EP4065279A1 - Verfahren zum dispensieren einer flüssigen probe mittels einer dispensiereinrichtung - Google Patents
Verfahren zum dispensieren einer flüssigen probe mittels einer dispensiereinrichtungInfo
- Publication number
- EP4065279A1 EP4065279A1 EP20811399.3A EP20811399A EP4065279A1 EP 4065279 A1 EP4065279 A1 EP 4065279A1 EP 20811399 A EP20811399 A EP 20811399A EP 4065279 A1 EP4065279 A1 EP 4065279A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- particle
- area
- dispensing device
- met
- target
- 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.)
- Withdrawn
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 106
- 238000000034 method Methods 0.000 title claims abstract description 92
- 239000002245 particle Substances 0.000 claims abstract description 271
- 230000008569 process Effects 0.000 claims abstract description 48
- 238000012544 monitoring process Methods 0.000 claims abstract description 35
- 238000004590 computer program Methods 0.000 claims description 9
- 230000007246 mechanism Effects 0.000 claims description 9
- 238000006073 displacement reaction Methods 0.000 claims description 6
- 238000011144 upstream manufacturing Methods 0.000 claims description 5
- 238000012360 testing method Methods 0.000 abstract description 5
- 238000003384 imaging method Methods 0.000 description 13
- 239000012530 fluid Substances 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 8
- 238000004062 sedimentation Methods 0.000 description 7
- 238000009826 distribution Methods 0.000 description 4
- 239000000428 dust Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 101100117236 Drosophila melanogaster speck gene Proteins 0.000 description 2
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- 230000003111 delayed effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
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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
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0289—Apparatus for withdrawing or distributing predetermined quantities of fluid
- B01L3/0293—Apparatus for withdrawing or distributing predetermined quantities of fluid for liquids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1016—Control of the volume dispensed or introduced
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/061—Counting droplets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L2200/0652—Sorting or classification of particles or molecules
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
-
- 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
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0663—Whole sensors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N2015/1006—Investigating individual particles for cytology
Definitions
- the invention relates to a method for dispensing a liquid sample by means of a dispensing device, in which it is determined whether a particle condition is met, the determination comprising checking whether a monitoring area of the dispensing device contains at least one target particle in a liquid of the liquid sample, wherein the monitoring area has an ejection area and a buffer area, the buffer area being an area from which the at least one target particle is dispensed into the at least one target particle during a time delay between the determination of whether the particle condition is met and a dispensing process of the dispensing device
- Ejection area is movable.
- the invention relates to a dispensing device for carrying out the method and a dispensing device with a dispensing device for dispensing a liquid sample, a determination device for determining whether a particle condition is met, the determination comprising the check of whether at least one in a liquid of the liquid sample contained target particles, wherein the monitoring area has an ejection area and a buffer area, wherein the buffer area is an area from which during a time delay between the determination of whether the particle condition is met and an output process of the dispensing device the at least a target particle in the
- Ejection area is movable.
- the invention also relates to a computer program, a data carrier on which the computer program is stored and a data carrier signal which the computer program transmits.
- monoclonal cell lines are populations of cells that are all descended from a single parent cell.
- monoclonal cell lines are populations of cells that are all descended from a single parent cell.
- the production of monoclonal cell lines is necessary because this is the only way to ensure that all cells of the population have approximately the same genome in order to produce the active ingredients with constant and reproducible quality.
- cells are transferred individually into the containers of a microtiter plate.
- the cells to be transferred are produced by genetically modifying a host cell line and isolating these modified cells.
- the depositing of individual cells in the receptacles of the microtiter plates is done, for example, by a dispensing device.
- a dispensing method in which a dispensing process depends on a single-particle condition. It is checked whether a single particle is contained in an ejection area of a drop dispenser and whether a sedimentation area, which is arranged adjacent to the ejection area, is free of particles. If this is the case, the particle condition is fulfilled and the drop is released onto a target. In the event that the condition is not met, the drop is released onto a reject carrier. A discharge to the reject carrier also takes place if no particle is arranged in the ejection area and a particle is arranged in the sedimentation area.
- a disadvantage of the dispensing method is that there are often cases in which the discharge area does not contain a target cell and the sedimentation area contains a first target cell. Since the present case according to EP 3 222 353 B1 leads to a direct ejection of the cell-free sample part in the ejection area, the first target cell thereby advances from the sedimentation area into the ejection area. If there is then no second target cell in the sedimentation area, the first can be ejected individually, albeit with a delay. Often, however, there is then already a second target cell in the sedimentation area and the first target cell is discarded in the reject container. This often leads to loss of target cells and a delay in operation.
