Ultrasound micropipetting device and method of controlling the same

Abstract

The present application provides an ultrasonic micro pipetting device and a control method thereof, wherein the pipetting device comprises a source liquid loading plate, a target liquid loading plate and an ultrasonic pipetting assembly, the ultrasonic pipetting assembly comprises an ultrasonic transducer assembly and a negative pressure liquid suction assembly, the ultrasonic transducer assembly comprises an ultrasonic transducer and a coupling liquid between the transducer head of the ultrasonic transducer and the bottom surface of the source liquid loading plate, and the negative pressure liquid suction assembly comprises a liquid suction head, and the liquid suction surface of the liquid suction head can be driven to be in contact with the bottom surface of the source liquid loading plate. One aspect of the present application can prevent the condensation generated on the bottom surface of the source liquid loading plate after being placed from mixing with air impurities, thereby adversely affecting the pipetting amount of ultrasonic pipetting, that is, improving the accuracy of the ultrasonic pipetting amount, and the other aspect can prevent the bottom surface of the source liquid loading plate from being polluted by the coupling liquid after ultrasonic pipetting and even the occurrence of freezing phenomenon.

Description

Technical Field

[0001] This invention belongs to the technical field of automated liquid processing equipment, specifically relating to an ultrasonic micro-pipette device and its control method. Background Technology

[0002] Micropipettes are a crucial component of scientific research and production testing in fields such as biology, chemistry, and medicine, serving as a fundamental operational procedure in experiments. The precision of micropipettes plays a vital role in the discovery of scientific findings, the accuracy of test results, and the stability of product performance. The urgent need to develop a mechanized, fully automated, and high-throughput pipetting method has led to the emergence of automated pipetting workstations.

[0003] Automated pipetting workstations based on multi-channel pipetting modules have become the mainstream pipetting paradigm due to their advantages such as precise quantification, high degree of automation, elimination of manual operation, and high throughput. However, regardless of whether it is a pipette based on the piston principle or various pipetting technologies based on solenoid valves, piezoelectric drives, electric fields, magnetic fields, and light, pipetting still requires the use of pipetting tips, capillaries, nozzles, etc. These pipetting tips need to be in direct contact with the liquid, posing risks of sample residue and cross-contamination, and resulting in significant sample loss. Furthermore, in high-precision pipetting, the orifices of pipetting tips, capillaries, nozzles, etc., are very small, making them prone to clogging. In addition, most pipetting tips are disposable consumables, leading to high costs and environmental pollution from large-scale use.

[0004] In recent years, non-contact pipetting technology using focused ultrasound has attracted considerable attention. This technology directly ejects droplets from a mother liquor container to a target container using ultrasound, eliminating the need for a pipette tip. The droplets do not come into contact with any other medium during the transfer process, resulting in no liquid adhesion or residue, no cross-contamination, reduced consumable costs, rapid pipetting speed, ultra-high pipetting accuracy exceeding nanoliters, reduced reagent costs, and preservation of the bioactivity of biological macromolecules. It holds immense promise for future applications.

[0005] Existing technology discloses a non-contact ultrasonic pipetting device and method, in which an ultrasonic coupling unit is set between the ultrasonic transducer and the source liquid orifice plate to maximize energy propagation and achieve heat dissipation. The coupling fluid of the ultrasonic coupling unit is mostly deionized water. During and after pipetting, coupling fluid will inevitably remain on the bottom wall of the source liquid orifice plate. After use, the source liquid orifice plate needs to be recycled and stored in a refrigerated device. The residual coupling fluid will contaminate the refrigeration device and may even freeze, which will adversely affect the subsequent use of the source liquid orifice plate. In addition, after the source liquid orifice plate is removed from the refrigerated device, its bottom wall will come into contact with the outside air and condensation will occur. This condensation mixed with impurities will adversely affect ultrasonic pipetting, thereby reducing the accuracy of pipetting volume. Based on this, the present invention is proposed. Summary of the Invention

[0006] This invention provides an ultrasonic micro-pipette device and its control method, which can solve the technical problems in the prior art where residual ultrasonic coupling liquid or condensation occurs on the bottom surface of the source liquid-carrying orifice plate, which easily contaminates the refrigeration device or even causes freezing and reduces the accuracy of the pipetting volume.

[0007] To address the aforementioned problems, this invention provides an ultrasonic micropipette, comprising a source liquid-carrying orifice plate, a target liquid-carrying orifice plate disposed above and opposite the source liquid-carrying orifice plate, and an ultrasonic pipetting assembly disposed below the source liquid-carrying orifice plate. The ultrasonic pipetting assembly includes an ultrasonic transducer and a negative pressure suction assembly. The ultrasonic transducer includes an ultrasonic transducer and a coupling fluid disposed between the transducer head of the ultrasonic transducer and the bottom surface of the source liquid-carrying orifice plate. The negative pressure suction assembly includes a suction head, the suction surface of which can be driven to contact the bottom surface of the source liquid-carrying orifice plate.

[0008] In some embodiments, the negative pressure liquid suction assembly further includes a first filter connected to the outlet of the suction head to separate and store the liquid absorbed by the suction head from the negative pressure airflow; and / or,

[0009] The ultrasonic transducer assembly further includes a liquid supply overflow housing and a liquid supply and return assembly. The liquid supply overflow housing includes an inlet pipe and a liquid recovery housing. The inlet pipe has a top opening. The ultrasonic transducer is assembled inside the inlet pipe and the transducer head is located inside the top opening. An outlet is formed between the transducer head and the top opening. The outlets are spaced around the transducer head. The liquid overflowing from the outlet can fall into the liquid recovery housing. The liquid supply and return assembly can supply coupling fluid into the inlet pipe and recover the coupling fluid in the liquid recovery housing to form a cycle.

