Systems and methods for probe tip heating

Abstract

Systems and methods for probe tip heating are disclosed. An exemplary system for probe tip heating can include a housing including a probe tip, a heating device, and a fan. The probe tip can be configured to enter an interior volume of a stopper container and to aspirate material from or dispense material to the interior volume of the stopper container. The heating device can be configured to heat air circulating within the housing. The fan can be positioned to circulate air within the housing to heat the tip of the probe.

Description

[0001] This application is a divisional application of the Chinese patent application filed on September 2, 2022, with application number 202211072221.0 and title "System and Method for Heating Probe Tip". Attached Figure Description

[0002] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate the disclosed embodiments and, together with the specification, serve to explain the disclosed embodiments. In the drawings:

[0003] Figure 1A A side view of an exemplary system for heating a probe tip according to a disclosed embodiment is depicted, with the probe tip in a retracted position.

[0004] Figure 1B A side view of an exemplary system according to a disclosed embodiment is depicted, wherein the probe is in the assignment position.

[0005] Figure 2 A cross-sectional view of an example housing and an example storage container according to the disclosed embodiments is depicted, wherein the probe is omitted and an example airflow circuit is shown.

[0006] Figure 3A A cross-sectional view of an example housing viewed from inside an example fan, according to a disclosed embodiment, is depicted, the cross-section being cut through a low-voltage storage unit.

[0007] Figure 3B A cross-sectional view of an example housing viewed from inside an example fan, according to a disclosed embodiment, is depicted, the cross-section being taken through a high-voltage storage unit.

[0008] Figure 4 Experimental data are depicted, showing the temperature of several example storage containers as a function of time.

[0009] Figure 5 This is an exemplary method for aspirating and dispensing materials according to the disclosed embodiments. Detailed Implementation

[0010] Exemplary embodiments are described with reference to the accompanying drawings. While examples and features of the disclosed principles are described herein, modifications, adaptations, and other implementations are possible without departing from the spirit and scope of the disclosed embodiments. The exemplary embodiments described herein may be independent of each other. Furthermore, the words “comprising,” “having,” “including,” and “containing,” and other similar forms are intended to be equivalent in meaning and are open-ended, as one or more items following any of these words are not intended to be an exhaustive list of those items or to be limited to the listed items. It should also be noted that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly indicates otherwise. For convenience, the terms “disclosed embodiment” or “exemplary embodiment” may be used herein to refer to one or more embodiments of this disclosure.

[0011] Chemical, fluid, or biochemical analysis (e.g., analysis) of samples using reagents can be performed in a test container (e.g., well, test tube, vial, etc.) separate from the reagent storage container (e.g., vial, bottle, test tube, etc.). The test container can be the same as or separate from the preparation container (e.g., test tube, vial, test tube, etc.) used to prepare the test. For example, reagents can be mixed in the preparation container. An automated testing machine or material preparation machine (which can be the same as or separate from the testing machine) can be configured to transfer an appropriate amount of reagent from the storage container to the test container or preparation container. The reagent can be a fluid. The automated testing machine or material preparation machine can include a probe with a probe tip. The probe tip can extend into the storage container to aspirate the reagent and then dispense the reagent into the test container or preparation container. For simplicity, the term "machine" is used for the testing or material preparation machine, and "target container" is used for the test container or preparation container.

[0012] The analysis can be performed at a temperature higher than the reagent storage temperature. For example, the specified temperature for the analysis might be 37°C, while the reagents can be stored between 4 and 20°C, such as 4 to 15°C or 4 to 8°C. Therefore, the reagents must be heated before being dispensed into the target container. In some cases, the analytical requirements may specify dispensing the reagents at a temperature higher than the reagent storage temperature.

[0013] Conventional machines may use heating elements positioned along or above the probe tip (e.g., resistance heating elements attached to the probe tip), or indirectly heat the probe tip (e.g., using a heating cylinder that contacts the probe, thus indirectly heating the probe tip). In some embodiments, such heating elements may be positioned along or above the probe tip. This conventional approach may be suitable for probes configured to enter unsealed reagent storage containers. Such probes may not need to penetrate the sealing plug of the storage container and may have relatively short probe tips (e.g., 6 mm to 8 mm).

[0014] While unsealed reagent storage containers are compatible with conventional methods involving probe tip heating, they expose stored reagents to the surrounding environment, thus shortening the lifetime of exposed reagents. Storing reagents in sealed containers extends their lifetime, improves analytical reliability, and reduces reagent waste. To extend reagent lifetime, reagent storage containers can be sealed with stoppers designed to be repeatedly pierced by probe tips. The instrument can use probe tips designed to penetrate resealable stoppers to aspirate reagents (e.g., penetrating probe tips).

[0015] Penetration probe tips may be incompatible with conventional methods of probe tip heating. Forcing the heating element through the resealable plug can damage either the heating element or the resealable plug. Therefore, the heating element cannot be positioned around or along the portion of the probe tip that penetrates the resealable plug. Consequently, this portion of the probe tip may be more difficult to heat directly than a conventional probe tip. Furthermore, the dimensions of a penetration probe tip can differ from those of a conventional probe tip. A penetration probe tip can be longer than a conventional probe tip because it may need to reach the bottom of the sealed storage container while the rest of the probe remains outside the resealable plug. For example, a conventional probe tip can be 5 to 15 mm long, while a penetration probe tip can be 60 to 80 mm long. A penetration probe tip can be thinner than a conventional probe tip to reduce damage to the resealable plug from repeated penetration. Because a penetration probe tip can be longer or thinner than a conventional probe tip, it may be more thermally insulated. Because a penetration probe tip is more thermally insulated, indirect heating with a penetration probe tip may be more difficult than with a conventional probe tip.

