Fluid dispenser and fluid container for supplying fluid to microfluidic system

Abstract

A fluid dispenser is configured to supply fluid to a microfluidic system, including a sample stage location configured to receive a sample stage. A sample stage is configured to receive a microscopic sample, including a microfluidic system having an injection port configured to receive a fluid intended to interact with the microscopic sample. The fluid dispenser also includes a microfluidic mixing chamber having a first input end, a second input end, and an output end. The microfluidic mixing chamber is configured to mix fluids provided through the first and second input ends and output the mixed fluids through the output end. The fluid dispenser further includes a first port configured to receive a fluid line for providing a first fluid to the first input of the microfluidic mixing chamber; a second port configured to receive a fluid container containing a second fluid to be mixed with the first fluid and to provide the second fluid to a second input of the microfluidic mixing chamber; and an adapter configured to connect the output end of the microfluidic mixing chamber with the injection port of the sample stage.

Description

Technical Field

[0001] The present invention relates to a fluid dispenser configured to supply fluid to a microfluidic system and a fluid container configured to be used with the fluid dispenser. Background Art

[0002] In the field of spatial omics, in order to study various biological processes, biological samples undergo multiple cycles of manipulation and treatment with various reagents. Reagents can be probes, antibodies, or chemicals such as hydrogen peroxide. In particular, when a reagent includes a fluorophore, it is also called a label. To observe the sample's response to the treatment, the sample is imaged during or after treatment with the reagents.

[0003] A typical experimental setup includes a dedicated microscope for imaging samples. The required staining and washing steps are usually performed outside the microscope: either manually on the bench or using an automated system, such as an immunohistochemistry (IHC) stainer. Manual sample processing is time-consuming and significantly reduces the throughput of the experiment. Integrated solutions now exist that combine a microscope and a stainer to reduce the time required to process samples.

[0004] A major drawback of the typical experimental setup described above is that many antibody stains, and especially many chemical probes, such as those used in fluorescence in situ hybridization (FISH) experiments, require large amounts of liquid during the wash cycle, but only a small volume is required during the actual staining cycle (e.g., when applying an antibody mixture). Typical injection systems use immersion and soaking methods, or simply pipette the liquid onto the sample surface. However, all known injection systems have the same problem, namely, they cannot handle very different volume sizes well. In particular, completely removing small volumes is very challenging because it is currently both time-consuming and expensive, for example requiring repeated rinsing with excess wash buffer. In addition, handling individual glass slides is a very challenging task for robotic systems because glass slides have a wide tolerance range. Glass dust is also a major problem for high-throughput systems. Batch processing, in contrast, is not easy to scale. The metal frame racks commonly used in batch processing are very large and take up a lot of space inside and outside the pipetting system when not fully loaded with slides. Summary of the Invention

[0005] An object of the present invention is to provide a fluid dispenser configured to supply fluid to a microfluidic system, and a fluid container configured for use with the fluid dispenser to facilitate easy-to-use, efficient, and automated sample preparation.

[0006] 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.

[0007] The proposed fluid dispenser is configured to supply fluid to a microfluidic system and includes a sample carrier position configured to receive a sample carrier. The sample carrier is configured to receive a microscopic sample and includes a microfluidic system having an injection port, which is configured to receive a fluid intended to interact with the microscopic sample. The fluid dispenser also includes a microfluidic mixing chamber having a first input end, a second input end, and an output end. The microfluidic mixing chamber is configured to mix the fluids provided through the first input end and the second input end and output the mixed fluid through the output end. The fluid dispenser also includes: a first port, which is configured to receive a fluid line for providing a first fluid to the first input end of the microfluidic mixing chamber; a second port, which is configured to receive a fluid container containing a second fluid to be mixed with the first fluid and provide the second fluid to the second input end of the microfluidic mixing chamber; and an adapter, which is configured to connect the output end of the microfluidic mixing chamber to the injection port of the sample carrier.

