magnification with a correspondingly lower speed.
• the speed observed in the image field is independent of the set magnification of the microscope.
• the gripping tool is designed to be rotatable at least about its longitudinal axis, so that the adhesive body can be rotated with the adhering sample in the direction of the observer or the camera. This can serve on the one hand to control that the sample was actually recorded, but on the other hand, the documentation that actually a previously selected sample was recorded.
• the rotation can also be performed by the manipulator, which can be configured with a corresponding rotating device. If, for example, a sample is taken, it is initially not visible to an observer, who observes the process through an upright stereomicroscope, on the underside of the adhesive body facing the removal surface.
• the underside is now turned into the field of view of the observer, who can recognize whether a sample actually adheres to the adhesive body.
• a camera that is accessible via the tube the entire process can be documented. If the camera is mounted below the sample holder, rotation can also be dispensed with, provided the sample holder is transparent. The sample can also be moved with the help of the micromanipulator to a corresponding location where a camera is installed.
• control means may also comprise at least one mirror
• the adhesive body may then be attached to the adhering sample via the at least one mirror.
• gel in the direction of an observer or the camera. Again, rotation may be waived depending on where the mirrors and camera are located relative to the area from which the sample is taken.
• the object is also achieved by a method for transferring a microscopic sample from a sample location to a storage location, in which a gripping tool receives an adhesive body with at least partially curved surface, which is at least partially adhesive with respect to the sample, the gripping tool receives the adhesive body is passed over the sample, the at least partially curved surface of the adhesive body is brought into contact with the sample and when removing from the sample location the sample adheres to the surface of the adhesive body, and the sample is deposited at the storage location.
• a gripping tool for example a pair of tweezers receives an adhesive body with an at least partially curved surface.
• the adhesive body may be configured for example as a ball.
• the partially curved surface is at least partially adhesive with respect to the sample.
• the gripping tool which can be guided, for example, by a micromanipulator, guides the adhesive body over the sample - this can be done either manually or automatically. Also manual guidance is possible. Sample selection can also be done manually or automatically if appropriate image processing algorithms are available.
• the gripping tool with the adhesive body is then lowered onto the sample, the at least partially curved surface of the adhesive body is thus brought into contact with the sample.
• the sample When removing the gripping tool with the adhesive body from the sample location, the sample remains adhered to the surface of the adhesive body. In order to facilitate the detachment of the sample from the sample surface, it may be advantageous to set the gripping tool in harmonic oscillations with an amplitude of a few micrometers, so-called microvibrations.
• the sample is deposited at the storage location. Depending on the type of sample or the type of analysis provided, the sample may then be deposited with or without an adhesive body. If the sample is to be deposited with an adhesive body, the gripping tool can advantageously be set into a shock vibration, also several times, in order to facilitate dispensing.
• the storage can be done for example on a biochip or on magnetic surfaces or in Eppendorf vessels.
• the shelf can be made with or without adhesive body. Without depositing the adhesive body, the sample, usually a single cell, for example, be stripped on a drop of a reaction liquid, wherein at a greater curvature of Surface of the reaction liquid - for example, an aqueous solution - the adhesion forces of the liquid with respect to the cell surpass the adhesion to the adhesive body.
• the movement of the gripping tool can be adjusted in the field of view of a switched-on microscope by an appropriate control so that the gripping tool for a viewer always moves at a substantially same speed, i. at high magnification with a correspondingly lower speed than at a small magnification.
• the recording of the sample is controlled by the gripping tool with adhesive body and sample rotated and / or moved and mapped into a camera.
• the adhesive body with the sample which is not visible on the underside of the adhesive body for an observer, made visible. It can thus be prevented that in unsuccessful sample receptacles analysis containers only seemingly filled. In the prior art, this lack of possibility of control leads to frequent false analyzes, i. for example, missing duplication reactions.
• the recording of the sample can also be documented by imaging the gripping tool with adhesive body and sample into at least one mirror in a camera. In this way, can be dispensed with the rotation when the surface from which the sample is removed, the mirror and the camera are arranged in corresponding positions to each other.
• the sample is fixed prior to removal by means of the adhesive body for carrying out a sample manipulation, in particular a microdissection.
• a sample manipulation in particular a microdissection.
• the gripping tool with the adhesive body is thus lowered to the sample, by exercising a corresponding low force from the gripping tool on the adhesive body to the sample, this can be fixed.
• the pressure or the force can also be generated by the micromanipulator. If the sample is fixed, a corresponding microdissection can be carried out by means of a further sample manipulator, for example a laser.