[0010] In some embodiments, the supply and return liquid assembly includes a storage bottle, a peristaltic pump, and a negative pressure degassing bottle. The storage bottle, peristaltic pump, negative pressure degassing bottle, inlet pipe, and liquid recovery shell are sequentially connected to form a liquid circulation loop. The negative pressure degassing bottle can use negative pressure to act on the coupling liquid flowing through it to eliminate the gas mixed in the coupling liquid.

[0011] In some embodiments, a temperature control component is connected in series on the pipeline between the outlet of the negative pressure degassing bottle and the inlet of the liquid inlet pipe. The temperature control component is used to adjust the temperature of the coupling liquid entering the liquid inlet pipe to be within the target temperature range.

[0012] In some embodiments, a gas-liquid circuit adapter is also included, which integrates a gas circuit connector and a liquid circuit connector. The gas circuit connector is used to connect the negative pressure source to the negative pressure liquid absorption component and the negative pressure degassing bottle, and the liquid circuit connector is used to connect the temperature control component to the negative pressure degassing bottle and the liquid inlet pipe.

[0013] In some embodiments, the gas connector is also used to connect the negative pressure source to the liquid storage bottle.

[0014] In some embodiments, the ultrasonic micropipette further includes an orifice for the source and target liquid-carrying plates to enter and exit the internal accommodating space. An electrostatic elimination component is provided inside the orifice, capable of eliminating static electricity on the source and target liquid-carrying plates entering the orifice; and / or,

[0015] The target liquid-carrying orifice plate is detachably assembled on the target plate support, which can be controlled to flip up and down. A high-voltage grid is provided between the target plate support and the bottom surface of the target liquid-carrying orifice plate to generate an adsorption force on the droplets of the ultrasonic pipetting assembly when the target liquid-carrying orifice plate is in the liquid-pipette condition.

[0016] In some embodiments, the target liquid-carrying orifice plate can be controlled to tilt up and down, and the electrostatic eliminator has two sets, which are arranged vertically spaced apart, wherein the upper electrostatic eliminator can be raised and lowered; and / or,

[0017] The ultrasonic micropipette also includes a positive pressure gas path assembly for providing a positive pressure gas flow into the electrostatic elimination assembly to form a positive and negative ion gas flow.

[0018] The present invention also provides a control method for the ultrasonic micropipette device as described above, comprising the following steps:

[0019] Control the target plate support used for assembling the target liquid-carrying orifice plate and / or the source plate support used for assembling the source liquid-carrying orifice plate to extend out of the orifice plate passage;

[0020] Place the target liquid-carrying orifice plate on the target plate support, and / or place the source liquid-carrying orifice plate on the source plate support;

[0021] Control the target board support and / or source board support to retract, and activate the static elimination component during the retraction process until the target board support and / or source board support retract to the preset target position, and control it to stop operating after the target board support and / or source board support are far away from the effective area of ​​the static elimination component;

[0022] When the source plate support retracts to the preset target position, the negative pressure liquid suction component is controlled to adsorb the condensation formed on the bottom surface of the source liquid carrier plate;

[0023] Subsequently, the ultrasonic transducer assembly is controlled to transfer the reagent solution from the source liquid-carrying plate to the target liquid-carrying plate.

[0024] After the liquid transfer is completed, the negative pressure liquid suction component is controlled to adsorb the coupling liquid remaining on the bottom surface of the source liquid carrier plate.

[0025] In some embodiments, during the operation of the ultrasonic transducer to perform ultrasonic pipetting, the high-voltage power grid is also energized.

[0026] The ultrasonic micropipette and its control method provided by this invention have the following beneficial effects:

[0027] By setting the negative pressure suction component to contact the bottom surface of the source liquid loading plate, the condensation or residual coupling liquid on the bottom surface of the source liquid loading plate can be absorbed cleanly. On the one hand, this can prevent the condensation and air impurities generated on the bottom surface of the newly placed source liquid loading plate from adversely affecting the volume of ultrasonic pipetting, thus improving the accuracy of ultrasonic pipetting. On the other hand, it can prevent the bottom surface of the source liquid loading plate from being contaminated by residual coupling liquid after ultrasonic pipetting, and even prevent the refrigeration unit from freezing. Attached Figure Description

[0028] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description are merely exemplary, and those skilled in the art can derive other embodiments based on the provided drawings without creative effort.

[0029] The structures, proportions, sizes, etc. illustrated in this specification are only for the purpose of assisting those skilled in the art in understanding and reading the content disclosed herein, and are not intended to limit the conditions under which the present invention can be implemented. Therefore, they have no substantial technical significance. Any modifications to the structure, changes in the proportions, or adjustments to the size, without affecting the effects and objectives that the present invention can produce, should still fall within the scope of the technical content disclosed in the present invention.

