Liquid treatment device and method for detecting fluorescence

Abstract

The invention relates to a liquid treatment device for transferring and treating a liquid. The liquid treatment apparatus includes an operation chamber disposed within a housing. A table region is arranged in the operating chamber, and a laboratory vessel, such as at least one orifice plate, at least one pipette tip container comprising at least one pipette tip, and at least one metering tool may be placed on the table region. A carrier arm is also included within the operating chamber for moving tools between laboratory utensils disposed on the table area. A light-emitting means is arranged in the liquid treatment device and configured to be arranged on the carrier arm, the light-emitting means comprising at least one probe having at least one light emitter for emitting a light-emitting signal and at least one light receiver for detecting the light-emitting signal.

Description

Background Technology

[0001] Liquid handling encompasses a wide range of products and processes, where handling liquid samples, such as blood and saliva samples, is critical, and even minor errors and mistakes can invalidate a test batch or, if undetected, could lead to inappropriate patient treatment.

[0002] Many different devices are available for liquid handling. This can be done manually, or specialized devices can be obtained to perform specific routines and applications within a confined area of ​​liquid handling. Furthermore, large-scale batch processing machines capable of achieving high throughput of liquid samples are also available.

[0003] However, for some applications, automated liquid handling units are required, designed to help automate routine liquid handling tasks to save time. In these cases, manual liquid handling is too cumbersome, and dedicated liquid handling machines do not provide sufficient flexibility, while high-capacity batch processing machines are too expensive and bulky.

[0004] For this field, benchtop automated liquid handling units are available, such as the epMotion series of liquid handling units from Eppendorf SE.

[0005] These automated liquid handling devices (also referred to herein as liquid handling units) enable a wide range of liquid handling applications. A common feature is that these automated liquid handling units include a workbench on which different types of laboratory glassware can be placed as needed.

[0006] Automated liquid handling apparatuses or systems are particularly used in biological, biochemical, medical, forensic, or chemical laboratories to process laboratory samples, which are predominantly in liquid form. Processing operations specifically include metering, mixing, dispensing, dilution, heating / cooling, and biochemical or chemical alterations or analyses of the samples. During these processes, samples may be altered in quantity, composition, or physical, biochemical, or chemical properties. Automated liquid handling apparatuses are particularly used for preparing dilution series, dispensing reagents, transferring samples from containers to plates, sample normalization, PCR system construction, real-time PCR, purifying nucleic acids using magnetic beads, preparing samples for next-generation sequencing, and handling cell analysis or routine pipetting procedures. Automated sample handling is faster, more accurate, and more reliable than manual handling. For example, EP2713166A1 describes an automated liquid handling apparatus and method for processing laboratory samples.

[0007] Automated liquid handling devices, such as Eppendorf AG's epMotion® 5070, 5073, and 5075, feature a workbench with a workstation for sample containers and a storage area for gripping and measuring tools. Samples can be stored and handled in sample containers. Sample containers include, for example, reagent containers, reaction vessels, reservoirs, microtiter plates (microplates), pipetting containers (such as pipette tips or syringes), and waste containers. As disclosed herein, sample containers are also commonly referred to as well plates, but may be any other type understood by those skilled in the art as the sample containers discussed herein.

[0008] Sample containers are typically placed directly on the workbench of a liquid handling apparatus or stored in a storage device on the workbench. In some cases, sample containers or storage devices may be placed outside the automated liquid handling apparatus. The storage device includes, for example, a pipette tip holder, a holder for the pipette tip holder, a support for a reservoir or container, and an adapter for adjusting the height of a microtiter plate. DE102009006511B4 describes a pipette tip carrier including a pipette tip holder and a pipette tip carrier. EP2168684B1 describes a modular storage system for laboratory liquids.

[0009] Furthermore, the automated liquid handling apparatus includes an XYZ robotic arm with a tool holder, to which gripping tools and / or metering tools are optionally connected. Gripping tools, pipetting tools, and tool holders for automated liquid handling apparatuses are described in EP1407861B1. The robotic arm can move in a programmable manner to pick up or place gripping or metering tools from a storage location, reposition sample containers within a work area using gripping tools, pick up and release pipetting containers (such as pipette tips or syringes) using pipette tips or syringes, and aspirate and dispense liquids using pipette tips or syringes.

[0010] Metrological instruments used with pipette tips have at least one neck onto which the pipette tip can be inserted in a sealed manner. Air is expelled through the upper opening of the pipette tip by a displacement device located within the instrument and connected via tubing to the neck, allowing liquid to be drawn in or expelled through the lower opening. In the case of multi-channel pipettes, the necks for inserting the pipette tips are arranged in one or more rows, with spacing corresponding at least to a portion of the wells in a standardized microtiter plate. Standardized microtiter plates with 96 or 384 wells and multi-channel metrological instruments adapted to these well spacings are particularly useful. Pipettes made of plastic can be detached from the pipette and discarded in a waste container after a single use to prevent cross-contamination of samples from different laboratories during metrology.

[0011] The workstation has a rectangular layout adapted to the footprint of standardized microtiter plates (SBS / ANSI format) to store standardized microtiter plates, pipette tip carriers, or other sample containers with footprints corresponding to those of the standardized microtiter plates. The workstation's footprint is defined by an alignment device that ensures precise positioning of the sample containers.

[0012] However, some applications and processes are not performed on the workbench but must be executed in another location. This requires manually removing samples from the workbench, interrupting the automated workflow, which is both time-consuming and introduces many other error risks, such as contamination and spills.

[0013] This is the case when a luminescent (usually fluorescent) detection step is introduced. Fluorescent detection is used in many liquid handling operations. A fluorescent dye is added to a sample that is bound to a specific component in the sample. By exciting the sample with light of a specific wavelength and detecting the radiation emitted by the fluorescent dye, the amount of the specific component bound to that dye in the sample can be deduced; this can be called the sample concentration. A large number of such luminescent dyes are available on the market, each with specific application focuses and using different wavelengths, but the general principle remains the same.

[0014] Automated liquid handling equipment is used to add fluorescent dyes to samples; however, for excitation and detection, the samples need to be removed from the stage and sent to a separate device for fluorescence detection. As mentioned above, this is both time-consuming and introduces error-prone steps into the process.

[0015] Therefore, there is a need to provide a solution for luminescence detection, especially fluorescence detection, on the workbench of an automated liquid handling unit. Summary of the Invention

[0016] On one hand, this document discloses a liquid handling apparatus for transferring and processing liquids. The liquid handling apparatus includes an operating chamber disposed within a housing, and a workbench area disposed within the operating chamber for receiving / placing laboratory glassware. Laboratory glassware may be, for example, at least one well plate, at least one pipette tip container containing at least one pipette tip, and / or at least one measuring instrument.

[0017] The operating room is also equipped with a carrier arm for moving tools between laboratory instruments arranged in the workbench area.

