Pipetting element, pipetting device and pipetting kit

By designing a pipetting element with a release part, the problem of injection residues during sample staining and bleaching in multiple applications is solved, and efficient and low-cost sample removal is achieved, reducing experimental costs and cross-contamination risks.

CN119947828APending Publication Date: 2025-05-06LEICA MICROSYSTEMS CMS GMBH
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Patent Information

Application Number
CN202280100928.X
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2022-08-19
Publication Date
2025-05-06

AI Technical Summary

Technical Problem

In multiple applications, especially in the field of spatial omics, samples are prone to residual between injections during multiple cycles of staining and bleaching, resulting in antibodies and other proteins adhering to the inside of the injection needle and tube, increasing experimental costs and risk of cross-contamination.

Method used

A pipetting element for use with a pipetting device is designed, which comprises at least two bore chambers arranged in the frame, each bore chamber is equipped with a release section to remove the sample at low cost and high efficiency through the trigger release section of the pipetting device, avoiding dead volume and residual problems.

Benefits of technology

It realizes efficient sample transfer in multiple applications, reduces the use of expensive reagents, reduces experimental costs and cross-contamination risks, and at the same time, the manufacturing cost of pipetting components is also low due to the absence of complex mechanical components.

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Abstract

A pipetting element (100) for use with a pipetting device (300). The pipetting element (100) comprises at least two apertures (104) arranged in or forming a frame (110), the frame (110) being configured to be received by a pipetting device (300). Each aperture chamber (104) is configured to receive a pipetting liquid (102) and has a release portion (108) disposed on one side of the aperture chamber (104). The release portion (108) is configured to be triggered by the pipetting device (300) to release the pipetting liquid (102).
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Description

Technical Field

[0001] The present invention relates to a pipetting element used with a pipetting device, a pipetting device and a pipetting kit. Background Art

[0002] In particular, in the field of spatial omics, in order to study various biological processes, samples are subjected to multiple cycles of manipulation and treatment using various reagents. Reagents are, for example, probes, antibodies or chemicals. In particular, when the reagents include fluorophores, the reagents are also referred to as markers. A single experiment may include multiple cycles of staining and bleaching. Typically, the cycle includes the following steps: in the first part, the sample is stained with one or more reagents by injecting the reagents into the sample, annealing the reagents 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 the markers and / or exposed epitopes from the first staining and washing the sample a second time with a wash buffer to remove the used reagents.

[0003] The required staining and washing steps can be performed manually on the bench or using an automated system such as an immunohistochemistry (IHC) stainer. All-in-one solutions exist that combine stainers with microscopes to reduce the time required to process samples.

[0004] In multiplex applications, multiple cycles of staining and bleaching are performed on the same sample, with different reagents used in each cycle. Especially in these multiplex applications, carryover between injections is a big problem, as antibodies and other proteins tend to stick to surfaces such as the inside of the injection needle and syringe. This precludes the use of standard injection solutions, which are usually used with only one syringe, in multiplex applications.

[0005] Furthermore, in immunofluorescence (IF) staining, for example, 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 too much staining solution per injection. Most of the volume in standard injection solutions is dead volume, such as in tubing and pumps. In addition, antibodies and IF staining solutions are sensitive to light and temperature, which also rules out most standard injection solutions. Summary of the invention

[0006] It is therefore an object of the present invention to provide a pipetting element and a pipetting device which enable efficient pipetting of samples, in particular in multiplex applications.

[0007] The above objects are achieved by the subject-matter of 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 comprises at least two pore chambers arranged in a frame or forming a frame. The frame is configured to be received by the pipetting device. Each pore chamber is configured to receive a pipetting liquid and has a release portion arranged on one side of the pore chamber. The release portion is configured to be triggered by the pipetting device to release the pipetting liquid. The pore chamber can be configured to be detachable from the frame. The release portion is preferably arranged at the bottom of each pore chamber thereof.

[0009] In the context of this article, liquid transfer can mean that fluid is dripped onto or distributed on sample, fluid is injected into sample or takes out fluid from sample or sample carrier. Liquid transfer element has 6,12,24 or 96 pore chambers usually. However, the number of pore chambers can be between 2 and 384.

