Pipetting elements, pipetting devices and pipetting kits

Abstract

A pipetting element (100) for use with a pipetting device (300). The pipetting element (100) has at least two wells (104) disposed in or forming a frame (110), the frame (110) configured to be accommodated by the pipetting device (300). Each well (104) is configured to accommodate a pipetting liquid (102) and has a discharge portion (108) disposed on one side of the well (104). The discharge portion (108) is configured to be triggered by the pipetting device (300) to discharge the pipetting liquid (102).

Description

[Technical Field]

[0001] The present invention relates to a pipetting element for use with a pipetting device. The present invention also relates to a pipetting device. The present invention further relates to a pipetting kit. [Background technology]

[0002] Particularly in the field of spatial omics, samples undergo multiple cycles of manipulation and treatment with various reagents to study various biological processes. Reagents can be, for example, probes, antibodies, or chemicals. Reagents are also referred to as markers, especially when they contain fluorophores. An experiment can have multiple cycles of staining and bleaching. Typically, a cycle includes the following steps: In the first part, the sample is stained with one or more reagents by injecting the reagent into the sample, annealing the reagent, and washing the sample with a wash buffer. The sample is then typically imaged using a microscope. In the second part, the sample is bleached by removing markers and / or epitopes from the first stain, and by washing the sample a second time with a wash buffer to remove the used reagents.

[0003] The necessary staining and washing steps are performed manually at the bench or using automated systems such as immunohistochemistry (IHC) stainers. To reduce the time required for sample handling, all-in-one solutions exist that combine the stainer with the microscope.

[0004] In multiplex applications, multiple cycles of staining and bleaching are performed on the same sample, using different reagents in each cycle. In particular, carryover between injections is a major problem in these multiplex applications, because antibodies and other proteins tend to adhere to surfaces, including the inside of injection needles and tubing. This precludes the use of standard injection solutions, which typically use only one injection tube, in multiplex applications.

[0005] Furthermore, for example, in immunofluorescence (IF) staining, the cost of staining solutions is very high because antibodies and stains are very expensive. Standard solutions are not suitable for these applications involving expensive reagents because they use excessive staining solutions per injection. Most of the volumes in standard injection solutions, such as the volumes in tubing and pumps, are dead volumes. In addition, antibodies and IF staining solutions are sensitive to light and temperature, which also precludes most standard injection solutions. Summary of the Invention [Problem to be solved by the invention]

[0006] It is therefore an object to provide a pipetting element and a pipetting device that allows efficient dispensing of samples, especially in multiplex applications. [Means for solving the problem]

[0007] The above-mentioned object is achieved by the subject matter set forth in the independent claims. Advantageous embodiments are defined in the dependent claims and in the following description.

[0008] The proposed pipetting element for use with a pipetting device has at least two wells arranged in or forming a frame. The frame is configured to be accommodated by the pipetting device. Each well is configured to accommodate a pipetting liquid and has a discharge portion arranged on one side of the well. The discharge portion is configured to be triggered by the pipetting device to discharge the pipetting liquid. The wells may be configured to be removable from the frame. The discharge portion is preferably arranged at the bottom of each well.

[0009] Within the context of this specification, dispensing can mean dropping or dispensing a fluid onto a sample, injecting a fluid into a sample, or removing a fluid from a sample or sample carrier. Pipetting elements typically have 6, 12, 24, or 96 wells. However, the number of wells can range from 2 to 384.

[0010] Pipetting fluids, i.e., reagents injected into samples, are stored in individual, separate wells. Therefore, cross-contamination between different pipetting fluids and carryover effects between staining cycles are not an issue with the proposed pipetting element. The pipetting fluids are not guided through pumps and tubing, so the pipetting fluids do not remain in dead volumes, such as pumps or fluid lines. Instead, the contents of the wells are added directly to the sample volume through outlets, as described further below. Individual wells can be partially or completely emptied through the outlets. This facilitates the use of very small volumes of pipetting fluid, such as a few microliters, with the pipetting element. This significantly reduces the cost of experiments involving expensive pipetting fluids, such as antibodies and stains used in immunofluorescence (IF). Furthermore, the pipetting element does not have complex mechanical components and can be manufactured at low cost. This allows the pipetting element to be used as a consumable item, further reducing the risk of cross-contamination and carryover effects and reducing the cost of experiments requiring the pipetting element. Overall, therefore, the proposed pipetting element allows efficient dispensing of samples, especially in multiplex applications.

[0011] In a preferred embodiment, the release is configured to be mechanically triggered by a trigger on the pipetting device or sample carrier to release the pipetting liquid. For example, the release may have a small latch that opens when the release engages with the trigger, thereby releasing the pipetting liquid. Mechanical solutions are simple and reusable, making the pipetting device more cost-effective and versatile.