[0018] Furthermore, a light-emitting tool is provided in the liquid handling apparatus, wherein the liquid handling apparatus includes at least one probe having at least one light emitter for emitting a light-emitting signal and at least one light receiver for detecting the light-emitting signal, wherein the light-emitting tool is configured to be arranged on the carrier arm.

[0019] Luminescence detection can be performed on a worktable by mounting a luminescence tool on the carrier arm. For example, it has been demonstrated that luminescence detection can be performed directly in a well plate using the luminescence tool disclosed herein. Generally, as used herein, the term "luminescence detection" should be understood as the act of both emitting a luminescence signal to a sample and subsequently detecting the luminescence signal returned from the sample. In luminescence excitation, it is well known that the signal emitted to the sample by the probe unit can have a wavelength different from the signal subsequently received from the sample by the probe unit.

[0020] Therefore, it is possible to avoid transferring the sample or the entire well plate to a separate luminescence detection device. This avoids separate sample handling and reduces or eliminates the risk of spillage, contamination, and other factors that may damage the sample.

[0021] Furthermore, in many cases, luminescence detection (e.g., fluorescence detection) is used in a liquid handling workflow where liquid handling is performed both before and after luminescence detection. This may be the case, for example, when a sample is being normalized. Therefore, the intermediate luminescence detection step typically requires user attention, either for sample handling or, for example, for exporting luminescence measurement data from the luminescence detection device and importing it into the liquid handling unit, and programming the liquid handling unit to perform proper normalization based on the luminescence measurement data. In other words, a liquid handling unit as disclosed herein would allow the user to step away from the process, increasing the user's time off (i.e., the time available for the user to perform other tasks in the laboratory while the liquid handling unit performs its application) and allowing the user to focus on other tasks.

[0022] Furthermore, luminescence is a general term encompassing a variety of different principles involving the ability of molecules to emit light. For example, this light emission can be triggered chemically, electrically, or by radiation. One type of luminescence is photoluminescence, which is triggered by exposing molecules to light of one wavelength, causing them to emit light of another wavelength. Generally, the well-known principles of photoluminescence are fluorescence and phosphorescence, with fluorescence, in particular, being widely used in the field of liquid handling.

[0023] For fluorescence, the time between absorption and emission of light by fluorescent molecules is very short, and in some cases it is almost instantaneous; while for phosphorescence, the time between absorption and emission is longer, such as minutes or hours.

[0024] Therefore, as used herein, terms such as luminescence, luminescence, and luminescence detection / measurement are generally used to refer to the principles applied herein. Although fluorescence is commonly used in the present field to apply these principles, this disclosure also covers the application of the teachings herein, particularly in other fields of photoluminescence such as phosphorescence.

[0025] When referring to the principles of luminescence or fluorescence, or the tools and objects used to utilize these principles, this document uses general terms such as luminescence and fluorescence. When referring to devices or samples that inherently exhibit this property, such as the luminescent or fluorescent dye itself, a sample in which the dye is mixed, or any other specific object or device exhibiting this property, the terms "luminescent" and "fluorescent" are used. As used herein, "luminescence / fluorescence measurement / detection" refers to the act of detecting the luminescent or fluorescent properties of an object, such as a sample.

[0026] Furthermore, when referring to luminescent or fluorescent signals or wavelengths, it should be understood that such signals or wavelengths are optical, and when such signals or wavelengths are emitted from, for example, a luminescent tool, the purpose is to excite luminescent or fluorescent dyes; the same purpose is also to measure / detect the optical wavelengths emitted from fluorescent dyes (after excitation).

[0027] Typically, luminescent and fluorescent dyes are labeled with specific excitation and emission values; however, in many cases, these dyes operate within a wavelength range where the labeled value is optimal. For example, a fluorescent dye might be labeled with an excitation wavelength of 560 nm; however, it will still be excited when exposed to light with wavelengths between 500 nm and 580 nm, but it will be most efficient at 560 nm.

[0028] In addition, a fluorescent dye may be labeled with an emission wavelength of 570 nm when excited, but it will still emit light in a range of wavelengths, such as 550 nm to 680 nm, but its energy content (intensity) will peak at 570 nm.

[0029] For the purposes of this disclosure, those skilled in the art will understand that commercially available luminescent and fluorescent dyes may be used herein without limiting or departing from the scope of this disclosure. Those skilled in the art will also understand that when referring to a luminescent or fluorescent signal or wavelength, a wavelength range may be encompassed. Furthermore, the term "signal" may refer to light having a certain wavelength or containing a wavelength spectrum. However, the term "signal" may also / additionally refer to a signal that represents or contains information relating to light having a certain wavelength or containing a wavelength spectrum. Such a signal may, for example, be a digital signal and processed on a computer (e.g., by a computer-implemented method).

[0030] In some liquid handling devices, a separate luminescence detection unit is placed on the worktable, and reagent kits or well plates must be inserted for luminescence detection. By arranging the luminescence tool above the worktable (e.g., on a carrier arm), as discussed, the worktable footprint can be kept small because it avoids placing a separate luminescence detection device on the worktable.

[0031] On the other hand, this document discloses a liquid handling apparatus for transferring and processing liquids. The liquid handling apparatus includes an operating chamber disposed within a housing, and a workbench area disposed within the operating chamber for receiving / placing laboratory glassware. As previously described, laboratory glassware may include at least one well plate, at least one pipette tip container containing at least one pipette tip, and / or at least one measuring tool.

[0032] The light-emitting tool may include at least one probe having at least one light emitter for emitting a light emission signal and at least one light receiver for detecting the light emission signal, wherein the probe is configured to move above a worktable area within an operating chamber. In this way, the probe can be moved to a sample, for example, in a well plate, for light emission detection.

[0033] Alternatively, the well plate can be moved to the probe for luminescence detection, or both can be moved to place the probe and sample in the correct relative position for luminescence detection.

[0034] Similarly, a luminescent tool that can be moved within the operating room of the liquid handling device is provided, eliminating the need for a separate luminescent detection device, thereby avoiding unnecessary sample handling and / or removing the sample from the liquid handling device workbench area.

[0035] In another aspect, this document discloses a liquid handling system comprising the liquid handling apparatus disclosed herein and at least one laboratory vessel arranged on a workbench area.

[0036] The at least one laboratory instrument may be, for example, at least one well plate, at least one pipette tip container containing at least one pipette tip, and / or at least one measuring tool.

[0037] As discussed, using a luminescent tool to perform luminescent detection directly on a sample within an orifice plate on the stage of a liquid handling device eliminates the need to transfer the sample to a separate luminescent detection device.

[0038] Therefore, by measuring directly in the well plate, the use of other peripheral and / or custom-made equipment can be avoided. For example, the liquid handling apparatus, systems, and methods described herein can generally avoid the use of kits and microfluidic systems for luminescence detection.