[0010] The liquid transfer liquid, i.e. the reagent to be injected into the sample, is stored in each different well chamber. Therefore, cross contamination between different liquid transfer liquids and residues between dyeing cycles are not a problem for the proposed liquid transfer element. The liquid transfer liquid is not guided by a pump and a pipeline, so there is no liquid transfer liquid residue at a dead volume such as a pump or a fluid line. On the contrary, the material in the well chamber is directly applied to the sample volume by a release portion, as further described below. Each well chamber can be partially or completely emptied by a release portion. Therefore, the liquid transfer element can more easily use a very small amount of liquid transfer liquid, such as as low as a few microliters. This significantly reduces the cost of experiments using expensive liquid transfer liquids (such as antibodies and stains used in immunofluorescence (IF)). In addition, the liquid transfer element does not include complex mechanical parts and can be manufactured at low cost. This makes the liquid transfer element usable as a consumable, thereby further reducing the risk of cross contamination and residue, and reducing the cost of experiments involving the liquid transfer element. Therefore, in general, the proposed liquid transfer element can achieve effective transfer of samples, especially in multiple applications.

[0011] In a preferred embodiment, the release portion is configured to be mechanically triggered by a trigger portion of the pipetting device or sample carrier to release the pipetting liquid. For example, the release portion may include a small latch that opens to release the pipetting liquid when the release portion engages with the trigger portion. The mechanical solution is simple and reusable, making the pipetting device more cost-effective and versatile.

[0012] In another preferred embodiment, the release parts each include a membrane, which is configured to be pierced by a piercing element of a pipetting device or a sample carrier to release the pipetting liquid. In this embodiment, when the release part is engaged with the piercing element, the membrane blocking the pipetting liquid is pierced by the piercing element, thereby releasing the pipetting liquid. This mechanical embodiment of the release part is particularly simple and cost-effective.

[0013] In another preferred embodiment, the release portion each includes a film of a slit, which is configured to release the liquid transfer when an overpressure is applied to the pore chamber. When no overpressure is applied to the pore chamber, the slit is closed and the film blocks the liquid transfer. When an overpressure is applied to the pore chamber, the slit in the film opens and releases the liquid transfer. Therefore, this embodiment requires that the elements of the liquid transfer device are not arranged near the release portion, making the liquid transfer device simpler and less messy. In addition, negative pressure can be applied to the pore chamber, thereby allowing liquid to be sucked into the pore chamber via the slit in the film. This makes the liquid transfer element can be used to distribute and remove fluids, thereby making the liquid transfer element more versatile.

[0014] In another preferred embodiment, the release portion is configured to be triggered by an electrical signal received from the pipetting device to release the pipetting liquid. As an alternative or supplement to the mechanical trigger, the release portion can also be electrically triggered. This allows very precise control of the release, because the release portion does not need to be mechanically engaged with any element of the pipetting device or sample carrier to release the pipetting liquid. This also allows the release portion to be triggered simultaneously or continuously in any order, so that the pipetting element has a strong flexibility. In this embodiment, the release portion can be formed, for example, by an electrically controlled valve (such as a diaphragm valve or an iris valve).

[0015] In another preferred embodiment, the inner surface of at least one of the wells comprises a functional coating, in particular 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 (e.g., antibodies or IF stains). The functional biocoating can include proteins, such as albumin (e.g., bovine serum albumin), which forms an interface between the pipetting liquid and the well, thereby limiting the contact of the pipetting liquid with the materials used in the well. Such a coating can protect very sensitive and usually very expensive pipetting liquids from deterioration.

[0016] In another preferred embodiment, the liquid transfer element comprises a cover, which is configured to be received on the frame, and the cover covers part or all of the wells when received on the frame. The cover can be, for example, a plastic cover, which is configured to cover one or more wells. The cover can also be a foil, such as aloe foil, plastic foil or aluminum foil. The cover prevents the liquid transfer from drying out or coming into contact with pollutants in the air. Therefore, the cover prevents the liquid transfer from deteriorating.

[0017] In another preferred embodiment, at least one of the wells is configured to be light-tight. In particular, antibodies and IF staining solutions are light-sensitive. By protecting these expensive pipetting liquids from light, the pipetting element can prevent the pipetting liquid from deteriorating, thereby making pipetting more efficient by reducing waste and costs.

[0018] In another preferred embodiment, the frame is rectangular and the wells are arranged in a grid-like manner within the frame. In particular, the frame can have the dimensions of a microplate or a standard microplate stage insert. This greatly 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 microplates.

[0019] In another preferred embodiment, the capacity of each well chamber is at least 10μl and at most 200μl, preferably at least 25μl and at most 100μl. Most applications require a pipetting volume within the above range. Therefore, the pipetting element according to this embodiment is compatible with a large number of applications, making it very versatile.

[0020] In another preferred embodiment, each well chamber includes an individual identifier. The individual identifier may include any of the following: a color, an alphanumeric string, a two-dimensional shape, and a three-dimensional shape. The individual identifier allows the user to quickly identify the well chamber and its contents, making the pipetting element easier to use. Preferably, the well chamber is configured to be detachable from the frame, and the frame includes a matching identifier to indicate the predetermined position of each well chamber within the frame. In this embodiment, the individual identifier also allows the user to quickly arrange or exchange the well chamber in its predetermined position in the frame, thereby facilitating operation.