[0012] In another preferred embodiment, the ejectors each have a membrane configured to be pierced by a piercing element of the pipetting device or sample carrier in order to eject the pipetting liquid. In this embodiment, when the ejectors engage with the piercing element, the membrane holding the pipetting liquid is pierced by the piercing element, thereby ejecting the pipetting liquid. This mechanical embodiment of the ejectors is particularly simple and cost-effective.

[0013] In another preferred embodiment, the discharge portions each have a membrane with a slit configured to release the pipetting liquid when overpressure is applied to the well, or the membrane described above. When no overpressure is applied to the well, the slit is closed and the membrane holds the pipetting liquid. When overpressure is applied to the well, the slit in the membrane opens and the pipetting liquid is released. Therefore, in this embodiment, there is no need to place elements of the pipetting device near the discharge portions, making the pipetting device simpler and less messy. Furthermore, negative pressure can also be applied to the well, and liquid can be aspirated into the well through the slit in the membrane. This allows the pipetting element to be used for both dispensing and removing fluid, making the pipetting element more versatile.

[0014] In another preferred embodiment, the release unit is configured to be triggered by an electrical signal received from the pipetting device to release the pipetting liquid. Alternatively or in addition to a mechanical trigger, the release unit may also be triggered electrically. This allows for very precise control over the release, since the release unit does not need to mechanically engage any element of the pipetting device or sample carrier to release the pipetting liquid. This also allows for triggering the release units in parallel or sequentially in any order, making the pipetting element very flexible. In this embodiment, the release unit can be formed, for example, by an electrically controllable valve, such as a diaphragm valve or an iris valve.

[0015] In another preferred embodiment, the inner surface of at least one well has a functional coating, particularly at least one of a biocoating, a nanocoating, a hydrophobic coating, and a hydrophilic coating. The functional coating can, for example, prevent the pipetting liquid from adhering to the inner surface of the well. This allows more pipetting liquid to be actually dispensed, which is particularly important when the pipetting liquid is very expensive, such as antibodies or IF stains. The functional biocoating can include a protein, e.g., albumin such as bovine serum albumin, which creates an interface between the pipetting liquid and the well, thereby limiting the pipetting liquid's contact with the material from which the well is made. Such a coating can protect the very sensitive and often very expensive pipetting liquid from being damaged.

[0016] In another preferred embodiment, the pipetting element has a lid that is accommodated in the frame and configured to cover some or all of the wells when the lid is accommodated in the frame. The lid may, for example, be a plastic lid configured to cover one or more wells. The lid may also be a foil, such as an aloe foil, a plastic foil, or an aluminum foil. The lid prevents the pipetting liquid from drying out or coming into contact with airborne contaminants. This prevents the pipetting liquid from being damaged.

[0017] In another preferred embodiment, at least one well is configured to be light-tight. Antibodies and IF staining solutions are particularly susceptible to light. Protecting these expensive pipetting solutions from light prevents the pipetting elements from damaging the pipetting solutions, reducing waste and costs, and making dispensing more efficient.

[0018] In another preferred embodiment, the frame is rectangular, and the wells are arranged in a grid pattern within the frame. The frame may have dimensions similar to those of a microwell plate or a standard microwell plate stage insert. This significantly increases the versatility and interoperability of the pipetting element. For example, this allows the pipetting element to be used in a variety of laboratory automation systems designed to use microwell plates.

[0019] In another preferred embodiment, each well has a volume of at least 10 μl and at most 200 μl, preferably at least 25 μl and at most 100 μl. Most applications require a volume of pipetting liquid within the aforementioned range. Therefore, the pipetting element according to this embodiment can be adapted to many applications, making the pipetting element very versatile.

[0020] In another preferred embodiment, each well has an individual identifier. The individual identifier may have any one of the following: color, alphanumeric string, two-dimensional shape, and three-dimensional shape. The individual identifier allows the user to quickly identify the well and its contents, making the pipetting element easier to use. The wells are preferably configured to be removable from the frame, and the frame has a matching identifier indicating a predetermined position for each well within the frame. In this embodiment, the individual identifier also allows the user to quickly place or replace wells in a predetermined position in the frame, facilitating easy operation.

[0021] The present invention also relates to a pipetting device for dispensing samples, comprising at least one pipetting element as described above and a pipetting unit having a sample location configured to accommodate a sample, a storage compartment configured to accommodate a pipetting element, a positioning unit configured to move the pipetting element at least between the storage compartment and the sample location, and a trigger unit configured to trigger the pipetting element to expel pipetting liquid.

[0022] The pipetting device has the same advantages as the pipetting element described above and can be supplemented using the features of the dependent claims directed to the pipetting element.

