Systems and methods for distributing solutions using a gravimetric diluter

Abstract

The present description of the invention describes systems and methods using a gravimetric diluter to accurately add two or more liquids / fluids (e.g., solutions) to a sample in a rapid manner. In some embodiments, the systems and methods of the present invention are configured to accurately dilute a "concentrated solution" (such as a broth solution, medium, selective agent solution, etc.), in addition to being configured to accurately dilute a "sample" (such as a food sample, a medical / cosmetic sample, etc.). Computer-implemented methods and systems are described.The systems and methods described in the present invention advantageously ensure the accuracy and precision of the distribution of several types of solutions, the rapid distribution of two or more solutions, durability, improved health and safety at work, and traceability of two or more solutions.

Description

Title of the invention: Systems and methods for dispensing solutions using a gravimetric diluter. Related applications.

[0001] This application claims priority from U.S. Provisional Application No. US63 / 723,604 filed on November 22, 2024. Its content is incorporated herein in full by way of reference. technical field

[0002] This patent description relates to the field of dispensing liquids or fluids, for example, solutions, using a gravimetric diluter. In particular, the patent description relates to systems and methods for accurately and rapidly dispensing two or more solutions into a sample using a gravimetric diluter. Prior state of the art

[0003] Gravimetric diluters, also called gravimetric dispensers, are generally used to dilute food samples for microbial enrichment and to analyze the presence of contaminants in these samples. Gravimetric dispensers can also be used in bioanalytical laboratories to analyze certain types of cosmetics, food supplements, drugs, chemicals, or pharmaceuticals, in addition to food samples.

[0004] Diluters currently available on the market are either gravimetric or volumetric. For example, volumetric diluters deliver a fixed volume of solution based on the dilution factor chosen by the user. Although some volumetric diluters available on the market can provide precise volumes of solution, the user must first, in a separate step, accurately measure a specific quantity (weight) of food sample before adding it to the diluter and selecting the desired dilution.

[0005] Gravimetric diluters offer the advantage of combining an integrated balance allowing for the accurate weighing of a food sample "as is", and then calculating the appropriate amount of solution to add to obtain the desired dilution.

[0006] In addition to an integrated balance, gravimetric diluters include one or more peristaltic pumps for dispensing a solution, and then, using weight-based feedback, the instrument calibrates the dispensed mass according to the number of rotations of the pump rollers. If two or more pumps are used, each is calibrated separately, since the dispensed volume depends on several factors, including the diameter and elasticity of the tubing, as well as the viscosity and mass of each distributed solution.

[0007] A common approach to dispensing two or more different solutions involves first calibrating a separate pump for each solution, and then simultaneously dispensing ("dosing") each solution in parallel, either using separate dosing lines or inline via a Y-splitter that merges the solutions, thus enabling efficient mixing. However, over time, the calibration of one or more pumps begins to drift and lose accuracy. The parallel dispensing method does not allow for adjusting the amount of one solution to be dispensed to compensate for an overdose or underdose of the other solution, which affects accuracy. Determining the reconstitution ratio is essential to ensure that the final mixture meets the user's tolerance limit for accuracy.For traceability purposes, the quantity of each solution, based on the weight of the distributed quantity, is necessary to calculate the reconstitution ratio.

[0008] Serial dispensing, which uses a separate dispensing head for each solution, where the quantity of the first solution dispensed is weighed, and then, based on this weight, the quantity of the second solution to be dispensed is calculated, offers greater accuracy and the required traceability. A disadvantage of serial dispensing compared to parallel dispensing is the increased dispensing time, parallel dispensing being generally faster. For laboratories analyzing a large number of food and other samples, speed is an advantage.

[0009] A common approach currently used to dispense two or more different solutions involves first calibrating a separate pump for each solution to be dispensed in a sample, and then simultaneously dispensing ("dosing") each solution in parallel, either using separate dosing lines or inline via a Y-splitter that merges the solutions, thus enabling efficient mixing. However, over time, the calibration of one or more pumps begins to drift and lose accuracy. The parallel dispensing method does not allow for adjusting the amount of one solution to be dispensed to compensate for an overdose or underdose of the other solution, which affects accuracy. Determining a reconstitution ratio is essential to ensure that the final mixture meets the user's tolerance limit for accuracy.For traceability purposes, the quantity of each solution, based on the weight of the distributed quantity, is needed to calculate the reconstitution ratio. However, if the solutions are mixed in-line and distributed together, traceability is lost.

[0010] In other existing methods, serial dispensing, which uses a separate dispensing head for each solution, where the quantity of the first solution dispensed is weighed, and then, based on this weight, the quantity of the second solution to be dispensed is calculated, offers greater accuracy and the required traceability. However, the disadvantage of serial dispensing compared to parallel dispensing is the increased dispensing time, parallel dispensing being generally faster. For laboratories that analyze a large number of food samples, speed is essential.

[0011] Moreover, none of the currently available gravimetric diluters describe or allow the dilution of a "concentrated broth solution"; at best, they only allow the dilution of a "sample" and are not able to dispense several different solutions.

[0012] For example, U.S. Patent No. 4350186 describes an apparatus comprising a means for weighing a sample and any diluent added to the container, a means for dispensing a diluent, a means for selecting and calculating a dilution factor, and a means for stopping the flow of the diluent when the final weight of the sample and diluent is reached. However, there is no disclosure regarding the addition of two or more different diluents.

[0013] In another example, U.S. Patent No. 9403608 describes gravimetric diluters equipped with up to six pumps for dispensing liquids. However, the instrument is designed to dispense a single liquid (into several containers, if necessary). To add a concentrated solution (lOx or other concentration factor) and a diluent to obtain a solution Ix containing the food sample, the end user must run two different programs and manually switch between them.

[0014] Another existing gravimetric diluter (such as Dilumat™) is designed to work only with medium or broth solutions Ix and cannot be used for concentrated diluents.

[0015] Current methods do not combine speed, precision and traceability and, in some cases, do not allow the distribution of multiple or concentrated diluents / solutions.

[0016] Consequently, existing methods and systems for distributing solutions using gravimetric distributors present several problems that need to be solved. Description of the invention

[0017] The patent presentation relates, in certain embodiments, to systems and methods using a gravimetric diluter to precisely add two or several liquids / fluids (e.g., solutions) to a sample rapidly. In some embodiments, the systems and methods of the present invention are configured to dilute a "concentrated solution" (such as a broth solution, medium, selective agent solution, etc.), in addition to being configured to dilute a "sample" (such as a food sample, a medical / cosmetic sample, etc.). In some embodiments, the systems and methods of the present invention advantageously allow for the traceability of the added solutions. In some embodiments, the systems and methods of the present invention advantageously allow for the dispensing of a plurality of solutions, the acceleration of the dispensing of one or more solutions, the improvement of the accuracy of the dispensing of one or more solutions, and the ensuring of the traceability of one or more solutions.

[0018] In some embodiments, the methods for serially distributing two or more solutions using a gravimetric distributor include: weighing a sample to determine its mass; distributing a first solution by gravimetry with a tolerance corresponding to the mass of the sample; weighing the combination of the mass of the sample and the first distributed solution; determining a quantity of a second concentrated solution to be distributed to the combination of the mass of the sample and the first distributed solution, in order to obtain a concentration Ix of the second solution; and distributing the quantity of the second concentrated solution by gravimetry into the combination of the first solution and the mass of the sample.

[0019] In some embodiments of the process, a sample is weighed on a balance integrated into the gravimetric dispenser to determine the mass of the sample. In some embodiments of the process, the combined mass of the sample and the first dispensed solution is weighed on a balance integrated into the gravimetric dispenser.

[0020] In some embodiments of the process, a second concentrated solution is located in the concentration range of > Ix to approximately 50x. In some embodiments, the quantity of a first solution dispensed is calculated by calibrating a peristaltic dosing volume of a first solution based on the number of revolutions of a pump in a gravimetric diluter, multiplied by the tube diameter. This calculated quantity of a first solution is then dispensed into the sample mass on the integrated balance of the gravimetric diluter. One or more pumps can be used to dispense solutions via tubing that can have different diameters.

[0021] In certain embodiments of the process, additional liquids, fluids or solutions (e.g., a third solution, a fourth solution, a fifth solution, etc.) may be mixed with the sample mass using the Gravimetric dispenser. Examples of supplementary solutions include buffer, antibiotic, selective agent, selective supplement, and combinations thereof. Non-limiting examples of antibiotics / selective agents and broths include novobiocin, vancomycin, 24 LEB buffer (Listeria broth), 24 LEB selective supplements, etc. The volume of added supplementary solutions is determined based on the mass of the preceding solutions. Additional pumps and / or tubing are typically used to dispense the supplementary solutions.

[0022] In some embodiments, the first solution is a diluent, water, or a concentrated solution. In some embodiments, the second solution is a concentrated solution, a diluent, or water. Non-limiting examples of diluents include sterile water, a single-concentration medium, or a buffer. Non-limiting examples of concentrated solutions include concentrated sterile broth. Other exemplary solutions include buffered peptone water (BPT), tryptone soy broth (TSB), phosphate-buffered saline (PBS), lactose broth, nutrient broth, Fraser broth, Rappaport-Vassiliadia broth, Listeria enrichment broth (LEB), 24 LEB (Listeria broth), etc. Solutions useful to the current methods can be any solutions that enrich or increase the number of microorganisms likely to contaminate a sample.