[0021] The present invention also relates to a pipetting device for transferring a sample, comprising at least one pipetting element as described above, and a pipetting unit. The pipetting unit comprises a sample position configured to receive the sample, a storage compartment configured to receive the pipetting element, a positioning unit configured to move the pipetting element at least between the storage compartment and the sample position, and a trigger unit configured to trigger the pipetting element to release the pipetting liquid.

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

[0023] In a preferred embodiment, the storage compartment includes a temperature control unit configured to control the temperature of the storage compartment. Alternatively, or additionally, the storage compartment may include a humidity control unit configured to control the humidity of the storage compartment. Many pipetting liquids are not only sensitive to light, but also have very specific temperature and / or humidity requirements, and they may decompose when the temperature and humidity in storage are not suitable. By storing the pipetting liquid in a controlled environment, waste can be further reduced and the efficiency of the staining and bleaching cycles can be further improved. In addition, storing the reagents in a controlled environment can improve the stability of the reagents, thereby allowing long-term experiments using the pipetting device.

[0024] In another preferred embodiment, the positioning unit comprises a movable shelf configured to receive the liquid transfer element. The positioning unit is configured to move the movable shelf between the storage compartment and the sample position. Preferably, the positioning unit is configured to fully retract the movable shelf into the storage compartment. The liquid transfer element can be easily inserted into and removed from the shelf, making the use of the liquid transfer device very quick and convenient.

[0025] Preferably, the trigger unit is configured to generate at least one of capillary force, gravity flow, overpressure and negative pressure in each well of the pipetting element. By generating capillary force, gravity flow or overpressure in one of the wells, the pipetting liquid received in this well is released. By generating negative pressure in one of the wells, the liquid can be sucked into the well, thereby removing it from the sample or the sample carrier receiving the sample. Other ways of distributing and removing liquids are also possible, and the above-mentioned ways are only mentioned as examples that are particularly easy to implement.

[0026] In another preferred embodiment, the trigger unit includes a pressure head configured to be arranged on top of the sample. The positioning unit is configured to position each well of the pipetting element between the pressure head and the sample individually. In addition, the pressure head is configured to generate an overpressure and / or negative pressure in the well between the pressure head and the sample. In this embodiment, the pressure head is an element of the trigger unit, which triggers the release portion to release the pipetting liquid. When an overpressure is applied in the well, the pipetting liquid is released. When a negative pressure is applied in the well, the pipetting liquid is removed from the sample. Therefore, the pressure head provides a means for distributing and removing liquids for the pipetting device, so that the pipetting device has stronger versatility.

[0027] In another preferred embodiment, the trigger unit comprises a trigger part configured to mechanically trigger each release part of the well chamber of the pipetting element to release the pipetting liquid individually. The mechanical solution for releasing the pipetting liquid is simple and reusable, making the pipetting device more cost-effective and versatile.

[0028] In another preferred embodiment, the trigger unit comprises a piercing element configured to pierce the membrane of each release portion of the pore chamber of the pipetting element individually in order to release the pipetting liquid. In this embodiment, the membrane blocks the pipetting liquid until it is pierced by the piercing element. The pierced membrane then allows the pipetting liquid to be dispensed from its pore chamber. 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 release in the pore chamber of the pipetting element to release the pipetting liquid. As an alternative or supplement to the mechanical trigger, the trigger unit can also be configured to electrically trigger the release. This allows very precise control of the release because the release does not need to be mechanically engaged with the trigger to release the pipetting liquid. This also allows many releases to be triggered simultaneously or continuously in any order, so that the pipetting device has a strong flexibility.

[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 position is configured to receive the sample carrier. The positioning unit is configured to selectively position each well of the pipetting element next to and / or above the at least one sample receiving compartment. The sample receiving compartment can be any part or element of the sample carrier that is configured to receive at least one sample. For example, when the sample carrier is formed as a microplate, the sample receiving compartment can be a well of the microplate. In this embodiment, the positioning unit is configured to selectively position each well of the pipetting element so that the pipetting liquid contained therein can be distributed into the sample receiving compartment. Therefore, each pipetting liquid received in the pipetting element can be distributed into the sample receiving compartment. This allows the user to select from a large number of pipetting liquids in a single experiment, or to perform multiple cycles of staining and bleaching without refilling the pipetting element, thereby increasing the versatility and unattended time of the pipetting device.