[0016] Without effective direct or indirect heating of the probe tip, material may not be dispensed by the probe at the specified analytical temperature. Material drawn into an unheated probe tip may not be heated to the specified temperature. Furthermore, drawing in cold material will cool the unheated probe tip. Dispensing material through a cooled probe tip can cool the dispensed material. Therefore, even when the material is heated to the specified temperature within the probe, drawing in and dispensing material through an unheated probe tip can result in the material being dispensed below the specified temperature.

[0017] The disclosed systems and methods improve upon conventional designs by controlling the temperature of the penetration probe tip using convection or conduction heating. This heating can be achieved by adjusting the temperature or flow rate of the air circulating around the probe tip to maintain the probe tip temperature at a desired value or within a desired range. This air can circulate within a housing to reduce the impact of the hot circulating air on the low-temperature surrounding environment of the stored reagent.

[0018] Machines using this improved temperature control mechanism can perform analysis with reagents at a precise desired temperature while storing the reagents in a sealed container at a lower temperature. This system enables reliable analysis while also extending reagent life and reducing waste. Furthermore, the probe tip can be heated instead of the target container, thereby accelerating analytical performance (e.g., by simultaneously transferring and heating the material) and potentially simplifying the machine (e.g., by reducing or eliminating the need for components that heat the target container).

[0019] Although reagents are described for convenience, samples (e.g., blood samples) can also be aspirated and dispensed into target containers by a machine. Such samples can be aspirated from a sample storage container (which may or may not be resealable) and dispensed into the target container using a penetrating probe or another probe suitable for aspirating and dispensing the sample. Such samples can be fluids. In some embodiments, heating can be used to control the temperature of the probe used for aspirating and dispensing the sample. By controlling the temperature of the probe, this heating can control the temperature of the sample. The temperature of the sample can be the same as or different from the temperature used when dispensing the reagents. It is understood that the analysis may include a variety of reagents that can be aspirated and dispensed using the same or different probes, and the desired temperatures for the different reagents may be the same or different.

[0020] Now turn to the attached image. Figure 1A An exemplary side view of an exemplary system 100 for heating a probe tip according to a disclosed embodiment is depicted, with the probe tip in a retracted position. The exemplary system 100 includes a housing 101 and a probe 103. The housing 101 can be manufactured using any suitable material, such as metal, plastic, etc. The exemplary system 100 may be part of a larger automated testing system.

[0021] Probe 103 may include a probe reservoir 105 and a probe tip 107. The probe tip 107 may enter the internal volume of the reservoir to aspirate material (e.g., reagents or samples) contained within the reservoir. In some embodiments, the probe tip 107 may have an inner cavity in fluid communication with the probe reservoir 105. Through the inner cavity, the aspirated material may be stored in the probe reservoir 105 for transfer. The material in the probe tip 107 or the probe reservoir 105 may be heated. In some embodiments, the probe reservoir 105 may be heated (e.g., by contact with the probe 103 or by a resistance heating element or other suitable heating element disposed therein using conductive heating). In some embodiments, the probe may be made of a corrosion-resistant material, such as stainless steel, cobalt-nickel steel, or another suitable corrosion-resistant material. In some embodiments, the probe reservoir 105 may have a diameter of 0.5 to 2.0 mm. 2 The cross-sectional area (e.g., 1.15 mm) 2Or another suitable cross-sectional area), a length of 60 to 240 mm (e.g., 120 mm or another suitable length), and an internal volume (e.g., capacity) of 70 to 280 µL (e.g., 140 µL or another suitable volume). Although Figure 1A The probe reservoir 105 is depicted with a circular cross-section and is coaxial with the inner sleeve space and the probe tip 107, but the disclosed embodiments are not limited thereto. In some embodiments, the probe reservoir 105 may have other cross-sectional shapes. The probe reservoir 105 may be attached to the proximal end of the probe tip 107. In some embodiments, the probe tip 107 and the probe reservoir 105 may be formed as a single component. In various embodiments, the probe tip 107 and the probe reservoir 105 may be formed as separate components and then connected. The disclosed embodiments are not limited to any particular method of forming or connecting the probe tip 107 and the probe reservoir 105. The probe tip 107 may have a diameter of 0.15 to 0.6 mm. 2 The cross-sectional area (e.g., 0.3 mm) 2 (or another suitable cross-sectional area), length of 35 to 140 mm (e.g., 76 mm or another suitable length), and internal volume (e.g., capacity) of 10 to 40 µL (e.g., 22 µL or another suitable volume).