[0008] The proposed fluid dispenser forms an integrated system that allows the user to prepare a mixture of a first fluid and a second fluid and apply the mixture directly to a sample. The first fluid is provided via a fluid line and can be a solvent or a buffer. The second fluid is provided via a replaceable fluid container and can be a reagent, such as a chemical such as hydrogen peroxide, an antibody mixture, or a similar fluid formulation. Compared to the amount of the first fluid that can be provided via the fluid line, the amount of the second fluid stored in the fluid container can be negligible, for example, only a few microliters provided in the fluid container, while a few milliliters are provided via the fluid line. The first fluid enters the microfluidic mixing chamber through the first port and the first input end. The second fluid enters the microfluidic mixing chamber through the second port and the second input end. Within the microfluidic mixing chamber, the first and second fluids mix, and the mixture then leaves the microfluidic mixing chamber through the output end. The output end is connected to an adapter, which connects the output end of the microfluidic mixing chamber to the injection port of a sample carrier that forms part of the microfluidic system. The mixture is then applied to the sample through the injection port of the sample carrier and the microfluidic system.

[0009] Before the mixture is injected into the sample carrier, a mixture of the first fluid and the second fluid is prepared. This is particularly useful for chemicals or probes that deteriorate rapidly after dilution and / or mixing with a buffer solution, such as hydrogen peroxide, which decomposes in less than a minute after mixing. Therefore, the proposed fluid dispenser allows efficient automated sample preparation. Providing the second fluid via a fluid container makes it possible, for example, to provide the correct amount and / or concentration of the second fluid for a particular experiment without the user having to pipette or otherwise measure out the correct amount during the experiment. This also makes the proposed fluid dispenser very easy to use. The fluid container can also be a consumable item, such as a small sealed bottle. Providing the fluid container as a disposable item prevents carryover and cross contamination.

[0010] In one embodiment, the fluid dispenser includes a pressurized fluid source and a pressure line connected to the pressurized fluid source. The pressure line is configured to be connected to a pressure port of a fluid container to provide pressurized fluid to the fluid container for discharging a second fluid from the fluid container into the microfluidic mixing chamber via the second port. The pressurized fluid replaces the second fluid in the fluid container. Therefore, the second fluid itself is pressurized and forced into the microfluidic mixing chamber via the second port. By forcing the second fluid to leave the fluid container, the fluid container is quickly emptied, which speeds up the mixing process. In addition, pressurizing the second fluid also greatly contributes to the mixing of the first and second fluids themselves, ensuring that the first and second fluids are properly mixed. The pressurized fluid can be a liquid or a gas. Preferably, the pressurized fluid is air. However, the pressurized fluid can also be a viscous liquid. In addition, a small membrane can be provided between the second fluid and the pressurized fluid to prevent the second fluid and the pressurized fluid from mixing. In such an embodiment, an aqueous solution can be used as the pressurized fluid.

[0011] In another embodiment, the fluid dispenser includes a temperature control unit configured to heat and / or cool the fluid container when the fluid container is received in the second port. The temperature control unit controls the temperature of the second fluid stored in the fluid container received in the second port. In particular, antibodies and many chemical probes, such as probes used in FISH experiments, are very sensitive to temperature. They have very specific temperature requirements and may decompose when stored at the wrong temperature. By storing the second fluid in a temperature-controlled environment, waste can be reduced. Temperature is also one of the key factors determining the specificity and efficiency of the staining process. Temperature is a further determining factor in the efficiency of the washing step and the overall speed of the staining and washing cycle. Therefore, by allowing fine control of the temperature of the second fluid, especially as a function of time, the fluid dispenser allows very precise control of the annealing step, thereby improving the overall efficiency of the staining and washing cycle.

[0012] In another embodiment, the fluid dispenser includes a bubble trap configured to remove bubbles from the first fluid and / or the second fluid. The bubble trap significantly reduces the risk of introducing bubbles into the microfluidic system of the sample carrier, thereby improving the accuracy and reliability of fluid flow control. This is crucial for ensuring consistent experimental conditions and repeatability of results in applications, particularly in applications where precise manipulation of small volumes of the second fluid is required. Multiple bubble traps may be provided. Each bubble trap may be part of a microfluidic mixing chamber and may be arranged between the first port and the first input end or between the second port and the second input end.

[0013] In another embodiment, the fluid dispenser includes a degasser configured to remove dissolved gases from the first fluid and / or the second fluid. Providing a degasser for the fluid dispenser can effectively remove dissolved gases from the first fluid and / or the second fluid. This prevents the formation of bubbles that can clog the microfluidic channels of the sample carrier and disrupt fluid flow, thereby maintaining the accuracy and consistency of microfluidic operations. Multiple degassers can be provided. Each degasser can be part of the microfluidic mixing chamber and can be arranged between the first port and the first input end or between the second port and the second input end.