• a device according to the invention is shown, with which also the inventive method can be performed.
• the device expediently comprises a stereomicroscope 1 with which, in particular with manual operation of the gripping tool, the sample intake can be spatially observed and carried out.
• the usually present objective turret is shown here symbolically by a lens 2.
• On the observer side there are two eyepieces 3 on the stereomicroscope 1 with which an observer can observe the sample intake and at least part of the transfer.
• a switching possibility for the beam path is provided, so that the beam path is directed instead of the eyepieces 3 on a camera 4.
• the beam path in the stereomicroscope is sketched by the two black lines that emanate from the eyepieces 3 and converge on a sample carrier 5.
• a sample 6 On the sample carrier 5 is a sample 6.
• a micromanipulator 7 Left of the stereomicroscope 1 is a micromanipulator 7, which can be moved in all three spatial directions limited. The intended holder - advantageous on the microscope body - is not shown.
• a pair of tweezers 8 is clamped as a gripping tool.
• an adhesive body At the tip of the tweezers 8 is held by their thighs an adhesive body, which here has the shape of a ball 9.
• the sample carrier 5 may be, for example, a slide, but also a piece of clothing. As a sample 6, for example, individual cells come into question.
• the stereomicroscope 1 may be capable of fluorescence, accordingly tweezers 8 and ball may also be at least partially provided with a fluorescent layer.
• the ball 9 serves to accommodate the cell and at the same time their transport.
• the ball 9 is preferably a plastic microbubble such as polystyrene or biopolymers.
• a glass ball as adhesive body 9, since in these the delivery into a water droplet with a corresponding surface curvature is more favorable.
• the diameter of the sphere can be between 10 ⁇ m and 500 ⁇ m. Smaller and larger diameter are also possible and depending on the Size of the sample may also be advantageous.
• FIGS. 2 a to 2 c show the recording of a sample, here one of a plurality of cells, with the tweezers 8.
• a ball 9 taken from the metering device and brought to the cell 10 to be isolated. This condition is shown in Fig. 2a.
• Fig.2b is shown how the ball 9 comes into contact with the cell 10.
• the cell 10 adheres to the ball 9.
• a suitable liquid for example fifty percent ethanol.
• the adhesion of the cell 10 on the ball 9 can also be promoted by the fact that the ball 9 is at least partially provided with a very thin adhesive layer.
• the adhesive layer may be, for example, a biosynthetically produced polypeptide of non-animal origin or alternatively a cellulose derivative polymer. Suitable coatings are those whose adhesion is limited to biological material but does not extend, for example, to the tweezers.
• FIG. 2 c shows how the cell 10 adheres to the ball 9 when the tweezers 8 and the ball 9 are removed.
• FIGS. 3 and 4 show how the recording of the cell 10 is documented.
• the tweezers 8 in the micromanipulator 7 or the micromanipulator 7 can be rotated as a whole about the longitudinal axis, as indicated by the arrow in Figure 3.
• the cell 10, which adheres to the ball 9, is now in the field of view of the lens 2 of the stereomicroscope 1.
• the image can be observed by an observer or imaged on a camera.
• An alternative using an upright microscope or stereomicroscope is shown in FIG.
• a mirror 11 is mounted on the sample carrier 5.
• the sample carrier 5 After receiving the cell 10, the sample carrier 5 is moved in the object plane until the mirror is in the field of view of the microscope.
• the sample carrier 5 symbolizes all possible types of work surfaces, for example a table with a recess for transparent slides on which the samples are arranged.
• FIGS. 5a and 5b show how the ball 9 with the cell 10 is guided to a further sample carrier 12 and is deposited there.
• the ball 9 becomes stored there together with the cell 10.
• This type of delivery is easier to implement than the delivery of the bare cell. It also ensures freedom from contamination.
• MALDI matrix assisted laser desorption and ionization
• the storage point on the sample carrier 12 is preferably coated with a thin adhesive film 13, which has, for example, special curing properties, so that the storage point can be coated weeks or months before its use with the adhesive film 13.
• the storage of the ball 9 can also be done on a magnetized surface.
• the ball is conveniently also made of magnetic material, or has at least one magnetic core. Also, a delivery of the ball 9 in a drop of liquid is possible, or a release alone of the cell 10 without the ball. 9
• the smallest objects can be isolated from specimens, recorded with pinpoint accuracy, transported to a storage location and deposited there precisely.
• the transfer is contamination-free and can be documented accordingly, which is why there are a multitude of applications, for example in basic biological research as well as in forensics.

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• Physics & Mathematics (AREA)
• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• General Physics & Mathematics (AREA)
• Optics & Photonics (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Sampling And Sample Adjustment (AREA)

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• 2006
  • 2006-09-25 DE DE102006045620A patent/DE102006045620B4/de not_active Expired - Fee Related
• 2007
  • 2007-07-04 US US12/440,679 patent/US8268265B2/en not_active Expired - Fee Related
  • 2007-07-04 EP EP07785890A patent/EP2067013A1/de not_active Withdrawn
  • 2007-07-04 WO PCT/EP2007/005899 patent/WO2008037305A1/de active Application Filing
  • 2007-07-04 JP JP2009528605A patent/JP2010504505A/ja active Pending

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