- the object of the invention is to provide a method by means of which the dispensing processes can be carried out efficiently.
- the invention is achieved by a method of the type mentioned at the outset, which is characterized in that it is determined that the particle condition is met when the at least one target particle is arranged in the buffer area and no target particle is arranged in the ejection area, and that the liquid Sample is released onto a target particle carrier when the particle condition is met.
- Another object of the invention is to provide a dispensing device by means of which the dispensing processes can be carried out efficiently.
- the invention is achieved by a dispensing device of the type mentioned at the outset, which is characterized in that the determination device determines that the particle condition is met when the at least one target particle is arranged in the buffer area and no target particle is arranged in the ejection area, and that a Control device is present which causes the liquid sample to be dispensed onto a target particle carrier when the particle condition is met.
- the number of dispensing processes in which the liquid sample is erroneously dispensed onto a collecting support can be reduced. This is possible because the fact that during the time delay the particle moves, for example due to sedimentation and / or post-flow, from the buffer area into the ejection area is exploited. Since there is always a time delay between the determination of whether the particle condition is met and the dispensing process, taking into account the time delay in the dispensing decision thus leads to an efficient method. The process is carried out automatically in the dispensing device.
- target particle is to be understood as a generic term that includes solid organic or inorganic microparticles as well as biological cells.
- the liquid sample includes a liquid and target particles such as cells.
- the liquid of the liquid sample can have a composition that is conducive to cell growth.
- the target particle can alternatively be a glass or polymer bead and have substantially the same volume as the cell.
- the liquid sample can have cells and / or glass or polymer beads.
- the discharge area comprises a sub-area of the dispensing device, in particular an output channel of the dispensing device.
- the discharge area can have an outlet opening of the dispensing device, through which the liquid sample is discharged from the dispensing device.
- the ejection area corresponds to a geometric area of the dispensing device in which the liquid sample is arranged, which is dispensed during the next dispensing process.
- the geometric area is selected in such a way that a particle arranged in the ejection area can be dispensed during the next dispensing process.
- the discharge area thus depends on the design of the dispensing device, in particular the dispensing channel.
- the discharge area also depends on the output volume. The larger the output volume, the larger the discharge area.
- the output volume is usually specified by the user, so that the output area is determined by the user.
- hydrodynamic effects in particular in connection with the inertia, the density, the deformability and the shape of the particles, influence whether a particle arranged in the ejection area is dispensed during the next dispensing process.
- a particularly inert particle will only be delayed and move more slowly at the beginning of the flow helps to understand it.
- especially smaller particles can be close to the wall and therefore only move slowly forward. This means that without precise knowledge of the position in three-dimensional space, the shape, the density, etc. of the particle and the flow in the dispensing device, the discharge area cannot be sharply defined. Because of this uncertainty, the discharge area can have a limit area.
- the boundary area is the area of the discharge area which is arranged adjacent to the buffer area.
- the border area is directly adjacent to the buffer area.
- the boundary area is an area of the discharge area in which one is not sure whether it is in the boundary area Target particle is expelled during the next dispensing process. Whether or not the target particle will be expelled the next time you dispense depends on the factors mentioned above.
- the buffer area corresponds to an area located upstream of the discharge area.
- the buffer area is arranged directly adjacent to the ejection area.
- the buffer area corresponds to an area in which a particle located in the buffer area can move into the ejection area during the time delay between the determination of whether the particle condition is fulfilled and the dispensing process by the dispensing device.
- the larger the time delay or the movement the larger the buffer area.
- the movement can result from a force acting on the target particle, such as a weight force.
- other forces acting on the target particle such as a magnetic force and / or a flow force, etc., can cause the particle to move into the ejection area.
- the liquid sample dispensed from the dispensing device cannot have a target particle.
- the dispensed liquid sample may have a single target particle.
- the dispensed liquid sample can have more than a single target particle.
- the liquid sample dispensed by means of the dispensing device can be a drop, in particular a free-flying drop.
- the sample output can be carried out according to a drop-on-demand mode of operation.
- the dispensing device results in a discrete and not a continuous sample output.
- the dispensing device can have an actuating means, which can be, for example, a piezoelectrically operated actuator.