[0022] In some embodiments, the probe tip can be heated inside the housing 101. A portion of the housing 101 can form a first reservoir 111 and a second reservoir 113. The first reservoir 111 and the second reservoir 113 can be separated by a fan 114 and a heating element 115. Figure 1A As shown, fan 114 can be an axial fan (although other types of fans can be used) and can have a diameter of 15 to 80 mm (e.g., 38 mm or another suitable diameter). Fan 114 can be configured to generate a static pressure of 1000 to 4000 Pa (e.g., 1700 Pa or another suitable static pressure). It is understood that the disclosed embodiments are not limited to fans having this specification. Fan 114 can be configured to circulate air between two reservoirs, for example from the first reservoir 111 to the second reservoir 113 and vice versa, or in one or more airflow loops. In some embodiments, fan 114 can be configured to maintain the second reservoir 113 at a higher static pressure than the first reservoir 111. The mechanical rotation of the fan can be converted into air velocity, which can be converted into a static pressure difference across the fan. Therefore, air can flow from the second reservoir 113 through two flow loops in housing 101 (e.g., referenced below). Figure 2 (The described heating and detection circuit) and returns to the first storage 111. The magnitude of the pressure difference depends on the resistance of the two flow circuits. The heating device 115 can be configured to heat the air flowing along or through the heating device 115. Figure 1AAs shown, the heating device 115 may be or include a heat sink. Such a heat sink may have dimensions of 38mm × 10mm × 57mm, although the disclosed embodiments are not limited to heating devices with this size. In some embodiments, the heating device 115 may also include a heater thermally connected to the heat sink. The heater may be a flat, flexible heater (e.g., silicone rubber, KAPTON, or think film heater) or a cylindrical heater. In some embodiments, the heater may be a resistive electric heater. In some embodiments, the heater may be a DC heater having a heat output controllable by pulse width modulation based on one or more thermal sensors disposed on or within the housing 101 (e.g., on the heat sink). The disclosed embodiments are not limited to any particular type of heating device.

[0023] The outer sleeve 117 and the inner sleeve 118 can be formed in part of the outer casing 101. Although Figure 1A An outer sleeve 117 and an inner sleeve 118, both having circular cross-sections and coaxial with each other and with the probe tip 107, are depicted, but the disclosed embodiments are not limited thereto. The outer sleeve 117 may be coaxial with the inner sleeve 118, or they may not be coaxial. The outer sleeve 117 may have a circular cross-section or may have another cross-sectional shape. The inner sleeve 118 may enclose the pressurization chamber (see below). Figure 2 The outer sleeve 117 allows heated air to circulate around the probe, thereby transferring heat to the probe. The outer sleeve 117 provides a path for air to return to the heater and fan after passing through the inner sleeve 118. The probe 103 can be disposed within the pressurization chamber, which can be shaped such that the probe 103 can translate vertically within the pressurization chamber. In some embodiments, the internal dimensions of the inner sleeve 118 can conform to at least a portion of the probe 103, preventing or reducing airflow through the top of the pressurization chamber out of the housing 101. In some embodiments, the inner sleeve 118 and the outer sleeve 117 can form an annular space with an opening as described herein. The inner sleeve 118 can enclose (and optionally support) the probe 103, while the outer sleeve 117 can isolate the path of circulating air from the surrounding environment. It is understood that the sleeve dimensions can be selected to accommodate probes 103 of different sizes. In this exemplary embodiment, the length of the outer sleeve 117 can be between 150 and 300 mm, or between 200 and 250 mm, and the diameter can be between 20 and 35 mm, or between 25 and 32 mm; the length of the inner sleeve 118 can be between 100 and 200 mm, or between 140 and 160 mm, and the diameter can be between 10 and 25 mm, or between 15 and 20 mm. Although Figure 1A The pressurization chamber is depicted as having a circular cross-section and being coaxial with probe 103, but the disclosed embodiments are not limited thereto. In some embodiments, the pressurization chamber may have another cross-sectional shape.

[0024] Throttling device 116 may be located below the heating element. Throttling device 116 may be configured to reduce airflow from the second reservoir 113 to the first reservoir 111 via heating device 115. In some embodiments, throttle device 116 may be formed as including louvers, baffles, valves, or other adjustable grilles that restrict airflow. Throttling device 116 may be adjustable (e.g., using a slider connected to louvers, etc.) to increase or decrease resistance to airflow through throttle device 116. Given a nearly constant static pressure provided by fan 114, increasing or decreasing resistance through throttle device 116 may respectively decrease or increase airflow through throttle device 116. Figure 1A As shown, the size of the throttle 116 can correspond to the size of the heating device 115. When the heating device 115 includes a radiator, the area of ​​the throttle 116 can correspond to the area of ​​the radiator. It is understood that the disclosed embodiments are not limited to throttles having this size. In some embodiments, the throttle 116 can be a screen, a filter, a constricted area of ​​the housing, or some other suitable mechanism for increasing the airflow resistance from the second reservoir 113 to the first reservoir 111. The throttle 116 can be formed as an integral part of the housing 101 or can be a separate component. The disclosed embodiments are not limited to any particular configuration of the throttle. The throttle 116 can be formed of metal, plastic, wood, paper, fabric, or any other suitable material. It is understood that the resistance of the throttle 116, the pressure difference across the fan 114, and the airflow through the fan 114 can be related (e.g., the head-flow relationship through the fan 114). In some embodiments, the throttle 116 can be selected to establish a pressure difference between the first and second reservoirs when the probe is retracted (e.g., ...). Figure 1A (as shown), thereby controlling the air velocity guided through the inlet slot to the probe tip, as described herein and Figure 3B As shown. In some embodiments, the throttle 116 can be adjusted to establish a pressure difference across the fan 114, such that the airflow through the inlet slot is between 50 and 200 L / min (e.g., about 100 L / min, or another suitable value that may depend on other machine parameters, such as the temperature of the heating element 115). In various embodiments, the throttle 116 can be selected to determine the proportion of air flowing through the heating element 115 when the probe is retracted. Increasing or decreasing the resistance of the throttle 116 can respectively decrease or increase the proportion of air flowing through the fan and then through the heating element 115.