[0023] In a preferred embodiment, the storage compartment has a temperature control unit configured to control the temperature of the storage compartment. Alternatively or additionally, the storage compartment may have a humidity control unit configured to control the humidity of the storage compartment. Many pipetting solutions are not only light-sensitive, but also have very specific temperature and / or humidity requirements, and can decompose if stored at the wrong temperature and humidity, respectively. Storing pipetting solutions in a controlled environment further reduces waste and improves the efficiency of staining and bleaching cycles. Furthermore, storing reagents in a controlled environment improves the stability of the reagents, allowing for long-term experiments to be performed with the pipetting device.

[0024] In another preferred embodiment, the positioning unit has a movable shelf configured to accommodate the pipetting elements. The positioning unit is configured to move the movable shelf between the storage compartment and the sample location. The positioning unit is preferably configured to fully retract the movable shelf into the storage compartment. The pipetting elements are easy to insert into and remove from the shelf, making the pipetting device very fast and easy to use.

[0025] The trigger unit is preferably configured to individually generate at least one of capillary force, gravity flow, overpressure, and negative pressure in each of the wells of the pipetting element. Generating capillary force, gravity flow, or overpressure in one of the wells causes the pipetting liquid contained in said well to be expelled. Generating negative pressure in one of the wells allows liquid to be aspirated into the well, thereby removing liquid from the sample or sample carrier in which the sample is contained. Other means for dispensing and removing liquid are possible, and the aforementioned means are mentioned only as examples that are particularly easy to implement.

[0026] In another preferred embodiment, the trigger unit has a pressure head configured to be positioned above the sample. The positioning unit is configured to individually position each of the wells of the pipetting element between the pressure head and the sample. The pressure head is further configured to generate overpressure and / or negative pressure in the wells positioned between the pressure head and the sample. In this embodiment, the pressure head is the element of the trigger unit that triggers the ejection part to eject the pipetting liquid. The pipetting liquid is ejected when overpressure is applied to the well. The pipetting liquid is removed from the sample when negative pressure is applied to the well. The pressure head thus provides the pipetting device with a means for dispensing and removing liquid, making the pipetting device extremely versatile.

[0027] In another preferred embodiment, the trigger unit comprises trigger portions configured to individually mechanically trigger each of the discharge portions of the wells of the pipetting element to discharge the pipetting liquid. The mechanical solution for discharging the pipetting liquid is simple and reusable, making the pipetting device more cost-effective and versatile.

[0028] In another preferred embodiment, the trigger unit has a piercing element configured to pierce the membrane of each or the membranes of the discharge portions of the wells of the pipetting element individually to expel the pipetting liquid. In this embodiment, the membrane holds the pipetting liquid until it is pierced by the piercing element. The pierced membrane then allows the pipetting liquid to be dispensed from the well. This is particularly simple and cost-effective.

[0029] In another preferred embodiment, the trigger unit is configured to send an electrical signal to the pipetting element to individually trigger each of the ejectors of the wells of the pipetting element to eject the pipetting liquid. Alternatively or in addition to mechanical triggers, the trigger unit may also be configured to electrically trigger the ejectors. This allows for extremely precise control over the ejection, as the ejectors do not need to mechanically engage with the trigger to eject the pipetting liquid. This further allows for triggering many ejectors in parallel or sequentially in any order, making the pipetting device very versatile.

[0030] In another preferred embodiment, the pipetting device includes at least one sample carrier having at least one sample-receiving compartment configured to receive a sample. The sample location is configured to receive the sample carrier. The positioning unit is configured to selectively position each of the wells of the pipetting element adjacent to and / or above the at least one sample-receiving compartment. The sample-receiving compartment may be any part or element of the sample carrier configured to receive at least one sample. For example, if the sample carrier is formed as a microwell plate, the sample-receiving compartment may be a well of the microwell plate. In this embodiment, the positioning unit is configured to selectively position each of the wells of the pipetting element so that pipetting fluid contained in the well can be dispensed into the sample-receiving compartment. This allows each pipetting fluid contained in the pipetting element to be dispensed into the sample-receiving compartment. This allows a user to select from multiple pipetting fluids in a single experiment or perform multiple cycles of staining and bleaching without refilling the pipetting element, thereby improving the versatility and walk-away time of the pipetting device.

[0031] The sample carrier may preferably have two or more sample-receiving compartments. When the sample carrier has two or more sample-receiving compartments, the positioning unit may be configured to selectively position each of the wells of the pipetting element next to and / or above each of the sample-receiving compartments. In this embodiment, the positioning unit is configured to selectively position each of the wells of the pipetting element so that the pipetting liquid contained in the well can be dispensed into any of the sample-receiving compartments. This allows each pipetting liquid contained in the pipetting element to be dispensed into any of the sample-receiving compartments.

[0032] In another preferred embodiment, the sample carrier has a trigger portion configured to individually mechanically trigger each of the discharge portions of the wells of the pipetting element to release the pipetting liquid, or the trigger portion described above. In this embodiment, the trigger portion is part of the sample carrier itself, and the trigger unit triggers the discharge portions by engaging the discharge portions of the pipetting element with the trigger portion of the sample carrier. Having the trigger portion as part of the sample carrier itself reduces the possibility of mismatch between the position of the discharge portion and the position of the sample-receiving compartment. This embodiment therefore allows for more accurate release of the pipetting liquid.