[0039] In another aspect, this document discloses a light-emitting tool configured to be arranged above the worktable area of ​​a liquid handling apparatus, such as on a carrier arm, wherein the light-emitting tool includes at least one probe having a light emitter for emitting a light-emitting signal and a light receiver for detecting the light-emitting signal.

[0040] In one embodiment of the luminescent tool, the tool is a fluorescent tool, and a probe unit integrating a probe is used to measure fluorescence intensity based on different voltages applied to the probe. This is described, for example, in WO2013 / 056820A1, and provides a very accurate method for determining sample concentration.

[0041] After detecting the fluorescence signal, the sample concentration can be calculated based on the fluorescence intensity of the standard.

[0042] On the other hand, this document discloses a light emission measurement shielding system comprising at least one probe having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal, wherein the shielding system further comprises a covering element that encloses the probe, wherein the covering element comprises a barrier that is opaque to light (e.g., the light emission signal) and a covering opening disposed in the barrier that allows light (e.g., the light emission signal) to pass through, wherein the probe and the covering opening are movable relative to each other.

[0043] In one embodiment, the probe and the covering opening are movable relative to each other at least along the light emission direction of the probe.

[0044] This provides a solution that can control the depth of light penetration into the sample (e.g., the focal point of the light) while reducing or even eliminating noise from ambient light during measurement.

[0045] Furthermore, the cover element will facilitate cleaning, especially in embodiments where the cover element completely covers the probe, as further disclosed herein.

[0046] One embodiment of the luminescence measurement shielding system may further provide a luminescence tool configured to be arranged above the workbench area of ​​a liquid handling apparatus (e.g., on a carrier arm), wherein the luminescence tool is disclosed to include at least one probe having a light emitter for emitting a luminescence signal and a light receiver for detecting the luminescence signal, wherein the luminescence tool includes a tool housing that at least partially surrounds the probe, and wherein the tool housing supports a probe unit including the probe, and wherein the probe unit is slidably arranged within the tool housing.

[0047] In one embodiment, the light-emitting tool may further include circuitry for communicating with the probe unit, the circuitry being arranged on the tool frame for electrical coupling to a corresponding electrical coupling interface on the carrier arm. Similarly, the light-emitting tool may include a mechanical coupling interface on the tool frame for mechanical coupling to a corresponding mechanical coupling interface in the carrier arm. The electrical and mechanical couplings may be separate or integrated into a common coupling interface that provides both mechanical and electrical connections within the same coupling structure. In yet another embodiment, the coupling may be, for example, magnetic, or a combination of magnetic, mechanical, and / or electrical coupling.

[0048] On the other hand, this document discloses a method using the discussed light-emitting shielding system. The disclosure includes a method for controlling the relative positions of a probe and a cover opening of a light-emitting shielding system as disclosed herein between a first relative position and a second relative position, and for controlling the distance between the cover opening and an orifice plate containing at least one hole containing a sample, wherein the cover opening and the orifice plate are arranged such that the cover opening is positioned between the orifice plate and the at least one probe along an axis A–A of the light-emitting shielding system, and the at least one hole is open toward the cover opening, wherein the method includes: - Maintain the hole distance between the cover opening and the orifice plate at the predetermined hole distance. - Determine the liquid level of the sample in the well. - Move the probe relative to the cover opening so that the distance between the probe and the sample liquid surface in the hole is at a predetermined liquid surface distance.

[0049] It is understandable that applying the above method to a light emission measurement shielding system significantly reduces the risk of ambient light interference with the measurement, while also allowing the system to adapt to different sample volumes provided in each well of the measurement plate.

[0050] In an alternative approach, the method using a light-emitting shielding system involves moving the sample relative to the covering opening such that the distance between the probe and the sample liquid surface in the hole is a predetermined liquid surface distance.

[0051] In one embodiment, the predetermined liquid level distance is determined based on the focal length of the light emission signal emitted from the probe, the liquid level height of the sample in the orifice, and the desired penetration depth of the light emission signal emitted from the probe, wherein the penetration depth is the distance from the sample liquid level to the focal point of the light emission signal in the sample.

[0052] In some embodiments, a penetration depth of 3.5 mm has been found to be preferred. However, this may depend on the sample type, the dye used, and other parameters. For example, the penetration depth may be between 2 and 5 mm; between 2 and 4 mm; between 2 and 3.5 mm; between 2 and 3 mm; or between 2 and 2.5 mm.

[0053] The liquid level in the sample within the well can be determined in different ways. In one embodiment, it is determined by detecting changes in the emission signal or changes in light refraction as the probe moves relative to the sample.

[0054] On the other hand, this paper discloses a method for measuring the luminescence of a sample in an orifice plate arranged in the stage area of ​​a liquid handling apparatus.

[0055] The method includes the following steps: - The probe of the light-emitting tool is positioned at the sample, wherein the light-emitting tool includes at least one probe having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal. - The sample is excited by emitting the light signal using the light emitter. - Use the light receiver to detect / record the light emission signal subsequently emitted by the sample.

[0056] In one embodiment, the method further includes adding a luminescent dye to the sample. In another embodiment, a standard solution may also be provided. Typically, the sample containing the dye and, where applicable, the standard solution are mixed and incubated for a period of time, the duration of which is determined by the specific application, the sample, the dye, and / or the standard solution.

[0057] After recording the emission of the samples, a normalized value can be determined for each sample. Therefore, in one embodiment, the method further includes the following steps: - Determine the normalized volume, and - Normalize the sample volume.

[0058] In one embodiment, the user inputs normalization values ​​before initiating luminescence detection. The user inputs values ​​such as the desired concentration and volume of the normalized sample. Based on these preset values ​​and the measured sample concentration, the system can calculate the required volume of sample and / or diluent for normalization.

[0059] Furthermore, in one aspect, the method disclosed herein for measuring sample luminescence can be implemented by a computer. In particular, the method for determining sample normalization based on luminescence detection can be implemented by a computer.

[0060] Understandably, one aspect of this document also discloses the use of liquid handling systems, liquid handling devices, and luminescence tools as disclosed herein to measure the luminescence of samples in a well plate. In particular, they are used to determine the normalization of the sample based on luminescence detection. Detailed Implementation

[0061] As discussed, this disclosure relates to a liquid handling apparatus or system having an operating chamber in which a luminescent tool can be moved above a workbench to interact with various laboratory glassware. The luminescent tool can be moved, for example, by arranging it on a carrier arm.

[0062] In one embodiment, the luminescent tool has a coupling interface for coupling or decoupling the luminescent tool to or from the carrier arm. As discussed herein, such coupling can include both electrical and mechanical coupling. This allows the liquid handling device to use different tools, such as selecting from tools placed on a worktable. Typical tools are different types of metering tools, for example, one metering tool providing a single-channel pipetting tool and another metering tool providing an eight-channel pipetting tool. By using different tools during liquid handling, the device can, in one case, handle batch pipetting operations using an eight-channel metering tool, while the handling of a single sample can be accomplished using a single-channel metering tool.