[0025] Figure 1AThe storage container 119 that contacts the housing 101 is further depicted. In this example, the machine is configured for the probe tip to advance and enter the internal volume of the storage container 119. A stopper 120 of the storage container 119 may contact the bottom surface of the housing. The bottom surface may include an opening that can be aligned with the probe tip 107. This alignment allows the probe tip to extend beyond the housing 101 and into the storage container 119. In some embodiments, when the housing 101 contacts the storage container 119, the stopper 120 may block the opening, preventing or reducing air exchange between the interior of the housing 101 and the surrounding environment. In this way, the heating of the surrounding environment can be reduced or prevented. In some embodiments, the shape of the storage container 119 may resemble the reagent container described in U.S. Patent Application 17 / 305504 ('504 application), filed July 8, 2021, which is incorporated herein by reference in its entirety. The shape of the stopper 120 may resemble the resealable stopper described in '504 application. The housing 101 and the storage container 119 can be aligned using the alignment system, method, and features described in application '504'. The stopper can be self-sealing.

[0026] like Figure 1B As shown, probe 103 can be translated downwards within the space of inner sleeve 118, causing probe tip 107 to advance through opening 121 of base 122 and penetrate stopper 120. The machine can then aspirate material (e.g., reagents or samples) from the internal volume 123 of storage container 119 into probe reservoir 105. In some embodiments, heating probe tip 107 can be combined with heating the aspirated material in probe reservoir 105. If probe tip 107 is colder than the specified temperature or temperature range for analysis, the material dispensed through probe tip 107 may be colder than the specified temperature or temperature range, and the analysis may be erroneous.

[0027] Although Figure 1A and 1B A single probe tip is depicted for use in dispensing reagents and samples, but the disclosed embodiments are not limited thereto. In some embodiments, the machine may include multiple probe tips. One of the multiple probe tips may be configured to aspirate a sample, while another of the multiple probe tips may be configured to aspirate a reagent. In some embodiments, the probe tip configured to aspirate a reagent may be thinner and have a rounded tip to avoid tearing or cutting the stopper in the reagent storage container, as described in '504 application. In some embodiments, the multiple probe tips may be coaxial, wherein the probe tips are configured to aspirate reagent disposed within the probe tip, and the probe tips are configured to penetrate a seal on the sample storage container. Conversely, in some embodiments, the axes of the multiple probe tips may be offset.

[0028] Figure 2A cross-sectional view of the outer casing 101 and the storage container 119 is depicted. For clarity, the probe 103 is omitted from this view. Figure 2 As shown, the outer sleeve 117 can be spaced apart from the inner sleeve 118. An upper space 201 can be formed between the outer sleeve 117 and the inner sleeve 118. The upper space 201 can be connected to the first reservoir 111 through an opening 202, allowing air to flow from the upper space 201 to the first reservoir 111. The upper space 201 can be connected to the pressurization chamber 203 through an outlet 204, allowing air to flow from the pressurization chamber 203 to the upper space 201. The pressurization chamber 203 can be defined above by the probe reservoir 105, surrounded by the inner sleeve 118, and limited below by the base 122. A lower space 205 can be formed between the outer sleeve 117 and the inner sleeve 118. The lower space 205 and the upper space 201 can be separated by a separator 206. The lower space 205 can be connected to the second reservoir 113 through an opening 207, allowing air to flow from the second reservoir 113 to the lower space 205. The lower space 205 can be connected to the pressurization chamber 203 through the inlet 208, allowing air to flow from the lower space 205 to the pressurization chamber 203.

[0029] like Figure 2 As shown, housing 101 can form a heating circuit and a probe circuit. In this example, heated air is indicated by dashed arrows, while cooled air is indicated by solid arrows. In the heating circuit, air moves from first reservoir 111 to second reservoir 113 via fan 114. The air then flows through throttle 116 to heating device 115. As the air passes through or through heating device 115, it can be heated or reheated. After leaving heating device 115, the heated air in the heating circuit returns and mixes with the air in first reservoir 111. In this way, the air circulating within housing 101 can be heated, allowing the circulating air to heat probe tip 107 again. In the probe circuit, air moves from first reservoir 111 to second reservoir 113 via fan 114. The air then flows into lower space 205 through opening 207. Air enters pressurization chamber 203 through inlet 208 to heat probe tip 107. In some embodiments, as per […] Figure 3B The inlet can be oriented and configured to focus airflow onto the probe tip 107. Air can flow around the probe tip 107 and heat it. Cooled air can exit through outlet 204 into the upper space 201. The cooled air can then return through opening 202 to mix with the air in the first reservoir 111.

[0030] In some embodiments, such as Figure 1BAs shown, probe reservoir 105 can at least partially block the outlet 204 and inlet 208 leading to pressurization chamber 203. This blockage can increase the proportion of air passing through heating device 115 via fan 114. The increased proportion of air passing through heating device 115 can increase the rate at which the air temperature in the first and second reservoirs approaches the temperature of heating device 115. Conversely, throttle 116 can be selected such that outlet 204 and inlet 208 are not blocked when probe 103 retracts (e.g., Figure 1A As shown, an increased proportion of air supplied by fan 114 passes through inlet 208 into pressurization chamber 203, increasing the rate at which probe tip 107 is heated. In some embodiments, when probe 103 retracts, most of the air supplied by fan 114 passes through inlet 208 into pressurization chamber 203. This division of the circulating air favors heating probe tip 107 rather than heating the circulating air. In some embodiments, when probe 103 advances, most of the air supplied by fan 114 passes through heating device 115. This division of the circulating air favors heating the circulating air rather than heating probe tip 107. Therefore, the machine can automatically favor heating or reheating the circulating air when probe tip 107 advances, and can automatically favor heating or reheating probe tip 107 when probe tip 107 retracts.