[0023] In certain embodiments, a method according to the present invention may further include reducing the distribution time of the first or second solution by adjusting one or more of the following parameters: tube diameter, tube elasticity, and / or the speed of one or more peristaltic pumps. This may, for example, consist of adjusting the tube diameter by using a larger diameter tube or a smaller diameter tube. In certain embodiments of a method according to the present invention, the speed of the peristaltic pump is increased or decreased.

[0024] In certain embodiments of a method according to the present invention, a first line of solution, i.e. a tubing intended to distribute the first solution, is distributed between two or more pumps, and the pumps containing the first solution operate simultaneously in parallel in order to reduce the time required to distribute the first solution.

[0025] In certain embodiments, the present invention describes a gravimetric dispensing system comprising: a gravimetric dispenser; one or more processors; and one or more hardware storage devices for storing instructions executable by the processor(s) to configure the gravimetric dispenser to: weigh a sample to determine its mass; dispense by gravimetrically a first solution with a tolerance corresponding to the mass of the sample; weigh the combination of the mass of the sample and the first distributed solution; determine a quantity of a second concentrated solution to distribute to the combination of the mass of the sample and the first distributed solution, in order to obtain a concentration Ix of the second solution; and distribute the quantity of the second concentrated solution by gravimetry in the combination of the first solution and the mass of the sample.

[0026] In some embodiments of a system, a processor determines the volume of the first solution and the volume of the second solution to be distributed, and the determination of the volumes of the first and second solutions is based on the mass of the sample.

[0027] In certain embodiments of a system, the processor continuously monitors and analyzes a trend in the total mass deviation (TMD) data and a trend in the reconstitution deviation (RD) data for a given operating cycle and automatically adjusts a stop anticipation (SA) and an approach zone (AZ) to counteract any drift in the system.

[0028] In certain embodiments of a system, the processor orders an increase in both the stop anticipation (SA) and the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) exceeds a target value. In certain embodiments of a system, the processor orders an increase in the stop anticipation (SA) and either an increase, a decrease, or no change in the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) exceeds a target value. When the trend in the data relating to the mean TMD exceeds a target value, this generally corresponds to an overdose of one of the two solutions (i.e., the first or second solution such as water, the medium, etc.).

[0029] In certain embodiments of a system, the processor orders a decrease in both the stop anticipation (SA) and the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) is less than a target value. When the trend in the data relating to the mean TMD is greater than a target value, this generally corresponds to an overdose of one of the two solutions (i.e., the first or the second solution, such as water, the medium, etc.). In certain embodiments of a system, the processor orders a decrease in the stop anticipation (SA) and, in certain embodiments, a modification (for example, an increase or a decrease) of the approach zone (AZ) if the data including the results of the mean reconstitution deviation (RD) are less than a target value. In certain embodiments of a system, the processor orders a decrease in the stop anticipation. (SA) and no change in the approach zone (AZ) if the data including the results of the mean reconstruction deviation (RD) are less than a target value.

[0030] Certain embodiments of the present invention relate to computer-implemented methods comprising: weighing a sample to determine its mass; distributing a first solution by gravimetry with a tolerance corresponding to the mass of the sample; weighing the combination of the mass of the sample and the first distributed solution; determining a quantity of a second concentrated solution to be distributed to the combination of the mass of the sample and the first distributed solution, in order to obtain a concentration Ix of the second solution; and distributing the quantity of the second concentrated solution by gravimetry in the combination of the first solution and the mass of the sample.

[0031] In certain embodiments of a computer-implemented process, a processor determines the volume of the first solution and the volume of the second solution to be distributed based on the mass of the sample. Additional solutions (a third solution, a fourth solution, such as water, etc.) may be distributed, the volumes of which may also be determined by a processor.

[0032] In certain embodiments of a computer-implemented process, the processor continuously monitors and analyzes a trend in the data relating to the total mass deviation (TMD) and the reconstitution deviation (RD) for a given operating cycle of a gravimetric dilution system and automatically adjusts a shutdown anticipation (SA) and an approach zone (AZ) in order to counteract any drift in the gravimetric dilution system.

[0033] In some embodiments of a computer-implemented process, the processor orders an increase in the stopping anticipation (SA) and, in some embodiments, an increase in the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) is greater than a target value. In some embodiments of a computer-implemented process, the processor orders an increase in both the stopping anticipation (SA) and the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) is greater than a target value. When the trend in the data of the average TMD results is greater than the average target value, this generally corresponds to an overdose of one (or more) of the two (or more) solutions (the first solution, the second solution, etc.).

[0034] In certain embodiments of a computer-implemented process, the processor orders a decrease in the stop anticipation (SA) and, in certain embodiments, a decrease in the approach zone (AZ) if the trend of data including the mean total mass deviation (TMD) is less than a target value. In some embodiments of a computer-implemented process, the processor orders a decrease in both the stop anticipation (SA) and the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) is less than a target value. When the trend in the data of the mean TMD results is less than the average target value, this generally corresponds to an underdosing of one (or more) of the two (or more) solutions (the first solution, the second solution, etc.).

[0035] In certain embodiments of a computer-implemented process, the processor orders an increase in the stop anticipation (SA) and, in certain embodiments, an increase in the approach zone (AZ) if the data including the results of the mean reconstruction deviation (RD) are greater than the target value.

[0036] In certain embodiments of a computer-implemented process, the processor orders a decrease in the stop anticipation (SA) and, in certain embodiments, a decrease in the approach zone (AZ) if the data including the results of the mean reconstruction deviation (RD) are less than the target value.

[0037] In certain embodiments of a computer-implemented process, the processor automatically selects an optimal program setting when a different sample mass is selected or entered. The sample mass can be selected by the user. This can be done manually in a computer / processor or by entering the sample mass via a user interface. It is also possible for the processor to automatically enter the sample mass when it is weighed.

[0038] In certain embodiments of a computer-implemented process, the processor selects an optimal pump from among a plurality of pumps, depending on the sample mass, in order to maximize accuracy and speed. In certain embodiments of a computer-implemented process, the processor selects an optimal combination of a pump and the corresponding tube diameter from among a plurality of pumps equipped with one or more tubes of varying diameters, depending on the sample mass, in order to maximize accuracy and speed.

[0039] In certain embodiments, the present invention describes a data processing system comprising means for implementing the steps of the processes described in the sections above and below.

[0040] In certain embodiments, the present invention relates to a computer-readable storage medium comprising instructions which, when they are executed by a computer, lead the computer to implement one or more steps of the processes described here.

[0041] In certain embodiments, the systems and methods of the present invention allow a gravimetric diluter to use a combination of a plurality of solutions (a first solution, a second solution, a third solution, a fourth solution, etc.) to accurately dilute a sample (for example, as required by ISO standards), thus facilitating automatic dispensing, based on the initial weight of a sample (for example, sample mass or sample mass). Samples that can be diluted by the systems and methods described in this disclosure include food samples, cosmetic samples, dietary supplement samples, medical samples, chemical samples, pharmaceutical samples, etc.

[0042] In certain exemplary embodiments, one or more of the multiple dispensed solutions include, but are not limited to, concentrated media, concentrated broths, concentrated boiling media, water, buffers, supplements, selective agents, antibiotics, and others. In one exemplary embodiment, the systems and methods of the present invention enable a gravimetric diluter to use a combination of sterile water and concentrated medium to dilute a food sample with accuracy conforming to ISO standards, based on the initial weight of the food sample (i.e., sample mass).

[0043] Certain embodiments of the present invention may offer one or more technical advantages. The methods and systems described in the present invention, in certain embodiments, advantageously reduce the time required to test samples (such as, but not limited to, food samples) by enabling the rapid and precise dispensing of volumetric solutions. The methods and systems described in the present invention, in certain embodiments, offer the advantage of improved traceability of the added solutions.In certain embodiments, the processes and systems of the present invention offer one or more advantages, such as: improved occupational health and safety (OHS) through the elimination of culture media powders that can disperse in the air, and / or the elimination of high-temperature activities such as autoclaving, and / or reduced consumption of plastic, consumables, and energy, and / or reduced heavy loads when transporting finished media weighing up to 20 kg, and / or reduced risk of media contamination. The methods can be implemented on automated, semi-automated, and / or manually.

[0044] Although specific advantages have been described above, it is understood that various embodiments may include all, some, or none of the advantages described above. Other technical advantages may become clear to those skilled in the art in light of the teachings in this disclosure. These and other features of these teachings will become clearer upon reading the detailed description in the sections below. Brief description of the drawings

[0045] One or more embodiments of the present invention can be better understood by referring to one or more of the drawings below. The skilled craftsman will understand that the drawings described below are provided for illustrative purposes only. The drawings are not intended to limit the scope of this instruction.