[0063] The flexibility of the liquid handling unit toolkit is further increased by providing light-emitting tools that can be coupled and decoupled from the carrier arm.

[0064] Furthermore, in another embodiment, different luminescence tools can be provided. For example, similar to the metrological tools discussed above, a luminescence tool with a single probe can be provided for recording the luminescence of one sample at a time, for example, by measurement through the wells of a well plate. Another luminescence tool may include eight probes spaced such that they can record the luminescence of a row of eight wells.

[0065] Typically, the probe spacing is nine millimeters, as this is the standard distance between wells in a 96-well plate. Those skilled in the art will understand the different types and sizes of well plates and their dimensions, for which the luminescent tools discussed herein can be configured and designed. In particular, those skilled in the art will refer to the positions and dimensions specified in recognized standards, such as ANSI SLAS 4-2004 (R2012) provided by the Advisory Committee on Microplate Standards of the Laboratory Automation and Screening Association (SLAS), under the guidance of the American National Standards Institute (ANSI).

[0066] Therefore, it can be understood that in the provided embodiments, one or more light-emitting tools may include a plurality of probes, such as 8, 12, 96, 384 and / or 1536 probes.

[0067] In another embodiment, it may be desirable to provide a liquid handling apparatus in which the luminescence tool is integrated into the carrier arm. This may be advantageous if the liquid handling apparatus is designed for specific liquid handling processes that frequently use luminescence detection, such as NGS (next-generation sequencing), which often uses normalization processes. Thus, by integrating the luminescence tool into the carrier arm, the tool switching step is eliminated, but the carrier arm may become more bulky, and the versatility of selecting between different luminescence tools is traded for a more specialized system.

[0068] Although it has been shown that liquid handling devices can be designed with negligible interference from crosstalk and ambient noise on luminescence detection, it may be desirable to further ensure that these risks are reduced.

[0069] Therefore, in one embodiment, the at least one perforated plate comprises a material that is opaque to the emission wavelength (e.g., the wavelength of light emitted by the probe's light emitter and / or the wavelength of light detected by the probe's light receiver). Typically, a dyed plastic (e.g., black) can be used to manufacture the perforated plate to make it opaque to the emission wavelength employed.

[0070] In another embodiment, the at least one pipette tip comprises a material that is opaque to the light emission wavelength (e.g., the wavelength of light emitted by the probe's light emitter and / or the wavelength of light detected by the probe's light receiver).

[0071] In one embodiment, the interface between the probe and the orifice plate can be shielded when performing luminescence detection. For example, in one embodiment, the probe can be at least partially enclosed by a cover that is opaque to the emission wavelength (e.g., the wavelength of light emitted by the probe's light emitter and / or the wavelength of light detected by the probe's light receiver). This can provide a skirt configured to cover the orifice when the probe is located in or inserted into the orifice of the at least one orifice plate, thereby reducing the risk of unwanted luminescence exposure during luminescence detection.

[0072] In an additional or alternative embodiment, the housing of the liquid handling device may include a material that is opaque to the light emission wavelength (e.g., the wavelength of light emitted by the probe's light emitter and / or the wavelength of light detected by the probe's light receiver), thereby protecting the entire operating room from ambient light emission.

[0073] Emission is a generally understood process. The phenomenon involves chemical molecules absorbing light of a specific wavelength (emitted by a probe). This is also known as the excitation wavelength. Subsequently, the chemical molecules emit light at different wavelengths (received by the probe), typically longer wavelengths.

[0074] For example, in one embodiment, the emission wavelength of the signal emitted by the light emitter is 520 or 600 nm. These wavelengths are commonly used for sequencing, such as DNA and RNA sequencing. It will be clearly understood from this disclosure that other wavelengths can be used for other applications.

[0075] In one embodiment, the probe is arranged to face the stage, for example, such that it will face the sample in the well plate when driven by the carrier arm during operation.

[0076] For example, during operation, at least the proximal end of the probe facing the stage area has a cross-section smaller than that of at least one orifice in the well plate. This allows the probe to be at least partially inserted into the orifice of the well plate, ensuring proximity to the sample and reducing the risk of ambient light interference with detection.

[0077] In one embodiment, when performing a test, the probe is positioned at a distance of 2–5 mm from the top opening of the hole.

[0078] As discussed, the light-emitting tool can be configured to be arranged on the carrier arm, or it can be integrated into the carrier arm.

[0079] For example, in one embodiment, a first coupling interface is disposed on the fluorescent tool, and the first coupling interface is configured to couple and decouple from a corresponding second coupling interface on the carrier arm of the liquid handling device.

[0080] In another embodiment, the light-emitting tool includes a tool frame for supporting a probe unit, the probe unit including a probe and circuitry for communicating with the probe unit, and wherein a coupling interface is arranged on the tool frame for mechanical and electrical coupling with a corresponding coupling interface.

[0081] In one embodiment, the circuit may include a dedicated system that provides a communication protocol between the light-emitting sensor and the liquid handling device.

[0082] In one embodiment, the probe is designed to emit and receive optical signals of a specific wavelength or band. As will be understood by those skilled in the art as described above, the emitted signals will be emitted and received as light of a specific wavelength, but in some embodiments, they will be further processed into digital signals that represent or contain information representing or relating to the wavelength emitted or received by the probe.

[0083] In another embodiment, the luminescence tool can be provided as a kit, wherein the probe is configured to emit and receive luminescence signals within a desired wavelength band or at a specific wavelength. In one embodiment, the probe and probe unit itself is configured to emit and receive luminescence signals over a wide wavelength range; however, a filter set is provided and can be arranged along the optical axis of the probe to configure the system for detecting the desired wavelength or band of emission and reception. For example, a filter set for fluorescence detection can be provided, wherein the emission wavelength is 520 or 600 nm.

[0084] In one embodiment, the probe unit is slidably arranged within the tool frame. This allows for fine-tuning of the probe relative to the sample to optimize luminescence detection.

[0085] Further embodiments of the light emission measurement shielding system (also referred to more briefly as the "shielding system" in this document) may be provided.

[0086] For example, in one embodiment, the probe has an annular shape, and the covering opening has an annular shape.

[0087] The cover opening and the probe can be arranged in a variety of ways, for example, the probe and the cover opening can be arranged coaxially along axis A–A.

[0088] In one embodiment, the system can be designed such that the probe and the coverage opening are movable relative to each other along axis A–A. In particular, the probe and the coverage opening can be restricted to relative movement only along axis A–A, which avoids any undesirable movement in directions other than axis A–A.

[0089] In some embodiments, the optical axis of the probe corresponds to axis A–A.

[0090] In some embodiments, the cover opening and the probe may be annular, and the radius of the cover opening and the radius of the probe may be the same.