[0031] Figure 3A A view depicting an entry point into housing 101 from above is shown, without probe 103. In this example, heated air is indicated by dashed arrows, while cooling air is indicated by solid arrows. In this embodiment, outer sleeve 117 and inner sleeve 118 are coaxial and both have circular cross-sections. It will be understood that other cross-sections may be used without departing from the contemplated embodiment. As described above regarding... Figure 2 The separator 206 divides the space between the inner sleeve 118 and the outer sleeve 117 into an upper space 201 and a lower space 205. Figure 3A (Not visible in the middle) Cooling air flows through the upper space 201, returns to the first reservoir 111 through the opening 202, and flows from the second reservoir 113 to the pressurization chamber 203 through the lower space 205. In this embodiment, a portion of the separator 206 extends through a semi-annular portion of the space between the inner and outer sleeves, forming the top of the lower space 205. Heated air also flows from the heating device 115 into the first reservoir 111. In this way, air can be recirculated within the housing 101. Recirculated air saves energy and prevents air from heating the rest of the machine, which can be configured to operate at lower temperatures (e.g., reagent storage temperatures).

[0032] Figure 3BA view is depicted entering the housing 101 from below, without the probe 103. In this example, heated air is indicated by dashed arrows, while cooling air is indicated by solid arrows. In this example, the outer sleeve 117 and the inner sleeve 118 are coaxial and both have a circular cross-section. It will be understood that other cross-sections may be used without departing from the contemplated embodiment. A divider 206 divides the space between the inner sleeve 118 and the outer sleeve 117 into an upper space 201 and a lower space 205. In this embodiment, a portion of the divider 206 is connected to... Figure 3A The semi-annular portions of the partition 206 shown are connected to form the wall of the lower space 205. It is understood that other partition arrangements may be used without departing from the intended embodiment. Heated air flows from the fan 114 into the choke 116 in the heating circuit. Heated air also flows into the lower space 205 through the opening 207, enters the pressurization chamber 203 through the inlet slot 301, and enters the upper space 201 in the probe circuit through the outlet slot 303.

[0033] like Figure 3B As shown, outlet 204 may include an array of outlet slots (e.g., outlet slot 303). This array may include a plurality of outlet slots vertically or horizontally distributed on the inner sleeve 118. The outlet slots may be vertically oriented. In some embodiments, the outlet slots may be parallel to the probe tip 107. The horizontal width of the outlet slots may be between 3 and 12 mm, or between 6 and 8 mm, and the vertical height of the outlet slots may be between 40 and 65 mm. Although Figure 3B An outlet 204 including a single outlet slot 303 is depicted, but the disclosed embodiments are not limited thereto. For example, two outlet slots may be vertically distributed (e.g., one above the other). The disclosed embodiments are not limited to outlet slots. Other mechanisms for controlling and directing airflow from the pressurization chamber 203 to the upper space 201, such as screens, grids, etc., may be used. Such mechanisms may be formed as part of the housing 101 (e.g., as part of the inner sleeve 118) or may be separate components.

[0034] like Figure 3B As shown, inlet 208 may include an array of inlet slots (e.g., inlet slot 301). This array may include a plurality of inlet slots vertically or horizontally distributed on the inner sleeve 118. The inlet slots may be vertically oriented. In some embodiments, the inlet slots may be parallel to the probe tip 107. The horizontal width of the inlet slots may be between 0.5 and 1.2 mm, and the vertical height of the inlet slots may be between 40 and 65 mm. Although Figure 3BTwo horizontally distributed inlet slots are depicted, but the disclosed embodiments are not limited thereto. For example, inlet 208 may include two sets of inlet slots, each set comprising a plurality of vertically distributed inlet slots (one slot above the other), with each set horizontally distributed (one set adjacent to the other). The disclosed embodiments are not limited to inlet slots. Other mechanisms for controlling and directing airflow from lower space 205 to pressurization chamber 203, such as screens, grids, etc., may be used. Such mechanisms may be formed as part of housing 101 (e.g., as part of inner sleeve 118) or may be separate components.

[0035] like Figure 3B As shown, the inlet slots 301 can be spaced at angles between 60 and 120 degrees, or at distances between 6 and 10 mm. Using multiple inlet slots spaced at such angles or distances prevents stagnation points from forming in front of the probe tip. Such stagnation points reduce the heated airflow above the probe tip, thus inhibiting probe heating.

[0036] like Figure 3B As shown, outlet 204 (and outlet groove 303) can be located on the side of inner sleeve 118 opposite to inlet 208 (and inlet groove 301). Although Figure 3B An outlet slot 303 and two inlet slots 301 are depicted, but the number of inlet slots and the number of outlet slots can vary. In some embodiments, the area of ​​the outlet slots can be greater than the sum of the areas of the inlet slots. In some embodiments, the outlet slot 303 and the inlet slots 301 can have similar heights, but the arc length of the outlet slot 303 can be greater than the sum of the arc lengths of the inlet slots 301. In some embodiments, the ratio of the outlet slot area to the inlet slot area can be a number between 2 and 30, or a number between 10 and 20. This configuration ensures that the pressure difference between the lower space 205 and the pressurization chamber 203 is approximately equal to the pressure difference between the second reservoir 113 and the first reservoir 111. In this way, for a given fan speed or pressure, the air velocity flowing through the inlet slots 301 and contacting the probe tip 107 can be increased or maximized. Increasing the air velocity can increase heat transfer to the probe tip 107, reducing the time required to heat or reheat the probe tip 107.