[0014] In another embodiment, the fluid dispenser includes at least one storage location configured to receive an additional fluid container. The fluid dispenser can also include a fluid container positioning unit configured to automatically replace the fluid container received at the second port with one of the additional fluid containers. This embodiment allows a variety of different reagents to be automatically applied to the sample, for example, to automate dyeing and washing cycles. Different reagents are stored in different fluid containers. When a specific reagent is needed, the fluid container positioning unit is placed in the second port with the corresponding fluid container. Once the fluid container currently arranged in the second port is emptied, the fluid container positioning unit can remove the fluid container.

[0015] In another embodiment, the fluid container positioning unit includes a main body having at least two storage positions. The main body can be moved in at least one direction for alternately positioning the fluid containers received in the storage positions at the second port. In this embodiment, the movable main body forms part of the fluid container positioning unit. By moving the main body, the fluid containers can be alternately positioned at the second port. This is a mechanically very simple embodiment of the fluid container positioning unit. The main body can be a frame-like structure, allowing the fluid containers to be stored in a grid-like arrangement. This makes it very easy to load the fluid containers into the fluid dispenser.

[0016] In another embodiment, the fluid dispenser includes a temperature control unit configured to heat and / or cool at least one fluid container received in the storage location. The temperature control unit controls the temperature of the second fluid stored in the fluid container received in the storage location. As mentioned above, many reagents are temperature sensitive and require specific storage temperatures, otherwise they will degrade. This embodiment allows such temperature sensitive reagents to be stored in the storage location.

[0017] In another embodiment, the fluid dispenser includes an opening creation unit that is configured to create an opening in the fluid container received at the second port to discharge the second fluid. Creating the opening enables the second fluid to leave the fluid container via the second port. In this embodiment, the fluid container can be provided as a sealing unit. An opening can be created in the fluid container just before the second fluid is needed. This further protects the second fluid stored therein from environmental influences, preventing degradation and waste. The opening creation unit is preferably arranged at the second port. In one example, the opening creation unit includes a piercing element that is configured to pierce the fluid container received at the second port to create an opening for discharging the second fluid. Alternatively, the opening creation unit includes a needle that is configured to pierce the seal of the fluid container received at the second port to create an opening for discharging the second fluid. In such an embodiment, the second fluid is discharged via the internal channel (also referred to as the lumen) of the needle. In another alternative, the opening creation unit includes a cutting element that is configured to cut the fluid container to create an opening for discharging the second fluid. In such an embodiment, the fluid container can include a protrusion that is configured to be cut by the cutting element.

[0018] In a further embodiment, the fluid dispenser is configured to move an adapter and / or a sample carrier arranged in a sample carrier position so as to arrange the adapter at the injection port of the sample carrier. In this embodiment, the adapter is moved to the injection port of the sample carrier. For example, the fluid dispenser can serve a plurality of sample carriers in this manner, each sample carrier comprising an injection port. Alternatively, the sample carrier is moved to the adapter. For example, by means of a robotic arm or similar device, the fluid dispenser can be supplied with a plurality of sample carriers, each sample carrier comprising an injection port. These two alternatives make it possible to serve a large number of sample carriers using the same fluid dispenser, thereby greatly increasing the throughput of the experiment.

[0019] In another embodiment, the microfluidic mixing chamber includes a mixing channel, a first inlet channel connecting the first port to the mixing channel, and a second inlet channel connecting the second port to the mixing channel. The mixing channel preferably includes at least one section in which the mixing channel is formed as a serpentine channel. The mixing channel is a microfluidic element that promotes mixing of a first fluid and a second fluid introduced through the first input end and the second input end, respectively. Microfluidic applications typically process very small fluid volumes. In these small volumes, fluids behave very viscous and do not mix well on their own. By forcing the first fluid and the second fluid through the serpentine channel, the two fluids are forced to mix, thereby ensuring uniform mixing of the fluids.

[0020] In another embodiment, the fluid line is pressurized. Providing the first fluid under pressure to the microfluidic mixing chamber helps to better mix the first fluid and the second fluid in the microfluidic mixing chamber.