[0031] Preferably, the sample carrier may include more than two sample receiving compartments. When the sample carrier includes more than one sample receiving compartment, the positioning unit may be configured to selectively position each well of the pipetting element beside and / or above each sample receiving compartment. In this embodiment, the positioning unit is configured to selectively position each well of the pipetting element so that the pipetting liquid contained therein can be dispensed into any sample receiving compartment. Therefore, each pipetting liquid received in the pipetting element can be dispensed into any sample receiving compartment.

[0032] In another preferred embodiment, the sample carrier includes a trigger portion, which is configured to mechanically trigger each release portion of the well chamber of the pipetting element individually to release the pipetting liquid. In this embodiment, the trigger portion is part of the sample carrier itself, and the trigger unit triggers the release portion by engaging the release portion of the pipetting element with the trigger portion of the sample carrier. The use of the trigger portion as part of the sample carrier itself reduces the possibility of mismatch between the position of the release portion and the position of the sample receiving compartment. Therefore, this embodiment allows for more accurate release of the pipetting liquid.

[0033] Preferably, the sample carrier comprises a piercing element which is configured to pierce the membrane of each release portion of the well of the pipetting element individually to release the pipetting liquid.This embodiment of the trigger portion is particularly simple and cost-effective.

[0034] In another preferred embodiment, the pipetting device comprises a cap handling unit configured to remove the cap from the pipetting element and to place the cap on the pipetting element. This further increases the degree of automation of the pipetting device, thereby increasing the ease of use and unattended time of the pipetting device. An exemplary cap handling unit is described in European patent application No. EP21186397.

[0035] In another preferred embodiment, the pipetting unit comprises a housing. The housing at least surrounds the storage compartment. Preferably, the housing is formed so that the storage compartment is opaque. The housing protects the storage compartment and the pipetting element received therein from environmental influences. This helps to prevent the pipetting liquid contained in the pipetting element from deteriorating, thereby reducing waste and improving the efficiency of the pipetting device. The housing may also include a sample position. Preferably, the housing includes an outer door that provides access to the sample position and / or the storage compartment.

[0036] In another preferred embodiment, the pipetting device comprises at least one light-tight door arranged between the sample position and the storage compartment. When the pipetting element is received in the storage compartment, the light-tight door shields the pipetting element from light, thereby preventing the light-sensitive reagent from deteriorating, especially when the outer door of the housing is opened.

[0037] In another preferred embodiment, the pipetting device comprises a second pipetting unit configured to transfer the sample. Preferably, the second pipetting unit has a larger pipetting liquid capacity than the first pipetting unit. The second pipetting unit is particularly useful for dispensing at least one washing buffer into the sample. In this embodiment, the pipetting device forms a fully integrated unit to allow the use of a single device to perform staining, bleaching and washing steps.

[0038] In another preferred embodiment, the pipetting device comprises a readout unit configured to read out an individual identifier of at least one well chamber of the pipetting element. The individual identifier allows the pipetting device to identify the well chamber and its contents, thereby further improving the degree of automation of the pipetting device. The individual identifier of the well chamber (e.g., a barcode or a number) enables the user to determine the contents of the well chamber. The correspondence between the individual identifier and the contents of the well chamber can be stored in a database.

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

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

[0041] In a preferred embodiment, the pipetting kit is configured as a disposable consumable. In an alternative embodiment, at least some of the wells are configured to be individually refilled with a pipetting fluid suitable for performing a specific sample preparation.

[0042] In another embodiment, the pipetting kit includes a plurality of wells, each well being filled with a separate pipetting liquid, and each well comprising a separate identifier. At least a portion of the wells in the plurality of wells are configured to be arranged at a predetermined position in a frame. The frame may include a plurality of identifiers that match the separate identifiers of the portion of the wells in the plurality of wells, each identifier of the frame indicating a predetermined position of a matching well. When the plurality of wells are arranged in a frame, the plurality of wells and the frame are configured to form a pipetting element as described above.

[0043] In another embodiment, the pipetting kit includes a frame, wherein the frame includes a plurality of identifiers that match individual identifiers of a plurality of wells, each identifier of the frame indicating a predetermined position of the matched well. When the plurality of wells are arranged in the frame, the plurality of wells and the frame are configured to form a pipetting element as described above. In this embodiment, the pipetting kit includes only the frame, and the wells of the pipetting element can be arranged in the frame. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Specific embodiments are described below with reference to the accompanying drawings, in which: Figure 1 is a schematic side view of a pipetting element according to an embodiment; Figure 2 is based on Figure 1 A schematic top view of a pipetting element; Figure 3 is a schematic diagram of a pipetting device according to an embodiment; Figure 4 is based on Figure 3 Schematic diagram of the pipetting device; Figure 5 is based on Figure 3 and Figure 4 Schematic detail view of a pipetting device; Figure 6 is based on Figures 3 to 5 A schematic top view of a pipetting device; and Figure 7 It is available according to Figures 3 to 6 Flowchart of the sample preparation method performed by the pipetting device. DETAILED DESCRIPTION

[0045] Figure 1is a schematic side view of a pipetting element 100 according to an embodiment.

