Device and method for producing a concentrated reagent from a solid substance

Description

1 / 26 “DEVICE AND METHOD FOR PRODUCING A CONCENTRATED REAGENT FROM A SOLID SUBSTANCE” FIELD OF THE INVENTION

[0001] The field of the invention relates to the production of concentrated reagents for the analysis of biological fluid samples, particularly in hematology. BACKGROUND OF THE INVENTION

[0002] Medical biology is a specialty that involves the analysis of biological fluids to determine the pathophysiological origin of a disease. A medical biology examination can also contribute to the prevention, screening, diagnosis, or risk assessment of pathological conditions, as well as to the determination or monitoring of a patient's physiological or pathophysiological state.

[0003] The biological fluid to be analyzed may be, for example, blood, urine, cerebrospinal fluid, pleural fluid, synovial fluid, or bone marrow collected by puncture.

[0004] A medical biology exam typically unfolds in three phases: - a pre-analytical phase, which includes the collection of a biological fluid sample from the patient, as well as the preparation, transport and storage of the sample; - an analytical phase, which corresponds to the technical process that allows the generation of a biological analysis result; and - a post-analytical phase, which corresponds to the contextual interpretation of the result.

[0005] Optimizing sample workflow management is currently a crucial aspect in the organization of a medical biology laboratory. In particular, the quality of sample workflow management can be assessed using two parameters: turnaround time (TAT) and full-time equivalent (FTE), which measures the staff workload required for the operation of the medical biology laboratory.

[0006] These two parameters are influenced by a key element that is intrinsically linked to the management of sample workflows: delivery. Petition 870260051189, dated 05 / 28 / 2026, page 12 / 44 2 / 26 of reagents.

[0007] The sample to be analyzed may contain all types of particles (cells, proteins, biomarkers, etc.) that will need to be counted and identified. Thus, before biological analysis, the sample may be diluted and treated with one or more reagents. The sample may then be sent to an automated flow-based measuring instrument – ​​that is, one that uses the principle of flow cytometry – capable of counting and identifying the particles present in the sample by means of electrical and / or optical measurements.

[0008] By way of example, in hematology, an automated instrument dedicated to counting and differentiating blood cells typically consumes dilution, staining, lysis, and sheath reagents. Specifically, the staining reagent allows the blood sample to be mixed with fluorophores during sample preparation in order to facilitate subsequent differentiation; and the sheath reagent – ​​also called the carrier fluid – allows the aspiration and direction of the blood sample through the instrument.

[0009] Still within the area of ​​hematology, a large part of the total volume of reagents consumed consists of dilution and rinsing reagents. On average, a volume of 40 milliliters (mL) of reagent is consumed per hematological analysis. In large laboratories, the daily reagent requirement can reach 40 liters (L).

[0010] In particular, a complete blood count (CBC) – also known as a blood count – is often preceded by a dilution step, which serves to reduce the concentration of blood cells in a sample in order to facilitate their counting.

[0011] Delivering reagents to a medical biology laboratory typically requires a dedicated team, which often faces handling challenges. The reagents are stored in large-capacity containers known as cubitainers, which are heavy, bulky, and require frequent refilling throughout the day. Petition 870260051189, dated 05 / 28 / 2026, page 13 / 44 3 / 26

[0012] To mitigate these limitations, it is common practice to produce reagents on-site at a so-called “working” concentration, that is, reagents ready for immediate use in biological analyses. To this end, some medical biology laboratories use devices capable of producing a working concentration reagent from a concentrated reagent and water purified by osmosis. This purified water is often produced on-site by a purification unit fed with untreated water and can be used directly by biochemical analyzers.

[0013] In this respect, European Patent EP 3 714 252 B1 proposes a diluent preparation module comprising a “combining device” connected to a purified water source and a “reagent concentrate” container. The combining device is configured to mix the purified water and the reagent concentrate in order to produce a diluent which is then stored while awaiting transport to an analyzer.

[0014] European patent EP 2 175 340 B1 describes, based on the same principle, a reagent preparation device comprising a “constant quantity liquid quantification unit” equipped with an instrument capable of simultaneously maintaining a “high concentration reagent” and a diluent in constant quantity, and transferring them to a single storage unit to produce the reagent present there by mixing.

[0015] These devices use a concentrated reagent manufactured from a liquid reagent, which has several disadvantages.

[0016] First of all, such a concentrated reagent is, at best, a 25x concentrate, that is, a reagent whose concentration is only 25 times greater than the working concentration. This concentration is limited, in particular, by the solubility of the salt or salts present in the liquid reagent used; this solubility cannot be exceeded without the risk of crystallization, which alters the physicochemical properties of the resulting concentrated reagent.

[0017] Such a low concentration results in a high consumption of concentrated reagent. In general, the manufacture of concentrated reagents from Petition 870260051189, dated 05 / 28 / 2026, page 14 / 44 4 / 26 liquid reagents entails logistical problems similar to those described above, related to the volumes involved, whether they are liquid or concentrated reagents; the transport and storage of concentrated reagents therefore require packaging in containers of 10 or even 20 liters (L).

[0018] In addition, these concentrated reagents contain chemicals with hazard pictograms, which complicates their transport and storage. In particular, concentrated diluents often contain preservatives and pH buffers, such as formaldehyde, imidazole, glutaraldehyde, or sodium azide. These substances are harmful to both the health of medical biology laboratory professionals and the environment.

[0019] The present invention seeks to improve this situation.

[0020] To that end, the invention relates to a device for producing concentrated reagent, comprising: - a reservoir for solvent, - a container that holds a solid substance having a solubility in water at 20°C greater than or equal to 340 g / L, - a bomb, and - a production circuit including a first tube fitted with a first valve and a second tube fitted with a second valve.