- the dispensing device can have a section, in particular a mechanical membrane, which can be actuated by the actuating means. When the actuating means is actuated, the liquid sample, in particular a drop, is ejected from the dispensing device.
- the time delay corresponds to the time interval between the determination of whether the particle condition is met and the dispensing process in which the liquid sample is dispensed from the dispensing device.
- the time delay depends on the time period that is required until the control device causes the actuating means to actuate the dispensing device, plus the time period that is required for the actual actuation process, in particular the actuation by the actuating means.
- the time delay can be stored in an electrical memory.
- the user can preset a fixed time delay and / or change it during operation of the dispensing device. Specifying the time delay offers the advantage that the size of the buffer area can be specified in a simple manner and does not depend on the components of the dispensing device.
- the time delay can be adapted according to the particle distribution in the dispensing device. This is particularly advantageous when a particle is located in a limit area explained in more detail below. A longer time delay can then ensure that the particle moves into the desired area, such as the buffer area or the ejection area. In particular, it can be ensured in this way that a particle that is located in the border area moves safely into the ejection area. With a given particle distribution, it can thus be ensured that the desired number of particles is ejected in each case.
- the dispensing volume corresponds to the volume that is dispensed during a dispensing process.
- the dispensing volume can also be adapted as a function of the particle distribution in the dispensing device.
- An increase in the output volume can be viewed as an increase in the discharge area and a shift in the buffer area. The same applies to a reduction in the output volume. In this way, with a given particle distribution, it can be ensured that the desired number of particles is ejected in each case.
- the dispensed liquid sample can be a liquid jet which, after being dispensed from a dispenser of the dispensing device, disintegrates into individual liquid droplets.
- the dispensing device can be a drop generator.
- the liquid drop can have a volume in a range between 1 pl (picoliter) to 1 pL (microliter).
- the target particle carrier can be a container base to which the liquid sample is applied.
- the container can be part of a microtiter plate which has a large number of containers.
- the target particle carrier can be a flat plate onto which the liquid sample is applied.
- the collecting support can be the bottom of a collecting container onto which the liquid sample is applied.
- the liquid samples deposited on the collecting support can be processed for other examinations.
- the collecting carrier can be a reject carrier if the deposited liquid samples are not processed further.
- the collecting support can be arranged laterally relative to the dispensing device, so that the liquid sample can be deflected in the direction of the collecting support by a sample deflection mechanism after it has been ejected.
- a sample deflection can be achieved, for example, by an air flow or an electric field.
- the dispensing device can have a sample collecting mechanism which is designed such that it moves the collecting carrier into the trajectory of the ejected liquid samples in order to receive the liquid sample, and also moves it out of the trajectory again.
- the determination device can additionally determine that the particle condition is met if the target particle is arranged in the ejection region and no target particle is arranged in the buffer region.
- This offers the advantage that it is ensured that the dispensed liquid sample contains a target particle. This increases the efficiency of the dispensing process because fewer dispensing processes are erroneously dispensed onto the collecting carrier.
- the determination of whether the target particle is located in the discharge area and in the No target particle is arranged in the buffer area can take place before or after or at the same time as the previously described determination as to whether the target particle is arranged in the buffer area and no target particle is arranged in the ejection area.
- the determination device can determine that the particle condition is met if, in addition to the target particle, at least one other particle that is not a target particle is arranged in the ejection area and / or the buffer area.
- the other particle can be, for example, a speck of dust or a cell fragment or a dead cell or a cell type that is not of interest for the analysis.
- the other particle also has no harmful influence on the target particle, so that the other particle can be released onto the target particle carrier together with the cell particle.
- the other particle can be a non-interfering particle, in particular when processing the target particle.
- the determination device can determine whether the monitoring area contains a predetermined number of target particles.
- the specified number can have a value of 1 or greater than 1.
- it can be determined whether the monitoring area, in particular in the buffer area or the ejection area, contains a single target particle.
- designs are possible in which it is determined whether the monitoring area contains more than a single target particle.
- the determination device can determine whether the target particle has a predetermined property.
- the size and / or morphology and / or granularity and / or color of the target particle can be determined.
- target particles can be easily distinguished from the other particles mentioned above.
- it can be recognized in a simple manner whether a determined particle is incorrectly viewed as a target particle. It can thus be achieved that the dispensing process depends on at least one property of the target particle.