[0037] Consistent with the disclosed embodiments, the machine can use rules (e.g., if-then rules, trial and error, decision trees, etc.), control laws (e.g., proportional, proportional-integral, or proportional-integral-derivative control laws, state-space control laws, adaptive control laws, nonlinear control laws, or other suitable control laws), or another suitable control framework to control the temperature of the probe tip. The control framework can control the temperature of the probe tip within a specified temperature range or close to a specified temperature value. In some cases, the control framework can control the temperature of the probe tip within a specified temperature range (or close to a specified temperature value) before at least one of aspirating reagent (e.g., from a storage container, etc.) or dispensing reagent (e.g., into a target container). In some embodiments, the inputs to such a framework may include at least one of the probe tip temperature, the air temperature inside the housing, the temperature of the heating device, or the current fan speed. In some embodiments, the output to such a framework may include at least one of the fan speed or the heating device temperature (or instructions to increase or decrease at least one of the fan speed or the heating device temperature).

[0038] While the disclosed embodiments are not limited to any particular control framework (e.g., a set of rules, control laws, etc.), machines can generally increase the temperature of the probe tip by increasing at least one of the heating element temperature or the fan speed. The increase in fan speed can be continuous or discontinuous (e.g., turning on the fan or switching the fan from a lower setting to a higher setting). Similarly, the increase in heating element temperature can be continuous or discontinuous (e.g., turning on the heating element or switching the heating element from a lower setting to a higher setting). Likewise, automated testing systems can generally decrease the temperature of the probe tip by decreasing at least one of the heating element temperature or the fan speed. In various embodiments, feedforward or feedback control can be used to maintain the probe tip 107 at a specified temperature or within a specified temperature range.

[0039] In some embodiments, the air temperature inside the housing can be measured directly (e.g., using one or more temperature sensors inside the housing). In various embodiments, the air temperature can be measured indirectly. In some embodiments, the air temperature can be estimated based on the temperature of the housing. For example, a relationship can be determined between the temperature of the outer surface of the housing and the air temperature inside the housing. The temperature of the outer surface of the housing can be measured using a temperature sensor disposed on the surface of the housing, or configured to measure the temperature of the housing surface.

[0040] In some embodiments, the frame used by the machine to control the temperature of the probe tip can take at least one of the following as input: the air temperature in the first storage 111, the air temperature in the second storage 113, the air temperature in the upper space 201, the air temperature in the lower space 205, the air temperature in the pressurization chamber 203, etc. In some embodiments, the frame can use multiple air temperatures as inputs to control the frame.

[0041] In some embodiments, the temperature of the heating device can be measured directly (e.g., using a temperature sensor disposed on the heating device, or otherwise configured to measure the temperature of the heating device). The temperature of the heating device can also be measured indirectly. For example, the heating device may exhibit a temperature-voltage relationship (or a temperature-current relationship). The temperature of the heating device can then be estimated from the applied voltage (or current).

[0042] In some embodiments, the fan speed can be measured directly. In such embodiments, the fan can provide a voltage or current output indicating the current fan speed. In some embodiments, the fan speed can be estimated from the voltage or current applied to the fan.

[0043] Consistent with the disclosed embodiments, the machine can use the second reservoir air temperature and the heating device temperature to control the fan speed and heating device temperature. These two temperatures can be directly measured using thermal sensors: a temperature sensor located within the second reservoir and a temperature sensor located on the heating device (or a portion thereof). In some embodiments, the machine can shut off the heating device when the second reservoir air temperature exceeds an upper threshold and turn it on when the second reservoir air temperature drops below a lower threshold. In some cases, the upper threshold may be between 37°C and 42°C, or another suitable threshold, depending on the reagent or the analysis to be performed. In some cases, the lower threshold may be between 30°C and 35°C, or another suitable threshold, depending on the reagent or the analysis to be performed.

[0044] In some embodiments, inputs to the control framework used by the machine may include at least one of the following: the volume of aspirated material (e.g., reagent or sample), the aspiration rate (e.g., flow rate), or the time between aspirating and dispensing the aspirated material. In some embodiments, the time between aspirating and dispensing the material may be between 1 second and 4 seconds. In some embodiments, as the duration of reagent aspiration increases, the temperature of the probe tip decreases after aspiration of cold material. The duration of material aspiration may increase with increasing material aspiration volume and decrease with increasing material aspiration rate. In some embodiments, the duration of aspiration or dispensing may be less than 1 second or less than 100 milliseconds. Therefore, consistent with some control frameworks, the machine may increase at least one of the fan speed or the temperature of the heating device to compensate for the increase in the aspirated material volume or the decrease in the material aspiration rate. In some embodiments, as the time between aspirating and dispensing the aspirated material increases, the temperature of the probe tip increases after aspiration of cold material. Therefore, consistent with some control frameworks, the machine may decrease at least one of the fan speed or the temperature of the heating device to compensate for the increase in the time between aspirating and dispensing the aspirated material.

[0045] In some embodiments, the inputs to the control framework used by the machine may include at least one of reagent temperature (e.g., reagent storage temperature) or analysis temperature. In some embodiments, the analysis temperature may be specified by the user of the machine. In various embodiments, the reagent storage temperature may be specified by the user of the machine or detected using the machine's temperature sensor. The disclosed embodiments are not limited to any particular location, type, or configuration of such a sensor. It will be understood that the greater the temperature difference between the reagent storage temperature and the analysis temperature, the higher the fan speed and / or the higher the heating element temperature.

[0046] It is understood that the control framework can be implemented using software, hardware, or a combination of both. In some embodiments, the automatic control framework can be implemented using software code that executes on a general-purpose computer. In various embodiments, the automatic control framework can be implemented using dedicated hardware or an embedded control system. The disclosed embodiments are not limited to any particular hardware or software implementation of the control framework.