[0021] The pump is fluidically connected to the reservoir and the container via the first and second tubes, respectively.

[0022] The device is configured to operate in at least the following modes: a solvent withdrawal mode, in which the first valve is open, the second valve is closed, and the pump is configured to draw solvent from the reservoir; and a concentrated reagent production mode, in which the first valve is closed, the second valve is open, and the pump is configured to discharge solvent into the container so that a concentrated reagent is produced by dissolving at least Petition 870260051189, dated 05 / 28 / 2026, page 15 / 44 5 / 26 a portion of the solid substance in the solvent, and to aspirate the concentrated reagent from the container.

[0023] In one or more embodiments, the device further comprises a storage tank for concentrated reagent, the production circuit also includes a third tube provided with a third valve, and the pump is also fluidically connected to the storage tank via the third tube. The third valve is closed in the solvent withdrawal mode and in the concentrated reagent production mode of the device.

[0024] The device is further configured to operate in a concentrated reagent storage mode, in which the first valve is closed, the second valve is closed, the third valve is open, and the pump is set to discharge the concentrated reagent into the storage tank.

[0025] In one or more embodiments, the device is further configured to operate in a concentrated reagent homogenization mode, in which the first valve is closed, the second valve is closed, the third valve is open, and the pump is configured to alternate between drawing concentrated reagent from the storage tank and discharging concentrated reagent back into the storage tank, one or more times.

[0026] In one or more embodiments, the storage tank is provided with a mixer configured to homogenize, by mixing, the concentrated reagent stored in the storage tank.

[0027] In one or more embodiments, the storage tank is provided with at least one level sensor configured to detect when a certain volume of concentrated reagent has been reached within the storage tank.

[0028] In one or more embodiments, the concentrated reagent is a diluting, lysis, entrainment, rinsing, or staining reagent.

[0029] In one or more embodiments, the reservoir is a reservoir for one or a combination of the following solvents: water purified by osmosis, water Petition 870260051189, dated 05 / 28 / 2026, page 16 / 44 6 / 26 distilled and organic solvents such as ethanol, methanol or ethylene glycol.

[0030] The invention also relates to a method for producing concentrated reagent, implemented by the device described above and comprising the following operations: - Remove the solvent from the reservoir by opening the first valve, closing the second valve, and drawing the solvent out with the pump; - To produce a concentrated reagent within the container by closing the first valve, opening the second valve, and discharging the solvent with the pump, so that a concentrated reagent is produced by dissolving at least part of the solid substance in the solvent; and - Remove the concentrated reagent from the container by aspirating it with the pump.

[0031] The invention also relates to a system for producing reconstituted reagent, comprising: - a dilution tank; - a device as described above, configured to supply concentrated reagent to the dilution tank; and - a solvent reservoir, configured to supply solvent to the dilution tank.

[0032] The dilution tank is configured to produce a reconstituted reagent by diluting the concentrated reagent in the solvent.

[0033] Finally, the invention also relates to a method for producing a reconstituted reagent, implemented by the system described above and comprising the following operations: - Supply concentrated reagent to the dilution tank using the device; - supply solvent to the dilution tank using the reservoir; and - To produce a reconstituted reagent in the dilution tank by diluting the concentrated reagent in the solvent. BRIEF DESCRIPTION OF THE DRAWINGS Petition 870260051189, dated 05 / 28 / 2026, page 17 / 44 7 / 26

[0034] Other features, details and advantages will become apparent after reading the detailed description below and examining the attached drawings, in which:

[0035] Figure 1 illustrates a device for producing concentrated reagent according to the invention.

[0036] Figure 2 illustrates a method for producing concentrated reagent according to the invention.

[0037] Figure 3 illustrates a system for producing reconstituted reagent according to the invention.

[0038] Figure 4 illustrates a method for producing reconstituted reagent according to the invention. DETAILED DESCRIPTION

[0039] Figure 1 illustrates a device 1 for producing concentrated reagent.

[0040] The term “concentrated reagent” here refers to a liquid reagent having a concentration higher than the working concentration, the latter being the concentration at which the reagent is ready for use in a biological analysis. The concentrated reagent is therefore intended to be diluted.

[0041] More specifically, device 1 is configured to produce concentrated reagent by dissolving a solid substance in a solvent. The concentrated reagent thus corresponds to a solution in which the solute is the originally solid substance. In this context, the “concentration” of the concentrated reagent here refers to the proportion of solute in the solution.

[0042] As examples, device 1 can be used to produce a dilution, lysis, entrainment, rinsing or staining reagent.

[0043] Device 1 is intended to be installed in a medical biology laboratory to meet the reagent requirements of that laboratory. Device 1 can be used in the context of a medical biology examination and, specifically, for in vitro diagnostic (IVD) purposes performed on a biological fluid sample.

[0044] Device 1 comprises a solvent reservoir 3, a container 5, a concentrated reagent storage tank 7, a pump Petition 870260051189, dated 05 / 28 / 2026, page 18 / 44 8 / 26 9, and a production circuit 11.

[0045] Reservoir 3 is configured to store a solvent.

[0046] Typically, reservoir 3 is a reservoir for water purified by osmosis, that is, purified water free of chemicals and pollutants. This water can be obtained using a reverse osmosis filtration system.

[0047] The water purified by osmosis stored in reservoir 3 is advantageously Type II purified water, obtained by combining reverse osmosis with demineralization. This water contains very low levels of inorganic, organic, or colloidal contaminants and has a resistivity greater than 1 MΩχ^ι and preferably between 10 and 15 MΩχ^ι. This water quality is generally expected for laboratory applications. Obviously, the water purified by osmosis stored in reservoir 3 can be of higher quality (Type II+, Type I, or even Type I+).