[0030] Figure 1 This is a three-dimensional structural diagram of the ultrasonic micropipette device according to an embodiment of the present invention at an angle (some components such as the outer casing are omitted);

[0031] Figure 2 This is a three-dimensional structural diagram of the ultrasonic micropipette device according to an embodiment of the present invention from another angle (some components such as the outer casing are omitted);

[0032] Figure 3 This is a cross-sectional view of the ultrasonic micropipette device according to an embodiment of the present invention;

[0033] Figure 4 for Figure 3 A schematic diagram of the assembly structure of the middle door panel and the static elimination component (partial components);

[0034] Figure 5 for Figure 4 A three-dimensional structural diagram of the static elimination rod in the static elimination assembly;

[0035] Figure 6 This is a three-dimensional structural schematic diagram of the ultrasonic pipetting assembly in an embodiment of the present invention;

[0036] Figure 7 yes Figure 6 A schematic diagram of the internal structure of an ultrasonic transducer.

[0037] Figure 8 yes Figure 3 A cross-sectional view of the target liquid-carrying orifice plate and the target plate support in the assembled state (the liquid inlet side of the target liquid-carrying orifice plate in the figure faces upward, and during the ultrasonic liquid transfer process, the liquid inlet side faces downward, that is, towards the source liquid-carrying orifice plate).

[0038] Figure 9 This is a three-dimensional structural diagram of the gas path and liquid path components in the assembled state according to an embodiment of the present invention;

[0039] Figure 10 yes Figure 1 A three-dimensional structural diagram of the control components.

[0040] The reference numerals in the attached figures are as follows:

[0041] 1. Ultrasonic pipetting assembly; 111. Ultrasonic transducer; 121. Aspiration head; 122. First filter; 13. Supply overflow housing; 131. Inlet pipe; 1311. Outlet; 132. Liquid recovery housing; 133. Temperature sensor; 134. Liquid level sensor; 135. Seal; 1361. Coupling fluid inlet; 1362. Coupling fluid outlet; 141. Storage bottle; 142. Peristaltic pump; 143. Negative pressure degassing bottle; 15. Gas-liquid connection; 151. Gas connector; 152. Liquid connector; 16. Assembly plate; 171. Ultrasonic pipetting assembly moving drive component ; 172. Moving guide; 21. Door panel; 211. Door panel lifting drive mechanism; 212. Second guide rail; 22. Static elimination component; 221. Component lifting drive mechanism; 222. First guide rail; 23. Device bracket; 241. Diaphragm pump; 242. Second filter; 25. Solenoid valve; 3. Source liquid carrier plate; 31. Source plate bracket; 32. High voltage grid; 4. Target liquid carrier plate; 41. Target plate bracket; 5. Control component; 51. Ultrasonic transducer control module; 52. Power supply module; 53. High voltage module; 54. Device motion control module; 55. Main control board. Detailed Implementation

[0042] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0043] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0044] It should be understood that the term "and / or" used in this article is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, and B existing alone. Additionally, the character " / " in this article generally indicates that the preceding and following related objects have an "or" relationship.

[0045] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps set forth in these embodiments do not limit the scope of the invention. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters in the following figures denote similar items; therefore, once an item is defined in one figure, it need not be further discussed in subsequent figures.

[0046] In the description of this invention, it should be understood that the orientation or positional relationship indicated by directional terms such as "front, back, up, down, left, right", "horizontal, vertical, horizontal" and "top, bottom" is generally based on the orientation or positional relationship shown in the accompanying drawings, and is only for the convenience of describing this invention and simplifying the description. Unless otherwise stated, these directional terms do not indicate or imply that the device or element referred to must have a specific orientation or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation on the scope of protection of this invention; the directional terms "inner" and "outer" refer to the inner and outer contours relative to the outline of each component itself.

[0047] For ease of description, spatial relative terms such as "above," "on top of," "on the upper surface of," "above," etc., are used herein to describe the spatial positional relationship of a device or feature as shown in the figures to other devices or features. It should be understood that spatial relative terms are intended to encompass different orientations in use or operation beyond the orientation of the device as described in the figures. For example, if the device in the figures were inverted, a device described as "above" or "on top of" other devices or structures would subsequently be positioned as "below" or "under" other devices or structures. Thus, the exemplary term "above" can include both "above" and "below." The device may also be positioned in other different ways (rotated 90 degrees or in other orientations), and the spatial relative descriptions used herein will be interpreted accordingly.

[0048] Furthermore, it should be noted that the use of terms such as "first" and "second" to define components is merely for the purpose of distinguishing the corresponding components. Unless otherwise stated, the above terms have no special meaning and therefore should not be construed as limiting the scope of protection of this invention.

[0049] See Figures 1 to 10As shown in the embodiment of the present invention, an ultrasonic micropipette is provided, comprising a source liquid-carrying plate 3 (for storing experimental reagents), a target liquid-carrying plate 4 (for receiving experimental reagents) disposed above and opposite to the source liquid-carrying plate 3, and an ultrasonic pipetting assembly 1 disposed below the source liquid-carrying plate 3. The ultrasonic pipetting assembly 1 includes an ultrasonic transducer assembly (not labeled in the figure) and a negative pressure aspiration assembly (not labeled in the figure). The ultrasonic transducer assembly includes an ultrasonic transducer 111 and a coupling fluid between the transducer head (not labeled in the figure) of the ultrasonic transducer 111 and the bottom surface of the source liquid-carrying plate 3. The coupling fluid may be, for example, deionized water to ensure the accuracy of ultrasonic pipetting volume. The negative pressure aspiration assembly includes an aspiration head 121, the aspiration surface of which can be driven to contact the bottom surface of the source liquid-carrying plate 3. The aspiration head 121 may be, for example, a hollow cavity with a slit.

