Preparation of substances in medical diagnostic systems

Abstract

Operations performed according to the exemplary techniques described herein include controlling a probe to puncture a stopper of a container containing a substance, wherein the stopper provides an airtight seal to the container, and wherein the airtight seal supports internal pressure within the container. The operation further includes: detecting internal pressure based on information from a pressure sensor; determining that the internal pressure is not at a target pressure; and, based on the determination that the internal pressure is not at the target pressure, controlling the probe to either draw air from the container or expel air into the container to move the internal pressure toward the target pressure.

Description

Technical Field

[0001] This specification generally relates to techniques for preparing substances for use in medical diagnostic systems. Background Technology

[0002] Medical diagnostic systems test samples (such as blood or tissue) obtained from patients. A test performed by a medical diagnostic system is called an assay. An exemplary assay is an investigative procedure used to qualitatively assess or quantitatively measure the presence, amount, or functional activity of an analyte in a sample. One or more substances (such as reagents, reference standards, or calibrators) may be used by a medical diagnostic system to assay a sample. Summary of the Invention

[0003] Exemplary techniques can be implemented using one or more non-transitory machine-readable media containing methods, systems, or instructions executable by one or more processing devices. Operations performed according to the exemplary techniques include controlling a probe to puncture a stopper of a container containing a substance, wherein the stopper provides an airtight seal to the container, and wherein the airtight seal supports internal pressure within the container. The operation further includes: detecting internal pressure based on information from a pressure sensor; determining that the internal pressure is not at a target pressure; and, based on the determination that the internal pressure is not at the target pressure, controlling the probe to either draw air from the container or expel air into the container to move the internal pressure toward the target pressure. The technique may include one or more of the following features, individually or in combination.

[0004] The following operations can be repeated until the internal pressure is within a predefined range of the target pressure: controlling the probe to either draw air from the container or purge air into the container. Determining that the internal pressure is not at the target pressure may include comparing the internal pressure with information based on the target pressure. The target pressure may be based on ambient pressure, and the probe may be controlled to transfer the contents into the container. Before transferring the contents into the container, the internal pressure may be lower than the target pressure. In this case, the probe may be controllable to purge air into the container before transferring the contents to increase the internal pressure. After at least some of the contents have been transferred into the container, the internal pressure may be higher than the target pressure. In this case, the probe may be controllable to draw air from the container after transferring at least some of the contents to adjust for the decrease in internal pressure.

[0005] Detecting internal pressure may include receiving data from a pressure sensor connected to, part of, or on a probe. Adjusting the internal pressure toward a target pressure may include maintaining the pressure within the container below ambient pressure. The probe may be controllably designed to repeatedly inject or extract air into or from the container to bring the internal pressure closer to the target pressure. The number of times may be predefined. The probe may be able to controllably extract additional contents from the container based on the expansion of air within it.

[0006] An exemplary probe is configured to aspirate or expel material. The probe includes a shaft for holding the material and a hydraulic line, the hydraulic line including hydraulic fluid to create negative or positive pressure in the shaft, respectively, to aspirate or expel the material. The probe can be controlled to aspirate air before aspirating the material, thereby creating an air gap in the shaft between the hydraulic fluid and the material. After aspirating the air, the probe can be controlled to alternately aspirate the material and air, thereby creating at least one air gap between sections of material contained in the shaft, in addition to the air gap between the hydraulic fluid and the material. The probe may include one or more of the following features, individually or in combination.

[0007] At least one air gap between material segments contained in the shaft may include at least two air gaps. Each of the at least two air gaps may be located between two material segments. At least three to five air gaps may exist in the shaft. The shaft may include metal and the hydraulic lines may include non-metallic materials, thereby creating an interface that allows hydraulic fluid to leak into the shaft. The probe may be controllable to vent material along with air on each side of the material to be vented from the shaft.

[0008] Exemplary techniques may be implemented using methods, systems, or a plurality of non-transitory machine-readable media storing instructions executable by one or more processing devices. Operations performed according to the exemplary techniques include controlling a probe to draw air into the probe's shaft and controlling the probe to discharge air from the shaft into a container to at least mix a first substance and a second substance. The technique may include one or more of the following features, individually or in combination.

[0009] The container may include a vial, the first substance may include a reagent in liquid or dry / lyophilized form, and the second substance may include a diluent. Air is expelled from the shaft to produce a mixture based on the diluent and reagent in the vial, and is at least partially homogeneous. Before air is aspirated, the probe may be controlled to aspirate the second substance into the shaft of the probe, so that the shaft enters the container containing the first substance, and to expel the second substance into the container. In addition to the first and second substances, the container may hold one or more other substances. Mixing may include mixing one or more other substances with the first and second substances. (i) Air is aspirated from inside the container or (ii) air is aspirated from outside the container, and in (ii), the shaft is controlled to enter the container to expel air. The air may be expelled at a rate that homogenizes the mixture.

[0010] Any two or more features described in the specification, including those in the overview section, can be combined to form an implementation not specifically described herein.

[0011] The systems, techniques, components, structures, and variations thereof described herein, or parts thereof, may be implemented or controlled by a computer program product comprising instructions stored on one or more non-transitory machine-readable storage media, and these instructions may be executed on one or more processing devices to perform at least some of the operations described herein. The systems, techniques, components, structures, and variations thereof described herein, or parts thereof, may be implemented as devices, methods, or electronic systems comprising one or more processing devices and memory for storing executable instructions to perform various operations. The systems, techniques, components, structures, and variations thereof described herein may be configured, for example, by design, construction, size, shape, arrangement, placement, programming, operation, activation, deactivation, and / or control.

[0012] Details of one or more embodiments are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will become apparent from the specification, drawings, and claims. Attached Figure Description

[0013] Figure 1 This is a block diagram illustrating components of an exemplary medical diagnostic system on which the exemplary technologies described herein may be implemented.

[0014] Figure 2 This is a cross-sectional side view of a portion of an exemplary vial and probe.

[0015] Figure 3 This is a cross-sectional side view of an exemplary robotic probe, which is part of a medical diagnostic system.

[0016] Figure 4 This is a flowchart illustrating an exemplary method of processing a substance using the techniques described herein.

[0017] Figure 5 This is an example diagram showing the pressure formed in a container in response to repeated suction of air into the container.

[0018] Figure 6 It is a cross-sectional side view of an exemplary probe shaft containing the aspirated air and material to be expelled.

[0019] Figure 7 This is a cross-sectional side view of an exemplary probe shaft containing the air and material to be pumped out, as well as a material zone and air for absorbing hydraulic fluid leaks.

[0020] Figure 8 This is a cross-sectional side view of an exemplary probe shaft containing the air and material to be pumped out, as well as two material sections and air sections for absorbing hydraulic fluid leaks.

[0021] Figure 9 This is a perspective view showing an exemplary vial containing a diluent, liquid substance, and lyophilized substance.

[0022] Figure 10 It is a perspective view conceptually showing the mixing of substances in a vial using forced air as a mixing agent.