[0047] Figure 4 A temperature / time plot was drawn, showing the temperatures of the three target containers during reagent dispensing. As described herein, reagents can be stored between 4°C and 8°C, while analyses may require performance at approximately 37°C. Therefore, as... Figure 4 As shown, the reagent applied through the unheated probe tip causes a temperature drop in the well. Because the three target containers are heated, their temperatures increase with reagent dispensing. This temperature drop affects the accuracy of the analysis, while delaying analysis until the target containers reach the specified temperature reduces machine productivity.

[0048] Figure 5 A method 500 is described, which involves aspirating material (e.g., reagents or samples) from a storage container and dispensing the material into a target container. The material may be a fluid. Method 500 can be performed using a storage container and the machine described herein, thereby improving the reliability of the analysis while also extending reagent life and reducing reagent waste.

[0049] Before executing method 500, the machine can be initialized. This initialization may include initiating airflow within the housing (e.g., housing 101) and bringing the airflow to a specified temperature. Airflow can be initiated by turning on a fan (e.g., fan 114). The airflow can be brought to the specified temperature by turning on a heating device (e.g., heating device 115).

[0050] In step 501 of method 500, the machine draws material (e.g., a reagent or sample) into a reservoir (e.g., probe reservoir 105) of the probe (e.g., probe 103) via a probe tip (e.g., probe tip 107). The probe may be located within a housing. The housing may include a heating device and a fan for circulating heated air. Material can be drawn from an internal volume (e.g., internal volume 123) of a storage container (e.g., storage container 119). The storage container may be sealed with a stopper (e.g., stopper 120). The machine can advance the probe tip into the storage container via the stopper (e.g., as shown in the image). Figure 1B (As shown). Once the probe tip is inside the storage container, the machine can aspirate fluid.

[0051] In step 503 of method 500, the machine may translate the probe to a retracted position within the housing (e.g., as shown in the image). Figure 1A (As shown). As described herein, the housing may include a heating circuit and a probe circuit. In some embodiments, the heating circuit may include a heating device, while the probe circuit may include a lower space (e.g., lower space 205), an inner sleeve space (e.g., pressurization chamber 203), and an upper space (e.g., upper space 201). A fan may be used to circulate air through the heating circuit and the probe circuit. In the probe circuit, the circulating heated air may be guided by an inlet slot (e.g., inlet slot 301) to flow over the probe tip.

[0052] As described herein, the machine can select fan speed and heating element temperature according to a control framework. The control framework may include at least one input. The at least one input may be the air temperature of the housing (or multiple such air temperatures), the temperature of the heating element, the volume of the aspirated fluid, the aspiration rate, the time between aspirating the fluid and dispensing that portion of the fluid, the temperature of the aspirated material (e.g., the storage temperature of a reagent or sample), or the desired analysis temperature. In some embodiments, consistent with the control framework, the machine may use circulating heated air to heat the probe tip to a specified temperature or temperature range before dispensing the aspirated fluid into the target container. In some embodiments, as described herein, the probe reservoir may include a heating element that can additionally heat the aspirated fluid during transfer.

[0053] In step 505 of method 500, the machine may translate the probe to a dispensing position within the housing. In some embodiments, the dispensing position may be the same as the suction position. In various embodiments, the dispensing position may include a greater or lesser vertical displacement of the probe than the suction position. The machine may then dispense fluid drawn from the probe reservoir into the target container. It will be understood that when the machine translates the probe to the suction or dispensing position, the proportion of air flowing through the heating circuit increases. Conversely, when the machine translates the probe to the retracted position, the proportion of air flowing through the heating circuit decreases.

[0054] In some embodiments, the machine may circulate air only when the housing is in contact with the storage container (e.g., when the housing is in contact with the stopper of the storage container). In this way, the storage container can prevent or reduce the amount of heated air escaping from the housing. In some embodiments, the machine may additionally or alternatively circulate air when the housing is not in contact with the storage container.

[0055] In some embodiments, in step 501, the machine may circulate air to preheat the probe tip before aspirating material from the storage container. In various embodiments, the machine may circulate air in step 503 after aspirating material and before dispensing fluid into the storage container.

[0056] The embodiments may be further described using the following terms:

[0057] 1. A system for heating a probe, comprising: a housing including: a tip of a probe configured to enter an internal volume of a stopper container and to draw material from or dispense material into the internal volume of the stopper container; a heating device; and a fan positioned to circulate air within the housing to heat the tip of the probe.

[0058] 2. The system of Clause 1, wherein: the housing includes a heating circuit and a probe circuit; and the fan is positioned to allow air to circulate within at least one of the heating circuit or the probe circuit.

[0059] 3. The system of Clause 2, wherein: the heating circuit includes a heating device and a throttle for restricting airflow through the heating circuit.

[0060] 4. The system of any one of Clauses 1 to 3, wherein: the housing includes: a high-pressure position; a low-pressure position, wherein a fan is disposed between the high-pressure position and the low-pressure position; and an inner sleeve including an inlet connecting the high-pressure position to the inner sleeve.

[0061] 5. The system of Clause 4, wherein: the inlet comprises at least two slots, each of the at least two slots being parallel to the probe tip.

[0062] 6. The system of any one of Clauses 4 to 5, wherein: the inner sleeve includes an outlet groove parallel to the probe tip.

[0063] 7. A system of any one of clauses 1 to 6, wherein: the system includes at least one of: a temperature sensor configured to measure the air temperature in the housing; or a temperature sensor configured to measure the temperature of the heating device.

[0064] 8. A system of any one of Clauses 1 to 7, wherein: the system includes a temperature sensor configured to directly measure the air temperature in a high-pressure position or a low-pressure position of the housing.