[0050] In this technical solution, by setting a negative pressure liquid suction component to contact the bottom surface of the source liquid carrier plate 3, the condensation or residual coupling liquid on the bottom surface of the source liquid carrier plate 3 can be cleaned up. On the one hand, this can prevent the condensation and air impurities generated on the bottom surface of the source liquid carrier plate 3 after placement from adversely affecting the liquid volume of ultrasonic liquid transfer, that is, improve the accuracy of ultrasonic liquid transfer. On the other hand, it can prevent the bottom surface of the source liquid carrier plate 3 from being contaminated by residual coupling liquid (such as deionized water) after ultrasonic liquid transfer, and even prevent the occurrence of freezing phenomenon.

[0051] In some embodiments, the negative pressure liquid suction assembly further includes a first filter 122, which is connected to the outlet of the suction head 121 to separate and store the liquid absorbed by the suction head 121 from the negative pressure airflow. That is, the liquid (condensation or coupling liquid) adsorbed by the suction head 121 under negative pressure is filtered out and stored in the first filter 122. When there is enough liquid, it can be removed. The aforementioned negative pressure airflow can specifically be an external negative pressure source (such as a negative pressure pump or negative pressure pipe).

[0052] See details Figure 6 and Figure 7As shown, the ultrasonic transducer assembly also includes a liquid supply overflow housing 13 and a liquid supply and return assembly (not labeled in the figure). The liquid supply overflow housing 13 includes an inlet pipe 131 and a liquid recovery housing 132. The inlet pipe 131 has a top opening (not labeled in the figure). The ultrasonic transducer 111 is assembled inside the inlet pipe 131, and the transducer head is located (e.g., fixedly connected) inside the top opening. An outlet 1311 is formed between the transducer head and the top opening. The outlets 1311 are spaced around the transducer head, so that after the coupling fluid in the inlet pipe 131 is filled, fluid flows out from each outlet 1311. A certain thickness of water film overflows upwards from point 11, forming a certain thickness of water film on the top surface of the transducer head. The ultrasonic transducer 111 acts on the bottom surface of the source liquid orifice plate 3 through this water film, and ultimately acts on the reagent inside the source liquid orifice plate 3, thereby achieving the purpose of ultrasonic liquid transfer. It can be understood that different liquid transfer volumes can be adjusted by adjusting the operating parameters of the ultrasonic transducer 111. The liquid overflowing from the outlet 1311 can fall into the liquid recovery shell 132. The supply and return liquid assembly can supply the coupling liquid into the inlet pipe 131 and recover the coupling liquid in the liquid recovery shell 132 to form a cycle. The bottom of the aforementioned inlet pipe 131 has a through hole for the cable of the ultrasonic transducer 111 to enter and exit. This through hole is constructed on a seal 135 to prevent the coupling liquid in the inlet pipe 131 from leaking out from the through hole. The aforementioned seal 135 is, for example, a silicone gasket. The inlet pipe 131 has a coupling fluid inlet 1361 for the coupling fluid to enter, and a coupling fluid outlet 1362 is formed on the bottom wall of the liquid recovery shell 132. The supply and return fluid assembly forms a liquid circulation with the supply overflow shell 13 via the aforementioned coupling fluid inlet 1361 and coupling fluid outlet 1362.

[0053] In this technical solution, the transducer head is set at the top opening of the liquid inlet pipe 131 and forms multiple liquid outlets 1311 arranged in a ring. When the liquid inlet pipe 131 is filled with coupling liquid, it will overflow from the liquid outlets 1311 to a certain height and form a stable hemispherical water bag. This height is also the required thickness of the coupling liquid. The transducer head acts on the reagent in the source liquid orifice plate 3 through the coupling liquid of this thickness to realize ultrasonic liquid transfer. The coupling liquid further falls into the liquid recovery shell 132 under its own weight and finally forms a coupling liquid circulation under the action of the supply and return liquid assembly. The structure is simple. It should be noted that the coupling fluid (e.g., deionized water) can contact the orifice plate in time when the overflow moves upward and contacts the orifice plate, forming a stable water column between the transducer and the bottom of the orifice plate. The water bag formed by this overflow is stable, which can ensure the stability of the transducer's feedback signal. That is, the water film in this application is formed by flowing from top to bottom. Compared with the traditional horizontal flow method, it is not necessary to consider the flow difference between the inlet and outlet water to form a stable water bag (i.e., water film). This is beneficial to the stabilizing effect of the ultrasonic transducer 111 on the reagent.

[0054] As is well known in the industry, the principle of ultrasonic pipetting is as follows: an ultrasonic transducer located below the liquid container (i.e., the source liquid-carrying orifice plate 3 mentioned above) emits focused ultrasonic waves, and the acoustic radiation force of the focused ultrasonic waves is used to spray tiny droplets directly from the surface of the liquid in the aforementioned liquid container upwards into the target liquid-carrying orifice plate 4 container above the liquid (i.e., the aforementioned target liquid-carrying orifice plate 4), thereby achieving high-precision contactless manipulation and transfer of micro-volume liquids.