[0033] The sample carrier preferably has a piercing element or said piercing elements configured to individually pierce the membrane or membranes of each of the discharge parts of the wells of the pipetting element in order to discharge the pipetting liquid. This embodiment of the trigger part is particularly simple and cost-effective.

[0034] In another preferred embodiment, the pipetting device comprises a lid handling unit configured to remove and place lids on the pipetting elements. This further increases the degree of automation of the pipetting device, thereby improving ease of use and walk-away time of the pipetting device. An exemplary lid handling unit is described in EP 4123355 A1.

[0035] In another preferred embodiment, the pipetting unit has a housing. The housing encloses at least the storage compartment. The housing is preferably configured so that the storage compartment is light-tight. The housing protects the storage compartment and the pipetting elements contained therein from the environment. This helps to prevent the pipetting liquid contained in the pipetting elements from being spoiled, thereby reducing waste and increasing the efficiency of the pipetting device. The housing may have a sample location. The housing preferably has an exterior door allowing access to the sample location and / or the storage compartment.

[0036] In another preferred embodiment, the pipetting device has at least one light-tight door arranged between the sample location and the storage compartment, which protects the pipetting elements from light when housed in the storage compartment, thereby preventing light-sensitive reagents from being damaged, especially when the outer door of the housing is open.

[0037] In another preferred embodiment, the pipetting device has a second pipetting unit configured to dispense the sample. The second pipetting unit preferably has a larger capacity for pipetting liquid than the first pipetting unit. The second pipetting unit can be used in particular to dispense at least one wash buffer into the sample. In this embodiment, the pipetting device forms a fully integrated unit, allowing the staining, bleaching, and washing steps to be performed by a single device.

[0038] In another preferred embodiment, the pipetting device has an individual identifier of at least one well of the pipetting element or a read-out unit configured to read out said individual identifier. The individual identifier allows the pipetting device to identify the well and its contents, further increasing the degree of automation of the pipetting device. The individual identifier of the well, e.g., a barcode or number, allows the user to identify the contents of the well. The assignment between the individual identifier and the contents of the well can be stored in a database.

[0039] The invention further relates to a pipetting kit comprising a pipetting element according to any one of claims 1 to 12, wherein at least one of the wells is filled with a pipetting liquid suitable for carrying out a specific sample preparation.

[0040] The pipetting kit has the same advantages as the pipetting element described above and can be supplemented using the features of the dependent claims directed to the pipetting element.

[0041] In a preferred embodiment, the pipetting kit is configured as a one-way consumable. In an alternative embodiment, at least some of the wells are configured to be individually refilled with pipetting fluid appropriate for a particular sample preparation.

[0042] In another embodiment, the pipetting kit includes a plurality of wells, each filled with a respective pipetting fluid and each having a respective identifier. At least some of the plurality of wells are configured to be positioned at predetermined positions in the frame. The frame may have a plurality of identifiers that match the respective identifiers of some of the plurality of wells, each identifier on the frame indicating the predetermined position of the corresponding well. The plurality of wells and the frame are configured to form the pipetting element described above when the plurality of wells are positioned on the frame.

[0043] In another embodiment, the pipetting kit includes a frame having a plurality of identifiers that match the individual identifiers of the plurality of wells, each identifier of the frame indicating a predetermined position of the corresponding well. The plurality of wells and the frame are configured to form the pipetting element described above when the plurality of wells are placed in the frame. In this embodiment, the pipetting kit includes only the frame in which the wells of the pipetting element can be placed.

[0044] In the following, specific embodiments will be described with reference to the drawings. [Brief explanation of the drawings]

[0045] [Figure 1] FIG. 1 is a schematic side view of a pipetting element according to one embodiment. [Figure 2] FIG. 2 is a schematic plan view of the pipetting element according to FIG. 1. [Figure 3] FIG. 1 is a schematic diagram of a pipetting device according to one embodiment. [Figure 4] FIG. 4 is a schematic diagram of the pipetting device according to FIG. 3. [Figure 5] FIG. 5 is a schematic detailed view of the pipetting device according to FIGS. 3 and 4. [Figure 6] FIG. 6 is a schematic plan view of the pipetting device according to FIGS. 3 to 5. [Figure 7] 7 is a flow chart of a method of preparing a sample that can be performed using the pipetting device according to FIGS. 3 to 6. DETAILED DESCRIPTION OF THE INVENTION

[0046] FIG. 1 is a schematic side view of a pipetting element 100 according to one embodiment.