[0091] To further improve the shielding system, various factors should be considered. For example, in one embodiment, the shielding system further includes an orifice plate containing at least one hole, wherein the orifice plate is arranged such that a cover opening is located between the orifice plate and the at least one probe, and the hole opens toward the cover opening.

[0092] In this embodiment, the first distance between the cover opening and the at least one hole in the first relative position can be the same as the second distance between the cover opening and the at least one hole in the second relative position. In other words, the position of the cover opening relative to the hole remains unchanged, while the probe can move relative to the hole.

[0093] In one embodiment, the first and second distances are kept constant in order to obtain comparable measurement results.

[0094] To further shield ambient light, in one embodiment, at least a portion of the barrier facing the perforated plate may have a coverage width transverse to axis A–A, which corresponds to at least three times the width of the perforation.

[0095] In another embodiment, at least a portion of the barrier facing the perforated plate may have a coverage length that is transverse to axis A–A and perpendicular to the width, the length of which corresponds to at least three times the length of the perforation.

[0096] In some embodiments, the covering opening may be arranged at the center of the portion of the barrier facing the perforated plate, which has the covering width and / or covering length.

[0097] The luminescence detection described in this article is particularly useful for sample normalization, such as in sequencing processes like NGS. Sample normalization is well-known and refers to adjusting the sample volume or concentration before or after data acquisition to enable sample comparisons.

[0098] For luminescence detection, the challenge is that it has always been done outside of automated liquid handling equipment, and due to the lack of proper integration, the data must be read out separately, normalized and calculated, and then programmed into the liquid handling equipment. This results in a lengthy and cumbersome process, and because each input is done manually, there is a risk of errors when inputting data, so the risk of error is also high.

[0099] Normalization can be automated by providing the disclosed fluorescence detection in automated liquid handling units, because the data can be relayed and processed within the system without external input from, for example, external data sources or manual input from the user. Attached Figure Description

[0100] The embodiments and examples will now be described in more detail with reference to the accompanying drawings: Figure 1 An embodiment of an automated liquid handling apparatus suitable for use with the luminescent tools disclosed herein is shown.

[0101] Figure 2a and 2b An embodiment of the fluorescent tool disclosed herein is shown, and Figure 3a and 3b The aforementioned fluorescence instrument is shown during fluorescence detection of samples in a well plate.

[0102] Detailed description of the attached figures Figure 1An automated liquid handling apparatus 100 is shown, having a housing 101 defining an operating chamber 102, in which a workbench 103 is arranged. The workbench is configured to receive various laboratory instruments (not shown), such as orifice plates, mixers, heaters, etc., in a designated area 104.

[0103] A carrier arm 105 is also arranged in the control room. The carrier can move within the volume of the control room in the x (width), y (depth) and z (height) directions.

[0104] In the current embodiment, this is achieved by providing a track system that includes a first track arm 106 at the rear of the housing 101, extending along the width of the operating chamber as indicated by the x-direction. A second track arm 107 is provided transversely to the first track arm 106, extending transversely to the first track arm in the direction of the operating chamber depth as indicated by the y-direction. The second track arm is arranged on the first track arm such that it can be controlled and moved along the width direction.

[0105] The third track arm 108 is slidably disposed on the second track arm 107. The third track arm extends in the height direction indicated by the z-direction. The third track arm 108 is disposed on the second track arm such that it can be controlled and moved along the second track arm in the depth direction.

[0106] The carrier arm 105 is arranged on the third track arm 108 and can move along the height direction on it.

[0107] This provides full maneuverability of the carrier arm 105 in all three dimensions within the operator's compartment. The described track systems 106, 107, and 108 for maneuvering the carrier arm 105 are generally known and are one example of enabling the carrier arm to move within the operator's compartment. Other configurations, such as a robotic arm, can be provided by those skilled in the art.

[0108] The carrier arm is configured to be connected via a coupling structure (e.g., Figure 1 The coupling structure 105' in the system can be releasably engaged with different tools (not shown). Such tools may be, for example, single-channel or eight-channel metrology tools. The carrier arm is also configured to releasably engage with the fluorescence tools discussed herein. The worktable also includes a tool storage area 109 in which different tools can be placed when not in use. The system can then move to the tool storage area and switch between tools during operation according to instructions.

[0109] The automated liquid handling unit 100 also includes a waste container 110 arranged on the workbench, in which the carrier arm can discard used consumables, especially used pipette tips. The front 114 of the housing 101 can be opened to access the operating room and workbench.

[0110] Terminal 115, including monitor 111, keyboard 112, and mouse 113, is linked to the automated liquid handling device, through which an operator can program the device, monitor it during operation, and / or intervene in the operating procedure when necessary. The terminal can be connected to the automated liquid handling device wired or wirelessly. Other types of terminals, such as laptops, smartphones, or tablets, are also possible.

[0111] Figure 2a and 2b An embodiment of a fluorescent tool 200 is shown. The fluorescent tool includes a housing 201, a portion of which has been opened to reveal a probe unit 202 containing a probe 203.

[0112] The probe unit can be slidably arranged in the housing along the focusing direction 204. Figure 2a The first position 205 shown and Figure 2b The second position 206 is shown. The focusing direction is parallel to the optical axis A–A of the probe unit. In the current embodiment, the optical axis can be considered as the rotational symmetry axis of the light emitted from the probe. The light contains the wavelength or wavelength band that is desired to excite the fluorescent dye.

[0113] The probe unit 202 is fixed to the mounting plate 207, which has first and second longitudinally extending slots 208 and 209 that extend parallel to each other. The housing has a first pin 210 and a second pin 211, which are arranged to guide each slot respectively, i.e., the first pin is received in the first slot and the second pin is received in the second slot.

[0114] By providing the two slots and pins configuration described above, the probe unit and the housing are locked relative to each other, allowing relative movement only along the longitudinal extension direction of the slots. In the current embodiment, the pins of the housing are arranged on a line parallel to / along the focusing direction, which results in the longitudinal extension direction of the slots being along the focusing direction. Therefore, this provides a configuration in which the movement of the probe unit relative to the housing is controlled by... Figure 2a and 2b The limitation of the longitudinal groove in the focusing direction of the fluorescence tool.

[0115] The housing 201 defines a barrier portion 212 that is opaque to ambient light and surrounds the probe. Furthermore, this barrier portion is formed of a material with low reflectivity, meaning that the material absorbs or disperses light, thereby minimizing or eliminating the risk of ambient light being reflected into the sample or probe.

[0116] An opening 213, allowing light to pass through, is arranged coaxially with the optical axis at the proximal end 214 of the housing. The proximal end of the housing is the end closest to the orifice plate during measurement. Therefore, as shown, a portion of the light from the probe can pass through the opening into the orifice plate, and a portion of the light emitted from the sample can pass through the opening and be received by the probe.