[0021] In further embodiments, the second port comprises threads configured to engage with complementary threads of the fluid container to attach the fluid container to the fluid dispenser.Threads are a very simple way to securely attach a fluid container to a fluid dispenser.

[0022] The present invention also relates to a fluid container configured for use with the aforementioned fluid dispenser. The fluid container has the same advantages as the aforementioned fluid dispenser. Specifically, the fluid container can supplement the features described herein with respect to the fluid dispenser. Furthermore, the aforementioned fluid dispenser can supplement the features described herein with respect to the fluid container.

[0023] In one embodiment, the fluid container includes a vent port and / or a pressure relief valve configured to allow gases to escape from the interior of the fluid container. Providing a vent port and / or a pressure relief valve on the fluid container prevents the accumulation of gases, such as oxygen produced during the decomposition of hydrogen peroxide. Gas accumulation can damage the fluid container, causing the fluid inside to escape and rendering the fluid unusable. In the case of hydrogen peroxide decomposition, the accumulation of oxygen can also pose a fire hazard.

[0024] In another embodiment, the fluid container is made of an opaque and / or light-proof material. Using an opaque and / or light-proof material to construct a fluid container protects the fluid stored within the fluid container from light, particularly sunlight, thereby preventing the degradation of light-sensitive fluids over time. For example, hydrogen peroxide is light-sensitive and will decompose even after brief exposure to light.

[0025] In another embodiment, the fluid container is made of a chemically resistant material and / or a material suitable for withstanding temperatures as low as -80°C and / or as high as 100°C while maintaining structural integrity and functional properties. Making the fluid container from a chemically resistant material ensures the purity of the second fluid stored therein, prevents reactions between the fluid container and the second fluid, and thus prevents contamination or degradation over time. Antibodies used to stain biological samples are typically stored at temperatures around -80°C. Therefore, making the fluid container suitable for withstanding temperatures as low as -80°C allows the fluid container to be used for storing antibodies and for use in applications utilizing antibodies. In molecular biology, staining of DNA is typically achieved by inserting dye molecules between the stacked base pairs of the DNA double helix, a process known as intercalation. Some staining protocols may involve thermal cycling or heating steps that require heating the DNA to +98°C. Therefore, making the fluid container suitable for withstanding temperatures as high as +98°C allows the fluid container to be used in such DNA staining protocols. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The specific embodiments are described below with reference to the accompanying drawings, in which:

[0027] Figure 1 is a schematic side view of a fluid dispenser according to an embodiment;

[0028] Figure 2 is based on Figure 1 A schematic top view of a fluid distributor;

[0029] Figure 3 is a schematic side view of a fluid dispenser including a temperature control unit according to another embodiment;

[0030] Figure 4 is a schematic side view of a fluid dispenser including a fluid container positioning unit according to another embodiment;

[0031] Figure 5 It can be used as a basis Figures 1 to 4 a schematic view of a degasser that is a portion of a fluid distributor of any of; and

[0032] Figure 6 It can be used as a basis Figures 1 to 4 Schematic view of a bubble trap as part of any one of the fluid dispensers. DETAILED DESCRIPTION

[0033] Figure 1 1 is a schematic side view of a fluid dispenser 100 according to an embodiment. The fluid dispenser 100 is configured to supply fluid to a microfluidic system 102 of a sample carrier 104.

[0034] The sample carrier 104 is arranged at the sample carrier position 200 below the fluid dispenser 100 (see Figure 2 ) and in Figure 1 The cutout extends along the length of the sample carrier 104, i.e. Figure 1 From left to right in FIG. The sample carrier 104 includes a sample receiving compartment 106 configured to receive a sample 202 (see FIG. Figure 2 In this embodiment, the sample receiving compartment 106 is configured to receive a sample 202 prepared on a microscope slide 108, particularly a biological sample 202 prepared on the microscope slide 108. A removable cover 110 is disposed on top of the microscope slide 108, covering the sample 202 from above. The cover 110 may be transparent, thereby allowing a user to observe the sample 202 from above and to image the sample 202 through the cover 110.