[0055] An ultrasonic transducer 111 is installed inside the ultrasonic transducer assembly. A liquid supply overflow housing 13 is connected to circulating water, which forms a water film on the transducer surface. When the ultrasonic transducer assembly is driven upwards towards the source liquid orifice plate 3, the water film connects to the lower surface of the source liquid orifice plate 3, thereby transmitting the ultrasonic waves emitted by the transducer along the water film to the reagent in the source liquid orifice plate 3. The reagent is then emitted as tiny droplets using acoustic radiation force. In some embodiments, the supply and return liquid assembly includes a storage bottle 141, a peristaltic pump 142, and a negative pressure degassing bottle 143. The storage bottle 141, peristaltic pump 142, negative pressure degassing bottle 143, inlet pipe 131, and liquid recovery housing 132 are sequentially connected to form a liquid circulation loop. The negative pressure degassing bottle 143 utilizes negative pressure to act on the coupling liquid flowing through it, thereby eliminating the gas mixed in the coupling liquid.

[0056] In this technical solution, the gas mixed in the coupling fluid flowing through the negative pressure degassing bottle 143 can be effectively prevented from mixing with the coupling fluid and reducing the effect of the ultrasonic transducer 111, thereby improving the accuracy of the ultrasonic liquid transfer of the ultrasonic transducer 111.

[0057] In some embodiments, a temperature control component (not shown in the figure) is connected in series on the pipeline between the outlet of the negative pressure degassing bottle 143 and the inlet of the liquid inlet pipe 131. The temperature control component is used to adjust the temperature of the coupling liquid entering the liquid inlet pipe 131 to be within the target temperature range. Specifically, the aforementioned temperature control component can be a cooling device (e.g., an air conditioning refrigeration device) located outside the device to prevent the heat generated by the operation of the electrical components inside the device during operation from causing the temperature of the coupling liquid to rise, thereby reducing the accuracy of ultrasonic liquid transfer, and to keep the experimental conditions unchanged.

[0058] See details Figure 7As shown, the aforementioned liquid recovery shell 132 is equipped with a temperature sensor 133 to detect the real-time temperature of the coupling fluid inside. If the real-time temperature exceeds a preset temperature range, the aforementioned temperature control component cools the coupling fluid to reduce its temperature to a reasonable preset range, thereby ensuring the accuracy of ultrasonic pipetting. The aforementioned liquid recovery shell 132 is also equipped with a liquid level sensor 134 for real-time detection of the coupling fluid level inside, preventing excessively high liquid levels from overflowing and damaging other components within the device. In one specific embodiment, when the liquid level is too high, the liquid level sensor 134 will trigger a water level alarm, at which point the device can be controlled to stop operating.

[0059] See details Figure 9 As shown, in some embodiments, the device further includes a gas-liquid path adapter 15, which is specifically assembled on an assembly plate 16. The assembly plate 16 is assembled on a device support 23. The gas-liquid path adapter 15 integrates a gas path connector 151 and a liquid path connector 152. The gas path connector 151 is used to connect the negative pressure source to the negative pressure liquid absorption component and the negative pressure degassing bottle 143. The liquid path connector 152 is used to connect the temperature control component to the negative pressure degassing bottle 143 and the liquid inlet pipe 131, thereby making the internal structure of the device more compact.

[0060] In some embodiments, the gas connector 151 is also used to connect the negative pressure source to the liquid storage bottle 141, so as to provide assistance to the peristaltic pump 142 through negative pressure, so that the flow and circulation of the coupling fluid is smoother.

[0061] In some embodiments, the ultrasonic micropipette further includes an outer housing (not shown in the figure) and a device support 23 located within the internal accommodating space of the outer housing. The ultrasonic micropipette also includes an orifice plate passage (not labeled in the figure) for the source liquid-carrying orifice plate 3 and the target liquid-carrying orifice plate 4 to enter and exit the internal accommodating space. The orifice plate passage is provided with a door plate 21 that can be opened and closed. When the source liquid-carrying orifice plate 3 and the target liquid-carrying orifice plate 4 are picked up or put down, the door plate 21 is opened, and at other times the door plate 21 is closed. The inner side of the door plate 21 is provided with an electrostatic elimination component 22. The electrostatic elimination component 22 specifically includes an electrostatic rod that can generate positive and negative ions. By contacting the generated positive and negative ions with the orifice plates, the static electricity on the source liquid-carrying orifice plate 3 and the target liquid-carrying orifice plate 4 entering the orifice plate passage can be eliminated. The electrostatic rod can be a commercially available part. The aforementioned door panel 21 is specifically implemented by a door panel lifting drive mechanism 211 (e.g., a combination of a motor and a lead screw). The left and right sides of the door panel 21 are slidably connected to the device bracket 23 via the second guide rail 212. The lifting of the static elimination component 22 is implemented by a component lifting drive mechanism 221 (e.g., a combination of a motor and a lead screw). The component lifting drive mechanism 221 is fixedly connected to the device bracket 23, and the static elimination component 22 is slidably connected to the device bracket 23 via the first guide rail 222.

[0062] Specifically, the orifice plate is generally made of plastic. During use, contact and friction with the hands can cause it to carry a certain amount of charge. Since the volume of the liquid being pipetted is only a few nanoliters, the force exerted by the tiny charge on the droplets of nanoliter size can cause the droplets to deviate from their movement path, resulting in reduced pipetting accuracy. Therefore, this invention includes an electrostatic elimination component 22 in the device, which releases a large number of positive and negative ions onto the orifice plate. When the orifice plate is within the effective area of ​​the electrostatic elimination component 22 (e.g., above or below the electrostatic elimination component 22), the tiny charge carried on the orifice plate will be neutralized and eliminated, thereby effectively preventing the phenomenon of electrostatic force on the droplets causing the droplets to deviate from their movement path and reduce pipetting accuracy.