[0117] The opening 213 is sealed by a glass element 219 that allows light to pass through. This glass element, together with the rest of the housing, acts as a physical barrier, preventing foreign objects from entering the housing and contaminating or blocking the probe, or otherwise impairing the function of the luminescent tool. This also facilitates the cleaning of the fluorescent tool 200.

[0118] In order to initiate the movement of the probe unit within the housing, shaft 215 is connected to the probe unit (or mounting plate 207) at connection end 216 and forms part of the spindle drive (not shown) at the spindle end.

[0119] The housing 201 has a coupling interface 218 at its distal end 217 (i.e., the end opposite to the proximal end), which is configured to couple with a matching portion (not shown in the current drawing, but...) provided on the carrier arm. Figure 1 In one embodiment, it is shown as a coupled structure 105'.

[0120] Furthermore, although not shown, the probe unit receives power and communicates with the processor via an electrical coupling interface provided in the electrical connection and coupling interface, in order to power the probe unit, control it, and read data from it.

[0121] Figure 3a and 3b The use of the fluorescent tool 200 is shown in a cross-sectional view. Figure 3a In the first position 205, it measures a relatively small sample 300 in the hole 301 of the orifice plate 302. Figure 3b In the second position 206, it measures the relatively large sample 310 in the hole 311 of the orifice plate 312.

[0122] In both locations, the proximal end 214 of the housing maintains the same distance relative to the orifice plate. The distance d between the surface 220 of the proximal end 214 and the tops 303, 313 of the orifice plates 302, 312 is so small that ambient light does not affect the measurement.

[0123] In other words, during operation, the proximal end of the housing acts as a shield, reducing or eliminating the openings that allow light to enter the sample being measured and / or reaching the probe.

[0124] Understandably, because Figure 3a and 3b The sample amounts in the two wells are different, which allows control over the focal point "p" of the excitation light 320 emitted by the probe unit 202, thereby controlling the desired penetration depth of the excitation light in the sample. At the same time, since the proximal end 214 acts as a barrier to prevent interference from ambient light, the influence of ambient light on fluorescence measurement can be minimized.

[0125] In one embodiment, the focal length f of the emitted light 320, i.e., the distance from the probe to the focal point "p", is 18 mm, while the movement distance "m", i.e., the relative distance the probe unit 202 moves relative to the housing 201 when it moves from the first position to the second position (or vice versa), is 5.5 mm. This allows the system to maintain an immersion depth "i", i.e., the distance from the sample liquid surface in the orifice to the focal point of the emitted light, at 3.5 mm in the first position, the second position, and all intermediate positions.

[0126] List of reference numerals Automated liquid handling unit 100 Casing 101 Operations Room 102 Workbench 103 Specified area 104 105-inch carrier arm Coupled structure 105' First track arm 106 Second rail arm 107 Third track arm 108 Tool storage area 109 Waste container 110 Front part 114 of housing 101 Terminal 115 Including monitor 111 Keyboard 112 Mouse 113 Fluorescent tools 200 Casing 201 Probe unit 202 Probe 203 Focus direction 204 First position 205 Second position 206 Mounting plate 207 First longitudinal extension groove 208 Second longitudinal extension groove 209 First sale 210 Second Sales 211 Barrier section 212 Opening 213 Proximal end 214 of housing 201 Glass Component 219 Shaft 215 Connection end 216; Distal end 217 of housing 201 Coupled interface 218 Surface 220 of proximal end 214 300 small samples Hole 301; 311 Orifice plate 302; 312 Large sample 310 The top of orifice plates 302 and 312; 303 and 313. 320 emitted light Example 1. A liquid handling apparatus for transferring and processing liquids, comprising an operating chamber disposed within a housing, and a workbench area disposed within the operating chamber for receiving / placing laboratory instruments, wherein the laboratory instruments include at least one well plate, at least one pipette tip container containing at least one pipette tip, and at least one measuring tool, wherein the operating chamber further comprises: - A carrier arm for moving tools between laboratory instruments arranged in the workbench area, and - A light-emitting tool, including at least one probe having at least one light emitter for emitting a light-emitting signal and at least one light receiver for detecting the light-emitting signal, wherein the light-emitting tool is configured to be arranged on the carrier arm.

[0127] 2. The liquid handling apparatus according to Embodiment 1, wherein the light-emitting tool has a coupling interface for coupling the light-emitting tool to and decoupling it from the carrier arm.

[0128] 3. The liquid handling apparatus according to Embodiment 1, wherein the light-emitting tool is integrated in the carrier arm.

[0129] 4. The liquid processing apparatus according to Embodiment 1, 2 or 3, wherein the at least one orifice plate comprises a material that is opaque to the emission wavelength.

[0130] 5. The liquid handling apparatus according to any one of Examples 1–4, wherein the at least one pipette tip comprises a material that is opaque to the emission wavelength.

[0131] 6. The liquid handling apparatus according to any one of Examples 1–5, wherein the probe head is at least partially surrounded / encircled by a skirt / cover / shield that is opaque to the emission wavelength.

[0132] 7. The liquid handling apparatus according to embodiment 6, wherein the skirt is configured to cover the orifice when the probe is disposed at or inserted into the orifice of the at least one orifice plate.

[0133] 8. The liquid handling apparatus according to any one of the foregoing embodiments, wherein the housing comprises a material that is opaque to the emission wavelength.

[0134] 9. The liquid handling apparatus according to any one of the foregoing embodiments, wherein the wavelength of the light emission signal emitted by the light emitter is 520 or 600 nm.

[0135] 10. The liquid handling apparatus according to any one of the foregoing embodiments, wherein the light-emitting tool comprises a plurality of probes, such as 8, 12, 96, 384 and / or 1536 probes.

[0136] 11. The liquid processing apparatus according to any one of Examples 1–10, wherein the at least one light emitter emits a fluorescent or phosphorescent signal, and the at least one light receiver receives the fluorescent or phosphorescent signal.

[0137] 12. The liquid handling apparatus according to any one of embodiments 1–11, wherein the probe faces the worktable when operated by the carrier arm.

[0138] 13. The liquid handling apparatus according to embodiment 12, wherein, during operation, at least the proximal end of the probe facing the stage region has a cross-section smaller than the cross-section of the hole in at least one orifice plate.

[0139] 14. The liquid handling apparatus according to any one of the foregoing embodiments, wherein the light-emitting tool includes a tool frame for supporting a probe unit, the probe unit including the probe and circuitry for communicating with the probe unit, and wherein a coupling interface is disposed on the tool frame for mechanical and electrical coupling with a corresponding coupling interface.

[0140] 15. The liquid handling apparatus according to Embodiment 14, wherein the probe unit is slidably arranged in the tool frame.