- the sample output is erroneously discharged onto the collecting carrier because, for example, a speck of dust or artifact has been identified as the target particle and it is therefore assumed that several target particles are arranged in the monitoring area.
- the samples are dispensed onto the collecting carrier because cells are arranged in the ejection area and / or the buffer area which are not relevant for the user, for example because they are dead and / or one is not of interest to the user Cell type are. As a result, the number of dispensing processes that are erroneously discharged onto the receiving carrier is reduced.
- the liquid sample can be dispensed onto the collecting support if the particle condition is not met.
- the determination device can determine that the particle condition is not met if more than a predetermined number, in particular more than a single target particle, is arranged in the monitoring area.
- the determination device can determine that the particle condition is not met if fewer than the specified number, in particular no target particles, are arranged in the monitoring area.
- the liquid sample is dispensed onto the collecting support.
- the number of target particles can be determined after determining the property of the target particles.
- the number of target particles and / or the property of the target particles can be determined based on at least one image of the monitoring area, in particular the ejection area and the buffer area.
- the determination device can have an imaging device, such as a camera, for example, which generates the image.
- the determination device can have an evaluation device by means of which the number of target particles and / or the property of the target particles can be evaluated based on the generated image.
- the evaluation device can be part of the imaging device. Alternatively, the evaluation device can be part of a computer.
- the control device can also be part of the computer. Alternatively, the control device can be part of another computer.
- the control device can control the actuation means by means of which the dispensing device is actuated in such a way that the dispensing time during which the liquid sample is dispensed from the dispensing device is changed if the particle condition is not met. This allows pro
- Dispensing process more or less liquid sample are dispensed from the dispensing device.
- a new test to determine whether the particle condition is met is carried out after the liquid sample has been dispensed.
- the control device can control the actuation means by means of which the dispensing device is actuated in such a way that the dispensing volume with which the liquid sample is dispensed from the dispensing device is changed if the particle condition is not met. This allows pro
- Dispensing process more or less liquid sample are dispensed from the dispensing device.
- a new test to determine whether the particle condition is met is carried out after the liquid sample has been dispensed.
- the time delay can be changed if the particle condition is not met.
- This increases or decreases the buffer area.
- the time increase can be increased in such a way that the buffer area becomes so large that it becomes a target particle contains. This can ensure that the next time the sample is dispensed, the liquid sample contains a target particle, in which case the ejection area does not contain a target particle.
- a new test to determine whether the particle condition is met is carried out after the liquid sample has been dispensed.
- a predetermined number of output processes can be carried out if the particle condition is not met.
- the portion of the liquid sample that is not of interest is quickly ejected from the dispensing device in a simple manner. After the specified number of output processes has been carried out, it can be determined again whether the particle condition is met.
- the dispensing device can have a displacement device.
- the dispensing device and / or the target particle carrier and / or the collecting carrier can be moved by means of the moving device.
- the movement process can depend on whether the liquid sample to be dispensed is to be dispensed onto the target particle carrier or onto the collecting carrier. In this way, the liquid sample is discharged onto the collecting support if the particle condition is not met.
- the dispensed liquid sample can be dispensed onto the target particle carrier if a single target particle is arranged in the liquid sample.
- the time delay can depend on the duration of a movement process from the dispensing device and / or the target particle carrier to an output position in which the liquid sample is dispensed onto the target particle carrier. This provides an efficient dispensing method because the time delay that inevitably occurs in the movement process is taken into account for the dispensing decision. Alternatively or additionally, the time delay can depend on the duration of a switching process of the sample deflection mechanism or the sample interception mechanism.
- a time delay, which is usually required for the movement process can be stored in an electrical memory. The time delay can alternatively or additionally be determined and stored during operation. The size of the buffer area can thus change during the operation of the dispensing device.
- the buffer area can have a boundary area.
- the border area is the area of the buffer area which is arranged adjacent to a remaining area of the dispensing device.
- the border area is directly adjacent to the remaining area.
- the remaining area of the dispensing device is understood to be an area that is not part of the monitoring area and is therefore not taken into account when checking the particle condition.
- the boundary area is an area of the buffer area in which it is not certain whether the target particle located in the boundary area will move into the ejection area during the time delay.
- the boundary area may have a target particle that moves into the ejection area during the time delay and another target particle that does not move into the ejection area during the time delay. Whether the target particle moves into the ejection area depends on the factors described below.
- the determination device can determine whether the target particle is arranged in the border area.