[0046] [Fig.1] represents an example of a gravimetric dilution system with a two-pump and single-tube configuration, according to an embodiment of the present invention;

[0047] [Fig.2] represents an example of a gravimetric dilution system with a configuration with two pumps and two tubes, according to an embodiment of the present invention;

[0048] [Fig.3] represents an illustration of a pump tube, according to a mode of realization of the present invention;

[0049] [Fig.4] represents an example of a tubing configuration allowing a transition from a tube to the other according to their diameter in order to optimize precision or speed, according to one embodiment of the invention;

[0050] [Fig. 5] represents an example of a flowchart of a process according to the present invention, according to an embodiment provided by way of example;

[0051] [Fig. 6A] illustrates, by way of example, the effects of tube size on dispensing precision / accuracy with respect to dispensing speed, according to an embodiment of the present invention; and

[0052] [Fig.6B] represents the effects, by way of example, of the size of the tubing on the precision / accuracy of the distribution with respect to the speed of distribution, in particular the speed times on the deviation of the broth, according to an embodiment of the invention.

[0053] Detailed description of particular embodiments

[0054] It is understood that the preceding general description and the detailed description that follows are given by way of example and explanation only and are not intended to limit the scope of the actual teachings. In this application, the use of the singular includes the plural, unless expressly stated otherwise. Similarly, the use of The terms "understand," "contain," and "include," or modifications of these root words, for example, but not limited to, "includes," "contains," and "includes," are not intended to be restrictive. Unless otherwise indicated, the use of the word "or" means "and / or." The term "and / or" means that the preceding and following terms can be taken together or separately. By way of illustration, but without limitation, "X and / or Y" can mean "X" or "Y" or "X and Y."

[0055] Whenever a range of values ​​is indicated in this document, that range is deemed to include the initial value and the final value, as well as any value or range of values ​​in between, unless expressly stated otherwise. For example, "from 0.2 to 0.5" means 0.2, 0.3, 0.4, 0.5; the intervals between these values, such as 0.2-0.3, 0.3-0.4, 0.2-0.4; the increments between these values, such as 0.25, 0.35, 0.225, 0.335, 0.49; the intervals of increments between these values, such as 0.26-0.39; and other similar values.

[0056] The section headings used in this document are for organizational purposes only and shall not be construed as limiting the subject matter described. All documents and other similar media cited in this application, including, but not limited to, patents, patent applications, articles, books, treaties, and web pages, regardless of format, are expressly incorporated by reference in their entirety for all purposes. In the event that one or more incorporated documents or other similar media define or use a term in a manner that contradicts the definition of that term in this application, this application shall prevail. Although the teachings presented herein are described in conjunction with various embodiments, they are not intended to be limited to those embodiments.On the contrary, the present teachings encompass various alternatives, modifications and equivalents, as those versed in the art will understand.

[0057] The term "or combinations thereof" as used herein refers to all permutations and combinations of the elements listed preceding the term. For example, "A, B, C or combinations thereof" is intended to include at least one of the following: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, ACB, CB A, BCA, BAC, or CAB. To continue with this example, combinations that contain repetitions of one or more elements or terms are expressly included, such as BB, AAA, AAB, BBC, AAABCCCC, CBBAAA, CABABB, etc. The skilled craftsman will understand that there is generally no limit to the number of elements or terms in a given combination unless otherwise indicated in the context.

[0058] This patent description relates to methods and systems for diluting samples in order to analyze the presence of various contaminants such as such as pathogens, etc. Samples include, but are not limited to, food samples, environmental samples, clinical samples, industrial samples, laboratory samples, air samples, and aquatic samples.

[0059] A food sample that can be tested by the methods described in the present invention can be any type of food source, including dry or moist foods, natural foods (natural and / or raw edible materials), processed and / or treated foods, and can include any material used at any stage of food processing or treatment. A food sample can include samples of meat or seafood, such as beef, pork, ham, chicken, turkey, poultry, fish, shrimp, crustaceans; pet food (dog food, cat food, etc.).); vegetables (leafy and others); fruits; nuts; cereals; dairy products, including milk, yogurt, cheeses, cream, yogurt drinks, juices, smoothies, soups, beverages, processed / prepared foods, such as hamburgers or sausages, frozen meals, canned foods, bottled foods, cereals, frozen foods, and may also include nutraceuticals and ingredients. A food sample may include a beverage sample, such as juices, sodas, bottled and canned drinks of any kind.

[0060] The term "tolerance" refers to an permissible error in the mass of a sample and is generally expressed as a percentage by weight. The term "percentage of reconstitution" refers to the ratio between the quantity of water and the quantity of concentrate (of a given solution). The distribution tolerances acceptable in the art for a 10 g sample are as follows: Total volume of broth ±2%; reconstitution error < 5%. The tolerance value is generally set by the International Organization for Standardization (ISO). The reconstitution error is not generally defined by ISO, as it can vary depending on the preparation method, such as the method of measuring a sample or the method of measuring the quantity of water added, for example, using a graduated cylinder, a peristaltic pump, or by weighing, etc. The reconstitution error desired by the customer is here < 5%.

[0061] The requirements of ISO 6887-1 relating to gravimetric dilution allow a tolerance of + / -2%. Consequently, the total mass deviation (TMD) corresponds to the difference between the mass actually distributed and the target or expected mass.

[0062] TMD(%) = (actual mass - target mass) / target mass x 100

[0063] These are the mass weights of broth (i.e., after deduction of the mass initial of the sample). The target mass of broth is equal to 9 times the mass weight of the sample, as specified in ISO 6887-1.

[0064] Deviation in % of the total mass of broth = ((observed mass of broth / expected mass of broth) - l)*100 %.

[0065] Reconstitution error (RE) or reconstitution error in % = ((observed ratio / expected ratio) - 1) x 100.

[0066] In some embodiments, the ratio of water to concentrate must be 9 parts water to 1 part concentrate for a 10% concentrate:

[0067] Ratio = Mass of concentration / (Mass of water + Mass of concentrate)

[0068] The ratio "Mass of concentrate / (total mass of solution)" must be = 0.1 for a 10% solution (using a 10x concentrate)

[0069] For example, = 9 g conc / (81 g water + 9 g conc) = 0.1 (10%)

[0070] Reconstitution error in % = ((observed ratio / expected ratio) - 1) x 100%

[0071] Reconstitution tolerance = ([[Mass of concentration / (Mass of water + Mass of concentrate)] / 0.l] - 1) * 100%

[0072] Each peristaltic pump generally has three parameters that determine its distribution profile:

[0073] 1. Approach Zone (AZ) - Mass difference relative to the target to which the The pump transitions from maximum speed to a reduced "approach speed." The approach zone (AZ) is the point at which the scale displays a deviation of less than "x" grams from its final mass. When this zone (AZ) is reached, the system's speed can decrease (approach speed (AS)). When the AZ value is too low, the pump remains at full speed for too long and tends to consistently overshoot the target value. This occurs because the system does not have enough time to slow down and stabilize before reaching the target. Undershooting can occur, but only when the AS value is high, causing the pump to shut down prematurely. A low AZ almost always results in overshooting rather than undershooting.

[0074] 2. Approach Speed ​​(AS) - Flow reduction applied after entering the zone approach. This slower speed allows sufficient time for the balance to stabilize before issuing the stop command.

[0075] 3. Early Stop (ES) - Predefined offset from the target to which the pump receives the order to stop. The SA compensates for the residual flow that persists after the pump stops due to tubing elasticity and pressure in the lines. Optimizing the SA ensures that the final dispensed mass closely matches the target after stabilization. Since the stop anticipation (SA) corresponds to the point at which the pump should cease running, e.g., at 1 g of the target, there may be a delay between the pump stopping and the liquid ceasing to be dispensed, depending on the line pressures in the tubing. AZ must always must be greater than SA. If AZ is equal to or less than SA, the pump will not enter the approach speed phase and the AZ parameter will have no effect.

[0076] Stopping anticipation (SA) and approach zone (AZ) are independent control parameters. Although they can be coordinated by the processor, they do not necessarily follow the same pattern or direction of adjustment. If the total mass deviation (TMD) is less than the target value, a processor commands a decrease in SA, while the AZ may or may not require adjustment. Similarly, if the TMD is greater than the target value, a processor commands an increase in SA, while the AZ may or may not require adjustment. The AZ is generally set at a level high enough relative to the target mass to allow the dilution pump sufficient time to decelerate and enable the balance to provide feedback for an accurate SA result, but not so high as to unnecessarily increase the overall dispensing time.

[0077] During dispensing, the scale continuously monitors the mass of the dispensed liquid. To account for system variables (e.g., line pressures) that affect accuracy, the system can be optimized by providing the pump with information on when it should stop running.

[0078] The TMD is determined by the mass of water dispensed (since this represents 90% of the broth mass). The RD is determined by the mass of concentrate dispensed, as it adjusts to the mass of water dispensed beforehand, as does the ratio between water and concentrate mixture. The AZ, AS, and SA parameters are adjusted and linked to each tube size. For example, if a 6.4 mm tube is used for the concentrate and a 6.4 mm tube for the water, the same AZ, AS, and SA settings will be used. However, this configuration is unlikely, because for 125 g samples, an 8 mm tube could be used for the water and a 6.4 mm tube for the concentrate, and for 10 g samples, a 1.6 mm tube could be used for the concentrate and a 6.4 mm or 8 mm tube for the water. For 25g samples, 1.6mm or 3.2mm tubes can be used for the concentrate and 8mm tubes for the water.