[0047] The pipetting element 100 is configured to store different pipetting liquids 102 and to release the pipetting liquids 102 onto a sample or sample carrier 304 (see FIG. 3). The pipetting liquids 102 may be reagents, such as probes, antibodies, or chemicals. The pipetting liquid 102 may also comprise a combination of affinity reagents and fluorophores, referred to as a marker or staining solution. The pipetting liquid 102 may also be a wash buffer configured to wash the aforementioned reagents, markers, and staining solutions from the sample.

[0048] The pipetting element 100 has separate wells 104. Each well 104 is configured to contain one of the pipetting liquids 102. In FIG. 1, only the leftmost well 104 is illustratively filled with the pipetting liquid 102. The wells 104 have a volume of at least 10 μL and at most 200 μL. The wells 104 may have a functional coating on their inner surfaces 106, for example, to prevent the pipetting liquid 102 from adhering to the inner surfaces 106. Each of the wells 104 has a discharge 108 illustratively located at the bottom of the well 104. The discharge 108 of each well 104 can be individually triggered to discharge the liquid contained in the well 104.

[0049] The pipetting element 100 further comprises a frame 110 in which the wells 104 are arranged. The frame 110 is configured to be housed in a pipetting device 300 (see FIG. 2 ). This allows the pipetting element 100 to be filled with pipetting liquid 102 outside of the pipetting device 300. The wells 104 may be removable from the frame 110, allowing the wells 104 to be individually removed from the frame 110, for example, in order to fill the removed well 104 with one of the pipetting liquids 102.

[0050] The lids 112 of the pipetting element 100 are configured to cover the wells 104. In this embodiment, the lids 112 are exemplarily formed as plastic or glass lids that cover all of the wells 104 at once. The lids 112 prevent the pipetting liquid 102 from drying out or coming into contact with environmental contaminants. In other embodiments, the lids 112 may be configured to cover only some of the wells 104 or individual wells 104. In another embodiment, the wells 104 may have individual lids. The lids 112 may be formed of foil, such as aloe foil, plastic foil, or aluminum foil.

[0051] FIG. 2 is a schematic plan view of the pipetting element 100 according to FIG.

[0052] A membrane 200 is disposed at the bottom of each well 104. The membrane 200 has a slit 202 that is closed as long as the pressure inside the well 104 is approximately equal to the pressure outside the well 104. As long as the slit 202 is closed, the pipetting liquid 102 contained in the well 104 is held back by the membrane 200. The slit 202 can be opened by applying overpressure to the well 104. When the slit 202 opens, the liquid contained in the well 104 is released.

[0053] As can be seen in FIG. 2 , the frame 110 has a rectangular shape, and the wells 104 are arranged in a grid pattern within the frame 110. Each well 104 has a predetermined position within the frame 110. To facilitate accurate assembly of the pipetting device 300, each well 104 has an individual identifier 204a that matches another identifier 204b located at the frame 110 at the well's predetermined position. The individual identifier 204a of each well 104 can also encode information about the pipetting fluid 102 contained in the well 104. The individual identifiers 204a, 204b may have any one of the following characteristics: color, alphanumeric string, two-dimensional shape, and three-dimensional shape. In particular, the individual identifiers 204a, 204b may be machine-readable so that a readout unit of the pipetting device 300 can identify the individual wells 104. For clarity, only one pair of individual identifiers 204a, 204b is shown.

[0054] FIG. 3 is a schematic diagram of a pipetting device 300 according to one embodiment.

[0055] The pipetting device 300 has a sample position 302 for a sample carrier 304. The sample carrier 304 has a sample-receiving compartment 306 configured to receive a sample. In FIG. 3, the sample-receiving compartment 306 is illustratively formed between a microscope slide placed on the sample carrier 304 and a cover slip 307. The sample carrier 304 has an inlet 308 for introducing the pipetting liquid 102 into the sample-receiving compartment 306. The inlet 308 has a lip 310, illustratively formed by an O-ring, configured to engage with the outlet 108 of the pipetting element 100 and to form a seal when engaged with the outlet 108. This seal prevents the pipetting liquid 102 from spilling when the pipetting liquid 102 is introduced into the sample-receiving compartment 306 via the inlet 308. The sample carrier 304 further has a vent port 312 through which gas, e.g., air, can escape from the sample-receiving compartment 306 when the pipetting liquid 102 is introduced into the sample-receiving compartment 306. The inlet 308 and the vent port 312 are each connected to the sample-receiving compartment 306 by a fluid flow path 314.

[0056] The storage compartment 316 of the pipetting device 300 is located to the right of the sample position 302 in FIG. 3 . The storage compartment 316 is surrounded by a housing 318 and configured to house the pipetting element 100. A door 320 is located to the left of the storage compartment 316 in FIG. 3 and provides access to the storage compartment 316. The door 320 may, in particular, be a sliding door. The storage compartment 316 further includes a temperature and humidity control unit 322 configured to control the temperature and humidity inside the enclosed storage compartment 316. Maintaining the pipetting element 100 and the liquid 102 stored therein in a controlled environment prevents the pipetting liquid 102 from being damaged and enables long-term experiments to be performed. In FIG. 3 , the pipetting element 100 is located inside the storage compartment 316.