[0048] Alternatively, reservoir 3 could be a reservoir for distilled water, that is, purified water obtained by distilling potable water. Distillation serves to eliminate a large proportion of the organisms and mineral salts present in potable water.

[0049] Alternatively, reservoir 3 may be a reservoir for an organic solvent, such as ethanol, methanol or ethylene glycol. In particular, ethanol is capable of dissolving a wide range of ionic compounds, such as: sodium and potassium hydroxides; magnesium, calcium and ammonium chlorides; or ammonium and sodium bromides.

[0050] Reservoir 3 can store a mixture of several of the solvents mentioned above. For example, reservoir 3 can store a mixture of water - purified by osmosis or distilled - and organic solvent.

[0051] Reservoir 3 can also store several different solvents in separate compartments.

[0052] Container 5 is configured to hold a solid substance intended to be dissolved in a solvent to produce a concentrated reagent. In the context of the invention, the solid substance has a solubility in water at 20°C. Petition 870260051189, dated 05 / 28 / 2026, page 19 / 44 9 / 26 greater than or equal to 340 grams per liter (g / L). The solid substance can be an elemental substance or a chemical compound.

[0053] The solid substance is, for example, potassium chloride (KCl), sodium chloride (NaCl), tris(hydroxymethyl)aminomethane (often abbreviated as “Tris”) or Tris-HCl.

[0054] The solid substance may be contained in container 5 in the form of powder, pellets or granules.

[0055] Container 5 can be made of a flexible or rigid material. Container 5 can be a flask, a jar, a bottle, or, more generally, any type of laboratory glassware in which dissolution can be carried out. Container 5 is not necessarily made of glass; for example, it can be made of stainless steel or ceramic. Advantageously, container 5 is made of plastic, preferably polyethylene and, even more preferably, high-density polyethylene (HDPE).

[0056] As detailed below in this description, the concentrated reagent is produced within container 5 by dissolving the solid substance in the solvent transported from reservoir 3 while device 1 is in operation. To facilitate the withdrawal of the concentrated reagent, container 5 can be provided with a sampling rod, optionally equipped with a check valve.

[0057] Storage tank 7 is configured to store the concentrated reagent.

[0058] More specifically, storage tank 7 is intended to store the concentrated reagent produced by dissolving the solid substance, contained in container 5, in the solvent supplied by reservoir 3.

[0059] As explained above, the concentrated reagent has a higher concentration than the working concentration. The applicant found that device 1 makes it possible to obtain a concentrated reagent at a concentration at least 60 times, and up to 120 times, higher than the working concentration.

[0060] The capacity of storage tank 7 can therefore be smaller Petition 870260051189, dated 05 / 28 / 2026, page 20 / 44 10 / 26 of that of storage tanks in known devices, which store a concentrated reagent obtained by mixing liquid reagent and purified water. In fact, such storage tanks store a concentrated reagent having a concentration that is, at most, only 25 times greater than the working concentration. These storage tanks are heavy and bulky, as they are sized to hold a large volume of concentrated reagent.

[0061] By way of example, storage tank 7 typically has a volume between 0.35 and 6 liters (L), whereas known devices require the use of containers with a capacity of 10 to 20 liters (L) to store the concentrated reagent. Such a reduced volume of concentrated reagent to be stored in storage tank 7 can be produced from a solid substance having a mass that is typically between 100 and 1,700 grams (g), which is a significantly smaller mass than the 10 or even 20 kilograms (kg) of liquid reagent needed to feed known devices.

[0062] Pump 9 is configured to move any liquid, whether solvent or concentrated reagent, within the production circuit 11, by suction or discharge. Pump 9 offers the advantage of allowing the movement of a desired volume. Typically, pump 9 has an accuracy of approximately 0.5%.

[0063] For example, pump 9 consists of a body within which a piston is arranged to slide in order to make a liquid circulate within the production circuit 11, exerting pressure on it.

[0064] In the example shown in Figure 1, pump 9 is a syringe, therefore, an instrument comprising a cylinder (which forms the body of the syringe) containing a piston and ending in a tip. The aspiration and injection functions of the syringe correspond to the aspiration and discharge functions of pump 9.

[0065] The piston can be controlled by a stepper motor, in which case the pump 9 and the stepper motor together constitute a motorized syringe. The stepper motor is configured to convert an electrical pulse into a sliding motion. Petition 870260051189, dated 05 / 28 / 2026, page 21 / 44 1 1 / 26 of the piston inside the body.

[0066] Production circuit 11 is configured to allow any liquid, whether solvent or concentrated reagent, to circulate between reservoir 3, container 5 and storage tank 7.

[0067] This circulation is activated and controlled by means of pump 9.

[0068] For this purpose, the production circuit 11 includes a pipe 13 fitted with a valve 15 leading to reservoir 3; a pipe 17 fitted with a valve 19 leading to container 5; and a pipe 21 fitted with a valve 23 leading to storage tank 7.

[0069] Pump 9 is fluidically connected to reservoir 3 via tube 13, to container 5 via tube 17, and to storage tank 7 via tube 21.

[0070] In the arrangement illustrated in Figure 1, tubes 13, 17 and 21 are connected to each other at a junction, thus allowing the liquid to flow directly from one tube to another.

[0071] Each of the valves 15, 19 and 23 is configured to be either open or closed. When open, a valve allows liquid to flow along the pipe in which it is mounted; conversely, when closed, a valve prevents the flow of liquid along the pipe.

[0072] A method for producing concentrated reagent, implemented by device 1, will now be described with reference to Figure 2.

[0073] In the context of implementing this method, container 5 contains a solid substance having a solubility in water at 20°C greater than or equal to 340 g / L.