[0079] For example, using the methods described in this document, accurate dosing was achieved for 10 g and 25 g samples with a 3.2 mm inner diameter (ID) tube for the concentrate line and a 6.4 mm ID tube for the 125 g samples, thus balancing accuracy and speed. In another example, a 1.6 mm inner diameter tube was initially used for the concentrate, and a 6.4 mm inner diameter tube was used for water when dispensing 10 g samples. After optimizing the dispensing parameters (AZ, AS, and SA), a 3.2 mm inner diameter tube proved optimal for the concentrate and an 8.0 mm inner diameter tube proved optimal for the water. These adjustments resulted in faster dispensing times. and to reduce the need to frequently change tube sizes between sample sets.

[0080] Another way to control accuracy is to further slow down the dispensing speed. Thus, in the event of overdosing or underdosing, this slowing of the pump speed gives the scale more time to signal the pump to continue or stop and for the pressure in the tubing to stabilize.

[0081] This patent description describes systems and methods for accurately adding or dispensing two or more liquids / fluids (e.g., solutions) to a sample within a reasonable dispensing time using a gravimetric diluter. In some embodiments, the systems and methods of the present invention allow a gravimetric diluter to use a combination of a plurality of solutions (a first solution, a second solution, a third solution, a fourth solution, etc.) to accurately dilute a sample (e.g., as required by ISO standards), thus facilitating automatic dispensing, based on the initial weight of a sample (e.g., sample mass or sample mass) to enable downstream analysis or processing of the sample.Non-limiting examples of samples that can be diluted by the systems and methods described in the present invention include food samples, cosmetic samples, dietary supplement samples, medical samples, chemical samples, pharmaceutical samples, etc. Systems:

[0082] The presentation of the invention, in certain embodiments, describes gravimetric dilution systems comprising: a gravimetric dispenser; one or more processors; and one or more hardware storage devices for storing instructions executable by the processor(s) in order to configure the gravimetric dispenser to: weigh a sample to determine its mass; gravimetrically distribute a first solution with a tolerance corresponding to the mass of the sample; weigh the combination of the mass of the sample and the first distributed solution; determine a quantity of a second concentrated solution to distribute to the combination of the mass of the sample and the first distributed solution, in order to obtain a concentration Ix of the second solution; and distribute the quantity of the second concentrated solution by gravimetry into the combination of the first solution and the mass of the sample.

[0083] In exemplary embodiments, the systems and methods described in the present invention describe a gravimetric diluter capable of dispensing a plurality of solutions (a first solution, a second solution, a third solution, etc.) to dilute a sample accurately (for example, as required by the ISO standards), thus facilitating automated dispensing based on the initial weight of a sample (e.g., sample mass or sample mass). Samples that can be diluted by the systems and methods described in this disclosure include food samples, cosmetic samples, dietary supplement samples, medicinal samples, chemical samples, pharmaceutical samples, etc.

[0084] In certain exemplary embodiments, one or more of the multiple dispensed solutions include, but are not limited to, concentrated media, concentrated broths, concentrated boiling media, water, buffers, supplements, selective agents, antibiotics, and others. In one exemplary embodiment, the systems and methods of the present invention enable a gravimetric diluter to use a combination of sterile water and concentrated medium to dilute a food sample with accuracy conforming to ISO standards, based on the initial weight of the food sample (i.e., sample mass).

[0085] [Fig-1] illustrates an example of a gravimetric system 100 according to the present invention, comprising a gravimetric dilution instrument 110, two (or more) pumps 120, a plurality of hose clamps 130, tubes 140 and 140', etc. (for example, representing tubes of different diameters), a plurality of containers represented by 150 and 160 to hold the plurality of solutions to be dispensed into a sample (for example, a first solution, a second solution, etc.), and a sample plurality of solutions 170 and 180, which may be either a first or a second solution. A system 100, by way of example, consists of the DILUWEL UP!TM gravimetric diluter from Alliance Bio Expertise (Guipry-Messac, France). The gravimetric diluters 110 include an integrated balance (not explicitly shown) for accurately weighing a sample "as is," and then calculating the appropriate amount of solution to add to obtain the desired sample dilution.Gravimetric diluters 110 also generally include additional devices or components, such as, but not limited to, a filter 190, clips 130, a power supply (not shown), a display unit 200 such as a monitor or user interface that can be operated to receive input or selection from a user or software and / or to view the processing and / or dispensing of a sample and the tracking of one or more solutions in a sample to be analyzed.

[0086] A computer system (not explicitly shown) comprising a central processing unit (CPU), herein referred to as the "processor", hardware and / or software components that may be physically located in the gravimetric diluter 110 or outside of it and that may be operationally connected to the instrument 110 for forming the gravimetric system 100. The computer system of the gravimetric dilution system 100 allows control of various components of the instrument 110 and its central processing unit, as well as the hardware and software elements enabling control and direction of all automated sample processing steps, including weighing, dilution, and dispensing of multiple solutions into the sample and / or processing of the data acquired during these steps and / or downstream data processing. Accordingly, the computer system of the gravimetric dilution system 100 may include a data analysis and control system, a data transfer system such as a readable and writable CD-ROM or DVD drive, at least one USB port, and / or at least one Ethernet port.In some embodiments, the computer system associated with the gravimetric diluter 110 may include pre-loaded software and / or application-specific integrated circuits (ASICs) that may allow control of the device 110 and / or other components of the system 100, including several components of the system 100, control of processing and analysis, and / or control of the display and / or export of results.

[0087] In some embodiments, the pumps 120 may be peristaltic pumps capable of dispensing one or more solutions. Then, using information returned by the computer processor based on the sample weight, the gravimetric dilution instrument 110 can calibrate the mass of the dispensed sample according to the number of rotations of the pump rollers. If two or more pumps 120 are used, each pump is calibrated separately, since the volume of a dispensed solution depends on several factors, including the diameter and elasticity of the tubing (140 or 140'), as well as the viscosity and mass of each dispensed solution.

[0088] In some embodiments, the computer system of the system 100 can be operational to control one or more of the following steps: distribute a quantity of sample, said quantity of sample being either entered by a user or determined by the processor, for example by controlling the movement of the sample from a compartment 110 to the integrated balance; distribute a quantity of one or more solutions in the sample in order to obtain a particular concentration of solution and / or sample; and / or regulate the rotation speed of one or more pumps 120 on the basis of information returned by the processor concerning the mass or weight of the sample; regulate the distribution speed and volume of liquid solutions distributed in the sample mass; track one or more solutions that are distributed in the sample; etc.Software for system 100 (not expressly shown) can be written to control one or more. several steps and parameters for the dilution and distribution of the sample and / or solution.

[0089] In some embodiments, the system 100 can be fully automated. In some embodiments, the system 100 can be a manually operated system. In some embodiments, the system 100 can be operated partly manually and partly automatically.

[0090] Embodiments of the present invention provide a data processing system comprising means for implementing the steps of the processes described herein. Embodiments of the present invention provide a computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to implement (the steps of) one or more processes described herein.

[0091] Fig. 2 represents another embodiment of a gravimetric dilution system 100' comprising two pumps 120 with a double tubing of 140' and 140", all other parts and components being numbered in the same way as the parts and components described in Fig. 1.

[0092] Fig. 3 represents an illustration of a pump 120 and a pump tube 121, according to an embodiment of the present invention, the white arrows indicating the direction of fluid flow and the black arrows indicating the direction of rotation 122 of the peristaltic pump 120.

[0093] Figure 4 illustrates an example of a pump 120 and tubing 140, 140' configured to switch from one tube to the other according to their diameter to ensure accuracy and speed, according to an embodiment of the present invention. As described in the sections above, existing systems and methods do not combine speed, accuracy, and traceability and, in some cases, do not allow for the dispensing of multiple diluents / solutions or concentrated diluents / solutions. In contrast, the systems and methods described here offer combinations of tubing diameters and pumping speeds that allow for the accurate and rapid dispensing of multiple solutions, as described here and in the examples that follow.

[0094] In some embodiments by way of example, the systems and methods implemented on the systems of the present invention allow a gravimetric diluter to use a combination of concentrated medium and water to dilute a food sample with the accuracy required by ISO standards, making it the first gravimetric diluter capable of automatically dispensing, according to the initial weight of a "sample mass", two or more solutions to obtain a precise dilution.

[0095] The embodiments described may include or use a special-purpose or general-purpose computer, including computer hardware, such as explained in more detail below. The described embodiments also include physical and other computer-readable media for transporting or storing computer-executable instructions and / or data structures. These computer-readable media can be any available medium accessible by a general-purpose or specialized computer system. Computer-readable media that store computer-executable instructions as data are one or more "physical computer storage media" or "hardware storage devices." Computer-readable media that merely transport computer-executable instructions without storing them are "transmission media."Thus, by way of example and without limitation, current embodiments may include at least two distinct types of computer-readable media: computer storage media and transmission media.