[0023] Figure 11 This is a flowchart illustrating an exemplary process of mixing substances in a vial using forced air as a mixing agent.

[0024] Figure 12 It is a perspective view that conceptually illustrates the mixing of substances in a vial using the suction and discharge of the substance itself as a mixing agent.

[0025] Figure 13 This is a flowchart illustrating an exemplary method of mixing substances in a vial using the substance itself as a mixing agent through suction and dispensing.

[0026] Figure 14 This is a flowchart illustrating an exemplary process for adjusting the pressure in a vial or other container having an initial pressure below a target pressure.

[0027] Figure 15 This is a flowchart illustrating an exemplary process for adjusting the pressure in a vial or other container having an initial pressure higher than a target pressure.

[0028] Figure 16 This is a flowchart illustrating an exemplary process for creating a section containing air and matter in a probe shaft.

[0029] Similar reference numerals in different figures indicate similar elements. Detailed Implementation

[0030] This document describes examples of medical diagnostic instruments, systems, and variations thereof (collectively, the “System”) that implement techniques for preparing substances used in assays. In this regard, the System may include a test container called a vial. The vial may include any substance required to perform the assay. Examples of substances that may be included in the vial include, but are not limited to, diluents and reagents. Examples of diluents that may be used include, but are not limited to, deionized (DI) water, buffer solutions, and liquid mixtures of different chemicals. Examples of reagents that may be used include, but are not limited to, simple and / or complex chemical mixtures.

[0031] When preparation for the assay is required before running a test on the system, the substance to be assayed is prepared in vials contained in a cartridge. In one example, the first vial may contain a lyophilized or liquid substance, and the second vial may contain a diluent, such as diluent (DI). To prepare the substance for the assay, a probe in the system can move the diluent from the first vial to the second vial to mix the diluent and the substance. Exemplary preparations include rehydrating the lyophilized component (substance) or mixing multiple components (substances) together before use. Typically, substances in dry (e.g., lyophilized) form are stored in vials with an internal pressure much lower than ambient pressure, such as under a vacuum or near a vacuum. Substances in liquid form may be stored in vials with a slightly positive internal pressure.

[0032] During the extraction or dispensing of substances from vials, the pressure difference between the inside and outside of the vial can cause problems. For example, if the pressure inside the second vial is significantly lower than ambient pressure (i.e., a significantly negative value), this could cause unwanted substances to be drawn into the vial through the probe (or needle) when the stopper is punctured. Conversely, if the pressure inside the vial is higher than ambient pressure (i.e., a positive value), puncturing the stopper could cause substances to erupt or leak from the vial.

[0033] Typically, before using the vial, the system performs pressure equalization on the vial so that the internal pressure of the vial reaches the target pressure. In some implementations, pressure equalization can be performed using the same probe as the probe used to aspirate material from the vial or a different device (such as a probe specifically designated to perform equalization). The benefit of using the same probe may be a potential reduction in contamination, while the benefit of using a different device is the additional flexibility that can be provided in the system design. Pressure equalization can be achieved by evacuating air from the vial or venting air into the vial to adjust the internal pressure of the vial toward the target pressure.

[0034] In an exemplary embodiment, a probe is controlled to pierce the stopper of a vial, which provides an airtight seal that maintains an internal, non-ambient pressure within the vial. A pressure sensor is connected to, is part of, or is on the probe. Based on information from the pressure sensor connected to, is part of, or is on the probe, the internal pressure of the vial is detected. The system determines that the internal pressure is not a target pressure or is within its acceptable range. Then, before moving any substance into or out of the vial, if the pressure is positive, the probe is controlled to draw air from the vial, or if the pressure is negative relative to the target pressure, air is expelled into the vial to move the internal pressure toward the target pressure.

[0035] Before or between the transfer of any substance into or out of the vial, the vial may be perforated to draw air from or expel air from the vial multiple times (e.g., a predetermined number of times) to bring the pressure in the vial to and / or maintain it at or near a target pressure. Other techniques for pressure regulation are also described herein.

[0036] As described above, the probe used for pressure balancing (referred to as the balancing probe) may be the same as or different from the probe used to deliver substance to or from a vial (referred to as the delivery probe). In some embodiments, any or all of the probes described herein are hydraulic. For example, a delivery probe may include a hydraulic line holding a hydraulic fluid (such as DI water). The flow rate of the hydraulic fluid may be controlled to create negative or positive pressure in its shaft to draw substance into or out of the shaft, respectively. The interface between the hydraulic fluid and the rest of the probe (including the shaft) may result in leakage of hydraulic fluid into the shaft. Leaking hydraulic fluid may contaminate the substance already drawn into the shaft. For example, substance drawn into the shaft to move from one vial to another (or another container, such as a cuvette) may be contaminated by leaking hydraulic fluid. In this case, contamination may include diluting the substance with the hydraulic fluid.

[0037] To reduce such contamination and its harmful effects, a control probe is used to create an air gap between the hydraulic fluid and the material within the shaft, and multiple material-air gap sections are created within the shaft, where each material layer is separated from the adjacent material layer by the air gap. In the event of a hydraulic fluid leak, the multiple air and material sections reduce the amount of hydraulic fluid that comes into contact with the material drawn into the probe.

[0038] In some examples, the probe may comprise a shaft with an internal lumen, such as a needle. To mix substances in a vial or cup, a probe, referred to as a mixing probe, can be controlled to draw air into its shaft. The mixing probe may be the same as the balancing probe and / or the delivery probe, or the mixing probe may be a different device. The advantages of using the same probe for balancing, delivery, and mixing may include, but are not limited to, efficiency and cost-effectiveness without compromising performance and / or increasing contamination / residue.

[0039] A controllable mixing probe is used such that its shaft pierces the stopper of a vial and forces air from the shaft into the vial to mix the substance within. Air can be forced into the vial at a rate that promotes or ensures sufficient homogenization of the substance, or the liquid mixture can be aspirated and expelled a sufficient number of times to ensure sufficient homogenization, for example, in such a way that the resulting homogenized substance exhibits analytical properties equivalent to standard determinations, such as experimental evaluation based on previous experiments. Other techniques for mixing substances are also described herein.

[0040] The apparatus used to perform balancing, transporting, and mixing can be any device other than a probe, such as, but not limited to, a robotic arm, provided that the apparatus performs the appropriate function, such as mixing / homogenizing, such that the analytical performance of the resulting homogenized material is equivalent to that of standard determinations, such as experimental evaluations. In the description below, any other type of apparatus may replace the probe.

[0041] Figure 1 A block diagram of an exemplary system 10 configured to implement the techniques described in the preceding paragraphs is shown. However, the techniques described herein are not limited to using, for example... Figure 1 The system shown. Figure 1 The system is provided as an example for illustration only.