[0074] During an operation 200, device 1 operates in solvent withdrawal mode.

[0075] For this, valve 15 is open, while valves 19 and 23 are closed. In this configuration of production circuit 11, pump 9 communicates only with reservoir 3.

[0076] Pump 9 draws at least some of the solvent from reservoir 3. The drawn solvent flows along tube 13, at least to the junction. Petition 870260051189, dated 05 / 28 / 2026, page 22 / 44 12 / 26 in production circuit 11, so that it can be subsequently transferred to another tube. If necessary, the solvent can be aspirated until it is partially or completely received into pump 9.

[0077] During operation 210, device 1 operates in a concentrated reagent production mode.

[0078] For this, valve 19 is opened while valve 15 is closed. As for valve 23, it remains closed. In this configuration of production circuit 11, pump 9 is in communication only with container 5.

[0079] Pump 9 discharges the removed solvent towards container 5. The solvent flows along tube 17 until it is delivered to container 5. It is possible to deliver only a portion of the solvent, especially when there is an excessive volume of solvent removed. Furthermore, it is possible to deliver the solvent to container 5 in multiple increments.

[0080] Once discharged through tube 17 into container 5, the solvent comes into contact with the solid substance. Due to its high solubility, at least some of the solid substance dissolves in the solvent, and this occurs almost immediately.

[0081] In general, dissolution results in the formation of a solution, that is, a homogeneous mixture composed of a solvent and one or more solutes. In the case in question, the dissolution carried out within container 5 produces a solution in which the solvent is the liquid drawn from reservoir 3, and the solute is the originally solid substance. When the solvent used is purified water, such as water purified by osmosis or distilled water, the resulting solution can be called an aqueous solution.

[0082] The resulting solution corresponds to the concentrated reagent that device 1 is configured to produce.

[0083] During operation 220, pump 9 draws up the concentrated reagent produced.

[0084] For this, the configuration of production circuit 11 remains identical to that of operation 210: valve 17 is open, while valves 15 and 23 Petition 870260051189, dated 05 / 28 / 2026, page 23 / 44 13 / 26 remain closed.

[0085] In practice, the volume aspirated by pump 9 during operation 220 is greater than the volume aspirated during operation 200, since the concentrated reagent comprises both the solvent aspirated during operation 200 and at least a portion of the solid substance that is present in the concentrated reagent in the form of solute. However, it is also possible to extract only a portion of the concentrated reagent from container 5.

[0086] The concentrated reagent flows along tube 17, at least up to the junction in the production circuit 11, so that it can be subsequently transferred to another tube. If necessary, the concentrated reagent can be aspirated until it is partially or completely received within pump 9.

[0087] During operation 230, device 1 operates in concentrated reagent storage mode.

[0088] For this, valve 23 is open, while valve 17 is closed. As for valve 15, it remains closed. In this configuration of production circuit 11, pump 9 is in communication only with storage tank 7.

[0089] Pump 9 discharges the extracted concentrated reagent towards storage tank 7. The concentrated reagent flows along tube 21 until it is delivered to storage tank 7.

[0090] The sequence of operations 200, 210, 220 and 230 corresponds to a production and storage cycle of concentrated reagent.

[0091] Each cycle serves to dissolve at least part of the solid substance contained in container 5 and to transport the resulting concentrated reagent to storage tank 7. Multiple cycles may be necessary to dissolve all of the solid substance contained in container 5. Advantageously, the total volume of solvent removed is substantially equal to the minimum volume of solvent required to completely dissolve the solid substance contained in container 5. “Substantially equal” is understood here to mean that, ideally, the total volume of solvent removed is equal to the volume Petition 870260051189, dated 05 / 28 / 2026, page 24 / 44 14 / 26 minimum amount of solvent required; however, in practice, the total volume of solvent actually withdrawn may differ slightly from the minimum volume of solvent required.

[0092] As an example, dissolving 200 grams (g) of powder contained in container 5 may require between 30 and 300 cycles, with each cycle producing between 2 and 20 milliliters (mL) of concentrated reagent.

[0093] Once the solid substance is completely dissolved, the volume of concentrated reagent stored in storage tank 7 is known, as it includes the volume corresponding to the solid substance initially contained in container 5, and the total volume of solvent removed. The concentration of the concentrated reagent is therefore also known.

[0094] Finally, during an optional operation 240, device 1 operates in a concentrated reagent homogenization mode.

[0095] For this, the configuration of production circuit 11 is identical to that of operation 230: valve 23 is open, while valves 15 and 19 are closed.

[0096] Pump 9 draws the concentrated reagent from storage tank 7 and then discharges the drawn reagent back into storage tank 7. The concentrated reagent thus circulates along tube 21, flowing first in one direction and then in the other. This alternating process of drawing and discharging can be repeated several times to induce agitation within storage tank 7, thereby homogenizing the concentrated reagent.

[0097] Operation 240 can be performed after one or more production and storage cycles of concentrated reagent, or after the complete set of production and storage cycles of concentrated reagent, i.e., once the solid substance has been completely dissolved.

[0098] The table below summarizes the operating modes of device 1, indicating the corresponding configuration of the production circuit 11 for each case:

[0099] TABLE 1 Petition 870260051189, dated 05 / 28 / 2026, page 25 / 44 15 / 26 Valve 15 Valve 19 Valve 23 Solvent withdrawal mode open closed closed Concentrated reagent production mode closed open closed Concentrated reagent storage mode closed closed open Concentrated reagent homogenization mode closed closed open

[0100] The Applicant noted that the method described above for producing concentrated reagent, implemented by device 1, allows the dissolution, on average, of a mass of solid substance between 100 and 1700 grams (g) in one hour, and the production of a volume of concentrated reagent between 0.35 and 6 liters (L).