[0065] 9. A system of any one of Clauses 1 to 7, wherein: the system includes a temperature sensor configured to indirectly measure the temperature of air or the temperature of a heating device.

[0066] 10. A system of any one of clauses 1 to 9, wherein: the probe tip includes a first reagent tip and a second sample tip.

[0067] 11. A method for heating the tip of a probe used for aspirating and dispensing fluid, comprising: using a fan to circulate air within a housing to contact a heating device and the tip of the probe located within the housing, the tip of the probe being configured to enter an internal volume of a stopper container, and aspirating material from or dispensing material into the internal volume of the stopper container.

[0068] 12. The method of Clause 11, wherein: the housing includes a heating circuit and a heating device is disposed within the heating circuit; the housing includes a probe circuit and a probe is located within the probe circuit; and allowing air to circulate within the housing to contact the heating device and the probe tip includes allowing air to circulate within the heating circuit and the probe circuit.

[0069] 13. The method of any one of Clauses 11 to 12, wherein: the housing includes a high-pressure reservoir, a low-pressure reservoir, and an inner sleeve; allowing air to circulate within the housing includes allowing a first proportion of air from the high-pressure reservoir to circulate through the inner sleeve and into the low-pressure reservoir; and allowing a second proportion of air from the high-pressure reservoir to circulate through a heating device and into the low-pressure reservoir.

[0070] 14. The method of Clause 13, further comprising: adjusting the temperature of the heating device based on at least one of: an air temperature measurement for the high-pressure reservoir; or the temperature of the heating device.

[0071] 15. The method of any one of Clauses 13 to 14, wherein: allowing the first proportional air to circulate through the inner sleeve includes allowing the first proportional air to circulate through an input slot, the input slot being configured to direct the first proportional air to the tip of the probe.

[0072] 16. A method for transferring fluid using a probe tip, comprising: drawing fluid into a reservoir of a probe through a probe tip that enters the internal volume of a stoppered container, the probe being located within a housing; translating the probe to a retracted position within the housing and allowing air to circulate within the housing to contact the probe tip, thereby heating the probe tip; and translating the probe to a dispensing position within the housing and dispensing a portion of the fluid from the reservoir.

[0073] 17. The method of Clause 16, wherein: the housing includes a heating circuit and a probe circuit; allowing air to circulate within the housing to contact the probe tip includes using a fan to circulate air through the probe circuit; and the method further includes using a fan to circulate air through the heating circuit to contact the heating device.

[0074] 18. The method of Clause 17, wherein: when the probe is translated to the dispensing position, the proportion of air flowing through the heating circuit increases.

[0075] 19. The method of any one of Clauses 17 to 18, wherein: the method further comprises controlling at least one of the temperature of a heating device or the speed of a fan to heat the probe tip to a temperature within a specified temperature range before dispensing the portion of fluid from the reservoir or before drawing fluid from the reservoir.

[0076] 20. The method of any one of clauses 17 to 19, wherein: the method further comprises controlling at least one of the following based on at least one of: the temperature of the heating device or the speed of the fan: the volume of fluid being drawn; the drawing speed; or the time between drawing the fluid and distributing the portion of the fluid.

[0077] Furthermore, although illustrative embodiments have been described herein, the scope includes any and all embodiments based on this disclosure that have equivalent elements, modifications, omissions, combinations (e.g., across aspects of various embodiments), adaptations, or variations. Elements in the claims are to be interpreted broadly based on the language used in the claims and are not limited to the examples described in this specification or in the course of the application, which are to be interpreted as non-exclusive. Moreover, the steps of the disclosed methods can be modified in any way, including by reordering steps or by inserting or deleting steps. Therefore, the specification and embodiments are to be considered merely illustrative, and the true scope and spirit are indicated by the full scope of the appended claims and their equivalents.

Claims

1. A system for heating a probe, the system comprising: The housing includes: fan, Heating device, for heating air flowing through or passing through the heating device, and An inner sleeve for accommodating a probe, the inner sleeve including a pressurization chamber that receives air heated by the heating device and circulates the heated air around the probe.

2. The system of claim 1, wherein the inner sleeve has a circular cross-section and is coaxial with the probe.

3. The system of claim 1, wherein the internal dimensions of the inner sleeve conform to at least a portion of the probe to prevent or reduce air leakage from the housing through the top of the pressurization chamber.

4. The system of claim 1, wherein the housing further comprises a first storage unit and a second storage unit, the first storage unit and the second storage unit being separated by the fan and the heating device.

5. The system of claim 4, wherein the fan is configured to circulate air from the first storage to the second storage, from the second storage to the first storage, or in one or more airflow loops.

6. The system of claim 4, wherein the fan is configured to circulate air from the first storage unit to the second storage unit to maintain a static pressure in the second storage unit higher than that in the first storage unit.

7. The system according to claim 1, wherein the heating device comprises a heater and a radiator.

8. The system of claim 7, wherein the heater comprises a flat flexible heater, a cylindrical heater, or a resistance heater.

9. The system of claim 1 further includes one or more temperature sensors, wherein the heat output of the heating device can be controlled according to the one or more temperature sensors.

10. The system of claim 1, wherein the housing is configured to prevent or reduce air leakage from the housing.

11. The system of claim 1, wherein the housing is configured to allow the heated air to circulate again within the housing.

12. The system of claim 1, wherein the heated air enters the pressurization chamber through one or more inlet slots of the inner sleeve and exits the pressurization chamber through one or more outlet slots of the inner sleeve.

13. The system of claim 12, wherein the orientation and configuration of the one or more inlet slots are configured to focus airflow onto the probe tip.

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