[0042] System 10 includes a medical diagnostic instrument 11 for receiving and holding test cartridges (“cassettes”) 12. Each cartridge contains a container, such as a vial containing a substance described herein for use in an assay. The substance in the vial and / or vial within the cartridge may be processed for use with a specific assay. Processing may include, but is not limited to, altering or balancing the internal pressure of the vial in the system prior to use in an assay, delivering the substance to and from the vial, and / or mixing the substance at the delivery location, such as in the vial, in a cup, or in another test-related container / chamber. Processing may be performed using one or more controllable robotic probes (“probes”), such as… Figure 2 probe 30 or Figure 3 and Figure 9The probe 44. For example, the probe can be controlled to move between and into vials to implement all or some of the techniques described herein. The probe can be hydraulic as described herein, and during material delivery, it can be controlled to create an air gap between the hydraulic fluid of the probe and the material in the shaft of the probe, and to create multiple layers of material in the shaft, wherein each layer of material is separated from the adjacent layer of material by the air gap. In other functions, as described below, the probe can also be injected with air (e.g. Figure 10 and 11 ) and / or by aspirating and dispensing liquid substances from vials (such as Figure 12 and 13 This is used to mix / homogenize the substances in the vial. The mixing process begins once all the necessary substances are in the container, as described in more detail below.

[0043] Control of system 10 can be achieved through a control system 20 embedded in and / or associated with instrument 11. In some embodiments, components of the control system may be distributed across instrument 11 and / or one or more computing devices 21 communicating with instrument 11. The control system may be or include one or more processing devices 22, examples of which are described herein. The processing device 22 may reside within instrument 11 or be located outside instrument 11, such as in a local area outside instrument 11 or remotely from instrument 11. In some embodiments, the processing device 22 may reside within computing system 21. Computing system 21 may be separate from instrument 11 but may be connected to instrument 11 directly or via a wired or wireless computer network to enable communication between instrument 11 and computing system 21. In some embodiments, control system 20 includes a controller printed circuit board (PCB) 23 having one or more processing devices 22 programmable to control the operation of various system components. Controller PCB 23 may be embedded in or outside instrument 11. The control system 20 may also include a machine-readable and writable memory 24, which may be internal and / or external to the instrument 11 and stores data and computer programs executable by one or more processing devices on the controller PCB and / or computing system. The instrument is capable of recognizing any contents loaded into the instrument and will execute balancing, conveying, and / or mixing instructions based on the substances contained in the vials loaded into the instrument.

[0044] refer to Figure 2 The cap of the exemplary vial 32, referred to above as the stopper, forms an airtight / flow-tight seal with the vial. Inside the vial, the unbalanced pressure can be positive or negative relative to ambient pressure, as described herein. The stopper can be made of plastic, rubber, or other elastic material that can be pierced by a probe. Figure 2 The probe shaft 29 is shown, penetrating the stopper 31 of the vial 32.

[0045] In this case, the stopper includes a top portion 31a and a side portion 32a, which conform to the inner wall of the vial and create an airtight / flow-tight seal between the stopper and the vial. For example... Figure 2 As shown, shaft 29 pierces and penetrates stopper 31 until it extends into the internal volume 34 of the vial. Shaft 29 can continue into the interior until it reaches the bottom 35 of the vial. After the shaft of the probe is withdrawn from the vial and stopper, the material forming the stopper sinks into the hole created by the shaft, thereby reforming the hermetic / flow-tight seal between the stopper and the vial. In other words, the stopper self-seales after the shaft of the probe is withdrawn, thereby reforming the hermetic / flow-tight seal. When the stopper self-seales, any balance previously performed can be maintained.

[0046] Figure 3 An example of a robotic probe 44 that can be used in system 10 is shown. In this example, probe 44 is robotic because it is mechanically controllable to move, aspirate, drain, and perform other operations without manual manipulation. In some embodiments, the robotic probe may be user-controllable because the control system can receive user input regarding how the probe should operate, such as what tests to perform. However, after receiving such user input, the robotic probe may be automatically controlled by the control system, for example, in the manner described herein, to balance pressure, deliver substances, and / or mix substances.

[0047] The probe 44 includes a housing 45 and a shaft 46 having an inner cavity 47. Figure 2 Shaft 29 may have the same construction as shaft 47. Exemplary shaft and cavity structures include needles. Figure 3 As shown, shaft 46 has a tip 48, which is directed to pierce vial 32. Figure 2 The stopper 31 is inserted into the vial. Liquid substance is drawn into or pumped into the vial through the inner cavity 47 in the shaft 46. A pressure sensor 50 is connected to, is part of, or is on the probe. The pressure sensor 50 can be a wired or wireless pressure sensor, and its readings can be transmitted to a control system via a wired or wireless connection. The pressure sensor 50 is configured to detect the pressure inside the vial after the stopper has been pierced by the shaft of the probe. Information indicating the pressure inside the vial is sent to the control system, which can then control the probe as described herein to change (e.g., increase or decrease) the pressure inside the vial.

[0048] refer to Figure 4The probe can be used for pressure equalization (26) or pressure correction on containers (such as vials). After pressure equalization correction, the same probe or different delivery probes can deliver the substance from different containers (27) to containers or vials that have been pressure equalized or corrected. Furthermore, after substance delivery, the same probe or different mixing probes can mix (28) the delivered substance with another substance, as described herein, in a container or vial.

[0049] Pressure equalization involves aspirating and / or displacing air as part of a transfer to maintain control of the vial pressure. Pressure equalization can be achieved in at least two examples: before using the sealed vial (e.g., to change the internal pressure set at manufacturing) or during the use of the vial. Some air transfers, particularly larger ones, such as 10 mL or more, can be implemented by actively controlling the operation of the probe. Techniques described below include actively adding air to or removing air from the vial. In some embodiments, the air moving to or from the vial is controlled to maintain the vial under a slight vacuum, i.e., under a slightly negative pressure relative to ambient pressure (such as those described above).

[0050] This slight negative pressure prevents liquid from escaping the vial as the probe is removed through a hole in a seal or stopper created by the probe. In some embodiments, the target pressure may be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, or 9% lower than ambient pressure. In one example, ambient pressure is standard atmospheric pressure, defined in various units as 760 mm (29.92 inches) of mercury at sea level, 14.70 pounds per square inch, 1013.25 × 10³ dynes per square centimeter, 1013.25 millibars, or 101.325 kPa. However, it is worth noting that target pressures other than those presented herein can be achieved using the systems, probes, and techniques described herein.

[0051] For example, the target pressure inside the vial can be set by the control system based on the type of measurement to be performed, the preparation process associated with the measurement, the substances in the vial, and / or the substances used in the measurement.

[0052] Balancing the pressure to near ambient pressure reduces the likelihood of unintentionally drawing substance into or expelling it from the vial due to internal pressure. If the internal pressure is significantly higher than ambient pressure, adding substance will increase the internal pressure, and when the probe is removed, some substance may be expelled from the stopper along with the probe due to the higher internal pressure. If the internal pressure is significantly lower than ambient pressure, when dispensing some substance into the vial, the lower pressure (vacuum) can draw more substance from the probe than needed, including introducing some hydraulic fluid into the vial and making dispensing more difficult to control.