[0046] The pipetting element 100 is configured to store different pipetting liquids 102 and release the pipetting liquids 102 into a sample or a sample carrier 304 (see Figure 3 ). The pipetting liquid 102 may be a reagent, such as a probe, an antibody, or a chemical. The pipetting liquid 102 may also include a combination of an affinity reagent and a fluorophore, referred to as a marker or a staining solution. In addition, the pipetting liquid 102 may also be a washing buffer configured to wash the above-mentioned reagents, markers, and staining solutions out of the sample.

[0047] The pipetting element 100 includes different wells 104. Each well 104 is configured to receive one of the pipetting liquids 102. Figure 1 , exemplarily, only the leftmost well chamber 104 is filled with the pipetting liquid 102. The capacity of the well chamber 104 is at least 10 μL and at most 200 μL. The inner surface 106 of the well chamber 104 may include a functional coating, for example to prevent the pipetting liquid 102 from adhering to the inner surface 106. Each well chamber 104 includes a release portion 108, which is exemplarily arranged at the bottom of the well chamber 104. The release portion 108 of each well chamber 104 can be individually triggered to release the liquid contained in the well chamber 104.

[0048] The pipetting element 100 further comprises a frame 110 in which the well chamber 104 is arranged. The frame 110 is configured to be received in the pipetting device 300 (see Figure 3 ). This allows the pipetting element 100 to be filled with the pipetting liquid 102 outside the pipetting device 300. The wells 104 can be detached from the frame 110, thereby allowing the wells 104 to be removed from the frame 110 individually, for example for filling the removed wells 104 with one of the pipetting liquids 102.

[0049] The cover 112 of the pipetting element 100 is configured to cover the wells 104. In the present embodiment, the cover 112 is exemplarily formed as a plastic or glass cover that covers all wells 104 at the same time. The cover 112 prevents the pipetting liquid 102 from drying out or contacting pollutants in the environment. In other embodiments, the cover 112 can be configured to cover only some wells 104 or a separate well 104. In another embodiment, the well 104 can include a separate cover. The cover 112 can also be formed by a foil, such as an aloe foil, a plastic foil, or an aluminum foil.

[0050] Figure 2 is based on Figure 1 Schematic top view of a pipetting element 100 .

[0051] A membrane 200 is arranged at the bottom of each chamber 104. The membrane 200 comprises a slit 202 which is closed as long as the pressure inside the chamber 104 is approximately equal to the pressure outside the chamber 104. As long as the slit 202 is closed, the pipetting liquid 102 contained in the chamber 104 is blocked by the membrane 200. The slit 202 can be opened by applying an overpressure to the chamber 104. When the slit 202 is open, the liquid contained in the chamber 104 is released.

[0052] like Figure 2 As shown, the frame 110 has a rectangular shape, and the wells 104 are arranged in a grid-like manner within the frame 110. Each well 104 has a predetermined position within the frame 110. In order to facilitate the correct assembly of the pipetting device 300, each well 104 has an individual identifier 204a, which matches another identifier 204b arranged at a predetermined position of the well 104 in the frame 110. The individual identifier 204a of each well 104 can also be encoded with information about the pipetting liquid 102 contained in the well 104. The individual identifiers 204a, 204b can include any of the following: color, alphanumeric string, two-dimensional shape and three-dimensional shape. In particular, the individual identifiers 204a, 204b can be machine readable so that the readout unit of the pipetting device 300 can identify the individual wells 104. For clarity, only a pair of individual identifiers 204a, 204b are shown.

[0053] Figure 3 is a schematic diagram of a pipetting device 300 according to an embodiment.

[0054] The pipetting device 300 includes a sample position 302 for a sample carrier 304. The sample carrier 304 has a sample receiving compartment 306 configured to receive a sample. Figure 3 , the sample receiving compartment 306 is illustratively formed between a cover glass 307 and a microscope slide arranged in the sample carrier 304. The sample carrier 304 includes an injection port 308 for introducing the pipetting liquid 102 into the sample receiving compartment 306. The injection port 308 includes a lip 310, which is illustratively formed by an O-ring, which is configured to engage with the release portion 108 of the pipetting element 100 and form a seal when it engages with the release portion 108. When the pipetting liquid 102 is injected into the sample receiving compartment 306 via the injection port 308, the seal prevents the pipetting liquid 102 from escaping. The sample carrier 304 also includes an exhaust 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 injection port 308 and the exhaust port 312 are connected to the sample receiving compartment 306 through a fluid channel 314, respectively.