[0101] The concentrated reagent stored in storage tank 7 has a concentration higher than the working concentration. Consequently, to be suitable for use in the analysis of a biological fluid sample, for example, a blood sample in the context of a hematological examination, the concentrated reagent must be diluted to reach the working concentration.

[0102] For this purpose, device 1 can be integrated or coupled to a system for producing reconstituted reagent, configured to dilute the concentrated reagent until the working concentration is reached.

[0103] As used in this document, the term “reconstituted reagent” refers to a liquid reagent with a concentration lower than that of the concentrated reagent, and as close as possible to the working concentration. This concentration is achieved by mixing the concentrated reagent with a solvent, so as to reduce the proportion of solute within the resulting dilute solution.

[0104] A person skilled in the art knows that there are various systems capable of producing reconstituted reagent from concentrated reagent. Such systems for producing reconstituted reagent comprise at least one source of concentrated reagent, a solvent reservoir, and a dilution tank. The source of Petition 870260051189, dated 05 / 28 / 2026, page 26 / 44 16 / 26 The concentrated reagent and solvent reservoir are configured to supply the dilution tank with concentrated reagent and solvent, respectively; and the dilution tank is configured to produce a reconstituted reagent by diluting the concentrated reagent in the solvent.

[0105] In this case, the source of concentrated reagent is device 1.

[0106] Reference is now made to Figure 3, in which device 1 is part of a system 25 for producing reconstituted reagent.

[0107] System 25 is configured to prepare a reconstituted reagent ready for use in a biological analysis. This preparation comprises, firstly, the production of concentrated reagent using device 1 described above and, secondly, the dilution of the concentrated reagent in a solvent.

[0108] It should be noted, first of all, that device 1 illustrated in Figure 3 presents several differences compared to that in Figure 1. In particular, storage tank 7 is equipped with a mixer 27, a low level sensor 29 and a high level sensor 31.

[0109] Mixer 27 is configured to mix the concentrated reagent stored in storage tank 7, in order to promote homogenization of the concentrated reagent.

[0110] The mixer 27 may be in the form of a blade mounted rotatably inside the storage tank 7, driven by a motor. When driven by the motor, this blade serves to mix the concentrated reagent.

[0111] Alternatively, mixer 27 may be a static mixer, for example, a static plate mixer, capable of generating strong turbulence in the flow of the concentrated reagent as the reagent passes through it.

[0112] Mixer 27 can be used in addition to, or in place of, the concentrated reagent homogenization mode of device 1 during operation 240 of the method to produce the concentrated reagent shown in Figure 2.

[0113] The low-level sensor 29 is configured to detect when the concentrated reagent reaches a predetermined minimum volume. In particular, when the volume of concentrated reagent falls below this minimum volume, the Petition 870260051189, dated 05 / 28 / 2026, page 27 / 44 17 / 26 low level sensor 29 serves to signal that the volume of concentrated reagent is insufficient and therefore that storage tank 7 needs to be refilled.

[0114] Storage tank 7 is filled in approximately one hour, while the concentrated reagent is consumed on demand over one or more days. The low-level sensor 29 therefore serves to prevent a possible shortage of concentrated reagent.

[0115] The high-level sensor 31 is used only in exceptional circumstances, namely when there is a loss of data regarding the volume of concentrated reagent contained within the storage tank 7. In fact, the storage tank 7 must be completely filled until the high-level sensor 31 flushes it before it is emptied.

[0116] In the example shown in Figure 3, the system 25 comprises, in addition to device 1, a concentrated reagent dilution tank 33, an additional pump 35, and a dilution circuit 37. A configuration in which a single pump is used to perform the functions of pump 9 and the additional pump 35 is also possible.

[0117] The dilution tank 33 is configured to bring the concentrated reagent into contact with a solvent, so as to reduce the concentration of the concentrated reagent and, ideally, to do so until the working concentration is reached for the reconstituted reagent. In practice, the dilution tank 33 allows reaching a concentration as close as possible to the working concentration.

[0118] As an example, the volume of dilution tank 33 is typically between 0.05 and 0.5 liters (L).

[0119] In addition, in the example shown in Figure 3, the dilution tank 33 is equipped with a mixer 39, a low level sensor 41, a high level sensor 43 and a conductivity measuring probe 45.

[0120] Mixer 39 is configured to mix the reconstituted reagent stored in dilution tank 33, in order to promote homogenization of the reconstituted reagent. Petition 870260051189, dated 05 / 28 / 2026, page 28 / 44 18 / 26

[0121] Similar to mixer 27 in storage tank 7, mixer 39 may be in the form of a blade mounted rotatably inside dilution tank 33 and driven by a motor, or a static mixer, such as a static plate mixer.

[0122] When the volume of reconstituted reagent falls below a predetermined minimum volume, the low level sensor 41 is set to signal that the volume of reconstituted reagent is insufficient and therefore the dilution tank 33 needs to be refilled.

[0123] When the volume of reconstituted reagent exceeds a predetermined maximum volume, the high-level sensor 43 is set to signal that the volume of reconstituted reagent is sufficient, or even that there is an excess of reconstituted reagent and therefore the dilution tank 33 needs to stop being refilled.

[0124] Probe 45 is configured to measure the conductivity of the reconstituted reagent within the dilution tank 33.

[0125] The conductivity of the reconstituted reagent depends on its concentration. As a result, measuring the conductivity allows us to estimate the concentration of the reconstituted reagent and verify if it corresponds to the expected concentration.

[0126] It should be noted that physical or chemical measurements other than conductivity measurement can be used to verify that the concentration of the reconstituted reagent is in accordance with the target concentration. For example, probe 45 can be configured to measure the hydrogen potential (pH) of the reconstituted reagent.