[0063] In some embodiments, the target liquid-carrying orifice plate 4 can be controlled to flip up and down. The electrostatic elimination component 22 has two sets, which are arranged vertically and horizontally. The upper electrostatic elimination component 22 can be raised and lowered. Specifically, when the target liquid-carrying orifice plate 4 moves from inside the device through the orifice plate passage to outside the device, the liquid inlet side of the target liquid-carrying orifice plate 4 faces upward. At this time, the upper set of electrostatic elimination components 22 is in the upper position after being raised. This can prevent interference between the target liquid-carrying orifice plate 4 and the electrostatic elimination component 22 when it flips. When the target liquid-carrying orifice plate 4 moves from outside the device to inside the device, the liquid inlet side of the target liquid-carrying orifice plate 4 faces downward. At this time, the upper set of electrostatic elimination components 22 is in the lower position after being lowered. This allows the electrostatic elimination component 22 to be close to the orifice plate, ensuring the electrostatic elimination effect.

[0064] The ultrasonic micro-pipette also includes a positive pressure gas path assembly for providing positive pressure airflow into the electrostatic elimination assembly 22 to form a positive and negative ion airflow. Specifically, the aforementioned positive pressure airflow is connected to the electrostatic rod of the electrostatic elimination assembly 22, thereby carrying out the positive and negative ions generated by the electrostatic rod, making the effective area of ​​the electrostatic elimination assembly 22 larger and ensuring effective removal of static electricity from the aforementioned source liquid-carrying plate 3 and target liquid-carrying plate 4. See details. Figure 9 As shown, the positive pressure airflow is generated by the operation of the diaphragm pump 241. A second filter 242 is installed on the air inlet pipe of the diaphragm pump 241 to filter the air entering the diaphragm pump 241 and prevent impurities in the air from contaminating the orifice plate.

[0065] See details Figure 8 As shown, the target liquid-carrying orifice plate 4 is detachably assembled on the target plate support 41. The target plate support 41 can be controlled to flip up and down (i.e., flip 180°). There is a high-voltage grid 32 between the target plate support 41 and the bottom surface of the target liquid-carrying orifice plate 4. When the target liquid-carrying orifice plate 4 is in the liquid-pumping condition, it is energized to form a stable electric field in the droplet rising area. When the droplet is emitted from the source liquid-carrying orifice plate 3 to the target liquid-carrying orifice plate 4, it ensures that the rising trajectory of the droplet is not affected by the external electric field and static electricity, and also prevents the droplet from splashing, further improving the liquid-pumping accuracy.

[0066] See details Figure 10As shown, the ultrasonic micropipette of the present invention also includes a control component 5, specifically comprising an ultrasonic transducer control module 51, a power supply module 52, a high-voltage module 53, a device motion control module 54, and a main control board 55. The ultrasonic transducer control module 51 provides stable excitation to enable the ultrasonic transducer 111 to output a fixed focused ultrasonic wave, thereby outputting the droplet at a certain volume and stable frequency. The power supply module 52 provides a stable low voltage required by the various hardware devices within the device. The high-voltage module 53 provides high-voltage electricity and low current to the aforementioned high-voltage grid 32. The device control module includes the aforementioned main control board 55 and the device motion control module 54, used to control the operation and signals of various electrical devices such as motors and solenoid valves 25 within the device, thereby driving the movement and position adjustment of each moving component. See details... Figure 6 As shown, the movement of the ultrasonic pipetting assembly 1 is specifically driven by the ultrasonic pipetting assembly moving drive 171, and the moving guide 172 guides the movement direction of the corresponding components. The aforementioned ultrasonic pipetting assembly moving drive 171 can be implemented by a combination of a drive motor and a lead screw, and the aforementioned moving guide 172 can be a linear guide rail. Theoretically, it can realize the lifting (Z-axis), horizontal (X-axis), and horizontal longitudinal (Y-axis) movement of the ultrasonic transducer assembly and the negative pressure suction assembly.

[0067] It is understandable, see Figure 9 As shown, a corresponding solenoid valve 25 is also provided in the corresponding air path so that the opening and closing of the corresponding air path can be achieved by controlling the opening and closing of the corresponding solenoid valve 25.

[0068] According to an embodiment of the present invention, a control method for the ultrasonic micropipette device as described above is also provided, comprising the following steps:

[0069] The target plate support 41 for assembling the target liquid-carrying orifice plate 4 and / or the source plate support 31 for assembling the source liquid-carrying orifice plate 3 can be controlled to extend out of the orifice plate passage, that is, the two orifice plates mentioned above can be controlled to extend out of the device at the same time, or can be controlled to extend out of the device individually, so as to facilitate the placement and removal of the corresponding orifice plates.

[0070] Place the target liquid-carrying orifice plate 4 on the target plate support 41, and / or place the source liquid-carrying orifice plate 3 on the source plate support 31;

[0071] The target plate support 41 and / or source plate support 31 are controlled to retract, and the electrostatic elimination component 22 is activated during the retraction process. The positive and negative ions generated by the electrostatic elimination component 22 neutralize the static electricity on the orifice plate within its effective area until the target plate support 41 and / or source plate support 31 retract to the preset target position (i.e., the position where ultrasonic pipetting is performed). After the target plate support 41 and / or source plate support 31 move away from the effective area of ​​the electrostatic elimination component 22, the operation is controlled to stop.