[0055] exist Figure 3In the embodiment, the storage compartment 316 of the pipetting device 300 is arranged on the right side of the sample position 302. The storage compartment 316 is surrounded by a housing 318 and is configured to receive the pipetting element 100. The door 320 is arranged at Figure 3 The left side of the storage compartment 316 in the storage compartment 316 provides access to the storage compartment 316. The door 320 can be a sliding door in particular. The storage compartment 316 also includes a temperature and humidity control unit 322, which is configured to control the temperature and humidity within the enclosed storage compartment 316. Keeping the pipetting element 100 and the pipetting liquid 102 stored therein in a controlled environment can prevent the pipetting liquid 102 from deteriorating and allow long-term experiments to be performed. Figure 3 In the embodiment, the pipetting element 100 is arranged in the storage compartment 316 .

[0056] The pipetting device 300 further includes a trigger unit 324 configured to trigger the release portion 108 of each well chamber 104. The trigger unit 324 illustratively includes a pressure head 326, which is connected to a pressure generating unit 328 via a pressure line 330. In the present embodiment, the trigger unit 324 is illustratively configured to generate an overpressure in the well chamber 104 arranged below the pressure head 326. The overpressure causes the pipetting liquid 102 to be released. The trigger unit 324 is also configured to generate a negative pressure in the well chamber 104 arranged below the pressure head 326, thereby sucking the liquid arranged in the sample receiving compartment 306 into the well chamber 104. The pressure head 326 includes a lip 332, which is illustratively formed by an O-ring, which forms a seal with the top of the well chamber 104 engaged by the pressure head 326. The readout unit 334 of the pipetting device 300 is illustratively positioned at the pressure head 326 and may be configured to determine whether the well chamber 104 is correctly positioned underneath and / or to read out an identifier of the well chamber 104 .

[0057] The positioning unit 336 of the pipetting device 300 comprises a movable shelf 338, which is configured to receive the pipetting element 100. The positioning unit 336 is configured to move the shelf 338 and the pipetting element 100 received therein between the storage compartment 316 and the sample position 302. The positioning unit 336 is also configured to position each well 104 of the pipetting element 100 between the pressure head 326 of the trigger unit 324 and the injection port 308 of the sample carrier 304. Thus, the positioning unit 336 allows selecting which well 104 is to be engaged with the injection port 308, for example, in order to inject a specific pipetting liquid 102 into the sample receiving compartment 306. The scope of the positioning unit 336 is Figure 3 Indicated by a dashed rectangle.

[0058] The pipetting device 300 further includes 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 above elements. The controller 340 is also connected to the user input device 342 and configured to receive user input from the user through the user input device 342. In particular, the controller 340 is configured to execute a method for preparing a sample received in the sample receiving compartment 306. The method is described below with reference to Figure 7 Give a description.

[0059] Figure 4 is based on Figure 3 Schematic diagram of a pipetting device 300.

[0060] exist Figure 4 In the embodiment, the pipetting element 100 is arranged at the sample position 302. The door 320 of the storage compartment 316 is opened, thereby allowing the positioning unit 336 to move the pipetting device 300 to the sample position 302 and back to the storage compartment 316. One of the wells 104 of the pipetting element 100 is arranged between the pressure head 326 of the trigger unit 324 and the injection port 308 of the sample carrier 304. This will be referred to below. Figure 5 Describe in more detail.

[0061] Figure 5 is based on Figure 3 and Figure 4 Schematic detail view of a pipetting device 300 .

[0062] exist Figure 5 In the embodiment of the present invention, the pressure head 326 engages with the top of one of the wells 104. The lip 332 of the pressure head 326 forms a seal between the pressure head 326 and the well 104. The release portion 108 of the well 104 engages with the lip 310 of the sample carrier 304 to form a seal. Once an overpressure is generated in the well 104 by the pressure head 326, the slit 202 of the well 104 will open, and the pipetting liquid 102 contained in the well 104 will be injected into the sample receiving compartment 306 through the injection port 308.

[0063] Figure 6 is based on Figures 3 to 5 Schematic top view of a pipetting device 300.

[0064] The positioning unit 336 of the pipetting device 300 is configured to move the pipetting element 100 in two perpendicular directions, such as Figure 6 This allows the positioning unit 336 to arrange each well chamber 104 of the pipetting element 100 between the pressure head 326 of the trigger unit 324 and the injection port 308 of the sample carrier 304 .

[0065] Figure 7 It is available according to Figures 3 to 6 Flow chart of a sample preparation method performed by the pipetting device 300.