[0096] Computer storage media (also called "hardware storage devices") are computer-readable hardware storage devices, such as RAM, ROM, EEPROM, CD-ROM, RAM-based "SSD" (Solid State Drive) disks, flash memory, phase-change memory ("PCM") or other types of memory, or any other optical storage medium, magnetic storage medium or other magnetic storage device, or any other medium that can be used to store the desired program code in the hardware in the form of computer-executable instructions, data or data structures accessible by a general-purpose or specialized computer.

[0097] A "network" is defined as one or more data links enabling the transport of electronic data between computer systems and / or modules and / or other electronic devices. When information is transferred or provided via a network or other communication connection (wired, wireless, or a combination of both) to a computer, the computer correctly considers this connection as a means of transmission. Transmission media may include a network and / or data links that can be used to transport program code in the form of computer-executable instructions or data structures, and which can be accessed by a general-purpose or specialized computer. Combinations of the foregoing are also included within the scope of computer-readable media.

[0098] Furthermore, once they have reached various components of the computer system, the program code, in the form of computer-executable instructions or data structures, can be automatically transferred from a computer-readable transmission medium to a computer-readable physical storage medium. computer (or vice versa). For example, computer-executable instructions or data structures received via a network or data link can be buffered in the RAM of a network interface module (e.g., a "network card") and then ultimately transferred to the computer system's RAM and / or to a less volatile, computer-readable physical storage medium within the computer system. Thus, computer-readable physical storage media can be included in computer system components that also (or even primarily) use transmission media.

[0099] Executable computer instructions include, for example, instructions and data that cause a general-purpose computer, a special-purpose computer, or a special-purpose processing device to perform a certain function or group of functions. Executable computer instructions may be, for example, binaries, instructions in an intermediate format such as assembly language, or even source code.

[0100] The described embodiments may include or use cloud computing. A cloud model may be composed of various features (e.g., on-demand self-service, wide area network access, resource pooling, fast elasticity, measured service, etc.), service models (e.g., Software as a Service (“SaaS”), Platform as a Service (“PaaS”), Infrastructure as a Service (“LaaS”) and deployment models (e.g., private cloud, community cloud, public cloud, hybrid cloud, etc.).

[0101] Those versed in the art will understand that the embodiments of the present invention can be implemented in networked computing environments comprising many types of computer system configurations, including personal computers, desktop computers, laptops, message processors, handheld devices, multiprocessor systems, microprocessor or programmable consumer electronics, networked PCs, minicomputers, mainframes, mobile phones, PDAs, pagers, routers, switches, handheld devices, etc.The present invention can also be implemented in distributed systems environments where multiple computer systems (e.g., local and remote systems), which are connected by a network (either by wired data links, wireless data links, or a combination of wired and wireless data links), perform tasks. In a distributed systems environment, the program modules can be located in local and / or remote memory storage devices.

[0102] Alternatively or in addition, the functionality described herein may be provided, at least in part, by one or more hardware logic components. For example, and without limitation, illustrative types of hardware logic components that may be used include field-programmable pre-diffused arrays (FPGAs), application-specific integrated circuits (ASICs), application-specific standard products (ASSPs), systems-on-chip (SoCs), complex programmable logic devices (CPLDs), central processing units (CPUs), graphics processing units (GPUs), and / or others.

[0103] In this document, the terms "executable module," "executable component," "component," "module," or "engine" may refer to hardware processing units or software objects, routines, or methods that can be executed on one or more computer systems. The various components, modules, engines, and services described herein may be implemented as objects or processors that run on one or more computer systems (for example, as separate threads).

[0104] In certain implementations, the systems of the present invention may include or be configured to execute any combination of software and / or hardware components that can be used to facilitate processing using machine learning models or other artificial intelligence-based structures / architectures. For example, one or more processors may include and / or use hardware components and / or computer-executable instructions that can be used to execute functional blocks and / or processing layers configured in the form of, by way of non-limiting example, single-layer neural networks, direct-propagating neural networks, radial basis function networks, deep direct-propagating networks, recurrent neural networks, long-term short-term memory (LSTM) networks, gated recurrent units, autoencoding neural networks, variational autoencoders,Denoising autoencoders, sparse autoencoders, Markov chains, Hopfield neural networks, Boltzmann machine networks, restricted Boltzmann machine networks, deep belief networks, deep convolutional networks (or convolutional neural networks), deconvolutional neural networks, deep convolutional inverse graph networks, generative adversarial networks, liquid-state machines, extreme learning machines, echo-state networks, deep residual networks, Kohonen networks, support vector machines, Turing neural machines, and / or others.

[0105] Various alterations and / or modifications of the inventive features illustrated herein, as well as additional applications of the principles illustrated herein, which might occur to a person competent in the relevant field and having been made aware of the present invention, may be made to the embodiments illustrated without departing from the spirit and scope of the present invention. as defined by the claims, and shall be considered as falling within the scope of the present invention. Thus, although various aspects and embodiments have been described here, other aspects and embodiments are conceivable. Although a number of methods and components similar or equivalent to those described herein may be used to implement embodiments of the present invention, only certain components and methods are described herein. Methods:

[0106] In certain embodiments, the present invention provides methods for the serial dispensing (dosing) of two or more solutions. In certain embodiments, the methods described in the present invention take into account the weight of the preceding solution for traceability purposes.

[0107] The methods described in the present invention take into account several factors that affect the accuracy and speed of existing gravimetric dispensing systems. For example, in existing systems, inline pressure fluctuations alter the dispensing accuracy (target concentration + / -0.3 g for 10 g samples). The integrated counterweight provides a negative feedback loop to the pump to regulate pump slowdown and shutdown. Despite optimal program settings before start-up, a known problem is over- or under-dispensing of solutions, which can occur when a gravimetric dilution system experiences fluctuations relative to the initial solution pressures, as shown in the examples below: • Hydrostatic pressure in the pipe - Water / Concentrate: pressure variation from high to low over time as the solution volume decreases • Concentration and water temperature (35°C at room temperature) - viscosity / friction increases as the solution cools • Water filter: surface area: negative pressure upstream of the pump, increases as the volume of a given solution decreases • Installing the pump clamp: the tension exerted on the tubing affects the motor resistance / back pressure • Hose material / length / wear / temperature (in the collar): shock elasticity, friction / resistance • Degradation of filter flow rate over the lifetime of a system, resulting in a decrease in flow rate in the pipes

[0108] The procedures described in the present invention use serial dilution to ensure accuracy and combine this approach with adjustments to the tubing and the speed of the peristaltic pump to obtain a dosage rapid, thus overcoming several limitations of existing methods and gravimetric systems.

[0109] Figure 5 illustrates an exemplary embodiment of a method according to the invention comprising the following steps: in step 10: automatic weighing of a sample (for example, a food sample) on an integrated scale of a gravimetric diluter to determine a sample mass (for example, a food sample mass); in step 11: gravimetric distribution of a first solution (for example, a sterile water-based diluent) until a given tolerance is reached (i.e., "X" times) of the mass of the sample weighed in step 10, (for example, by calibrating a peristaltic dosed volume of the first solution, the number of pump turns "x" the diameter of the tube, relative to its dosed mass on the integrated scale);in step 12: weighing of the combination of the sample and the first distributed solution (i.e., [mass of the first combined solution and the mass of the sample weighed in step 12] - [mass of the mass of the sample weighed in step 10] = mass of the first solution), in step 13: determination of a quantity of a second concentrated solution (e.g., a concentrated sterile broth solution) to be distributed in the combination of the mass of the sample and the first distributed solution, to obtain a concentration IX of the Second Solution (e.g., a simple broth solution with a final concentration IX); in step 14: gravimetric distribution of the quantity of the second concentrated solution determined in step 13 in the combination of the first solution and the sample;and in step 15: optionally, the addition of one or more additional solutions using, for example, one or more additional pumps, based on the determined mass of the previous solutions (for example, for additions of selective supplements or buffers).

[0110] In certain embodiments, the methods for serially dispensing two or more solutions using a gravimetric dispenser include: weighing a sample to determine its mass; dispensing a first solution by gravity with a tolerance corresponding to the mass of the sample; weighing the combination of the mass of the sample and the first dispensed solution; determining the quantity of a second concentrated solution to be dispensed into the combination of the mass of the sample and the first dispensed solution, in order to obtain a concentration Ix of the second solution; and dispensing the quantity of the second concentrated solution by gravity into the combination of the first solution and the mass of the sample. An example of a diluter suitable for applying the procedures described in the present invention is the DILUWEL UP!TM gravimetric diluter from Alliance Bio Expertise.

[0111] In some embodiments of the process, a sample is weighed on a balance integrated into the gravimetric dispenser to determine the mass of the sample. In some embodiments of the process, the combined mass of the sample and the first dispensed solution is weighed on a balance integrated into the gravimetric dispenser.

[0112] In some embodiments of the process, a second concentrated solution is located in the concentration range of approximately >1x to approximately 50x. In some embodiments, the quantity of a first solution dispensed is calculated by calibrating a peristaltic dosing volume of a first solution based on the number of revolutions of a pump in a gravimetric diluter, multiplied by the tube diameter. This calculated quantity of a first solution is then dispensed into the sample mass on the integrated balance of the gravimetric diluter. One or more pumps can be used to dispense solutions via tubing that can have different diameters.