- the determination device can determine that the particle condition is not met if the target particle is arranged in the border area.
- the time delay and / or the output volume can be adapted so that the target particle is no longer located in the border area, but in the remaining part of the buffer area.
- the provision of the limit area takes into account that the test as to whether the particle condition is met is based on a two-dimensional image. However, it cannot be seen from the illustration whether the target particle is arranged in the center of the dispensing device, in particular the dispensing channel, or closer to the edge. This is relevant because the speed of the target particle, especially in the case of small target particles, depends on its position in the dispensing device.
- the limit area takes into account hydrodynamic effects that result from the inertia, density, deformability and shape of the particles. To understand this, the idea that a particularly inert particle will only be delayed and move more slowly at the beginning of the flow helps to understand it.
- the buffer area cannot be sharply defined and / or cannot be sharply delimited from the remaining area. It is therefore advantageous to take into account a border area of the buffer area when making the dispensing decision. It can therefore be advantageous to introduce further areas, in particular further boundary areas.
- the dispensing device can have a further area which is arranged upstream of the monitoring area.
- the further area can be at a distance from the buffer area and / or the ejection area.
- the further area cannot be directly adjacent to the ejection area and / or the buffer area.
- part of the remaining area can be arranged between the further area and the monitoring area.
- This further area can, however, also be arranged directly adjacent to the buffer area, in particular the border area.
- the determination device can determine whether a target particle is arranged in the further area. In the event that the particle condition is not met and that a target particle is arranged in the further area, the control device can control the actuation means in such a way that the dispensing time during which the liquid sample is dispensed from the dispensing device is increased. Alternatively or in addition, the output volume can be increased before it is checked again whether the particle condition is met. As an alternative or in addition, the time delay can be increased and / or a predetermined number of output processes can be carried out before it is checked again whether the particle condition is met. All of these methods make use of the knowledge that the liquid samples to be dispensed in the next dispensing processes are of no interest and must therefore be dispensed onto the collecting carrier. Therefore, there is no need for these liquid samples to be dispensed It is time-consuming to determine whether the particle condition is met. As a result, the output operations can be carried out quickly.
- the dispensing device can again be releasably connected to the remaining components of the dispensing device, in particular mechanically. This allows the dispensing device to be exchanged in a simple manner.
- the dispensing device can have the sample deflection mechanism for deflecting the dispensed liquid samples and / or the sample interception mechanism for intercepting the dispensed liquid sample.
- the sample is deflected or intercepted before it hits the target particle carrier.
- the deflection and / or interception of the dispensed liquid sample can depend on whether the particle condition is met.
- a dispensing device which has means by means of which a method according to the invention can be carried out is particularly advantageous.
- a computer program is particularly advantageous which comprises commands which, when the program is executed by a computer, cause the computer to carry out the method according to the invention.
- a data carrier on which the computer program according to the invention is stored is advantageous.
- a data carrier signal that transmits a computer program according to the invention is advantageous.
- FIG. 2 shows part of a dispensing device of the dispensing device according to the invention shown in FIG. 1,
- FIG. 1 shows a schematic representation of a dispensing device 1.
- the dispensing device 1 has a dispensing device 8 by means of which a liquid sample 22 can be dispensed.
- the dispensed liquid sample 22 has a liquid 5 and a single target particle 4.
- the dispensing device 1 has an actuating means 14 that is used to actuate the dispensing device 8.
- the liquid sample 22 is dispensed by the dispensing device 8 in that the actuating means 14 actuates the dispensing device 8.
- the liquid sample 22 can be dispensed onto a target particle carrier 11 or onto a collecting carrier 12.
- the target particle carrier 11 and the collecting carrier 12 are each designed as a container.
- the target particle carrier 11 is in a dispensing position 20 in which it can receive the dispensed liquid sample 20.
- the dispensing device 1 also has a displacement device 16, by means of which the dispensing device 8 and / or the target particle carrier 11 and / or the collecting carrier 12 are moved, as shown by the dashed line.
- the displacement device 16 is electrically connected to a control device 10 of the dispensing device 1. In this case, the control device 10 controls the movement process of the dispensing device 8 and / or the target particle carrier 11 and / or the collecting carrier 12 by means of the movement device 16.
- the dispensing device 1 also has a determination device 2, by means of which it is determined whether a particle condition is met.
- the determination device 2 has an imaging device 23 and an evaluation device 24 and is electrically connected to the control device 10.