[0066] The process starts at step S700. In step S702, the user loads the pipetting liquid 102 into the pipetting element 100 by loading at least part of the well 104 with one of the pipetting liquids 102. Preferably, this step is performed outside the pipetting device 300, for example, on a workbench. Optionally, in this step, the pipetting element 100 is covered by a cover 112. In step S704, the user issues a command through the user input device 342 to load the pipetting element 100 into the pipetting device 300. 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, so that the user can load the pipetting element 100 into the shelf 338. Once the pipetting element 100 is positioned in the shelf 338, the user issues another command through 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 the amount and type of the pipetting liquid 102 received in each well chamber 104 into the controller 340 via the user input device 342. Alternatively, the information may be provided to the pipetting device 300 via a network or wireless connection to a server.

[0067] In step S708, the user loads the sample carrier 304 including the 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 order of pipetting liquid 102 to be injected into the sample carrier 304. The pipetting program may also specify that the liquid is aspirated back into one of the wells 104 at a specific time. In step S712, the pipetting device 300 executes the pipetting program. In step S714, the process ends.

[0068] In all figures, elements with the same or similar functions are indicated by the same reference numerals. The term "and / or" as used herein includes any and all combinations of one or more of the relevant listed items and may be abbreviated as " / ". The individual features of the embodiments and all combinations of the individual features of the embodiments with each other and with the individual features or feature groups of the preceding description and / or claims are considered disclosed.

[0069] Although some aspects are described in the context of an apparatus, it is clear that these aspects also represent a description of the corresponding method, where a block or device corresponds to a method step or a feature of a method step. Similarly, aspects described in the context of a method step also represent a description of a corresponding block or item or feature of the corresponding apparatus.

[0070] Reference numerals list 100 Pipette Elements 102 Pipetting liquids 104 Hole Chamber 106 Inner surface 108 Release Department 110 Frame 112 Cover 200 Membrane 202 Slit 204a, 204b Identifier 300 Liquid Handling Device 302 Sample location 304 Sample carrier 306 Sample receiving compartment 307 Cover glass 308 Inlet 310 Lips 312 Exhaust port 314 Fluid Channel 316 Storage Compartment 318 Housing 320 doors 322 Control Unit 324 Trigger Unit 326 Pressure Head 328 Pressure generating unit 330 Pressure Line 332 Lips 334 Readout unit 336 Positioning unit 338 Shelves 340 Controller 342 Input Device P1, P2 arrows

Claims

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

2. The pipetting element (100) according to claim 1, wherein: The release portion (108) is configured to be mechanically triggered by a trigger portion of the pipetting device (300) or the sample carrier (304) to release the pipetting liquid (102).

3. The pipetting element (100) according to claim 1 or 2, wherein: Each release portion (108) comprises a membrane (200) configured to be pierced by a piercing element of the pipetting device (300) or the sample carrier (304) to release the pipetting liquid (102).

4. The pipetting element (100) according to any one of the preceding claims, wherein: Each release portion (108) includes a membrane (200) having a slit (202) configured to release the pipetting liquid (102) when an overpressure is applied to the well chamber (104).

5. The pipetting element (100) according to any one of the preceding claims, wherein The release portion (108) is configured to be triggered by an electrical signal received from the pipetting device (300) to release the pipetting liquid (102).

6. The pipetting element (100) according to any one of the preceding claims, wherein: The inner surface (106) of at least one of the wells (104) includes a functional coating, in particular at least one of a bio-coating, a nano-coating, a hydrophobic coating and a hydrophilic coating.

7. The pipetting element (100) according to any of the preceding claims, comprising a cover (112) configured to be received on a frame (110) and the cover (112) covers part or all of the well chamber (104) when received on the frame (110).

8. The pipetting element (100) according to any one of the preceding claims, wherein The at least one cell (104) is configured to be light-tight.

9. The pipetting element (100) according to any one of the preceding claims, wherein: The frame (110) is rectangular, and the cells (104) are arranged in a grid-like manner within the frame (110).

10. The pipetting element (100) according to any one of the preceding claims, wherein: The capacity of each well chamber (104) is at least 10 μl and at most 200 μl, preferably at least 25 μl and at most 100 μl.

11. The pipetting element (100) according to any one of the preceding claims, wherein Each cell (104) includes an individual identifier (204).

12. A liquid transfer device (300) for transferring a sample, comprising: at least one pipetting element ( 100 ) according to any of the preceding claims, and a pipetting unit; wherein the pipetting unit comprises a sample position (302) configured to receive a sample; a storage compartment (316) configured to receive the pipetting element (100); a positioning unit (336) configured to move the pipetting element (100) at least between the storage compartment (316) and the sample position (302); and A trigger unit (324) is configured to trigger the pipetting element (100) to release the pipetting liquid (102).