[0113] In certain embodiments of the process, additional liquids, fluids, or solutions (e.g., a third solution, a fourth solution, a fifth solution, etc.) may be mixed with the sample mass using the gravimetric dispenser. Exemplary additional solutions may be a buffer, an antibiotic, a selective agent, a selective supplement, and combinations thereof. Non-limiting examples of antibiotics / selective agents and broths include novobiocin, vancomycin, 24 LEB buffer (Listeria broth), 24 LEB selective supplements, etc. The volume of the additional solutions added is determined based on the mass of the preceding solutions. Additional pumps and / or tubing are generally used to dispense the additional solutions.In some embodiments, since supplements are generally added in very small quantities, they can be added manually using a pipette rather than a pump, and the system records the weight of the solution added for traceability purposes.

[0114] In some embodiments, the first solution is a diluent, water, or a concentrated solution. In some embodiments, the second solution is a concentrated solution, a diluent, or water. Non-limiting examples of diluents include sterile water, a single-concentration medium, or a buffer. Non-limiting examples of concentrated solutions include concentrated sterile broth. Other solutions by way of example include buffered peptone water (BPW), tryptone soy broth (TSB), phosphate-buffered saline (PBS), lactose broth, nutrient broth, Fraser broth, Rappaport-Vassiliadia broth, Listeria enrichment broth, 24 LEB (Listeria broth), etc. Solutions useful to the current methods can be any solutions that enrich or increase the number of microorganisms likely to contaminate a sample.

[0115] In certain embodiments, a method according to the present invention may further include reducing the distribution time of the first or second solution by adjusting one or more of the following parameters: tube diameter, tube elasticity, and / or the speed of one or more peristaltic pumps. This may, for example, consist of adjusting the tube diameter by using a larger diameter tube or a smaller diameter tube. In certain embodiments of a method according to the present invention, the speed of the peristaltic pump is increased or decreased.

[0116] In certain embodiments of a method according to the present invention, a first solution line, i.e., a tube for distributing the first solution, is distributed between two or more pumps, and the pumps containing the first solution operate simultaneously in parallel in order to reduce the time required for the distribution of the first solution. A first solution line may be a tube for distributing a first solution.

[0117] In some embodiments, the methods can be implemented automatically or by a combination of manual inputs and automatic steps on a system of the present invention. The methods described in the present invention can be implemented by a computer processor. In some embodiments, the processes described in the present invention are computer-implemented processes.

[0118] Accordingly, in certain embodiments, the methods of the present invention are implemented on a gravimetric dispensing system comprising: a gravimetric dispenser; one or more processors; and one or more hardware storage devices for storing instructions executable by the processor(s) in order to configure the gravimetric dispenser to: weigh a sample to determine its mass; gravimetrically dispense a first solution with a certain tolerance (selected, given or calculated) with respect to the mass of the sample; weigh the combination of the mass of the sample and the first dispensed solution; determine a quantity of a second concentrated solution to dispense to the combination of the mass of the sample and the first dispensed solution, in order to obtain a concentration IX of the second solution;and distribute by gravimetry the quantity of the second concentrated solution in the combination of the first solution and the sample. The processor determines the volume of the first solution (solution one) and the volume of the second solution (solution two) to be distributed as a function of the weighed mass of the sample.

[0119] In certain embodiments, the processor continuously monitors and analyzes a trend in the data relating to the total mass deviation (TMD) and the reconstitution deviation (RD) for a given operating cycle, and automatically adjusts a shutdown anticipation (SA) and an approach zone (AZ) to counteract any system drift. The processor of a system according to the present invention, while executing a method according to the present invention, commands an increase in the shutdown anticipation (SA) and, in certain embodiments, an increase in the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) exceeds a target value. When the trend in the data relating to the mean TMD results exceeds a target average value, this corresponds to an overdose of one or more of the two solutions (e.g., water, medium, etc.).

[0120] The processor of a system according to the present invention, while executing a method according to the present invention, commands a decrease in the stop anticipation (SA) and, in certain embodiments, a change in the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) is less than a target value. When the trend in the data relating to the mean TMD is less than the average, this corresponds to an underdosing of one of the two solutions (for example, water, medium, etc.).

[0121] In certain embodiments of the processor-controlled process, the processor orders an increase in the standby anticipation (SA) and, in some embodiments, an increase in the approach zone (AZ), or, in other embodiments, no change in the approach zone (AZ), if the data including the results of the mean recovery deviation (RD) are greater than the target. Similarly, the processor orders a decrease in the standby anticipation (SA) and, in some embodiments, a decrease, or in other embodiments, no change, in the approach zone (AZ) if the data including the results of the mean recovery deviation (RD) are less than the target.

[0122] Embodiments of the present invention describe a computer-implemented method comprising: 1) weighing a sample to determine the mass of the sample; 2) the gravimetric distribution of a first solution with a tolerance of the mass of the sample; 3) weighing the combination of the mass of the sample and the first distributed solution; 4) determining a quantity of a second concentrated solution to be distributed to the combination of the mass of the sample and the first distributed solution, in order to obtain a concentration IX of the second solution; and 5) the gravimetric distribution of the quantity of the second concentrated solution in the combination of the first solution and the sample.

[0123] In the computer-implemented embodiments of the process described above, the processor determines the volume of the first solution and the volume of the second solution to be distributed based on the sample mass. The processor continuously monitors and analyzes a trend in the data relating to the total mass deviation (TMD) and the reconstitution deviation (RD) for a given operating cycle, and automatically adjusts the stop anticipation (SA) and the approach zone (AZ) to counteract any system drift.

[0124] In computer-implemented embodiments of the process, the processor orders an increase in the stop anticipation (SA) and, in some embodiments, an increase in the approach zone (AZ) if the trend in the data, including the mean total mass deviation (TMD), exceeds a target value. When the trend in the data for the mean TMD results is greater than the average, this corresponds to an overdose of one of the two solutions (such as water, the medium, etc.).In computer-implemented embodiments of the process, when the processor commands a decrease in the standstill anticipation (SA) and, in some embodiments, a change (e.g., a decrease or an increase), or, in some embodiments, no change (e.g., no increase or decrease) in the approach zone (AZ), if the trend in the data including the mean total mass deviation (TMD) is less than a target value. When the trend in the data relating to the mean TMD results is less than the mean, this corresponds to an underdosing of one of the two solutions (such as water, medium, etc.).

[0125] In computer-implemented embodiments of the process, the processor orders an increase in the standby anticipation (SA) and, in some embodiments, an increase in the approach zone (AZ) if the data including the results of the mean reconstitution error (RD) are greater than the target. In other embodiments of the computer-implemented process, the processor orders an increase in the standby anticipation (SA) and, in some embodiments, a decrease, or in other embodiments, no change in the approach zone (AZ) if the data including the results of the mean reconstitution error (RD) are greater than the target.In some embodiments, the processor orders a decrease in the standby anticipation (SA) and, in some embodiments, a decrease in the approach zone (AZ) if the data including the mean recovery deviation (RD) results are less than the target. In other embodiments, the processor orders a decrease in the standby anticipation (SA) and, in some embodiments, no change in the approach zone (AZ) if the data including the mean recovery deviation (RD) results are less than the target.

[0126] In some embodiments, the processor automatically selects an optimal program setting when a different sample mass is selected. Sample mass selection can be performed by the user. The user can enter the sample mass via a user interface or manually via the computer. Alternatively, the sample mass is entered automatically by the processor when the sample mass is weighed (on the integrated balance, for example). In some embodiments, a software algorithm can be coded to automatically select an optimal program setting for dispensing solutions based on different sample masses (such as 10 g, 25 g, or 125 g). Alternatively, the user can manually select the required program.

[0127] In computer-implemented embodiments of the process, the processor selects an optimal pump from a plurality of pumps, based on the sample mass, to maximize accuracy and speed. For example, the processor selects an optimal combination of a pump and the corresponding tube diameter from several pumps equipped with tubes of different diameters, based on the sample mass, to optimize accuracy and speed.

[0128] Furthermore, if three or four pumps were connected to the diluter (for example, one for water / diluent and the other two or three for the second concentrated solution (and any additional solution)), the processor could select the optimal pump to use (for example, a pump pre-charged with a 1.6 mm, 3.2 mm, 4.8 mm or 6.4 mm tube for the concentrated medium line and 8.0 mm for the water line) depending on the sample size, in order to maximize accuracy and speed.

[0129] Embodiments of the present invention provide a data processing system comprising means for implementing the steps of the processes described herein. Embodiments of the present invention provide a computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to implement (the steps of) one or more processes described herein.