[0127] Pump 35 is configured to move any liquid, whether solvent or concentrated reagent, within the dilution circuit 37, either by suction or discharge. Pump 35 offers the advantage of allowing the movement of a desired volume. Typically, pump 35 has an accuracy of approximately 0.5%.

[0128] For example, pump 35 consists of a body within which a piston is arranged to slide in order to circulate a liquid within the dilution circuit 37, exerting pressure on it. Petition 870260051189, dated 05 / 28 / 2026, page 29 / 44 19 / 26

[0129] In the example shown in Figure 3, pump 35 is a syringe, which can be coupled to a stepper motor to form a motorized syringe.

[0130] The dilution circuit 37 is configured to allow any liquid, whether solvent or concentrated reagent, to circulate between the storage tank 7, a solvent reservoir, and the dilution tank 33.

[0131] This circulation is activated and controlled by pump 35.

[0132] For this purpose, the dilution circuit 37 includes a tube 47 fitted with a valve 49 leading to storage tank 7; a tube 51 fitted with a valve 53 leading to reservoir 3; and a tube 55 fitted with a valve 57 leading to dilution tank 33.

[0133] Pump 35 is fluidically connected to storage tank 7 via tube 47, to solvent reservoir via tube 41, and to dilution tank 33 via tube 55.

[0134] In the example shown in Figure 3 and throughout the remainder of this description, the solvent reservoir connected to the dilution circuit 37 is reservoir 3, which is already connected to the production circuit 11. However, the system 25 may comprise two separate solvent reservoirs.

[0135] In the configuration illustrated in Figure 3, tubes 47, 51 and 55 communicate with each other at a junction, thus allowing liquid to flow directly from one tube to another.

[0136] Each of the valves 49, 53 and 57 is configured to be open or closed and therefore to selectively allow or prevent the flow of liquid along the corresponding tube.

[0137] The assembly consisting of the solvent reservoir (here, reservoir 3), the dilution tank 33, the pump 35 and the dilution circuit 37 can be considered a dilution device.

[0138] A method for producing reconstituted reagent, implemented by system 25, will now be described with reference to Figure 4.

[0139] An initial operation 400 corresponds to the production of concentrated reagent, carried out by device 1. This production of concentrated reagent is Petition 870260051189, dated 05 / 28 / 2026, pp. 30 / 44 20 / 26 implemented according to the method shown in Figure 2 and results in the storage, in storage tank 7, of the concentrated reagent obtained by dissolving the solid substance (contained in container 5) in the solvent supplied by reservoir 3.

[0140] During a 410 operation, system 25 operates in a concentrated reagent withdrawal mode.

[0141] For this purpose, valve 49 is opened, while valves 53 and 57 are closed. In this configuration of the dilution circuit 37, pump 35 is in communication only with storage tank 7.

[0142] Pump 35 draws at least part of the concentrated reagent from storage tank 7. The received concentrated reagent flows along tube 47, proceeding at least to the junction in the dilution circuit 37, so that it can be subsequently transferred to another tube. If necessary, the concentrated reagent can be drawn until it is received, partially or completely, within pump 35.

[0143] In addition, it is preferable to close valve 23 to allow pump 35 to draw the concentrated reagent more efficiently and to avoid drawing residual liquids from the production circuit 11.

[0144] During operation 420, system 25 operates in concentrated reagent delivery mode.

[0145] For this, valve 57 is opened, while valve 49 is closed. As for valve 53, it remains closed. In this configuration of the dilution circuit 37, pump 35 communicates only with the dilution tank 33.

[0146] Pump 35 sends the withdrawn concentrated reagent towards the dilution tank 33. The concentrated reagent flows along tube 55 until it is delivered to the dilution tank 33.

[0147] The sequence of operations 410 and 420 constitutes a cycle for transferring the concentrated reagent to the dilution tank 33. This cycle can be repeated several times, including consecutively, in order to transfer the desired volume of concentrated reagent to the dilution tank 33. Petition 870260051189, dated 05 / 28 / 2026, pp. 31 / 44 21 / 26

[0148] During operation 430, system 25 operates in solvent withdrawal mode.

[0149] For this, valve 53 is opened, while valve 57 is closed. As for valve 49, it remains closed. In this configuration of the dilution circuit 37, pump 35 communicates only with reservoir 3.

[0150] Pump 35 draws at least part of the solvent from reservoir 3. The drawn solvent flows along tube 51, at least to the junction in the dilution circuit 37, so that it can be subsequently transferred to another tube. If necessary, the solvent can be drawn until it is received, partially or totally, within pump 35.

[0151] During a 440 operation, system 25 operates in concentrated reagent dilution mode.

[0152] For this, valve 57 is opened, while valve 53 is closed. As for valve 49, it remains closed. In this configuration of the dilution circuit 37, pump 35 communicates only with dilution tank 33.

[0153] Pump 35 sends the removed solvent towards the dilution tank 33. The solvent flows along the tube 55 until it is delivered to the dilution tank 33. It is possible to deliver only a portion of the solvent, especially when there is an excessive volume of solvent removed. In addition, it is possible to dispense the solvent into the dilution tank 33 in multiple increments.

[0154] Once discharged through tube 55 into dilution tank 33, the solvent mixes with the concentrated reagent, which is thus diluted.

[0155] The sequence of operations 430 and 440 corresponds to a cycle of transferring the solvent to the dilution tank 33. This cycle can be repeated several times, including consecutively, to transfer the desired volume of solvent to the dilution tank 33.

[0156] In the example shown in Figure 4, the concentrated reagent transfer cycle is performed before the solvent transfer cycle. However, the concentrated reagent transfer cycle can also be performed after the solvent transfer cycle. Petition 870260051189, dated 05 / 28 / 2026, pages 32 / 44 22 / 26

[0157] Finally, during an optional operation 450, the system 25 operates in a homogenization mode of the reconstituted reagent.