13. The liquid transfer device (300) according to claim 12, wherein: The storage compartment (316) includes a temperature control unit (322) configured to control the temperature of the storage compartment (316).

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

15. The pipetting device (300) according to any one of claims 12 to 14, wherein: The positioning unit (336) comprises a movable shelf (338) configured to receive the pipetting element (100); and wherein the positioning unit (336) is configured to move the movable shelf (338) between the storage compartment (316) and the sample position (302).

16. The pipetting device (300) according to any one of claims 12 to 15, wherein: The trigger unit (324) is configured to generate at least one of capillary force, gravity flow, overpressure and negative pressure individually in each well chamber (104) of the pipetting element (100).

17. The pipetting device (300) according to claim 16, wherein: The trigger unit (324) includes a pressure head (326) configured to be arranged on top of the sample; wherein the positioning unit (336) is configured to individually position each hole chamber (104) of the pipetting element (100) between the pressure head (326) and the sample; and wherein the pressure head (326) is configured to generate an overpressure and / or a negative pressure in the hole chamber (104) located between the pressure head (326) and the sample.

18. The pipetting device (300) according to any one of claims 12 to 17, wherein: The trigger unit (324) includes a trigger portion configured to mechanically trigger each release portion (108) of the well chamber (104) of the pipetting element (100) individually to release the pipetting liquid (102).

19. The pipetting device (300) according to any one of claims 12 to 18, wherein: The trigger unit (324) comprises a piercing element configured to individually pierce the membrane (200) of each release portion (108) of the well chamber (104) of the pipetting element (100) to release the pipetting liquid (102).

20. The pipetting device (300) according to any one of claims 12 to 19, wherein: The trigger unit (324) is configured to send an electrical signal to the pipetting element (100) for individually triggering each release portion (108) of the well chamber (104) of the pipetting element (100) to release the pipetting liquid (102).

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

22. The pipetting device (300) according to claim 21, wherein: The sample carrier (304) includes a trigger portion configured to mechanically trigger each release portion (108) of a well chamber (104) of a pipetting element (100) individually to release the pipetting liquid (102).

23. The pipetting device (300) according to claim 21 or 22, wherein: The sample carrier (304) comprises a piercing element configured to individually pierce the membrane (200) of each release portion (108) of the well chamber (104) of the pipetting element (100) to release the pipetting liquid (102).

24. The pipetting device (300) according to any one of claims 12 to 23, wherein: The pipetting unit comprises a housing (318) which surrounds at least the storage compartment (316).

25. The pipetting device (300) according to claim 24, wherein: The housing (318) is formed such that the storage compartment (316) is light-tight.

26. The pipetting device (300) according to any one of claims 11 to 25, comprising at least one light-tight door (320) arranged between the sample position (302) and the storage compartment (316).

27. The pipetting device (300) according to any one of claims 12 to 26, comprising a second pipetting unit configured to pipette the sample.

28. The pipetting device (300) according to any one of claims 11 to 27, comprising a read-out unit (334) configured to read out an individual identifier (204) of at least one well chamber (104) of the pipetting element (100).

29. A pipetting kit comprising a pipetting element (100) according to any one of claims 1 to 12, wherein: The at least one well chamber (104) is filled with a pipetting liquid (102) suitable for performing a specific sample preparation.

30. The pipetting kit according to claim 29, which is configured as a disposable consumable.

31. The pipetting kit according to claim 29, wherein: 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.

32. A pipetting kit comprising a plurality of well chambers (104), wherein: Each chamber (104) is filled with a separate pipetting liquid (102), and each chamber (104) includes a separate identifier (204); wherein at least some of the plurality of chambers (104) are configured to be arranged at predetermined positions in a frame (110); wherein the frame (110) includes a plurality of identifiers (204), the plurality of identifiers matching the separate identifiers (204) of the portion of the plurality of chambers (104), each identifier (204) of the frame (110) indicating a predetermined position of a matching chamber (104); and wherein, when the plurality of chambers (104) are arranged in the frame (110), the plurality of chambers (104) and the frame (110) are configured to form a pipetting element (100) according to any one of claims 1 to 12.

33. A pipetting kit, comprising a frame (110), wherein: The frame (110) includes a plurality of identifiers (204) that match individual identifiers (204) of a plurality of wells (104), each identifier (204) of the frame (110) indicating a predetermined position of a matching well (104); and wherein, when the plurality of wells (104) are arranged in the frame (110), 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 12.

Citation Information

Patent Citations

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    EP4123355A1