[0035] The microfluidic system 102 of the sample carrier 104 illustratively includes an injection port 112, a first fluid channel 114, a second fluid channel 116, and an exhaust port 118. The injection port 112 and the exhaust port 118 are illustratively arranged on opposite sides of the sample receiving compartment 106. The injection port 112 is arranged on Figure 1 The exhaust port 118 is arranged on the left side of the sample receiving compartment 106 and is connected to the sample receiving compartment 106 through the first fluid channel 114. Figure 1 The second fluid channel 116 is connected to the sample receiving compartment 106. Various fluids (e.g., reagents or wash buffers) can be introduced into the sample receiving compartment 106 via the injection port 112, where they can interact with the sample 202 disposed therein. Any liquid or gas already within the sample receiving compartment 106 can escape through the exhaust port 118.

[0036] The fluid dispenser 100 includes a microfluidic mixing chamber 120 having a first input end 122, a second input end 124, and an output end 126. The microfluidic mixing chamber 120 is configured to mix fluids provided via the first input end 122 and the second input end 124, and output the mixed fluid via the output end 126. To this end, the mixing chamber 120 includes a mixing channel 128 disposed between the first and second input ends 122, 124 and the output end 126. The mixing channel 128 will be referred to hereinafter. Figure 2 Describe in more detail.

[0037] The output end 126 of the mixing channel 128 is connected to an adapter 130 of the fluid dispenser 100, which is configured to be connectable to the injection port 112 of the sample carrier 104. In the present embodiment, the adapter 130 illustratively includes a seal 132 in the form of an O-ring surrounding the discharge opening of the adapter 130. The seal 132 ensures a leak-proof connection to the injection port 112 and compensates for mechanical tolerances within the connection.

[0038] The first fluid can be a solvent or a buffer and is provided via a fluid line 134. By providing the first fluid via a dedicated fluid line 134, a large amount of the first fluid, for example, up to several milliliters, can be provided. The fluid line 134 can be attached to the fluid dispenser 100 at a first port 136, which is connected to the first input end 122 of the microfluidic mixing chamber 120. Thus, the first fluid is provided to the microfluidic mixing chamber 120.

[0039] The second fluid is a reagent to be applied to sample 202, such as an antibody mixture, a dye or a chemical such as hydrogen peroxide. In contrast to the first fluid, only a small amount of the second fluid is required, typically within the range of several microliters. Therefore, the second fluid is provided via a dedicated fluid container 138. Fluid container 138 can be attached to fluid dispenser 100 at a second port 140, which is connected to the second input 124 of microfluidic mixing chamber 120. The second port 140 is exemplarily shown as a thread, which is engaged by the complementary thread of fluid container 138 to attach fluid container 138 to fluid dispenser 100. In the present embodiment, fluid dispenser 100 includes a pressurized fluid source 142, such as pressurized air. A pressure line 144 connects pressurized fluid source 142 to a pressure port 146 of fluid container 138. Pressurized fluid can be introduced into fluid container 138 to force the second fluid to flow out of fluid container 138 via the second port 140, thereby providing the second fluid to the second input 124 of microfluidic mixing chamber 120.

[0040] The fluid container 138 can be provided with a vent port 148 to allow the escape of accumulated gases, such as oxygen produced by the decomposition of hydrogen peroxide. Alternatively, or in addition, a pressure relief valve can be provided at the same location. To prevent degradation of the second fluid stored therein, the fluid container 138 can be made of a chemically resistant material and / or a light-proof material (e.g., a chemically inert black plastic). In addition to being stable at room temperature, the fluid container 138 can also be made of a material that is stable at temperatures as low as -80°C to allow storage of antibodies, and / or made of a material that is stable at temperatures as high as 100°C to allow the fluid container 138 to be used in certain DNA staining protocols.

[0041] Figure 2 is based on Figure 1 Schematic top view of the fluid dispenser 100. Figure 2 Also shown are a sample carrier position 200 and a sample 202 in the sample receiving compartment 106 of the sample carrier 104 .

[0042] like Figure 2 As shown, in this embodiment, the microfluidic mixing chamber 120 includes a first inlet channel 204 and a second inlet channel 206. The second inlet channel is partially covered by the fluid container 138. Figure 2 The first inlet channel 204 connects the first port 136 with the mixing channel 128 , and the second inlet channel 206 connects the second port 140 with the mixing channel 128 .

[0043] In this embodiment, mixing channel 128 comprises a serpentine channel with multiple bends. The bends lengthen the paths of the first and second fluids through microfluidic mixing chamber 120, thereby increasing the interaction between them. The increased path length and repeated changes in direction also induce a chaotic flow pattern, thereby improving the uniformity of the mixed fluids without the need for external stirring.