[0130] An example of implementing the method, illustrated by a food sample and solutions such as a concentrated medium and water, is described here. The volume of broth is to be 9 times greater than the mass of the sample and is allocated 90% to the aqueous diluent and 10% to a concentrated medium (this may vary depending on the concentration of the concentrated medium used). In this example, water is dispensed as the first solution and a concentrated solution is dispensed as the second solution (although the user can choose to dispense any other solution as the first or second solution using the software). The second solution is adjusted according to the final mass of the first solution distributed in order to make the ratio of reconstitution of water and concentrate more accurate. Overview of the different aspects:

[0131] The present invention relates to certain aspects of a serial gravimetric dispensing method for two or more solutions. The method comprises the steps of weighing a sample to determine its mass; dispensing a first solution by gravimetry with a tolerance relative to the determined mass of the sample in order to produce a combination of the mass of the sample and the first dispensed solution; weighing the combination of the mass of the sample and the first dispensed solution; determining an amount of a second concentrated solution to be dispensed into the combination of the sample and the first solution in order to obtain a final concentration Ix of the second solution; and dispensing the determined amount of the second concentrated solution into the combination of the first solution and the sample by gravimetry.

[0132] In one or all of the above aspects, the sample and the combination of the sample and the first solution are weighed using a balance integrated into the gravimetric dispenser.

[0133] In all or part of the above aspects, the mass of the sample is weighed on a balance integrated into the gravimetric dispenser. In all or part of the above aspects, one or more peristaltic pumps and / or tubing are used to dispense the first and second solutions.

[0134] In all or part of the above aspects, the second concentrated solution has a concentration between more than Ix and about 50x.

[0135] In all or part of the above aspects, the quantity of first solution dispensed is calculated by calibrating a peristaltic dosed volume of the first solution on the basis of the number of pump turns multiplied by the diameter of the tubing, relative to the mass of the sample.

[0136] In all or part of the above aspects, additional solutions may be mixed using the gravimetric dispenser, the additional solutions being selected from a buffer, an antibiotic, a selective agent, a selective supplement, or combinations thereof. For example, a third solution selected from a buffer, an antibiotic, a selective agent, a selective supplement, and combinations thereof is mixed using the gravimetric dispenser. Similarly, a fourth, fifth, sixth, etc., solution(s) may be mixed.

[0137] In all or part of the above aspects, the choice or quantity of additional solutions is determined according to the mass of the solutions previously distributed, and these solutions can be administered using additional pumps and / or tubular channels.

[0138] In one or all of the above aspects, the first solution comprises a diluent, water, or a concentrated solution. In some cases, the diluent is sterile water, a single-concentration medium, or a buffer, and the concentrated solution is a concentrated sterile broth solution.

[0139] In all or part of the above aspects, the second solution comprises a concentrated solution, a diluent or water, in which the concentrated solution is a concentrated sterile broth solution.

[0140] In all or some of the above aspects, the distribution time of the first or second solution is reduced by adjusting one or more of the following: the tube diameter, the peristaltic pump speed, or a combination thereof. Adjusting the tube diameter may involve using a larger or smaller diameter tube, and the pump speed may be increased to shorten the distribution time. In some embodiments, the first solution line, i.e., a tube intended to distribute the first solution, is divided between two or more pumps, with the pumps operating simultaneously in parallel to reduce the distribution time.

[0141] The present invention also relates to certain aspects of a gravimetric distribution system comprising a gravimetric distributor, one or more processors and one or more hardware storage devices storing instructions executable by the processors in order to configure the distributor to execute the steps of the process described above.

[0142] In one or all of the above aspects, in the systems of the present invention, a processor determines the volume of the first and second solutions to be dispensed based on the measured mass of the sample. In all or some of the above aspects, a processor continuously monitors and analyzes data trends, including the total mass deviation (TMD) and the reconstitution deviation (RD) during a given operating cycle, and automatically adjusts the stopping anticipation (SA) and, in some embodiments, a modification of the approach zone (AZ) parameters to compensate for drift within the system. For example, in some embodiments, the processor orders an increase in SA and AZ when the average TMD or RD values ​​exceed the target thresholds, and a decrease in SA and AZ when the average values ​​fall below the target thresholds.In other embodiments, for example, the processor orders an increase in SA and no change in AZ when the average TMD or RD values ​​exceed the target thresholds, and a decrease in SA and no change in AZ when the average values ​​fall below the target thresholds.

[0143] In certain aspects, in disclosure systems in which the approach zone (AZ) and the stop anticipation (SA) are selected such that the approach zone (AZ) is always greater than the stop anticipation (SA).

[0144] The present invention also relates to certain aspects of a computer-implemented method comprising the same gravimetric distribution steps as described above, in which a processor determines the volumes to be distributed as a function of the mass of the sample and dynamically adjusts the control parameters (SA and AZ) as a function of real-time performance data in order to maintain precision and accuracy.

[0145] In all or part of the above aspects, the processor automatically selects an optimal program setting when selecting different sample masses, the sample mass being able to be entered by a user via a user interface or automatically detected by the system during weighing.

[0146] In one or all of the above aspects, the processor selects an optimal pump / tubing combination from a plurality of available pumps equipped with tubes of varying diameters, in order to maximize both accuracy and speed for a given sample mass.

[0147] The present invention relates to certain aspects of a data processing system comprising means for implementing the gravimetric distribution method described herein. Furthermore, the aspects described in this document include a computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to implement one or more of the methods described in this document.

[0148] The section entitled "Examples" below describes several examples of workflow methods and protocols tested using the methods, and / or devices, and / or systems and / or compositions of the present invention. EXAMPLES

[0149] Aspects of the present teachings can be better understood in the light of the following examples, which should not be interpreted as limiting in any way the scope of the present teachings. Example 1 Gravimetric distribution methods

[0150] In an example of an implementation in the present invention, where 25.4 g of a food sample are weighed on a balance integrated into a gravimetric diluter (such as the DILUWEL UP!TM gravimetric diluter from Alliance Bio Expertise), for a 1Ox concentrate, an example of a software method according to the present invention performs the following operations:

[0151] Step 1: Aqueous diluent = (25.4 x 9) x 90% = 205.74 g (theoretical mass required). If the tolerance = + / -2%, then the tolerance mass is + / -4.11 g. The tolerance of + / -2% applies to the broth as a whole, and not just to the water. Thus, 25.4 x 9 = 228.6, or 2% = 4.57 g in total for the TMD.

[0152] Step 2: An algorithm then calculates the actual amount of water added by deducting the mass of the food sample from the weight of the balance after step 1.

[0153] If the scale reads 233.14 g: (233.14 - 25.4) = 207.74 g of water added (i.e., 2 g of additional water). Theoretical concentrate required = (207.74 / 90%) * 10% = 23.08 g. If the scale then reads 256.81 g, then (256.81 - 233.14) = 23.67 g of concentrate have "actually" been added.

[0154] The percentage (%) of reconstitution tolerance (water / concentrate ratio) must be between + / -3.5% and <4%. This varies; if the Voice of Customer (VoC) is <5%, and the customer has hydrated the DryBag with + / -0.5% powder and + / -0.5% water, this allows a reconstitution error of <4% for the diluter to mix the concentrate with the water.

[0155] Reconstitution deviation in % = (actual concentration - desired concentration) / (desired concentration) x 100%:

[0156] Expected concentration = 23.08 / (23.08 + 207.74) = 23.08 / 230.82 = 0.10 or 10%

[0157] Expected concentration = 23.67 / (23.67 + 207.74) = 23.67 / 231.41 = 0.1023 or 10.23 %

[0158] % reconstitution error = (10.23 - 10) / 10 x 100% = 2.3%, which is within the tolerance of + / -3.5%. Example 2 Accuracy and speed of distribution

[0159] In an example, where a first solution, for example a (aqueous) diluent, is required at a higher volume / mass than the second concentrated solution and can be distributed through a larger diameter tube in order to accelerate the distribution rate.

[0160] When configuring the diluter, the user selects the tube size on the user interface or computer, and the software algorithm takes this into account in the dispensing rate. The processor and software will determine the rate at which the solution is dispensed. The peristaltic pump clamp must also be adjusted to ensure it is set for the correct tubing diameter to provide sufficient compression. Typically, the user manually adjusts the clamp setting according to the selected tubing diameter, using the indicator arrows on the clamp, to achieve optimal compression. This is usually described in the user manual for a gravimetric dilution instrument (e.g., DILUWEL UP!TM user manual).

[0161] If the diluent has a higher volume / mass tolerance, i.e., in an example where the second solution is a concentrated solution, for example a 1.8% diluent "against" a 0.2% concentrate tolerance, and if the limit is a tolerance of + / -2% of the final broth (or a diluent (first solution) tolerance 9 times greater than that of the concentrate (second solution)), then:

[0162] 100 g of the first total solution (tolerance + / -2%): 9 volumes of water to 1 volume of concentrate (concentration lOx): 90 g of water (+ / -1.8 g): 10 g of concentrate (+ / -0.2 g)

[0163] Although using a larger tube for the diluent helps to resolve certain speed issues (i.e., a 6.4 mm tube has a surface area (irr2) 4x greater than that of a 3.2 mm tube, the overall diluent dispensing rate remains more than 2x greater than the concentrate dispensing rate for a 10x concentrate in this configuration: 6.4 mm tube "versus" 3.2 mm tube, i.e. (90 g of water / 10 g of concentrate 10x) / 4 (tube surface area ratio) = 2.25. Consequently, the dispensing time will be 2.25x longer if the peristaltic pump speed is similar for the dispensing accuracy of the diluent and the concentrate.