[0053] In the exemplary pressure balancing process 115 ( Figure 14 In ), the probe's axis 46 ( Figure 10 and Figure 12 ) enters the internal volume of vial 32 (115a). This is inside the vial with pressure sensor 50 ( Figure 3 A fluid path is created along the inner cavity of the shaft between the two vials. A pressure sensor 50, connected to, or part of, the shaft 46, or on the shaft 46, detects (115b) the internal pressure of the vial. The pressure sensor sends data representing the internal pressure to the control system. The control system compares the detected pressure with a target pressure (such as a pressure slightly less than ambient pressure) to determine if the detected pressure deviates from the target pressure by an acceptable amount. For example, unacceptable deviations may include a 2% deviation, a 5% deviation, or more. The target pressure for each vial may be stored in a memory within the control system. Based on this target pressure, the control system may control the operation of the probe to adjust the internal pressure of the vial.

[0054] The control system determines that the internal pressure of the (115C) vial deviates from the target pressure by an unacceptable amount. Therefore, the control system controls probe 44 ( Figure 3 The internal pressure of the vial is adjusted towards the target pressure. As mentioned earlier, the target pressure can be a negative or positive pressure, different from the initial detected internal pressure of the vial. In this regard, assuming the target pressure is slightly less than the ambient pressure and the internal pressure is negative and lower than the target pressure, the control system controls the probe to draw pressure from the outside of the vial. Figure 14 Air (115e) enters its shaft, moves to the position of the vial, punctures the vial's stopper with the probe shaft, and injects (115f) the drawn-out air into the vial, thereby increasing the air pressure inside the vial. The amount of air drawn can be a predefined amount programmed into the control system. Then, a pressure sensor 50 connected to, or being part of, the probe or on the probe reads the new pressure in the vial, i.e., the pressure generated after air was added to the vial. The pressure sensor then sends the data representing the new pressure to the control system.

[0055] Then, the system can repeat operations 115b to 115f. Figure 14 This continues until the target pressure is reached inside the vial, or until a pressure within an acceptable range of the target pressure is reached inside the vial. In this regard, examples of acceptable ranges in some embodiments may include deviations of 1%, 2%, 3%, 4%, 5%, 10%, etc., from the target pressure.

[0056] For vials that have not been used previously (e.g., manufactured and known to be under a predetermined pressure close to a vacuum), air can be repeatedly injected into the vial without the probe leaving the vial. For example, after the first injection of outside air into the vial via the probe, the probe can repeatedly draw air from the vial and inject the drawn air back into the vial without leaving the vial. This repetition can cause the air pressure in the vial to reach equilibrium with the ambient pressure.

[0057] In some examples, the probe can be preprogrammed to draw air and inject it into the vial a predefined number of times, independent of pressure sensor measurements. In one example, the control system identifies a previously unused vial from a known near-vacuum source. Air is injected a predefined number of times, such as 4 to 7 times, to reach equilibrium. In other examples, the probe can draw air and inject it into the vial 20 times; however, other numbers can be used, such as 10, 30, 40, etc.

[0058] Figure 5 Pressure 120 is shown in pounds per square inch, gauge pressure (psig). In this respect, a container initially vacuum-sealed (e.g., without retaining any air (e.g., at an internal pressure close to a vacuum) will be approximately -14.7 psig. 0 psig is used as ambient air pressure. In this example, the pressure 121 inside the vial starts at a level 122 close to vacuum pressure. In this embodiment, air is pumped into the vial 20 times, where each peak 123 represents one air pump. Each individual volume of air injected may be less than the volume of air required to reach equilibrium, where equilibrium is reached after multiple injections. The final pressure 124 in the vial is at or slightly below ambient air pressure, as shown in the figure.

[0059] refer to Figure 14For vials under unknown vacuum pressure, operations 115C to 115F can be repeated based on readings from pressure sensor 50, as described above. Each time air is added to the vial, pressure sensor 50, connected to, or being part of, the probe, or on the probe, reads the new pressure in the vial, i.e., the pressure generated after air was added. The pressure sensor then sends data representing the new pressure to the control system. These operations can be repeated multiple times to achieve the target pressure within the vial. If the pressure unacceptably exceeds the target pressure due to adding too much air to the vial, a certain amount of air can be removed from the vial to maintain the pressure within the vial at the target pressure (e.g., ambient pressure), as described below.

[0060] in this regard, Figure 14 The exemplary process 115 shows the case where the internal pressure of the vial is negative. Figure 15 The exemplary process 117 includes an operation performed by the system when the internal pressure in the vial is positive relative to a target pressure. This operation can be performed on a previously unused vial or a vial to which too much air has been added, causing the internal pressure to exceed the target pressure. More specifically, in vial 32 ( Figure 2 In the case of the target vial, the probe axis is 46 ( Figure 3 First, the internal volume of vial (117a) is entered. A pressure sensor 50, connected to or being a part of shaft 46 or on shaft 46, detects the internal pressure of vial (117B) in the manner described above relative to process 115. The pressure sensor sends data representing the internal pressure to the control system.

[0061] The control system compares the detected pressure with a target pressure (such as a pressure slightly less than ambient pressure) to determine if the detected pressure deviates from the target pressure by an acceptable amount. The control system determines that the internal pressure of the vial (117C) deviates from the target pressure. Therefore, the control system controls the probe to adjust the internal pressure of the vial toward the target pressure. In this example, the internal pressure is positive, and the target pressure is slightly less than ambient pressure. Therefore, the probe draws (117e) a predefined amount of air from the vial, thereby reducing the air pressure inside the vial. The predefined amount can be programmed into the control system based on the substance in the vial and the measurements to be performed using the vial. The pressure sensor 50 then reads (117f) the new pressure in the vial, i.e., the pressure generated after air was drawn from the vial into the probe. The pressure sensor 50 then sends data representing the new pressure to the control system. The probe also leaves the vial and expel (117g) the air drawn from the vial into an area outside the vial.

[0062] The control system may then repeat process 117 or a portion thereof until the target pressure, or a pressure within an acceptable range of the target pressure, is reached inside the vial. Regarding the repetition of the process, the control system determines whether the new internal pressure of the vial deviates from the target pressure (117C). If so, the control system controls the probe to further adjust the new internal pressure of the vial toward the target pressure.

[0063] As described above, assuming the internal pressure is positive and the target pressure is slightly lower than the ambient pressure, the control system controls the probe to fully retract from the vial, expelling the air already drawn from the vial, then piercing the vial stopper again with the shaft, and drawing additional air from the vial. The pressure sensor 50, connected to, part of, or on the probe, then reads the new pressure in the vial—that is, the pressure generated after drawing additional air from the vial. The pressure sensor sends data indicating the new pressure to the control system. These operations can be repeated multiple times to reach the target pressure within the vial. If the pressure is unacceptably lower than the target pressure, possibly due to removing too much air from the vial, then, as described above, a certain amount of air can be added to the vial to maintain the pressure within the vial at the target pressure.