[0072] When the source plate support 31 retracts to the preset target position, the negative pressure liquid suction component is controlled to rise and contact the bottom surface (i.e., lower surface) of the source liquid carrier plate 3 and run to adsorb the condensation formed on the bottom surface of the source liquid carrier plate 3, so as to prevent the condensation and any impurities that may be mixed in it from reducing the accuracy of ultrasonic liquid transfer.

[0073] Subsequently, the ultrasonic transducer is controlled to rise to a preset height and its operation is controlled to transfer the reagent liquid from the source liquid-carrying plate 3 to the target liquid-carrying plate 4. It is understood that the ultrasonic transducer should also be controlled to move to the corresponding horizontal position. During the ultrasonic transfer process, preferably, the negative pressure suction component is also controlled to descend and disengage from the source liquid-carrying plate 3. In addition, before controlling the operation of the ultrasonic transducer to realize ultrasonic transfer, the vertical alignment of any hole in the upper and lower plates is also controlled.

[0074] After the liquid transfer is completed, the negative pressure liquid suction component is controlled to adsorb the coupling liquid remaining on the bottom surface of the source liquid carrier plate 3, so as to prevent the coupling liquid remaining on the bottom surface of the source liquid carrier plate 3 from causing contamination or even freezing when placed in the refrigeration device.

[0075] In some embodiments, when a high-voltage grid 32 is provided on the target plate support 41, during the ultrasonic transducer assembly's operation to realize ultrasonic pipetting, the high-voltage grid 32 is also energized to enhance the adsorption force on the droplets generated by the ultrasonic pipetting assembly 1, prevent droplet splashing, and further improve pipetting accuracy.

[0076] The following describes the operation method of the ultrasonic micropipette of the present invention:

[0077] The device starts working, and the door panel 21 opens upwards. The source liquid carrier orifice plate 3 is driven out of the device door along with the source plate support 31. The experimenter manually places the source liquid carrier orifice plate 3 on the source plate support 31. Then the source plate support 31 is driven to retract. During the retraction process, the electrostatic elimination component 22 releases a large number of positive and negative ions to the orifice plate to eliminate the trace electrostatic charge carried on the orifice plate. The target liquid carrier orifice plate 4 extends out of the device door along with the target plate support 41. The experimenter manually places the target liquid carrier orifice plate 4 on the target plate support 41. Then the target plate support 41 is driven to retract. During the retraction process, the electrostatic elimination component 22 releases a large number of positive and negative ions to the orifice plate to eliminate the trace electrostatic charge carried on the orifice plate. The volume of the emitted droplet is only a few nanoliters. The electrostatic charge on the orifice plate will cause the droplet to be attracted by electrostatic charge during the upward emission and will not be emitted to the designated position, resulting in inaccurate droplet transfer volume.

[0078] The source plate support 31 moves to the working position (i.e., the aforementioned preset target position). The ultrasonic transducer 111 in the ultrasonic pipetting assembly 1 operates to detect the liquid level height of each hole in the source liquid-carrying orifice plate 3 using acoustic ranging, and the data is recorded by the computer. The ultrasonic pipetting assembly 1 uses a motor to drive the ultrasonic transducer 111 to move along the X, Y, and Z axes so that the focal point of the ultrasonic transducer 111's acoustic radiation force coincides with each liquid level in the orifice plate, and emits nano-sized droplets to the target liquid-carrying orifice plate 4 fixed to the target plate support 41. The high-voltage grid 32 on the target plate support 41 is connected to a high-voltage module 53 (i.e., energized), which provides an adsorption force to the droplets emitted to the target liquid-carrying orifice plate 4, so that the droplets will not splash out after colliding with the target liquid-carrying orifice plate 4.

[0079] The ultrasonic transducer 111 needs to be immersed in water during operation. In order to improve the transmission efficiency of ultrasonic waves, there is a set of liquid circulation system (i.e., the aforementioned liquid supply and return assembly) and temperature control system (i.e., the aforementioned temperature control component) to ensure that the ultrasonic transducer and the orifice plate are filled with water, maintain a fixed water temperature, and ensure the stability of experimental conditions.

[0080] After the liquid is transferred to the target liquid-carrying plate 4, a small amount of water (coupling fluid) will be adhering to the bottom of the source liquid-carrying plate 3. The negative pressure liquid suction component moves to the bottom of the source liquid-carrying plate 3 and starts to pump air, using negative pressure to remove the small amount of water at the bottom of the source liquid-carrying plate 3, thereby ensuring the surface of the experimental consumables is clean.

[0081] The static eliminator 22 requires a micro-airflow to perform static elimination (in one specific embodiment, the pressure of the micro-airflow is 0.3 MPa). The device of the present invention uses a diaphragm pump 241 to provide a small airflow, which ensures the supply of micro-airflow and low noise, and saves the space occupied by the air source.

[0082] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention. The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the protection scope of the present invention.