[0044] Figure 3 is a schematic side view of a fluid dispenser 300 according to another embodiment.

[0045] according to Figure 3 The distributor 300 is configured according to Figure 1 The difference between the fluid dispenser 100 and the microfluidic dispenser 100 is that the former has a temperature control unit 302. The temperature control unit 302 is illustratively arranged above the microfluidic mixing chamber 120 and is configured to control the temperature of the fluid container 138 currently received in the second port 140. In order to control the temperature, the temperature control unit 302 may include heating and / or cooling elements, such as electric heating elements and Peltier elements. These heating and / or cooling elements are preferably arranged near the fluid container 138. The temperature control unit 302 may also include an insulator arranged around the fluid container 138. By using the temperature control unit 302, the user can very accurately control the temperature of the second fluid stored in the fluid container 138.

[0046] according to Figure 3 The fluid dispenser 300 is configured according to Figure 1 The difference between the fluid dispenser 300 and the fluid dispenser 300 is that the former exemplarily includes a degasser 304 disposed between the first port 136 and the first input end 122 of the microfluidic mixing chamber 120. The degasser 304 is configured to remove dissolved gas from the first fluid before the first fluid enters the microfluidic mixing chamber 120. Alternatively, a bubble trap 600 (see Figure 6 ), which is configured to remove bubbles trapped in the first fluid. Figure 5 and Figure 6The degasser 304 and the bubble trap 600 are described in more detail. The degasser 304 or the bubble trap 600 can also be provided between the second port 140 and the second input end 124 of the microfluidic mixing chamber 120 to remove dissolved bubbles and trapped bubbles, respectively, from the second fluid, or between the output end 126 of the microfluidic mixing chamber 120 and the adapter 130 to remove dissolved bubbles and trapped bubbles, respectively, from the mixed fluid.

[0047] Figure 4 is a schematic side view of a fluid dispenser 400 according to another embodiment.

[0048] according to Figure 4 The distributor 400 is configured according to Figure 1 The difference between the fluid dispenser 100 and the fluid dispenser 100 is that the former has a fluid container positioning unit 402. The fluid container positioning unit 402 includes a main body 404, which forms a plurality of storage locations 406. Each storage location 406 is configured to receive a fluid container 138. For example only, the main body 404 is formed as a grid-like shelf, and the fluid container 138 is inserted into it from the top. The main body 404 can be Figure 4 Move from left to right in Figure 4 Move up and down, such as Figure 4 Adaptively, the main body 404 can be perpendicular to Figure 4 The movable body 404 allows the fluid container positioning unit 402 to alternately position one of the fluid containers 138 received by the body 404 in the second port 140. As a result, the second fluid stored in the fluid container 138 can be discharged into the microfluidic mixing chamber 120. The body 404 also includes a temperature control unit 408, which is configured to control the temperature of the fluid container 138 received in the storage position 406. The temperature control unit 408 can be configured to heat and / or cool the fluid container 138 using, for example, an electric heating element and / or a Peltier element. The temperature control unit 408 can also include an insulator arranged around the storage position 406.

[0049] according to Figure 4 The fluid dispenser 400 further includes an opening creation unit 410 disposed at the second port 140. The opening creation unit 410 is configured to create an opening in the fluid container 138 received at the second port 140, through which the second fluid can be discharged into the microfluidic mixing chamber 120. This allows the fluid container 138 to be sealed after being filled with the second fluid and remain sealed until the second fluid is needed in an experiment. In this embodiment, the opening creation unit 410 includes a hollow needle that is configured to be inserted into the fluid container 138 from below to create the opening. The second fluid is discharged into the second port 140 via the lumen of the hollow needle.

[0050] In this embodiment, the fluid dispenser 400 further includes an additional hollow needle 412, which is disposed at one end of the pressure line 144 and above the second port 140. The hollow needle 412 can be moved up and down to pierce, from above, the fluid container 138 currently disposed at the second port 140. Through the lumen of the hollow needle 412 and the piercing created by the hollow needle 412, pressurized fluid can be injected into the fluid container 138 to replace the second fluid, thereby draining it.