[0064] In some implementations, after the initial pressure measurement, the control system can determine the number of times the probe needs to draw air from the vial to achieve the target pressure. For example, the control system may know the volume that the probe can draw air from, and the amount of air required to draw air from the vial to reach the target pressure. The control system can then control the probe to draw air from the vial a certain number of times to maintain the pressure inside the vial at the target pressure.

[0065] Due to the minute air exchange as the probe enters or exits the vial, some air transfer can self-equilibrium. In an exemplary embodiment, air can be drawn into the probe before it enters the vial. As the probe penetrates the vial, the pressure difference between the probe and the inside of the vial causes air to enter or exit the vial, thus self-equilibrating the internal pressure. For example, if the pressure in the vial is greater than the pressure in the probe, air can be transferred from the vial to the probe, thereby reducing the pressure in the vial. In another example, if the pressure in the vial is less than the pressure in the probe, air can be transferred from the probe to the vial, thereby increasing the pressure in the vial. This can be achieved without actively injecting or removing air. Such techniques are called passive pressure control techniques because they do not require hydraulic operation of the probe to achieve air transfer while the probe is in the vial. These techniques can be used, for example, if too much air is added to or removed from the vial and a small additional pressure change is required. However, passive techniques are not limited to use in this situation.

[0066] The aforementioned operations can be performed to achieve pressure equilibrium between the internal pressure of the vial and the target pressure. Once the target pressure is reached or within an acceptable range, the probe can recover the material and deliver the recovered material back into the vial for addition.

[0067] In some implementations (such as those described below), adding a substance to the vial may also include adding air to the vial. Additionally, air may be extracted from or leak from the vial. This can alter the pressure within the vial – for example, increasing the pressure inside the vial to an unacceptable level. Therefore, the techniques described herein can be used to adjust the pressure inside the vial during substance transfer (e.g., between two consecutive substance transfers). For example, when a substance is discharged into the vial, a pressure sensor connected to, or part of, a probe shaft, or on the probe shaft sends data indicating the pressure inside the vial to a control system. The control system determines whether the internal pressure of the vial deviates from a target pressure by an unacceptable amount. If so, the control system controls the probe to adjust the internal pressure of the vial toward the target pressure. In one example, the internal pressure exceeds the target pressure by an unacceptable amount. Therefore, the control system controls the probe to move to a position within the vial that does not contain the substance to be mixed and draws air from the vial, thereby reducing the air pressure inside the vial. The amount of air drawn may be based on the desired pressure change. Then, a pressure sensor 50, connected to, or part of, the probe or on the probe, reads the new pressure in the vial, i.e., the pressure generated after air is drawn from the vial into the probe. The pressure sensor then sends data indicating the new pressure to the control system. The control system can then repeat the above operation until the target pressure is reached inside the vial, or the pressure inside the vial is within an acceptable range of the target pressure (e.g., a deviation of 1%, 2%, etc.). If the pressure is unacceptably below the target pressure, a certain amount of air can be added to the vial to maintain the pressure inside the vial at the target pressure, as described above. For example, as described above, the control system controls the probe to retract from the vial, drawing air into its shaft, piercing the stopper of the vial again, and expelling (i.e., injecting) the drawn air into the vial. The pressure sensor 50, connected to, or part of, the probe or on the probe, reads the new pressure in the vial, i.e., the pressure generated after air is added to the vial. The pressure sensor then sends data indicating the new pressure to the control system, which can further adjust the pressure if necessary. Therefore, pressure control and / or balancing can be performed between and / or during the transfer of substances to vials, as described above.

[0068] When a substance, such as a liquid (e.g., a reagent), is drawn from the vial, the pressure inside the vial decreases. One effect of this pressure change is the expansion of any air gaps in the probe, for example, as described below regarding... Figure 7 and Figure 8In the probe shaft, when these air gaps expand, the total volume of material that can be drawn into the probe decreases. To address this issue, particularly in the case of liquid aspiration, the control system can track the volume of material aspirated into the probe and predict the expansion of the air gaps in the probe using gas expansion calculations (such as the ideal gas law). The volume of material in the probe can be tracked by maintaining a record of the volume of material (including both material and air) aspirated into the probe. Based on the predicted air expansion, the control system can perform corrections to account for the predicted air expansion. For example, after the probe has been emptied of its discharged material, the control system can control the probe to aspirate additional material, such as a liquid reagent, from the vial to ensure that the appropriate amount of material has been transferred and that the pressure in the vial is maintained at the target pressure. If necessary, pressure balancing can be performed after the material transfer.

[0069] Return to reference Figure 3 In one example, probe 44 includes a hydraulic connection, which may be or includes a tube 51 (also referred to as a "line") for holding hydraulic fluid. An example of hydraulic fluid is DI water; however, other types of fluids, such as ACL TOP flushing solution, may be used as hydraulic fluid. Tube 51 is in fluid communication with the cavity 47 of shaft 46. This fluid connection allows air to flow between the shaft and the tube; that is, from the tube into the shaft and from the shaft into the tube. The latter flow can occur when air or material is drawn into the probe, and the former flow occurs when air or material is discharged from the probe. That is, the airflow from the shaft to the tube creates a suction force capable of drawing. The airflow from the tube to the shaft creates pressurized air in the shaft capable of discharge. Therefore, the hydraulic fluid can be controlled by a control system to flow in a direction toward the shaft to create a positive pressure in the shaft of the probe to discharge air or material from the shaft of the probe. The hydraulic fluid can also be controlled by a control system to flow in a direction away from the shaft of the probe to create a negative pressure in the shaft of the probe to draw air or material into the shaft of the probe.

[0070] In some embodiments, the housing 45 and shaft 46 are made of metal, such as a stainless steel alloy or any material that produces properties similar to or better than stainless steel alloys, and the tube 51 is made of plastic, rubber, or any other flexible material that produces properties similar to or better than plastic or rubber. Due to the difference in flexibility between the housing / shaft portion of the tube and the probe, the interface between the housing / shaft portion of the tube and the probe may not be airtight / fluid-tight. Due to this imperfect seal at the interface, hydraulic fluid can leak from tube 51 into shaft 46, thereby contaminating (e.g., diluting) the material drawn into the shaft, as previously described. To address this potential contamination, the probe can be controlled by a control system to create multiple segments, such as air and liquid material segments, between the hydraulic fluid and the material to be pumped by the probe. For example, the probe can be controlled by a control system to create an air gap in the shaft between the hydraulic fluid and the material and to create multiple downstream material layers in the shaft, wherein each material layer is separated from the adjacent material layer by the air gap. As described below, there can be a range of three to five air and material segments, or more if desired. However, the system is not limited to any specific amount of air and matter pairs.