[0158] For this, the configuration of the dilution circuit 37 is identical to that of operation 420 and operation 440: valve 57 is open, while valves 49 and 53 are closed.

[0159] Pump 35 draws the reconstituted reagent from the dilution tank 33 and then discharges the drawn reagent back into the dilution tank 33. The reconstituted reagent therefore circulates along tube 55, flowing first in one direction and then in the other. This alternating process of drawing and discharging can be repeated several times to induce agitation within the dilution tank 33, thus homogenizing the reconstituted reagent.

[0160] Note that mixer 39 can be used in addition to or instead of the reconstituted reagent homogenization mode of system 25.

[0161] The table below summarizes the operating modes of system 25, indicating the corresponding configuration of the dilution circuit 37 for each mode:

[0162] TABLE 2 Valve 49 Valve 53 Valve 57 Concentrated reagent withdrawal mode open closed closed Concentrated reagent delivery mode closed closed open Solvent withdrawal mode closed open closed Concentrated reagent dilution mode closed closed open Concentrated reagent homogenization mode closed closed open

[0163] The Applicant noted that the method described above for producing reconstituted reagent, implemented by system 25, provides a medical biology laboratory with operational autonomy ranging from half a day to several days. This allows sufficient time to replace container 5 without interrupting routine operations, since – as mentioned above – the Petition 870260051189, dated 05 / 28 / 2026, pages 33 / 44 23 / 26 Dissolving the solid substance takes only one hour on average.

[0164] Referring again to Figure 3, system 25 is coupled to a dispensing circuit 59.

[0165] The dispensing circuit 59 is configured to dispense the reconstituted reagent from the dilution tank 33 to one or more biological analysis devices 61.

[0166] Each biological analysis device 61 is configured to analyze a sample of biological fluid, for example, a sample of blood, urine, cerebrospinal fluid, pleural fluid, synovial fluid or bone marrow collected by puncture. The operation of a biological analysis device 61 depends on the use of one or more reagents, such as dilution, lysis, entrainment, rinsing or staining reagents.

[0167] To supply the reconstituted reagent to the biological analysis devices 61, the dispensing circuit 59 may comprise, as illustrated in Figure 3, a dispensing tank 63 that is fluidically connected to each biological analysis device 61.

[0168] For reference, the volume of dispensing tank 63 is typically between 3 and 10 liters (L).

[0169] Dispensing tank 63 is fluidically connected to dispensing tank 33 by a tube 65 fitted with a valve 67, a transfer pump 69 and a filter 71.

[0170] Valve 67 is configured to be open or closed and thus selectively allow or prevent the flow of reconstituted reagent along tube 65.

[0171] Transfer pump 69 is set, when valve 67 is open, to transport the reconstituted reagent to dispensing tank 63.

[0172] Filter 71 is configured to filter the reconstituted reagent flowing along tube 65, in order to remove impurities that could subsequently impair the operation of a biological analysis device 61. Typically, filter 71 serves to retain all foreign bodies smaller than 0.2 micrometers (µm) and preferably smaller than 0.5 micrometers (µm). Petition 870260051189, dated 05 / 28 / 2026, pages 34 / 44 24 / 26

[0173] In the example shown in Figure 3, the dispensing tank 63 is equipped with a low level sensor 73 and a high level sensor 75.

[0174] When the volume of reconstituted reagent to be dispensed falls below a predetermined minimum volume, the low-level sensor 73 is set to signal that the volume of reconstituted reagent available for dispensing is insufficient and therefore the dispensing tank 63 needs to be refilled.

[0175] When the volume of reconstituted reagent to be dispensed exceeds a predetermined maximum volume, the high-level sensor 75 is set to signal that the volume of reconstituted reagent available for dispensing is sufficient or even that there is an excess of reconstituted reagent and therefore the dispensing tank 63 needs to stop being refilled.

[0176] In the example in Figure 3, the dispensing circuit 59 also includes a waste container 77 into which liquids can be drained, whether concentrated reagents or reconstituted reagents.

[0177] For this purpose, the dispensing tank 63 is fluidically connected to the waste container 77 by means of a tube 79 provided with a valve 81; the storage tank 7 is fluidically connected to the waste container 77 by means of a tube 83 provided with a valve 85; and the dilution tank 33 is fluidically connected to the waste container 77 by means of a tube 87 provided with a valve 89.

[0178] Each of the valves 81, 85 and 89 is configured to be open or closed and therefore to selectively allow or prevent the flow of liquid to be drained through the corresponding tube.

[0179] In addition, in all cases, the transfer of the liquid to be drained to the waste container 77 is ensured by a transfer pump 91.

[0180] Figure 3 and Figure 4 represent a configuration in which device 1 is integrated into a system for producing reconstituted reagent, in this case system 25. However, device 1 can be used to directly produce reconstituted reagent, in which case device 1 alone constitutes a complete system for producing reconstituted reagent. In such a configuration, the Petition 870260051189, dated 05 / 28 / 2026, pages 35 / 44 The 25 / 26 storage tank 7 also serves as a dilution tank.

[0181] The difference between a concentrated reagent and a reconstituted reagent lies in its concentration. As a result, the conversion of device 1 into a system for producing reconstituted reagent can be achieved by increasing the total volume of solvent withdrawn from reservoir 3 and discharged into container 5. In other words, the total volume of solvent used is no longer merely the minimum volume required to completely dissolve the solid substance contained in container 5; instead, it corresponds to the volume required to achieve the desired working concentration within the storage tank 7.