[0051] Figure 5 is a schematic view of a degasser 304, which may be a Figures 1 to 4 A portion of any one of the fluid dispensers 100, 300, 400.

[0052] The degasser 304 can be arranged between the first port 136 and the first input end 122 of the microfluidic mixing chamber 120, for example, on the first inlet channel 204. In this configuration, the degasser 304 removes dissolved gases from the first fluid before the first fluid is mixed with the second fluid. In an alternative, the degasser 304 is arranged between the second port 140 and the second input end 124 of the microfluidic mixing chamber 120, for example, on the second inlet channel 206. In this configuration, the degasser 304 removes dissolved gases from the second fluid before the first fluid and the second fluid are mixed. In another alternative, the degasser 304 is arranged between the output end 126 of the microfluidic mixing chamber 120 and the adapter 130, thereby removing dissolved gases from the mixed fluid before the mixed fluid is introduced into the microfluidic system 102. More than one degasser 304 can be provided, each degasser 304 arranged at a different location.

[0053] The degasser 304 includes an inlet channel 500, a degassing channel 502, and an outlet channel 504. The fluid to be degassed enters the degasser 304 via the inlet channel 500, is guided by the degassing channel 502, and leaves the degasser 304 via the outlet channel 504. The degassing channel 502 includes a semipermeable membrane 506 that allows gas to pass through the fluid while preventing the fluid itself from escaping. A vacuum line 508 can be attached to the degasser 304 to create a partial vacuum in a chamber 510 that is arranged on the side of the semipermeable membrane 506 opposite the degassing channel 502. Using the vacuum line 508, a partial vacuum can be created in the chamber 510, thereby creating a pressure differential that removes dissolved gases from the fluid by drawing gas molecules from the fluid through the semipermeable membrane 506.

[0054] Figure 6 is a schematic diagram of a bubble trap 600 that can be used as a Figures 1 to 4 Any one of the fluid dispensers 100 .

[0055] The bubble trap 600 may be arranged in the above reference Figure 5 The degasser 304 is arranged at any position to remove trapped bubbles from the first fluid, the second fluid or the mixed fluid. A plurality of bubble traps 600 may be provided, each bubble trap 600 being arranged at a different position.

[0056] The degasser 304 includes an inlet channel 602, a bubble chamber 604, and an outlet channel 606. The fluid to be deaerated enters the bubble trap 600 via the inlet channel 602 and is directed into the bubble chamber 604. The outlet channel 606 is connected to the bubble chamber 604 but is arranged below the inlet channel 602. The bubble chamber 604 has a larger diameter than the inlet channel 602, thereby slowing the fluid flow rate. This allows the bubbles to rise and separate from the fluid in the bubble chamber 604 due to the difference in buoyancy, and the fluid then leaves the bubble chamber 604 through the outlet channel 606.

[0057] In all figures, the same or similar elements are denoted by the same reference numerals. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ".

[0058] 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.