[0071] Figure 6 The diagram illustrates the result of a control system that controls a probe to draw air 61 into shaft 62 and then draws the substance 64 to be discharged into the shaft. The air 61 drawn before the substance 64 creates an air gap between the substance 64 and the hydraulic fluid 65 (DI water) in pipe 67. This air gap creates pressure in the shaft, which reduces hydraulic fluid leakage into the substance 64. The control system also controls the probe to draw air 69 into shaft 62 after drawing the substance 64. This creates a second air gap, which reduces the chance of unintentional leakage of the substance 64 from the probe. Although leakage is reduced, Figure 6 The configuration produces sufficient hydraulic fluid leakage to significantly contaminate the substance to be drained 64. Therefore, as Figure 7 and 8 The area shown has been expanded with additional sections to address this issue.

[0072] Figure 7 The results of an exemplary technique are shown, wherein a control system controls a probe to aspirate a section 71 comprising both substance and air, located upstream of the substance 72 to be ejected from shaft 73. In this example, the substance 72 to be ejected by the probe corresponds to... Figure 6 Substance 64. In some examples, the volume of substance transferred is always the same for a particular transfer, regardless of how many segments are used. That is, in some examples, the volume of substance in a segment does not change the volume of the substance to be transferred, which is the volume required for preparation.

[0073] However, Figure 7 The air gap in the middle can have the same characteristics as Figure 6 The air gaps in the middle have the same or smaller volume. Figure 7 In the example, before aspirating the substance 72 to be discharged, the control system controls the probe to aspirate a first volume of air 76 from the outside of the vial to create an air gap, then a first volume of substance 77 is aspirated from the inside of the vial, and then a second volume of air 78 is aspirated from the outside of the vial. The resulting section 71 of air 76 and substance 77 separates the substance 72 to be discharged from the hydraulic fluid 79 (e.g., DI water) in the tube 80. As previously described, the air pressure provided by air 76 reduces leakage of the hydraulic fluid 79. However, if the hydraulic fluid leaks into the shaft, then all or some of the hydraulic fluid can be absorbed by the substance 77 in section 71. Therefore, compared with... Figure 6 Compared to the previous configuration, no or very little hydraulic fluid will come into contact with the substance 72 to be pumped. As previously described, the pressure generated by air 78 reduces the likelihood and / or amount of fluid leakage into the substance 72. Therefore, the substance 72 will not be contaminated, or will have less contamination, compared to the absence of section 71 in the shaft. The control system also controls the probe to draw air 72a into the shaft after drawing in the substance 72. This creates an air gap, which reduces the chance of the substance 72 unintentionally leaking from the probe.

[0074] Figure 8 Showing the extension relative to Figure 7 The described example demonstrates the results of exemplary techniques. More specifically, Figure 8 The results of an exemplary technique are shown, wherein the control system controls the probe to aspirate two segments 56 and 57 upstream of the substance 53 to be expelled by the probe, each segment consisting of substance and air. In this example, the substance and air 82 to be expelled by the probe corresponds to... Figure 7 The substance and air 74. The air gap can have the same properties as... Figure 7 The volume corresponding to the air gap is the same, or it may have a smaller volume. In this example, before aspirating the substance 53 to be dispensed, the control system controls the probe to aspirate a first volume of air 83 from the outside of the vial to create an air gap, and then aspirates a first volume of substance 84 from the inside of the vial. Then the control system controls the probe to aspirate a second volume of air 86 from the outside of the vial to create an air gap, and then aspirates a second volume of substance 88 from the inside of the vial. The control system then controls the probe to aspirate a third volume of air 89 from the outside of the vial.

[0075] Sections 56 and 57 separate the substance 53 to be drained from the hydraulic fluid 90 (DI water) in pipe 91. As previously described, the air pressure provided by each air gap reduces leakage of hydraulic fluid through and beyond the air gap. However, if hydraulic fluid leaks into the shaft, all or some of the hydraulic fluid can be absorbed by substances 84 and 88. Therefore, no or less hydraulic fluid will reach the substance 53 to be drained. More specifically, hydraulic fluid leaking through air 83 will be absorbed by substance 84. Hydraulic fluid leaking through both substance 84 and air 86 will be absorbed by substance 88. As previously described, the pressure generated by air 89 reduces the likelihood and / or amount of fluid leaking into substance 53. Therefore, substance 53 will not be contaminated, or will have less contamination, compared to sections 56 and 57 not being present in the shaft.

[0076] exist Figure 7 and 8 In some implementations, for example, by using material layers separated by segments of air gaps or material-gas gaps, the probe can reduce the amount of hydraulic fluid discharged into the vial to a negligible level. That is, while some hydraulic fluid may leak into material layers closer to the interface even in the presence of air gaps, by separating the hydraulic fluid from the rest of the probe, most or all of the hydraulic fluid will be absorbed by the material layer closest to the interface before it reaches one or more material layers to be discharged into the vial (or absorber).

[0077] In some implementations, there may be more than two air and material sections 56 and 57 upstream of the substance to be discharged 53 on the shaft. For example, there may be three air and material sections (three sections) upstream of the substance to be discharged on the shaft. For example, there may be four air and material sections (four sections) upstream of the substance to be discharged on the shaft. For example, there may be five air and material sections (five sections) upstream of the substance to be discharged on the shaft. For example, there may be six air and material sections (six sections) upstream of the substance to be discharged on the shaft. The number of sections created may be predefined by the control system and may be based on, for example, a measurement to be performed. In some examples, the more sections upstream of the substance to be discharged, the less likely the contents to be discharged will be contaminated by the hydraulic fluid.

[0078] refer to Figure 16 Exemplary processes and Figure 7For example, to generate segment 71, the control system controls the probe to draw (125) air 76 from the outside of the vial containing the substance to be discharged. The control system can control the probe to enter (126) the vial containing the substance and draw (127) the substance from the vial. The control system can control the probe to draw (128) air 78 from the inside or outside of the vial based on considerations such as the pressure inside the vial as described herein. For example, if the pressure in the vial exceeds a target pressure, then air 78 can be drawn from the inside of the vial. If the pressure in the vial is at the target pressure, then the probe can be removed from the vial and air 78 can be drawn from the outside of the vial. The probe can re-enter the vial to draw (129) substance 72. Thereafter, air 72a can be drawn (130) from the inside or outside of the vial, as described above. The amount drawn can be controlled by the control system, for example, based on predefined parameters or an ongoing measurement. These operations can be repeated as necessary based on the number of segments to be formed within the probe, the number of segments to be formed can be based on factors such as the measurement to be performed or the substance used in the measurement.

[0079] A positive pressure is determined and controlled in the probe to vent one or more layers of material (e.g., material 72 or 53) from the shaft, the layers being furthest from the interface between the hydraulic fluid and the rest of the probe. These layers may be free of, or contain reduced or minimal contamination from the hydraulic fluid. The control system determines the positive pressure applied to the probe based on, for example, predefined parameters stored in memory, the measurements being performed, the material being aspirated, and any other information required for accurate and effective pressure adjustment and balancing. In some embodiments, the amount of material to be vented may be based on the shaft size and the number of air and material sections preceding the material to be vented. In some embodiments, the volume of the material to be aspirated is five or tens of microliters, for example, 5 μL, 10 μL, 15 μL, 20 μL, 25 μL, 30 μL, 35 μL, 40 μL, 45 μL, 50 μL, etc. This amount may be greater than the amount of material used in the sections. Figure 7 and 8 In one exemplary embodiment, the shaft can aspirate a total of 1,100 microliters (μL) of contents, including air gaps, material, and segments; however, in other embodiments, the amount of contents aspirated may vary in part depending on the size of the probe.