[0057] The pipetting device 300 also includes a trigger unit 324 configured to trigger the ejection portions 108 of the individual wells 104. The trigger unit 324 illustratively includes a pressure head 326 connected to a pressure generation unit 328 by a pressure line 330. In this embodiment, the trigger unit 324 is illustratively configured to generate an overpressure in the wells 104 located below the pressure head 326. The overpressure ejects the pipetting liquid 102. The trigger unit 324 is further configured to generate a negative pressure in the wells 104 located below the pressure head 326, thereby drawing liquid located in the sample-receiving compartments 306 into the wells 104. The pressure head 326 includes a lip 332, illustratively formed by an O-ring, that forms a seal with the top of the wells 104 when engaged with the pressure head 326. The readout unit 334 of the pipetting device 300 is illustratively positioned on the pressure head 326 and may be configured to identify whether the well 104 is properly positioned underneath and / or to read out the identifier of the well 104.

[0058] The positioning unit 336 of the pipetting device 300 has a movable shelf 338 configured to accommodate the pipetting elements 100. The positioning unit 336 is configured to move the shelf 338 and the pipetting elements 100 accommodated therein between the storage compartment 316 and the sample location 302. The positioning unit 336 is further configured to position each of the wells 104 of the pipetting element 100 between the pressure head 326 of the trigger unit 324 and the inlet 308 of the sample carrier 304. This allows the positioning unit 336 to select which wells 104 are to engage with the inlet 308, for example, to inject a particular pipetting liquid 102 into the sample-receiving compartment 306. The extent of the positioning unit 336 is indicated by a dashed rectangle in FIG. 3 .

[0059] The pipetting device 300 further comprises a controller 340 connected to the temperature and humidity control unit 322, the trigger unit 324 and the positioning unit 336 and configured to control the aforementioned elements. The controller 340 is further connected to a user input device 342 and configured to receive user input from a user via the user input device 342. The controller 340 is particularly configured to implement a method for preparing a sample contained in the sample-receiving compartment 306. The method is described below with reference to Figure 7.

[0060] FIG. 4 is a schematic diagram of the pipetting device 300 according to FIG.

[0061] In Fig. 4, the pipetting element 100 is positioned at the sample position 302. The door 320 of the storage compartment 316 is open, allowing the positioning unit 336 to move the pipetting element 100 to the sample position 302 or back to the storage compartment 316. One of the wells 104 of the pipetting element 100 is positioned between the pressure head 326 of the trigger unit 324 and the inlet 308 of the sample carrier 304, as will be explained in more detail below with reference to Fig. 5.

[0062] FIG. 5 is a schematic detailed view of the pipetting device 300 according to FIGS.

[0063] 5, a pressure head 326 is engaged with the top of one of the wells 104. A lip 332 of the pressure head 326 forms a seal between the pressure head 326 and the well 104. The outlet 108 of the well 104 engages with a lip 310 of the sample carrier 304 to form a seal. When an overpressure is created in the well 104 by the pressure head 326, the slit 202 of the well 104 opens and the pipetting liquid 102 contained in the well 104 is injected into the sample-receiving compartment 306 via the inlet 308.

[0064] FIG. 6 is a schematic plan view of the pipetting device 300 according to FIGS.

[0065] The positioning unit 336 of the pipetting device 300 is configured to move the pipetting element 100 in two vertical directions, as indicated by the two double-headed arrows P1 and P2 in Fig. 6. This allows the positioning unit 336 to position each of the wells 104 of the pipetting element 100 between the pressure head 326 of the trigger unit 324 and the inlet 308 of the sample carrier 304.

[0066] FIG. 7 is a flow chart of a method of preparing a sample that can be performed using the pipetting device 300 according to FIGS.

[0067] In step S700, the process begins. In step S702, a user fills the pipetting element 100 with one of the pipetting fluids 102 by filling at least some of the wells 104 with one of the pipetting fluids 102. Preferably, this step is performed outside the pipetting device 300, for example, at a work bench. Optionally, this step involves covering the pipetting element 100 with the lid 112. In step S704, the user issues a command to the pipetting device 300 via the user input device 342 to load the pipetting element 100. In response to the command, the controller 340 controls the positioning unit 336 to move the shelf 338 from the storage compartment 316 to the sample position 302, allowing the user to load the pipetting element 100 onto the shelf 338. Once the pipetting element 100 is positioned on the shelf 338, the user gives another command via the user input device 342 to retract the shelf 338 into the storage compartment 316. In response to the second command, the controller 340 controls the positioning unit 336 to move the shelf 338 back into the storage compartment 316. In step S706, the user inputs to the controller 340 via the user input device 342 the amount and type of pipetting fluid 102 to be contained in each of the wells 104. Alternatively, the information can be provided to the pipetting device 300 via a network or wireless connection to a server.