[0059] Reference numerals

[0060] 100 Fluid Dispenser

[0061] 102 Microfluidic Systems

[0062] 104 Sample stage

[0063] 106 Sample receiving compartment

[0064] 108 microscope slides

[0065] 110 lid

[0066] 112 injection port

[0067] 114, 116 fluid channels

[0068] 118 exhaust port

[0069] 120 Microfluidic Mixing Chamber

[0070] 122, 124 input terminals

[0071] 126 output

[0072] 128 mixing channels

[0073] 130 adapter

[0074] 132 seals

[0075] 134 fluid lines

[0076] Port 136

[0077] 138 Fluid containers

[0078] Port 140

[0079] 142 Source

[0080] 144 pressure lines

[0081] Port 146

[0082] 148 ventilation ports

[0083] 200 Sample stage position

[0084] 202 samples

[0085] Entrances 204 and 206

[0086] 300 Fluid Dispenser

[0087] 302 Temperature Control Unit

[0088] 304 Degasser

[0089] 400 Fluid Dispenser

[0090] 402 Fluid Container Positioning Unit

[0091] 404 Body

[0092] 406 Storage Location

[0093] 408 Temperature Control Unit

[0094] 410 Opening Creation Unit

[0095] 412 hollow needle

[0096] Channels 500, 502, and 504

[0097] 506 membrane

[0098] 508 vacuum line

[0099] 510 Chamber

[0100] 600 Bubble Trap

[0101] 602 channels

[0102] 604 Chamber

[0103] Channel 606

Claims

1. A fluid dispenser (100, 300, 400) configured to supply fluid to a microfluidic system (102), comprising: a sample carrier position (200) configured to receive a sample carrier (104) configured to receive a microscopic sample (202) and comprising a microfluidic system (102) having an injection port (112) configured to receive a fluid intended to interact with the microscopic sample (202); a microfluidic mixing chamber (120) having a first input end (122), a second input end (124), and an output end (126), the microfluidic mixing chamber (120) being configured to mix fluids provided via the first input end (122) and the second input end (124) and to output (126) the mixed fluid via the output end (126); a first port (136) configured to receive a fluid line (134) for providing a first fluid to a first input end (122) of the microfluidic mixing chamber (120); a second port (140) configured to receive a fluid container (138) containing a second fluid to be mixed with the first fluid and provide the second fluid to a second input (124) of the microfluidic mixing chamber (120); as well as An adapter (130) is configured to connect the output end (126) of the microfluidic mixing chamber (120) to the injection port (112) of the sample carrier (104).

2. The fluid dispenser (100, 300, 400) according to claim 1 comprises a pressurized fluid source (142) and a pressure line (144) connected to the pressurized fluid source (142), wherein the pressure line (144) is configured to be connected to a pressure port (146) of the fluid container (138) to provide pressurized fluid to the fluid container (138) to discharge the second fluid from the fluid container (138) into the microfluidic mixing chamber (120) via the second port (140).

3. The fluid dispenser (300) according to claim 1 or 2, comprising a temperature control unit (302) configured to heat and / or cool the fluid container (138) when the fluid container (138) is received in the second port (140).

4. The fluid dispenser (300) according to any one of the preceding claims, comprising a bubble trap (600) configured to remove air bubbles from the first fluid and / or the second fluid.

5. The fluid dispenser (300) according to any one of the preceding claims, comprising a degasser (304) configured to remove dissolved gases from the first fluid and / or the second fluid.

6. A fluid dispenser (400) according to any of the preceding claims, comprising at least one storage position (406) configured to receive an additional fluid container (138), and wherein the fluid dispenser (400) comprises a fluid container positioning unit (402) configured to automatically replace the fluid container (138) received at the second port (140) with one of the additional fluid containers (138).

7. A fluid dispenser (400) according to claim 6, wherein the fluid container positioning unit (402) includes a main body (404) having at least two of the storage positions (406), and wherein the main body (404) is movable in at least one direction to alternately position the fluid container (138) received in the storage position (406) at the second port (140).

8. The fluid dispenser (400) according to claim 6 or 7, comprising a temperature control unit (408) configured to heat and / or cool at least one of the fluid containers (138) received in the storage position (406).

9. The fluid dispenser (400) according to any one of the preceding claims, comprising an opening creation unit (410) configured to create an opening in a fluid container (138) received at the second port (140) to discharge the second fluid.

10. A fluid dispenser (100, 300, 400) according to any one of the preceding claims, wherein the fluid dispenser (100, 300, 400) is configured to move an adapter (130) and / or a sample carrier (104) arranged in the sample carrier position (200) to arrange the adapter (130) at an injection port (112) of the sample carrier (104).

11. A fluid dispenser (100, 300, 400) according to any one of the preceding claims, wherein the microfluidic mixing chamber (120) includes a mixing channel (128), a first inlet channel (204) connecting a first port (136) with the mixing channel (128), and a second inlet channel (206) connecting a second port (140) with the mixing channel (128), wherein the mixing channel (128) preferably includes at least one section at which the mixing channel (128) is formed as a serpentine channel.

12. A fluid container (138) configured for use with the fluid dispenser (100, 300, 400) according to any one of the preceding claims.

13. The fluid container (138) of claim 12, wherein the fluid container (138) includes a vent port (148) and / or a pressure relief valve configured to allow gas to escape from an interior of the fluid container (138).

14. The fluid container (138) according to claim 12 or 13, wherein the fluid container (138) is made of an opaque material and / or a light-proof material.

15. A fluid container (138) according to any one of claims 12 to 14, wherein the fluid container (138) is made of a chemically resistant material and / or made of a material suitable for withstanding temperatures as low as -80°C and / or as high as 100°C while maintaining structural integrity and functional properties.

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