[0080] In some embodiments, each air gap contains approximately a few microliters (μL) of air, such as 1 μL, 5 μL, 10 μL, 15 μL, 20 μL, 25 μL, 30 μL, 35 μL, 40 μL, 45 μL, 50 μL, etc. Air gaps with volumes different from these can also be used. In some embodiments, the substance in each segment can be 10 μL, 20 μL, or other amounts, such as 5 μL, 15 μL, 25 μL, 30 μL, 35 μL, 40 μL, 45 μL, 50 μL, etc. In some examples, each segment has the same volume of substance, regardless of the number of segments used. In some embodiments, the more segments used, the smaller the amount of substance in each volume.

[0081] The material included in the segments (such as segments 56 and 57) is the same material that will be ejected by the probe. The control system calibrates the positive pressure in the shaft based on the size and / or number of segments to ensure that segments are not ejected with the material, or to reduce the chance of segments being ejected with the material. For calibration, the pressure is measured by a pressure sensor and balanced based on the difference relative to ambient pressure. The volume to be ejected is specified by a command in the preparation software, which determines how much (in μL) to eject. This information is based on previous experiments.

[0082] In some examples, the same probe used to aspirate and discharge substances from vials (e.g., for substance delivery) can also be used to mix two or more substances. For example, two or more substances can be mixed in the container where the substances are discharged (e.g., a vial or cup) or in another container before being transferred to a vial. Mixing two or more substances can be performed to perform an assay. For example, each vial may hold a substance that can be used to determine the sample. However, to perform an assay, it may be necessary to mix two or more substances beforehand. In some embodiments, this mixing may need to have sufficient duration and be performed with sufficient force to produce a completely or at least partially homogeneous mixture of the two substances (e.g., the mixing can be performed in such a way that the analytical performance of these homogeneous substances is equivalent to that of a standard assay, as evaluated experimentally). Homogenization involves combining two substances such that they are both uniformly or consistently distributed in the resulting mixture.

[0083] In one example, the mixture may be in a vial and may be based on one or both of, for example, a diluent (e.g., a liquid) and a liquid substance or a dry substance (e.g., a reagent), and may be at least partially homogeneous. For example, the duration and force applied to produce the mixture may be based on the substances in the vial and the total combined volume of the substances. The mixing process is controlled by a control system using a computer program specific to the substances to be mixed and the determinations performed using the substances. The volume and flow rate of the air to be aspirated, the depth of the probe for displacing air from the liquid, and the number of times this process occurs are controlled by the control system.

[0084] In one example, reference Figure 9 The control system can control probe 44 to move the diluent from a first vial 95 to a second vial 96 containing a liquid substance and / or to a third vial 97 containing a lyophilized (dry / solid) substance. While liquid diluent and dry substance are used in these examples, the probe can be used to mix any two or more substances. The probe for moving substances can also be used to mix substances. Reference Figure 10 and 11 In order to mix the liquid substance and other substances according to process 102, the control system can control the probe to move (102d) into the vial so that the probe is no longer in the substance to be mixed, so as to draw air (102E) from the vial into the axis of the probe; and to draw air 103 in the direction of arrow 104 with sufficient force. Figure 10 An airflow is pumped from shaft 46 (102F) into the vial to generate an airflow rate sufficient to mix the two substances to a level deemed adequate, for example, such that the analytical performance of these homogenized substances is equivalent to standard determinations, as experimentally evaluated. Parameters related to air volume and flow rate are obtained from previous experiments and can be used as information for software commands used in the mixing / homogenization procedure. This mixing is performed by air turbulence within the vial caused by the airflow.

[0085] In some embodiments, the shaft may be higher than the substance to be mixed during air purging. In some embodiments, the shaft may be immersed in the substance to be mixed during air purging. For example, the tip of the shaft may be at or near the bottom of the vial to purge air into the vial. For example, the tip of the shaft may be in the middle of the substance to be mixed during air purging.

[0086] After all air is expelled from the probe, additional mixing may be required. The mixing procedure for each substance can be programmed into software executed by a control system, for example, based on previous experiments showing how many mixing cycles are needed for each specific substance or combination of substances. Mixing protocols can be specifically developed and fixed for each particular material / assay and programmed into its specific preparation procedure software, which can be executed by the control system.

[0087] In other mixing cases, the process of mixing 10²d to 10²g can be repeated as needed to achieve the desired mixture, resulting in a homogeneous mixture with analytical performance equivalent to standard determinations, as assessed experimentally. In some examples, based on previous experiments, the mixing process can be repeated an arbitrary number of times as required.

[0088] In some embodiments, air for mixing can be drawn from outside the vial and introduced into the vial and used to perform mixing as described above. For example, the control system can control the probe to move out of the vial (e.g., retract from the vial), drawing air from outside the vial into the probe's shaft; causing the shaft to re-enter the vial containing both substances, and expelling air from the shaft into the vial. These operations can be repeated if necessary. Pressure equalization can be performed if necessary.

[0089] Using air can be advantageous, at least because the forces for mixing / homogenizing substances can be stronger than those for using liquids. For example, a larger volume of air can be used than a liquid, and air can be used at a higher flow rate than a liquid.

[0090] Mixing with air may produce bubbles. In some cases, if the mixture does not contain chemicals that stabilize the bubbles, the bubbles will quickly burst on their own. If bubbles do not burst on their own within a predetermined time period (such as 60 seconds or 30 seconds), then the bubbles are considered stable. In such cases, air may not be the best way to mix these substances.

[0091] Whether to use mixing / homogenization that causes bubbles in a substance can be controlled by a mixing program specifically written for each substance and included in the software executed by the control system for the determination of that substance. The volume and flow rate of the air to be aspirated, the depth of the probe for displacing air in the liquid, its flow rate and volume, and the number of times this process occurs can also be specified in the software.