[0068] In step S708, the user loads a sample carrier 304 with a sample into the pipetting device 300. In step S710, the user inputs a pipetting program into the controller 340 via the user input device 342. The pipetting program defines the amount, type, and sequence in which the pipetting liquid 102 is dispensed into the sample carrier 304. The pipetting program may also specify that the liquid be aspirated back into one of the wells 104 at a specific time. In step S712, the pipetting program is executed by the pipetting device 300. The process ends in step S714.

[0069] In all figures, identical or similarly operating elements are marked with the same reference numerals. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ". All individual features of the embodiments and combinations of individual features of the embodiments are considered to be disclosed both in combination with each other and with any individual feature or group of features in the preceding description and / or claims.

[0070] While some aspects have been described in the context of an apparatus, it will be apparent that these aspects also represent a description of a corresponding method, where a block or apparatus corresponds to a step or feature of a step, and similarly, aspects described in the context of a step also represent a description of a corresponding block or item or feature of a corresponding apparatus. [Explanation of symbols]

[0071] 100 pipetting elements 102 Pipetting Fluid 104 wells 106 Inside 108 Emission part 110 frames 112 Lid 200 membrane 202 Slit 204a,204b Identifier 300 Pipetting Device 302 sample positions 304 Sample Carrier 306 Sample Containment Area 307 Cover Glass 308 Inlet 310 Lip 312 Gas vent 314 Fluid Flow Path 316 Storage Area 318 Housing 320 doors 322 Control Unit 324 Trigger Unit 326 pressure head 328 Pressure Generation Unit 330 Pressure Pipeline 332 Lip 334 Readout Unit 336 Positioning Unit 338 Shelf 340 Controller 342 Input Device P1,P2 arrows

Claims

1. A pipetting element (100) for use with a pipetting device (300), comprising: the pipetting element (100) has at least two wells (104) arranged in or forming a frame (110), the frame (110) being configured to be received by the pipetting device (300); Each well (104) is configured to contain a pipetting liquid (102) and has a discharge (108) located on one side of the well (104), the discharge (108) being configured to be triggered by the pipetting device (300) to discharge the pipetting liquid (102). A pipetting element (100).

2. the ejection portion (108) is configured to be mechanically triggered by a trigger portion of the pipetting device (300) or a sample carrier (304) to eject the pipetting liquid (102); The pipetting element (100) of claim 1.

3. the discharge portions (108) each have a membrane (200) configured to be pierced by a piercing element of the pipetting device (300) or a sample carrier (304) to expel the pipetting liquid (102); The pipetting element (100) according to claim 1 or 2.

4. The ejection portions (108) each have a membrane (200) or membrane (200) with a slit (202) configured to eject the pipetting liquid (102) when overpressure is applied to the well (104). A pipetting element (100) according to any one of claims 1 to 3.

5. the ejection portion (108) is configured to be triggered by an electrical signal received from the pipetting device (300) to eject the pipetting liquid (102); A pipetting element (100) according to any one of claims 1 to 4.

6. the inner surface (106) of at least one of the wells (104) has a functional coating, in particular at least one of a biocoating, a nanocoating, a hydrophobic coating and a hydrophilic coating; A pipetting element (100) according to any one of claims 1 to 5.

7. The pipetting element (100) has a lid (112) that is configured to be received in the frame (110) and to cover some or all of the wells (104) when the lid (112) is received in the frame (110). A pipetting element (100) according to any one of claims 1 to 6.

8. At least one of the wells (104) is configured to be light-tight. A pipetting element (100) according to any one of claims 1 to 7.

9. The frame (110) is rectangular, and the wells (104) are arranged in a grid pattern inside the frame (110). A pipetting element (100) according to any one of claims 1 to 8.

10. Each well (104) has a volume of at least 10 μl and at most 200 μl, preferably at least 25 μl and at most 100 μl; A pipetting element (100) according to any one of claims 1 to 9.

11. Each of the wells (104) has an individual identifier (204). A pipetting element (100) according to any one of claims 1 to 10.

12. A pipetting device (300) for dispensing a sample, said pipetting device (300) comprising: At least one pipetting element (100) according to any one of claims 1 to 11, a pipetting unit having a sample position (302) configured to receive said sample; a storage compartment (316) configured to accommodate said pipetting element (100); a positioning unit (336) configured to move the pipetting element (100) at least between the storage compartment (316) and the sample location (302); a trigger unit (324) configured to trigger the pipetting element (100) to release the pipetting liquid (102); A pipetting device (300) having:

13. The storage compartment (316) has a temperature control unit (322) configured to control the temperature of the storage compartment (316). The pipetting device (300) of claim 12.

14. The storage compartment (316) has a humidity control unit (322) configured to control the humidity of the storage compartment (316). A pipetting device (300) according to claim 12 or 13.