[0164] Increasing the pump speed reduces the time required, but at a certain point, increasing the speed can reduce accuracy. Another option is to divide the (aqueous) diluent line between two or more pumps and operate all the diluent pumps simultaneously in parallel to reduce the time required to distribute the diluent. [Tables 1] Ix bouillon concentrate Powder weight ±1% ±0.5% Water addition ±4% ±0.5% Reconstitution deviation <±5% ±1.0%* Broth preparation: Superior precision for better distribution tolerance

[0165] Table 1 indicates the reconstitution accuracy requirements for a single-strength broth (Ix) versus a single-strength concentrate (lOx). ISO Standard (11133:2014, section 4.3.4) requires that the powder be weighed to an accuracy of 1%, but does not specify the accuracy required for the addition of water. This therefore depends in part on the method used to add the water (e.g., graduated cylinder, pump, weighing). The generally accepted limit is + / -5% reconstitution error (mixing of powder and water).

[0166] For the lOx concentrate, the required tolerances are slightly different, but this is due to the additional steps required for manufacturing and diluting the concentrate (i.e., adding the powder to the sachet, hydrating the sachet, diluting the concentrate). For an lOx concentrate, since larger masses are involved, it is easier to be more precise during preparation and hydration. To prepare a simple 5 L BPW solution at 20 g / L, the user must weigh out 100 g of powder + / - 1 g (1%). For an lOx bag sufficient for 100 liters of medium, the user would weigh out 2000 g of powder + / - 10 g (0.5%), so it is easier to achieve a higher tolerance as the quantity of powder weighed increases.

[0167] For a single-concentration broth, the preparation error can reach 4% (1 to 3% for the graduated cylinder and 1 to 3% for water loss during autoclaving). For 2000 g of powder in a sachet of lOx concentrate, 8200 g of water + / -40 g (0.5%) is required. Since the powder is already sterilized by irradiation, no autoclaving step is necessary. The procedure for lOx would consist of accurately weighing this mass during the preparation of the concentrate before adding it to the powder. A more precise reconstitution tolerance for the concentrate allows for greater variation when mixing the concentrate with the aqueous diluent using the diluter (i.e., up to 3.5%, as shown in Table 2). Single-concentration media do not require any further dilution steps, unlike the concentrate, which is not applicable here. [Tables 2] Ix bouillon concentrated Ox Component Mass Early mass deviation Total mass deviation Reconstitution deviation 10 g of food 10 g ±5% (or 0.5 g) ±5% (or 0.5 g) Ix bouillon 90 g ±2% (1.8 g) Aqueous diluent 81 g Combined ±2% (1.8 g) N / A: Distributed first Ox bouillon 9 g ±3.5% (0.3 g)

[0168] It has been determined that the distribution of lOx broth must be 6x more accurate than the distribution of Ix broth. Table 2 lists the tolerances with a concentrated Ix (single concentration) or lOx medium. The food mass must be between + / -5% and the total mass deviation between + / -2% (in accordance with ISO standard). 6887-1:2017). The reconstitution deviation is not detailed in the ISO standards, but for medium lOx, it would be <4% based on a maximum variation of 1% in the dry sachet preparation steps (detailed in Table 1) and a maximum reconstitution deviation of <5% observed with the preparation of medium Ix. Example 3

[0169] Tube size on dispensing precision / accuracy versus dispensing speed

[0170] [Fig.4] illustrates an example of a distribution configuration for a concentrate and Water was dispensed using tubing of varying diameters. For concentrate dispensing, a 1.6 mm diameter tube was used for the 10 g and 25 g samples, while a 3.2 mm diameter tube was used for the 25 g and 125 g samples. Water was dispensed using an 8 mm diameter tube for all sample sizes. The tube diameter was selected to achieve acceptable TMD and RD dispensing tolerances, balancing speed and accuracy, as illustrated in Figures 6A and 6B. Average dispensing speeds are shown in Figure 6B (where T1 = -12 s; T2 = -26 s; T3 = -16 s; T4 = -60 s). With 125g samples, a 6.4mm diameter tube achieved dispensing velocities of approximately 46, with a similar level of accuracy.

[0171] Each embodiment disclosed herein may be used or combined with any other embodiment described. Any element of one embodiment may be used in any other embodiment. Although the invention has been described with reference to specific embodiments, those familiar with the field will understand that various changes may be made and equivalents may be substituted for elements thereof without departing from the true spirit and scope of the invention. Furthermore, modifications may be made without departing from the essential teachings of the invention.

Claims

Demands

1. A method for dispensing two or more solutions in series using a gravimetric dispenser, the method comprising: weighing a sample to determine a mass of the sample; gravimetric dispensing a first solution with a tolerance of the mass of the sample in order to produce a combination of the mass of the sample and the first dispensed solution; weighing the combination of the mass of the sample and the first dispensed solution; determining an amount of a second concentrated solution to be dispensed into the combination of the mass of the sample and the first dispensed solution, in order to obtain a concentration IX of the second solution; and gravimetric dispensing the amount of the second concentrated solution into the combination of the first solution and the sample.

2. A method according to claim 1, wherein one or more peristaltic pumps and / or tubing are used to distribute the first solution and the second solution.

3. A method according to claim 1, wherein the combination of the sample mass and the first dispensed solution is weighed on a balance integrated into the gravimetric dispenser.

4. A method according to claim 1, wherein the second concentrated solution is in a concentration range between 50x and > Ix.

5. A method according to claim 2, wherein the quantity of first solution dispensed is calculated by calibrating a volume of first solution dosed by peristalsis on the basis of the number of pump revolutions multiplied by the diameter of the tubing, relative to the weighed mass of the sample.

6. A method according to claim 1, wherein a third solution selected from a buffer, an antibiotic, a selective agent, a selective supplement and combinations thereof is mixed using the gravimetric distributor.

7. A method according to claim 6, wherein additional pumps and / or tubing are used to distribute the third solution.

8. A method according to claim 1, wherein the first solution and / or the second solution is a diluent, water or a concentrated solution.

9. A method according to claim 8, wherein the diluent is sterile water, a single-concentration medium, or a buffer.

10. A method according to claim 8, wherein the concentrated solution is a concentrated sterile broth solution.

11. A method according to claim 1, further comprising modifying the distribution flow rate of the first solution or the second solution by adjusting the diameter of the tube or the speed of one or more peristaltic pumps and combinations thereof.

12. A method according to claim 11, wherein a tube for distributing the first solution is divided between two or more pumps, and the pumps containing the first solution operate simultaneously in parallel in order to reduce the time required to distribute the first solution.

13. A gravimetric dispensing system comprising: a gravimetric dispenser; one or more processors; and one or more hardware storage devices storing instructions executable by the processor(s) to configure the gravimetric dispenser to: Weigh a sample to determine the mass of the sample; gravimetrically dispense a first solution with a tolerance of the sample mass to produce a combination of the sample mass and the first dispensed solution; weigh the combination of the sample mass and the first dispensed solution; determine an amount of a second concentrated solution to dispense into the combination of the sample mass and the first dispensed solution to obtain a concentration Ix of the second solution; and distribute the quantity of the second concentrated solution gravimetrically into the combination of the first solution and the sample.

14. System according to claim 13, wherein the processor determines the volume of the first solution and the volume of the second solution to be distributed as a function of the mass of the sample.

15. System according to claim 13, wherein the processor continuously monitors and analyzes a trend in the data relating to the total mass deviation (TMD) and the rebuild deviation (RD) for a given operating cycle, and automatically adjusts a stop anticipation (SA) and an approach zone (AZ) to counteract any drift in the system.

16. System according to claim 13, wherein the processor orders an increase in the stop anticipation (SA) and the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) or the data including the mean reassembly deviation (RD) is greater than a target value, and wherein the processor orders a decrease in the stop anticipation (SA) and the approach zone (AZ) if the trend in the data including the mean total mass deviation (TMD) or the data including the mean reassembly deviation (RD) is less than a target value.

17. System according to claim 13, wherein the approach zone (AZ) and the stop anticipation (SA) are selected such that the approach zone (AZ) is always greater than the stop anticipation (SA).

18. A computer-implemented method comprising: weighing a sample to determine the sample mass; gravimetrically distributing a first solution with a tolerance of the sample mass to produce a combination of the sample mass and the first distributed solution; weighing the combination of the sample mass and the first distributed solution; determining the quantity of a second concentrated solution to be distributed to the combination of the sample mass and the first distributed solution, in order to obtain a concentration Ix of the second solution; and the gravimetric distribution of the quantity of the second concentrated solution in the combination of the sample mass and the first distributed solution.

19. A computer-implemented method according to claim 18, wherein a processor determines the volume of the first solution and the volume of the second solution to be distributed as a function of the mass of the sample.

20. A computer-implemented method according to claim 18, wherein the processor continuously monitors and analyzes a trend in the data relating to the total mass deviation (TMD) and the rebuild deviation (RD) for a given operating cycle, and automatically adjusts a stop anticipation (SA) and an approach zone (AZ) to counteract any drift in the system.

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