[0092] In embodiments where air is determined not to be the optimal mixing method, the substance can be mixed by aspirating the mixture from the container into the probe and then reintroducing the aspirated mixture into the container. (Reference) Figure 12 and 13 Prior to the exemplary mixing process 105, probe 44 can be controlled to draw diluent or another substance 100 into its shaft, causing the shaft to enter the interior of vial 96 containing reagent 101, and discharging diluent or another substance 100 into the vial. To mix the substances according to process 105, the control system can control shaft 46 to move (105d) into the mixture of substances in the vial, such that at least the tip 48 of the probe (… Figure 3The probe is immersed in the substance. The probe can be controlled to aspirate (105e) the substance (e.g., a combination of substances contained in the vial) from the vial into the probe shaft, and to reintroduce / discharge (105f) the substance from the probe into the vial to mix the substances (in this embodiment, diluent and reagent). These operations are indicated by arrow 107. Figure 12 Example from [example description]. In this exemplary mixing process, the probe does not need to be removed from the vial or withdrawn from the vial for mixing to be performed. Therefore, while at least a portion of the probe's axis remains within the vial, the control system controls the probe to expel the contents from the axis into the vial at a certain rate to mix the two substances to a level obtained through previous experiments, such that the analytical performance of the homogenized substance is equivalent to that of a standard assay, as evaluated experimentally. Exemplary mixing procedures (using either air or liquid) have previously been studied and established to produce mixed substances with analytical results comparable to each specific assay. The type of mixing procedure specific to each substance / assay is written into the specific preparation procedure software for each substance / assay executed by the control system.

[0093] Mixing / homogenization is achieved through turbulence in the vial caused by the reintroduction of contents into the mixture. Operations 105e and 105f can be repeated multiple times to achieve a level of mixing such that the analytical performance of the homogenized substance is equivalent to that of standard determinations, as experimentally evaluated. The number of repetitions, including the required number, is programmable into the control system and is at least in part based on the contents and physical properties of the substance (such as whether the substance is liquid or solid, its viscosity, etc.) and has been experimentally evaluated in previous studies. The duration of mixing can be programmed by substance-specific program software executed by the control system.

[0094] According to the above technology, substances can be drawn from the vial into the shaft from any position (horizontal height) within the vial. For example, see reference. Figure 12 Contents can be aspirated from the surface layer 110, the intermediate layer 111, or from the layer located at or near the bottom 112 of the vial 96, as shown in the figure, and can be dispensed into different layers as evaluated in previous studies. By aspirating material from or near the bottom 112 of the vial, the probe may be better able to capture sediments or other material components that have separated and settled to the bottom of the vial. As previously described, such material components can be aspirated into the shaft and reintroduced into the vial.

[0095] One or two of the aforementioned mixing techniques can be used to periodically remix the contents of vials. For example, the mixed components in the vial may separate and settle over time. The probe can be controlled, for example, based on a schedule set by a control system, to repeat the mixing operation as needed to counteract sedimentation. The repetition frequency can be programmed into software executed by the control system for each specific substance / analysis.

[0096] As previously described, probes can be used to draw air from a vial (or other container) and / or expel / inject air into a vial (or other container) to adjust the internal pressure of the vial toward a target pressure, for example, to drive the internal pressure or move the internal pressure closer to the target pressure. In this regard, during mixing, the internal pressure in some vials may increase above the target pressure. Therefore, probe 44 or another probe can be controlled by a control system to change the pressure in the vial (or other container) containing the mixture in the manner described herein.

[0097] The control system described herein can be implemented using a computing system or any other computing device. The control system can be implemented at least in part using one or more computer program products, such as one or more computer programs tangibly embodied in one or more information carriers, such as one or more non-transitory machine-readable media, for execution or control of its operation by one or more data processing devices (e.g., programmable processors, computers, multiple computers, and / or programmable logic components).

[0098] Computer programs can be written in any programming language, including compiled or interpreted languages, and can be deployed in any form, including as standalone programs or as subroutines of module components or other units suitable for use in a computing environment. Computer programs can be deployed to execute on one or more computers located at a single site or distributed across multiple sites and interconnected via a network.

[0099] Actions associated with implementing all or part of a control system can be performed by one or more programmable processors executing one or more computer programs to perform the functions described herein. All or part of the control system can be implemented using dedicated logic circuitry (e.g., FPGAs (Field-Programmable Gate Arrays) and / or ASICs (Application-Specific Integrated Circuits)).

[0100] Processors suitable for executing computer programs include, for example, general-purpose and special-purpose microprocessors, and any one or more processors of any kind of digital computer. Typically, a processor receives instructions and data from read-only memory or random access memory, or both. Computer components (including servers) include one or more processors for executing instructions and one or more storage area devices for storing instructions and data. Typically, a computer will also include, or be operatively coupled to, receiving data from or transferring data to one or more machine-readable storage media, or both, such as large-scale storage devices for storing data, such as magnetic, magneto-optical, or optical discs. Machine-readable storage media suitable for implementing computer program instructions and data include all forms of non-volatile storage areas, including, for example, semiconductor storage area devices, such as EPROM, EEPROM, and flash memory storage area devices; magnetic disks, such as internal hard disks or removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

[0101] Elements from the different embodiments described herein can be combined to form other embodiments not specifically elaborated above. Elements can be excluded from the structures described herein without adversely affecting their operation. Furthermore, various separate elements can be combined into one or more individual elements to perform the functions described herein.

Claims

1. A non-transitory machine-readable medium storing instructions executable by one or more processing means to perform operations, the operations including: Control the probe to draw air into the shaft of the probe; as well as The probe is controlled to expel air from the shaft into the container to at least mix the first and second substances; The executable instructions are specific to the substances to be mixed, which include the first substance and the second substance, and the executable instructions are specific to a determination performed using the first substance and the second substance; and The operation includes controlling the probe to draw the second substance into the shaft before drawing in the air, so that the shaft enters the container containing the first substance, and discharging the second substance into the container.

2. The non-transitory machine-readable medium according to claim 1, wherein, The container includes a vial, the first substance comprises a reagent in liquid or dry / lyophilized form, and the second substance comprises a diluent; and The air is injected from the shaft into the vial to produce a mixture based on the diluent and the reagent and is homogenized.

3. The non-transitory machine-readable medium according to claim 1, wherein, In addition to the first and second substances, the container also holds one or more other substances; and The one or more additional substances are mixed with the first substance and the second substance.

4. The non-transitory machine-readable medium of claim 1, wherein (i) the air is drawn from inside the container by a probe or (ii) the air is drawn from outside the container by a probe and the shaft is controlled to enter the container to purge the air.

5. The non-transitory machine-readable medium according to claim 1, wherein, The air injected into the container homogenizes the mixture comprising the first and second substances.

6. A system for preparing a substance, comprising: The non-transitory machine-readable medium according to claim 1; and The probe includes: A shaft for holding the substance, the substance comprising a first substance or a second substance; and Hydraulic lines, including hydraulic fluid, to generate negative or positive pressure in the shaft, respectively, to draw in or discharge the substance; and The probe is configured to draw in air before drawing in the substance, thereby creating an air gap in the shaft between the hydraulic fluid and the substance. After the air is drawn in, the probe is configured to alternately draw in material and air, thereby creating at least one additional air gap between the sections of material contained in the shaft, in addition to the air gap between the hydraulic fluid and the material.

7. The system according to claim 6, wherein, The at least one additional air gap between the segments of the material comprises at least two air gaps, each of the at least two air gaps being between the segments of the two materials.

8. The system according to claim 7, wherein, There are at least three to five air gaps in the shaft.

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