15. the positioning unit (336) has a movable shelf (338) configured to accommodate the pipetting element (100), and the positioning unit (336) is configured to move the movable shelf (338) between the storage compartment (316) and the sample location (302); A pipetting device (300) according to any one of claims 12 to 14.

16. the trigger unit (324) is configured to individually generate at least one of capillary force, gravity flow, overpressure, and underpressure in each of the wells (104) of the pipetting element (100); A pipetting device (300) according to any one of claims 12 to 15.

17. the trigger unit (324) has a pressure head (326) configured to be placed above the sample, the positioning unit (336) configured to individually position each of the wells (104) of the pipetting element (100) between the pressure head (326) and the sample, and the pressure head (326) configured to generate overpressure and / or underpressure in the wells (104) positioned between the pressure head (326) and the sample. The pipetting device (300) of claim 16.

18. the trigger unit (324) has trigger portions configured to individually mechanically trigger each of the discharge portions (108) of the wells (104) of the pipetting element (100) to discharge the pipetting liquid (102); A pipetting device (300) according to any one of claims 12 to 17.

19. the trigger unit (324) has a piercing element configured to pierce the membrane (200) of each of the discharge portions (108) of the wells (104) of the pipetting element (100) individually to eject the pipetting liquid (102); A pipetting device (300) according to any one of claims 12 to 18.

20. the trigger unit (324) is configured to send an electrical signal to the pipetting element (100) to individually trigger each of the discharge portions (108) of the wells (104) of the pipetting element (100) to discharge the pipetting liquid (102). A pipetting device (300) according to any one of claims 12 to 19.

21. the pipetting device (300) has at least one sample carrier (304) having at least one sample receiving compartment (306) configured to receive a sample, the sample location (302) is configured to receive the sample carrier (304), and the positioning unit (336) is configured to selectively position each of the wells (104) of the pipetting element (100) next to and / or above the at least one sample receiving compartment (306); A pipetting device (300) according to any one of claims 12 to 20.

22. the sample carrier (304) has a trigger portion or trigger portions configured to individually mechanically trigger the ejection portions (108) of each of the wells (104) of the pipetting element (100) to eject the pipetting liquid (102); 22. The pipetting device (300) of claim 21.

23. the sample carrier (304) has a piercing element (304) configured to pierce the membrane (200) or the membrane (200) individually of each of the discharge portions (108) of the wells (104) of the pipetting element (100) in order to discharge the pipetting liquid (102), 23. A pipetting device (300) according to claim 21 or 22.

24. The pipetting unit has a housing (318) that surrounds at least the storage compartment (316). A pipetting device (300) according to any one of claims 12 to 23.

25. The housing (318) is configured to provide a light-tight seal to the storage compartment (316).

25. The pipetting device (300) of claim 24.

26. The pipetting device (300) has at least one light-tight door (320) disposed between the sample location (302) and the storage compartment (316). A pipetting device (300) according to any one of claims 12 to 25.

27. the pipetting device (300) having a second pipetting unit configured to dispense the sample; A pipetting device (300) according to any one of claims 12 to 26.

28. the pipetting device (300) comprises an individual identifier (204) of at least one of the wells (104) of the pipetting element (100) or a read-out unit (334) configured to read out the identifier (204); A pipetting device (300) according to any one of claims 12 to 27.

29. A pipetting kit comprising a pipetting element (100) according to any one of claims 1 to 11, At least one of the wells (104) is filled with a pipetting liquid (102) suitable for carrying out a particular sample preparation; Pipetting kit.

30. The pipetting kit is configured as a one-way consumable item.

30. The pipetting kit of claim 29.

31. At least some of the wells (104) are configured to be individually refilled with a pipetting fluid (102) suitable for performing a particular sample preparation.

30. The pipetting kit of claim 29.

32. A pipetting kit having a plurality of wells (104), Each of the wells (104) is filled with a respective pipetting liquid (102), each of the wells (104) has a respective identifier (204), at least a portion of the plurality of wells (104) is configured to be arranged at a predetermined position in a frame (110), the frame (110) has a plurality of identifiers (204) that match the respective identifiers (204) of the portion of the plurality of wells (104), each identifier (204) of the frame (110) indicating the predetermined position of the corresponding well (104), and the plurality of wells (104) and the frame (110) are configured to form a pipetting element (100) according to any one of claims 1 to 11 when the plurality of wells (104) is arranged in the frame (110). Pipetting kit.

33. A pipetting kit having a frame (110), The frame (110) has a plurality of identifiers (204) that match the individual identifiers (204) of the plurality of wells (104), each identifier (204) of the frame (110) indicating a predetermined position of the corresponding well (104), and the plurality of wells (104) and the frame (110) are configured to form a pipetting element (100) according to any one of claims 1 to 11 when the plurality of wells (104) are arranged on the frame (110). Pipetting kit.

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