Claims

1. An ultrasonic micropipette, comprising a source liquid-carrying orifice plate (3), a target liquid-carrying orifice plate (4) disposed above and opposite to the source liquid-carrying orifice plate (3), and an ultrasonic pipetting assembly (1) disposed below the source liquid-carrying orifice plate (3), characterized in that, The ultrasonic pipetting assembly (1) includes an ultrasonic transducer assembly and a negative pressure suction assembly. The ultrasonic transducer assembly includes an ultrasonic transducer (111) and a coupling liquid between the transducer head of the ultrasonic transducer (111) and the bottom surface of the source liquid orifice plate (3). The negative pressure suction assembly includes a suction head (121), the suction surface of which can be driven to contact the bottom surface of the source liquid orifice plate (3). The suction head (121) is a hollow cavity with a slit. The negative pressure suction assembly is used to adsorb condensation formed on the bottom surface of the source liquid orifice plate (3) and the coupling liquid remaining on the bottom surface of the source liquid orifice plate (3). The ultrasonic transducer assembly also includes a liquid supply overflow housing (1 3) and the liquid supply and return assembly, wherein the liquid supply overflow housing (13) includes an inlet pipe (131) and a liquid recovery housing (132). The inlet pipe (131) has a top opening. The ultrasonic transducer (111) is assembled inside the inlet pipe (131) and the transducer head is located inside the top opening. An outlet (1311) is formed between the transducer head and the top opening. The outlet (1311) is spaced around the transducer head. The liquid overflowing from the outlet (1311) can fall into the liquid recovery housing (132). The liquid supply and return assembly can supply the coupling liquid into the inlet pipe (131) and recover the coupling liquid in the liquid recovery housing (132) to form a cycle.

2. The ultrasonic micropipette according to claim 1, characterized in that, The negative pressure liquid suction assembly also includes a first filter (122), which is connected to the outlet of the suction head (121) to separate and store the liquid absorbed by the suction head (121) from the negative pressure airflow.

3. The ultrasonic micropipette according to claim 2, characterized in that, The liquid supply and return assembly includes a liquid storage bottle (141), a peristaltic pump (142), and a negative pressure degassing bottle (143). The liquid storage bottle (141), peristaltic pump (142), negative pressure degassing bottle (143), liquid inlet pipe (131), and liquid recovery shell (132) are connected in sequence to form a liquid circulation loop. The negative pressure degassing bottle (143) can use negative pressure to act on the coupling liquid flowing through it to eliminate the gas mixed in the coupling liquid.

4. The ultrasonic micropipette according to claim 3, characterized in that, A temperature control component is also connected in series on the pipeline between the outlet of the negative pressure degassing bottle (143) and the inlet of the liquid inlet pipe (131). The temperature control component is used to adjust the temperature of the coupling liquid entering the liquid inlet pipe (131) to be within the target temperature range.

5. The ultrasonic micropipette according to claim 4, characterized in that, It also includes a gas-liquid circuit adapter (15), which integrates a gas circuit connector (151) and a liquid circuit connector (152). The gas circuit connector (151) is used to connect the negative pressure source to the negative pressure liquid absorption component and the negative pressure degassing bottle (143), and the liquid circuit connector (152) is used to connect the temperature control component to the negative pressure degassing bottle (143) and the liquid inlet pipe (131).

6. The ultrasonic micropipette according to claim 5, characterized in that, The gas connector (151) is also used to connect the negative pressure source to the liquid storage bottle (141).

7. The ultrasonic micropipette according to claim 1, characterized in that, The ultrasonic micropipette further includes a perforated plate passage for the source liquid-carrying plate (3) and the target liquid-carrying plate (4) to enter and exit the internal accommodating space. An electrostatic elimination component (22) is provided inside the perforated plate passage, which can eliminate static electricity on the source liquid-carrying plate (3) and the target liquid-carrying plate (4) at the perforated plate passage; and / or, The target liquid-carrying orifice plate (4) is detachably assembled on the target plate support (41). The target plate support (41) can be controlled to flip up and down. There is a high voltage grid (32) between the target plate support (41) and the bottom surface of the target liquid-carrying orifice plate (4) to generate an adsorption force on the droplets generated by the ultrasonic pipetting assembly (1) when the target liquid-carrying orifice plate (4) is in the liquid-pipette working condition.

8. The ultrasonic micropipette according to claim 7, characterized in that, The target liquid-carrying plate (4) can be controlled to rotate up and down. The electrostatic eliminator (22) has two sets, which are spaced vertically apart. The upper electrostatic eliminator (22) can be raised and lowered. And / or, The ultrasonic micropipette also includes a positive pressure gas path assembly for providing a positive pressure gas flow into the electrostatic elimination assembly (22) to form a positive and negative ion gas flow.

9. A control method for an ultrasonic micropipette device as described in any one of claims 1 to 8, characterized in that, Includes the following steps: Control the target plate support (41) used for assembling the target liquid-carrying orifice plate (4) and / or the source plate support (31) used for assembling the source liquid-carrying orifice plate (3) to extend out of the orifice plate passage; Place the target liquid-carrying orifice plate (4) on the target plate support (41), and / or place the source liquid-carrying orifice plate (3) on the source plate support (31); Control the target board support (41) and / or source board support (31) to retract, and activate the electrostatic elimination component (22) during the retraction process until the target board support (41) and / or source board support (31) retract to the preset target position, and control it to stop operating after the target board support (41) and / or source board support (31) are far away from the effective area of ​​the electrostatic elimination component (22); When the source plate support (31) retracts to the preset target position, the negative pressure liquid suction component is controlled to adsorb the condensation formed on the bottom surface of the source liquid carrier plate (3); Then, the ultrasonic transducer is controlled to operate so that the reagent solution is transferred from the source liquid carrier plate (3) to the target liquid carrier plate (4); After the liquid transfer is completed, the negative pressure liquid suction component is controlled to adsorb the coupling liquid remaining on the bottom surface of the source liquid carrier plate (3).

10. The control method according to claim 9, characterized in that, During the operation of the ultrasonic transducer to realize ultrasonic pipetting, the high-voltage power grid (32) is also energized.

Images