[0141] 16. A liquid handling apparatus for transferring and processing liquids, comprising an operating chamber disposed within a housing, and a workbench area disposed within the operating chamber for receiving / placing laboratory instruments, wherein the laboratory instruments include at least one well plate, at least one pipette tip container including at least one pipette tip, and at least one measuring tool, wherein the operating chamber further comprises: - A light-emitting tool, comprising at least one probe having at least one light emitter for emitting a light-emitting signal and at least one light receiver for detecting the light-emitting signal, wherein the probe is configured to move within the operating chamber above the workbench area.

[0142] 17. A liquid handling system comprising a liquid handling device according to any one of embodiments 1–16 and at least one laboratory vessel arranged on the workbench area.

[0143] 18. The liquid handling system according to Example 17, wherein the at least one laboratory vessel comprises at least one well plate, at least one pipette tip container including at least one pipette tip, and at least one metering tool.

[0144] 19. The liquid handling system according to any one of the foregoing embodiments, wherein when the system is operated, the probe is positioned at a distance of 2–5 mm from the orifice of the hole.

[0145] 20. A light-emitting tool configured to be arranged above a workbench area of ​​a liquid handling apparatus, such as on a carrier arm, wherein the light-emitting tool includes at least one probe having a light emitter for emitting a light-emitting signal and a light receiver for detecting the light-emitting signal.

[0146] 21. The light-emitting tool according to embodiment 20, wherein the light-emitting tool is configured to be arranged on the carrier arm.

[0147] 22. The light-emitting tool according to embodiment 21, wherein the light-emitting tool is integrated into the carrier arm.

[0148] 23. The light-emitting tool according to embodiment 20 or 21, wherein a first coupling interface is disposed on the light-emitting tool, the first coupling interface being configured to couple and decouple from a corresponding second coupling interface on the carrier arm of the liquid handling device.

[0149] 24. A light-emitting tool according to any one of embodiments 20, 21, 22 or 23, wherein the light-emitting tool includes a tool frame for supporting a probe unit, the probe unit including the probe and circuitry for communicating with the probe unit, and wherein a coupling interface is arranged on the tool frame for mechanical and electrical coupling with a corresponding coupling interface.

[0150] 25. The light-emitting tool according to embodiment 24, wherein the probe unit is slidably arranged in the tool frame.

[0151] 26. A method for measuring the luminescence of a sample in an orifice plate arranged in a stage area of ​​a liquid handling apparatus, wherein the method comprises the following steps: - The probe of the light-emitting tool is positioned at the sample, wherein the light-emitting tool includes at least one probe having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal. - The sample is excited by emitting the light signal using the light emitter, and - Use the light receiver to detect / record the light emission signal subsequently emitted by the sample.

[0152] 27. The method according to embodiment 26, wherein the method further comprises the following steps: - Determine the normalized volume, - Normalize the sample volume.

[0153] 28. A computer-implemented method for determining sample normalization based on luminescence measurements according to Embodiment 26 or 27.

[0154] 29. Measure the luminescence of a sample in a well plate using the liquid processing apparatus according to any one of Examples 1–16, the liquid processing system according to any one of Examples 17–19, or the luminescence tool according to any one of Examples 20–25.

[0155] 30. A light emission measurement shielding system comprising at least one probe having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal, wherein the shielding system further comprises a covering element that closes the probe, wherein the covering element comprises a barrier that is opaque to the light and a covering opening disposed in the barrier that allows light to pass along an axis A–A, wherein the probe and the covering opening are movable relative to each other between a first relative position and a second relative position.

[0156] 31. The light emission measurement shielding system according to embodiment 30, wherein the light emission measurement shielding system includes a light emission tool configured to be arranged above the worktable area of ​​a liquid handling device, for example on a carrier arm, wherein the light emission tool includes at least one probe having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal, wherein, The light-emitting tool includes a tool housing with the covering element and the covering opening therein, such that the tool housing at least partially surrounds the probe, and wherein the tool housing supports a probe unit including the probe, and wherein the probe unit is slidably arranged in the tool housing between a first relative position and a second relative position.

[0157] 32. The light emission measurement shielding system according to embodiment 31, wherein the light emission tool further includes a circuit and / or coupling interface for communicating with the probe unit, the coupling interface being arranged on the tool frame for mechanical and electrical coupling with the corresponding coupling interface.

[0158] 33. The system according to any one of embodiments 30, 31 or 32, wherein the probe has an annular shape and the covering opening has an annular shape.

[0159] 34. The system according to any one of embodiments 30–33, wherein the probe and the covering opening are arranged coaxially along the axis A–A.

[0160] 35. The system according to any one of embodiments 30–34, wherein the probe and the covering opening are movable relative to each other along the axis A–A.

[0161] 36. The system according to embodiment 35, wherein the probe and the covering opening are restricted to relative movement only along the axis A–A.

[0162] 37. The system according to any one of embodiments 30–36, wherein the optical axis of the probe corresponds to the axis A–A.

[0163] 38. The system according to any one of embodiments 33–37, wherein the cover opening and the probe are annular, and the radius of the cover opening and the radius of the probe are the same.

[0164] 39. The system according to any one of embodiments 30–38, wherein the system further comprises an orifice plate including at least one hole, wherein the orifice plate is arranged such that the cover opening is located between the orifice plate and the at least one probe, and the hole is open toward the cover opening.

[0165] 40. The system according to embodiment 39, wherein a first distance between the covering opening and the at least one hole in the first relative position of the system is the same as a second distance between the covering opening and the at least one hole in the second relative position of the system.

[0166] 41. The system according to embodiment 39 or 40, wherein at least a portion of the barrier facing the perforated plate has a coverage width transverse to axis A–A, the coverage width corresponding to at least three times the width of the perforation.

[0167] 42. The system according to embodiment 41, wherein at least a portion of the barrier facing the perforated plate has a coverage length transverse to axis A–A and perpendicular to the width, the coverage length corresponding to at least three times the length of the perforation.

[0168] 43. The system according to embodiment 41 or 42, wherein the covering opening is disposed at the center of the portion of the barrier facing the perforated plate, having the covering width and / or covering length.

[0169] 44. A method for controlling the relative position of a probe and a cover opening of a light-emitting shielding system according to any one of embodiments 30–43 between a first relative position and a second relative position, and for controlling the distance between the cover opening and an orifice plate comprising at least one hole containing a sample, wherein the cover opening and the orifice plate are arranged such that the cover opening is positioned between the orifice plate and the at least one probe along an axis A–A, and the at least one hole is open toward the cover opening, wherein the method comprises: - Maintain the hole distance between the cover opening and the perforated plate at a predetermined hole distance. - Determine the liquid level height of the sample in the orifice. - Move the probe relative to the covering opening so that the distance between the probe and the liquid surface of the sample in the hole is at a predetermined liquid surface distance.

[0170] 45. The method according to Example 44, wherein the predetermined liquid level distance is determined based on the focal length of the light emission signal emitted from the probe, the liquid level height of the sample in the orifice, and the desired penetration depth of the light emission signal emitted from the probe, wherein the penetration depth is the distance from the sample liquid level to the focal point of the light emission signal in the sample.