[0182] Each cycle corresponding to the sequence of operations 200, 210, 220 and 230 shown in Figure 2 is a cycle for the production and storage of the reconstituted reagent.This implies that the sum of the volumes of solvent withdrawn during the respective cycles, more specifically during operation 200 of each cycle, is substantially equal to a volume such that the ratio between the total mass of the solid substance and this volume is equal to the desired working concentration. “Substantially equal” here means that, ideally, the total volume of solvent withdrawn is exactly equal to the volume required to achieve the desired working concentration in storage tank 7; however, in practice, the actual total volume of solvent withdrawn may differ slightly from this desired volume.

[0183] Still following the principle of using device 1 to directly produce the reconstituted reagent, it is also possible to proceed in the same manner described above with reference to Figure 2, that is, performing multiple cycles of production and storage of concentrated reagent until the solid substance is completely dissolved and then supplying solvent to storage tank 7 to achieve the desired working concentration.

[0184] To this end, device 1 can implement the following additional operations: open valve 15, close valves 19 and 23, and remove the solvent from reservoir 3 by suction with pump 9; then close valve 15, open valve 23, and send the removed solvent to storage tank 7 by discharging it with pump 9. These additional operations can be performed Petition 870260051189, dated 05 / 28 / 2026, pages 36 / 44 26 / 26 as many times as necessary to achieve the working concentration and thus produce the reconstituted reagent within storage tank 7. Petition 870260051189, dated 05 / 28 / 2026, pages 37 / 44

Claims

1 / 3 CLAIMS 1. Device (1) for producing concentrated reagent, characterized in that it comprises: - a reservoir (3) for solvent, - a container (5) containing a solid substance having a solubility in water at 20°C greater than or equal to 340 g / L, - a pump (9), and - a production circuit (11) including a first tube (13) provided with a first valve (15) and a second tube (17) provided with a second valve (19), the pump (9) being fluidically connected to the reservoir (3) and to the container (5) through the first tube (13) and the second tube (17), respectively, the device (1) being configured to operate in at least the following modes: a solvent withdrawal mode, in which the first valve (15) is open, the second valve (19) is closed, and the pump (9) is configured to draw solvent from the reservoir (3), and a concentrated reagent production mode, in which the first valve (15) is closed,The second valve (19) is open, and the pump (9) is set to discharge solvent into the container (5) so that a concentrated reagent is produced by dissolving at least part of the solid substance in the solvent, and to draw concentrated reagent from the container (5).

2. Device (1), according to claim 1, characterized in that it further comprises a storage tank (7) for concentrated reagent, wherein the production circuit (11) further includes a third tube (21) provided with a third valve (23), and the pump (9) is also fluidically connected to the storage tank (7) via the third tube (21), the third valve (23) being closed in solvent withdrawal mode and in concentrated reagent production mode of the device (1), wherein the device (1) is further configured to operate in a concentrated reagent storage mode in which the first valve (15) is closed, the second valve (19) is closed, the third valve (23) is open and the pump (9) is configured to discharge concentrated reagent to the storage tank (7).

3. Device (1), according to claim 2, characterized in that the device (1) is additionally configured to operate in a concentrated reagent homogenization mode in which the first valve (15) is closed, the second valve (19) is closed, the third valve (23) is open, and the pump (9) is configured to alternate between aspirating concentrated reagent from the storage tank (7) and discharging concentrated reagent back to the storage tank (7), one or more times.

4. Device (1), according to claim 2 or 3, characterized in that the storage tank (7) is provided with a mixer (27) configured to homogenize, by mixing, the concentrated reagent stored in the storage tank (7).

5. Device (1), according to any one of claims 2 to 4, characterized in that the storage tank (7) is provided with at least one level sensor (29) configured to detect when a certain volume of concentrated reagent has been reached within the storage tank (7).

6. Device (1), according to any one of claims 1 to 5, characterized in that the concentrated reagent is a diluting, lysis, entrainment, rinsing or staining reagent.

7. Device (1), according to any one of claims 1 to 6, characterized in that the reservoir (3) is a reservoir for one or a combination of the following solvents: water purified by osmosis, distilled water and organic solvents such as ethanol, methanol or ethylene glycol.

8. Method for producing concentrated reagent implemented by the device (1) as defined in any of claims 1 to 7, characterized in that it comprises the following operations: Petition 870260051189, dated 05 / 28 / 2026, page 39 / 44 3 / 3 - withdrawing (200) solvent from the reservoir (3) by opening the first valve (15), closing the second valve (19), and aspirating the solvent with the pump (9); - producing (210) concentrated reagent inside the container (5) by closing the first valve (15), opening the second valve (19), and discharging the solvent with the pump (9), so that a concentrated reagent is produced by dissolving at least part of the solid substance in the solvent; and - withdrawing (220) concentrated reagent from the container (5) by aspirating the concentrated reagent with the pump (9).

9. System (1,25) for producing reconstituted reagent, characterized in that it comprises: - a dilution tank (7, 33), - a device (1) as defined in any one of claims 1 to 7, configured to supply concentrated reagent to the dilution tank (7, 33), and - a reservoir (3) for solvent, configured to supply solvent to the dilution tank (7, 33), wherein the dilution tank (7, 33) is configured to produce a reconstituted reagent by diluting the concentrated reagent in the solvent.

10. Method for producing reconstituted reagent, implemented by system (1, 25) as defined in claim 9, characterized in that it comprises the following operations: - supplying concentrated reagent to the dilution tank (7, 33) using device (1), - supplying solvent to the dilution tank (7, 33) using reservoir (3), and - producing a reconstituted reagent in the dilution tank (7, 33) by diluting the concentrated reagent in the solvent. Petition 870260051189, dated 05 / 28 / 2026, pp. 40 / 44

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