- the imaging device 23 generates at least one image of the dispensing device 8, in particular at least part of an output channel 15 of the dispensing device 8.
- the image shows at least one monitoring area 3.
- the imaging device 23 can also generate an image that shows a further area 19. The same image can show both the monitoring area 3 shown in FIG. 2 and the further area 19.
- the light emanating from or received by the imaging device 23 for generating the image is shown in dashed lines.
- the evaluation device 24 evaluates the generated image and transmits the evaluation result to the control device 10.
- the dispensing device 8 has a fluid chamber 21.
- the liquid sample 22 is introduced into the fluid chamber 21 through an opening in the fluid chamber 21.
- the dispensing device 8 has the output channel 15.
- the output channel 15 is fluidically connected to the fluid chamber 21.
- the liquid sample 22 is dispensed from the dispensing device 8 through the dispensing channel 15.
- the dispensing channel 15 and the fluid chamber 21 are delimited by a transparent wall 25 of the dispensing device 8.
- the actuation means 14 and the determination device 12 are opposite one another with respect to the dispensing device 8.
- FIG. 2 shows part of the dispensing device 8 shown in FIG. 1.
- An outlet opening 7 of the dispensing channel 15 is arranged at one end of the dispensing channel 15, which is arranged at a distance from the fluid chamber 21.
- the liquid sample 22 located in the output channel 15 has a liquid 5 and target particles 4. The liquid sample 22 is dispensed from the dispensing channel 15 via the outlet opening 7.
- the monitoring area 3 of the output channel 15 is considered.
- the monitoring area 3 has an ejection area 6 and a buffer area 9.
- the discharge area 6 can contain the outlet opening 7 and comprises the area of the dispensing channel 15, which contains liquid sample 22, which is dispensed during the next dispensing process.
- the ejection region 6 is selected in such a way that it is ensured that the target particles 4 arranged in the ejection region 6 are ejected during the next dispensing process.
- the buffer area 9 corresponds to an area of the discharge channel 15 in which a target particle 4 moves into the discharge area 6 during a time delay between the determination of whether the sample condition is met and the discharge process. The movement of the target particle 4 results, for example, due to the force of gravity.
- the buffer area 9 has a border area 17.
- the border area 17 is arranged at the end of the buffer area 9 remote from the ejection area 6.
- the limit area is the limit area
- the monitoring area 3 is monitored by the determination device 2.
- at least one image of the monitored area 3 is generated by means of the imaging device 23, which is then evaluated by the evaluation device 24.
- a further area 19 of the output channel 15 is considered.
- the further area 19 is arranged upstream of the buffer area 9 and / or the discharge area 6.
- the further area 19 is arranged at a distance from the buffer area 9.
- the further area 19 is separated from the buffer area 9 by part of the remaining area 18.
- the further area 19 is also monitored by the determination device 2. In this case, at least one image of the further area 19 is generated by means of the imaging device 23.
- the further area 19 is not used to determine whether the particle condition is met.
- a target particle 4 is arranged in the ejection region 6.
- another, in particular non-interfering, particle 13 which is not a target particle but, for example, a grain of dust, in the ejection area 6 and the boundary area 17.
- No target particle 4 is arranged in the buffer area 9.
- FIG. 3 shows a flow chart of the method according to the invention.
- the user introduces the liquid sample 22, which has liquid 5 and target particles 4, into the fluid chamber 21.
- the liquid sample 22 partially flows from the fluid chamber 21 into the output channel 15.
- the imaging device 23 determines an image of the monitoring area 3, in particular the ejection area 6 and the buffer area 9.
- a third method step S3 the determination device 2 then determines, based on the generated image, whether a first particle condition is met. In particular, in the third method step S3 it is determined whether a predetermined number of target particles 4, in particular a single target particle 4, is arranged in the buffer region 9 and no target particle 4 is arranged in the ejection region 6. If the first particle condition is met, the control device 10 causes the liquid sample 22 to be dispensed onto the target particle carrier 11 in a fourth method step S4. To this end, the control device 10 can control the displacement device 16 in such a way that the target particle carrier 11 is displaced into the output position 20. The output process then takes place. A new image of the monitored area 3 is then generated again by means of the imaging device 23 in the second method step S2.