[0171] 46. ​​The method according to Example 45, wherein the penetration depth is 3.5 mm.

Claims

1. A liquid handling apparatus (100) for transferring and processing liquids, comprising an operating chamber (102) disposed within a housing (101), and a workbench area (103) disposed within the operating chamber (102) for receiving / placing laboratory instruments, wherein the laboratory instruments include at least one perforated plate (302; 312), at least one pipette tip container including at least one pipette tip, and at least one measuring tool, wherein the operating chamber further comprises: - A carrier arm (105) for moving tools (200) between laboratory vessels arranged on the workbench area (103), and - A light-emitting tool (200) including at least one probe (203) having at least one light emitter for emitting a light-emitting signal and at least one light receiver for detecting the light-emitting signal, wherein the light-emitting tool (200) is configured to be arranged on the carrier arm (105).

2. The liquid handling apparatus (100) according to claim 1, wherein the light-emitting tool (200) has a coupling interface (218) for coupling the light-emitting tool (200) to and decoupling from the carrier arm (105).

3. The liquid handling apparatus according to claim 1, wherein the light-emitting tool is integrated in the carrier arm.

4. The liquid handling apparatus (100) according to any one of claims 1–3, wherein the probe (203) faces the worktable (103) when operated by the carrier arm (105).

5. The liquid handling apparatus (100) according to claim 4, wherein, During operation, at least the proximal end of the probe (203) facing the stage area has a cross-section smaller than that of the hole (301; 311) of at least one orifice plate (302; 312).

6. The liquid handling apparatus (100) according to any one of the preceding claims, wherein the light-emitting tool (200) comprises a tool frame (201) for supporting a probe unit (202), the probe unit comprising the probe (203) and circuitry for communicating with the probe unit (202), and wherein, The coupling interface (218) is arranged on the tool frame (201) for mechanical and electrical coupling with the corresponding coupling interface (105').

7. The liquid handling apparatus (100) according to claim 6, wherein the probe unit (202) is slidably arranged in the tool frame (201).

8. A light-emitting tool (200) configured to be arranged above a workbench area (103) of a liquid handling device (100), for example on a carrier arm (105), wherein the light-emitting tool (200) includes at least one probe (203) having a light emitter for emitting a light-emitting signal and a light receiver for detecting the light-emitting signal.

9. The light-emitting tool (200) according to claim 8, wherein the light-emitting tool (200) is configured to be disposed on the carrier arm (105).

10. The light-emitting tool (200) according to claim 8 or 9, wherein a first coupling interface (218) is disposed on the light-emitting tool, the first coupling interface being configured to couple and decouple from a corresponding second coupling interface (105') on the carrier arm (105) of the liquid handling device (100).

11. The light-emitting tool (200) according to any one of claims 8, 9, or 10, wherein the light-emitting tool (200) comprises a tool frame (201) for supporting a probe unit (202), the probe unit comprising the probe (203) and circuitry for communicating with the probe unit (202), and wherein, The coupling interface (218) is arranged on the tool frame (201) for mechanical and electrical coupling with the corresponding coupling interface (105').

12. The light-emitting tool (200) according to claim 11, wherein the probe unit (202) is slidably arranged in the tool frame (201).

13. A method for measuring the luminescence of a sample (300; 310) in an orifice plate (302; 312) arranged in a stage area (103) of a liquid handling apparatus (100), wherein the method comprises the following steps: - The probe (203) of the light-emitting tool (200) is positioned at the sample (300; 310), wherein the light-emitting tool (200) includes at least one probe (203), the at least one probe having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal. - The sample is excited by emitting the light signal using the light emitter, and - Use the light receiver to detect / record the subsequent emission signal emitted by the sample (300; 310).

14. A light emission measurement shielding system comprising at least one probe (203) having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal, wherein the shielding system further comprises a cover element (201) that closes the probe (203), wherein the cover element (201) comprises a light-opaque barrier and a cover opening (213, 219) disposed in the barrier to allow light to pass along an axis A–A, wherein the probe (203) and the cover opening (213, 219) are movable relative to each other between a first relative position (205) and a second relative position (206).

15. The light emission measurement shielding system according to claim 14, wherein the light emission measurement shielding system includes a light emission tool (200) configured to be arranged above a workbench area (103) of a liquid handling device (100), for example on a carrier arm (105), wherein the light emission tool (200) includes at least one probe (203) having a light emitter for emitting a light emission signal and a light receiver for detecting the light emission signal, wherein, The light-emitting tool (200) includes a tool housing (201), wherein the covering element (201) and the covering opening (213, 219) are configured such that the tool housing (201) at least partially surrounds the probe (203), and wherein the tool housing (201) supports a probe unit (202) including the probe (203), and wherein the probe unit (202) is slidably arranged in the tool housing (201) between a first relative position (205) and a second relative position (206).

16. The luminescence measurement shielding system according to claim 14 or 15, wherein the system further comprises an orifice plate (302; 312) including at least one hole (301; 311), wherein the orifice plate (302; 312) is arranged such that the cover opening (213; 219) is located between the orifice plate (302; 312) and the at least one probe (203), and the hole (301; 311) is open toward the cover opening.

17. The light emission measurement shielding system according to claim 16, wherein the first distance between the covering opening (213; 219) and the at least one perforated plate (302; 312) in the first relative position (205) of the system is the same as the second distance between the covering opening (213; 219) and the at least one perforated plate (302; 312) in the second relative position (206) of the system.

18. A method for controlling the relative positions of a probe (203) and a cover opening (213; 219) of a light-emitting shielding system according to any one of claims 15–17 between a first relative position (205) and a second relative position (206), and for controlling the distance between the cover opening (213; 219) and an orifice plate (302; 312) comprising at least one hole (301; 311) containing a sample (300; 310), wherein the cover opening (213; 219) and the orifice plate (302; 312) are arranged such that the cover opening (213; 219) is positioned along axis A–A between the orifice plate (302; 312) and the at least one probe (203), and the at least one probe (203) and the at least one hole (301; 311) are open toward the cover opening (213; 219), wherein the method comprises: - Maintain the hole distance between the cover opening (213; 219) and the perforated plate (302; 312) at a predetermined hole distance. - Determine the liquid level height of the sample (300; 310) in the orifice (301; 311). - Move the probe (203) relative to the covering opening (213; 219) such that the distance between the probe (203) and the liquid surface of the sample (300; 310) in the hole (301; 311) is at a predetermined liquid surface distance.

19. The method of claim 18, wherein the predetermined liquid level distance is determined based on the focal length of the light emission signal emitted from the probe (203), the liquid level height of the sample in the aperture (301; 311), and the desired penetration depth of the light emission signal emitted from the probe (203), wherein the penetration depth is the distance from the liquid level of the sample (300; 310) to the focal point of the light emission signal in the sample (300; 310).

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