- a fifth method step S5 checks whether a second particle condition is fulfilled. In particular, it is checked whether a predetermined number of target particles 4, in particular a single target particle 4, is arranged in the ejection region 6 and no target particle 4 is arranged in the buffer region 9. If the second particle condition is met, the control device 10 causes the liquid sample 22 to be dispensed onto the target particle carrier 11 in the fourth method step S4.
- control device 10 causes the liquid sample 22 to be discharged onto the collecting support 12.
- the control device 10 can control the displacement device 16 in such a way that the collecting carrier 12 is displaced into the output position 20.
- the output process then takes place.
- a new image of the monitored area 3 is then generated again by means of the imaging device 23 in the second method step S2.
- control device 11 target particle carrier 12 collecting carrier
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- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Dispersion Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
LU101494A LU101494B1 (de) | 2019-11-27 | 2019-11-27 | Verfahren zum Dispensieren einer flüssigen Probe mittels einer Dispensiereinrichtung |
PCT/EP2020/083662 WO2021105380A1 (de) | 2019-11-27 | 2020-11-27 | Verfahren zum dispensieren einer flüssigen probe mittels einer dispensiereinrichtung |
Publications (1)
Publication Number | Publication Date |
---|---|
EP4065279A1 true EP4065279A1 (de) | 2022-10-05 |
Family
ID=69158281
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP20811399.3A Withdrawn EP4065279A1 (de) | 2019-11-27 | 2020-11-27 | Verfahren zum dispensieren einer flüssigen probe mittels einer dispensiereinrichtung |
Country Status (6)
Country | Link |
---|---|
US (1) | US20220413002A1 (de) |
EP (1) | EP4065279A1 (de) |
AU (1) | AU2020392521A1 (de) |
CA (1) | CA3158702A1 (de) |
LU (1) | LU101494B1 (de) |
WO (1) | WO2021105380A1 (de) |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011185924A (ja) * | 2010-02-09 | 2011-09-22 | Microjet:Kk | 吐出装置、ヘッドおよびヘッドを用いて吐出する方法 |
DK2577254T3 (en) * | 2010-06-10 | 2015-06-01 | Albert Ludwigs Universität Freiburg | An apparatus and method for delivering cells or particles that are encased in a freely suspended droplet |
US8820538B1 (en) * | 2014-03-17 | 2014-09-02 | Namocell LLC | Method and apparatus for particle sorting |
EP3222353B1 (de) | 2016-03-23 | 2019-04-24 | Scienion AG | Verfahren für einzelpartikeldeposition |
WO2017184776A1 (en) * | 2016-04-22 | 2017-10-26 | Becton, Dickinson And Company | High density deposition for array production |
BR112018074337B1 (pt) * | 2016-07-26 | 2021-05-04 | Hewlett-Packard Development Company, L.P | aparelhos microfluídicos e método |
EP4029939B1 (de) * | 2017-01-30 | 2023-06-28 | 10X Genomics, Inc. | Verfahren und systeme für eine einzelzellbarcodierung auf tröpfchenbasis |
EP3453455B1 (de) * | 2017-09-07 | 2023-11-01 | Scienion GmbH | Verfahren und vorrichtung zur einzelpartikelabscheidung |
LU100777B1 (de) * | 2018-04-23 | 2019-10-23 | Cytena Gmbh | Verfahren zum Untersuchen einer Flüssigkeit, die wenigstens eine Zelle und/oder wenigstens ein Partikel enthält |
LU100778B1 (de) * | 2018-04-23 | 2019-10-23 | Cytena Gmbh | Dispensievorrichtung mit einem Dispenser zum Ausgeben einer wenigstens eine Zelle und/oder wenigstens ein Partikel enthaltenen Flüssigkeit |
-
2019
- 2019-11-27 LU LU101494A patent/LU101494B1/de active IP Right Grant
-
2020
- 2020-11-27 US US17/780,045 patent/US20220413002A1/en active Pending
- 2020-11-27 WO PCT/EP2020/083662 patent/WO2021105380A1/de unknown
- 2020-11-27 AU AU2020392521A patent/AU2020392521A1/en active Pending
- 2020-11-27 EP EP20811399.3A patent/EP4065279A1/de not_active Withdrawn
- 2020-11-27 CA CA3158702A patent/CA3158702A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
US20220413002A1 (en) | 2022-12-29 |
CA3158702A1 (en) | 2021-06-03 |
AU2020392521A1 (en) | 2022-06-30 |
LU101494B1 (de) | 2021-05-28 |
WO2021105380A1 (de) | 2021-06-03 |
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